Mortality Study of Patients with Omicron Infection Before and After the Implementation of the New Crown Standard.

Objective: To investigate the mortality rate of patients with Omicron infection before and after the implementation of the new crown standard, and to evaluate the impact of new treatment protocols on the mortality rate of patients with Omicron infection. Methods: Clinical data of 1419 Omicron-infected patients treated in our hospital from April 10, 2022 to June 3, 2022 were collected(Patients diagnosed with Omicron infection who met the diagnostic criteria in the "Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 9)"15 and whose nasal/pharyngeal swab samples were typed as Omicron variants by laboratory viral genotyping). They were divided into the observation group (April 25 2022 - June 3 2022) and the control group (April 10 2022 - April 24 2022) before and after the implementation criteria. Clinical data of 1419 patients were collected and compared between the two groups on whether to use anticoagulant drugs, whether to use antiplatelet drugs, gender, whether to use new drugs of thymosin/thymus method, age, whether to use herbal medicine, whether to use Fuzheng prescription, blood routine, liver function, kidney function indicators, mortality of patients. Results: A total of 1419 patients were initially selected; 501 patients with incomplete information were excluded, and finally, 918 patients were included. According to the time period before and after the application criteria, they were divided into an observation group (586 cases) and a control group (332 cases). There were no statistically significant differences in gender, age, antiplatelet drug use, and herbal medicine use between the two groups (P < .05). However, there were significant differences in the use of anticoagulant drugs, thymidine/thymidine drugs, and Fu Zhengfang between the two groups. It was statistically significant that the mortality rate in the observation group (2.39)% was significantly lower than that in the control group (5.12)%. P < .05 White blood cell count, red blood cell ratio, lymphocyte count, hemoglobin, neutrophil count, and neutrophil ratio were not significantly different between the two groups (P < .05) .In comparison to the control group (4.92±8.00)10^9/L, the platelet count in the observation group (4.77±3.41)109/L was considerably lower. The difference was statistically significant (P < .05). The comparison of total bilirubin, total protein values and alkaline phosphatase values between the two groups was not significant (P < .05). In the observation group, albumin (38.71±6.39) g/L, glutamate transaminase (23.93±26.03) U/L, glutathione transaminase (26.12±25.53) U/L, gamma-glutamyltransferase (34.28±52.3) U/L, globulin values (28.13±5.55) g/L were significantly lower than those of the control group (36.66±7.08) g/L, (30.36±65.77) U/L, (33.29±49.72) U/L, (43.76±80.23) U/L, (29.85±5.67) g/L, the difference was statistically significant (P < .05). Between the two groups, there were no significant differences in the values of uric acid or creatinine (P > .05). Levels and uric acid readings did not differ significantly, P > .05. The difference between the urea values of the observation group (7.44±6.34 mmol/L) and the control group (8.75±7.51 mmol/L) was statistically significant (P < .05). Conclusion: After the implementation of the treatment protocol for COVID-19 (Trial Version 9), the number of death cases among patients with Omicron variant infection has significantly decreased. The treatment protocol is safe and feasible and can be widely applied in clinical settings..And it will further promote the development and administration of vaccines to prevent and control the spread of the novel coronavirus, reducing the occurrence of patients and death cases.

PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. METHODS: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. RESULTS: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. CONCLUSION: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

Effects of different phosphorus fertilizers on cadmium absorption and accumulation in rice under low-phosphorus and rich-cadmium soil.

Rice is the main food crops with the higher capacity for cadmium (Cd) uptake, necessitating the urgent need for remediation measures to address Cd in paddy soil. Reasonable agronomic methods are convenient and favorable for fixing the issue. In this study, a pot experiment was employed to evaluate the effects of two foliar (NaH2PO4, SDP; KH2PO4, PDP) and two solid phosphate fertilizers (double-superphosphate, DSP; calcium-magnesium phosphate, CMP) on uptake and remobilization of Cd in rice plants under the low-P and rich-Cd soil. The results revealed that these four phosphorus fertilizer significantly down-regulated the relative expression of OsNRAMP5 involved in Cd absorption, while up-regulated OsPCS1 expression and increased distribution of Cd into the cell wall in roots. Furthermore, phosphorus fertilizer resulted in a significant decrease in the relative expression of OsLCT1 in stems and OsLCD in leaves, decreased the transfer factor of Cd from shoots to grains, and ulterior reduced the Cd accumulation in three protein components of globulin, albumin, and glutelin, making the average Cd concentration of brown rice decreased by 82.96%. These results comprehensively indicate that in situations with similar soil backgrounds, the recommended application of solid CMP and foliar PDP can alleviate the toxicity of Cd by reducing its absorption and remobilization.

High Internal Phase Emulsions Synergistically Stabilized by Sodium Carboxymethyl Cellulose and Palm Kernel Oil Ethoxylates as an Essential Oil Delivery System.

High internal phase emulsions (HIPEs) with an internal phase fraction of 84 vol % were prepared using carboxymethyl cellulose (CMC) and palm kernel oil ethoxylates (SOE-N-60) as a dual emulsifier. Effects of the oil-phase volume fraction, CMC concentration, and SOE-N-60 concentration on oil-in-water HIPEs stability were systematically studied by a Mastersizer 2000 instrument, Lx POL polarizing microscope, rheometer, etc. The bioavailability of tea tree oil can be effectively protected using HIPEs as a delivery system. The experimental results showed that, with the increase of the concentrations of CMC and SOE-N-60, the droplet size of HIPEs gradually decreases and the HIPEs showed good static stability. In addition, it was observed by scanning electron microscopy that the polyHIPEs materials using HIPEs stabilized by different SOE-N-60 and CMC concentrations as templates had different structures. Moreover, the synergism between CMC and SOE-N-60 surfactants plays a significant role in the preparation and stability of HIPEs.

4-Methoxydalbergione is a potent inhibitor of human astroglioma U87 cells in vitro and in vivo.

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.

Low level prenatal exposure to a mixture of Sr, Se and Mn and neurocognitive development of 2-year-old children.

The excess or deficiency of trace metals can cause adverse neurocognitive development. Evidence of health effect of trace metal mixtures on neurocognitive development is limited in children. We evaluated associations of prenatal exposure to trace metals and metal mixtures with neurocognitive development of 2-year-old children. A total of 544 mother-child pairs were included in the study. The concentrations of 10 trace metals in maternal urine were monitored before delivery. Neurocognitive development indexes, including mental development index (MDI) and psychomotor development index (PDI), were assessed using the Bayley Scales of Infant Development. Linear regression analysis was performed to explore the effects of single-metal and multi-metal exposures. Bayesian Kernel Machine regression (BKMR) was used to investigate overall effect of exposure to metal mixtures and potential interactions among mixture components. We found positive associations of urinary strontium (Sr) and Selenium (Se) levels with MDI scores among all children in the single-metal model. Sr was positively related to MDI, while Manganese (Mn) was negatively associated with PDI in the multi-metal model. The results from BKMR model in girls revealed that MDI scores were improved with the increasing concentrations of Sr, Se and Mn mixture until the concentrations reached their 30th percentiles (Sr: 149.49 µg/g creatinine, Se:18.38 µg/g creatinine, Mn:1.96 µg/g creatinine), with no effect after that threshold level. Sr played a positive role in mental development among mixture components, which was consistent with the results of Sr in the multi-metal models. No signification association of mixture with MDI/PDI was found in boys. The study suggested potential sex-specific association of Sr, Se and Mn mixture levels (at or below their 30th percentiles) with improved mental development, and beneficial role of Sr.

Nano magnetic liposomes-encapsulated parthenolide and glucose oxidase for ultra-efficient synergistic antitumor therapy.

Multifunctional nanoplatforms yield extremely high synergistic therapeutic effects on the basis of low biological toxicity. Based on the unique tumor microenvironment (TME), a liposomes (Lips)-based multifunctional antitumor drug delivery system known as GOD-PTL-Lips@MNPs was synthesized for chemotherapy, chemodynamic therapy (CDT), starvation therapy, and magnetic targeting synergistic therapy. Evidence has suggested that parthenolide (PTL) can induce apoptosis and consume excessive glutathione (GSH), thereby increasing the efficacy of chemodynamic therapy. On the other hand, glucose oxidase (GOD) can consume intratumoral glucose, lower pH and increase the level of H2O2 in the tumor tissue. Integrated Fe3O4 magnetic nanoparticles (MNPs) containing Fe2+ and Fe3+ effectively catalyzes H2O2 to a highly toxic hydroxyl radical (•OH) and provide magnetic targeting. During the course of in vitro and in vivo experiments, GOD-PTL-Lips@MNPs demonstrated remarkable synergistic antitumor efficacy. In particular, in mice receiving a 14 day treatment of GOD-PTL-Lips@MNPs, tumor growth was significantly inhibited, as compared with the control group. Moreover, toxicology study and histological examination demonstrated low biotoxicity of this novel therapeutic approach. In summary, our data suggests great antitumor potential for GOD-PTL-Lips@MNPs which could provide an alternative means of further improving the efficacy of anticancer therapies.

Ecological risk assessment of petroleum hydrocarbons on aquatic organisms based on multisource data.

From the perspective of ecological risk, this study uses a multisource data method to search for global data, uses the acute and chronic ratio method to process the data, uses the species-sensitive distribution method to evaluate the ecological risk that petroleum hydrocarbons pose to aquatic organisms, and evaluates the ecological risk of the water environment in five Chinese water bodies. The results are as follows. First, in an aquatic ecosystem, the toxicological effects of petroleum hydrocarbons were found to be more obvious on consumers, and the sensitivity of fish was found to be higher than that of crustaceans. Second, the acutely lethal effects of petroleum hydrocarbons, fluorene, and benzo [a] pyrene on aquatic ecosystems were fitted by using the documentary method of multisource data collection and a Log-logistic curve. Third, in the case study evaluation of five Chinese water bodies, the ecological risks of polycyclic aromatic hydrocarbons were ranked (from low to high) as fluorene < benzo [a] pyrene. The ecological risk values of benzo [a] pyrene were all greater than 1. These risks should not be underestimated, and prevention and control work should be performed.

iGlu-Lys: A Predictor for Lysine Glutarylation Through Amino Acid Pair Order Features.

As one of the new posttranslational modification, lysine glutarylation has been identified in both prokaryotic and eukaryotic cells. These glutarylated proteins are involved in various cellular functions, such as translation, metabolism, and exhibited diverse subcellular localizations. Experimental identification of lysine glutarylation sites was founded in 2014 and also identified its deglutarylase sirturn 5(SIRT 5). Computational prediction of lysine glutarylation could be a complementary way to the experimental technique. In this work, the lysine glutarylation predictor iGlu-Lys has been developed based on the machine learning scheme. We have selected the best feature scheme which took the amino acid pair order and special-position information into account from four constructions. The machine learning algorithm support vector machine has been adopted and its performance has been measured for different window length of peptides. In the 10-fold cross-validation with window length 19, the AUC and MCC were 0.8944 and 0.5098, respectively. Different ROC curves in 6-, 8-, and 10-fold cross-validations were very close which illustrated the robustness of our predictor. The results of iGLu-Lys were better than the existing method GlutPred. Meanwhile, a free webserver for iGlu-Lys is accessible at http://app.aporc.org/iGlu-Lys/.

A study on isolation of chemical constituents from Sophora flavescens Ait. and their anti-glioma effects.

BACKGROUND: Sophora flavescens Ait. is a traditional Chinese medicine with a long history in China. It is mainly used in the treatment of heat dysentery and similar ailments in the clinical. The objective of this paper was to isolate, purify and identify alkaloids from Sophora flavescens Ait. and to explore their inhibitory effects on C6 glioma cells. MATERIALS AND METHODS: Column chromatography, extraction and NMR spectroscopy were used to structurally identify the isolated compounds. MTT assay and flow cytometry were used to detect the inhibitory effect of matrine on C6 cells. RESULTS: Three compounds were isolated from Sophora flavescens Ait., namely matrine, oxymatrine and lupeol. Different concentrations of matrine solution all had inhibitory effects on growth of C6 cell lines, which showed apparent dose-effect relationship. Compared with the control group, proportion of G0/G1 phase cells increased in each matrine concentration group to a maximum of 79.8%; proportion of S phase cells reduced, and proportion of G2/M phase cells declined slightly to a minimum of 6.3%, suggesting that after the action of matrine proliferation of C6 cells was significantly inhibited and the cells were arrested in the G1 phase. CONCLUSION: We concluded that Sophora flavescens Ait. has an inhibitory effect on C6 cell proliferation.

Preventive effect of Qianggan-Rongxian Decoction on rat liver fibrosis.

AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups (12 rats in each group). Except for the normal control group, all the rats received 1% DMN (10 muL/kg body weight, i.p), 3 times a week for 4 wk. The rats in the 3 treatment groups including a high-dose DMN group (10 mL/kg), a medium-dose DMN group (7 mL/kg), and a low-dose DMN group (4 mL/kg) were daily gavaged with Qianggan-Rongxian Decoction, and the rats in the model and normal control groups were given saline vehicle. Enzyme-linked immunosorbent assay (ELISA) was used to determine the changes in serum hyaluronic acid (HA), laminin (LN), and type IV collagen levels. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using routine laboratory methods. Pathologic changes, particularly fibrosis, were examined by hematoxylin and eosin (HE) and Sirius red staining. Hepatic stellate cells (HSC) were examined by transmission electron microscopy. RESULTS: Compared with the model control group, the serum levels of HA, LN, type IV collagen, ALT and AST were decreased markedly in the other groups after treatment with Qianggan-Rongxian Decoction, especially in the medium-dose DMN group (P < 0.05). Moreover, the area-density percentage of collagen fibrosis was lower in the Qianggan-Rongxian Decoction treatment groups than in the model group, and a more significant drop was observed in the medium-dose DMN group (P < 0.05). CONCLUSION: Qianggan-Rongxian Decoction can inhibit hepatic fibrosis due to chronic liver injury, delay the development of cirrhosis, and notably ameliorate liver function. It may be used as a safe and effective thera-peutic drug for patients with fibrosis.

Latent production of angiotensin I-converting enzyme inhibitors from buckwheat protein.

The latent production of angiotensin I-converting enzyme (ACE) Inhibitors from tartary buckwheat (BW) was investigated, and the peptides responsible for ACE inhibition characterized. Intact buckwheat was found to exhibit ACE inhibitory activity having an IC50 value of 3.0 mg/ml. The activity of the protein fraction (IC50: 0.36 mg protein/ml) was not enhanced by pepsin treatment. Pepsin, followed by chymotrypsin and trypsin hydrolysis, resulted in a significant increase in the ACE inhibitory activity (IC50: 0.14 mg protein/ml). The rutin contained in the buckwheat did not exhibit any ACE inhibition. A single oral administration of BW digest lowered the systolic blood pressure of a spontaneously hypertensive rat. Thus, BW proteins offer a potential resource for producing ACE inhibitory peptides during the digestion process. From the di-/tri-peptide fraction (DTPF) of the BW digest, inhibitory peptides were identified. The magnitude (%) of the total ACE inhibitory contribution of each identified peptide, relative to the overall inhibition of the DTPF, was about 41%.