Metabolomics combined with physiology and transcriptomics reveal key metabolic pathway responses in apple plants exposure to different selenium concentrations.

Selenium (Se) can be absorbed by plants, thereby affects plant physiological activity, interferes gene expression, alters metabolite content and influences plant growth. However, the molecular mechanism underlying the plant response to Se remains unclear. In this study, apple plants were exposed to Se at concentrations of 0, 3, 6, 9, 12, 24, and 48 µM. Low concentrations of Se promoted plant growth, while high Se concentrations (≥24 µM) reduced photosynthesis, disturbed carbon and nitrogen metabolism, damaged the antioxidant system, and ultimately inhibited plant growth. The transcriptome and metabolome revealed that Se mainly affected three pathways, namely the 'biosynthesis of amino acids', 'starch and sucrose metabolism', and 'phenylpropanoid biosynthesis' pathways. 9 µM Se improved the synthesis, catabolism and utilization of amino acids and sugars, ultimately promoted plant growth. However, 24 µM Se up-regulated the related genes expression of PK, GPT, P5CS, SUS, SPS and CYP98A, and accumulated a large number of osmoregulation substances, such as citric acid, L-proline, D-sucrose and chlorogenic acid in the roots, ultimately affected the balance between plant growth and defense. In conclusion, this study reveals new insights into the key metabolic pathway in apple plants responses to Se.

Magnesium alleviates aluminum-induced growth inhibition by enhancing antioxidant enzyme activity and carbon-nitrogen metabolism in apple seedlings.

Previous studies have determined that magnesium (Mg) in appropriate concentrations prevents plants from suffering from abiotic stress. To better understand the mechanism of Mg alleviation of aluminum (Al) stress in apple, we investigated the effect of Mg on plant growth, photosynthetic fluorescence, antioxidant system, and carbon (C) and nitrogen (N) metabolism of apple seedlings under Al toxicity (1.5 mmol/L) via a hydroponic experiment. Al stress induced the production of reactive oxygen in the leaves and roots and reduced the total dry weight (DW) by 52.37 % after 20 days of treatment relative to plants grown without Al, due to hindered photosynthesis and alterations in C and N metabolism. By contrast, total DW decreased by only 11.07 % in the Mg-treated plants under Al stress. Supplementation with 3.0 mmol/L Mg in the Al treatment decreased Al accumulation in the apple plants and reduced Al-induced oxidative damage by enhancing the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and reducing the production of H2O2 and malondialdehyde (MDA). Under Al stress, the Mg-treated plants showed a 46.17 % higher photosynthetic rate than the non-treated plants. Supplementation with Mg significantly increased the sucrose content by increasing sucrose synthase (SS) and sucrose-phosphate synthase (SPS) activities. Moreover, Mg facilitated the transport of 13C-carbohydrates from the leaves to roots. Regarding N metabolism, the nitrate reductase (NR), glutamine synthase (GS), and glutamate synthase (GOGAT) activities in the roots and leaves of the Mg-treated plants were significantly higher than those of the non-treated plants under Al stress. Compared with the non-treated plants under Al stress, the Mg-treated plants exhibited a significantly high level of NO3- and soluble protein content in the leaves, roots, and stems, but a low level of free amino acids. Furthermore, Mg significantly improved nitrogen accumulation and enhanced the transport of 15N from the roots to leaves. Overall, our results revealed that Mg alleviates Al-induced growth inhibition by enhancing antioxidant capacity and C-N metabolism in apple seedlings.

Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study.

BACKGROUND: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up. FINDINGS: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators. INTERPRETATION: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population. FUNDING: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Efficacy of Huangqi Injection in the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

Background: Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed to be an important adjuvant therapy for hypertensive nephropathy. Objective: To evaluate the efficacy of HQI combined with antihypertensive drugs in the treatment of hypertensive nephropathy. Materials and Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Knowledge Service Platform (WanfangData), Chinese Biomedical Database (CBM), EMBASE, PubMed and Cochrane Library from their inception to April 23st, 2021. All studies were independently screened by two auditors according to the inclusion and exclusion criteria. Randomized controlled trials comparing HQI in combination with antihypertensive drugs vs. antihypertensive drugs alone were extracted. Results: The meta-analysis included 15 studies involving 1,483 participants.The effect of HQI combined with antihypertensive drugs is better than that of antihypertensive drugs alone in regulating hypertensive nephropathy for reducing 24-h urinary total protein (24 h UTP) [WMD=-0.29, 95% CI (-0.40, -0.18), P = 0.000], microalbuminuria (mALB) [WMD = -17.04, 95% CI (-23.14, -10.94), P = 0.000], serum creatinine (SCr) [WMD = -40.39, 95% CI (-70.39, -10.39), P = 0.008], systolic blood pressure (SBP) [WMD = -9.50, 95% CI (-14.64, -4.37), P = 0.000], diastolic blood pressure (DBP) [WMD = -4.588, 95% CI (-6.036, -3.140), P = 0.000], cystatin-C (Cys-c) [WMD = -0.854, 95% CI (-0.99, -0.72), P = 0.000], blood urea nitrogen (BUN) [WMD = -4.155, 95% CI (-6.152, -2.157), P = 0.000]. Conclusion: The combination of HQI and antihypertensive drugs is more efficient in improving the related indexes of patients with hypertensive nephropathy than using antihypertensive drugs alone, and a moderate dose of HQI (no more than 30 mL) may benefit more. However, the quality of the methodology is low and the number of samples is small, the results need to be confirmed by more stringent randomized controlled trials.

Enhanced angiogenesis with dl-3n-butylphthalide treatment after focal cerebral ischemia in RHRSP.

Appropriate restoration of blood flow via angiogenesis is critical for the recovery from ischemic stroke. Previously, we reported that treatment with dl-3n-butylphthalide (NBP) increases the number of local potent cerebral microvessels. However, the underlying mechanism remained unclear. The present study was conducted to test whether NBP enhances post-ischemic cerebral angiogenesis via vascular endothelial growth factor (VEGF) and hypoxia induced factor-1 alpha (HIF-1 alpha). Stroke-prone renovascular hypertensive rats (RHRSP) were used to create middle cerebral artery occlusion (MCAO) model. NBP was given 80 mg/kg per d for 10 consecutive days, starting 12, 24, 48 and 72 h respectively after MCAO. Neurological function was assessed daily and infarct volume as well as the expressions of CD31, VEGF, HIF-1 alpha and bFGF was detected 13 days after MCAO. The administration of NBP starting within 24 h after MCAO enhanced recovery of neurobehavioral function, reduced infarct volume, increased the quantity of CD31 positive vessels, and up-regulated expressions of VEGF and HIF-1 alpha. These findings suggest that treatment with NBP within 24 h post-ischemic stroke rescues brain tissue by enhancing angiogenesis associated with up-regulation of VEGF and HIF-1 alpha expressions.

[Study on tissue culture of Ficus hirta].

The tissue culture of Ficus hirta Vahl. was studied. The nodes were used as explants and 1/2MS media with different plant growth regulators were tested. The result showed that the adventitious bud differentiation medium was 1/2MS + BA1.0 mg/L + NAA1.0 mg/L and 1/2MS + BA1.5 mg/L + NAA0.5 mg/L, the media for multiplication was 1/2MS +6 - BA0.5 mg/L, and the medium for rooting was 1/2MS + IBA1 mg/L. The cause of nigrescence in the tissue culture and its preventive methods were also discussed in this paper.

[Content determination of psoralen in root of Ficus hitra by HPLC method].

OBJECTIVE: To investigate the contents of psoralen in Ficus hitra. METHODS: High Performance Liquid Chromatography was performed on Diamonsil C18. The chromatographic conditions were as follows: methanol-water (60:40) as mobile phase, flow rate being 1 ml/min and detecting wavelength at 245nm. RESULTS: A good linearity of psoralen was shown in range of 0. 356 - 2. 848 mg/ml (r = 0.9999), the average recovery is 103.99%, RSD = 3.07% (n = 5). The method has good reproducibility, RSD = 1.59% CONCLUSION: This method can supply evidence for the quality evaluation of Ficus hitra.