ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective To observe the clinical effect and safety of recombinant human interferon-α2b(rhIFN-α2b)combined with 5-aminolaevulinic acid photodynamic therapy(ALA-PDT)in the treatment of patients with cervical intraepithelial lesions and human papilloma virus(HPV)infection.Methods The clinical data of patients with cervical intraepithelial lesions and HPV infection were analyzed retrospectively.The patients were divided into control group and treatment group according to cohort method.The control group was treated with rhIFN-α2b gel at posterior fornix,qd.On this basis,the treatment group was treated with ALA-PDT,namely applying 5％ALA temperature-sensitive gel prepared by 118 mg of ketone valerate hydrochloride powder for external use on vaginal surface,combined with photodynamic therapy,once a week.The clinical efficacy,time to recovery from clinical symptoms,recurrence rate,changes in cytokines[interleukin-6(IL-6),interleukin-8(IL-8)and interferon-γ(IFN-γ)]and immune function[T cell subsets CD3+,CD4+,CD8+and CD4+/CD8+],and safety were compared between the two groups.Results There were 98 cases in treatment group and 100 cases in control group.The total effective rates in treatment group and control group were 93.88％and 83.00％,with statistically significant difference(P＜0.05).The relief time of lower abdominal pain in treatment group and control group were(3.65±0.52)and(5.26±0.65)d;the time to recovery from abnormal vaginal discharge were(5.77±0.83)and(7.16±0.92)d;the time to recovery from irregular vaginal bleeding were(4.82±0.62)and(6.94±0.77)d;HPV clearance rates were 58.16％and 42.00％;IL-6 levels were(0.16±0.09)and(0.23±0.05)mg·L-1;IL-8 levels were(0.47±0.05)and(0.66±0.07)mg·L-1;IFN-γ levels were(10.07±0.98)and(7.24±0.65)ng·mL-1;CD3+were(71.06±8.29)％and(61.36±6.88)％;CD4+were(48.25±5.94)％and(42.25±5.13)％;CD8+were(20.37±2.42)％and(24.69±2.51)％;CD4+/CD8+were 2.11±0.27 and 1.36±0.16;the differences were all statistically significant(all P＜0.05).Recurrence rates in treatment group and control group were 5.10％and 14.00％,with statistically significant difference(P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 26.53％and 21.00％,without statistically significant difference(P＞0.05).Conclusion The combined treatment of rhIFN-α2b and ALA-PDT is effective for patients with cervical intraepithelial lesions and HPV infection.It has obvious advantages in improving immunity,relieving inflammatory response and reducing recurrence rate,with good safety.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Background At present, occupational poisoning has become one of the most serious occupational diseases that jeopardize the health of workers in China, in addition to pneumoconiosis, with a wide range of impacts and heavy social and economic losses. Objective To analyze the characteristics and patterns of the incidence of occupational poisoning in Tianjin from 2006 to 2020, and to provide a scientific basis for the development of effective intervention measures and prevention strategies. Methods The Occupational Diseases and Health Hazards Monitoring Information System, a module of the China Disease Prevention and Control Information System, was the primary data source of the study. The case files of acute and chronic occupational poisoning diagnosed by occupational disease diagnostic institutions in Tianjin from January 1, 2006 to December 31, 2020 were retrieved from the system. The data included basic information, occupational history, disease characteristics, and employer information. Excel 2016 was used to establish database, and frequencies and composition ratios were reported. Results From 2006 to 2020, a total of 234 cases of occupational chemical poisoning were reported in Tianjin, including 49 cases of acute occupational poisoning (20.94%) and 185 cases of chronic occupational poisoning (79.06%). The number of acute occupational poisoning cases showed a rising and then falling trend, and the number of chronic occupational poisoning cases showed an overall decreasing trend. Acute occupational poisoning mainly occurred in the four districts around the city (22 cases, 44.90%), and chronic occupational poisoning mainly occurred in Binhai New Area (90 cases, 48.65%). More male cases were reported than female cases. The age of onset was concentrated at 45-55 years old. The acute occupational poisoning cases were concentrated in the group with less than 5 years of service (22 cases, 44.90%), mainly asphyxiating gas poisoning, and the highest incidence was reported in chemical raw materials and chemical products manufacturing industry. The chronic occupational poisoning cases were concentrated in the groups with a working age of 5-14 years (70 cases, 37.84%), mainly organic solvent poisoning, and the highest incidence was also reported in chemical raw materials and chemical products manufacturing industry. Conclusion The prevention and control of occupational poisoning as well as health surveillance and management in Tianjin shall be carried out in a hierarchical and focused manner in accordance with types of acute and chronic occupational poisoning chemicals in the city, regional economic differences, types of industries, and distribution of workers.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Objective:To investigate the health status and the influencing factors of abnormal lung function of welding fumes exposure workers in Tianjin from 2020 to 2022, and to provide theoretical basis for the protection and intervention of key occupational diseases.Methods:In October 2023, the relevant data of occupational health examination of welding fumes exposure workers in Tianjin from 2020 to 2022 (10831, 10758 and 21717 in 2020, 2021 and 2022, respectively) were collected from the China Disease Prevention and Control Information Platform. The electrocardiogram, chest radiograph and lung function abnormalities of workers in each year were analyzed, as well as the association between lung function abnormalities and gender, age, working age, region, etc. With gender, age and years of service as independent variables, logistic regression analysis was performed year by year on the influencing factors of abnormal lung function.Results:From 2020 to 2022, electrocardiogram, chest radiograph and lung function abnormality rates of workers exposed to welding fumes had statistical significances (χ 2=301.79, 7.87, 1614.54, P<0.05), and the lung function abnormality rate showed a downward trend year by year (χ 2trend=1516.19, P<0.001). The abnormal rates of lung function in male workers exposed to welding fumes were higher than those in female workers (χ 2=61.65, 8.04, 15.22, P<0.05). With the increase of age, the abnormal rate of lung function showed an increasing trend (χ 2trend=6.47, 10.81, 4.72, P<0.05). The abnormal rates of lung function in the four districts around the city in each year were 22.05% (318/1442), 8.91% (171/1919) and 6.48% (273/4212), respectively. Year by year logistic regression analysis showed that females were the protective factors for abnormal lung function ( OR=0.369, 0.568, 0.546; 95% CI: 0.298-0.458, 0.367-0.879, 0.388-0.767; P<0.05) . Conclusion:Attention should be paid to the health status of welding fumes workers in Tianjin, focusing on the protection of middle-aged male workers, and effective prevention measures should be taken for key areas and industries such as the four districts around the city.

Objective:To investigate the health status and the influencing factors of abnormal lung function of welding fumes exposure workers in Tianjin from 2020 to 2022, and to provide theoretical basis for the protection and intervention of key occupational diseases.Methods:In October 2023, the relevant data of occupational health examination of welding fumes exposure workers in Tianjin from 2020 to 2022 (10831, 10758 and 21717 in 2020, 2021 and 2022, respectively) were collected from the China Disease Prevention and Control Information Platform. The electrocardiogram, chest radiograph and lung function abnormalities of workers in each year were analyzed, as well as the association between lung function abnormalities and gender, age, working age, region, etc. With gender, age and years of service as independent variables, logistic regression analysis was performed year by year on the influencing factors of abnormal lung function.Results:From 2020 to 2022, electrocardiogram, chest radiograph and lung function abnormality rates of workers exposed to welding fumes had statistical significances (χ 2=301.79, 7.87, 1614.54, P<0.05), and the lung function abnormality rate showed a downward trend year by year (χ 2trend=1516.19, P<0.001). The abnormal rates of lung function in male workers exposed to welding fumes were higher than those in female workers (χ 2=61.65, 8.04, 15.22, P<0.05). With the increase of age, the abnormal rate of lung function showed an increasing trend (χ 2trend=6.47, 10.81, 4.72, P<0.05). The abnormal rates of lung function in the four districts around the city in each year were 22.05% (318/1442), 8.91% (171/1919) and 6.48% (273/4212), respectively. Year by year logistic regression analysis showed that females were the protective factors for abnormal lung function ( OR=0.369, 0.568, 0.546; 95% CI: 0.298-0.458, 0.367-0.879, 0.388-0.767; P<0.05) . Conclusion:Attention should be paid to the health status of welding fumes workers in Tianjin, focusing on the protection of middle-aged male workers, and effective prevention measures should be taken for key areas and industries such as the four districts around the city.

Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.