Fluorogenic Rhodamine-Based Chemigenetic Biosensor for Monitoring Cellular NADPH Dynamics.

Ratiometric biosensors employing Förster Resonance Energy Transfer (FRET) enable the real-time tracking of metabolite dynamics. Here, we introduce an approach for generating a FRET-based biosensor in which changes in apparent FRET efficiency rely on the analyte-controlled fluorogenicity of a rhodamine rather than the commonly used distance change between donor-acceptor fluorophores. Our fluorogenic, rhodamine-based, chemigenetic biosensor (FOCS) relies on a synthetic, protein-tethered FRET probe, in which the rhodamine acting as the FRET acceptor switches in an analyte-dependent manner from a dark to a fluorescent state. This allows ratiometric sensing of the analyte concentration. We use this approach to generate a chemigenetic biosensor for nicotinamide adenine dinucleotide phosphate (NADPH). FOCS-NADPH exhibits a rapid and reversible response toward NAPDH with a good dynamic range, selectivity, and pH insensitivity. FOCS-NADPH allows real-time monitoring of cytosolic NADPH fluctuations in live cells during oxidative stress or after drug exposure. We furthermore used FOCS-NADPH to investigate NADPH homeostasis regulation through the pentose phosphate pathway of glucose metabolism. FOCS-NADPH is a powerful tool for studying NADPH metabolism and serves as a blueprint for the development of future fluorescent biosensors.

Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Heterologous expression of taxane genes confers resistance to fall armyworm in Nicotiana benthamiana.

KEY MESSAGE: Taxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Multi-Omics Analysis Reveals the Distinct Features of Metabolism Pathways Supporting the Fruit Size and Color Variation of Giant Pumpkin.

Pumpkin (Cucurbita maxima) is an important vegetable crop of the Cucurbitaceae plant family. The fruits of pumpkin are often used as directly edible food or raw material for a number of processed foods. In nature, mature pumpkin fruits differ in size, shape, and color. The Atlantic Giant (AG) cultivar has the world's largest fruits and is described as the giant pumpkin. AG is well-known for its large and bright-colored fruits with high ornamental and economic value. At present, there are insufficient studies that have focused on the formation factors of the AG cultivar. To address these knowledge gaps, we performed comparative transcriptome, proteome, and metabolome analysis of fruits from the AG cultivar and a pumpkin with relatively small fruit (Hubbard). The results indicate that up-regulation of gene-encoded expansins contributed to fruit cell expansion, and the increased presence of photoassimilates (stachyose and D-glucose) and jasmonic acid (JA) accumulation worked together in terms of the formation of large fruit in the AG cultivar. Notably, perhaps due to the rapid transport of photoassimilates, abundant stachyose that was not converted into glucose in time was detected in giant pumpkin fruits, implying that a unique mode of assimilate unloading is in existence in the AG cultivar. The potential molecular regulatory network of photoassimilate metabolism closely related to pumpkin fruit expansion was also investigated, finding that three MYB transcription factors, namely CmaCh02G015900, CmaCh01G018100, and CmaCh06G011110, may be involved in metabolic regulation. In addition, neoxanthin (a type of carotenoid) exhibited decreased accumulation that was attributed to the down-regulation of carotenoid biosynthesis genes in AG fruits, which may lead to pigmentation differences between the two pumpkin cultivars. Our current work will provide new insights into the potential formation factors of giant pumpkins for further systematic elucidation.

Mini-review of sewage sludge parameters related to system modelling.

System modelling of sewage sludge (SS) treatment attracts a growing interest for better comparison and optimisation of technologies. However, SS parameters need to be generalised to be used in holistic assessments, since scattered data may inhibit the development and interpretation of system models. A review of the literature on SS parameters relevant to modelling SS treatment systems revealed 208 datasets published in 162 publicly available scientific papers. We treated thickened and dewatered sludge in the same data analysis, but in some cases, this was an incorrect assumption. The compositional data showed significant variations, but most of the data subscribed to a lognormal distribution, albeit with varying levels of significance. On average, the thickened sludge contained 3.3 ± 1.7% total solid (TS), and the dewatered sludge contained 21.0 ± 6.7% TS. For the combined data, the average Ash content was 32.4 ± 11.8% of TS. Other characteristic parameters were the lower heating value (LHV) of 22.1 ± 2.1 MJ kg-1 volatile solid (VS) and the biochemical methane potential (BMP) of 0.25 ± 0.11 m3 CH4 kg-1 VS. Fertiliser-related elements were on average 53.3 ± 9.3% C in VS, 6.8 ± 2.2% N in VS, 6.7 ± 2.4% P in Ash and 1.7 ± 1.3% K in Ash. The data reviewed herein provide a good basis for assessing the generality of individual SS data and for selecting key parameters for modelling SS treatment systems. However, the review reveals a need for the better characterisation of SS in the future.

Mini-review of inventory data for the dewatering and drying of sewage sludge.

Technological comparison and system modelling of sewage sludge treatment are important in terms of sustainable development and climate change mitigation. Dewatering and drying are important processes for reducing volume for transportation and often a requirement for further sludge treatment. Inventory data on mass transfers and material and energy consumptions are therefore crucial in improving and understanding sludge management systems. Reviewing the scientific literature (2003-2021) revealed 55 and 21 datasets on dewatering and drying of sewage sludge, respectively. The scarcity of data did not allow for identifying detailed relationships between inputs and outputs for the technologies, but the reviewed data can serve as the first port of call when planning sludge management. The average total solid (TS) content obtained was statistically different for mechanical dewatering (MDW), deep dewatering, bio-drying (BDR) and thermal drying (TDR). Loss of volatile solids (VS) during dewatering is barely described, but a substantial VS loss was observed for TDR (8%) and BDR (27%). The use of chemical agents in MDW showed typical values of 5-15 g kg-1 TS. The use of energy is low for MDW (average of 0.12 and 0.26 kWh kg-1 TS for raw and digested sludges, respectively) but substantially higher for TDR (average of 3.8 kWh kg-1 TS). The justified inventory data for sludge dewatering and drying provide essential support to system modelling and technological comparison in future studies, but additional data from full-scale plants on energy consumption and the composition of removed water are strongly requested to improve the inventory.

Durability of single tablet regimen for patients with HIV infection in Southern Taiwan: data from a real-world setting.

BACKGROUND: A single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan. METHOD: This was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation. RESULTS: Two hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48-101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98-35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39-29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25-11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18-4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08-0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21-12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64-28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04-0.62, p = 0.006). CONCLUSION: Younger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection.

Climate Change Impact of the Development in Household Waste Management in China.

The potential climate change impacts of the development in Chinese household waste management, with less landfilling, more incineration with energy recovery, and source-separated food waste treated in biorefineries, were assessed through a life cycle assessment. When the waste management system interacts with a fossil-based energy system, landfilling produces a load of 144 kg CO2-eq/ton wet waste, while incineration shows a saving of 36 kg CO2-eq/ton wet waste. The introduction of food waste source separation lowers climate change impacts by an additional 33 kg CO2-eq/ton at a 60% sorting efficiency. As the Chinese energy system lowers its climate change impact over the next 30 years, energy recovery from waste treatment will change its relative contribution to climate change. In nonfossil energy systems, landfilling is estimated to have a climate change load of 180-240 kg CO2-eq/ton wet waste, while incineration, including combinations with the source-separation of food waste, will have a load of 310-540 kg CO2-eq/ton wet waste. These large intervals are due to waste composition uncertainty. However, considering a 20 year CH4 characterization factor representing a shorter time perspective, the impacts from landfilling are more dramatic due to the large methane release. This significant climate change impact calls for an increased focus on the developments in Chinese household waste management. The key issues identified may also apply to other countries.

Target of Rapamycin Regulates Photosynthesis and Cell Growth in Auxenochlorella pyrenoidosa.

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about the TOR signalling in Auxenochlorella pyrenoidosa. Here, we found a conserved ApTOR protein in Auxenochlorella pyrenoidosa, and the key components of TOR complex 1 (TORC1) were present, while the components RICTOR and SIN1 of the TORC2 were absent in Auxenochlorella pyrenoidosa. Drug sensitivity experiments showed that AZD8055 could effectively inhibit the growth of Auxenochlorella pyrenoidosa, whereas rapamycin, Torin1 and KU0063794 had no obvious effect on the growth of Auxenochlorella pyrenoidosaa. Transcriptome data results indicated that Auxenochlorella pyrenoidosa TOR (ApTOR) regulates various intracellular metabolism and signaling pathways in Auxenochlorella pyrenoidosa. Most genes related to chloroplast development and photosynthesis were significantly down-regulated under ApTOR inhibition by AZD8055. In addition, ApTOR was involved in regulating protein synthesis and catabolism by multiple metabolic pathways in Auxenochlorella pyrenoidosa. Importantly, the inhibition of ApTOR by AZD8055 disrupted the normal carbon and nitrogen metabolism, protein and fatty acid metabolism, and TCA cycle of Auxenochlorella pyrenoidosa cells, thus inhibiting the growth of Auxenochlorella pyrenoidosa. These RNA-seq results indicated that ApTOR plays important roles in photosynthesis, intracellular metabolism and cell growth, and provided some insights into the function of ApTOR in Auxenochlorella pyrenoidosa.

HDAC3 Knockdown Dysregulates Juvenile Hormone and Apoptosis-Related Genes in Helicoverpa armigera.

Insect development requires genes to be expressed in strict spatiotemporal order. The dynamic regulation of genes involved in insect development is partly orchestrated by the histone acetylation-deacetylation via histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although histone deacetylase 3 (HDAC3) is required for mice during early embryonic development, its functions in Helicoverpa armigera (H. armigera) and its potential to be used as a target of insecticides remain unclear. We treated H. armigera with HDAC3 siRNA and RGFP966, a specific inhibitor, examining how the HDAC3 loss-of-function affects growth and development. HDAC3 siRNA and RGFP966 treatment increased mortality at each growth stage and altered metamorphosis, hampering pupation and causing abnormal wing development, reduced egg production, and reduced hatching rate. We believe that the misregulation of key hormone-related genes leads to abnormal pupa development in HDAC3 knockout insects. RNA-seq analysis identified 2788 differentially expressed genes (≥two-fold change; p ≤ 0.05) between siHDAC3- and siNC-treated larvae. Krüppel homolog 1 (Kr-h1), was differentially expressed in HDAC3 knockdown larvae. Pathway-enrichment analysis revealed the significant enrichment of genes involved in the Hippo, MAPK, and Wnt signaling pathways following HDAC3 knockdown. Histone H3K9 acetylation was increased in H. armigera after siHDAC3 treatment. In conclusion, HDAC3 knockdown dysregulated juvenile hormone (JH)-related and apoptosis-related genes in H. armigera. The results showed that the HDAC3 gene is a potential target for fighting H. armigera.

Genetic algorithm (GA) - Artificial neural network (ANN) modeling for the emission rates of toxic volatile organic compounds (VOCs) emitted from landfill working surface.

Volatile organic compounds (VOCs) emitted from the working surface of landfills have received increasing attention due to the potential risks to human health. Quantifying the emission rates of risky VOCs is important to their health risk assessment but is also challenging because of their high variation and complicated relationship between the emission rates and various influencing factors. In this study, a continuous nine-month sampling of VOCs was conducted on a landfill working surface to identify dominant VOCs that are risky to human health and to construct artificial neural network (ANN) models for their emission rates by involving 105 datasets. Among the 63 detected VOCs, ethanol presented the highest emission rate (885.28 ± 1398.10 µg·m-2·s-1), and the dominant compounds with high emission rates and detection frequencies were characterized in each category. According to the human toxicity impact scores calculated with USEtox method, carbon tetrachloride, ethanol, tetrachloroethylene, 1, 2-dichloroethane, benzene, ethylbenzene, and chloroform were identified as the dominant carcinogenic VOCs, and acrolein, carbon tetrachloride, and 1, 2-dichloropropane were the dominant noncarcinogenic VOCs. ANN models were established for the emission rates of six typical risky VOCs, with meteorological conditions and waste compositions as input parameters and emission rates as output parameters. With the structure optimization and genetic algorithm, all the ANN models achieved good performance and excellent prediction capability with high R2 and low root mean square error (RMSE) values. The emission rates under a 95% probability were predicted for each risky VOCs via the established ANN models, by randomly sampling the input parameters under their data distribution. The approach proposed and results obtained can provide scientific methodology and important information for the monitoring, prediction, and health risk assessment of the VOCs emitted from MSW landfills.

Efficacy and safety of switching from nevirapine immediate-release twice daily to nevirapine extended-release once daily in virologically suppressed HIV-infected patients: a retrospective cohort study in Taiwan.

BACKGROUND: Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens. METHODS: We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events. RESULTS: During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group (82.9% vs. 85.7%; P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response (hazard ratio: 0.940; P = 0.754). Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients (5145.0 ng/mL vs. 6775.0 ng/mL; P = 0.267). The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups. CONCLUSIONS: We found that switching from NVP-IR to NVP-XR appeared to have similar safety and efficacy compared with continuing NVP-IR among virologically suppressed, HIV-infected Taiwanese patients. Our finding of higher Ctrough levels in both groups compared with other studies conducted in Caucasian populations and the high prevalence of CYP2B6 516 GT requires further investigation in a larger Taiwanese cohort.

[Clinical analysis of bone flap craniotomy for 17 patients with chronic subdural hematomas].

OBJECTIVE: To deepen the understanding of chronic subdural hematoma and to seek the effective treatment for chronic subdural hematoma (CSDH). METHODS: We retrospectively reviewed a series of 17 consecutive patients with CSDH, who received the treatment of bone flap craniotomy. To explore the surgical indications for CSDH, the data of imaging appearance, intraoperative findings and postoperative complications were analyzed. RESULTS: Among the patients, 13 were septated CSDH, with the characteristic imaging features such as anti-"3" impression in the inner edge of the hematoma and fibrous strap structure in the hematoma. Four patients were organized CSDH, with strong signals of T1 and T2 as well as hypointense netlike structure within the hematoma cavity while low signal on MRI in the thickened inner membrane. Burr hole trepanation was performed, but no improvement were achieved, whereas the bone flap craniotomy removed the hematoma completely without serious surgical complication except 1 case. CONCLUSION: Based on the preoperative imaging data, flap bone craniotomy seems to be the first choice for treatment of CSDH.

Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2-3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.

[Discussion and analysis the value of supine median³ nystagmus in the diagnosis and treatment of HC-BPPV].

Objective:To explore the clinical value of supine median³ nystagmus in the accurate diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo（HC-BPPV）. Methods:A total of 187 patients with HC-BPPV admitted to the First Affiliated Hospital of Xi'an Jiaotong University from June 2020 to March 2021 were selected. Among them 42 cases of Cupulolithiasis and 145 cases of Canalithiasis. The nystagmus parameters of patients left and right supine position and supine median³ position were recorded in detail by RART. According to the direction of supine median³ nystagmus, patients were divided into three groups: group A（nystagmus to weak side）, group B（nystagmus to strong side）, group C（negative nystagmus）. The canalith repositioning manoeuvres（CRM） was carried out by utility of an automatic vestibular function diagnosis and therapy system（SRM-IV）. The cure rate of CRM in three groups of HC-BPPV patients was compared, Multivariate logistic regression analysis was performed to analyze the influencing factors of CRM for HC-BPPV. Results:The cure rates of group A, group B and group C were 81.58%, 16.13% and 56.25%, respectively. The difference among the three groups was statistically significant. Then a pairwise comparison of group A, B and C, the difference was statistically significant（χ²A-B=40.294,P<0.001,χ²B-C=14.528, P<0.001,χ²A-C=11.606, P=0.001）; the results of multivariate logistic regression analysis showed that the direction of supine median³ nystagmus and BMI were the influencing factors of CRM for HC-BPPV. Conclusion:The direction, intensity and duration of supine median³ nystagmus play an important role in determining the responsibility semicircular canal of HC-BPPV.

Plant-derived strategies to fight against severe acute respiratory syndrome coronavirus 2.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented crisis, which has been exacerbated because specific drugs and treatments have not yet been developed. In the post-pandemic era, humans and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will remain in equilibrium for a long time. Therefore, we still need to be vigilant against mutated SARS-CoV-2 variants and other emerging human viruses. Plant-derived products are increasingly important in the fight against the pandemic, but a comprehensive review is lacking. This review describes plant-based strategies centered on key biological processes, such as SARS-CoV-2 transmission, entry, replication, and immune interference. We highlight the mechanisms and effects of these plant-derived products and their feasibility and limitations for the treatment and prevention of COVID-19. The development of emerging technologies is driving plants to become production platforms for various antiviral products, improving their medicinal potential. We believe that plant-based strategies will be an important part of the solutions for future pandemics.

[Development and characteristics of a moxa floss shaping and spreading device].

This paper introduces a moxa floss shaping and spreading device for governor vessel moxibustion. This device is consisted of a storage unit and a propulsion unit, capable of automatically shaping moxa sticks for governor vessel moxibustion. The device allows for the flexible adjustment of moxa stick length, better conforming to the physiological curvature of the spine, and avoiding potential burns associated with governor vessel moxibustion. It simplifies the operational procedures for healthcare professionals, offering the advantages of ease of use, safety, and efficiency.

Electroacupuncture pretreatment mediates sympathetic nerves to alleviate myocardial ischemia-reperfusion injury via CRH neurons in the paraventricular nucleus of the hypothalamus.

BACKGROUND: Myocardial ischemia-reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia-reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. METHODS: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. RESULTS: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. CONCLUSION: EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

iJAZ-based approach to engineer lepidopteran pest resistance in multiple crop species.

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.