Lirispirolides A-L (1-12), twelve novel sesquiterpene-monoterpene heterodimers featuring distinctive carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree [Liriodendron chinense (L. chinense)], a rare medicinal and ornamental plant endemic to China. The structural elucidation was accomplished through comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray crystallography. These heterodimers exhibit a characteristic 2-oxaspiro[4.5]decan-1-one structural motif, biosynthetically formed through intermolecular [4 + 2]-cycloaddition between a germacrane-type sesquiterpene and an ocimene-type monoterpene. The majority of the isolated compounds demonstrated significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells by reducing the production of pro-inflammatory mediators, specifically tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further investigation revealed that the lirispirolides' inhibition of NO release correlated with decreased messenger ribonucleic acid (mRNA) expression of inducible NO synthase (iNOS).
Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Mice ; Tumor Necrosis Factor-alpha/genetics* ; Nitric Oxide/immunology* ; Microglia/immunology* ; Molecular Structure ; Liriodendron/chemistry* ; Monoterpenes/isolation & purification* ; Plants, Medicinal/chemistry* ; Cell Line ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; China

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

To investigate the impact of miR-142-5p on intestinal epithelial cells,an expression vector for overexpressing miR-142-5p lentivirus was constructed and administered to mice to observe pathological changes in their colon tissue.The miR-142-5p gene was integrated into the green fluo-rescent lentiviral vector plenti-CMV/TO eGFP-Puro(plenti),and the resulting recombinant vec-tor was named plenti miR-142-5p following confirmation through sequencing.293T cells were transfected with the recombinant plasmid and packaging-assisted plasmid,yielding a packaged miR-142-5p overexpressing lentiviral vector(LV-miR-142-5p).The recombinant lentivirus suspen-sion was collected and concentrated via ultrafast centrifugal precipitation.Virus titer was deter-mined using real-time PCR.The virus suspension was then injected into the tail vein of 6-8-week-old BALB/c mice,after which their colonic tissues were dissected for HE staining and microscopic observation.The results showed that miR-142-5p homologous recombination into plenti vector and sequencing results were consistent with the expected sequence.plenti-miR-142-5p was co-transfect-ed with the packaging helper plasmid in 293T cells,and the successful transfection was confirmed based on the green fluorescence expression,and the real-time PCR results showed that the lentiviral titer was 1.23 × 109 IU/mL.Colon tissue slices from infected mice exhibited compromised colon integrity and significant inflammatory response.It was proved that LV-miR-142-5p was suc-cessfully constructed,and miR-142-5p caused damage to intestinal epithelial cells of mice.

To investigate the impact of miR-142-5p on intestinal epithelial cells,an expression vector for overexpressing miR-142-5p lentivirus was constructed and administered to mice to observe pathological changes in their colon tissue.The miR-142-5p gene was integrated into the green fluo-rescent lentiviral vector plenti-CMV/TO eGFP-Puro(plenti),and the resulting recombinant vec-tor was named plenti miR-142-5p following confirmation through sequencing.293T cells were transfected with the recombinant plasmid and packaging-assisted plasmid,yielding a packaged miR-142-5p overexpressing lentiviral vector(LV-miR-142-5p).The recombinant lentivirus suspen-sion was collected and concentrated via ultrafast centrifugal precipitation.Virus titer was deter-mined using real-time PCR.The virus suspension was then injected into the tail vein of 6-8-week-old BALB/c mice,after which their colonic tissues were dissected for HE staining and microscopic observation.The results showed that miR-142-5p homologous recombination into plenti vector and sequencing results were consistent with the expected sequence.plenti-miR-142-5p was co-transfect-ed with the packaging helper plasmid in 293T cells,and the successful transfection was confirmed based on the green fluorescence expression,and the real-time PCR results showed that the lentiviral titer was 1.23 × 109 IU/mL.Colon tissue slices from infected mice exhibited compromised colon integrity and significant inflammatory response.It was proved that LV-miR-142-5p was suc-cessfully constructed,and miR-142-5p caused damage to intestinal epithelial cells of mice.

ObjectiveTo explore the rehabilitation outcome of personalized pulmonary rehabilitation therapy in pneumoconiosis patients in the rehabilitation station. Methods A total of 42 pneumoconiosis patients were selected as the study subjects from seven pneumoconiosis rehabilitation stations in Xinjiang Uygur Autonomous Region using the judgment sampling method. Patients were treated with personalized rehabilitation therapy for three months, and the outcome was analyzed. Results The six-minute walking test distance, maximum inspiratory pressure, maximum expiratory pressure, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FVC ratio of the pneumoconiosis patients were higher after rehabilitation therapy than those before therapy (all P<0.05). The score of Chronic Obstructive Pulmonary Disease Assessment Test of patients after therapy was lower than that in pre-treatment (P<0.05). There was no significant difference in respiratory difficulty, Borg scale, balance ability, depression symptoms, anxiety symptoms, nutritional status scores, body mass index, blood oxygen saturation, and heart rate before and after rehabilitation therapy (all P>0.05). Conclusion The individualized pulmonary rehabilitation therapy of pneumoconiosis patients at pneumoconiosis rehabilitation station can improve the respiratory muscle strength and lung function of patients, and improve their quality of life.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Given that current axial flow blood pumps have certain structural defects,resulting in poor performance and inferior blood compatibility,an integrated axial flow blood pump is developed,and its geometry is optimized using computational fluid dynamics method.The study also investigates the effects of different operational parameters on the performance of the blood pump and compares with experimental data to determine the optimal conditions.Additionally,the flow patterns of the blood pump are comprehensively analyzed for further revealing the internal flow phenomena,and the behavior of red blood cells in the blood flow and their response to shear stress are simulated using discrete phase model to evaluate the blood compatibility of the blood pump.The study shows that the novel blood pump performed well in terms of head.Under the optimal condition with a rotational speed of 9 000 r/min and a flow rate of 6.24 L/min,the blood pump improves the head by 16%as compared with the original structure,and reaches 25%efficiency,which can meet the physiological needs of most people.The pressure gradient and velocity gradient in most areas within the blood pump are smooth,and the internal flow patterns are generally stable,effectively avoiding the occurrence of hemolysis.The optimized blood pump can ensure high-level performance and favorable flow field characteristics while maintaining superior blood compatibility,which provides important reference for the structural optimization of axial flow blood pumps.

Objective: To examine the association of long working hours and shift work with occupational stress among medical staff in level A tertiary hospitals, so as to provide insights into promotion of physical and mental health among medical personnel. Methods: One level A tertiary hospital was sampled using a stratified cluster sampling method from southern and northern Xinjiang Uygur Autonomous Region, and all medical personnel were recruited from these two hospitals. Participants' demographics, working duration, and working in shifts were collected using questionnaires, and occupational stress was measured using the Core Scale for Measurement of Occupational Stress proposed by National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention. The associations of long working hours (weekly working duration of >40 hours) and shift work with occupational stress were examined using a multiple linear regression model. Results: A total of 2 529 questionnaires were allocated, and 2 262 were valid, with an effective rate of 89.44%. The respondents had a mean age of (35.12±8.71) years, and included 1 696 women (74.98%). Of all respondents, there were 722 doctors (31.92%), 1 033 nurses (45.67%), 361 medical or pharmaceutical technicians (15.96%), 1 808 with long working hours (79.93%) and 1 264 with shift work (55.88%). The score of occupational stress was (44.79±8.49) points, and the prevalence of occupational stress was 28.69% among respondents. Multiple linear regression analysis showed that after adjustment for age, marital status, length of service, position, smoking and physical exercise, long working hours (>40 h, β'=0.124; >48 h, β'=0.175; ≥55 h, β'=0.323) and shift work (β'=0.203) were influencing factors for occupational stress among medical personnel（P<0.05）; however, there was no interaction between long working hours and shift work (P>0.05). Conclusion Long working hours and shift work may increase the risk of occupational stress among medical personnel in level A tertiary hospitals.

OBJECTIVE：To compare the protective effects of different effective components of Astragali radix against DNA damage of human bone marrow mesenchymal stem cells （BMSCs）induced by ionizing radiation. METHODS ：2 Gy X-rays were used to directly irradiate BMSCs to establish a radiation model. CCK- 8 method was used to detect the effects of different mass concentrations（25，50，75，100 μg/mL）of astragalus polysaccharide ，astragalus saponin and astragalus flavonoids for 1 day before radiation + 1 to 5 days after radiation on the proliferation of BMSCs. The dose concentration and the duration of intervention after radiation were selected. The irradiated BMSCs were divided into radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group. The last three groups were treated with appropriate dosage of corresponding drugs before and 2 days after radiation ，and a blank groupwas set for comparison. Cytoplasmic division arrest qq.com micronucleus method was used to detect micronucleus cell rate and cell micronucleus rate after appropriate time of was used to detect th e number of 53BP1 foci in cells after appropriare time of intervention following radiation ；the number of 53BP1 foci were compared among different time points （0.5，2，12，24 h）. RESULTS ：Compared with blank group ，OD values of BMSCs were decreased significantly in radiation group （P＜0.05 or P＜0.01）. Compared with radiation group ，the OD values of BMSCs were significantly increased when 50 μ g/mL astragalus polysaccharide，astragalus saponin and astragalus flavonoids continuously intervened radiation for 2-3 days，there was significant difference in other groups at some time point （P＜0.05 or P＜ 0.01）. After consideration ，drug concentration was determined to be 50 μg/mL，and the continuous intervention time was 2 days after radiation. Compared with blank group ，the micronucleus cell rate and cell micronucleus rate of radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group increased significantly ，and the number of 53BP1 focus cluster in radiation group and astragalus polysaccharide group increased significantly （P＜0.01）. Compared with radiation group and astragalus flavonoids group ，the micronucleus cell rate ，cell micronucleus rate and the number of 53BP1 focus cluster （continued intervention for 0.5，2，12 h）in the astragalus polysaccharide group and astragalus saponin group were significantly reduced，and the micronucleus cell rate and cell micronucleus rate in the astragalus polysaccharide group were significantly lower than astragalus saponin group （P＜0.05）. 53BP1 focus cluster could not be detected 24 h later （P＜0.05）. CONCLUSIONS ： Astragalus polysaccharide and astragalus saponin both have protective effects on BMSCs DNA damage induced by radiation ，and the protective effect of astragalus polysaccharide is better than that of astragalus saponin ；astragalus flavonoids has no protective effect on radiation-induced DNA damage.

Objective:To explore the risk factors of hepatocellular carcinoma (HCC) in patients with hepatitis B cirrhosis receiving nucleoside/nucleotide analogues (NAs) antiviral therapy.Methods:The clinical data of 253 patients receiving NAs antiviral therapy in Zhejiang Provincial People’s Hospital from November 2014 to October 2019 were retrospectively analyzed. During treatment, HCC occurred in 116 patients. Multivariate logistic regression was used to analyze the risk factors of progression to HCC in patients with hepatitis B cirrhosis.Results:Multivariate logistic regression analysis showed that age( OR=1.094, 95% CI 1.034-1.158, P<0.01), smoking history( OR=5.056, 95% CI 1.453-17.594, P<0.05), family history of hepatocellular carcinoma( OR=6.763, 95% CI 1.253-36.499, P<0.05), Lamivudin (LAM) resistance( OR=6.097, 95% CI 1.370-27.134, P<0.05), fasting blood glucose(FBG)level( OR=7.219, 95% CI 3.716-14.024, P<0.01) were independent risk factors for the progression of hepatitis B cirrhosis to HCC; while HBV DNA negative conversion( OR=0.028, 95% CI 0.006-0.137, P<0.01) was a protective factor. Conclusions:For hepatitis B cirrhosis patients receiving antiviral therapy, drug resistance, HBV DNA, FBG levels should be closely monitored, intervention measures such as quitting smoking should be taken and NAs with high drug resistance gene barrier should be selected to prevent the occurrence of HCC.