Tunability of electronic properties in the 2D MoS2/α-tellurene/WS2 heterotrilayer via biaxial strain and electric field.

Alpha-tellurene (α-Te), a two-dimensional (2D) material that has been theoretically predicted and experimentally verified, has garnered significant attention due to its unique properties. In this study, we investigated the 2D trilayer MoS2/α-Te/WS2 van der Waals heterostructure with different stacking orders using first-principles calculations. Our results indicate that this heterotrilayer exhibits an intrinsic type-I band alignment and an indirect band gap similar to that of monolayer α-Te. Notably, the band edges of the heterostructure can be modulated by biaxial strain and an external electric field, enabling these edges to arise from different monolayers. This controlled manipulation facilitates the effective separation of photogenerated electron-hole pairs and prolongs the carrier lifetime. Moreover, the heterostructure can undergo a transition from an indirect to a direct band gap under biaxial compressive strain or a moderate negative electric field, and semiconductor-to-metal transition can also be achieved by intensifying the biaxial strain and external electric field. Overall, our research provides valuable theoretical insights into the potential applications of α-Te-based heterostructures, rendering them promising candidates for the next generation of nanodevices.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

How do we share data in COVID-19 research? A systematic review of COVID-19 datasets in PubMed Central Articles.

OBJECTIVE: This study aims at reviewing novel coronavirus disease (COVID-19) datasets extracted from PubMed Central articles, thus providing quantitative analysis to answer questions related to dataset contents, accessibility and citations. METHODS: We downloaded COVID-19-related full-text articles published until 31 May 2020 from PubMed Central. Dataset URL links mentioned in full-text articles were extracted, and each dataset was manually reviewed to provide information on 10 variables: (1) type of the dataset, (2) geographic region where the data were collected, (3) whether the dataset was immediately downloadable, (4) format of the dataset files, (5) where the dataset was hosted, (6) whether the dataset was updated regularly, (7) the type of license used, (8) whether the metadata were explicitly provided, (9) whether there was a PubMed Central paper describing the dataset and (10) the number of times the dataset was cited by PubMed Central articles. Descriptive statistics about these seven variables were reported for all extracted datasets. RESULTS: We found that 28.5% of 12 324 COVID-19 full-text articles in PubMed Central provided at least one dataset link. In total, 128 unique dataset links were mentioned in 12 324 COVID-19 full text articles in PubMed Central. Further analysis showed that epidemiological datasets accounted for the largest portion (53.9%) in the dataset collection, and most datasets (84.4%) were available for immediate download. GitHub was the most popular repository for hosting COVID-19 datasets. CSV, XLSX and JSON were the most popular data formats. Additionally, citation patterns of COVID-19 datasets varied depending on specific datasets. CONCLUSION: PubMed Central articles are an important source of COVID-19 datasets, but there is significant heterogeneity in the way these datasets are mentioned, shared, updated and cited.

Efferocytosis and Respiratory Disease.

Cells are the smallest units that make up living organisms, which constantly undergo the processes of proliferation, differentiation, senescence and death. Dead cells need to be removed in time to maintain the homeostasis of the organism and keep it healthy. This process is called efferocytosis. If the process fails, this may cause different types of diseases. More and more evidence suggests that a faulty efferocytosis process is closely related to the pathological processes of respiratory diseases. In this review, we will first introduce the process and the related mechanisms of efferocytosis of the macrophage. Secondly, we will propose some methods that can regulate the function of efferocytosis at different stages of the process. Next, we will discuss the role of efferocytosis in different lung diseases and the related treatment approaches. Finally, we will summarize the drugs that have been applied in clinical practice that can act upon efferocytosis, in order to provide new ideas for the treatment of lung diseases.

PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases.

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are critical areas of medical research, as millions of people are affected worldwide. In fact, more than 9 million deaths worldwide were associated with respiratory diseases in 2016, equivalent to 15% of global deaths, and the prevalence is increasing every year as the population ages. Due to inadequate treatment options, the treatments for many respiratory diseases are limited to relieving symptoms rather than curing the disease. Therefore, new therapeutic strategies for respiratory diseases are urgently needed. Poly (lactic-co-glycolic acid) micro/nanoparticles (PLGA M/NPs) have good biocompatibility, biodegradability and unique physical and chemical properties, making them one of the most popular and effective drug delivery polymers. In this review, we summarized the synthesis and modification methods of PLGA M/NPs and their applications in the treatment of respiratory diseases (asthma, COPD, cystic fibrosis (CF), etc.) and also discussed the research progress and current research status of PLGA M/NPs in respiratory diseases. It was concluded that PLGA M/NPs are the promising drug delivery vehicles for the treatment of respiratory diseases due to their advantages of low toxicity, high bioavailability, high drug loading capacity, plasticity and modifiability. And at the end, we presented an outlook on future research directions, aiming to provide some new ideas for future research directions and hopefully to promote their widespread application in clinical treatment.

General Model for Defect Dynamics in Ionizing-Irradiated SiO2 -Si Structures.

Irradiation damage is a key issue for the reliability of semiconductor devices under extreme environments. For decades, the ionizing-irradiation-induced damage in transistors with silica-silicon (SiO2 -Si) structures at room temperature has been modeled by a uniform generation of E'γ centers in the bulk silica region through the capture of irradiation-induced holes, and an irreversible conversion from E'γ to Pb centers at the SiO2 /Si interface through reactions with hydrogen molecules (H2 ). However, the traditional model fails to explain experimentally-observed dose dependence of the defect concentrations, especially at low dose rate. Here, it is proposed that the generation of E'γ centers is decelerated because the holes migrate dispersively in disordered silica and the diffusion coefficient decays as the irradiation goes on. It is also proposed that the conversion between E'γ and Pb centers is reversible because the huge activation energy of the reverse reaction can be reduced by a "phonon-kick" effect of the vibrational energy of H2 and Pb centers transferred from nearby nonradiative recombination centers. Experimental studies are carried out to demonstrate that the derived analytic model based on these two new concepts can consistently explain the fundamental but puzzling dose dependence of the defect concentrations for an extremely wide dose rate range.

Recent Advances in Nanomaterials for Asthma Treatment.

Asthma is a chronic airway inflammatory disease with complex mechanisms, and these patients often encounter difficulties in their treatment course due to the heterogeneity of the disease. Currently, clinical treatments for asthma are mainly based on glucocorticoid-based combination drug therapy; however, glucocorticoid resistance and multiple side effects, as well as the occurrence of poor drug delivery, require the development of more promising treatments. Nanotechnology is an emerging technology that has been extensively researched in the medical field. Several studies have shown that drug delivery systems could significantly improve the targeting, reduce toxicity and improve the bioavailability of drugs. The use of multiple nanoparticle delivery strategies could improve the therapeutic efficacy of drugs compared to traditional delivery methods. Herein, the authors presented the mechanisms of asthma development and current therapeutic methods. Furthermore, the design and synthesis of different types of nanomaterials and micromaterials for asthma therapy are reviewed, including polymetric nanomaterials, solid lipid nanomaterials, cell membranes-based nanomaterials, and metal nanomaterials. Finally, the challenges and future perspectives of these nanomaterials are discussed to provide guidance for further research directions and hopefully promote the clinical application of nanotherapeutics in asthma treatment.

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma.

Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma.

A comparative study of patients' satisfaction with different levels of hospitals in Beijing: why do patients prefer high-level hospitals?

BACKGROUND: To promote the integration of medical resources, Beijing has built medical alliances since 2012, but this reform has not changed the state of disordered medical treatment. Patients are still willing to go to high-level hospitals for medical treatment. What causes patients to prefer high-level hospitals? To explore the reasons behind this preference for high-level medical treatment among patients and to guide patients to make visits in an orderly manner, we conducted this study and compared patients' satisfaction with hospitals of different levels in the context of medical resource integration. METHODS: This study conducted a questionnaire survey among 1250 patients who were selected in 18 medical alliances in Beijing from October to December 2016. The study type is a comparative study based on cross-sectional data. Patient satisfaction was the main outcome, and descriptive analysis, chi-square tests, nonparametric tests and binary logistic regression analysis were used. The level of statistical significance was set at p < 0.05. RESULTS: The overall satisfaction score of the medical alliances was 3.375, and the satisfaction scores of core hospitals and cooperative hospitals were 2.77 and 3.07, respectively. The overall patient satisfaction rate was 44.62%, and the satisfaction rates of core hospitals and cooperative hospitals were 34.34 and 50.43%, respectively. The type of hospital and understanding of medical alliance policy were the factors associated with patient satisfaction with the medical alliance. CONCLUSIONS: The patients' satisfaction with cooperative hospitals was higher than their satisfaction with core hospitals. Although the patients were more satisfied with the service attitude of the cooperative hospitals, they still preferred core hospitals due to their higher expectations for their medical treatment and greater trust in their medical technology. It is necessary to explore the establishment of closed medical alliances under the unified management of human and financial resources to enable medical alliances to become a community of common interests and provide integrated medical services for patients.

Identification of lncRNA-miRNA-mRNA regulatory network associated with epithelial ovarian cancer cisplatin-resistant.

To construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network related to epithelial ovarian cancer (EOC) cisplatin-resistant, differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) between MDAH and TOV-112D cells lines were identified. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. Downstream mRNAs or upstream lncRNAs for miRNAs were analyzed at miRTarBase 7.0 or DIANA-LncBase V2, respectively. A total of 485 significant DEGs, 85 DELs, and 5 DEMs were identified. Protein-protein interaction (PPI) network of DEGs contrains 81 nodes and 141 edges was constructed, and 25 hub genes related to EOC cisplatin-resistant were identified. Subsequently, a lncRNA-miRNA-mRNA regulatory network contains 4 lncRNAs, 4 miRNAs, and 35 mRNAs was established. Taken together, our study provided evidence concerning the alteration genes involved in EOC cisplatin-resistant, which will help to unravel the mechanisms underlying drug resistant.

The willingness of patients to make the first visit to primary care institutions and its influencing factors in Beijing medical alliances: a comparative study of Beijing's medical resource-rich and scarce regions.

BACKGROUND: To improve the efficiency of the use of medical resources, China has implemented medical alliances (MAs) to implement a hierarchical diagnosis and treatment system. The willingness to undertake a first visit to primary care institutions (PCIs) is an important indicator of the effect of this system. Beijing has also built MAs since 2013, but to date, there have been few studies on the first visit to PCIs in Beijing. The purpose of this study is to analyze patients' willingness to make their first visit to PCIs and its influencing factors to provide references for the realization of a hierarchical diagnosis and treatment system. METHODS: Two relatively different districts with large differences in resources in Beijing, D and F, were selected, and a self-reported questionnaire and convenience sampling method were applied. A cross-sectional survey was administered to 1221 patients of MAs. The chi-square test and binary logistic regression were used to analyze the influencing factors of patients' willingness to undertake a first visit to a PCI. RESULTS: Fewer patients in District D received medical alliance services (44.42%) than those in District F (59.25%), but patients in District D had a higher degree of satisfaction with the services they received (72.04%) than those in District F (28.96%). Patients in District D had a higher willingness to undertake a first visit (64.00%) than those in District F (58.18%). Patients of an older age, low medical expenses, participation in urban employees' basic medical insurance, a high understanding of MAs and high satisfaction with medical services were indicators of being more willing to choose primary care institutions for their first visit. CONCLUSIONS: The different medical resources and MA constructions in the two districts have resulted in a difference between the two districts in terms of the willingness of individuals to make their first visit to PCIs. Strengthening the service capabilities of PCIs remains a priority. The government should propose solutions to solve the problems encountered in practice and actively promote the realization of MAs and hierarchical diagnosis and treatment.

Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway.

Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Although the anti-inflammatory activity of CBN has been reported, the underpinning mechanism of this remains unclear. In this study, we investigated the anti-inflammatory effect of CBN on lipopolysaccharide (LPS)-stimulated THP-1 cells and explored the possible underlying molecular mechanisms. The results showed that CBN suppressed LPS-mediated inflammatory response mainly through the inactivation of the NOD1 and NF- κ B p65 signaling pathways. Knockdown of NOD1 reduced the degree to which inflammatory cytokines decreased following CBN treatment, whereas forced expression of NOD1 and CBN treatment reduced NF- κ B p65 activation and the secretion of inflammatory cytokines. Furthermore, CBN significantly reduced cellular apoptosis by inhibiting the NOD1 pathway. Collectively, our results indicate that CBN suppressed the LPS-mediated inflammatory response by inhibiting NOD1/NF- κ B activation. Further investigations are required to determine the mechanisms of action of CBN in the inhibition of NOD signaling: However, CBN may be employed as a therapeutic agent for multiple inflammatory diseases.

[miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1].

More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.

Downregulation of miR-199b promotes the acute spinal cord injury through IKKß-NF-κB signaling pathway activating microglial cells.

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

Down-regulation of ether-a-go-go-related gene potassium channel protein through sustained stimulation of AT1 receptor by angiotensin II.

We investigated the effects of AT1 receptor stimulation by angiotensin II (Ang II) on human ether-a-go-go-related gene (hERG) potassium channel protein in a heterogeneous expression system with the human embryonic kidney (HEK) 293 cells which stably expressed hERG channel protein and were transiently transfected with the human AT1 receptors (HEK293/hERG). Western-blot analysis showed that Ang II significantly decreased the expression of mature hERG channel protein (155-kDa band) in a time- and dose-dependent manner without affecting the level of immature hERG channel protein (135-kDa band). The relative intensity of 155-kDa band was 64.7±6.8% of control (P<0.01) after treatment of Ang II at 100nM for 24h. To investigate the effect of Ang II on the degradation of mature hERG channel protein, we blocked forward trafficking from ER to Golgi with a Golgi transit inhibitor brefeldin A (10µM). Ang II significantly enhanced the time-dependent reduction of mature hERG channel protein. In addition, the proteasomal inhibitor lactacystin (5µM) inhibited Ang II-mediated the reduction of mature hERG channel protein, but the lysosomal inhibitor bafilomycin A1 (1µM) had no effect on the protein. The protein kinase C (PKC) inhibitor bisindolylmaleimide 1 (1µM) antagonized the reduction of mature hERG channel protein induced by Ang II. The results indicate that sustained stimulation of AT1 receptors by Ang II reduces the mature hERG channel protein via accelerating channel proteasomal degradation involving the PKC pathway.

[Cardiovascular protection and mechanisms of actions of aerobic exercise].

It is well established that aerobic exercise exerts beneficial effect on cardiovascular system, but the underlying mechanisms are yet to be elucidated. Recent studies have shown that aerobic exercise ameliorates insulin resistance, inflammation and mitochondrial dysfunction which play important roles in the development of cardiovascular disease. In this review, we discussed the underlying mechanisms of the cardioprotective role of aerobic exercise, especially the latest progress in this field.

Exploring the Impact of Adequate Energy Supply on Nutrition, Immunity, and Inflammation in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Background: Chronic Obstructive Pulmonary Disease (COPD) progression in the elderly is notably influenced by nutritional, immune, and inflammatory status. This study aimed to investigate the impact of adequate energy supply on these indicators in COPD patients. Methods: COPD patients meeting specific criteria were recruited and categorized into energy-adequate and energy-deficient groups based on their energy supply. Comparable demographic factors such as age, gender, smoking and drinking history, COPD duration, inhaled drug classification, and home oxygen therapy application were observed. Notable differences were found in BMI and inhaled drug use between the two groups. Results: The energy-adequate group exhibited significant improvements in various health indicators, including lymphocyte count, hemoglobin, CRP, total cholesterol, prealbumin, albumin, PNI, SII, SIRI, CAR, and CONUT scores in the secondary auxiliary examination. These positive changes suggest a notable enhancement in nutritional, immune, and inflammatory status. Conclusion: This research highlights the substantial benefits of adequate energy supply in elderly COPD patients. The observed improvements in nutritional, immune, and inflammatory markers underscore the importance of addressing energy needs to positively influence disease-related outcomes in this population. These findings have implications for developing targeted interventions to optimize the well-being of elderly individuals with COPD.

Pharmacokinetics and bioequivalence evaluation of two oral formulations of cotrimoxazole tablets in healthy Chinese volunteers under fasting conditions.

This bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00-125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions.

Traditional Chinese medicine for acute myelocytic leukemia therapy: exploiting epigenetic targets.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with historically high mortality rates. The treatment strategies for AML is still internationally based on anthracyclines and cytarabine, which remained unchanged for decades. With the rapid advance on sequencing technology, molecular targets of leukemogenesis and disease progression related to epigenetics are constantly being discovered, which are important for the prognosis and treatment of AML. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity and limited side effects. Several biologically active ingredients of TCM are effective against AML. This review focuses on bioactive compounds in TCM targeting epigenetic mechanisms to address the complexities and heterogeneity of AML.

Preparation of Budesonide-Loaded Liposomal Nanoparticles for Pulmonary Delivery and Their Therapeutic Effect in OVA-Induced Asthma in Mice.

Purpose: Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment. Methods: BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed. Results: The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD. Conclusion: BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.