Metformin promotes anti-tumor immunity in STK11 mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites

Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/threonine kinase 11(STK11)mutant non-small cell lung cancer(NSCLC)through an axis inhibition protein 1(AXIN1)-dependent manner.However,the alterations of tumor metabolism and metabolites upon metformin administration remain unclear.Methods:We performed untargeted metabolomics using liquid chromatography(LC)-mass spectrometry(MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis.Results:According to the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database,most metabolites were annotated into metabolism,including nucleotide metabolism.Next,the differentially expressed metabolites in H460(refers to H460 cells),H460_met(refers to metformin-treated H460 cells),and H460_KO_met(refers to metformin-treated Axin1-/-H460 cells)were distributed into six clusters based on expression patterns.The clusters with a reversed expression pattern upon metformin treatment were selected for further analysis.We screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were upregulated.Furthermore,these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes(STING)pathway independently of AXIN1.Conclusion:Relying on AXIN1,metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC,indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC.

Analysis of Changing Factors on Airborne Allergenic Pollens Distribution in Taiyuan Downtown, North China

To study and analyse 2 surveys on airborne allergenic pollens distribution in Taiyuan Downtown, North China 30 years apart, the surveys focused on the phenomenon and the influence factors on types, counts, drift patterns, growth and decline rhythm and distribution features of airborne pollen with the same methods in the region in March 1977 to February 1978 and July 2008 to June 2009, respectively. The data of two airborne pollens surveys were treated with statistics, comparation and analysis, and the influence factors of pollen distribution in Taiyuan Downtown were explored. In the 2 surveys, 24 species and 35 species of pollen were collected in the region, respectively. Two pollen drift peaks were formed in spring and autumn in the two surveys. Artemisia L. is still the absolute dominant allergy airborne pollen. The types, counts, drift patterns and composition of pollen in air could be changed by the plants variation. Climate warming might affect pollen peak appearing time and lasting time, climate warming and Poplar & Willow contents changes in spring and autumn reversed the airborne pollen peak. It was found that Humulus L. had become the region’s main allergic pollen. Invasive strong allergen ragweed was spread to the inland city Taiyuan. Allergists should focus on exotic invasive harmful plants in the region.

Beneficial Effects of Traditional Chinese Medicine Fuzheng Huayu on the Occurrence of Hepatocellular Carcinoma in Patients with Compensated Chronic Hepatitis B Cirrhosis Receiving Entecavir:A Multicenter Retrospective Cohort Study

Background and Aims:The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma(HCC)has not been established.Here,we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu(FZHY)on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir(ETV).Methods:A multicenter retrospective cohort study was performed.Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment.The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests.Propensity score matching was used for confounding factors.Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation.Results:Out of 910 chronic hepatitis B patients,458 were in the ETV+FZHY group and 452 were in the ETV group.After propensity score matching,the 5-year cumulative incidence of HCC was 9.8%in the ETV+FZHY group and 21.8%in the ETV group(p<0.01).The adjusted hazard ratio for HCC was 0.216(0.108,0.432)when FZHY treatment was>36 months.Age,diabetes,alanine aminotransferase,-glutamyl transpeptidase,albumin,hepatitis B e-antigen,and fibrosis 4 score were associated with the occurrence of HCC.FZHY decreased the risk of HCC in patients aged>45 years with a hepatitis B virus DNA level of2,000 IU/l.Conclusion:Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV,possibly due to the antifibrotic properties of FZHY.

Suno:potential,prospects,and trends

Suno has attracted wide attention due to its impressive capabilities.It demonstrates technological advancements and opens up new possibilities for music composition,representing a milestone in the development of artificial intelligence(AI)music generation.In this paper,we first introduce the background and summarize the general technical framework of AI music generation,followed by an analysis of Suno’s advantages and disadvantages.Finally,we discuss the future trends in Music and AI.

Visual knowledge guided intelligent generation of Chinese seal carving

We digitally reproduce the process of resource collaboration,design creation,and visual presentation of Chinese seal-carving art.We develop an intelligent seal-carving art-generation system(Zhejiang University Intelligent Seal-Carving System,http://www.next.zju.edu.cn/seal/;the website of the seal-carving search and layout system is http://www.next.zju.edu.cn/seal/search_app/)to deal with the difficulty in using a visual knowledge guided computational art approach.The knowledge base in this study is the Qiushi Seal-Carving Database,which consists of open datasets of images of seal characters and seal stamps.We propose a seal character generation method based on visual knowledge,guided by the database and expertise.Furthermore,to create the layout of the seal,we propose a deformation algorithm to adjust the seal characters and calculate layout parameters from the database and knowledge to achieve an intelligent structure.Experimental results show that this method and system can effectively deal with the difficulties in the generation of seal carving.Our work provides theoretical and applied references for the rebirth and innovation of seal-carving art.