The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

OBJECTIVE: To prepare and develop a GDH-2 air sampling tube for detecting 12 kinds of chlorobenzenes(CBs) in workplace air and to establish a matching detecting method. METHODS: The self-developed GDH-2 air sampling tube was filled with ion exchange resin and activated carbon, and the mass ratio was 10 ∶1. The GDH-2 air sampling tube was used to collect 12 kinds of CBs with coexistence of gaseous and aerosol in the air. After elution with toluene, they were separated on a chromatographic column and determined by microcell electron capture detector. RESULTS: The quantitative detecting range of the method was 0.51×10~(-3)-6 000.00 mg/L, with the correlation coefficients greater than 0.999 4. The minimum detection concentration was 0.02-61.99 μg/m~3, and the minimum quantitative concentration was 0.05-206.62 μg/m~3. The average desorption efficiency was 90.8%-104.0%. The within-run relative standard deviation(RSD) was 1.0%-5.7%, and the between-run RSD was 3.0%-7.3%. The samples can be stored at room temperature for at least 26 days. CONCLUSION: The self-developed GDH-2 air sampling tube and its matching measuring method can be used for the collection and determination of the 12 kinds of CBs in the air of workplace.

OBJECTIVE:To provide reference for development and application of Korean medicine Atractylodes japonica. METHODS:Using"Guancangsu""Huaxue chengfen""Yaoli zuoyong""Atractylodes japonica""Chemical constituents""Pharmacological effects"as Chinese and English key words,relevant literatures published during 1983-2017 were retrieved from CNKI, PubMed, ScienceDirect full-text database, the chemical constituents and pharmacological effects of A. japonica were reviewed. RESULTS & CONCLUSIONS:As of June 21,2017,a total of 226 literatures were collected,including 43 valid literatures. A. japonica mainly contains terpenoids,aliphatic,aromatic in volatile oil,glycosides active constituents in roots,and shows anti-inflammatory and analgesic,cardio cerebral vascular protection,contianaphylaxis,antibacterial,antiviral and anti-ulcer effects. Currently,the research of A. japonica on the chemical constituents and pharmacological effects has achieved initial results, however, reports of its toxicity are rare. Therefore, the safety evaluation should be taken into account in the study of its pharmacological effects.

Objective To evaluate the effect of zinc deficiency factor on cognitive function after isoflurane anesthesia in mice with Alzheimer's disease (AD).Methods One hundred and forty-four APP/ PS1 transgenic mice with AD,weighing 22-28 g,aged 8-10 months,were divided into 6 groups (n=24 each) using a random number table:zinc adequate group (group ZA),zinc adequate plus isoflurane anesthesia group (group ZA+Iso),zinc deficiency group (group ZD),zinc deficiency plus isoflurane anesthesia group (group ZD+Iso),zinc treatment group (group ZT) and zinc treatment plus isoflurane anesthesia group (group ZT+Iso).The mice were fed a diet adequate in zinc and deionized water for 2 months in ZA and ZA+Iso groups.The mice were fed a diet low in zinc (0.01‰ zinc) and deionized water for 1 month in ZD and ZD+Iso groups.The mice were fed a diet adequate in zinc and 0.12‰ ZnSO4 · 7H2O water for 2 months in ZT and ZT+Iso groups.The mice underwent 2 h of anesthesia with 1.4％ isoflurane starting from the end of feeding in ZA+Iso,ZD+Iso and ZT+Iso groups.At 24 h after anesthesia,the mice were sacrificed and hippocampal tissues were obtained for determination of the contents of soluble amyloid beta protein 40 (Aβ40) and Aβ42 and insoluble Aβ40 and Aβ42 (using enzyme-linked immunosorbent assay) and expression of total Aβ,Aβ40,Aβ42,tau pSer396,tau pSer262 and tau pThr231 (by Western blot).Morris water maze test was performed at 24 h after anesthesia.Results There was no significant difference in each parameter between group ZA and group ZA+Iso and between group ZT and group ZT+Iso (P＞0.05).Compared with group ZD or group ZT+Iso,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of hippocampal Aβ42,tau pSer396,tau pSer262 and tau pThr231 was up-regulated,and the contents of soluble and insoluble Aβ42 were increased in group ZD+Iso (P＜0.05 or 0.01).Conclusion Zinc deficiency can aggravate the impairment of cognitive function after isoflurane anesthesia in mice with AD,and the mechanism is related to the promotion of hippocampal Aβ aggregation and tau protein phosphorylation.

Lagerstroemia speciosa Pers,also known as banaba,belongs to Lythraceae and contains ursolic acid,corosolic ac?id,asiatic acid and 30 other kinds of effective components.It has multiple pharmacological activities,including hypoglycemic,hypo?lipidemic,anti-oxidant and anti-viral activities,and is mainly used for the treatment of obesity and diabetes in folk medcine.This re?view summarizes the recent advances in chemical composition and pharmacological effects of L.speciosa Pers,so as to provide the theo?retical basis and reference for its further research and application.

OBJECTIVETo investigate serum procalcitonin (PCT) concentrations in premature infants with different gestational ages at different times after birth.

METHODSA total of 217 neonates without infection, including 102 premature infants and 115 full-term infants, were enrolled in this study. The premature infants were further divided by gestational age into three subgroups: 30-32 weeks (n=30), 33-34 weeks (n=35) and 35-36 weeks (n=37). All the infants were studied to evaluate serum PCT concentrations at 0-12, 13-24, 25-36, 37-48, 49-72, 73-96, 97-120 and 121-144 hours after birth.

RESULTSIn the newborns, serum PCT concentrations increased gradually after birth, reached peak values at about 24 hours after birth, and then gradually declined and dropped to normal values for children at about 96 hours after birth. In the premature infants, serum PCT concentrations reached peak values at about 36 hours after birth, later than in the full-term infants, then declined slowly and dropped to levels similar to the full-term infants at 96 hours after birth. Serum PCT concentrations in the 30-32 week subgroup remained at low levels after birth, and increased gradually, later than in other premature infants, at 37-48 hours after birth.

CONCLUSIONSEarly after birth, neonates have a changing serum PCT concentration, increasing first and then decreasing. Peak serum PCT levels appear later in premature infants than in full-term infants. Serum PCT concentrations of premature infants with a gestational age of under 32 weeks remain at relatively low levels within 36 hours after birth.

Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; blood ; Protein Precursors ; blood ; Time Factors

OBJECTIVETo screen the differently expressed proteins related to regulating the depolymerization of microtubules in the spinal cord of hens exposed to tri-o-cresyl phosphate (TOCP) and to provide target protein evidence for exploring the mechanisms of the delayed neurotoxicology (OPIDN) induced by organophosphorus compounds (OPs).

METHODSForty two Roman hens were randomly divided into three groups, i.e. TOCP group treated with 1000 mg/kg TOCP; intervention group treated with 40 mg/kg phenylmethanesulfonyl fluoride (PMSF) before 1000 mg/kg TOCP treatment and control group treated with tap water. Four hens in each group were sacrificed on the 5th and 20th days after exposure, respectively. Spinal cords were separated and homogenates at low temperature, and the total proteins were extracted. The OPIDN symptoms observed and recorded in the remaining 6 hens in each group. The differently expressed proteins related to regulating the depolymerization of microtubules were screen by two-dimensional electrophoresis and mass spectroscopy (MS).

RESULTSThe OPIDN symptoms appeared on the 5th day after exposure in TOCP group, which were gradually serious with time. The results by two-dimensional electrophoresis and MS showed that the Stathmin expression was downregulated 3.4 times and 2.8 times in TOCP group, respectively, as compared with the control and PMSF intervention groups. However, there was no significant difference of the Stathmin expression between control group and PMSF intervention group.

CONCLUSIONThe Stathmin expression in the spinal cord tissues of hens exposed to TOCP significantly downregulated. Moreover, the downregulated Stathmin expression may be related to excess polymerization of microtubules and the mechanism of OPIDN.

Animals ; Chickens ; Environmental Exposure ; Female ; Spinal Cord ; metabolism ; Stathmin ; metabolism ; Tritolyl Phosphates ; toxicity

OBJECTIVETo screen the proteins with differential expression levels in the cerebral tissue of hens exposed to tri-ortho-cresyl phosphate (TOCP), and to provide target proteins for studying the mechanism of organophosphoms ester-induced delayed neurotoxicity (OPIDN).

METHODSThirty two adult Roman hens were randomly divided into four groups: TOCP group was exposed to 1000 mg/kg TOCP, PMSF group was exposed to 40 mg/kg PMSF, PMSF plus TOCP group was exposed to 40 mg/kg PMSF and after 24 h exposed to 1000 mg/kg TOCP, control group was exposed to normal saline. All hens exposed to chemicals by gastro-intestine for 5 days were sacrificed, and the cerebral tissue were dissected and homogenized in ice bath. Total proteins extracted from the cerebral tissue were separated by isoelectric focusing as the first dimension and SDS-PAGE as the second dimension. The 2-DE maps were visualized after silver staining and analyzed by Image Master 2D software. At last ,the expressed protein spots were identified by Mass spectrometry.

RESULTSFrom total proteins in TOCP group, the PMSF plus TOCP group and PMSF group, 1185, 1294 and 1063 spots were detected, respectively. One thousand three hundred thirty two spots from total proteins in control group were detected. The match rates of protein spots in TOCP group, the PMSF plus TOCP group and PMSF group were 78.32 %, 79.56 % and 80.93%, respectively. There were 235 protein spots with differential expression levels between TOCP group and control group, which included 158 up regulation spots and 77 down regulation spots. According to the PMSF features, there were 102 spots with differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF plus TOCP group, among them there were 13 spots with 4 fold differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF group. Seven protein spots (homer-1b, Destrin, heat shock protein 70, eukaryotic translation initiation factors, proteasome alpha1 subunit, lactate dehydrogenase B, glutamine synthetase) were detected by Mass spectrometry.

CONCLUSIONThere are 112 protein spots with differential expression levels of the cerebral tissue in TOCP group, which may be related to OPIDN, among them 13 protein spots with differential expression levels are associated closely with OPIDN. Seven protein spots detected by Mass spectrometry may be related to the mechanism induced by OPIDN.

Animals ; Brain ; metabolism ; Cerebrum ; drug effects ; metabolism ; Chickens ; Neurofilament Proteins ; metabolism ; Phenylmethylsulfonyl Fluoride ; toxicity ; Proteome ; analysis ; Tritolyl Phosphates ; toxicity

OBJECTIVETo examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences.

METHODSMetal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann-Whitney nonparametric U-tests and multiple linear regression.

RESULTSThe concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 μg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 μg/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (<500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens.

CONCLUSIONBoth mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.

Carcinogens, Environmental ; toxicity ; Environmental Exposure ; Environmental Pollutants ; toxicity ; Female ; Humans ; Maternal-Fetal Exchange ; Metals ; toxicity ; Pregnancy ; Time Factors

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y4 receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y4 receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y2 receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y1, 2, 5 receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y3 receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y2 receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y4 and Y2 receptor differently regulate the release of atrial ANP.
Animals ; Arginine/analogs & derivatives/pharmacology ; Atrial Natriuretic Factor/*metabolism ; Benzazepines/pharmacology ; Gene Expression Regulation ; Pancreatic Polypeptide/pharmacology ; Peptide YY/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Neuropeptide Y/agonists/antagonists & inhibitors/*metabolism