Cardioprotective effect of saffron total glycoside tablets in patients with breast cancer receiving anthracycline-based chemotherapy: study protocol for a multicentre, randomised, parallel, double-blind, placebo-controlled clinical trial.

BACKGROUND: Breast cancer is the most common cancer worldwide. Anthracyclines, alone or in combination with other chemotherapeutic agents, are the most effective chemotherapy agents against breast cancer. However, the dose-dependent cardiotoxicity of anthracyclines is a serious drawback in clinical treatment. Considerable efforts have been made to establish suggestions to avoid anthracycline-induced cardiotoxicity. Crocin extracted from saffron has potential cardioprotective effects against anthracycline-induced cardiotoxicity. The aim of this study was to estimate the cardioprotective effects and safety of saffron total glycoside tablets relative to placebo in patients with breast cancer undergoing anthracycline-based chemotherapy. METHODS: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A sample of 200 participants (100 per group) with breast cancer will be randomly assigned to receive either saffron total glycoside tablet or placebo (four tablets each time, three times each day) for 6 months. Each participant will be interviewed three times: baseline (visit 1), after 3 months (visit 2), and after 6 months (visit 3). The primary outcome is to confirm if administration of saffron total glycoside tablets reduces the rate of cardiotoxicity relative to that with placebo. Secondary outcomes include new arrhythmic events, and cardiac troponin I and N-terminal pro-B-type natriuretic peptide levels. The quantity, quality, and severity of the adverse events will be carefully documented. DISCUSSION: We look forward to obtaining high-quality evidence that can be used to formulate clinical practice guidelines. Thus, the findings of this study are expected to help fill the current gap in cardiotoxicity prevention drugs. TRIAL REGISTRATION: This trial was published in the Chinese Clinical Trial Registry (No. ChiCTR2000041134, registered on 19th December 2020).

First report of Nigrospora sphaerica causing fruit dried-shrink disease in Akebia trifoliata from China.

Akebia trifoliata, a recently domesticated horticultural crop, produces delicious fruits containing multiple nutritional metabolites and has been widely used as medicinal herb in China. In June 2020, symptoms of dried-shrink disease were first observed on fruits of A. trifoliata grown in Zhangjiajie, China (110.2°E, 29.4°N) with an incidence about 10%. The infected fruits were shrunken, colored in dark brown, and withered to death (Figure S1A, B). The symptomatic fruits tissues (6 × 6 mm) were excised from three individual plants, surface-disinfested in 1% NaOCl for 30s and 70% ethanol solution for 45s, washed, dried, and plated on potato dextrose agar (PDA) containing 50 mg/L streptomycin sulfate in the dark, and incubated at 25℃ for 3 days. Subsequently, hyphal tips were transferred to PDA to obtain pure cultures. After 7 days, five pure cultures were obtained, including two identical to previously reported Colletotrichum gloeosporioides causing leaf anthracnose in A. trifoliata (Pan et al. 2020) and three unknown isolates (ZJJ-C1-1, ZJJ-C1-2, and ZJJ-C1-3). The mycelia of ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3 were white, and formed colonies of approximate 70 mm (diameter) in size at 25℃ after 7 days on potato sucrose agar (PSA) plates (Figure S1C). After 25 days, conidia were formed, solitary, globose, black, shiny, smooth, and 16-21 µm in size (average diameter = 18.22 ± 1.00 µm, n = 20) (Figure S1D). These morphological characteristics were similar to those of N. sphaerica previously reported (Li et al. 2018). To identify species of ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3, the internal transcribed spacer (ITS) region, ß-tubulin (TUB2), and the translation elongation factor 1-alpha (TEF1-α) were amplified using primer pairs including ITS1/ITS4 (Vilgalys and Hester 1990), Bt-2a/Bt-2b (Glass and Donaldson 1995), and EF1-728F/EF-2 (Zhou et al. 2015), respectively. Multiple sequence analyses showed no nucleotide difference was detected among genes tested except ITS that placed three isolates into two groups (Figure S2). BLAST analyses determined that ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3 had 99.73% to N. sphaerica strains LC2705 (KY019479), 100% to LC7294 (KY019397), and 99.79-100% to LC7294 (KX985932) or LC7294 (KX985932) based on sequences of TUB2 (MW252168, MW269660, MW269661), TEF-1α (MW252169, MW269662, MW269663), and ITS (MW250235, MW250236, MW192897), respectively. These indicated three isolates belong to the same species of N. sphaerica. Based on a combined dataset of ITS, TUB2 and TEF-1α sequences, a phylogenetic tree was constructed using Maximum likelihood method through IQ-TREE (Minh et al. 2020) and confirmed that three isolates were N. sphaerica (Figure S2). Further, pathogenicity tests were performed. Briefly, healthy unwounded fruits were surface-disinfected in 0.1% NaOCl for 30s, washed, dried and needling-wounded. Then, three fruits were inoculated with 10 µl of conidial suspension (1 × 106 conidia/ml) derived from three individual isolates, with another three fruits sprayed with 10 µl sterilized water as control. The treated fruits were incubated at 25℃ in 90% humidity. After 15 days, all the three fruits inoculated with conidia displayed typical dried-shrink symptoms as those observed in the farm field (Figure S1E). The decayed tissues with mycelium and spores could be observed on the skin or vertical split of the infected fruits after 15 days' inoculation (Figure S1F-H). Comparably, in the three control fruits, there were no dried-shrink-related symptoms displayed. The experiment was repeated twice. The re-isolated pathogens were identical to N. sphaerica determined by sequencing the ITS, TUB2 and TEF-1α. Previous reports showed N. sphaerica could cause postharvest rot disease in kiwifruits (Li et al. 2018). To our knowledge, this is the first report of N. sphaerica causing fruits dried-shrink disease in A. trifoliata in China.

Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues-Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6. Our study provides a new potential way to explore potential inhibitors from TCMS.

Dietary supplementation with polypeptides improved growth performance, antibacterial immune and intestinal microbiota structure of Litopenaeus vannamei.

Antibacterial peptides (AMPs) are expected to replace some or all of the antibiotics and become a new feed additive. However, the high production cost and unclear mechanism limited the application of AMPs. In this research, the effects of a commercial polypeptide (Polypeptide S100) whose main components are AMPs on the growth, antibacterial immune and intestinal microbial of Litopenaeus vannamei were study. L. vannamei (initial weight of 0.16 ±â€¯0.03 g) were fed for 123 days with basal diet added Polypeptide S100 at two levels each (0.5% and 1%) as experimental groups, and a basal diet as control. Dietary inclusion of Polypeptide S100 at 1% level significantly increased the weight gain (WG) and specific growth rate (SGR) of L. vannamei. The survival rates of L. vannamei in 0.5% and 1% Polypeptide S100 groups were significantly higher than the control when infected by Vibrio harveyi but not Vibrio parahaemolyticus. The activities of total superoxide dismutase (T-SOD) and lysozyme (LZM) in the two experimental groups were all significantly higher than the control. Differently, the activities of amylase (AMS) and lipase (LPS) were significantly higher in 0.5% Polypeptide S100 group but lower in 1.0% Polypeptide S100 group. Illumina MiSeq high-throughput sequencing showed that the dominant phyla in the intestine of L. vannamei were Proteobacteria, followed by Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Fusobacteria and Tenericutes, and the abundance of predominant phyla Cyanobacteria were upregulated significantly in the experimental groups. At the family level, significant increase was observed in Pseudomonadaceae and Xanthomonadaceae but decrease in Vibrionaceae in the 1.0% Polypeptide S100 group. The abundance of predominant genus Photobacterium were obviously downregulated in the two experimental groups. Unlikely, the abundance of Pseudomonas and Stenotrophomonas were distinctly increased in the 1.0% Polypeptide S100 group but not significantly different from the control in 0.5% Polypeptide S100 group. All these results suggested that Polypeptide S100 could improve the growth performance, antibacterial immune and intestinal microbiota structure of L. vannamei.

Cerebral arterial air embolism after computed tomography-guided hook-wire localization of a pulmonary nodule: A case report.

RATIONALE: Cranial arterial air embolism is a rare but potentially fatal complication after computed tomography (CT)-guided pulmonary interventions. PATIENT CONCERNS: A 64-year-old man was diagnosed with a pulmonary nodule (diameter: approximately 1 cm) in the right lower lobe. The patient developed convulsions after CT-guided hook-wire localization. DIAGNOSIS: Cranial CT revealed arborizing/linearly distributed gas in the territory of the right middle cerebral artery. INTERVENTIONS: The patient was administered hyperbaric oxygen, antiplatelet aggregation therapy, and dehydration treatment. OUTCOMES: Clinical death occurred 55 hours after air embolism. LESSONS: Systemic air embolism is a serious complication of lung puncture. Clinicians should improve their understanding of this complication and remain vigilant against air embolism.

[Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].

In order to explore how the modification of succinic acid improves the adsorption of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by succinic acid, after the pretreatments of crushing, screening, alkalization and acidification. Infrared analysis indicated carboxylic acid groups and ester groups were added to the sawdust after modification, and scanning electron microscope demonstrated after modification the appearance of tea oil tree sawdust was transferred from the structure like compact and straight stripped into the structure like loose and wrinkled leaves, which meant modification increased its inner pores. By the static experiments, effects of reaction time between adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial concentration of uranium were investigated. The results showed that after the modification by succinic acid, the absorption rate of tea oil tree sawdust for uranium increased significantly by about 20% in 12.5 mg · L(-1) initial concentration uranium solution. Adsorption equilibrium was achieved within 180 min, and the kinetic data can be well described by the pseudo-second-order kinetic model. The experimental adsorption isotherm followed the Langmuir and Freundlich models. In addition, the maximum adsorption amounts of tea oil tree sawdust after modification calculated from Langmuir equation raised from 21.413 3 to 31.545 7 mg · g(-1) at 35°C and pH 4.0.

Hydrogen sulfide prolongs postharvest shelf life of strawberry and plays an antioxidative role in fruits.

Accumulating evidence shows that hydrogen sulfide (H(2)S) plays various physiological roles in plants, such as seed germination, root organogenesis, abiotic stress tolerance, and senescence of cut flowers. However, whether H(2)S participates in the regulation of ripening and senescence in postharvest fruits remains unknown. In the present study, the effect of H(2)S on postharvest shelf life and antioxidant metabolism in strawberry fruits was investigated. Fumigation with H(2)S gas released from the H(2)S donor NaHS prolonged postharvest shelf life of strawberry fruits in a dose-dependent manner. Strawberry fruits fumigated with various concentrations of H(2)S sustained significantly lower rot index, higher fruit firmness, and kept lower respiration intensity and polygalacturonase activities than controls. Further investigation showed that H(2)S treatment maintained higher activities of catalase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase and lower activities of lipoxygenase relative to untreated controls. H(2)S also reduced malondialdehyde, hydrogen peroxide, and superoxide anion to levels below control fruits during storage. Moreover, H(2)S treatment maintained higher contents of reducing sugars, soluble proteins, free amino acid, and endogenous H(2)S in fruits. We interpret these data as indicating that H(2)S plays an antioxidative role in prolonging postharvest shelf life of strawberry fruits.

Zooming in on a quantitative trait for tomato yield using interspecific introgressions.

To explore natural biodiversity we developed and examined introgression lines (ILs) containing chromosome segments of wild species (Solanum pennellii) in the background of the cultivated tomato (S. lycopersicum). We identified Brix9-2-5, which is a S. pennellii quantitative trait locus (QTL) that increases sugar yield of tomatoes and was mapped within a flower- and fruit-specific invertase (LIN5). QTL analysis representing five different tomato species delimited the functional polymorphism of Brix9-2-5 to an amino acid near the catalytic site of the invertase crystal, affecting enzyme kinetics and fruit sink strength. These results underline the power of diverse ILs for high-resolution perspectives on complex phenotypes.