The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NP_FeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H₂S amplification. The bioactive NP_FeS/GD exhibited controlled release of GSDMD plasmid, H₂S, and Fe²⁺ in response to the tumor microenvironment. Fe²⁺, H₂S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H₂S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NP_FeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H₂S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

Objective To explore the optimal extraction process of flavonoids from Epimedii folium by deep eutectic solvent method.Methods Using the extraction rate of epimedin A,epimedin B,epimedin C and icariin in Epimedii folium as evaluation indices,the extraction process of flavonoids in Epimedii folium was optimized based on single factor experiments such as solid-liquid ratio,molar ratio,moisture content,extraction temperature,and extraction time,combined with orthogonal experimental design,and the components in the solvent were recovered using macroporous resin.Results The deep eutectic solvent formed by choline chloride and ethanolamine had the best extraction effect.When the molar ratio of choline chloride to ethanolamine was 1:4,the solid-liquid ratio was 0.5 g:25 mL,the water content was 50％,the extraction temperature was 70 ℃,and the extraction time was 15 minutes,the total extraction rate was(20.07±0.43)mg/g,and the AB-8 macroporous resin could recover flavonoids in the eutectic solvent with an average recovery rate of 88.29％.Conclusion Deep eutectic solvents have great potential in the extraction of active ingredients in traditional Chinese medicine due to their simple preparation and higher extraction efficiency compared to traditional solvents.

Objective To observe the protective effect of electroacupuncture(EA)on ankle joint synovitis and HIF-1 α/MDM2/p53 signaling pathway in adjuvant arthritis(AA)rats.Methods SD rats were randomly divided into control group,model group,sham EA group,agonist group,EA group,EA+antagonist group,antagonist group,with 10 rats in each group.Preparation of AA rat model by injecting Freund's complete adjuvant into bilateral foot pads of rats.EA(2 Hz,3 V)was applied to bilateral ST36 and GB39 or two control points(5 mm left to ST36 and GB39)for 15 min,once every other day for a total of 8 times.HIF-1 α agonists and antagonists were injected into the tail vein of rats in the corresponding groups.The inflammatory conditions of the ankle joint were observed by HE staining,and the contents of serum HIF-1 α was assayed by ELISA.mRNA expression of HIF-1α,VEGF,MDM2 and p53 were detected by RT-PCR,protein expression of HIF-1α,VEGF,MDM2 and p53 were detected by Western blot in synovium of AA rats.Results The results of HE staining showed that compared with the control group,the synovial cells in the model group had significant proliferation and inflammatory cell infiltration(P<0.01);Compared with the model group,the arthritic reaction of the rats in the EA group,the EA+antagonist group and the antagonist group was significantly reduced(P<0.01),while the arthritic reaction of the rats in the sham EA group and the agonist group was still serious(P>0.05).The results of ELISA showed that compared with the control group,the serum HIF-1αexpression of the model group rats was significantly increased(P<0.01);Compared with model group,serum HIF-1αexpression of rats in EA group,EA+ antagonist group and antagonist group was significantly decreased(P<0.01);There was no significant difference in serum HIF-1αexpression among the model group,sham EA group and agonist group(P>0.05).RT-PCR results showed that compared with the control group,the mRNA expression of HIF-1α,VEGF,MDM2 and p53 of model group rats increased significantly;Compared with model group,the mRNA expression of HIF-1α,VEGF and MDM2 of rats in EA group,EA+antagonist group and antagonist group decreased significantly,while the mRNA expression of p53 increased significantly.Western blot results showed that compared with the control group,the protein expression of HIF-1α,VEGF,MDM2 and p53 of model group rats increased significantly;Compared with model group,the mRNA expression of HIF-1α,VEGF and MDM2 of rats in EA group,EA+antagonist group and antagonist group decreased significantly,while the mRNA expression of p53 increased significantly.Conclusion Electroacupuncture intervention has significant protective effect on ankle inflammation in AA rats,HIF-1 α/MDM2/p53 signaling pathway plays a key role in this process.

Microbial cell factories capable of producing valuable chemicals from renewable feedstocks provide a promising alternative towards sustainability. However, environmental stress remarkably affects the performance of microbial cell factories. By extending the chronological lifespan of microbial cells, the performance of microbial cell factories can be greatly improved. Firstly, an evaluation system for chronological lifespan and semi-chronological lifespan was established based on the changes in survival rates. Secondly, the addition of anti-aging drugs such as cysteine, carnosine, aminoguanidine and glucosamine increased the chronological lifespan of E. coli by 80%, 80%, 50% and 120%, respectively. Finally, we demonstrated that extending the chronological lifespan of E. coli increased the yield of metabolites produced by E. coli cell factories with endogenous (lactic acid and pyruvic acid) or exogenous (malic acid) metabolic pathway by 30.0%, 25.0%, and 27.0%, respectively. The strategy of extending chronological lifespan of E. coli provides a potential approach for enhancing the performance of microbial cell factories.
Escherichia coli/genetics* ; Lactic Acid ; Longevity ; Metabolic Engineering ; Metabolic Networks and Pathways

In industrial fermentation processes, bacteria have to adapt environmental stresses. Sometimes, such a self-adaption does not work and will cause fermentation failures, although such adaptation also can generate unexpected positive effects with improved fermentation performance. Our review introduces cell self-adaption to environmental variations or stress, process optimization based on such self-adaptions, with heterologous proteins production by Pichia pastoris and butanol fermentation as examples. Our review can sever as reference for fermentation optimization based on cell self-adaption.
Adaptation, Physiological ; Butanols ; metabolism ; Environment ; Fermentation ; Pichia ; cytology ; metabolism

Alpha-keto acid is a bifunctional organic compound containing both carboxyl and ketone groups, and widely applied in the industries of food, pharmaceutical and cosmetics. Based on the demand of eco-friendly process, safety and sustainable development, production of α-keto acids by enzymatic conversion technology has been paid more and more attention. In this article, we review the status of α-keto acids biosynthesis from three aspects: enzymatic screening, enzymatic modification and optimization of enzymatic conversion conditions. Meanwhile, we also indicate future research directions for further improving α-keto acids production.
Keto Acids ; metabolism

Since the Eighteenth National Congress of the Communist Party of China, China has constantly innovated and developed its diplomatic concept, and proposed the important idea of the Community of Shared Future for Mankind (CSFM), which contributes a discourse system with Chinese characteristics to the world. It is indicated that discourse builds its subject and governs the subject’s discourse practices, and the discourse subject strengthens and reiterates discourse rules in discourse practices. China aid project of schistosomiasis control in Zanzibar is a discourse subject of the CSFM discourse system. This paper analyzes the discourse status, discourse practices and the reiteration of discourse rules of China aid project of schistosomiasis control in Zanzibar.

L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.

As a platform chemical, acetoin has a great potential of application in medicine and food industries. In order to improve the efficiency of acetoin production, Bacillus amyloliquefaciens was treated by atmospheric and room temperature plasma and gamma rays. Two-round screening was adopted for obtaining positive mutants, and the best mutant B. amyloliquefaciens H-5 produced acetoin up to 68.2 g/L in shake flask. Then, culture conditions were optimized in 5-L fermentor to enhance acetoin production. Finally, 85.2 g/L acetoin was produced by B. amyloliquefaciens H-5, which was increased by 26.8% compared with that of the original strain B. amyloliquefaciens FMME088. These results indicated that the high-producing strain can be obtained efficiently by compound mutagenesis, which has a promising prospect for commercial scale process.

Objective To investigate the influence of preoperative anxiety-depression status on the postoperative pain in patients undergoing gynecologic laparoscope surgery.Methods Ninety pa-tients,aged 18-65 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,undergoing gynecologic laparoscope surgery were included in this single-center observational study.All the patients were in-terviewed by anesthetists the afternoon before surgery and completed a Hospital Anxiety and Depres-sion Scale (HADS)to evaluate the anxiety-depression status.Then the patients were divided into two groups,low HADS group (group L)(HADS score≤9)and high HADS group (group H)(HADS score>9).Patients'visual analogue scores (VAS)were recorded at the time 30 min,60 min,6 h, 12 h,24 h after operation.The correlation analysis between HADS before operation and VAS scores at different time point was performed.The use of analgesia medicine,exhausting time and complica-tions such as nausea, vomiting, dizzy, pain of shoulder and back were also recorded. Results Compared to group H,VAS score was lower in group L at 6 hour after surgery but no sig-nificant different was found at 30 min,60 min,12 h,24 h after surgery.There was a significant asso-ciation between preoperative HADS scores and VAS at 6 hour after surgery (r=0.634,P=0.01);but no significant association was found between preoperative HADS scores and VAS at the other time point after surgery.The exhausting time was significantly longer in group H than group L (P<0.05).There was no significant difference in the incidence of nausea,vomiting,dizzy or pain of shoulder and back between the two groups.Conclusion Preoperative anxiety-depression status has a positive influence on postoperative pain at 6 hour after gynecologic laparoscope surgery,and also can delay the recovery of gastrointestinal function.