The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Animals ; Escin ; pharmacology ; Intestines ; blood supply ; Lipid Peroxidation ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; prevention & control

Objective To investigate the clinicopathological factors related with the lymph node ratio (LNR) in colorectal cancer patients.Methods The clinical and pathological data of 177 colorectal cancer patients who were treated by surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2011 to December 2013 were collected.The association between LNR and clinicopathological factors were evaluated by single factor analysis nsingx x2 test.Results Gender,age,tumor location,tumor size,gross type,depth of infiltration,infiltration extent around bowel wall and preoperative serum CA199 concentration were not related with LNR (P ＞0.05),but tumor histological type,tumor differentiation,preoperative serum CEA,CA125 concentration were related with LNR (P =0.001,0.004,0.004,0.025).Conclusions Tumor histological type,tumor differentiation,preoperative serum CEA,CA125 may be the important factors related with LNR in colorectal cancer.

A system analysis about the microbial flora of normal and abnormal soybean sauce liquor from the high-salt-level watery state fermentation was made and the dominant bacteria and yeasts were identified.On the other hand,a discussion of effect of temperature on microbial flora was made.The results indicated that there were no obvious differences about the count of aerobe,spore-producing bacteria,enterobacteriaceae,lactic acid bacteria and anaerobe between the normal and abnormal soybean sauce liquor and there were marked differences about the count of yeasts and salt-tolerant bacteria.The predominant yeasts in normal soybean sauce were Torulopsis and Saccharomyces,accounting for 55.9% and 35.3% of the total yeasts separately,and in abnormal soybean sauce were Pichia,candida and Saccharomyces,accounting for 62.8%,17.9% and 9.0% respectively.

These years with industrial antiseptics and disinfectants widely used, especially unscientifically used, the resistance of microorganisms is more and more serious, which brought much more difficulties to industrial producing. The developments on the resistance of microorganisms to industrial antiseptics and disinfectants, their resistant mechanisms and the control strategies are reviewed, which aids us to reasonably use industrial organic antiseptics and disinfectants in existence and provides academic and scientific basis.

BACKGROUND:Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a control ed experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture (CLP) model in rats. METHODS:After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group (2.5 μg·kg-1·h-1); (3) medium-dose treatment group (5.0 μg·kg-1· h-1);and (4) large-dose treatment group (10.0 μg·kg-1·h-1). HLA-DR and plasma cytokine (IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure (MAP), heart rate (HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS:The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups (DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels (Pgroup=0.0202) and increased IL-6 production, which was increased at 3 h (P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR (P<0.001) while maintaining MAP (Pgroup=0.1238), and remarkably improving lactate (P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7％, 66.7％, 25％ and 18％ for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively. CONCLUSION:Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dose-dependently.

OBJECTIVE: To explore alcohol pharmacokinetics as well as acetaldehyde level in peripheral blood in human subjects with different ALDH2 genotypes after drinking. METHODS: Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length polymorphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. RESULTS: According to the results of electrophoresis, 5 people carried ALDH2*1/*1 as wild group and 9 people carried ALDH2*1/*2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7 microg/mL and 0-5.1772 microg/mL, respectively. The AUC values of alcohol and acetaldehyde and the t1/2Z value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group (P<0.05). CONCLUSION After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2*1/*2 mutation group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.
Alcohol Drinking ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Ethanol/metabolism* ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic

A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.
Animals ; Capsules ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Panax notoginseng ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

Mycoplamas are a group of wall-less prokaryotes widely distributed in nature, some of which are pathogenic for humans and animals. There are many lipoproteins anchored on the outer face of the plasma membrane, called lipid-associated membrane proteins (LAMPs). LAMPs are highly antigenic and could undergo phase and size variation, and are recognized by the innate immune system through Toll-like receptors (TLR) 2 and 6. LAMPs can modulate the immune system, and could induce immune cells apoptosis or death. In addition, they may associate with malignant transformation of host cells and are also considered to be cofactors in the progression of AIDS.
Animals ; Humans ; Lipids ; Membrane Proteins ; metabolism ; Mycoplasma ; physiology ; Mycoplasma Infections ; immunology ; metabolism ; microbiology ; pathology ; Protein Binding ; Signal Transduction

Heroin can be metabolized easily in body and the mail metabolites are 6-MAM, morphine and so on. At present, there are urine, blood, hair and so on as specimens for detection, while the analytical technology conclude TLC, GC, HPLC, GC/MS, LC/MS, IA, CE etc. In this paper, these technologies used for heroin's metabolites were viewed in order to provide some reference to the study in relative field.
Chromatography, High Pressure Liquid ; Forensic Medicine ; Gas Chromatography-Mass Spectrometry ; Hair/chemistry* ; Heroin/metabolism* ; Heroin Dependence/metabolism* ; Humans ; Morphine/analysis* ; Morphine Derivatives/analysis* ; Substance Abuse Detection/methods*