Hyaluronic acid modified nanocarriers for aerosolized delivery of verteporfin in the treatment of acute lung injury.

Verteporfin (VER), a photosensitizer used in macular degeneration therapy, has shown promise in controlling macrophage polarization and alleviating inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, its hydrophobicity, limited bioavailability, and side effects hinder its therapeutic potential. In this study, we aimed to enhance the therapeutic potential of VER through pulmonary nebulized drug delivery for ALI/ARDS treatment. We combined hydrophilic hyaluronic acid (HA) with an oil-in-water system containing a poly(lactic acid-co-glycolic acid) (PLGA) copolymer of VER to synthesize HA@PLGA-VER (PHV) nanoparticles with favorable surface characteristics to improve the bioavailability and targeting ability of VER. PHV possesses suitable electrical properties, a narrow size distribution (approximately 200 nm), and favorable stability. In vitro and in vivo studies demonstrated the excellent biocompatibility, safety, and anti-inflammatory responses of the PHV by suppressing M1 macrophage polarization while inducing M2 polarization. The in vivo experiments indicated that the treatment with aerosolized nano-VER (PHV) allowed more drugs to accumulate and penetrate into the lungs, improved the pulmonary function and attenuated lung injury, and mortality of ALI mice, achieving improved therapeutic outcomes. These findings highlight the potential of PHV as a promising delivery system via nebulization for enhancing the therapeutic effects of VER in ALI/ARDS.

Generation of a human induced pluripotent stem cell line (JSPHi003-A) from a patient with atrial fibrillation and ventricular tachycardia carrying LMNA frame shift mutation (c.1304_1307dup).

The iPSC line was generated from the peripheral blood mononuclear cells (PBMCs) from a 53-year-old female patient carrying the LMNA gene mutation (c.1304_1307dup) diagnosed with atrial fibrillation and paroxysmal ventricular tachycardia. Through comprehensive detection, it was verified that the cell line had the LMNA gene mutation, normal karyotype, and the potential to differentiate into the three germ layers. This cell line may reveal potential therapeutic targets for atrial and ventricular arrhythmias caused by LMNA mutations.

Febuxostat Increases Ventricular Arrhythmogenesis Through Calcium Handling Dysregulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Febuxostat is a xanthine oxidase inhibitor used to reduce the formation of uric acid and prevent gout attacks. Previous studies have suggested that febuxostat was associated with a higher risk of cardiovascular events, including atrial fibrillation, compared with allopurinol, another anti-hyperuricemia drug. Whereas in our clinical practice, we identified 2 cases of febuxostat-associated ventricular tachycardia (VT) events. The proarrhythmogenic effects of febuxostat on human cardiomyocytes and underlined mechanisms remain poorly understood. In this study, we employed real-time cell analysis and calcium transient to investigate the effects of febuxostat on the cytotoxicity and electrophysiology properties of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Up to 10 µM febuxostat treatment did not show toxicity to cell viability. However, 48-h febuxostat exposure generated dose-dependent increased irregular calcium transients and decreased calcium transient amplitude. Furthermore, RNA-seq analysis indicated that the MAPK signaling pathway was enriched in the febuxostat-treated group, especially the protein kinases c-Jun N-terminal kinase (JNK). Western blotting of 3 main protein kinases demonstrated that JNK activation is related to febuxostat-induced arrhythmia rather than extracellular signal regulated kinases (ERK) or p38. The dysfunctional calcium dynamics of febuxostat-treated hiPSC-CMs could be ameliorated by SP600125, the inhibitor of JNK. In conclusion, our study demonstrated that febuxostat increases the predisposition to ventricular arrhythmia by dysregulating calcium dynamics.

Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress.

Hypoglycemicagents have been shown to reduce the incidence of atrial fibrillation (AF) in patients with diabetes mellitus. Azoramide is a novel anti-diabetic agent which protects cells against endoplasmic reticulum (ER) stress; however, the cardioprotective effect of azoramide against AF is not clear. In this study, we aimed to investigate the protective effect of azoramide in human iPS-derived atrial myocytes (a-iCMs) against injury induced by high-frequency electrical stimulation. Human-induced pluripotent stem cells were differentiated into a-iCMs by treatment of retinoic acid. The tachypacing group was subjected to 7 Hz tachypacing for 48 h. Azoramide was preconditioned 2-hours before tachypacing. a-iCMs expressed atria-specific genes and the characteristics of the action potential were analogous to those of human atrial myocytes. Tachypacing induced disorder of intracellular calcium homeostasis, apoptosis, depressed ATP level, and severer myofilament dissolution. MetaboAnalysis revealed that tachypacing induced remarkable changes in metabolites involved in energy, amino acid, and glucose metabolism, whereas there was no significant effect on lipid metabolism. Azoramide pretreatment partly alleviated tachypacing-induced calcium dyshomeostasis, ATP consumption, and accelerated apoptosis, which was likely achieved by regulating the PERK/CHOP/CaMKII pathway. Azoramide protected atrial myocytes against injury induced by high-frequency electrical stimulation by regulating ER stress, which may inhibit cell apoptosis and calcium dyshomeostasis via the PERK/CHOP/CaMKII pathway.

Genetic findings in patients with primary fibrotic atrial cardiomyopathy.

Primary fibrotic atrial cardiomyopathy (PF-ACM) is a novel type of cardiomyopathy characterized by primary atrial fibrosis with arrhythmogenicity and increased stroke risk without ventricular myocardium involvement. However, genetic analysis regarding PF-ACM and genotype-phenotype correlations is lacking. A cohort of PF-ACM patients was recruited and followed up. Whole-exome sequencing (WES) was applied, and genes were screened using a cardiovascular disease (CVD)-related gene panel. Echocardiography and cardiac magnetic resonance (CMR) were performed. The pathogenicity of the identified mutations was evaluated using in silico analysis. Thirty-three unrelated patients were referred for WES. Thirty-three rare variants of 19 CVD-related genes were identified in 21 patients, with 10 patients harboring more than one variation. TTN was the most frequent gene observed. Further analysis demonstrated that variations in sarcomeric (SV) or non-sarcomeric (NSV) genes were found in 16 and 10 patients, respectively. Patients carrying variants regardless of SV or NSV had larger left atrial dimensions determined by echo and larger left atrium areas determined by CMR. There was no discrepancy in disease severity between SV carriers and NSV carriers. Our genetic investigation into PF-ACM has identified several genetic culprits, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing for this condition.

Oral azoxystrobin driving the dynamic change in resistome by disturbing the stability of the gut microbiota of Enchytraeus crypticus.

Pesticides are continually entering the soil ecosystem because of safety assurance of high-yield food in agricultural intensification. It is highly urgent to evaluate their effects on the soil biota. This study characterized the dose-dependent changes in the gut bacterial and fungal community of Enchytraeus crypticus after oral exposure to an environmental dose of the fungicide azoxystrobin (AZ; 0.5, 1, and 10 mg/L) for 21 days. AZ not only induced the growth opportunistic pathogens and reduced the relative abundance of beneficial bacteria in the E. crypticus gut, but also destroyed the stability of the gut microecology of E. crypticus. Meanwhile, the dose-dependent effects of AZ were observed on the number and normalized abundance of antibiotic resistance genes (ARGs; copies/bacterial cell), and trace dose of AZ (> 0 and < 0.085 µg/individual) might enrich the ARG numbers in the gut of E. crypticus. Moreover, we used structural equation modeling to speculate that apart from mobile genetic elements and the bacterial community, the microbial interaction of E. crypticus gut might be another key contributor that drived the emergence and dissemination of ARGs. This study provides new perspectives in assessing the gut health of soil fauna under pesticide pollution in intensive agricultural production.

New fossil giant lacewings from the Middle Jurassic Jiulongshan Formation of China (Neuroptera, Ithonidae).

A new genus with a new species, Fuscopolystoechotes reticulatus Xu, Zheng, Shih Wang, gen. et sp. nov., and a new species Lichenipolystoechotes fenestratus Xu, Fang, Shih Wang, sp. nov. of Ithonidae, are described from the Middle Jurassic Jiulongshan Formation, Inner Mongolia, China. Both new species are assigned to Polystoechotes genus-group mainly based on the combination of following characters: the distinctly narrowed costal space in distal half, presence of recurrent humeral veinlet and ScA, absence of interlinked crossveins in between costal crossveins, converged ScP and RA and pectinately branched MA and MP in distal. But the new genus of Fuscopolystoechotes gen. nov. is differentiated from all other genera by a combination of characters, i.e., specialized markings on forewing; scp-ra crossveins absent; CuP with pectinate branches and crossveins in RPA area complicated. These two new species with the remarkable markings in forewings are considered to be adapted for the particular Mesozoic environments for camouflage or mimicry.

Lichen mimesis in mid-Mesozoic lacewings.

Animals mimicking other organisms or using camouflage to deceive predators are vital survival strategies. Modern and fossil insects can simulate diverse objects. Lichens are an ancient symbiosis between a fungus and an alga or a cyanobacterium that sometimes have a plant-like appearance and occasionally are mimicked by modern animals. Nevertheless, lichen models are almost absent in fossil record of mimicry. Here, we provide the earliest fossil evidence of a mimetic relationship between the moth lacewing mimic Lichenipolystoechotes gen. nov. and its co-occurring fossil lichen model Daohugouthallus ciliiferus. We corroborate the lichen affinity of D. ciliiferus and document this mimetic relationship by providing structural similarities and detailed measurements of the mimic's wing and correspondingly the model's thallus. Our discovery of lichen mimesis predates modern lichen-insect associations by 165 million years, indicating that during the mid-Mesozoic, the lichen-insect mimesis system was well established and provided lacewings with highly honed survival strategies.

Many insects mimic other organisms or use camouflage to hide from predators. For example, some modern animals mimic the organism lichens, which are formed from algae and fungus, and grow almost everywhere on Earth, from the Arctic to the desert. The most iconic example of an insect mimicking a species of lichen is the peppered moth. During the industrial revolution, darker colored moths were better at surviving. But when the revolution ended and pollution levels declined, species of lichen began to re-emerge and increase the survival of paler moths. Yet, it is unclear how and when insects first evolved this ingenious survival strategy, as distinctive examples of insects mimicking lichens are missing from fossil records. To answer this question, Fang et al. set out to find fossils of lichen-mimicking insects that occurred at the same time as fossils of lichens. This approach led to the discovery of two new species of lacewing insects and their related species of foliose lichen. Previous work suggested that the foliose lichen, which has a lobe like shape, did not exist more than 65 million years ago. However, the findings of Fang et al. indicate that the foliose lichen existed 165 million years ago during the age of dinosaurs, and therefore arose much earlier than previously thought. The two new species found in north-eastern China, form a new subgroup within the moth lacewing family that Fang et al. have named 'Lichenipolystoechotes'. Close examination of both species of lacewing and the lichen under the microscopy revealed a near perfect match in their appearance. The branching patterns of the insects' wing markings fit the branching patterns of the lichen. Taken together, these findings suggest that, not only did lichen mimics exist in the age of the dinosaurs, but that this strategy of using lichen mimicry as a form of survival was already very effective during this time period. This discovery suggests that, 165 million years ago, a micro-ecosystem of lichens and insects existed in north-eastern China. It invites new questions about how that ecosystem worked. For example, how did the lichen benefit from its relationship with lacewing insects? Further investigations could reveal the answers and uncover more interesting insects hidden in the fossil record.

A new species of Lasiosmylus from the Early Cretaceous, China clarifies its genus-group placement in Ithonidae (Neuroptera).

A new species, Lasiosmylus longussp. n., is described from the Early Cretaceous Yixian Formation of Huangbanjigou Village, Liaoning Province, China. Based on the characters of the new species and nine new specimens of Lasiosmylus newi Ren & Guo, 1996, the generic diagnosis of Lasiosmylus is emended and the taxonomic position of Lasiosmylus Ren & Guo, 1996 is re-evaluated, and Lasiosmylus should be assigned to the ithonid genus-group.

Suspended sludge and biofilm shaped different anammox communities in two pilot-scale one-stage anammox reactors.

The abundance and diversity of anammox bacteria was investigated in two pilot-scale integrated fixed-film activated sludge (IFAS) reactors treating high ammonium wastewater. Reactor A was inoculated with nitrifying sludge, while Reactor B was inoculated with suspended anammox sludge with the dominant anammox bacteria of Candidatus 'Kuenenia'. After 180days' operation, the predominate anammox bacteria was Candidatus 'Brocadia' (65%) in the biofilm, while Candidatus 'Kuenenia' (86%) outcompeted with other anammox bacteria in suspended sludge in Reactor A. Candidatus 'Kuenenia' were dominated in suspended sludge through the entire experiment in Reactor B. In contrast, the predominated species shifted from Candidatus 'Kuenenia' (89%) into Candidatus 'Brocadia' (66%) in the biofilm of Reactor B. This study indicated that Candidatus 'Brocadia' preferred to grow in the biofilm, while Candidatus 'Kuenenia' would dominant over other anammox bacteria in the suspended sludge. Further studies are required to identify the internal factors affecting the distribution of anammox bacteria.

[Distribution and influence factors of Anammox bacteria in sewage treatment systems].

Nitrogen removal techniques based on Anammox process are developing rapidly these years. The distribution and diversity of Anammox have become important research directions. A variety of Anammox have been detected till now, of which only Kuenenia and Brocadia are often detected in wastewater treatment systems. In addition, in a single niche there is only one type of Anammox bacteria. However, the distribution mechanism and transformation of Anammox bacteria in different niches are still ambiguous. Therefore, the distribution of Anammox in various conditions was summarized and analyzed in this article. And the key factors influencing the distribution of Anammox were concluded, including substrate concentration and the specific growth rate, sludge properties and microbial niche, the joint action and influence of multiple factors. The engineering significance research on the distribution and influencing factors of Anammox bacteria in the sewage system and proposed research prospects were expounded.