ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Rapid and accurate detection methods for food-borne pathogens are essential to ensure food safety and human health.One promising innovation in this area is the clustered regularly interspaced short palindromic repeats/CRISPR-associated systems(CRISPR/Cas)biosensor,which utilizes Cas protein and CRISPR RNA(crRNA)ribonucleo protein to specifically recognize target genes,and converts target signals into detectable physical and chemical signals.The CRISPR/Cas biosensor shows many advantages,such as high specificity,programmability,and ease of use,making it promising to pathogen detection.This paper introduced the principles and characteristics of CRISPR/Cas systems,along with the strategies for signal recognition,amplification,and output based on different CRISPR/Cas biosensors,and their respective applications in food-borne pathogen detection.Furthermore,the construction principles and challenges of multiple biosensors based on CRISPR/Cas were explored,as well as their potential for simultaneous detection of multiple pathogens.Finally,the challenges and future development trends of CRISPR/Cas-based biosensors in rapid pathogen detection were discussed,aiming to provide valuable reference and inspiration for biosensor designers and food safety practitioners.

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.

Objective To survey and analysis of cephalometric indicators of Wa adults in China.Methods Cephalometric parameters were measured in 1996 cases(858 males and 1138 females)of Wa adults in China,including 927 cases(381 males and 546 females)of the Baraoke ethnic group,564 cases(241 males and 323 females)of the A Wa ethnic group,and 505 cases(236 males and 269 females)of the Wa ethnic group by using sliding caliper and spreading caliper.Seventeen direct cephalofacial parameters and one indirect parameter for each of the three dialect ethnic groups were derived separately and analyzed for age correlations,inter-sex u-tests,and multiple comparisons.Finally,the three dialect ethnic groups were subjected to cluster analysis and principal component analysis with 15 ethnic groups in China.Results Nose breadth,mouth breadth and physiognomic ear length were significantly and positively correlated with age for both sexes in the three Wa dialect ethnic groups,while head breadth and lip height were significantly and negatively correlated with age.Except for the interocular breadth,there were gender differences between males and females in the cephalometric parameters of the three Wa dialect ethnic groups.The cephalofacial features of the Baraoke,A Wa and Wa ethnic groups were different,as evidenced by the fact that males and females of the Baraoke and Wa dialect ethnic group had higher lip height,wider nasal breadth and wider mouth breadth,while males and females of the A Wa ethnic group had lower nasal height.Conclusion The cephalofacial features of the three Wa dialect ethnic groups are close to those of the Khmus and Mang,who have their origins in the ancient Baipu people and are also members of the Mon-Khmer language group of the Austroasiatic linguistic.

Objective To investigate the effect of early postoperative abnormal blood glucose on the short-term prognosis of non-small cell lung cancer(NSCLC),and to analyze the clinical characteristics and risk factors related to poor early prognosis.Methods A total of 897 patients with NSCLC who underwent thoracoscopic surgery in Huadong Hospital,Fudan University from Jan 2020 to Aug 2021 were divided into hyperglycemia(HG)group(>7.8 mmol/L)and normal blood glucose(NG)group(≤7.8 mmol/L and≥3.9 mmol/L)according to the early postoperative blood glucose values.Additionally,the patients were divided into higher blood glucose fluctuation group(≥4 mmol/L)and the group with lower blood glucose fluctuation(<4 mmol/L)basing on the fasting blood glucose.Using Logistic regression models,column line charts,ROC curves and other methods,we aimed to clarify the impact of early postoperative blood glucose abnormalities on short-term prognosis,explore clinical characteristics associated with poor short-term outcomes,identify other high-risk factors,and establish relevant risk prediction models.Results Compared with the NG group,the incidence of postoperative pneumonia,thromboembolism,ICU admission rate,total length of hospital stay and hospital cost were significantly higher in the HG group(P<0.05).Higher blood glucose fluctuation group had a greater risk of ICU admission(P=0.003).Logistic regression analysis showed that age,preoperative fasting glucose,white blood cell count and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)were risk factors for postoperative hyperglycemia(P<0.05).Contrary to the effect of BMI,diabetes,male patients,higher blood glucose fluctuation,white blood cell count and age were the risk factors for postoperative adverse events(P<0.05).The AUC of the column line chart model was 0.661(95%CI:0.624-0.698),indicating good discriminative ability for predicting poor short-term prognosis postoperatively.Calibration curves also demonstrated good consistency between predicted and actual probabilities.Conclusion Early postoperative blood glucose fluctuations independently impact the short-term prognosis of thoracoscopic NSCLC patients.Blood glucose combined with gender,BMI,white blood cell count,age and diabetes history can serve as predictive factors for poor short-term prognosis postoperatively.Additionally,a column line chart constructed based on these factors may aid clinicians in early intervention for NSCLC patients with indications.

Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.

As a key epigenetic regulator, histone deacetylases (HDACs) play a crucial role in cancer development. Small molecule HDAC inhibitors have been shown to inhibit tumor proliferation and induce apoptosis, attracting significant research attention. In this study, we designed and synthesized a series of novel saccharin derivatives as HDAC inhibitors. Biological experiments demonstrated that the target compound 9a exhibited superior HDACs inhibition activity to vorinostat and demonstrating promising in vitro and in vivo anti-tumor activity against triple-negative breast cancer (TNBC). All animal experiments in this study were performed in strict accordance with the protocols approved by the Ethical Committee of School of Pharmaceutical Sciences in Shandong University (Approval No. 230094). This work represents an initial exploration of developing saccharin-based HDAC inhibitors, and the active compound 9a could serve as a lead compound for further study.

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation

Objective To investigate the pharmacodynamic effects of Poria triterpenes on tumor suppression in mice with ascites tumors,and to detect and identify the chemical components of Poria triterpenes using HPLC-LTQ-Orbitrap method,and to explore the potential mechanism of action of Poria triterpenes on tumor suppression in mice with ascites tumors based on both of them using non-labeled definitive proteomics techniques.Methods Poria triterpene parts were extracted by solvent method,and the main components were detected and identified by HPLC-LTQ-Orbitrap liquid mass spectrometer;mice were randomly divided into model group,Poria triterpene group and positive control group(mushroom polysaccharide group),after 21 days of continuous administration,to establish After continuous administration for 21 days,the H22 ascites tumor mouse model was established,and the effect of each drug group on the amount of ascites,spleen index,thymus index,liver index,serum TNF-Alpha and IL-2 in H22 ascites tumor mice was observed after one week of continued administration;then H22 cells were extracted from the ascites of mice,and the H22 cells in the model group and Poria triterpene group were detected by non-lable-free quantitative proteomics technique.The differentially expressed proteins(DEPs)were screened out by using GO,KEGG and other analyses.Results The abdominal water volume in the mouse Poria triterpene group was significantly lower than that in the model group(P<0.05);the thymus index in the mouse Poria triterpene group was significantly higher than that in the model group(P<0.05);the serum levels of TNF-Alpha in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01),and the serum levels of IL-2 in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01).Through the analysis of the chemical composition of Poria triterpene parts,a total of 19 triterpenoids were identified,with four main structural types.A total of 188 differentially expressed proteins were identified in the Poria triterpene group compared with the model group,of which 86 differentially expressed proteins were up-regulated and 102 differentially expressed proteins were down-regulated;GO database analysis showed that the differentially expressed proteins in the Poria triterpene group were mainly involved in the regulation of interleukin-1 production The KEGG database analysis showed that the differentially expressed proteins in the Poria triterpene group were involved in signaling pathways closely related to tumor,mainly MAPK,Apoptosis,mTOR,Wnt and p53 pathways,etc.The genes coding for the seven representative differential proteins were validated at the mRNA level by RT-qPCR.Conclusion The pharmacodynamic study found that Poria triterpenes had tumor suppressive effect on H22 ascites tumor mice,then by proteomics found Poria triterpenes group ascites H22 cell protein compared to the model group changed significantly,the study thus showed that Poria triterpenes for mice ascites tumor mechanism of tumor suppressive effect mainly involves apoptosis,inflammatory response and immune process.