Protein-enriched extracts from housefly (Musca domestica) maggots alleviates atherosclerosis in apolipoprotein E-deficient mice by promoting bile acid production and consequent cholesterol consumption.

Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein-enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti-atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE-/- ) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8-week-old male ApoE-/- mice were recruited and fed on a cholesterol-enriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real-time quantitative polymerase chain reaction and western blot were employed to determine the expression of hepatic ATP-binding cassette transporter A1 (ABCA1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor-γ (PPAR-γ). Serum levels of high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), and total cholesterol (TC) were determined by enzyme-linked immunoassay. Results revealed that PE reversed the formation of atherosclerotic lesion; increased the expression of PPAR-γ, LXRα, and ABCA1; increased the amount of bile flow and total bile acid; reduced the serum level of LDL and TC; and increased the level of HDL. In conclusion, enhancement on bile acid production and consequent cholesterol consumption may partially contribute to the anti-atherosclerotic effects of PE. The reversal of PPARγ-LXRα-ABCA1 signaling pathway may be involved in this process.

Low-loss and polarization insensitive 32 × 4 optical switch for ROADM applications.

Integrated switches play a crucial role in the development of reconfigurable optical add-drop multiplexers (ROADMs) that have greater flexibility and compactness, ultimately leading to robust single-chip solutions. Despite decades of research on switches with various structures and platforms, achieving a balance between dense integration, low insertion loss (IL), and polarization-dependent loss (PDL) remains a significant challenge. In this paper, we propose and demonstrate a 32 × 4 optical switch using high-index doped silica glass (HDSG) for ROADM applications. This switch is designed to route any of the 32 inputs to the express ports or drop any channels from 32 inputs to the target 4 drop ports or add any of the 4 ports to any of the 32 express channels. The switch comprises 188 Mach-Zehnder Interferometer (MZI) type switch elements, 88 optical vias for the 44 optical bridges, and 618 waveguide-waveguide crossings with three-dimensional (3D) structures. At 1550 nm, the fiber-to-fiber loss for each express channel is below 2 dB, and across the C and L bands, below 3 dB. For each input channel to all 4 drop/add channels at 1550 nm, the loss is less than 3.5 dB and less than 5 dB across the C and L bands. The PDLs for all express and input channels to the 4 drop/add channels are below 0.3 dB over the C band, and the crosstalk is under -50 dB for both the C and L bands.

Pathogenesis of pulmonary hypertension caused by left heart disease.

Pulmonary hypertension has high disability and mortality rates. Among them, pulmonary hypertension caused by left heart disease (PH-LHD) is the most common type. According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, PH-LHD is classified as group 2 pulmonary hypertension. PH-LHD belongs to postcapillary pulmonary hypertension, which is distinguished from other types of pulmonary hypertension because of its elevated pulmonary artery wedge pressure. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. The primary strategy in managing PH-LHD is optimizing treatment of the underlying cardiac disease. Recent clinical studies have found that mechanical unloading of left ventricle by an implantable non-pulsatile left ventricular assist device with continuous flow properties can reverse pulmonary hypertension in patients with heart failure. However, the specific therapies for PH in LHD have not yet been identified. Treatments that specifically target PH in LHD could slow its progression and potentially improve disease severity, leading to far better clinical outcomes. Therefore, exploring the current research on the pathogenesis of PH-LHD is important. This paper summarizes and classifies the research articles on the pathogenesis of PH-LHD to provide references for the mechanism research and clinical treatment of PH-LHD, particularly molecular targeted therapy.

Nuciferine attenuates atherosclerosis by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT pathway in ApoE(-/-) mice fed with High-Fat-Diet.

BACKGROUND: Atherosclerosis (AS) is the pathological basis of multiple cardiovascular diseases. The pathogenesis of AS is closely related to the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Nuciferine, an aporphine alkaloid from lotus leaf, has various pharmacological activities. However, the effect and mechanism of nuciferine on regulating proliferation and migration of VSMCs against AS is still unclear. PURPOSE: To elucidate the pharmacological effect and molecular mechanism of nuciferine on AS in ApoE(-/-) mice fed with High-Fat-Diet (HFD). STUDY DESIGN: HFD-fed ApoE(-/-) mice and 3% fetal bovine serum (FBS) induced mouse aortic vascular smooth muscle cells (MOVAS) were used to investigate the protective effect and mechanism of nuciferine on AS. METHODS: Oil red O staining was used to detect the atherosclerotic lesions. Western blotting and immunofluorescence were used to determine calmodulin 4 (Calm4) expression and localization. CCK-8 assay, transwell and wound-healing assays were used to measure the migration and proliferation of MOVAS cells. RESULTS: Nuciferine at 40 mg/kg significantly ameliorated the aortic lesion and vascular plaque in AS model, which was equal to the effect of the positive control drug (atorvastatin). In addition, nuciferine attenuated the migration and proliferation of VSMCs in vivo and in vitro. Importantly, nuciferine down-regulated the increase of Calm4 induced by HFD-fed in ApoE(-/-) mice or 3% FBS induced MOVAS cells. However, the inhibitory effect of nuciferine on the migration and proliferation of MOVAS cells was blocked when Calm4 was overexpressed. Furthermore, we found that nuciferine suppressed MMP12 and PI3K/Akt signaling pathway via Calm4. CONCLUSION: Our results illustrated that Calm4 promoted the proliferation and motility of MOVAS by activating MMP12/Akt signaling pathway in AS. Nuciferine has a significant anti-atherogenic effect by regulating the proliferation and migration of VSMCs through the Calm4/MMP12/AKT signaling pathway. Thus, Calm4 could potentially be a new target for AS therapy, and nuciferine could be a potential drug against AS.

Ecological Restoration and Carbon Sequestration Regulation of Mining Areas-A Case Study of Huangshi City.

As an important carbon sink indicator, the vegetation net primary productivity (NPP) is key and helpful for understanding regional carbon sequestration and storage of mining areas. Systematic analysis of NPP of the ecological reconstruction process in mining areas can effectively contribute to local governments and related departments for making ecological decisions under the "double carbon goals" ("peak of carbon release" and "carbon neutrality") and help to promote regional sustainable development. In this study, we used the CASA model to systematically assess the temporal and spatial evolution characteristics of NPP of Huangshi City from 1990 to 2018. Meanwhile, various scenarios were set up to study the effects of climate factors, landscape pattern evolution, and ecological restoration on regional carbon storage. Our results documented that (1) NPP of the study area an increasing trend from 1990-2018 shows and exhibits significant spatial heterogeneity; (2) the significant increase of NPP was mainly in the restored mining areas, indicating that the ecological restoration of mining areas can effectively improve the regional carbon sequestration capacity; (3) from 1990 to 2018, climate change released 0.136 TgC, while landscape pattern change contributed to carbon storage with 0.266 TgC; and (4) the restoration and reconstruction of vegetation in the mining areas is an important way to achieve carbon neutrality of Huangshi City in the future, and the changes of NPP varied among different ecological restoration modes.

Spatial and Temporal Variations of Habitat Quality and Its Response of Landscape Dynamic in the Three Gorges Reservoir Area, China.

Habitat quality is an important indicator for assessing biodiversity and is critical to ecosystem processes. With urban development and construction in developing countries, habitat quality is increasingly influenced by landscape pattern changes. This has made habitat conservation to be an increasingly urgent issue. Despite the growing interest in this issue, studies that reveal the role of land use change in habitat degradation at multiple scales are still lacking. Therefore, we analyzed the spatial and temporal variations of habitat quality of the Three Gorges Reservoir area by the InVEST habitat quality model and demonstrated the responses of habitat quality to various landscape dynamics by correspondence analysis. The result showed that the habitat quality score of this area increased from 0.685 in 2000 to 0.739 in 2015 and presented a significant spatial heterogeneity. Habitat quality was significantly higher in the northeastern and southwestern parts of the reservoir area than in other regions. Meanwhile, habitat quality improved with altitude and slope, and increased for all altitude and slope zones. The habitat quality of >1000 m and >25° zone exceeds 0.8, while the habitat quality of <500 m and <15° zone is less than 0.6. Habitat quality significantly varied among landscape dynamics and was extremely sensitive to vegetation recovery and urban expansion. The vegetation restoration model of returning farmland to forest is difficult to sustain, so we suggest changing the vegetation recovery model to constructing complex vegetation community. This study helps us to better understand the effects of landscape pattern changes on habitat quality and can provide a scientific basis for formulating regional ecological conservation policies and sustainable use of land resources.

Landscape Dynamics Improved Recreation Service of the Three Gorges Reservoir Area, China.

Spatio-temporal variations of recreation service not only could help to understand the impact of cultural services on human well-being but also provides theoretical and technical support for regional landscape management. However, previous studies have avoided deeply quantifying and analyzing it or have simply focused on assessing recreational service at a single period in time. In this study, we used the InVEST model to evaluate the spatio-temporal variations of recreation service in the Three Gorges Reservoir Area and demonstrated the impact of recreation service on landscape dynamics. The results demonstrated that recreation service increased significantly and presented a significant spatial heterogeneity. Although afforestation and urban expansion both could significantly increase recreation service, the recreation service proxy of the non-vegetation landscape is far higher than that of the vegetation landscape. This finding indicated that human landscape is more attractive to tourists than the natural landscape, so we recommend to strengthen the infrastructure construction for enhancing the accessibility of natural landscapes. Moreover, we propose other constructive suggestions and landscape-design solutions for promoting recreation service. This study shifted the static environmental health assessment to the analysis of recreation service dynamics, bridging the regulatory mechanisms of ecosystem services involved in cultural services.

Mechanism and therapeutic strategies of depression after myocardial infarction.

Depression resulted as an important factor associated with the myocardial infarction (MI) prognosis. Patients with MI also have a higher risk for developing depression. Although the issue of depression after MI has become a matter of clinical concern, the molecular mechanism underlying depression after MI remains unclear, whereby several strategies suggested have not got ideal effects, such as selective serotonin reuptake inhibitors. In this review, we summarized and discussed the occurrence mechanism of depression after MI, such as 5-hydroxytryptamine (5-HT) dysfunction, altered hypothalamus-pituitary-adrenal (HPA) axis function, gut microbiota imbalance, exosomal signal transduction, and inflammation. In addition, we offered a succinct overview of treatment, as well as some promising molecules especially from natural products for the treatment of depression after MI.

Plumula Nelumbinis: A review of traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety. METHODS: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis. RESULTS: Plumula Nelumbinis is used to treat hypertension, arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects, such as protective effects against cardiovascular diseases, neurological diseases, lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in cardiovascular and neurological diseases and perspectives on Plumula Nelumbinis research were discussed. CONCLUSION: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of cardiovascular and neurological diseases, have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary.

Therapeutic potential of ALKB homologs for cardiovascular disease.

Cardiovascular diseases (CVDs) are the leading causes of human death. Recently, ALKB homologs, including ALKBH1-8 and FTO, have been found to have a variety of biological functions, such as histone demethylation, RNA demethylation, and DNA demethylation. These functions may regulate the physiological and pathological processes of CVDs, including inflammation, oxidative stress, cell apoptosis, and mitochondrial, endothelial, and fat metabolism dysfunction. In the present review, we summarize the biological functions of ALKB homologs and the relationship between the ALKB homologs and CVDs. Importantly, we discuss the roles of ALKB homologs in the regulation of oxidative stress, inflammation, autophagy, and DNA damage in CVDs, as well as the practical applications of ALKB homologs inhibitors or agonists in treating CVDs. In conclusion, the ALKBH family might be a promising target for CVDs therapy.

Musca domestica Cecropin (Mdc) Alleviates Salmonella typhimurium-Induced Colonic Mucosal Barrier Impairment: Associating With Inflammatory and Oxidative Stress Response, Tight Junction as Well as Intestinal Flora.

Salmonella typhimurium, a Gram-negative food-borne pathogen, induces impairment in intestinal mucosal barrier function frequently. The injury is related to many factors such as inflammation, oxidative stress, tight junctions and flora changes in the host intestine. Musca domestica cecropin (Mdc), a novel antimicrobial peptide containing 40 amino acids, has potential antibacterial, anti-inflammatory, and immunological functions. It remains unclear exactly whether and how Mdc reduces colonic mucosal barrier damage caused by S. typhimurium. Twenty four 6-week-old male mice were divided into four groups: normal group, control group (S. typhimurium-challenged), Mdc group, and ceftriaxone sodium group (Cs group). HE staining and transmission electron microscopy (TEM) were performed to observe the morphology of the colon tissues. Bacterial load of S. typhimurium in colon, liver and spleen were determined by bacterial plate counting. Inflammatory factors were detected by enzyme linked immunosorbent assay (ELISA). Oxidative stress levels in the colon tissues were also analyzed. Immunofluorescence analysis, RT-PCR, and Western blot were carried out to examine the levels of tight junction and inflammatory proteins. The intestinal microbiota composition was assessed via 16s rDNA sequencing. We successfully built and evaluated an S. typhimurium-infection model in mice. Morphology and microcosmic change of the colon tissues confirmed the protective qualities of Mdc. Mdc could inhibit colonic inflammation and oxidative stress. Tight junctions were improved significantly after Mdc administration. Interestingly, Mdc ameliorated intestinal flora imbalance, which may be related to the improvement of tight junction. Our results shed a new light on protective effects and mechanism of the antimicrobial peptide Mdc on colonic mucosal barrier damage caused by S. typhimurium infection. Mdc is expected to be an important candidate for S. typhimurium infection treatment.

Production of bioactive liver-targeting interferon Mu-IFN-CSP by soluble prokaryotic expression.

A novel liver-targeting interferon (IFN-CSP) was successfully over-expressed in our previous work. The in vitro and in vivo investigation revealed that IFN-CSP has significant anti-hepatitis B virus (HBV) effect and liver-targeting capacity. However, due to the IFN-CSP tends to form inclusion bodies in recombinant Escherichia coli (E. coli), efficient production of the soluble liver-targeting interferon is a challenge. In view of biomedical application, novel strategies for efficiently expressing liver-targeting interferon and overcoming its poor solubility are necessary and important. In the present study, a modified mu-IFN-CSP was designed base on the amino acid mutant of the native IFN-CSP. Meanwhile, the coding sequence of mu-IFN-CSP was optimized for E. coli preferred codon and the induction conditions for expression were optimized by an orthogonal test. After amino acid mutant, codon optimization and induction conditions optimization, the solubility of Mu-IFN-CSP in E. coli was up to 98.4%. The structural comparison and molecular dynamic simulation showed that the Mu-IFN-CSP formed three structure changes and were more stable than the native IFN-CSP. Tissue sections binding assays revealed that Mu-IFN-CSP was also able to specific binding to liver. In vitro anti-HBV activity assays showed that the soluble Mu-IFN-CSP has improved anti-HBV effect in HepG2.2.15 cells compared to the native IFN-CSP. The present study reports for the first time that liver-targeting interferon Mu-IFN-CSP can be expressed as soluble form, and also contributes to further support its application as liver-targeting anti-HBV medicine.