In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Development and applications of lipid hydrophilic headgroups for nucleic acid therapy.

Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest obstacle to this therapy is delivery of the nucleic acids to the target site, which requires overcoming problems such as capture by the immune system, the need to penetrate biofilms, and degradation of nucleic acid performance. Designing suitable delivery vectors is key to solving these problems. Lipids-which consist of a hydrophilic headgroup, a linker, and a hydrophobic tail-are crucial components for the construction of vectors. The headgroup is particularly important because it affects the drug encapsulation rate, the vector cytotoxicity, and the transfection efficiency. Herein, we focus on various headgroup structures (tertiary amines, quaternary ammonium salts, peptides, piperazines, dendrimers, and several others), and we summarize and classify important lipid-based carriers that have been developed in recent years. We also discuss applications of cationic lipids with various headgroups for delivery of nucleic acid drugs, and we analyze how headgroup structure affects transport efficiency and carrier toxicity. Finally, we briefly describe the challenges of developing novel lipid carriers, as well as their prospects.

Application of machine learning for high-throughput tumor marker screening.

High-throughput sequencing and multiomics technologies have allowed increasing numbers of biomarkers to be mined and used for disease diagnosis, risk stratification, efficacy assessment, and prognosis prediction. However, the large number and complexity of tumor markers make screening them a substantial challenge. Machine learning (ML) offers new and effective ways to solve the screening problem. ML goes beyond mere data processing and is instrumental in recognizing intricate patterns within data. ML also has a crucial role in modeling dynamic changes associated with diseases. Used together, ML techniques have been included in automatic pipelines for tumor marker screening, thereby enhancing the efficiency and accuracy of the screening process. In this review, we discuss the general processes and common ML algorithms, and highlight recent applications of ML in tumor marker screening of genomic, transcriptomic, proteomic, and metabolomic data of patients with various types of cancers. Finally, the challenges and future prospects of the application of ML in tumor therapy are discussed.

Sucrose ester embedded lipid carrier for DNA delivery.

Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs' carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems.

Development and applications of mRNA treatment based on lipid nanoparticles.

Nucleic acid-based therapies such as messenger RNA have the potential to revolutionize modern medicine and enhance the performance of existing pharmaceuticals. The key challenges of mRNA-based therapies are delivering the mRNA safely and effectively to the target tissues and cells and controlling its release from the delivery vehicle. Lipid nanoparticles (LNPs) have been widely studied as drug carriers and are considered to be state-of-the-art technology for nucleic acid delivery. In this review, we begin by presenting the advantages and mechanisms of action of mRNA therapeutics. Then we discuss the design of LNP platforms based on ionizable lipids and the applications of mRNA-LNP vaccines for prevention of infectious diseases and for treatment of cancer and various genetic diseases. Finally, we describe the challenges and future prospects of mRNA-LNP therapeutics.

Remarkably Enhanced Room-Temperature Hydrogen Sensing of SnO2 Nanoflowers via Vacuum Annealing Treatment.

In this work, SnO2 nanoflowers synthesized by a hydrothermal method were employed as hydrogen sensing materials. The as-synthesized SnO2 nanoflowers consisted of cuboid-like SnO2 nanorods with tetragonal structures. A great increase in the relative content of surface-adsorbed oxygen was observed after the vacuum annealing treatment, and this increase could have been due to the increase in surface oxygen vacancies serving as preferential adsorption sites for oxygen species. Annealing treatment resulted in an 8% increase in the specific surface area of the samples. Moreover, the conductivity of the sensors decreased after the annealing treatment, which should be attributed to the increase in electron scattering around the defects and the compensated donor behavior of the oxygen vacancies due to the surface oxygen adsorption. The hydrogen sensors of the annealed samples, compared to those of the unannealed samples, exhibited a much higher sensitivity and faster response rate. The sensor response factor and response rate increased from 27.1% to 80.2% and 0.34%/s to 1.15%/s, respectively. This remarkable enhancement in sensing performance induced by the annealing treatment could be attributed to the larger specific surface areas and higher amount of surface-adsorbed oxygen, which provides a greater reaction space for hydrogen. Moreover, the sensors with annealed SnO2 nanoflowers also exhibited high selectivity towards hydrogen against CH4, CO, and ethanol.

An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV.

BACKGROUND: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes serious problems in immunocompromised or immunologically immature hosts. Vaccination is the preferred approach for prevention of HCMV infection, but so far no approved HCMV vaccine is available. In this study, we assessed the immunogenicity and protective immunity of a formalin-inactivated murine cytomegalovirus vaccine (FI-MCMV) in a mouse model in combination with adjuvants MF59, alum, or chitosan. METHODS: Specific-pathogen-free BALB/c mice aged 6-8 weeks were immunized twice, 3 weeks apart, with various doses of FI-MCMV (0.25 µg, 1 µg, 4 µg) with or without adjuvant. Mice were challenged with a lethal dose (5 × LD50) of a more virulent mouse salivary gland-passaged MCMV 3 weeks after the second immunization. The protective immunity of the vaccine was evaluated by determining the survival rates, residual spleen and salivary gland viral loads, body weight changes, and serum anti-MCMV IgG titers. RESULTS: Immunization with FI-MCMV vaccine induced a high level of specific antibody response. Antigen sparing was achieved by the addition of an adjuvant, which significantly enhanced the humoral response to vaccine antigens with a wide range of doses. The level of live virus detected in the spleen on day 5 and in the salivary glands on day 21 after the lethal challenge was significantly lower in adjuvant-treated groups than in controls. Survival rates in adjuvant-treated groups also increased significantly. Furthermore, these protective immune responses were sustained for at least 6 months following immunization. CONCLUSIONS: These results show that inactivated MCMV vaccine is effective, and that the adjuvanted FI-MCMV vaccine provides more effective and longer-term protection than the adjuvant-free vaccine.

Resonant absorption and scattering suppression of localized surface plasmons in Ag particles on green LED.

The metallic-structure dependent localized surface plasmons (LSPs) coupling behaviors with InGaN QWs in a green LED epitaxial wafer are investigated by optical transmission, scanning electron microscopy (SEM) and photoluminescence (PL) measurements. Ag nanoparticles (NPs) are formed by thermal annealing Ag layer on the green LED wafer. SEM images show that for higher annealing temperature and/or thicker deposited Ag layer, larger Ag NPs can be produced, leading to the redshift of absorption peaks in the transmission spectra. Time resolved PL (TRPL) measurements indicate when LSP-MQW coupling occurs, PL decay rate is greatly enhanced especially at the resonant wavelength 560 nm. However, the PL intensity is suppressed by 3.5 folds compared to the bare LED. The resonant absorption and PL suppression are simulated by three dimension finite-difference-time-domain (FDTD), which suggests that Ag particle with smaller size and lower height lead to the larger dissipation of LSP.

GaN-based light-emitting diodes with photonic crystals structures fabricated by porous anodic alumina template.

In this paper, we propose and demonstrate a convenient and flexible approach for preparation large-area of photonic crystals (PhCs) structures on the GaN-based LED chip. The highly-ordered porous anodic alumina (AAO) with pitch of wavelength scale was adopted as a selective dry etching mask for PhCs-pattern transfer. The PhCs with different pore depths were simultaneously formed on the entire surfaces of GaN-based LED chip including ITO, GaN surrounding contacts and the sidewall of the mesa by one-step reactive ion etching (RIE). The light output power improvement of PhCs-based GaN LED was achieved as high as 94% compared to that of the conventional GaN-based LED.