Gait impairment-related axonal degeneration in Parkinson's disease by neurite orientation dispersion and density imaging.

Microstructural alterations in the brain networks of Parkinson's disease (PD) patients are correlated with gait impairments. Evaluate microstructural alterations in the white matter (WM) fiber bundle tracts using neurite orientation dispersion and density imaging (NODDI) technique in PD versus healthy controls (HC). In this study, 24 PD patients and 29 HC were recruited. NODDI and high-resolution 3D structural images were acquired for each participant. The NODDI indicators, including the intracellular neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), were compared between the two groups. Diffusion-weighted (DW) images were preprocessed using MRtrix 3.0 software and the orientation distribution function to trace the main nerve fiber tracts in PD patients. Quantitative gait and clinical assessment scales were used to compare the medication "ON" and "OFF" states of PD patients. The NDI, ODI, and ISO values of the WM fiber bundles were significantly higher in PD patients compared to HC. Fiber bundles, including the anterior thalamic radiation, corticospinal tract, superior longitudinal fasciculus, forceps major, cingulum, and inferior longitudinal fasciculus, were found to be significantly affected in PD. The NDI changes of PD patients were well correlated with stride lengths in the "ON" state; ODI changes were correlated with the stride time in the "ON" and "OFF" states and ISO changes were correlated with the stride time and cadence in the "ON" state. In conclusion, combination of NODDI technique and gait parameters can help detect gait impairment in PD patients early and accurately.

Regulatory effect of graphene on growth and carbon/nitrogen metabolism of maize (Zea mays L.).

BACKGROUND: Leakage of graphene into the environment has resulted from its increasing use. Although the impact of graphene on ecosystems is already in full swing, information regarding its impact on plants is lacking. In particular, the effects of graphene on plant growth and development vary, and basic information on the regulation of carbon and nitrogen metabolism is missing. In the current study, the way in which graphene (0, 25, 50, 100, and 200 g kg-1 ) affects maize seedlings was studied in terms of morphological and biochemical indicators. The purpose of this study was to understand better how graphene regulates plant carbon and nitrogen metabolism and to understand its interactions with leaf structure and plant growth. RESULTS: The results showed that 50 g kg-1 graphene increased plant height, stem diameter, leaf area, and dry weight; however, this was inhibited by the high level of graphene (200 g kg-1 ). Further studies indicated that different concentrations of graphene could increase leaf thickness and vascular bundle area as well as the net photosynthetic rate (Pn) of leaves; 25 and 50 g kg-1 graphene enhanced the leaves stomatal conductance (Cond), transpiration rate (Tr), intercellular carbon dioxide (Ci), and chlorophyll content. Higher concentrations decreased the above indicators. At 50 g kg-1 , graphene increased the activity of carbon/nitrogen metabolism enzymes by increasing carbon metabolites (fructose, sucrose, and soluble sugars) and soluble proteins (nitrogen metabolites). These enzymes included sucrose synthase (SS), sucrose phosphate synthase (SPS), nitrate reductase (NR), glutamine synthase (GS), and glutamate synthase (GOGAT). CONCLUSION: These results indicate that graphene can regulate the activities of key enzymes involved in carbon and nitrogen metabolism effectively and supplement nitrogen metabolism through substances produced by carbon metabolism by improving photosynthetic efficiency, thus maintaining the balance between carbon and nitrogen and promoting plant growth and development. The relationship between these indexes explained the mechanism by which graphene supported the growth of maize seedlings by enhancing photosynthetic carbon metabolism and maintaining metabolic balance. For maize seedling growth, graphene treatment with 50 g kg-1 soil is recommended. © 2023 Society of Chemical Industry.

Foliar spraying of exogenous uniconazole (S3307) at the flowering stage as an effective method to resist low-temperature stress on mung bean [Vigna radiata (L.) Wilczek].

Low temperature is one of the major constraints on agricultural productivity worldwide and is likely to further increase. Several adaptations and mitigation strategies are required to cope with low-temperature stress. Uniconazole (S3307) could play a significant role in the alleviation of abiotic stress in plants. In this study, the effects of S3307 on the reactive oxygen species (ROS) and antioxidant metabolism were studied in the leaves of mung bean [Vigna radiata (L.) Wilczek]. The experimental results showed that the low-temperature induced accumulation of superoxide anion (O2-) production rate, and malonaldehyde (MDA) contents. Increased proline content and enzymatic antioxidants, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to alleviate oxidative damage under low temperatures. While, S3307 could reduce O2- production rate and MDA contents and increase the activities of SOD, POD, and CAT, slowed the decrease in ascorbic acid (AsA), dehydroascorbic acid (DHA), glutathione (GSH), and oxidized glutathione (GSSG), and promoted increase in soluble sugars (SS), soluble proteins (SP), and proline (Pro) content under low-temperature. At the same time, low temperature leads to lower 100 grain weight and number of grains per plant, which eventually causes yield reduction decreased. Foliar spraying of S3307 could alleviate the yield loss caused by low temperature, and the increase of S3307 treatment was 5.1%-12.5% and 6.3%-32.9% for the two varieties, respectively, compared with CK. In summary, exogenous S3307 pretreatment enhances plant tolerance to low-temperature by improving the antioxidant enzyme activities, increased non-enzymatic antioxidants content, and decreased O2- production rate and MDA contents and inducing alterations in endogenous S3307, and reduce the decrease in mung bean yield.

Hypochlorite activatable ratiometric fluorescent probe based on endoplasmic reticulum stress for imaging of atherosclerosis.

Endoplasmic reticulum (ER) stress can induce reactive oxygen (ROS) generation which is directly associated with the emergence of atherosclerosis. Foam cells could promote atherogenesis by inducing ER stress. To understand hypochlorite (ClO-) levels in foam cells under ER stress, novel ER-targeted ClO- activatable ratiometric fluorescence probes Rx-NE and Rx-NCE were designed using a classical rhodamine dye and coumarin dye bridge moiety as the fluorescent skeleton. Both Rx-NE and Rx-NCE demonstrated ratiometric detection capabilities for ClO-, with Rx-NCE showing better sensitivity compared to Rx-NE. The probe Rx-NCE could detect the upregulation of ClO- in foam cells under ER stress and clearly outline delineation of the boundary of atherosclerotic plaques by dual-color imaging. Importantly, the hypochlorite-activated ratiometric probe Rx-NCE had been innovatively applied to the distinction of atherosclerotic blood vessels in atherosclerosis-bearing transgenic (tg) (flk1: eGFP) zebrafish. The probe Rx-NCE is of significant value for investigating the pathological role of ER stress and atherosclerotic diseases, as well as offering new insights into the identification of atherosclerosis.

DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining.

DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) in response to ionizing radiation (IR) to govern genome integrity. The interaction of the catalytic subunit of DNA-PK (DNA-PKcs) with the Ku70/Ku80 heterodimer on DSBs leads to DNA-PK activation; however, it is not known if upstream signaling events govern this activation. Here, we reveal a regulatory step governing DNA-PK activation by SIRT2 deacetylation, which facilitates DNA-PKcs localization to DSBs and interaction with Ku, thereby promoting DSB repair by NHEJ. SIRT2 deacetylase activity governs cellular resistance to DSB-inducing agents and promotes NHEJ. SIRT2 furthermore interacts with and deacetylates DNA-PKcs in response to IR. SIRT2 deacetylase activity facilitates DNA-PKcs interaction with Ku and localization to DSBs and promotes DNA-PK activation and phosphorylation of downstream NHEJ substrates. Moreover, targeting SIRT2 with AGK2, a SIRT2-specific inhibitor, augments the efficacy of IR in cancer cells and tumors. Our findings define a regulatory step for DNA-PK activation by SIRT2-mediated deacetylation, elucidating a critical upstream signaling event initiating the repair of DSBs by NHEJ. Furthermore, our data suggest that SIRT2 inhibition may be a promising rationale-driven therapeutic strategy for increasing the effectiveness of radiation therapy.

Plastid Phosphatidylglycerol Homeostasis Is Required for Plant Growth and Metabolism in Arabidopsis thaliana.

A unique feature of plastid phosphatidylglycerol (PG) is a trans-double bond specifically at the sn-2 position of 16C fatty acid (16:1t- PG), which is catalyzed by FATTY ACID DESATURASE 4 (FAD4). To offer additional insights about the in vivo roles of FAD4 and its product 16:1t-PG, FAD4 overexpression lines (OX-FAD4s) were generated in Arabidopsis thaliana Columbia ecotype. When grown under continuous light condition, the fad4-2 and OX-FAD4s plants exhibited higher growth rates compared to WT control. Total lipids were isolated from Col, fad4-2, and OX-FAD4_2 plants, and polar lipids quantified by lipidomic profiling. We found that disrupting FAD4 expression altered prokaryotic and eukaryotic PG content and composition. Prokaryotic and eukaryotic monogalactosyl diacylglycerol (MGDG) was up-regulated in OX-FAD4 plants but not in fad4-2 mutant. We propose that 16:1t-PG homeostasis in plastid envelope membranes may coordinate plant growth and stress response by restricting photoassimilate export from the chloroplast.

Effects of concentration-dependent graphene on maize seedling development and soil nutrients.

The long-term use of chemical fertilizers to maintain agricultural production has had various harmful effects on farmland and has greatly impacted agriculture's sustainable expansion. Graphene, a unique and effective nanomaterial, is used in plant-soil applications to improve plant nutrient uptake, reduce chemical fertilizer pollution by relieving inadequate soil nutrient conditions and enhance soil absorption of nutrient components. We investigated the effects of graphene amendment on nutrient content, maize growth, and soil physicochemical parameters. In each treatment, 5 graphene concentration gradients (0, 25, 50, 100, and 150 g kg-1) were applied in 2 different types (single-layer and few-layers, SL and FL). Soil aggregates, soil accessible nutrients, soil enzyme activity, plant nutrients, plant height, stem diameter, dry weight, and fresh weight were all measured throughout the maize growth to the V3 stage. Compared to the control (0 g kg-1), we found that graphene increased the percentage of large agglomerates (0.25-10 mm) in the soil and significantly increased the geometric mean diameter (GMD) and mean weight diameter (MWD) values of > 0.25 mm water-stable agglomerates as the increase of concentration. Soil available nutrient content (AN, AP, and AK) increased, peaking at 150 g kg-1. Graphene boosted nutrient absorption by maize plants, and aboveground total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents rose with the increasing application, which raised aboveground fresh weight, dry weight, plant height, and stalk thickness. The findings above confirmed our prediction that adding graphene to the soil may improve maize plant biomass by enhancing soil fertility and improving the soil environment. Given the higher manufacturing cost of single-layer graphene and the greater effect of few-layer graphene on soil and maize plants at the same concentration, single-layer graphene and few-layer graphene at a concentration of 50 g kg-1 were the optimal application rates.

Quantitative Measurement Reveals Dynamic Volatile Changes and Potential Biochemical Mechanisms during Green Tea Spreading Treatment.

Quantitative data provide clues for biochemical reactions or regulations. The absolute quantification of volatile compounds in tea is complicated by their low abundance, volatility, thermal liability, matrix complexity, and instrumental sensitivity. Here, by integrating solvent-assisted flavor evaporation extraction with a gas chromatography-triple quadrupole mass spectrometry platform, we successfully established a method based on multiple reaction monitoring (MRM). The method was validated by multiple parameters, including the linear range, limit of detection, limit of quantification, precision, repeatability, stability, and accuracy. This method was then applied to measure temporal changes of endogenous volatiles during green tea spreading treatment. In total, 38 endogenous volatiles were quantitatively measured, which are derived from the shikimic acid pathway, mevalonate pathway, 2-C-methylerythritol-4-phosphate pathway, and fatty acid derivative pathway. Hierarchical clustering and heat-map analysis demonstrated four different changing patterns during green tea spreading treatment. Pathway analysis was then conducted to explore the potential biochemistry underpinning these dynamic change patterns. Our data demonstrated that the established MRM method showed high selectivity and sensitivity for quantitative tea volatile measurement and offered novel insights about volatile formation during green tea spreading.

Metabolomic Profiling in Combination with Data Association Analysis Provide Insights about Potential Metabolic Regulation Networks among Non-Volatile and Volatile Metabolites in Camellia sinensis cv Baijiguan.

The non-volatile and volatile metabolites in tea confer the taste and odor characteristics of tea fusion, as well as shape the chemical base for tea quality. To date, it remains largely elusive whether there are metabolic crosstalks among non-volatile metabolites and volatile metabolites in the tea tree. Here, we generated an F1 half-sib population by using an albino cultivar of Camellia sinensis cv Baijiguan as the maternal parent, and then we quantified the non-volatile metabolites and volatile metabolites from individual half-sibs. We found that the EGC and EGCG contents of the albino half-sibs were significantly lower than those of the green half-sibs, while no significant differences were observed in total amino acids, caffeine, and other catechin types between these two groups. The phenylpropanoid pathway and the MEP pathway are the dominant routes for volatile synthesis in fresh tea leaves, followed by the MVA pathway and the fatty acid-derivative pathway. The total volatile contents derived from individual pathways showed large variations among half-sibs, there were no significant differences between the albino half-sibs and the green half-sibs. We performed a comprehensive correlation analysis, including correlations among non-volatile metabolites, between volatile synthesis pathways and non-volatile metabolites, and among the volatiles derived from same synthesis pathway, and we identified several significant positive or negative correlations. Our data suggest that the synthesis of non-volatile and volatile metabolites is potentially connected through shared intermediates; feedback inhibition, activation, or competition for common intermediates among branched pathways may co-exist; and cross-pathway activation or inhibition, as well as metabolome channeling, were also implicated. These multiple metabolic regulation modes could provide metabolic plasticity to direct carbon flux and lead to diverse metabolome among Baijiguan half-sibs. This study provides an essential knowledge base for rational tea germplasm improvements.

Probiotics for constipation and gut microbiota in Parkinson's disease.

INTRODUCTION: Constipation is one of the common non-motor symptoms in Parkinson's disease that significantly impacts patient quality of life. Probiotics supplementation may improve constipation symptoms, but its effect on the gut microbiota population is unclear. METHODS: In this randomized controlled study, 46 PD patients with constipation according to Rome Ⅲ criteria were recruited. The number of complete bowel movements per week, degree of defecation effort, Bristol stool Scale (BSS), Patient Assessment of Constipation symptom (PAC-SYM) and Patient assessment of constipation quality of life questionnaire (PAC-QOL) were collected pre- and post-intervention to evaluate the constipation symptoms. In addition, fresh feces of subjects before and after intervention and healthy controls were collected for 16s rRNA gene V3-V4 region sequencing to compare bacterial flora differences. RESULTS: Compared with the control group, the treatment group increased the average number of complete bowel movements per week (1.09 ± 1.24 vs. 0.04 ± 0.64, P < 0.001). Probiotics supplementation reduced the BSS score (0.65 ± 0.93 vs. -0.17 ± 0.94, P = 0.004), PAC-SYM score (4.09 ± 6.31 vs. -1.83 ± 4.14, P < 0.001), PAC-QOL score (10.65 ± 16.53 vs. 0.57 ± 12.82, P = 0.042), and degree of defecation effort score (1.00 ± 0.80 vs. 0.00 ± 0.30, P < 0.001). The improvement rate of constipation in the probiotics group was significantly higher than that in the control group (52.2% vs. 8.7%, P = 0.001). PD patients showed intestinal flora disorders compared to healthy controls. After 12 weeks of probiotics treatment, g_Christensenella_sp._Marseille-P2437 significantly increased, while g_Eubacterium_oxidoreducens_group, g_Eubacterium_hallii_group and s_Odoribacter_sp._N54.MGS-14 decreased (p < 0 0.05). CONCLUSIONS: Probiotics treatment can effectively improve the constipation symptoms of PD patients and positively affected the gut microbiota.

Effect of Chaihu plus Longgu Muli decoction plus five-element music therapy in the treatment of cancer-related depression.

BACKGROUND: Ninety percent of tumour patients have negative emotions during or after anti-tumour treatment, resulting in depression. Western medicine antidepressants have many adverse reactions. Patients often discontinue antidepressants due to intolerance. AIM: This study aims to observe the clinical effect of Chaihu plus Longgu Muli decoction with five-element music therapy in treating cancer-related mild and moderate depression. METHODS: A total of 120 patients with depression in the Oncology Department of Tangshan Hospital of Traditional Chinese Medicine, Hebei Province, from July 2017 to March 2019, were selected and randomly divided into the control and study groups (60 cases each) by the random number table method. The study group was treated with Chaihu plus Longgu Muli decoction with five-element music therapy for depression. The control group was treated with escitalopram tablets. After three courses of treatment, the degree of depression, clinical efficacy, quality of life, serum norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels were observed. RESULTS: After treatment, the HAMD-24 (Hamilton Depression 24) scale scores of the study group (13.93 ± 6.32) were lower than the control group (19.04 ± 7.46), and the difference was statistically significant (x2 = 4.048, p = 0.008). The total effective rate of the study group (93.33%) was higher than the control group (73.33%), and the difference was statistically significant (x2 = 7.260, p = 0.000). After treatment, according to the QLQ-C30 (quality of life questionnaire) scale, the functional score of the study group was higher than the control group (p < 0.05), and the symptom score of the study group was lower than the control group (p < 0.05). After treatment, the serum NE and 5-HT levels in the study group were higher than the control group, and the difference was statistically significant (p < 0.05) (NE: 221.81 ± 31.14 vs 198.91 ± 29.97, t = 4.078, p = 0.000; 5-HT: 141.41 ± 20.35 vs 125.32 ± 14.58, t = 5.781, p = 0.000). CONCLUSION: Chaihu plus Longgu Muli decoction with five-element music therapy can effectively alleviate patients' cancer-related depression and improve their quality of life, which is worthy of promotion.

Effect of IFN-α and other commonly used nebulization drugs in different nebulization methods on the resistance of breathing circuit filters under invasive mechanical ventilation.

Background: Interferon (IFN) is widely used in clinical practice and nebulization inhalation is one of the commonly used routes of administration. However, nebulization drugs such as interferon-α (IFN-α) with large molecular weights may deposit in the membrane of the breathing filters, causing its resistance to gradually increase. Thus, our study explores the effect of IFN-α and other nebulization drugs on the resistance of breathing circuit filters under invasive mechanical ventilation. Methods: We divided 96 breathing filters into eight groups. The baseline group was not treated while the blank group was installed but were not nebulized. The remaining groups received jet nebulized or vibrating nebulized with either normal saline, Combivent, Amphotericin B, or IFN-α at a frequency of once every 12 hours separately and were removed from the breathing circuit after 24 hours. The resistance of the filter of each group was then measured and statistical comparisons were made. Results: Filter resistance of the IFN-α jet nebulization group was greater than that of the other groups, and there were statistical differences except for the Amphotericin B jet nebulization group. Comparison of the resistance [cmH2O/(L·s)] of the IFN-α jet nebulization group vs. the baseline group showed 2.56 (2.40, 2.68) vs. 2.26 (2.03, 2.40), P=0.037; of the IFN-α jet nebulization group vs. the blank group showed 2.56 (2.40, 2.68) vs. 2.11 (1.98, 2.27), P=0.003; of the IFN-α jet nebulization group vs. the normal saline group: 2.56 (2.40, 2.68) vs. 2.16 (2.08, 2.32), P=0.023; of the IFN-α jet nebulization group vs. the Combivent jet nebulization group: 2.56 (2.40, 2.68) vs. 2.18 (2.14, 2.27), P=0.018; and of the IFN-α jet nebulization group vs. the Amphotericin B jet nebulization group: 2.56 (2.40, 2.68) vs. 2.33 (2.05, 2.45), P=0.221. The effect of jet nebulization and vibrating mesh nebulization on the resistance of breathing filters showed no significant statistical difference. Conclusions: Jet nebulization with IFN-α significantly increased the resistance of the breathing filter within 24 hours and there was no significant difference in filter resistance between jet nebulization and vibrating mesh nebulization of IFN-α or Amphotericin B.

Physiological response of soybean leaves to uniconazole under waterlogging stress at R1 stage.

Waterlogging is a major limiting factor in global crop production and seriously endangers growth and yield improvement in low-lying, rainfed regions. Soybean is an important economic crop affected by waterlogging stress. The current study investigates the effects of waterlogging stress on the leaf physiology and yield of two soybean varieties (Kenfeng 14, waterlogging-tolerant and Kenfeng 16, waterlogging-sensitive) and the mitigation effect of uniconazole (S3307) in promoting growth and productivity under waterlogging conditions. The results showed that waterlogging stress increased antioxidant enzyme activity and decreased the contents of non-enzymatic antioxidants such as AsA and GSH. Furthermore, the content of MDA and H2O2 increased significantly, indicating oxidative stress and O2-· production rate also improved, and the increase in the waterlogging-sensitive variety Kenfeng 16 was greater than that of the waterlogging-tolerant variety Kenfeng 14. Spraying S3307, however, increased the activities of antioxidants such as SOD, POD, CAT, and APX. GR, MDHAR, and DHAR increased the content of non-enzymatic antioxidants, effectively inhibited the increase of MDA, H2O2 content, and O2-· production rate, and alleviated the loss of yield factors caused by waterlogging stress. The waterlogging-tolerant variety Kenfeng 14 recovered better than the waterlogging-sensitive variety Kenfeng 16. In summary, S3307 ameliorated the effects of waterlogging stress on the physiological characteristics of soybean leaves and improved yield as a result of improved antioxidant defense mechanisms that impeded lipid peroxidation. Thus, S3307 could decelerate the damages caused by waterlogging stress to some extent.

The role of microglia in Alzheimer's disease and progress of treatment.

Microglia are permanent immune cells of the central nervous system. Microglia play an important role in the pathological process of Alzheimer's disease (AD). They are mainly involved in the uptake and clearance of amyloid-ß (Aß), as well as the formation of neuroinflammation. We found that overactivated microglia increase Aß and Tau, and Aß and Tau in turn act as activators of microglia. Additionally, various cytokines and proteins, high cholesterol, and telomere shortening are all associated with microglia activation. More activated microglia induce the release of inflammatory and anti-inflammatory factors to regulate inflammation, while microglia express multiple homologous receptors that bind to neuroimmunomodulators to prevent microglia overactivation. Moreover, aging of the body promotes neuroinflammation by increasing the response to IFN-γ (interferon-γ), and aging of the microglia themselves promotes AD by inducing the accumulation of large amounts of iron and reducing autophagy by regulating protein levels. Cognitive dysfunction occurs when activated microglia induce an increase in beta oligomers, promoting the production of pro-inflammatory factors that alter the shape, composition, and density of synapses. Based on their correlation, microglia-mediated AD therapy as well as the corresponding targets and drugs are discussed. In contrast to similar reviews, this article also summarizes some novel microglia-mediated AD treatment methods over the recent years.

Changes in microglia during drug treatment of stroke.

Microglia are the main immune cells in the brain and the first defense barrier of the nervous system. Microglia play a complex role in the process of stroke. A growing number of studies focus on the mechanism of action of drugs functions and how to regulate microglia. Therefore, we talk about the pathophysiological mechanisms of stroke and elaborate on the microglia signaling pathways of drug action in stroke models and how these drugs play a role in stroke treatment in this review. Understanding how drugs modulate proinflammatory and anti-inflammatory responses of microglia may be critical to implementing therapeutic strategies using immune interventions in stroke.

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway.

Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

Effect of sequential high-flow nasal cannula oxygen therapy and non-invasive positive-pressure ventilation in patients with difficult weaning from mechanical ventilation after extubation on respiratory mechanics.

BACKGROUND: Patients with difficult weaning who undergo mechanical ventilation are more likely to be at risk of reintubation and the sequential use of oxygen therapy after extubation is a concern for clinicians. Therefore, the aim of the present study was to compare the effects of transnasal high-flow nasal cannula (HFNC) oxygen therapy and non-invasive positive-pressure ventilation (NIV) on respiratory mechanics in patients with difficult weaning. METHODS: The present study was a single-center, retrospective, observational study. Twenty-nine patients with difficult weaning off invasive mechanical ventilation from the Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, from December 2018 to April 2021, were included. Within 48 h after extubation, alternate respiratory support with HFNC and NIV was provided. Relevant indicators were recorded after each support mode had been maintained for at least 60 min. These included esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), pressure-time product of Pes (PTPes), pressure-time product of Pga (PTPga), pressure-time product of Pdi (PTPdi), ratio of the PTPdi to the PTPes (PTPdi/PTPes), and ratio of the Pes to the Pdi (Pes/Pdi), diaphragmatic electromyogram (EMGdi), percentage of esophageal pressure coefficient of variation (CVes%),diaphragmatic electromyogram coefficient of variation (CVEMG),inspiratory time (Ti), expiratory time (Te) and respiratory cycle time (Ttot). RESULTS: Of the 29 patients included, 22 were males and 7 were females [age: 63.97±15.34 years, Acute Physiological and Chronic Health Estimation II (APACHE II) score: 18.00±5.63]. The CVes% and the Pes/Pdi were significantly higher in patients with NIV than HFNC using 40 L/min, CVes%: 9 (-6, 20) vs. -7 (-23, 6) and Pes/Pdi: 0.17 (-0.1, 0.53), vs. -0.12 (-0.43, 0.08) (P<0.05). The remaining indicators were not statistically different. CONCLUSIONS: The sequential NIV and HFNC can be tolerated in patients with such difficult weaning off mechanical ventilation after extubation, and more patients tend to choose HFNC subjectively. Compared with HFNC, NIV reduces the work of adjunctive respiratory muscle, but the patient's Pes dispersion is high when NIV is used, and it is necessary to pay attention to patient-ventilator coordination in clinical practice. We recommend alternating HFNC and NIV during the sequential respiratory therapy after extubation.

[Comparison of the effects between low-level assisted ventilation and T-piece method on respiratory mechanics during weaning of mechanically ventilated patients].

OBJECTIVE: To compare the difference of low-level assisted ventilation and T-piece method on respiratory mechanics of patients with invasive mechanical ventilation during spontaneous breathing trial (SBT) within 3 days before extubation. METHODS: A retrospective observational study was conducted. Twenty-five patients with difficulty in weaning or delayed weaning from invasive mechanical ventilation who were admitted to department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2018 to June 2020, and were in stable condition and entered the weaning stage after more than 72 hours of invasive mechanical ventilation were studied. A total of 119 cases of respiratory mechanical indexes were collected, which were divided into the low-level assisted ventilation group and the T-piece group according to the ventilator method and parameters used during the data collection. The different ventilation modes related respiratory mechanics indexes such as the esophageal pressure (Pes), the gastric pressure (Pga), the transdiaphragmatic pressure (Pdi), the maximum Pdi (Pdimax), Pdi/Pdimax ratio, the esophageal pressure-time product (PTPes), the gastric pressure-time product (PTPga), the transdiaphragmatic pressure-time product (PTPdi), the diaphragmatic electromyography (EMGdi), the maximum diaphragmatic electromyography (EMGdimax), PTPdi/PTPes ratio, Pes/Pdi ratio, the inspiratory time (Ti), the expiratory time (Te) and the total time respiratory cycle (Ttot) at the end of monitoring were recorded and compared between the two groups. RESULTS: Compared with the T-piece group, Pes, PTPes, PTPdi/PTPes ratio, Pes/Pdi ratio and Te were higher in low-level assisted ventilation group [Pes (cmH2O, 1 cmH2O = 0.098 kPa): 2.84 (-1.80, 5.83) vs. -0.94 (-8.50, 2.06), PTPes (cmH2O×s×min-1): 1.87 (-2.50, 5.93) vs. -0.95 (-9.71, 2.56), PTPdi/PTPes ratio: 0.07 (-1.74, 1.65) vs. -1.82 (-4.15, -1.25), Pes/Pdi ratio: 0.17 (-0.43, 0.64) vs. -0.47 (-0.65, -0.11), Te (s): 1.65 (1.36, 2.18) vs. 1.33 (1.05, 1.75), all P < 0.05], there were no significant differences in Pga, Pdi, Pdimax, Pdi/Pdimax ratio, PTPga, PTPdi, EMGdi, EMGdimax, Ti and Ttot between the T-piece group and the low-level assisted pressure ventilation group [Pga (cmH2O): 6.96 (3.54,7.60) vs. 7.74 (4.37, 11.30), Pdi (cmH2O): 9.24 (4.58, 17.31) vs. 6.18 (2.98, 11.96), Pdimax (cmH2O): 47.20 (20.60, 52.30) vs. 29.95 (21.50, 47.20), Pdi/Pdimax ratio: 0.25 (0.01, 0.34) vs. 0.25 (0.12, 0.41), PTPga (cmH2O×s×min-1): 7.20 (2.54, 9.97) vs. 7.97 (5.74, 13.07), PTPdi (cmH2O×s×min-1): 12.15 (2.95, 19.86) vs. 6.87 (2.50, 12.63), EMGdi (µV): 0.05 (0.03, 0.07) vs. 0.04 (0.02, 0.06), EMGdimax (µV): 0.07 (0.05, 0.09) vs. 0.07 (0.04, 0.09), Ti (s): 1.20 (0.95, 1.33) vs. 1.07 (0.95, 1.33), Ttot (s): 2.59 (2.22, 3.09) vs. 2.77 (2.35, 3.24), all P > 0.05]. CONCLUSIONS: When mechanically ventilated patients undergo SBT, the use of T-piece method increases the work of breathing compared with low-level assisted ventilation method. Therefore, long-term use of T-piece should be avoided during SBT.

Diversified Regulation of Cytokinin Levels and Signaling During Botrytis cinerea Infection in Arabidopsis.

Cytokinins (CKs) can modulate plant immunity to various pathogens, but how CKs are involved in plant defense responses to the necrotrophic pathogen Botrytis cinerea is still unknown. Here, we found that B. cinerea infection induced transcriptional changes in multiple genes involved in the biosynthesis, degradation, and signaling of CKs, as well as their contents, in pathogen-infected Arabidopsis leaves. Among the CKs, the gene expression of CYTOKININ OXIDASE/DEHYDROGENASE 5 (CKX5) was remarkably induced in the local infected leaves and the distant leaves of the same plant without pathogen inoculation. Cis-zeatin (cZ) and its riboside (cZR) accumulated considerably in infected leaves, suggesting an important role of the cis-zeatin type of CKs in the plant response to B. cinerea. Cytokinin double-receptor mutants were more susceptible to B. cinerea infection, whereas an exogenous CK treatment enhanced the expression levels of defense-related genes and of jasmonic acid (JA) and ethylene (ET), but not salicylic acid (SA), resulting in higher resistance of Arabidopsis to B. cinerea. Investigation of CK responses to B. cinerea infection in the JA biosynthesis mutant, jar1-1, and ET-insensitive mutant, ein2-1, showed that CK signaling and levels of CKs, namely, those of isopentenyladenine (iP), isopentenyladenine riboside (iPR), and trans-zeatin (tZ), were enhanced in jar1-1-infected leaves. By contrast, reductions in iP, iPR, tZ, and tZ riboside (tZR) as well as cZR contents occurred in ein2-1-infected leaves, whose transcript levels of CK signaling genes were likewise differentially regulated. The Arabidopsis Response Regulator 5 (ARR5) gene was upregulated in infected leaves of ein2-1 whereas another type-A response regulator, ARR16, was significantly downregulated, suggesting the existence of a complex regulation of CK signaling via the ET pathway. Accumulation of the cis-zeatin type of CKs in B. cinerea-infected leaves depended on ET but not JA pathways. Collectively, our findings provide evidence that CK responds to B. cinerea infection in a variety of ways that are differently modulated by JA and ET pathways in Arabidopsis.

[Analysis of the function of diaphragm and its influencing factors in mechanical ventilation patients by using fully automatic trigger twitch tracheal pressure].

OBJECTIVE: To understand the function of diaphragm and analyze the clinical factors affecting the function of diaphragm by measuring twitch tracheal pressure (TwPtr) in patients with mechanical ventilation and in the weaning phase. METHODS: Patients with more than 48 hours of invasive mechanical ventilation admitted to the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2015 to March 2017 were enrolled. After the patient entered the weaning stage, TwPtr of patients was monitored by two-way non repetitive automatic respiratory trigger device, the effects of duration of mechanical ventilation, severe pulmonary infection, sedative application and chronic obstructive pulmonary disease (COPD) on weaning were analyzed. RESULTS: A total of 62 patients were included, of which 45 were male and 17 were female. The average age was (66.8±11.7) years old. Twenty-three cases had severe pneumonia. The absolute value of TwPtr in severe pneumonia group was lower than that in non-severe pneumonia group [cmH2O (1 cmH2O = 0.098 kPa): 10.40±5.81 vs. 14.35±5.22, P = 0.021]. However, there was no significant difference in the duration of mechanical ventilation between the severe pneumonia group and non-severe pneumonia group [days: 26 (17, 43) vs. 15 (11, 36), P = 0.091]. In 62 patients with mechanical ventilation, there was a negative correlation between TwPtr and duration of mechanical ventilation (r = 0.414, P = 0.002), there was also a negative correlation between the duration of mechanical ventilation and TwPtr after the assessment of diaphragm function (r = 0.277, P = 0.039). There was a linear relationship between TwPtr and sedatives (r = 0.220, P = 0.040), but there was no correlation between TwPtr and COPD (r = -0.178, P = 0.166). CONCLUSIONS: For patients in the weaning stage of mechanical ventilation, severe pulmonary infection is one of the factors that affect the diaphragm dysfunction. There is a certain correlation between the diaphragm dysfunction and the use of sedatives.