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Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11‐like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT‐ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7‐SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development. Summary statement: Efectors SJP1 and SJP2 interact with and destabilise the bifunctional regulator ZjTCP7 to modulate flowering‐related ZjFT‐ZjFD pathway and branching signalling controlled by ZjBRC1 in jujube, suggesting a novel regulatory mechanism mediated by JWB phytoplasmas to modulate host plant development. [ABSTRACT FROM AUTHOR]

Aim: We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation. Methods: The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpredictable mouse stress (CUMS) model. Through open field, elevated plus maze, forced swimming, and tail suspension tests, the effects of GAS on the CUMS mice behaviors were examined, and the levels of neurotransmitters were detected. The histopathological changes were assayed by H&E and IHC staining, and the protein expressions were detected by Western blotting. Small molecule‐protein docking and molecular dynamics experiments were conducted to simulate the binding mode between GAS and Caspase‐3. Results: Network pharmacological analysis revealed that Caspase‐3 was the action target of GAS. GAS could improve depression‐like behaviors in CUMS mice, elevate their neurotransmitter levels, ameliorate their nerve cell injury, and inhibit their Caspase‐3 expression. After knocking out Caspase‐3, the effects of GAS were inhibited. Molecular dynamics simulation and small molecule‐protein docking found that GAS bound to Caspase‐3 at SER25, inhibiting the maturation and activation of Caspase‐3. Conclusion: We find that GAS can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis. [ABSTRACT FROM AUTHOR]

To explore the antidepressant effects and targets of atractylenolide I (ATR) through a network pharmacological approach. Relevant targets of ATR and depression analyzed by network pharmacology were scored (identifying 5‐HT2A targets). Through elevated plus maze, open field, tail suspension, and forced swimming tests, the behavioral changes of mice with depression (chronic unpredictable mild stress [CUMS]) were examined, and the levels of neurotransmitters including serotonin, dopamine, and norepinephrine (5‐HT, DA, and NE) were determined. The binding of ATR to 5‐HT2A was verified by small molecular‐protein docking. ATR improved the behaviors of CUMS mice, elevated their levels of neurotransmitters 5‐HT, DA, and NE, and exerted a protective effect on their nerve cell injury. After 5‐HT2A knockout, ATR failed to further improve the CUMS behaviors. According to the results of small molecular‐protein docking and network pharmacological analysis, ATR acted as an inhibitor by binding to 5‐HT2A. ATR can improve the behaviors and modulate the neurotransmitters of CUMS mice by targeting 5‐HT2A. [ABSTRACT FROM AUTHOR]

Aim: We investigated the mechanism, whereby tumor necrosis factor‐like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD). Methods: The cognitive and behavioral abilities of mice were assessed by Morris water maze and open field tests, while the levels of key A1 and A2 astrocyte factors were detected by RT‐qPCR. Immunohistochemical (IHC) staining was used to examine the expression of GFAP, western blot was used to assay the levels of related proteins, and enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. Results: The results showed that TL1A could promote the progression of cognitive dysfunction in mice. Astrocytes differentiated into A1 phenotype, while unobvious changes were noted in astrocyte A2 biomarkers. Knockout of NLRP3 or intervention with NLRP3 inhibitor could inhibit the effect of TL1A, improving the cognitive dysfunction and suppressing the A1 differentiation. Conclusion: Our results demonstrate that TL1A plays an important role in POCD in mice, which promotes the A1 differentiation of astrocytes through NLRP3, thereby exacerbating the progression of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Aim of this research was to examine the impact of paeoniflorin (Pae) in suppressing the occurrence of ferroptosis in individuals with Alzheimer's disease (AD). The study utilized APP/PS1 mice with AD as the experimental subjects. Following the administration of Pae, the cognitive behaviors of mice were evaluated and the key indexes of ferroptosis were measured, as well as levels of oxidative stress (OS). For in‐vitro experiments, Erastin was adopted for inducing the ferroptosis of PC12 cells, and the level of cell ferroptosis was detected after Pae treatment. Pae improved the cognitive ability of AD mice, reduced the level of ferroptosis, decreased the iron ion and MAD levels in brain tissues, and increased SOD expression. In PC12 cells, Pae suppressed the Erastin‐induced ferroptosis, mitigated oxidative damage, and reduced the level of ROS. Based on the findings from our research, it was observed that Pae exhibited a specific binding affinity to P53, leading to the suppression of ferroptosis. This mechanism ultimately resulted in the improvement of nerve injury in mice with AD. [ABSTRACT FROM AUTHOR]

This work aimed to investigate the role and mechanism of NADPH oxidase 4 (NOX4) in the polarization of microglial cells. Microglial cells were transfected with the NOX4 overexpression plasmid (pGL3‐NOX4), and later treated with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ) to induce its M1 polarization. Later, the F4/80 + CD86 + cell proportion was detected by flow cytometry (FCM), the inflammatory factor expression levels were analyzed through enzyme‐linked immunosorbent assay (ELISA), while ionized calcium binding adapter molecule 1 (IBA‐1) and PKM2 expression were measured by immunofluorescence (IF) staining. In addition, dichlorodihydrofluorescein diacetate probe was utilized to detect the reactive oxygen species (ROS) levels, glucose uptake, and glycolysis, as well as lactic acid level. The expression of glycolytic enzymes PKM2, HK2, and citrate (Si)‐synthas (CS) was detected by Western‐blot (WB) assay. Moreover, the polarization level of microglial cells was detected after ROS expression was suppressed by the ROS inhibitor N‐acetylcysteine (NAC). In mouse experiments, LPS was applied in inducing central neuroinflammation in NOX4 knockdown mouse model (KO) and wild‐type mice (WT). Thereafter, the inflammatory factor levels and lactic acid level in mouse tissues were detected; IBA‐1 and CD86 expression in mice was measured by IF staining; and the expression of glycolytic enzymes PKM2, HK2, and CS in the central nervous system (CNS) was also detected. After NOX4 overexpression in microglial cells, the M1 polarization level was upregulated, the F4/80 + CD86 + cell proportion increased, and inflammatory factors were upregulated. At the same time, the expression of glycolytic enzymes PKM2, HK2, and CS was upregulated. NAC pretreatment suppressed the effects of NOX4, reduced the F4/80 + CD86 + cell proportion, and suppressed the expression of PKM2, HK2, and CS. In the mouse model, the expression levels of CD86 in KO group decreased, and the inflammatory factors were also downregulated. NOX4 promotes glycolysis of microglial cells via ROS, thus accelerating M1 polarization and inflammatory factor expression. In this regard, NOX4 is promising as a new target for the treatment of neuroinflammation. Highlight: 1.NOX4 can promote microglial cells M1 polarization.2.NOX4 promotes glycolysis of microglial cells via reactive oxygen species, thus accelerating M1 polarization and inflammatory factor expression.3.NOX4 is promising as a new target for neurological treatment. [ABSTRACT FROM AUTHOR]

Visit-to-visit variability of glycated hemoglobin (HbA1c) is a marker of long-term glycemic fluctuation, which has been related to increased risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM). The association between HbA1c variability and retinopathy in patients with T2DM, however, has been inconsistent in previous studies. In order to fully evaluate the above association, we conducted a meta-analysis. Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Web of Science, and Embase databases. Studies with HbA1c variability evaluated as the standard deviation (SD) and/or the coefficients of variation (CV) of HbA1c were included. The results were analyzed using a random-effects model that incorporated potential heterogeneity between studies. Twelve observational studies involving 44 662 T2DM patients contributed to the meta-analysis. Overall, 5150 (11.5%) patients developed retinopathy. Pooled results showed that compared to patients with lower HbA1c variability, T2DM patients with higher HbA1c-SD (relative risk [RR]: 1.48, 95% confidence interval [CI]: 1.24 to 1.78, p<0.001, I2=34%) and higher HbA1c-CV (RR: 1.29, 95% CI: 1.05 to 1.59, p=0.02, I2=0%) were both associated with higher risk of DR. For studies with HbA1c-SD, the association was not significantly affected by study characteristics such as country, study design, mean age, disease duration, adjustment of mean HbA1c, or quality scores (p for subgroup difference all>0.05). In conclusion, higher HbA1c variability may be associated with an increased risk of retinopathy in patients with T2DM. [ABSTRACT FROM AUTHOR]

Toll‐like receptor 4 (TLR4) is a signaling molecule responsible for the expression of hepcidin (Hepc), while myeloid differentiation protein 2 (MD2) is one major accessory protein of TLR4. This study focuses on exploring the neurocyte ferroptosis mediated through the regulation of Hepc expression by MD2, which is also one of the mechanisms for postoperative cognitive dysfunction (POCD). An experimental study was carried out using aged wild‐type (Wt) and MD2 transgenic (Tg) mice. The neurocyte ferroptosis and POCD in the mice were assessed following splenectomy. Morris water maze was utilized to assess the neurocognitive abilities, hematoxylin and eosin (H&E) assay was performed to examine histopathology, and Nissl staining was used to evaluate the neurocyte damage. The Fe2+, superoxide dismutase(SOD), malondialdehyde (MDA), glutathione(GSH), and glutathione peroxidase 4 (GPX4) levels were determined with kits. The expressions of transferrin receptor (TFR), Hepc, and MD2 were measured by Western blotting, while the expressions of TFR and GPX4 were measured by immunohistochemical staining. In Tg mice, we observed neurocyte ferroptosis and POCD following treatment with an MD2 inhibitor. PC12 cells were used as a neurocyte model. Ferroptosis was induced after treatment with an MD2 inhibitor, and the cell viability was assayed by Cell Counting Kit‐8. Immunofluorescent staining was used to measure the TFR and GPX4 expressions. Meanwhile, the intracellular levels of Fe2+, SOD, MDA, GSH, GPX4, and Hepc were also measured. POCD occurred among aged Wt and Tg mice. The Tg‐POCD mice had more apparent POCD than the Wt‐POCD mice. Nissl and H&E staining revealed neurocyte damage in brain tissues. Besides this, the Fe2+ and MDA expressions were upregulated, while the SOD, GSH, and GPX4 expressions were downregulated. Elevations in tissue levels of TFR, Hepc, and MD2 were observed, which were higher than those of Wt‐POCD mice. After treatment with an MD2 inhibitor, the POCD could be prominently ameliorated in Tg‐POCD mice, the Fe2+ and MDA levels could be reduced, while the SOD, GSH, and GPX4 levels could be elevated. In the PC12 model, ferroptosis could be suppressed by inhibiting the expression of MD2. MD2 is capable of regulating neurocyte ferroptosis by promoting Hepc expression, which has great potential as a novel target for POCD therapy. [ABSTRACT FROM AUTHOR]

This paper takes the 2014 pilot project of accelerated depreciation of fixed assets as a quasi-natural experiment, and builds a Propensity Score Matching–Difference in Differences (PSM-DID) model based on the data of Chinese listed companies from 2000 to 2019 to test the impact of tax preference on enterprise investment efficiency and its mechanism. The results show that the policy inhibits supported enterprises investment efficiency significantly. Heterogeneity analysis shows that the policy causes greater investment efficiency losses for small and medium-sized enterprises, non-state-owned enterprises and asset-heavy enterprises. The mechanism test found the reason why the policy eased financing constraints but inhibited investment efficiency in short-term. After a variety of robustness tests, the above basic conclusions are still valid. Although the accelerated depreciation policy of fixed assets is conducive to expanding the scale of investment, the incentive effect on investment efficiency is not obvious, and even shows a restraining effect. Given the existence of heterogeneity, the design of the policy should not only distinguish industries, but also pay attention to the differences between different enterprises in the same industry. Strengthening research and development (R&D) innovation and improving the matching mechanism between human capital and fixed investment will help give full play to the incentive effect of this policy. The research in this paper helps to deepen the understanding of the microeconomic effects of tax policy and identify the internal mechanism, which not only enriches the relevant literature, but also provides a reference for the government to better use tax policy to promote the high-quality development of enterprises. [ABSTRACT FROM AUTHOR]

M1 microglia predominated in AD mice, which promoted the inflammatory cytokine expressions significantly. The microglia can clear A through phagocytosis and release pro-inflammatory cytokines and cytotoxic substances.4 In AD, microglia polarize to pro-inflammatory M1 phenotype upon stimulation. Nevertheless, RBAP can significantly reduce the proportion of M1 cells and inhibit the inflammatory cytokine expressions in M1 cells. [Extracted from the article]

The previous study by our group has found that miRNA‐22 can inhibit pyroptosis by targeting GSDMD and improve the memory and motor ability of mice with Alzheimer's disease (AD) mice by inhibiting inflammatory response. In recent years, stem cells and their exosomes have been reported to have good therapeutic effects on AD; therefore, we hypothesize that miRNA‐22 is likely to play a synergistic therapeutic effect. In this study, adipose‐derived mesenchymal stem cells (ADMSCs) were transfected into miRNA‐22 mimic to obtain miRNA‐22 loaded exosomes (Exo‐miRNA‐22), which was further used for the treatment and nerve repair of AD. In brief, 4‐month‐old APP/PS1 mice were assigned into the control group, Exo and Exo‐miRNA‐22 groups. After exosome transplantation, we observed changes in the motor and memory ability of mice. In addition, ELISA was used to detect the expression of inflammatory factors in cerebrospinal fluid and peripheral blood, Nissl staining was used to assess the survival of mouse nerve cells, immunofluorescence staining was used to determine the activation of microglia, and Western blot was utilized to detect the expression of pyroptosis‐related proteins. As a result, the nerve function and motor ability were significantly higher in mice in the Exo‐miRNA‐22 group than those in the control group and Exo group. Meanwhile, the survival level of nerve cells in mice was higher in the Exo‐miRNA‐22 group, and the expression of inflammatory factors was lower than that of the Exo group, indicating Exo‐miRNA‐22 could significantly suppress neuroinflammation. In vitro culture of PC12 cells, Aβ25‐35‐induced cell damage, detection of PC12 apoptotic level, the release of inflammatory factors and the expression of pyroptosis‐related proteins showed that Exo‐miRNA‐22 could inhibit PC12 apoptosis and significantly decrease the release of inflammatory factors. In this study, we found that miRNA‐22‐loaded ADMSC‐derived exosomes could decrease the release of inflammatory factors by inhibiting pyroptosis, thereby playing a synergetic therapeutic role with exosomes on AD, which is of great significance in AD research. [ABSTRACT FROM AUTHOR]

Syringaresinol-di-O-β-D-glucoside (SOG) is a phenolic compound extracted from Polygonatum sibiricum. The present study aimed to investigate the antidiabetic effect of SOG on streptozocin (STZ)-induced diabetic mice and determine the potential underlying mechanisms. In the present study, fasting blood glucose and organ indexes of mice were analyzed. Body weight, water intake and food intake were also recorded. Furthermore, serum fasting insulin, pancreatic insulin and pancreatic interleukin-6 levels of mice were determined using ELISA kits to investigate the effect of SOG on the levels of insulin. Levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and free fatty acid (FFA) in the serum of mice, and levels of TC, TG and total protein in the kidney, were also determined to investigate the effects of SOG on lipid and protein metabolism in mice. Furthermore, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, as well as total antioxidant capacity (T-AOC), in the kidneys of mice were determined to investigate the effect of SOG on oxidative stress. Western blotting was also performed to determine the expression of proteins associated with oxidative stress. The results demonstrated that SOG (25, 50 and 75 mg/kg) induced a significant antidiabetic effect in mice. Treatment with SOG promoted insulin secretion and decreased TC, TG, LDL-C, VLDL-C, FFA, MDA, SOD, CAT, AST, ALT and ALP levels in the kidneys of mice, as well as kidney TC and TG levels, but increased the levels of kidney total protein and the T-AOC in kidneys. Furthermore, SOG treatment could significantly downregulate the expressions of nitrotyrosine and transforming growth factor-β1 in diabetic mice. Therefore, the present study indicated that SOG may exert an antidiabetic effect on STZ-induced diabetic mice and that the mechanism of SOG may be associated with its antioxidative activity. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19 pandemic; big data capability; strategic flexibility; financial performance; environmental psychological dynamics EN COVID-19 pandemic big data capability strategic flexibility financial performance environmental psychological dynamics 1 1 1 05/12/22 20220510 NES 220510 In the original article the authors neglected to include a Funding statement. COVID-19 pandemic, financial performance, big data capability, environmental psychological dynamics, strategic flexibility. [Extracted from the article]

Aim: We investigated the effect and mechanism of Icariin (ICA) on improving neurobehavioral ability of mice with Alzheimer's disease (AD)., Methods: We selected 10-month-old APP/PS1 mice (AD) and wild-type C57BL/6J mice (Normal). After intragastric administration of ICA, Morris water maze was employed to detect neurobehavioral improvements, and to assay key ferroptosis indicators and oxidative stress levels. The common target of ICA for resisting ferroptosis and AD was predicted by network pharmacology., Results: ICA could improve the neurobehavioral, memory and motor abilities of AD mice. It could lower the ferroptosis level and enhance the resistance to oxidative stress. After inhibition of MDM2, ICA could no longer improve the cognitive ability of AD mice, nor could it further inhibit ferroptosis. Network pharmacological analysis revealed that MDM2 might be the target of ICA action., Conclusions: We found that ICA can inhibit ferroptosis of nerve cells, thereby ameliorating neural damage in mice with AD.

Aim: This study was aimed at exploring the mechanism by which aurantiamide (Aur) targeted NLRP3 to suppress microglial cell polarization., Methods: The 7-month-old APP/PS1 mice and C57BL/6 mice were applied to be the study objects, and Aur was administered intragastrically to APP/PS1 mice at 10 mg/kg and 20 mg/kg. The changes in the neurocognitive function of mice were measured by Morris Water Maze (MWM) test. In the in vitro experiments, the mouse BV2 cells were employed as the study objects, which were subject to treatment with 10 μM and 20 μM Aur and induced with LPS and IFN-γ in order to activate BV2 cells and induce their M1 polarization., Results: Aur was found to suppress the M1 polarization of mouse microglia, reduce central neuroinflammation, and improve the cognitive function in mice. Meanwhile, Aur suppressed the activation and the expression of NLRP3 inflammasome. The results of experiments in vitro demonstrated that Aur inhibited the activation and M1 polarization of BV2 cells., Conclusion: Aur targets NLRP3 and suppresses the activation of NLRP3 inflammasome., (© 2022 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

This work aimed to investigate the effect of aurantiamide (Aur) in promoting the M2 polarization of microglial cells to improve the cognitive ability of mice with Alzheimer's disease (AD). The M2 polarization of BV2 cells was induced by interleukin-4 (IL-4) treatment.Aur promoted the M2 polarization of BV2 cells, and up-regulated the expression of CD206 and SOCS3. In the meantime, it increased TGF-β1, Arg-1 and IL-10 levels, and promoted the polarization of JAK1-STAT6. Treatment with STAT6 inhibitor antagonized the effect of Aur. Besides, the cognitive ability of AD mice was improved after Aur treatment, meanwhile, the expression of CD206 was up-regulated, while that of IBA-1 was down-regulated. Aur promotes the M2 polarization of microglial cells to improve the cognitive ability of AD mice, and such effect is related to the STAT6 signal., (© 2022 John Wiley & Sons Ltd.)

Background: Among patients with peritoneal dialysis-associated peritonitis (PDAP), It has been regarded as an indicator of deterioration of clinical condition that peritoneal dialysis effluent leukocyte count (PDELC) cannot be restored to normal after initial antibiotic therapy. However, the precise relationship between PDELC on day 5 and the clinical outcomes of PDAP episodes remains uncertain., Aims: To explore the association between PDELC on day 5 and clinical outcomes of PDAP episodes., Methods: This retrospective study was based on the medical chart database of the Affiliated Hospital of Guangdong Medical University. Multivariable regressions were used to evaluate the association between PDELC on day 5 and 60-day mortality, half-year mortality, treatment failure, and the length of stay in hospital with adjustment for confounding factors., Results: A total of 549 PDAP episodes in 309 patients were enrolled. The total 60-day mortality, half-year mortality, and rate of treatment failure was 6.0%, 9.8%, and 14.2%, respectively. Compared with patients with normal PDELC, those with PDELC ≥2000 × 10 6 /L on day 5 had significantly higher 60-day mortality (31.1% vs 2.7%), half-year mortality (35.6% vs 5.6%), and treatment failure (46.7% vs 5.7%). In multivariate adjusted regression, the ORs (95%CI) were 6.99 (2.33, 20.92; p  = 0.001), 4.97(1.93, 12.77; p  = 0.001), and 5.77 (2.07, 16.11; p  = 0.001), respectively. Patients with PDELC were 100-2000 × 10 6 /L on day 5 had a higher rate of treatment failure than those with normal PDELC (26.9% vs 5.7%) (OR = 3.03, 95%CI 1.42, 6.46; p  = 0.004). After sensitivity analysis, the results remained robust., Conclusions: Among patients with PDAP, increased PDELC on day 5 was associated with a greater risk of 60-day mortality, half-year mortality, and treatment failure.

Aim: This work aimed to investigate the mechanism of NOX4 in promoting Kupffer cells (KCs) activation and tissue inflammatory response in acute liver injury., Methods: Initially, the mouse KCs were cultured in vitro . Thereafter, the NOX4 overexpression plasmid was transfected into KCs to construct the overexpression cell line. Then, KCs inflammatory response was induced by LPS + Nigericin treatment. CCK-8 assay was performed to detect cell viability, flow cytometry (FCM) was conducted to measure cell apoptosis, enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory factor levels in the culture medium, NLRP3 and ASC expression in cells was detected by immunofluorescence (IF) staining, and ROS expression was detected by the DCFH-DA probe. Furthermore, the expression levels of NLRP3, ASC and Caspase-1 proteins were detected by Western-Blot (WB) assay. Furthermore, cells were pre-treated with NOX inhibitor or NAC to suppress NOX4 expression or ROS production, aiming to further investigate the effect on KCs inflammatory response. In mouse experiments, the NOX4 knockdown mice and wild-type (WT) mice were adopted for carrying out experiments. The mouse model of ALI was constructed with LPS and D-GalN treatment. Thereafter, the changes in tissue samples were detected by H&E staining, NLRP3 expression was measured by histochemical staining, inflammatory factors in tissues were analyzed by ELISA, and the levels of NLRP3, ASC and Caspase-1 proteins in tissues were detected by WB assay., Results: LPS induced KCs inflammatory response. NOX4 overexpression decreased the mouse viability and increased the apoptosis rate. The levels of inflammatory factors were up-regulated in the culture medium. In addition, ROS were activated, and the positive cell number increased. Moreover, NOX4 promoted NLRP3 activation and significantly increased the expression of NLRP3 and ASC. Pretreatment with NOX4 inhibitor or NAC antagonized the effects of NOX4 and suppressed the KCs inflammatory response. In the mouse model, NOX4 knockdown significantly suppressed the activation and inflammatory response of microglial cells in tissues, reducing the NLRP3 expression in tissues., Conclusion: NOX4 activates the NLRP3 inflammasome via ROS to promote inflammatory response in KCs and the release of inflammatory factors, suppressing NOX4 can improve ALI in mice, and NOX4 is promising as a new target for ALI treatment.

Short-chain fatty acids (SCFAs) are a product of intestinal bacteria metabolism. Our previous study has found that intestinal bacteria in patients with Alzheimer's disease (AD) can promote the activation of NLRP3 inflammasome and mediate neuroinflammation. In this study, we mainly explored the regulation of intestinal microenvironmental immunity by intestinal bacterial metabolite SCFAs and the mechanism of NLRP3 activation. First, wild-type (WT) and APP/PS1 mice were intervened with SCFAs. As a result, the proportion of double-negative T cells (CD3 + CD4 - CD8 - , DNTs) in the intestine was increased, SCFAs could promote the expression of intestinal NLRP3 and inflammatory factors (IL-18, IL-6 and TNF-α). Moreover, SCAFs could also promote the level of inflammatory factors in the cerebrospinal fluid (CSF) of mice and aggravate the cognitive impairment in AD mice. CD3 + T cells isolated from the spleen were pre-treated with SCFAs, followed by detection of the proportion of DNTs. Consequently, SCFAs could promote the formation of DNTs, activate OX40 signal and simultaneously up-regulate the protein expression of Bcl-2, Bcl-xl and Survivin. Knockdown of OX40 could inhibit SCFAs-induced differentiation of DNTs. The co-culture of DNTs and intestinal macrophages showed that DNTs could activate Fas/FasL-TNF-α signal and induce the activation of NLRP3 inflammasome. In AD mouse models, treatment with Fas and TNFR1 inhibitors could significantly inhibit SCFAs-induced NLRP3 activation and inflammatory factors, while attenuate the inflammatory response in the brain tissue of mice and improve the cognitive ability of mice, however, without significant effect on the level of DNTs. The present study showed that SCFAs can promote the formation of DNTs through OX40. DNTs could induce the activation of NLRP3 inflammasome and the release of inflammatory factors in macrophages through Fas/FasL-TNF-α signals, thereby increasing the level of inflammatory factors in the central nervous system. When Fas and TNFR1 were inhibited by suppressing the functions of DNTs and macrophages, the activation of NLRP3 was inhibited. DNTs are affected by SCFAs, which is a new mechanism of neuroinflammation in AD.

Objective: To explore the application value of ultrasonic measurement of optic nerve sheath diameter in elderly patients with craniocerebral injury., Methods: 86 cases of elderly patients with craniocerebral injury treated in our hospital between January 2017 and December 2018 were included, all of whom had the invasive monitoring of intracranial pressure (ICP) and optic nerve sheath diameter (ONSD) in ultrasonic testing. According to ICP measurement results, patients were divided into a normal ICP group (n = 44) and an increased ICP group (ICP ≥ 20 mmHg stood for increased ICP, n = 42). Gender, age, systolic blood pressure, blood glucose, hospital stay, oxyhemoglobin saturation, ISS score, ONSD value, hematoma type, primary injury, associated injury and complications of the patients were compared., Results: The univariate analysis showed that the systolic blood pressure in the ICP increased group was significantly decreased while the blood glucose, ISS and ONSD values showed significant increase (P < 0.05). The multivariate analysis showed that associated injury, systolic blood pressure and ONSD value had a significant influence on the increase of intracranial pressure (all P < 0.05). ONSD is positively correlated with ICP (r = 0.855, P = 0.000). The areas of systolic blood pressure and ONSD value under the curve in diagnosis of increased intracranial pressure in elderly patients with craniocerebral injury were 0.717 and 0.780, respectively. When the ONSD value was 4.90 mm, the area under the curve was 0.780, the sensitivity and specificity were 89.00% and 91.00%, respectively. When the ONSD value predicted that the critical value of good/poor prognosis of patients was 4.70 mm, the area under the curve was 0.796, the sensitivity was 91.00%, and the specificity was 90.00%., Conclusion: Ultrasound measurement of optic nerve sheath diameter can diagnose the increase of intracranial pressure in elderly patients with craniocerebral injury, and can better predict the prognosis., Competing Interests: None., (AJTR Copyright © 2021.)

Resting-state functional magnetic resonance imaging (R-fMRI) signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN) have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs) were analyzed using amplitude of low-frequency fluctuation (ALFF). The ALFF was computed across different frequencies (slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz; and typical band: 0.01-0.08 Hz) in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions) of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4) and extensive default mode network and right postparietal results in lower frequencies (slow-5). Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4) blood oxygen level-dependent (BOLD) signals in pain localization brain regions and lower frequencies (slow-5) in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly correlated with pain duration in the patients. This result supports our hypothesis that trigeminal pain has a characteristic spatiotemporal distribution of low-frequency BOLD signals. These findings might contribute to a better understanding of the impact of CTN on the brain's intrinsic architecture. Future studies should take the frequencies into account when measuring brain resting BOLD signals of patients with CTN., Competing Interests: Disclosure The authors report no conflicts of interest in this work.