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Pressure‐induced emission enhancement (PIEE) is a novel phenomenon in contrast to conventional pressure‐induced emission quenching, and has attracted considerable attention owing to the potential application of materials with this effect as optical pressure‐sensing devices. The urgent need and significant significance lie in the design and exploration of systems that possess high‐efficiency PIEE. Here, a large PIEE in a novel zero‐dimensional (0D) hybrid manganese bromide is realized, (BPPH)2MnBr4·1.5CH3CN [BPPH+ = bis(triphenylphosphine)iminium]. The experimental and theoretical results demonstrate that such emission enhancement is primarily attributed to the pressure‐induced reconfiguration of electronic band alignment and resultant redistribution of band‐edge excitons. Under compression, the electronic bandgap of (MnBr4)2− experiences a more rapid reduction compared to that of the organic cations. Consequently, this leads to the gradual closure of the charge transfer pathway from (MnBr4)2− to BPPH+. This progression results in a higher retention of excitons on (MnBr4)2−, amplifying the efficiency of Mn2+d–d transitions, and leading to a substantial enhancement in emission. This study not only offers fresh insights into the behavior of carrier dynamics induced by pressure in hybrid manganese halides but also presents a promising avenue for the advancement of PIEE systems. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) organic–inorganic halide perovskites (OIHPs) usually show broadband emission characteristics, which are useful for obtaining white light emissions. However, achieving high standard white light emission using a single halide remains challenging under ambient conditions. Here, we report pressure-induced high-standard white light emission and significant emission enhancement of a 2D OIHP, (CHA)2PbBr4 (CHA = cyclohexylamine). It was found that (CHA)2PbBr4 exhibited significant pressure-induced emission enhancement: a 20- and 3-fold enhancement of the narrow and broadband emissions, respectively, from free excitons and self-trapped excitons. Such a prominent enhancement gives illumination chromaticity coordinates of (0.32, 0.34) at 2.0 GPa, being significantly close to the ideal white light of (0.33, 0.33). Our high-pressure synchrotron powder X-ray diffraction and theoretical calculations reveal that this phenomenon mainly arises from the pressure-induced distortion of the PbBr6 octahedra. This work opens up possibilities for realizing high-standard white light emission of 2D OIHPs via strain engineering. [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction. [ABSTRACT FROM AUTHOR]

The chemical diversity and structural flexibility of lead halide perovskites (LHPs) offer tremendous opportunities to tune their optical properties through internal molecular engineering and external stimuli. Herein, we report the wide‐range and ultrapure photoluminescence emissions in a family of homologous 2D LHPs, [MeOPEA]2PbBr4−4xI4x (MeOPEA=4‐methoxyphenethylammonium; x=0, 0.2, 0.425, 0.575, 1) enabled through internal chemical pressure and external hydrostatic pressure. The chemical pressure, induced by the C−H⋅⋅⋅π interactions and halogen doping/substitution strengthens the structural rigidity to give sustained narrow emissions, and regulates the emission energy, respectively. Further manipulation of physical pressure leads to wide‐range emission tuning from 412 to 647 nm in a continuous and reversible manner. This work could open up new pathways for developing 2D LHP emitters with ultra‐wide color gamut and high color purity which are highly useful for pressure sensing. [ABSTRACT FROM AUTHOR]

Association is the basic unit of plant community classification. Exploring the distribution of plant associations can help improve our understanding of biodiversity conservation. Different associations depend on different habitats and studying the association level is important for ecological restoration, regional ecological protection, regulating the ecological balance, and maintaining biodiversity. However, previous studies have only focused on suitable distribution areas for species and not on the distribution of plant associations. Larix gmelinii is a sensitive and abundant species that occurs along the southern margin of the Eurasian boreal forests, and its distribution is closely related to permafrost. In this study, 420 original plots of L. gmelinii forests were investigated. We used a Maxent model and the ArcGIS software to project the potential geographical distribution of L. gmelinii associations in the future (by 2050 and 2070) according to the climate scenarios RCP 2.6, RCP 4.5, and RCP 8.5. We used the multi‐classification logistic regression analysis method to obtain the response of the suitable area change for the L. gmelinii alliance and associations to climate change under different climate scenarios. Results revealed that temperature is the most crucial factor affecting the distribution of L. gmelinii forests and most of its associations under different climate scenarios. Suitable areas for each association type are shrinking by varying degrees, especially due to habitat loss at high altitudes in special terrains. Different L. gmelinii associations should have different management measures based on the site conditions, composition structure, growth, development, and renewal succession trends. Subsequent research should consider data on biological factors to obtain more accurate prediction results. [ABSTRACT FROM AUTHOR]

Grapevine-related microorganisms affect the health and yield of grapes, the metabolic pathways of the fermentation process, and the regional characteristics of wine. However, the diversity of epidermal microorganisms during the development of berries under the ecological viticulture model has not been described in detail. In this study, high-throughput amplicon sequencing technology was used to perform ITS and 16S sequencing of Cabernet Sauvignon epidermal microbes at different developmental stages in the Wuhai region to investigate the succession of epidermal microbes and their response to developmental stages and vineyard weather. The results showed that the diversity of fungi and bacteria decreased during development. Epidermal microorganisms recruited members according to their developmental stages, but retained the core taxa, such as the fungi genera Alternaria , Jattaea , and Jattaea and the bacteria genera Brevundimonas , Sphingomonas , Acinetobacter , and Pseudomonas. In addition, the microbial diversity was associated with specific meteorological parameters, implying that there was a connection between the environmental conditions of the vineyard and the microbial distribution pattern such as the fungus genus Filobasidium was positively correlated with relative humidity and negatively correlated with average high temperature, average low temperature, and average ground temperature; the bacterium genus Lactobacillus was positively correlated with sunlight time, and negatively correlated with relative humidity. In conclusion, this study can help vineyard managers understand the microbial consortia associated with particular diseases, and also the dynamics of infection processes in order to take preventive actions, especially at the most critical moments. [ABSTRACT FROM AUTHOR]

2D hybrid organic–inorganic perovskites (HOIPs) are highly responsive to external stimuli and therefore have application potential as sensing materials. Though their optical properties upon singular thermal or pressure stimulation have been recently investigated, their dual‐stimuli‐responsive behaviors have not yet been explored. Here, the dual‐stimuli‐responsive luminescence of a pair of new enantiomeric 2D Dion–Jacobson HOIPs, R+[(4‐aminophenyl)ethylamine]PbI4 and S‐[(4‐aminophenyl)ethylamine]PbI4, is reported. The photoluminescence results show that their 485 nm emissions can be red‐shifted by ≈6 nm upon heating, and further increased to 529 nm under pressure. Such dual‐stimuli‐responsive emissions expand their Commission Internationale de L'Eclairage coordinates successively from (0.140, 0.272) to (0.283, 0.473). Detailed structural analysis and first principles calculations reveal that the temperature‐ and pressure‐responsive behaviors arise from the predominant electron–phonon interactions over thermal expansion effect and pressure‐induced in‐plane PbI bond contraction, respectively. The findings open up a new pathway to successively tune the optical emission of 2D HOIPs via a dual‐stimuli‐responsive approach. [ABSTRACT FROM AUTHOR]

Fas‐associated factor 1 (FAF1) has gained a reputation as a member of the FAS death‐inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE‐19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii‐induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii‐induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1‐dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation. [ABSTRACT FROM AUTHOR]

Introduction: Overexpressed inflammatory cytokines are the main factors causing rheumatoid arthritis (RA) tissue damage and pathological deterioration, and lncRNAs has found to beinvolved in some autoinflammatory diseases. Methods: We designed this study to investigate the effect of lncRNA linc00152 on rheumatoid arthritis inflammation and explore its molecular mechanism.Result: We found that linc00152 was not only up‐regulated in rheumatoid arthritis fibroblast‐like synoviocytes (RAFLS), but also stimulated by TNF‐α/IL‐1β in adose‐ and time‐dependent manner in RAFLS and this expression depends on the NF‐κB signaling pathway. Conversely, linc00152 promoted TNF‐α/IL‐1β expression in RAFLS induced by TNF‐α/IL‐1β. In addition, we found that linc00152 promoted TAK1 expression by targeting inhibition of miR‐103a and activated TAK1‐mediated NF‐κB pathway. NF‐kB indirectly promotes linc00152 expression by promoting the transcription activity of YY1, and YY1 directly promotes linc00152 expression by binding the promoter of linc00152. Conclusion: Our data suggested that the linc00152/NF‐κB feedback loop promotes RAFLS inflammation via regulating miR‐103a/TAK1 axis and YY1 expression. Thus, linc00152 acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Methods: Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. Results: AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through NOX4 and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, NOX4 expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. Conclusion: AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways. [ABSTRACT FROM AUTHOR]

Piezoelectric hybrid organic–inorganic perovskites have attracted significant attention due to their outstanding piezoelectricity comparable to perovskite oxides. However, their elastic properties, which determine the piezoelectric performance, have not yet been explored. Here, the elastic properties of a perovskite ferroelectric TMCM-CdCl3 (TMCM = trimethylchloromethyl ammonium) with a large piezoelectric effect are comprehensively investigated. High-pressure synchrotron powder x-ray diffraction experiments reveal that it exhibits a low bulk modulus of 14.58 GPa, which is an order of magnitude lower than those of perovskite oxides. In addition, Young's moduli and shear moduli were calculated using density functional theory, and their values are significantly smaller than perovskite piezoceramics. Furthermore, the acoustic properties of TMCM-CdCl3 were calculated. Its longitudinal wave velocity is 3.86 km s−1–4.94 km s−1, and the corresponding specific acoustic impedance is 8.28 MRayl–10.21 MRayl. These maximum values are, respectively, 31.5%, 74.4%, and 8.4%, 73.1% lower than those from BaTiO3 and PbTiO3. Our findings disclose the soft nature and low acoustic impedance of hybrid perovskite piezoelectrics, which are critical to their applications in energy conversion devices. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of moxibustion at different times of the menstrual cycle for patients with primary dysmenorrhea (PD). Patients and Methods: Participants were 208 patients allocated to three controlled groups: one pre-menstrual treatment group (Group A), one menstrual-onset treatment group (Group B), and one waiting-list group (Group C). Groups A and B received the same intervention of moxibustion on points SP6 and RN4 but at different times. Group C, the waiting-list group, received no treatment throughout the study. Cox Menstrual Symptom Scale (CMSS) score was the primary outcome. Secondary outcomes were visual analog scale (VAS) score of pain intensity, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score. CMSS and VAS scores were obtained at the baseline stage (three cycles), treatment stage (three cycles), and follow-up stage (three cycles), a total of seven evaluations. SAS and SDS scores were obtained on the day of group allocation and the first day of the follow-up stage, a total of two evaluations. Results: Baseline characteristics were comparable across the three groups. Pain duration (CMSS score) was significantly higher in Group C than in the other two groups at each evaluation (P< 0.001). There was also a significant difference in the improvement in pain duration between Group B and Group C (P< 0.001) throughout the trial. There were no significant changes in pain severity (CMSS score) after the 3-month treatment in Group A and Group B (P> 0.05). Secondary outcomes showed that pre-menstrual moxibustion (Group A) was as effective as menstrual-onset moxibustion (Group B) in relieving pain intensity (VAS score) and negative mood (SDS and SAS scores). Conclusion: Moxibustion appears as an effective treatment for PD. Pre-menstrual application is more effective than menstrual-onset application. Trial Registration Chictr.org.cn Identifier: ChiCTR-TRC-14004627. [ABSTRACT FROM AUTHOR]

The retina is the primary site of Toxoplasma gondii infection in the eye, and choroidal neovascularization in ocular toxoplasmosis is one of the most important causes of visual impairment. Vascular endothelial growth factor (VEGF) is one of the key regulators of blood vessel development, however, little is known about the mechanisms of T. gondii -induced VEGF production in ocular toxoplasmosis. Here, we investigate the effect of T. gondii on VEGF production regulation in human retinal pigment epithelium ARPE-19 cells and attempted to unveil the underlying mechanism of this event by focusing on the interaction between parasite and the selected host intracellular signaling pathways. T. gondii infection increased the expression of VEGF mRNA and protein in ARPE-19 cells in parasite burden- and infection time-dependent manner. The proportional increase of VEGF upstream regulators, HIF-1α and HO-1, was also observed. T. gondii induced the activation of host p-AKT, p-ERK1/2, and p-p38 MAPK in ARPE-19 cells in a parasite-burden dependent manner. However, VEGF expression decreased after the pre-treatment with PI3K inhibitors (LY294002 and GDC-0941), ERK1/2 inhibitor (PD098059), and p38 MAPK inhibitor (SB203580), but not JNK inhibitor (SP600125), in a dose-dependent manner. The anti-VEGF agent bevacizumab or VEGF siRNA transfection prominently inhibited the activation of p-AKT and p-ERK1/2, but not p-p38 MAPK and JNK1/2 in T. gondii -infected ARPE-19 cells. Bevacizumab treatment or VEGF siRNA transfection significantly inhibited the proliferation of T. gondii tachyzoites in the host cell, dose-dependently, but not invasion of parasites. VEGF-receptor 2 (VEGF-R2) antagonist, SU5416, attenuated VEGF production and tachyzoite proliferation in T. gondii -infected ARPE-19 cells in a dose-dependent manner. Collectively, T. gondii prominently induces VEGF production in ARPE-19 cells, and VEGF and AKT/ERK1/2 signaling pathways mutually regulate each other in T. gondii -infected ARPE-19 cells, but not p38 MAPK and JNK1/2 signaling pathways. VEGF and VEGF-R2 control the parasite proliferation in T. gondii -infected ARPE-19 cells. From this study, we revealed the putative mechanisms for VEGF induction as well as the existence of positive feedback between VEGF and PI3K/MAPK signaling pathways in T. gondii -infected retinal pigment epithelium. [ABSTRACT FROM AUTHOR]

Abstract: Arginyl-fructose (AF) and arginyl-fructosyl-glucose (AFG) are products of the Maillard reaction between arginine and reducing sugars during the thermal treatment of Asian ginseng (Panax ginseng C.A. Meyer). AF and AFG are widely distributed in red ginseng. Because there is no AFG in fresh Asian ginseng, the objective of the present study was to identify the arginine derivatives present in fresh Panax quinquefolius L. Two compounds obtained from P. quinquefolius L. were identified as AF and AFG by comparing the 13C NMR and MS (mass spectrometry) spectra with those of standards. We propose that the Maillard reaction may exist in the fresh plant and not only during the thermal processing of ginseng. The antioxidant activities of AF and AFG were investigated in vitro. The data indicate that the Maillard reaction products AF and AFG contribute to the antioxidant activity of P. quinquefolius L. [Copyright &y& Elsevier]

It is found that Professor Yuan Deyu is the first one in China who defined the technology as a process after reading lots of earlier works of Chinese scientific history and Japanese theory of technology. He has expressed and expounded the argument in many works. Based on the Sino-Japanese comparative technology studies, he turned his study from the theory defining technology as a process into the study on technological innovation, in which the technological innovation is considered as the process of technological industrialization, commercialization and socialization, thus laying a theoretical foundation preliminarily for further studies on the theories of both technology and technological innovation. A comprehensive review is given to his theory defining technology as a process as well as the theory of technological innovation, and three important revelations are thus given. [ABSTRACT FROM AUTHOR]

Two-dimensional lead halide perovskites (2D LHPs) can be generally categorized into the Ruddlesden-Popper (RP) and Dion-Jacobson (DJ) phases, with unbiased and biased structural packing manners, respectively. To distinguish the two different phases during materials discovery, the synthesis has heavily relied on the traditional trial-and-error methods which severely delay the rapid development of these emerging 2D materials. In this work, we applied machine learning (ML) to accelerate the synthetic development of (100)-oriented 2D A 2 BX 4 and ABX 4 LHPs (A = organic amine cation, B = Pb, X = halide). The experimentally available 264 crystal structures were used as training data for our ML model to identify the descriptors influencing the formation of the RP- and DJ-phases. The number of nitrogen atoms able to be protonated, the heteroatom type, and the nitrogen content of the organic amine are identified as the most influential factors. To validate our model, three organic amines were tested by growing single crystals and two of the three new structures are consistent with our ML results. This study takes one step further toward the rational synthesis of RP- and DJ-phase hybrid 2D LHPs via an approach of ML. [Display omitted] [ABSTRACT FROM AUTHOR]

Understanding the diversity and evolution of microorganisms during wine fermentation is essential for controlling its production. However, the flavors profiles associated with microbiota changes during the spontaneous fermentation have not yet been described in detail. In this study, we explored the correlations between microbial community with physicochemical properties and flavor components during the spontaneous fermentation of Cabernet Sauvignon wine. Microbial community diversity at different fermentation stages was identified using high-throughput sequencing, and physicochemical properties and volatile compounds were identified through fermentation features testing and headspace solid phase microextraction gas chromatography mass spectrometry. First, the diversity of the fungi community decreased with the fermentation process, whereas the bacteria did not change significantly until the end of the fermentation. Second, the changes of the fermentation environment had reshaped the diversity and composition of the microbial community. Finally, Aureobasidium , Cladosporium , Filobasidium , Hanseniaspora , Hannaella , Saccharomyces , Alternaria , Wickerhamomyce , Starmerella , Candida , Papiliotrema , Bradyrhizobium , Gluconobacter , Leuconostoclia , Comamonas , Acetobacter , and Massilia , were significantly correlated with changes of physicochemical properties and volatile compounds. Overall, our research results provide important insights for understanding the metabolically active microbiota, which is conducive to the expression of wine " terroir ". • Microbial community succession during the spontaneous fermentation of Cabernet Sauvignon wine. • The changes of the fermentation environment had reshaped the diversity and composition of the microbial community. • Volatile compounds varied with fermentation stage. • The OPLS-DA model was used to determine differential metabolites. • Metabolic map of important genera during the spontaneous fermentation of Cabernet Sauvignon wine. [ABSTRACT FROM AUTHOR]

Targeting altered expression and/or activity of GABA transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABA A inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon (IFN I)-independent manner. Stimulation of the STING-GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GATs expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits. Significance Statement GABA concentration in extracellular space is maintained by GABA release and clearance of GABA back to brain cells for degradation. GABA clearance from the synaptic cleft predominantly depends on level and activity of GABA transporters (GATs) in the brain. Insufficient GABA clearance resulted to an aberrant tonic GABA A inhibition in brain. In this study, we have identified an unusually high GABA content in brain of STING-deficient mice, resulting in cognitive impairment. Our results show that STING regulates GATs expression through STING-TBK1-IRF3 pathway and thus regulates GABAergic tone. This is the first study that indicates that the STING-TBK1-IRF3 signaling pathway maintains GABA homeostasis in brain, which may offer a novel therapeutic target for modulating GABAergic tone in cases of cognitive dysfunction., (Copyright © 2024 the authors.)

The engineering of tunable photoluminescence (PL) in single materials with a full-spectrum emission represents a highly coveted objective but poses a formidable challenge. In this context, the realization of near-full-spectrum PL emission, spanning the visible light range from 424 to 620 nm, in a single-component two-dimensional (2D) hybrid lead halide perovskite, (ETA)2PbBr4 (ETA+ = (HO)(CH2)2NH3+), is reported, achieved through high-pressure treatment. A pressure-induced phase transition occurs upon compression, transforming the crystal structure from an orthorhombic phase under ambient conditions to a monoclinic structure at high pressure. This phase transition driven by the adaptive and dynamic configuration changes of organic amine cations enables an effective and continuous narrowing of the bandgap in this halide crystal. The hydrogen bonding interactions between inorganic layers and organic amine cations (N-H…Br and O-H…Br hydrogen bonds) efficiently modulate the organic amine cations penetration and the octahedral distortion. Consequently, this phenomenon induces a phase transition and results in red-shifted PL emissions, leading to the near-full-spectrum emission. This work opens a possibility for achieving wide PL emissions with coverage across the visible light spectrum by employing high pressure in single halide perovskites., (© 2024 Wiley‐VCH GmbH.)

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Chen, Jiang, Han, Lin, Yang, Quan, Xiong and Chen.)

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3 -/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1β and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3 -/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.

Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, CK2β, VEGF, GCL, GST, and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

Objective: To observe the curative effect of porous tantalum rod and Gugutou Huaisiyu Capsule (GHC) for steroid-induced osteonecrosis of femoral head (SONFH)., Methods: A total 60 hips of 50 SONFH patients were randomly assigned to the treatment group and the control group according to grouping time, 25 in each group (30 hips). Patients in the control group were implanted with porous tantalum rod, while those in the treatment group additionally took GHC (5 pills each time, three time per day for 2 successive months; and then twice per day for 4 successive months). Then all patients were followed-up to observe Harris hip score. The curative effect and the femoral head survival time were assessed., Results: A total of 49 patients (59 hips) were followed-up. The Harris hip score of the two groups at the final follow-up was significantly improved after treatment, with statistical difference when compared with before treatment (P < 0.01). Besides, it was higher in the treatment group than in the control group. The curative effect and the survival time were superior in the treatment group, with statistical difference when compared with the control group (P < 0.05)., Conclusions: Porous tantalum rod combined GHC got better effect in treating SONFH. It could significantly improve the function of affected hips and prolong the survival time of femoral head.

With adjacent semi-moving dune as the control, this paper studied the effects of 5-, 10- and 22-year old Hedysarum fruticosum plantations on the nutrient status, microbial biomass, and enzyme activities at the soil depths 0-10, 10-20 and 20-30 cm. The results showed that with the establishment of H. fruticosum plantation on moving dune, soil C, N, P and K contents and biological activities increased obviously with the increasing age of the plantation, and the increment was much higher at 0-10 cm than at 10-20 and 20-30 cm. At 0-30 cm, soil C/N increased from 7.3 to 8.5, and microbial biomass C, N and P as well as the activities of urease, protease, saccharase, phosphomonoesterase, dehydrogenase, polyphenol oxidase and nitrate reductase all increased. Among the test enzyme activities, saccharase activity had the most significant increase, with its value at 0-10 cm being 49.7-284.5 times of the control. There were significant positive correlations between soil microbial biomass C, N and P and organic C, total N and total P, respectively, and between soil microbial biomass and enzyme activities.