ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

ObjectiveTo investigate the relationship between periodontitis severity and brain functional indices-amplitude of low-frequency fluctuations （ALFF） and fractional ALFF （fALFF） in cognitively normal middle-aged and older adults， and to examine their associations with cognitive performance. Methods42 cognitively normal middle-aged and older participants were enrolled. Periodontal data—including the number of remaining teeth （NTP）， bleeding on probing positivity rate （BOP%）， probing depth （PD）， and clinical attachment loss （CAL） as well as resting-state functional magnetic resonance imaging data were collected. Participants were divided into a mild periodontitis group and a moderate-to-severe periodontitis group according to periodontitis severity. Group differences in ALFF and fALFF were compared， and correlation analyses were performed. ResultsCompared with the mild periodontitis group， the moderate-to-severe group showed decreased ALFF values in the right lingual gyrus， superior occipital gyrus， paracentral lobule， and in the left calcarine cortex as well as the precentral and postcentral gyri. Decreased fALFF values were observed in the right lingual gyrus， cuneus， and left calcarine cortex. Indicators related to periodontitis progression ［BOP%， PD=4-5 mm （%）， PD≥6 mm （%）， CAL=3-4 mm （%） and CAL≥5 mm （%）］ were negatively correlated with ALFF， fALFF and cognitive performance， whereas indicators reflecting better periodontal function ［PD=1-3 mm （%） and CAL=0-2 mm （%）］ were positively correlated with these measures. ConclusionIn cognitively normal middle-aged and older adults， periodontitis severity is associated with alterations in brain functional activity and cognitive performance.

Objective To investigate the effect of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AngII receptor (ATR) gene polymorphisms combined with climatic factors on the incidence of essential hypertension (EH) in Tibetan population in Gannan area. Methods A follow-up study was conducted to select 671 Tibetan people in Gannan area who were physically examined in April 2019 at the Health Management Center of the Second Hospital of Lanzhou University and agreed to be enrolled as a fixed cohort, and the blood pressure values of the enrolled subjects were measured after 3.5 years of follow-up, and a total of 501 cases were obtained. At the same time, the peripheral blood of all subjects was collected and the polymorphisms of AGT, ACE and ATR genes were detected by gene chip technology, and the possible interactions were analyzed by logistic regression model, fork generation method and multifactor-dimensionality reduction (MDR). Results Sunshine time was a protective factor for the incidence of hypertension in the Tibetan population of Gannan (OR=0.781), while relative humidity (OR=1.182), air pressure (OR=1.338) and temperature (OR=1.449) were the risk factors for the incidence of hypertension. According to the results of partial correlation analysis, temperature had no effect on the incidence of hypertension after controlling air pressure. There was an additive interaction between high air pressure and the polymorphisms of rs699 (OR=1.650, 95%CI: 1.293-2.399, P<0.001) and rs5049 (OR=1.711, 95%CI: 1.337-4.920, P<0.001) genes of AGT gene; there was a multiplicative interaction between relative humidity and rs699 (OR=0.472, 95%CI: 0.120-0.783, P<0.05);there was a multiplicative interactions between the altitude ≥ 3000m and rs699 (OR=1.503, 95%CI: 1.220-3.174, P<0.01), rs5049 (OR=1.673, 95%CI: 1.380-3.961, P<0.001) or rs2148582 (OR=0.519, 95%CI: 0.284-0.716, P<0.05).However, there was no interaction between climatic factors and ACE or ATR gene polymorphisms on the incidence of hypertension. Conclusion Climatic factors and altitude ≥3 000 m are closely related to the incidence of hypertension in the Tibetan population of Gannan area, and the interaction between AGT gene polymorphisms and climatic factors affects the incidence of hypertension in the population of this area.

ObjectiveTo investigate the alleviating effect of calcium cyanamide （CaCN₂） soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil （NP） was used as the control group， while three treatment groups were established： replanted soil （RP）， newly soil treated with CaCN₂ （120 g·m²， tillage depth 25 cm） （NPCC）， and replanted soil treated with CaCN₂ （RPCC）. R. glutinosa was cultivated in all groups. At harvest， the tuber agronomic traits （number of enlarged roots， maximum root diameter， fresh weight， dry weight） were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography （UPLC） to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 （ITS2） sequencing and 16S rDNA sequencing， respectively. ResultsCompared with NP， the RP group showed obviously reduced in tuber agronomic traits and quality indicators （P0.05）. However， the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP （P0.05）. The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP （P0.05）. The polyphenol oxidase soil （S-PPO） activity in RP was obviously lower than in NP （P0.05）， while sucrose soil （S-SC）， acid phosphatase soil （S-ACP）， and S-PPO activities in RPCC were obviously higher than in RP （P0.05）. Microbial richness and diversity in RP were obviously higher than in NP （P0.05）， whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria， Myrothecium， Tomentella， and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP （P0.05）. Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D （P0.05）. Fungal genera Engyodontium and Alternaria， and bacterial genera Pir4 lineage， Pirellula， Methyloversatilis， Brevundimonas， Ralstonia， and Acidibacter were obviously positively correlated with tuber dry weight （P0.05）. Conversely， fungal genera Pseudaleuria， Nectria， Haematonectria， Ceratobasidium， and bacterial genera Streptomyces， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated with dry weight （P0.05）. The fungal genus Alternaria and bacterial genera Brevundimonas， Ralstonia， Acidibacter， and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber， while fungal genera Pseudaleuria， Nectria， Stachybotrys， Fusarium， Gibberella， Ceratobasidium， and bacterial genera Sphingomonas， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated （P0.05）. ConclusionCaCN₂ soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil， enhance the utilization of available nutrients， reshape microbial community structure of replanted R.glutinosa at the family and genus level， and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques， including soil disinfection， nutrient-targeted regulation， and microbial inoculant application.

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective:To explore the clinical utility of peripheral immune-inflammatory markers in predicting late-life depression with cognitive impairment(LLD+ CI + ). Methods:A cross-sectional study was conducted between January 2020 and December 2021, collecting demographic data, peripheral blood inflammatory markers, and cognitive function scores from 40 patients with LLD+ CI + , 38 patients with late-life depression without cognitive impairment(LLD+ CI -), and 26 healthy controls(HCs). Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were employed to assess the value of peripheral blood inflammatory markers in differentiating LLD+ CI + . Results:Patients with LLD+ CI + exhibited significantly different levels of lymphocytes, C-reactive protein(CRP), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio(NHR), and neutrophil-to-lymphocyte ratio (NLR)compared with the LLD+ CI - group and the HGs group( F=4.000, 11.642, 13.541, 10.441, 6.623, 4.193; P=0.022, 0.003, 0.001, 0.005, 0.036, 0.018). The multivariate logistic regression analysis of factors influencing LLD+ CI + revealed that elevated levels of CRP( OR=4.933, 95% CI: 1.385-17.563, P=0.014), SII( OR=5.534, 95% CI: 1.336-22.927, P=0.018), and NLR( OR=3.386, 95% CI: 1.470-7.797, P=0.004)constitute risk factors for geriatric depression with cognitive impairment, while an increased lymphocyte count( OR=0.206, 95% CI: 0.058-0.725, P=0.014)serves as a protective factor.Further analysis identified CRP, lymphocytes, SII, and NLR as significant predictors for LLD+ CI + , with areas under the curve (AUC) values of 0.849(95% CI: 0.760-0.934), 0.847(95% CI: 0.761-0.933), 0.860(95% CI: 0.777-0.943), and 0.857(95% CI: 0.777-0.938), respectively, in distinguishing LLD with or without cognitive impairment. Conclusions:Peripheral immune-inflammatory markers represent an economical and effective approach for investigating the pathophysiological changes and predictive factors associated with LLD+ CI + .These findings provide valuable insights into the underlying mechanisms and potential therapeutic avenues.

To enhance the trustworthiness,security,and convenience of research data management and pro-mote the deep utilization of clinical research data,it introduces core technologies such as data sandboxing,ze-ro-trust architecture,elastic resource scheduling in cloud computing,and data lakes to construct a clinical research trusted data space with trusted management,resource interaction,and value co-creation capabilities.This trusted data space provides a secure and efficient platform for data processing and analysis through strict network access control,dynamic authentication,data anonymization,and digital watermarking technologies.It ensures the secure flow and precise traceability of research data throughout its lifecycle,effectively facilitating resource interaction and value co-creation.The implementation offers a valuable technical reference and practical guidance for other hospitals aiming to build trusted research data platforms.

Objective To investigate the role of Insulin like growth factor 2 mRNA binding protein 1(IGF2BP1)and long non-coding RNA LINC00160(LINC00160)in gastric cancer,and its potential mechanism of regulating the proliferation and invasion of gastric cancer cells.Methods Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression level of LINC00160 in gastric cancer tissues and cells.Bioinformatics prediction,RNA-binding protein immunoprecipitation(RIP)and methylated RNA immunoprecipitation(MeRIP)were used to verify the binding effect of LINC00160 and IGF2BP1.The correlation between the expression of LINC00160 and IGF2BP1 in gastric cancer tissues was analyzed by Pearson assay.CCK-8 assay and Transwell assay were used to detect cell proliferation and invasion.The changes of aerobic glycolysis index[glucose intake,lactate production,and Adenosine-triphosphate(ATP),extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)]were detected and analyzed.Results Compared with normal tissues,the expression of LINC00160 in gastric cancer tissues(5.13±0.62 vs 1.02±0.03)was significantly up-regulated,and the difference was statistically significant(t=-36.266,P<0.001).The expression level of LINC00160 in gastric cancer cells was higher than that of human normal gastric epithelial cell line GES-1,and the difference was statistically significant(F=24.595,P<0.001).Compared with the control group,silenting LINC00160 significantly inhibited the proliferation(0.42±0.03 vs 1.03±0.04)and invasion(22.13%±1.97%vs 42.15%±2.67%)of AGS cells,decreased glucose uptake(2.11±0.26mmol/L vs 4.22±0.37mmol/L)and lactate production(6.84±1.25mmol/L vs 11.68±1.55mmol/L),decreased ECAR,and increased ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)levels and OCR,and the differences were statistically significant(t=4.188～24.423,all P<0.01).The expression of IGF2BP1 protein in gastric cancer tissues(4.07±0.36)was significantly higher than that in adjacent tissues(1.01±0.03),and the difference was statistically significant(t=-46.396,P<0.01),and was positively correlated with the expression of LINC00160(r2=0.774 5,P<0.01).Mechanistic studies revealed that IGF2BP1 upregulated LINC00160 expression by binding m6A modified LINC00160 to promote its stability.Silencing IGF2BP1 significantly inhibited the expression of LINC00160 and the proliferation,invasion and aerobic glycolysis of gastric cancer cells,and the differences were statistically significant(t=4.386～11.989,all P<0.01).Overexpression of LINC00160 reversed the effect of IGF2BP1 silencing on AGS cells.Conclusion LINC00160 is significantly up-regulated in gastric cancer,and IGF2BP1 may stably regulate the expression of LINC00160 through m6A modification,promote the aerobic glycolysis of tumor cells,and participate in the occurrence and development of gastric cancer.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.