Exploring the influence of pulmonary pathological state on the in vivo fate of inhaled microparticles with different structural characteristics.

Currently, marketed inhalation products for treatment of pulmonary arterial hypertension (PAH) have limited time of action due to pulmonary clearance mechanism and short of sustained-release characteristics. Meanwhile, little is known on how the pathological state of PAH affects the in vivo fate of inhaled microparticles. Thus, the objective of this study is to elucidate the influence of pulmonary pathological state on the in vivo behavior of inhaled microparticles with different structural characteristics.

Elucidating structure of endogenous phospholipids on in vivo absorption of octreotide following lung administration.

Phospholipids as endogenous pulmonary components have received extensive attention on promoting the transmembrane absorption of peptides and proteins. However, considering their diversified structure, influence of phospholipid structural characteristics on drug absorption across lung epithelial cells, together with the underlying absorption-promoting mechanisms, remain unclear. Therefore, in this study, taking octreotide as a model drug, phospholipids with different "tail" and "head" structures were adopted in the form of blank liposomes to investigate their structural characteristics on drug absorption utilizing both 3D Transwell cell models and Sprague Dawley rats.

Environmental, socioeconomic, and sociocultural drivers of monkeypox transmission in the Democratic Republic of the Congo: a One Health perspective.

Background: Monkeypox (mpox) is an emerging zoonotic disease that has persistently impacted public health in endemic regions of West and Central Africa for over half a century. The Democratic Republic of the Congo (DRC) remains one of the countries most affected. Understanding the risk factors for disease transmission from a One Health perspective is of great importance in the risk assessment, prevention, and control of zoonotic diseases.

Predicting the risk of malaria importation into Jiangsu Province, China: a modeling study.

Background: The World Health Organization certified China malaria-free in 2021. Consequently, preventing the risk of malaria re-introduction caused by imported malaria has now become a major challenge. This study aims to characterize the dynamics and predict the risk of malaria importation in Jiangsu Province, where the number of imported malaria cases ranks among the highest in China.

Construction and performance evaluation of polyguluronic acid polysaccharides-based drug delivery systems.

Polysaccharides have garnered significant attention as potential nanoparticle carriers for targeted tumor therapy due to their excellent biodegradability and biocompatibility. Polyguluronic acid (PG) is a homogeneous acidic polysaccharide fragment derived from alginate, which is found in brown algae, possesses excellent bioactivities, unique properties. This study explored the immunomodulatory activity of PG and developed PG-based nanogels through modified disulfide bonds and Ca dual crosslinking.

Integrated serum pharmacochemistry, network pharmacology, and pharmacokinetics to clarify the effective components and pharmacological mechanisms of the proprietary Chinese medicine Jinkui Shenqi Pill in treating kidney yang deficiency syndrome.

The proprietary Chinese medicine Jinkui Shenqi Pill (PCM-JKSQP) is a classic compound used for the effective clinical treatment of kidney yang deficiency syndrome (KYDS), a metabolic disease accompanied by kidney injury. However, its active ingredients and therapeutic mechanisms are not clear. This study employed serum pharmacochemistry, network pharmacology, and pharmacokinetics (PK) to identify the bioactive components of PCM-JKSQP and preliminarily clarify its mechanism in treating KYDS.

Study on the mechanism of methane "solid-liquid-gas" conversion controlled by the evolution of coal micro- and nanopore structure.

Currently, the utilization of coalbed methane resources in the Guizhou region faces challenges such as complex reservoir structure, high gas content, and microporous development. Based on these, the pore structure and adsorption capacity of Guizhou tectonic deformed coals (TDCs) were evaluated using a suite of integrated diagnostic techniques including low-temperature nitrogen adsorption (LT-NA), mercury intrusion porosimetry (MIP), methane isothermal adsorption. Through the above methods, the pore structure and adsorption characteristics of the samples were characterized; The samples were divided into the range of joint pores by combining the results of MIP and LT-NA; Using the molecular simulation software, the 2 nm, 4 nm, 10 nm pores affecting the methane endowment state were investigated respectively, and from the perspective of the heat of adsorption and energy, the concept of the three-phase transition of methane was proposed, and explore the change of the pore spacing affecting the endowment state of methane from the solid state pore to the gas state pore.

Experimental research on the influence of acid on the chemical and pore structure evolution characteristics of Wenjiaba tectonic coal.

The chemical and pore structures of coal play a crucial role in determining the content of free gas in coal reservoirs. This study focuses on investigating the impact of acidification transformation on the micro-physical and chemical structure characteristics of coal samples collected from Wenjiaba No. 1 Mine in Guizhou.

Enhanced brain distribution of Ginsenoside F1 via intranasal administration in combination with absorption enhancers.

Ginsenoside F1 (GF1) is a potential drug candidate for the treatment of Alzheimer's disease. Nevertheless, its low oral bioavailability and poor solubility limit clinical application. By utilizing either a direct or indirect approach, intranasal administration is a non-invasive drug delivery method that can deliver drugs to the brain rapidly.

Acidification-Induced Micronano Mechanical Properties and Microscopic Permeability Enhancement Mechanism of Coal.

An acid solution improves the pore-plugging problem in hydraulic fracturing, which in turn improves the permeability of the coal seam. The study aimed to investigate the effect of mixed acid on the micronano mechanical properties and permeability of the coal seam. The surface morphology of acidified coal was analyzed from the micronano scale using atomic force microscopy (AFM) and scanning electron microscopy.

Delayed care-seeking in international migrant workers with imported malaria in China.

Background: Imported malaria cases continue to pose major challenges in China as well as in other countries that have achieved elimination. Early diagnosis and treatment of each imported malaria case is the key to successfully maintaining malaria elimination success. This study aimed to build an easy-to-use predictive nomogram to predict and intervene against delayed care-seeking among international migrant workers with imported malaria.

Construction and performance evaluation of pH-responsive oxidized hyaluronic acid hollow mesoporous silica nanoparticles.

In this study, hollow mesoporous silica (HMSN) was created to facilitate drug distribution using the hard template method. The oxidized hyaluronic acid (oxiHA) was coated on the carrier surface by the Schiff base reaction, producing the pH-responsive nanoparticles HMSNs-DOX-oxiHA targeted by CD44 and preventing drug leakage from mesopores. The prepared nanoparticles had a size of 151.

Identification of Key Novel lncRNAs and that Construct ceRNA Networks Associated with Recurrence and Metastasis in Colon Cancer.

Background: Colon adenocarcinoma (COAD) is a major cause of cancer mortality worldwide. The occurrence and development of colon cancer is regulated by complex mechanisms that require further exploration. Recently, long non-coding RNAs (lncRNAs) were found to be related to the mortality of colon cancer patients through their participation in competing endogenous RNA (ceRNA) networks.

Preparation and Properties of Natural Polysaccharide-Based Drug Delivery Nanoparticles.

In recent years, natural polysaccharides have been widely used in the preparation of drug delivery systems. In this paper, novel polysaccharide-based nanoparticles were prepared by layer-by-layer assembly technology using silica as a template. The layers of nanoparticles were constructed based on the electrostatic interaction between a new pectin named NPGP and chitosan (CS).

Dual functional pullulan-based spray-dried microparticles for controlled pulmonary drug delivery.

Two main challenges are associated with current spray-dried microparticles for inhalation, including the enhancement of aerosolization performance of microparticles and the creation of sustained drug release for continuous treatment on-site. For achieving these purposes, pullulan was explored as a novel excipient to prepare spray-dried inhalable microparticles (with salbutamol sulphate, SS, as a model drug), which were further modified by additives of leucine (Leu), ammonium bicarbonate (AB), ethanol and acetone. It was demonstrated that all pullulan-based spray-dried microparticles had improved flowability and enhanced aerosolization behavior, with the fine particle (<4.

Design, synthesis and structure-activity relationship of N-phenyl aromatic amide derivatives as novel xanthine oxidase inhibitors.

Our previous studies suggested that N-phenyl aromatic amides are a class of promising xanthine oxidase (XO) inhibitor chemotypes. In this effort, several series of N-phenyl aromatic amide derivatives (4a-h, 5-9, 12i-w, 13n, 13o, 13r, 13s, 13t and 13u) were designed and synthesized to carry out an extensive structure-activity relationship (SAR). The investigation provided some valuable SAR information and identified N-(3-(1H-imidazol-1-yl)-4-((2-methylbenzyl)oxy)phenyl)-1H-imidazole-4-carboxamide (12r, IC = 0.

(E)-2-styrylanthracene-9,10-dione derivatives as novel fluorescent probes: synthesis, photophysical properties and application in mitochondria imaging.

Our previous work firstly reported that (E)-2-styrylanthracene-9,10-dione is a novel fluorescent core (EK01) with the ability of specific mitochondria imaging. In this effort, we mainly focused our attention on the structure-photophysical property relationship and application in cells imaging of this new fluorescent chemotype. A series of the structural derivatives (TZ series) were designed and synthesized by introducing some substituents onto the 2-styryl moiety.

A possible covalent xanthine oxidase inhibitor TS10: Inhibition mechanism, metabolites identification and PDPK assessment.

Xanthine oxidase (XO) inhibitors are widely used in the control of serum uric acid levels in the clinical management of gout. Our continuous efforts in searching novel amide-based XO inhibitors culminated in the identification of N-(4-((3-cyanobenzyl)oxy)-3-(1H-tetrazol-1-yl)phenyl)isonicotinamide (TS10), which exhibited comparable in vitro inhibition to that of topiroxostat (TS10, IC = 0.031 μM; topiroxostat, IC = 0.

Design, synthesis and biological evaluation of N-(4-alkoxy-3-(1H-tetrazol-1-yl)phenyl) heterocyclic aromatic amide derivatives as xanthine oxidase inhibitors.

Xanthine oxidase (XO) is a flavoprotein that exists in various organisms and can catalyze the uric acid formation in the human body. Based on the amide framework of N-(4-((3-cyanobenzyl)oxy)-3-(1H-tetrazol-1-yl)phenyl)isonicotinamide (compound 1) reported in our previous work, a series of N-(4-alkoxy-3-(1H-tetrazol-1-yl)phenyl) heterocyclic aromatic amide derivatives were designed, synthesized and evaluated as novel amide-based XO inhibitors. Structure-activity relationship campaign identified the most promising compound g25 (IC = 0.

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment.

Alzheimer's disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults.

The neuroprotective mechanism of lithium after ischaemic stroke.

Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We discover that Li inhibits activation of nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the middle cerebral artery occlusion (MCAO) stroke model in mice.

Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel.

Most biopharmaceutics classification system (BCS) class IV drugs, with poor solubility and inferior permeability, are also substrates of P-glycoprotein (P-gp) and cytochrome P450 (CYP450), leading to their low oral bioavailability. The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles (PLHNs) to enhance the oral absorption of BCS IV drugs. In this paper, taking paclitaxel (PTX) as a drug model, PTX-loaded PLHNs were prepared by a self-assembly method.

Inhalable PLGA microspheres: Tunable lung retention and systemic exposure via polyethylene glycol modification.

Polyethylene glycol (PEG) modification is one of the promising approaches to overcome both mucus and alveolar macrophage uptake barriers in the deep lung for sustained therapy of pulmonary diseases such as asthma. To investigate the feasibility of using PEG-modified microspheres to bypass both barriers, we prepared a collection of polyethylene glycol-distearoyl glycero-phosphoethanolamine (PEG-DSPE)-modified poly (lactide-co-glycolide) (PLGA) microspheres bearing specific PEG molecular weights (0.75, 2, 5, and 10 kDa) and PEG-DSPE/PLGA molar ratios (0.

Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol.

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear.

Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice.

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear.