The mechanism of melatonin promotion on cucumber seedling growth at different nitrogen levels.

The supply level of exogenous nitrogen has a very important influence on the growth and development of cucumber. Insufficient or excessive nitrogen application will lead to metabolic disorders in the body and affect the formation of yield. Therefore, it is of great scientific and practical significance to explore the corresponding mitigation measures. Melatonin (MT) is a multi-regulatory molecule with pleiotropic effects on plant growth and development. A large number of studies have shown that the appropriate amount of melatonin supplementation is beneficial to plant growth and development by promoting root development, delaying leaf senescence, and improving fruit yield. However, the study of MT function combined with a detailed physiological analysis of nitrogen (N) absorption and metabolism in cucumber plants needs further strengthening. We performed hydroponic tests at different nitrogen levels to determine the metabolic processes associated with the enhanced tolerance to nitrogen in melatonin-treated cucumber (Cucucumis sativus L.) seedlings. Cucumber seedlings were sprayed with 100 µM melatonin or water and treated with different nitrogen in the growth chamber for 7 days. Nitrogen deficiency significantly inhibited seedling growth, and this growth inhibition was partially alleviated by melatonin. The expression analysis of related carbon and nitrogen genes showed that the genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. By enzyme activity and reactive oxygen content data analysis, melatonin-treated cucumber seedlings showed relatively stable carbon and nitrogen levels compared to untreated ones. In conclusion, MT can repair the impaired growth and development situation by regulating the nitrogen assimilation capacity and the balance between oxidation and oxidative metabolism and carbon metabolism in the cucumber under different nitrogen levels.

[Effect of moxibustion with deqi on Aß-receptor mediated transport and enzymatic degradation in hippocampus in rats with Alzheimer's disease].

OBJECTIVE: To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on ß-amyloid (Aß) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function. METHODS: Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aß1-42 at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi, the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aß and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2]. RESULTS: Compared with the sham-operation group, in the model group, the escape latency was prolonged (P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced (P<0.01); the brain tissue was seriously damaged; the expression of hippocampal Aß and RAGE was increased (P<0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased (P<0.01). Compared with the model group, the escape latency was shortened in the deqi group (P<0.05, P<0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 (P<0.05, P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aß and RAGE was decreased (P<0.01, P<0.05) and the expression of LRP1 and IDE was increased in each moxibustion group (P<0.01, P<0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the expression of NEP was increased in deqi group (P<0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group (P<0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 (P<0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased (P<0.05, P<0.01). Compared with the non-deqi group, the expression of Aß was reduced (P<0.05), the expression of LRP1 and ApoE was increased in the deqi group (P<0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group (P<0.05). CONCLUSION: Compared with non-deqi, moxibustion with deqi could promote Aß transport and degradation, thereby reducing Aß level in the brain and improving cognitive function for AD rats.

Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury.

Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI-AKI) remains unclear. Using single-cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte-derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9hi Ly6chi IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9+ macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small-molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long-term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI.

Complementary and alternative therapies for generalized anxiety disorder: A protocol for systematic review and network meta-analysis.

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent and impairing psychiatric disorder, which is a great threat to people's mental health, and imposes a major burden on individuals, families and society. Complementary and alternative medicine (CAM) therapies is a potential treatment for GAD, however, the selection strategies of different CAM therapies in clinical practice is still unclear, and the purpose of this study is to evaluate the efficacy and acceptability of different CAM interventions using systematic review and network meta-analysis (NMA). METHODS: Based on the strategy, the authors will retrieve a total of 9 electronic databases by January 2023. After a series of screening, the 2 researchers will use Aggregate Data Drug Information System (ADDIS) and Stata software to analyze the data extracted from randomized controlled trials (RCTs) of CAM therapies for the GAD. Finally, the evidence grade of the results will be evaluated. RESULTS: This study will provide a reliable evidence for the selection of CAM therapies for GAD. CONCLUSION: The results of this study will provide references for evaluating the influence of different CAM therapies for GAD, and provide a choice basis for clinical decision-making.

[Systematic review and Meta analysis on the effectiveness and safety of tuina in treatment of functional constipation].

OBJECTIVE: To review systematically the effectiveness and safety of tuina (Chinese massage)in treatment of functional constipation. METHODS: The articles on functional constipation treated with tuina were collected by computer retrieval from 7 databases from the date of establishment to March 28, 2020, including Chinese biomedical literature database (SinoMed), China journal full-text database (CNKI), full-text database of Wanfang academic journals (Wanfang), VIP Chinese science and technology journal database(VIP), PubMed, Dutch medical literature database (EMbase) and the Cochrane Library. After data extraction and quality evaluation of the included articles, Meta analysis was conducted with RevMan5.3 software. RESULTS: A total of 16 articles were included, with 1424 cases involved. Meta analysis results showed: ①The total effective rate in the treatment group was higher than that in the control group (RR=1.28, 95%CI: 1.16-1.42, P<0.000 01). ②The effective rate for the symptoms of functional constipation in traditional Chinese medicine in the treatment group was higher than that in the control group (RR=1.38, 95%CI :1.25-1.52, Z=6.31, P<0.000 01). ③Adverse reactions in the treatment group in the treatment of functional constipation were less than those in the control group (RR=0.10, 95%CI: 0.02-0.49, Z=2.81, P=0.005).④The effective rate of functional constipation treated on the base of syndrome differentiation in the treatment group was higher than that of the control group (RR=1.50, 95%CI: 1.08-2.10, Z=2.39, P=0.02).⑤The improvements in fecal characteristics, defecation time and defecation frequency of the patients with functional constipation in the treatment group were better than those in the control group (P<0.05). CONCLUSION: Tuina therapy presents a certain advantages on its curative effect on functional constipation, has less adverse reactions and relieves the relevant symptoms of functional constipation. But more randomized controlled trials with high quality and large sample are required to provide further verification of its effect.

Clinical analysis of 132 cases COVID-19 from Wuhan.

Numerous cases of pneumonia from a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China during December 2019.We determined the correlations of patient parameters with disease severity in patients with COVID-19.A total of 132 patients from Wuhan Fourth Hospital who had COVID-19 from February 1 to February 29 in 2020 were retrospectively analyzed.Ninety patients had mild disease, 32 had severe disease, and 10 had critical disease. The severe/critical group was older (P < .05), had a higher proportion of males (P < .05), and had a greater mortality rate (0% vs 61.9%, P < .05). The main symptoms were fever (n = 112, 84.8%) and cough (n = 96, 72.7%). Patients were treated with antiviral agents (n = 94, 71.2%), antibiotics (n = 92, 69.7%), glucocorticoids (n = 46, 34.8%), intravenous immunoglobulin (n = 38, 27.3%), and/or traditional Chinese medicine (n = 40, 30.3%). Patients in the severe/critical group received mechanical ventilation (n = 22, 16.7%) or high-flow nasal can-nula oxygen therapy (n = 6, 4.5%). Chest computed tomography (CT) indicated bilateral pneumonia in all patients. Relative to the mild group, the severe/critical group had higher levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, B-type natriuretic peptide (BNP), liver enzymes, and myocardial enzymes (P < .05), and decreased levels of lymphocytes and blood oxygen partial pressure (P < .05).The main clinical symptoms of patients from Wuhan who had COVID-19 were fever and cough. Patients with severe/critical disease were more likely to be male and elderly. Disease severity correlated with increased leukocytes, CRP, PCT, BNP, D-dimer, liver enzymes, and myocardial enzymes, and with decreased lymphocytes and blood oxygen partial pressure.

Effect of CaCl2 pre-treatment on the succinylation of potato starch.

Potato starch was pre-treated with CaCl2 solutions prior to modification with octenyl succinic anhydride (OSA). Starch pre-treated with 1.0 M CaCl2 showed higher degree of substitution (DS) and reaction efficiency (RE) on OSA modification, whereas pre-treatment with CaCl2 solutions at 0.05 M, 0.1 M and 0.5 M had no effect on DS and RE. CaCl2 pre-treatment decreased the swelling power, paste clarity, peak viscosity (PV), breakdown (BD) and some textural parameters of potato starch, with the effects being greater at higher concentrations of CaCl2. Pre-treatment with 1.0 M CaCl2 caused a small disruption to starch crystallinity and granule morphology. OSA modification significantly decreased the textural parameters, PV, BD, relative crystallinity, swelling power, gelatinization temperatures and enthalpy of potato starch, but it increased the paste clarity and emulsifying activity. OSA-1.0 M-starch showed improved functional properties over OSA-starch, indicating that CaCl2 pre-treatment provides advantages for improving the functional characters of succinylated starch.

Association between plasma phosphorus and renal outcome: A prospective cohort of patients majorly with glomerulonephritis.

AIM: Studies investigating the association between blood phosphorus and renal outcomes yielded inconsistent results, and studies from Asian population are extremely limited. We initiated the present cohort study, aiming to prospectively examine the association between blood phosphorus and adverse renal outcomes in a prospective chronic kidney disease (CKD) cohort of Chinese patients majorly with glomerulonephritis. METHODS: A total of 1430 patients were involved in the study. Linear regression analyses were used to assess the relationship between phosphorus and the slope of estimated glomerular filtration rate (eGFR). Cox regression analyses were used to assess the association between phosphorus and composite outcomes, which were defined as the presence of at least one of: eGFR halving, end stage renal disease, or death. RESULTS: During follow-up for an average of 41.4 months, 196 patients developed composite outcomes. The time-average plasma phosphorus was independently associated with the slope of eGFR (ß = -0.18, 95% CI: -4.42 to -2.19, P < 0.001). Each 1 mg/dL increases of baseline and time-average phosphorus were respectively associated with a 1.33 (95% confidence interval (CI): 1.09-1.63; P = 0.005) and 2.79 (95%CI: 2.21-3.52; P < 0.001) fold higher risk of composite outcomes. Compared with participants in the bottom quartile of time-average phosphorus, those in the top quartile were at increased risk of composite outcomes, with a hazard ratio of 6.52 (95% CI: 3.05-13.90; P < 0.001). CONCLUSION: Plasma phosphorus level is an independent risk factor of adverse renal outcomes in Chinese CKD patients majorly with glomerulonephritis. Compared with baseline value, time-average phosphorus has a stronger relationship with renal prognosis.

Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease.

BACKGROUND: Mineral and bone disorder (MBD), especially hyperphosphatemia, is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD). However, CKD-MBD among Chinese population was poorly studied. This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD. METHODS: Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China. Markers of MBD, including serum phosphorus, calcium, and intact parathyroid hormone, were measured in baseline samples at the patients' entry. The association between serum phosphorus and abdominal aortic calcification (AAC), left ventricular hypertrophy (LVH) were examined by logistic regression models. RESULTS: Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml.min-1.1.73 m-2 were included. The proportion of patients with hyperphosphatemia were 2.6%, 2.9%, 6.8%, and 27.1% in CKD Stages 3a, 3b, 4, and 5, respectively. Moreover, 71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB). Lateral abdominal X-rays were obtained in 2280 patients, 9.8% of the patients were diagnosed as having AAC. Altogether 2219 patients had data of echocardiography, and 13.2% of them were diagnosed with LVH. Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH. CONCLUSIONS: In Chinese patients with CKD, the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal. The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.

Levels of Serum Phosphorus and Cardiovascular Surrogate Markers.

AIM: This study aimed to evaluate the cross-sectional association between serum phosphorus and arterial stiffness among a health checkup population. METHODS: The study population included 26791 individuals without impaired kidney function. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), ankle brachial index (ABI), and augmentation index (AI) by the radial artery waveform analysis. Linear or logistic regression model was used to appropriately evaluate the association between phosphorus levels and arterial stiffness markers. RESULTS: The mean age of the population was 49 years and 67% were male. The phosphorus level was divided into quintiles. After multivariate adjustments, participants in the fourth (3.90-4.17 mg/dL) and fifth quintile (≥ 4.18 mg/dL) of serum phosphorus had increased the level of baPWV with linear regression coefficients of 11.9 [95% confidence interval (CI): 5.6-18.2] and 17.2 (95% CI: 10.9-23.5), respectively, compared with those in the first quintile (＜3.34 mg/dL). No significant associations were found between each quintile of phosphorus and ABI ＜0.9. However, participants in the fifth quintile of phosphorus had an increased risk of ABI ≥ 1.3 with an odds ratio (OR) of 1.2 (95% CI: 1.0-1.5) compared with the reference quintile. Furthermore, the increased risks could be observed for AI ＞97% throughout the second to fifth quintile of phosphorus and the ORs were 1.1 (95% CI: 1.0-1.3), 1.2 (95% CI: 1.0-1.4), 1.3 (95% CI: 1.1-1.5), and 1.5 (95% CI: 1.3-1.7), respectively. CONCLUSIONS: Higher serum phosphorus levels, even within the normal range, are associated with markers of arterial stiffness among general population with normal kidney function.

Serum Phosphorus and Progression of CKD and Mortality: A Meta-analysis of Cohort Studies.

BACKGROUND: Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Non-dialysis-dependent patients with CKD (transplant recipients were excluded). SELECTION CRITERIA FOR STUDIES: Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non-dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. PREDICTOR: Serum phosphorus level. OUTCOME: Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. RESULTS: In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). LIMITATIONS: Existence of potential residual confounding could not be excluded. CONCLUSIONS: This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non-dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.

Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs.

A series of achiral hypoxia-activated prodrugs were synthesized on the basis of the DNA cross-linking toxin of the prodrug, ifosfamide. The hypoxia-selective cytotoxicity of several of the compounds was improved over previously reported racemic mixtures of chiral bioreductive phosphoramidate prodrugs. Prodrugs activated by 2-nitroimidazole reduction demonstrated up to 400-fold enhanced cytotoxicity toward H460 cells in culture under hypoxia versus their potency under aerobic conditions. Compounds were further assessed for their stability to cytochrome P450 metabolism using a liver microsome assay. The 2-nitroimidazole containing lead compound 3b (TH-302) was selectively potent under hypoxia and stable to liver microsomes. It was active in an in vivo MIA PaCa-2 pancreatic cancer orthotopic xenograft model as a monotherapy and demonstrated dramatic efficacy when used in combination with gemcitabine, extending survival with one of eight animals tumor free at day-44. Compound 3b has emerged as a promising antitumor agent that shows excellent in vivo efficacy and is currently being evaluated in the clinic.