Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.

We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.

Treatment and outcomes of immune checkpoint inhibitors-associated colitis/diarrhea: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment of ICIs-associated colitis/diarrhea and outcomes. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies which investigated the treatment and outcomes of colitis/diarrhea developing in patients who received ICIs. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea as well as the pooled rates of response to treatment, mortality, and ICIs permanent discontinuation and restarts in patients with ICIs-associated colitis/diarrhea were estimated using a random-effects model. RESULTS: Among the 11,492 papers initially identified, 27 studies were included. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea were 17%, 3%, 17%, 13%, and 15%, respectively. The pooled rates of overall response, response to corticosteroid therapy, and response to biological agents were 88%, 50%, and 96%, respectively. The pooled short-term mortality in patients with ICIs-associated colitis/diarrhea was 2%. The pooled incidences of ICIs permanent discontinuation and restarts were 43% and 33%, respectively. CONCLUSION: ICIs-associated colitis/diarrhea is common, but rarely lethal. Half of them are responsive to corticosteroid therapy. There is a fairly high rate of response to biological agents in steroid-refractory colitis/diarrhea patients.

Fecal Microbiota Transplantation Alleviated Cerebral Ischemia Reperfusion Injury in Obese Rats.

This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol and triglyceride levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species, superoxide dismutase and malondialdehyde were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum total cholesterol and triglyceride levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels. In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.

Nurses' practice and educational needs in oral care for postoperative patients with oral cancer in ICUs: a multicenter cross-sectional study.

BACKGROUND: Surgical incision, endotracheal intubation, structural changes in the oral cavity, and other factors lead to a divergence in oral care between patients after oral surgery and ordinary inpatients. High-quality oral care can reduce the incidence of incision infection and ventilator-associated pneumonia. However, there is a lack of guidelines or expert consensus on oral care after oral cancer surgery. Therefore, the aim of this study was to assess the practicing situation of nurses in the intensive care unit (ICU) for postoperative patients with oral cancer and their need for training. METHODS: A multicenter cross-sectional study design was conducted in 19 ICUs of 11 tertiary hospitals from Henan province in China. Data were collected from 173 nurses and 19 head nurses online using a structured questionnaire. Mann-Whitney U and Kruskal-Wallis H tests were performed to analyze the data using SPSS (Version 25.0). RESULTS: Seven ICUs (36.8%) developed evaluation regulations for the oral care of postoperative patients with oral cancer, and eight ICUs (42.1%) described the operating standards. A total of 173 nurses completed the questionnaire, and the median score was 75 (68, 78). Almost all of the examined nurses (91.2%) assessed patients' oral hygiene at a fixed time, while in 52.0% and 28.3% of nurses, the first oral care and frequency of oral care after surgery was determined based on the individual patient's situation. More than half of the nurses (55.5%) spent approximately 5-10 min conducting oral care for patients. Physiological saline solution (82.7%), swabbing (91.9%), and oral care package with cotton ball (86.1%) were the most popular oral care mouthwash, method, and tool, respectively. Nurses sought help from senior nurses (87.3%) and doctors (83.8%), mostly to solve difficulties of oral care. Moreover, 76.9% of the nurses believed that the lack of knowledge and skills surrounding oral care was the main barrier for nurses to implement oral care. The majority of participants (69.4%) had never received continuing education or training in oral care for postoperative patients with oral cancer, and almost all (98.8%) of the respondents stated their preference to receive training in standardized oral care skills. Indications and contraindications (84.4%), tools (81.5%), and mouthwash (80.9%) of oral care were the items that the respondents were most eager to learn about. Approximately three quarters of nurses preferred scenario simulation practice as the training method. CONCLUSION: Although the participants had high oral care scores for postoperative patients with oral cancer, there was great diversity in the practice. The lack of oral care knowledge was deemed the main barrier in delivering quality oral care, and the educational need was stated by almost all participants. We suggest that a standard protocol or clinical practice guidelines for oral care for postoperative patients with oral cancer should be developed, and nurses should be educated to equip them with professional knowledge and skills.

Elevated NT-proBNP levels are associated with CTP ischemic volume and 90-day functional outcomes in acute ischemic stroke: a retrospective cohort study.

OBJECTIVE: To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). METHODS: A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. RESULTS: NT-proBNP was positively correlated with CTP ischemic volume (p < 0.001), infarct core volume (p < 0.001), and ischemic penumbra volume (p < 0.001). Univariate analysis showed that the influence of NT-proBNP and functional outcomes were statistically significant in model 1 (p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p < 0.001), and adjusted for TnI, D-dimer, PLT, Cr, TC, TG, HDL-C, treatment decisions, and NIHSS score in model 4 (p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups. CONCLUSION: Elevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.

Effect of moisture gradient on rice yields and greenhouse gas emissions from rice paddies.

Fluxes of methane (CH4) and nitrous oxide (N2O) from two rice varieties, Huayou 14 and Hanyou 8, were monitored using closed chamber/gas chromatography method. Huayou 14 is a commonly grown variety of rice whereas Hanyou 8 is a water-saving and drought-resistant rice (WDR) variety. Low soil volumetric water content (VWC) existed in the treatments on the slope (W5 < W4 < W3 < W2). On the slope, rice yields of Hanyou 8 decreased by 12-39%, and Huayou 14 by 11-46% as compared to the plots on the flat. The total compatible solutes in Hanyou 8 had a greater variational range than Huayou 14. Compared to W1, CH4 emissions from W2-W5 decreased by 58-86% in Hanyou 8 and 38-86% in Huayou 14, whereas those of N2O increased by 26-121% in Hanyou 8 and 49-189% in Huayou 14 across both two seasons, which was mainly because the VWC varied in W2-W5 treatment. Under the treatments in the slope (W2, W3, W4, and W5), the global warming potential (GWP) was dominated by N2O emissions, which accounted for 69-90% of the GWP. Hanyou 8 had greater tolerance for water stress than Huayou 14 did, as evident from the smaller reductions in rice yield and greater variational range of total compatible solutes content. Water stress could reduce CH4 emissions but decrease N2O emissions for both rice varieties. This results suggest that planting WDR varieties under water shortage irrigation (such as W4, W5) will be able to maintain rice yields and reduce the GWP with less water.

Effects of Xie-Zhuo-Chu-Bi-Fang on miR-34a and URAT1 and their relationship in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xie-Zhuo-Chu-Bi-Fang (XZCBF) is an empirical formula that was developed based on the principles of traditional Chinese medicine, for the therapeutic purpose of treating hyperuricemia. XZCBF has been clinically utilized in the Department of Traditional Chinese Medicine at General Hospital of Guangzhou Military Command of PLA for many years and has exhibited favorable efficacy. The aim of the study is to evaluate the effects of XZCBF on the expression of uric acid transporter 1 (URAT1) and miR-34a in hyperuricemic mice and to determine, the correlation between the two expression levels. MATERIALS AND METHODS: A hyperuricemic animal model was created by administering adenine and allantoxanic acid potassium salt to mice. The blood uric acid levels were measured in these model mice after treatment with XZCBF for 15 days. The potential targets of miR-34a were screened. The expression levels of miR-34a and URAT1 in the renal tissues collected from the model mice were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was further established by immunohistochemistry and in situ hybridization. RESULTS: The uric acid levels in the model mice were significantly higher than those in the blank controls (P<0.05). These levels were significantly lower in the three groups receiving different doses of XZCBF (P<0.05), which was, in agreement with the downregulation of URAT1 and the upregulation of miR-34a in each group. The mRNA expression level of URAT1 was positively correlated with the concentration of uric acid but, negatively correlated with the expression level of miR-34a. CONCLUSIONS: The ability of XZCBF to facilitate the excretion of uric acid and to lower its level in the model group was mediated by the upregulation of miR-34a and the inhibition of URAT1 mRNA expression, which suggests that XZCBF could be an option for the treatment of hyperuricemia in mice.

Comparison of greenhouse gas emissions from rice paddy fields under different nitrogen fertilization loads in Chongming Island, Eastern China.

Rice is one of the major crops of southern China and Southeast Asia. Rice paddies are one of the largest agricultural greenhouse gas (GHG) sources in this region because of the application of large quantities of nitrogen (N) fertilizers to the plants. In particular, the production of methane (CH4) is a concern. Investigating a reasonable amount of fertilizers to apply to plants is essential to maintaining high yields while reducing GHG emissions. In this study, three levels of fertilizer application [high (300 kg N/ha), moderate (210 kg N/ha), and low (150 kg N/ha)] were designed to examine the effects of variation in N fertilizer application rate on carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) emissions from the paddy fields in Chongming Island, Shanghai, China. The high level (300 kg N/ha) represented the typical practice adopted by the local farmers in the area. Maximum amounts of CH4 and N2O fluxes were observed upon high-level fertilizer application in the plots. Cumulative N2O emissions of 23.09, 40.10, and 71.08 mg N2O/m(2) were observed over the growing season in 2011 under the low-, moderate-, and high-level applications plots, respectively. The field data also indicated that soil temperatures at 5 and 10 cm soil depths significantly affected soil respiration; the relationship between Rs and soil temperature in this study could be described by an exponential model. Our study showed that reducing the high rate of fertilizer application is a feasible way of attenuating the global-warming potential while maintaining the optimum yield for the studied paddy fields.

MicroRNA expression patterns of the kidney in hyperuricemia mice treated with Xiezhuo Chubi Decoction.

OBJECTIVE: To investigate the effects of Xiezhuo Chubi Decoction (XZCBD) on the microRNA expression patterns of kidney in mice with hyperuricemia. METHODS: Sixty Kunming male mice were randomly divided into the high-, medium-, and low-dose XZCBD groups, benzbromarone group, model group, and control group. Except the control group, all mice were established with yeast method combined with uricase inhibition method to build hyperuricemia model, and the corresponding drugs (37.5 g/kg, 18.75 g/kg, 9.375 g/kg, and 0.02 g/kg per day) were administrated on the 7th day. On the 22nd day, the blood uric acid concentration was detected, and microRNA with obvious changes in kidney was screened with qRT-PCR. RESULTS: The uric acid in the model group was higher than that in the control group, and the levels of the uric acid were reduced after being treated with XZCBD; the differences among groups were significant (P<0.05). Compared with the control group, 32 kinds of microRNA expression changes were detected on the 15th day after being treated with high-dose XZCBD by microRNA expression profile screening. Among them, miR-34a could inhibit the expression of human urate anion exthanger 1, and miR-146a might have inhibited the inflammatory reaction. CONCLUSION: XZCBD could significantly reduce the serum uric acid level; its effect on hyperuricemia might be through affecting microRNA expressions.