[Spatial distribution characteristics of metabolities in rhizome of Paris polyphylla var. yunnanensis: based on MALDI-MSI].

In this study, a method was established for in-situ visualization of metabolite distribution in the rhizome of Paris polyphylla var. yunnanensis. To be specific, through matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI), the spatial locations of steroidal saponins, amino acids, organic acids, phytosterols, phytoecdysones, nucleosides, and esters in rhizome of the medicinal plant were directly analyzed, and six unknown compounds with differential distribution in rhizome tissues were identified. The specific procedure is as follows: preparation of rhizome tissue section, matrix screening and optimization, and MALDI-MSI analysis. The results showed that the steroidal saponins were mainly distributed in the central, amino acids in epidermis and cortex, low-molecular-weight organic acids in central epidermis, phytosterols in the epidermis and lateral cortex, the phytoecdysones in epidermis and cortex, nucleosides(uneven distribution) in epidermis and cortex, growth hormones around the epidermis and cortex, particularly outside the cortex, and esters in cortex with unobvious difference among different tissues. In this study, the spatial distribution of meta-bolites in the rhizome of P. polyphylla var. yunnanensis was characterized for the first time. The result can serve as a reference for identifying and extracting endogenous metabolites of P. polyphylla var. yunnanensis, exploring the synthesis and metabolism mechanisms of the metabolites, and evaluating the quality of medicinal materials.

[Effect of 18-ß Glycyrrhetinic Acid on the Endoplasmic Reticulum of Nasal Epithelial Cells in Allergic Rhinitis Model Rats].

OBJECTIVE: To explore the effect of 18-ß glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats. METHODS: Totally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention. RESULTS: The overlapping score was 2.10 ± 0.45 in the blank group, 5.10 ± 0.56 in the loratadine group, 5.10 ± 0.56 in the AR model group, 5.20 ± 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group. CONCLUSION: 18-ß GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats.

[An investigation of the relationship of inflammatory response and insulin and its components during stress hyperglycemia in critically ill patients].

OBJECTIVE: To observe the relationship between inflammatory response and the constituents of islet ß cell secretion during stress hyperglycemia (SHG) in critically ill patients, in order to study the impact of inflammatory response on insulin resistance and the secretion function of islet ß cells. METHODS: According to the state of inflammatory response, 45 critical patients with SHG were divided into two groups: stress and the convalescence period. Twenty five healthy individuals were enrolled as control group. The blood levels of tumour necrosis factor ß (TNF-ß), blood glucose (BG), and insulin components including proinsulin (PI), immunoreactive insulin (IRI), true insulin (TI), C-peptide (C-P) were measured respectively. The levels of BG, TNF-ß, insulin components, insulin resistance index (HOMA-IR) and the secretion index (HOMA-ß) were compared among groups. The relationship between TNF-ß and BG, insulin components, HOMA-IR, HOMA-ß were analyzed. RESULTS: (1)There was no difference in concentrations of TI among stress period, convalescence stage and control group [3.68 (1.57, 7.70), 3.42 (2.41, 7.40), 1.46 (0.35, 4.90) mU/L, all P >0.05], whereas the concentration of BG [(10.04 ± 2.43) mmol/L], TNF-ß [13.70 (11.77, 20.00) ng/L], PI [6.20 (3.22, 9.27) pmol/L], IRI [13.45 (9.88, 19.88) mU/L] and C-P [3.01 (2.37, 4.00) µg/L]in stress period were significantly higher than those in the convalescence stage[BG: (6.09 ± 0.84) mmol/L, TNF-ß: 11.58 (8.80, 13.22) ng/L,PI: 1.54 (0.36, 11.82) pmol/L, IRI: 10.80 (5.35, 12.60) mU/L, C-P: 2.42 (1.17, 3.56) µg/L] and control group [BG: (4.87 ± 0.56) mmol/L,TNF-ß: 9.27 (7.48, 12.16) ng/L, PI: 2.20 (1.88, 4.54) pmol/L, IRI: 5.50 (4.00, 8.00) mU/L, C-P: 1.15 (0.87, 1.76) µg/L, P <0.05 or P <0.01]. (2)The HOMA-IR [5.17 (3.41, 11.51)] in stress period was significantly higher than that in the convalescence[3.24 (1.51, 6.95)] and control group [1.14 (0.81, 1.79), P <0.05 and P<0.01]. The HOMA-ß [10.80 (3.72, 31.40)] of isletß cell in stress period was significantly lower than that in the convalescence [28.42 (6.46, 125.01)] and control group [21.94 (7.77, 62.01), P <0.01 and P <0.05]. (3)There were positive correlations between the concentration of TNF-ß and PI, IRI, C-P and HOMA-IR ( r 1=0.292, r 2=0.344, r 3=0.397, r 4=0.324, P <0.05 or P <0.01). There were negative correlation between concentration of TNF-ß and HOMA-ß ( r =-0.235 , P <0.05) . CONCLUSION: The severer the inflammatory response, the higher PI, IRI and C-P, while the secretion of TI is relatively deficient.Inflammatory response could affect insulin resistance and the secretion function of islet ßcell during SHG in critically ill patients.

Development a multi-immunoaffinity column LC-MS-MS method for comprehensive investigation of mycotoxins contamination and co-occurrence in traditional Chinese medicinal materials.

Mycotoxins are poisonous secondary fungal toxic metabolites and harmful to human health. Traditional Chinese medicinal materials (TCMs), including more than two hundred functional foods, are vulnerably bred fungi, causing spoilage and multi-mycotoxins contamination. This study established a simultaneous analytical method by using multi-mycotoxins immunoaffinity column (multi-IAC) and HPLC-MS/MS to evaluate mycotoxins' contamination levels and natural incidence in TCMs. Aflatoxins (AFs, including AFB1, AFB2, AFG1 and AFG2), ochratoxin A (OTA), fumonisins (FB1 and FB2), zearalenone (ZEN), deoxynivalenol (DON) and T-2 toxins in three TCMs or functional foods of Polygalae Radix (PR), Coicis Semen (CS) and Eupolyphaga Steleophaga (ES) were detected. The systematically investigated results of 30 batch AFB1 positive samples revealed co-occurrence and correlation of multi-mycotoxins are significant differences in various matrices. All the samples in this study contain more than 5 mycotoxins. AFB1-AFs, AFB1-FBs, AFB1-DON, and AFB1-T-2 are the most observed co-occurrence, AFB1-OTA is also of concern due to its synergistic toxicity. This study's results can be used to establish guidelines for screening mycotoxin contaminants and limitations on acceptable levels in TCMs. Simultaneously, mycotoxin's correlation results in different matrices can also provide a reference for the standardization of TCM production and processing.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

The behaviors of Microcystis aeruginosa cells and extracellular microcystins during chitosan flocculation and flocs storage processes.

This work aimed to study the effects of chitosan on cell integrity and extracellular microcystins (MCs) of Microcystis aeruginosa cells during flocculation and flocs storage processes. The impacts of chitosan addition, flocculation stirring and flocs storage time were comprehensively detected to prevent or reduce cell lysis and MCs release. Response surface method (RSM) was applied to optimize the chitosan flocculation. Under chitosan concentration 7.31 mg/L and optimized mechanical conditions, 99% of M. aeruginosa cells were integrated removed. Furthermore, amounts of extracellular MCs were adsorbed by chitosan polymers in this process. With chitosan flocs protect, though cells showed some damage, extracellular MCs concentration in flocculated samples lower than background level within first 2 d. However, lots of MCs release was observed after 4d which may result from chitosan degradation and cells lysis. Therefore, chitosan flocs should be treated within 2d to prevent the adsorbed MCs releasing again.

A class-information-based penalized matrix decomposition for identifying plants core genes responding to abiotic stresses.

In terms of making genes expression data more interpretable and comprehensible, there exists a significant superiority on sparse methods. Many sparse methods, such as penalized matrix decomposition (PMD) and sparse principal component analysis (SPCA), have been applied to extract plants core genes. Supervised algorithms, especially the support vector machine-recursive feature elimination (SVM-RFE) method, always have good performance in gene selection. In this paper, we draw into class information via the total scatter matrix and put forward a class-information-based penalized matrix decomposition (CIPMD) method to improve the gene identification performance of PMD-based method. Firstly, the total scatter matrix is obtained based on different samples of the gene expression data. Secondly, a new data matrix is constructed by decomposing the total scatter matrix. Thirdly, the new data matrix is decomposed by PMD to obtain the sparse eigensamples. Finally, the core genes are identified according to the nonzero entries in eigensamples. The results on simulation data show that CIPMD method can reach higher identification accuracies than the conventional gene identification methods. Moreover, the results on real gene expression data demonstrate that CIPMD method can identify more core genes closely related to the abiotic stresses than the other methods.

Draft Genome Sequence of Haemophilus parasuis gx033, a Serotype 4 Strain Isolated from the Swine Lower Respiratory Tract.

Haemophilus parasuis serotype 4 is a Gram-negative pathogen that is the most prevalent H. parasuis serovar in the world, but its genome sequence information has not yet been reported. Thus, we determined the genome of H. parasuis strain gx033, a serovar 4 strain isolated from a lung specimen of a diseased piglet in southwestern China. Here, we present the first draft genome sequence of this species.