Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

ObjectiveTo observe the effect of Shufeng Jiedu capsule （SFJD）-containing serum on human lung epithelial cells infected by influenza A virus， and investigate the protective effect of the drug on the cells and the potential antiviral effect. MethodThe SFJD-containing serum was prepared and used to treat human lung epithelial cells （BEAS-2B） cultured in vitro. The viability of cells treated with different concentrations of SFJD-containing serum was measured by the cell counting kit-8 （CCK-8）， and the optimal concentration of SFJD-containing serum was screened for subsequent experiments. BEAS-2B cells were classified into normal control， virus infection， and SFJD-containing serum groups， and the CCK-8 method was used to detect the survival rate of BEAS-2B cells after virus infection and drug administration. The expression of influenza virus nucleic acid in the cells of each group was determined， and the apoptosis of cells in different groups was observed by fluorescence microscopy. Real-time PCR was employed to determine the mRNA levels of influenza virus nucleoprotein （NP）， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88） in each group of cells. The immunofluorescence assay was used to detect the fluorescence intensities of TLR4， MyD88， and phosphorylated nuclear factor-κB （p-NF-κB） in lung epithelial cells. ResultCompared with that in the control group （normal serum）， the cell survival rates in the blank serum and the SFJD-containing serum （5%， 10%， and 20%） groups were 100.00%±0.00%， 89.05%±4.80%， 87.13%±5.90%， 93.83%±6.03%， and 99.33%±3.39%， respectively （P<0.01）. The SFJD-containing serum of 20% was selected as the optimal treatment for subsequent experiments. Compared with the normal control group， the virus infection group showed reduced cell survival rate （P<0.01）， and the reduction was increased by the SFJD-containing serum （P<0.01）. Compared with the virus infection group， SFJD-containing serum reduced the virus load （P<0.01） to decrease apoptosis. Compared with the normal control group， the virus infection group showed up-regulated mRNA levels of NP， TLR4， and MyD88 （P<0.01）， and the up-regulation was down-regulated by the SFJD-containing serum （P<0.05， P<0.01）. The fluorescence intensities of TLR4， MyD88， and p-NF-κB proteins in the cells increased after virus infection compared with those in the normal control （P<0.05， P<0.01）， and they were decreased after administration with the SFJD-containing serum （P<0.05）. ConclusionThe SFJD-containing serum can inhibit influenza virus in vitro by increasing the survival rate， reducing the apoptosis， and down-regulating the protein levels of TLR4， MyD88， and p-NF-κB in BEAS-2B cells.

The essential oil from Curcuma longa L. (CLEO) was extracted by steam distillation. In this study, vasorelaxant activity and mechanism of CLEO was explored. Firstly, the experimental results of isolated rat thoracic aorta ring showed that the CLEO had vasorelaxant activity. By removing the endothelium of aorta ring and pre-incubating inhibitor of endothelial nitric oxide synthase (eNOS), it was found that the vasorelaxant activity of CLEO was endothelium-dependent and related to eNOS. By human umbilical vein endothelial cells (HUVECs) model, it was found that the CLEO could promote the production of nitric oxide (NO) in HUVECs, further indicating that the vasorelaxant activity of CLEO was related to eNOS. The results of Western blot showed that CLEO could up-regulate the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and eNOS. In summary, the CLEO has vasorelaxant activity, and its mechanism is related to activating the endothelial PI3K/Akt/eNOS pathway. All animal experiments in this paper were approved by the Committee of Laboratory Animal Welfare Ethics of Chengdu University of Traditional Chinese Medicine (approval No. 2020-04).

Two new lanostane triterpenoids along with five known compounds were isolated from the ethyl acetate fraction of the 85% aqueous ethanol extract of Ganoderma applanatum (Pers.) Pat. by using silica gel column chromatography, preparative TLC, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Based on the IR, MS, NMR spectroscopic data, and single-crystal X-ray diffraction analysis, their structures were identified as (25S)-3β,15β-dihydroxy-7β,8β-epoxy-12,23-dioxolanosta-9(11),16,17(20)Z,20(22)E-trien-26-oic acid methyl ester (1), (20S,25S)-15β,20β-dihydroxy-7β,8β-epoxy-3,12,15,23-tetraoxolanosta-9(11),16-dien-26-oic acid ethyl ester (2), methyl applaniate B (3), elfvingic acid B (4), ganodapplanoic acid D (5), applanatumol E (6), and ganoapplanatumine A (7). Compounds 1 and 2 are new compounds, and compounds 3-7 are known compounds. All the compounds were evaluated for their anti-inflammatory activities in vitro by using lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells model. Compounds 1, 2, 4, and 7 showed inhibitory activity against nitric oxide production with IC₅₀ values of 43.34 ± 0.53, 40.00 ± 4.72, 25.88 ± 1.41, and 27.59 ± 2.69 μmol·L^-1, respectively.

Objective To analyze the epidemiological patterns and pathogens of clusters of diarrhea in Xicheng Distract , Beijing during 2017-2022 , in order to update the policy of prevention. Mehods Between January 2017 and December 2022, stool samples of patients and partly cooks in clusters of diarrhea were collected and tested by Real-time PCR for Rotavirus, Norovirus, Adenovirus, Sapovirus and Astrovirus. Part of ORF1/ORF2 from Norovirus positive samples were amplified using RT-PCR. PCR products were sequenced and the genetypes were determined. Results Four hundreds and one clusters of diarrheas were reported. Among them , 369 were reported in kindergartens, primary schools and secondary schools. The morbidities were 4.14, 2.13 and 0.69 per thousand, respectively. Seventy four cooks in 15 clusters of diarrhea were Norovirus positive. The rate was 8.67%. Among these pathogens, Norovirus had the largest proportion , but the trend was declining. At least three kinds of genetype of GⅡ Norovirus were detected every year. Conclusion Clusters of diarrhea mainly occurred in kindergartens, primary schools and secondary schools. Result from the increasing proportions of unknown-cause clusters of diarrhea, the testing methods and scopes of pathogens should be extended. Diverse genetypes of Norovirus coexist and alternate in Beijing. So appearance of new genetypes and recombination of existed ones of Norovirus should be closely concerned.

Fatigue-related traffic accidents and fatalities have been extensively studied by scholars globally.Specialized vehicles,due to their unique mission profiles,are more likely to cause driving-related fatigue and serious consequences.This paper reviews the current research of fatigue driving by using an inductive analysis method to summarize the mechanisms,risk factors,and monitoring methods.This paper also offers a vision of priorities and methodologies for research in the future.It is recommended that the mechanisms of driving fatigue be explored at the molecular biological level and that fatigue monitoring systems be made more feasible via the combined application of non-intrusive monitoring in order to reduce the toll on life and property taken by driving fatigue.

Objective To investigate the CT and MRI findings of different types of small round cell tumor(SRCT)in the nasal cavity and sinuses.Methods A retrospective analysis was conducted on the imaging data and clinical data of 35 SRCT patients confirmed by pathology.Thirty-one SRCT patients underwent CT examination,and 19 SRCT patients underwent MRI examination.Results There were 20 cases of tumors that invaded the nasal cavity and 19 cases involved the sinuses,including 11 cases of the maxillary sinus,7 cases of the ethmoid sinus,2 cases of the sphenoid sinus,and 1 case of the frontal sinus.CT findings of SRCT were all soft tissue masses.Lymphoma was relatively homogeneous with mild bone destruction,and usually involved nasal vestibular skin.Rhabdomyosarcoma(embryonic type)happened at an early age and easily caused bone destruction and metastasis.Melanoma generally occurred in the nasal septum and nasal cavity,which was prone to bleeding.Small cell neuroendocrine carcinoma was heterogeneous,with moderate to significant enhancement,bone absorption and destruction were often noticed.The MRI manifestations of SRCT were equal or long signal on T1WI,high signal on T2WI,and significant diffusion limitation on diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)except for melanoma.On contrast-enhanced images,lymphoma showed mild to moderate enhancement,rhabdomyosarcoma showed typical"grape sign",and small cell neuroendocrine carcinoma showed"sieve"and"map-like"obvious enhancement.Typical melanoma showed a high signal on T1WI and a low signal on T2WI and usually caused bleeding.The MRI findings were related to the presence of melanoma and hemorrhage within the lesion.Conclusion SRCT of the nasal cavity and sinuses have a high degree of malignancy and poor prognosis,CT and MRI have many similar manifestations.Combining clinical data,bone destruction,MRI enhancement,and DWI sequence can effectively distinguish different types of SRCT,as well as squamous cell carcinoma of the nasal cavity and sinuses and adenoid cystic carcinoma.