Thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in Talaromyces marneffei infection.

Macrophage-derived inflammatory cytokines are critical for host defense against Talaromyces marneffei (T. marneffei) infection among HIV/AIDS patients, and excessive inflammatory cytokines are associated with poor outcomes of AIDS-associated talaromycosis. However, the underlying mechanisms of macrophage-caused pyroptosis and cytokine storm are poorly understood. Here, in the T. marneffei-infected mice and macrophages, we show that T. marneffei induced pyroptosis in macrophages through the NLRP3/caspase-1 pathway. The immunomodulatory drug thalidomide could promote the pyroptosis of macrophages infected T. marneffei. In T. marneffei-infected mice, the splenic macrophages underwent increasing pyroptosis as talaromycosis deteriorated. Thalidomide ameliorated inflammation of mice, while amphotericin B (AmB) in combination with thalidomide did not improve overall survival compared with AmB alone. Taken together, our findings suggest that thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in T. marneffei infection.

A Reliable Murine Model of Disseminated Infection Induced by Talaromyces Marneffei.

Talaromycosis (penicilliosis) caused by Talaromyces marneffei is one of the most important opportunistic infection diseases in tropical countries of South and Southeast Asia. Most infections occurred in individuals with human immunodeficiency virus (HIV) and the primarily reason for the increase in the number of the cases is HIV pandemic. The pathogenesis of T. marneffei infection is unclear. There is still no ideal animal model for studying talaromycosis. In this study, we developed a stable, safe and maneuverable murine model that mimics human T. marneffei disseminated infection using T. marneffei yeast intraperitoneal injected to BALB/c nude mice. We successfully observed symptoms similar to those seen in clinical patients in this murine model, including skin lesions, hepatosplenomegaly, pulmonary infection and mesenteric lesions. We further studied the pathological changes of various tissues and organs in the infected animals to help better understand the severity of the infection. This model may provide a good tool for studying disseminated infection induced by T. marneffei.

[An Integrated Digital Magnetic Resonance Imaging Spectrometer].

An integrated digital magnetic resonance imaging spectrometer was proposed in this study. By using the FPGA chip Artix7 200T, timing control, data processing, digital frequency conversion and phase control were implemented into a single-chip, thus effectively improved timing accuracy and phase accuracy, while avoided the structural design complexity caused by multi-board connection and improved system integration and imaging quality.

Full spectral optical modeling of quantum-dot-converted elements for light-emitting diodes considering reabsorption and reemission effect.

Quantum dots (QDs) have attracted significant attention in light-emitting diode (LED) illumination and display applications, owing to their high quantum yield and unique spectral properties. However, an effective optical model of quantum-dot-converted elements (QDCEs) for (LEDs) that entirely considers the reabsorption and reemission effect is lacking. This suppresses the design of QDCE structures and further investigation of light-extraction/conversion mechanisms in QDCEs. In this paper, we proposed a full spectral optical modeling method for QDCEs packaged in LEDs, entirely considering the reabsorption and reemission effect, and its results are compared with traditional models without reabsorption or reemission. The comparisons indicate that the QDCE absorption loss of QD emission light is a major factor decreasing the radiant efficacy of LEDs, which should be considered when designing QDCE structures. According to the measurements of fabricated LEDs, only calculation results that entirely consider reabsorption and reemission show good agreement with experimental radiant efficacy, spectra, and peak wavelength at the same down-conversion efficiency. Consequently, it is highly expected that QDCE will be modeled considering the reabsorption and reemission events. This study provides a simple and effective modeling method for QDCEs, which shows great potential for their structure designs and fundamental investigations.

Lactobacillus murinus: A key factor in suppression of enterogenous Candida albicans infections in Compound Agrimony enteritis capsules-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Agrimony (FuFangXianHeCao, FFXHC) Enteritis Capsules is an ethnomedicine that is derived from Yi Nationality Herbal Medicine for enteritis treatment. We found that FFXHC reduced the mortality outcomes in enterogenic Candida albicans infected mice models and increased the abundance of Lactobacillus murinus in the intestines. Lactobacillus murinus exhibited comparable therapeutic effects to those of FFXHC in enterogenic Candida albicans infected mice. This study provides novel perspectives into the pharmacological mechanisms of FFXHC. AIM OF THE STUDY: We investigated the mechanisms via which FFXHC inhibits C. albicans infections and its effects on L. murinus. MATERIALS AND METHODS: Enterogenous C. albicans infection mice models were established and various parameters, including survival rate, weight change, number of colonies, treatment effects on intestinal mucosa, microecology, and immune cytokines evaluated. Susceptibility of C. albicans to L. murinus was evaluated in vitro. RESULTS: Treatment with FFXHC reduced the number of colonies, improved the health status, enhanced the survival rates, increased the abundance of L. murinus, reduced damage to the intestinal mucosa, and elevated occludin as well as claudin-1 levels. Interestingly, TNF-α, IFN-γ, IL-10, IL-22, and IL-17A levels were increased while IL-1ß levels were suppressed in the intestinal mucosa without any change in peripheral blood cytokine levels. Moreover, FFXHC promoted L. murinus proliferation. This study also confirmed the incubation-dependent anti-C. albicans effects exerted by the metabolic supernatants of L. murinus. CONCLUSIONS: FFXHC effectively alleviated intestinal infections of C. albicans in mice and increased the abundance of L. murinus. Supplementation of L. murinus in food can achieve the effects that are comparable to those of FFXHC. Thus, L. murinus maybe essential in FFXHC-based treatment of intestinal C. albicans infections.

Perovskite-Gallium Nitride Tandem Light-Emitting Diodes with Improved Luminance and Color Tunability.

Tandem structures with different subpixels are promising for perovskite-based multicolor electroluminescence (EL) devices in ultra-high-resolution full-color displays; however, realizing excellent luminance- and color-independent tunability considering the low brightness and stability of blue perovskite light-emitting diodes (PeLEDs) remains a challenge. Herein, a bright and stable blue gallium nitride (GaN) LED is utilized for vertical integration with a green MAPbBr3 PeLED, successfully achieving a Pe-GaN tandem LED with independently tunable luminance and color. The electronic and photonic co-excitation (EPCE) effect is found to suppress the radiative recombination and current injection of PeLEDs, leading to degraded luminance and current efficiency under direct current modulation. Accordingly, the pulse-width modulation is introduced to the tandem device with a negligible EPCE effect, and the average hybrid current efficiency is significantly improved by 139.5%, finally achieving a record tunable luminance (average tuning range of 16631 cd m-2 at an arbitrary color from blue to green) for perovskite-based multi-color LEDs. The reported excellent independent tunability can be the starting point for perovskite-based multicolor EL devices, enabling the combination with matured semiconductor technologies to facilitate their commercialization in advanced display applications with ultra-high resolution.

Toward 200 Lumens per Watt of Quantum-Dot White-Light-Emitting Diodes by Reducing Reabsorption Loss.

In this study, we analyze the influence of the pore structure of an SBA-15 particle on the light emission from its inner adsorbed quantum dots (QDs) and outer light-emitting diode (LED) chips. It is found that the particle features of a high refractive index, comparable feature size of pore structure, and lower amount of QD adsorption help with QD light extraction, demonstrating a mechanism to suppress QD light propagating through pores and thus reducing the reabsorption loss. We consequently developed highly efficient QD white LEDs with wet-mixing QD/SBA-15 nanocomposite particles (NPs) by further optimizing the packaging methods and the introduced NP mass ratio. The LEDs demonstrated a record luminous efficacy (the ratio of luminous flux to electrical power) of 206.8 (entrusted test efficiency of 205.8 lm W-1 certificated by China National Accreditation Service) and 137.6 lm W-1 at 20 mA for white LEDs integrating only green QDs and green-red QD color convertors, respectively, with improved operating stability. These results are comparable to conventional phosphor-based white LEDs, which can be a starting point for white LEDs only using QDs as convertors toward commercialization in the near future.

Antifungal Activity and Potential Mechanism of 6,7, 4'-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans.

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4'-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188-0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

Activity of Compound Agrimony Enteritis Capsules against invasive candidiasis: Exploring the differences between traditional Chinese medicine prescriptions and its main components in the treatment of diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Agrimony Enteritis Capsules (FFXHC) is an ethnomedicine derived from Yi Nationality Herbal Medicine for the treatment of enteritis. We found that compared to berberine hydrochloride (BBR), a component of this medicine, FFXHC was more efficacious in the mouse model of IC mice in significantly alleviating lung and intestinal lesions. " Our study provides a novel perspective into the pharmacological mechanism of action of the ethnic compound FFXHC. AIM OF THE STUDY: To determine the underlying mechanism of the superiority of FFXHC over BBR in IC. MATERIALS AND METHODS: The susceptibility of Candida albicans to FFXHC was evaluated in vitro. The mouse model of IC was established and the survival rate, weight change, the number of organ colonies, and immune organ coefficient of the mice were determined, the effect of FFXHC on the immune function of mice, including changes in the number of immune cells, levels of the related inflammatory cytokines (INF-γ, TNF-α, MCP-1, IL-6, and IL-17A), and the antimicrobial peptide, LL-37 (CRAMP in mice), were determined. Mice feces were collected and changes in the intestinal microecology were studied. RESULTS: Our findings indicated that FFXHC was not active against Candida albicans and did not restore the sensitivity of the resistant strain in vitro; however, it had a therapeutic effect that improve survival rate on mice with IC. The number of lymphocytes and neutrophils of mice with IC treated with FFXHC increased significantly. The intestinal microecology of mice was restored and the abundance of the probiotic Bacteroides was increased, which further stimulated the production of the antimicrobial peptide, LL-37, which is required for acquired immunity. Furthermore, the levels of Th cell-related cytokines, including INF-γ, TNF-α, and IL-17A were significantly increased, whereas those of the proinflammatory cytokines, IL-6 and MCP-1, decreased. With the activation of acquired immunity, the immune function of mice was restored, the body weight and survival rate of mice improved considerably, the coefficients of the thymus and spleen increased, and the number of fungal colonies in the lung and kidney decreased. CONCLUSIONS: FFXHC could eliminate fungi by increasing the relative abundance of probiotics in Bacteroides and the number of neutrophils, thereby promoting the production of CRAMP and resulting in a fungicidal effect, leading to acquired immunity. Although BBR has an antifungal effect, we found that it was not as effective as FFXHC.