Objective High-altitude chronic hypoxia can alter the immune status,yet the immune regulatory characteristics of various vaccine adjuvants in this environment remain to be fully elucidated.Accordingly,emphasis is placed on evaluating the regulatory effects of chronic hypoxia on specific humoral,cellular,and memory T cell responses elicited by different adjuvants.Methods Using ovalbumin(OVA)as the antigen,Th2-biased adjuvant aluminum hydroxide(Alum),Th1-biased adjuvant CpG,and Th1/Th2-balanced adjuvant QML were combined for intramuscular immunization in mice on days 0 and 14.Th1-biased adjuvant CpG,or Th1/Th2-balanced adjuvant QML for intramuscular immunization on day 0 and 14(n=16).A total of 160 SPF female C57BL/6 mice(6 to 8 weeks old,weighing 16 to 18 g)were randomly divided into 5 groups(n=32):PBS group(sterile PBS),OVA group(5 μg OVA),OVA+Alum group(5 μg OVA and 100 μg Alum),OVA+CpG group(5 μg OVA and 20 μg CpG),and OVA+QML group(5 μg OVA and 50 μL QML).Each group was further divided into normoxia control(n=16,housed in 21%O ₂ environment)and chronic hypoxia(n=16,simulated altitude 5 800 m)subgroups.On days 14 and 60 after the last immunization,the serum levels of specific IgG,IgG1,and IgG2c antibodies were measured by ELISA;enzyme-linked immunospot assay(ELISpot)was used to detect the numbers of cells secreting IFN-γ,IL-4,and IL-17A in the splenocytes.On day 14 after the last immunization,flow cytometry was performed to determine the proportions of CD4 ⁺ IFN-γ ⁺,CD4 ⁺ IL-4 ⁺,CD4 ⁺ IL-17A ⁺,CD8 ⁺ IFN-γ ⁺,and CD8 ⁺ IL-2 ⁺ cell subsets in the spleen.Results Chronic hypoxia significantly inhibited the ability of OVA alone to induce IgG antibodies(P<0.01),and all 3 adjuvants reversed this effect.QML exerted a stable and superior enhancing effect on serum-specific IgG,IgG1,and IgG2c levels compared to CpG(P<0.05).Notably,CpG induced significantly higher levels of total IgG(P<0.01)and IgG1(P<0.05)in the chronic hypoxia group than in the corresponding normoxia group at days 60 after the final immunization.For cellular immunity,QML stably increased the proportions of CD4⁺IFN-γ⁺ and CD4⁺IL-17A⁺ cells,as well as the secretion levels of IFN-γ and IL-4,under both normoxic and hypoxic conditions.In contrast,the T cell regulatory effects of CpG were hypoxia-dependent,with significant enhancement of IFN-γ-secreting cell numbers in the hypoxia group at both short-term(14 d,P<0.01)and long-term(60 d,P<0.05)time points.Analysis of memory T cells showed that all 3 adjuvants maintained CD4⁺Tcm levels under hypoxia.Additionally,CpG increased the proportions of CD8 ⁺ Tcm(P<0.05)and CD8 ⁺ Tem(P<0.01)in the hypoxic group,while Alum only specifically elevated CD4 ⁺ Tem levels under hypoxic conditions(P<0.05).Conclusion QML stably induces comprehensive immune responses under both normoxic and hypoxic conditions,while CpG exhibits advantages in Th1-type response enhancement and CD8⁺memory T cell expansion under chronic hypoxia,providing experimental evidence for adjuvant selection in chronic hypoxic environments such as high-altitude regions.

The pervasive accumulation of plastic waste exacerbates environmental degradation and undermines resource circularity. Selective thermal catalysis emerges as a transformative pathway for valorizing waste plastics into value-added chemicals, yet persistent challenges in catalytic activity and product selectivity demand systematic resolution. This review decodes cutting-edge advances in thermal depolymerization by converging two critical dimensions: atomic-scale active site engineering-where rational design of coordination features and interfacial architectures regulates C-C cleavage energetics and intermediate adsorption-and macromolecular-scale manipulation of polymer transient states-leveraging nanoconfinement effects, chain folding dynamics, and thermal fragmentation to accelerate conversion kinetics. We further highlight breakthroughs in operando characterization techniques that resolve time-evolving reaction coordinates across catalytic systems. By establishing multiscale structure-activity relationships linking catalyst configurations to polymer dynamics, this analysis derives design paradigms for next-generation upcycling systems. These principles enable economically viable, industrially scalable plastic valorization while charting a strategic trajectory toward carbon-circular economies.

Vaccines represent the most cost-effective and efficacious approach for preventing gastrointestinal infections,and adjuvants play a pivotal role in enhancing and modulating immune responses.In this article,we summarize the mechanisms,advantages,and limitations of molecular adjuvants that induce gastrointestinal mucosal immune responses,as well as of delivery systems with dual adjuvant and carrier functions.We also analyze the principal challenges encountered in the development of such adjuvants,encompassing issues related to safety,efficacy,and adaptability.Furthermore,this article provides perspectives on future research directions for mucosal immunity-based adjuvants for gastrointestinal vaccines,including design of programmed adjuvants targeting specific gastrointestinal receptors,composite strategies integrating delivery systems with adjuvants,and adjuvant optimization tailored for special populations.

The limitations of existing drugs and the development of drug resistance make it urgent to develop new drugs against methicillin-resistant Staphylococcus aureus (MRSA). The re-development of the antibacterial activity of drugs that have already been proven safe for human use is an effective way. In this study, we discovered that the Src homology region 2 domain-containing phosphatase-1 (SHP-1) agonist SC-43, exhibits potent activity against Gram-positive bacteria, including MRSA. The mode of action studies revealed that SC-43 inhibits the key enzyme coproporphyrin ferrochelatase (CpfC) of the coproporphyrin-dependent (CPD) heme synthesis pathway and interferes with the bacterial porphyrin metabolism. The determination of the structure of CpfC derived from S. aureus (SACpfC) in this study allowed us to reveal the inhibitory effect of SC-43 at the molecular level. Animal experiments showed that SC-43 has the potential to become a new anti-MRSA drug. In conclusion, this study discovered a new anti-MRSA activity of a drug currently undergoing clinical trials and simultaneously verified the feasibility of developing new anti-Gram-positive bacteria drugs by inhibiting the CPD pathway.

Infections caused by Acinetobacter baumannii (A. baumannii) have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting A. baumannii has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of A. baumannii were isolated in a high-throughput manner. The ability of Omp38-specific mAbs to bind to A. baumannii strains from diverse sources was confirmed via enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the Omp38-specific mAbs significantly improved the survival rate and reduced the bacterial load in a mouse model of lethal A. baumannii infection. Flow cytometry and ELISA confirmed that immune cell infiltration and cytokine production, respectively, decreased in a mouse model of sublethal A. baumannii infection. In addition, analysis of the Omp38-mAb C3 binding conformation revealed the potential mechanism of broad-spectrum binding activity of this mAb against A. baumannii. Taken together, these findings indicate that mAbs against Omp38 facilitate bacterial clearance from host, minimize inflammatory mediator release and reduce host damage, highlighting the potential of Omp38-specific mAbs in the clinical treatment of A. baumannii infection.

The advent of precision medicine has spotlighted subunit and peptide-based vaccines, which offer high safety but often require potent adjuvants to enhance immunogenicity. Self-assembled peptides have emerged as a promising adjuvant platform due to their ease of synthesis, excellent biocompatibility, and tunable structural properties. Recent advances highlight their potential in boosting vaccine efficacy, with self-assembled peptides forming highly ordered architectures that are conducive to immune system activation. This review discusses the key factors driving peptide self-assembly and explores their evolving role as innovative vaccine adjuvants, alongside challenges and future development directions.

Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the global health landscape has confronted an unprecedented and formidable challenge. The SARS-CoV-2 receptor-binding domain (RBD) is a key antigen in vaccine design. However, its low immunogenicity has been a hurdle, resulting in the production of minimal anti-RBD antibodies even when combined with alum adjuvant. Outer membrane vesicles (OMVs), secreted by Gram-negative bacteria, are nanospherical structures that can display or deliver antigens while also providing adjuvant activity through pathogen-associated molecular patterns (PAMPs). In this study, we utilized the SpyTag (ST)/SpyCatcher (SC) bioconjugation system to couple OMV and SARS-CoV-2 RBD in vitro. We successfully prepared a ‘plug-and-display’ nanovaccine OMV-RBD, which demonstrated good safety profiles and promoted the uptake of antigens by DCs and the maturation of BMDCs by activating TLR3 and NOD2 signaling pathways. Both intranasal and intramuscular immunization with OMV-RBD vaccine elicited robust antigen-specific humoral and cellular immune responses. Importantly, the induced antibodies effectively inhibited the binding of RBD to human angiotensin-converting enzyme 2 (hACE2) and neutralized SARS-CoV-2 pseudoviruses. This vaccine platform offers an alternative strategy for developing recombinant subunit vaccines against SARS-CoV-2, potentially enhancing immune responses and improving vaccine efficacy.

Parenteral subunit vaccines typically elicit systemic humoral immune responses but often struggle to induce mucosal immunity. Herein, we developed a promising adjuvant system, TB/P2C-NE, a tamibarotene-loaded nanoemulsion incorporating the TLR2/6 agonist Pam2CSK4. Upon intramuscular vaccination, TB/P2C-NE promoted antigen-specific mucosal immune responses in the gastrointestinal tract, accompanied by systemic humoral and cellular response. Mechanistically, tamibarotene upregulated the intestinal homing molecule CCR9 on lymphocytes through dendritic cell modulation, while Pam2CSK4 increased IL-6 secretion at the injection sites, further amplifying CCR9 expression and lymphocyte activation and leading to enhanced lymphocyte homing to the intestinal mucosa and a subsequent boost in mucosal immunity. Notably, TB/P2C-NE induced long-term gastrointestinal mucosal responses, maintaining elevated sIgA levels for up to three months post-immunization, and also induced gastrointestinal mucosal immunity in combination with a polysaccharide conjugate antigen. Immunization with recombinant intimin using TB/P2C-NE as the adjuvant resulted in a robust protective effect against the EHEC O157:H7 challenge. In summary, TB/P2C-NE offers an adjuvant strategy potentially accelerating the development of vaccines targeting gastrointestinal infections.

Iron-based metal-organic framework (MOF) nanozymes have garnered considerable attention owing to a large specific surface area, adjustable porosity, large Fe-O clusters, and unsaturated Fe sites. However, the sluggish charge-transfer rate and restricted active sites of the nanozymes lead to poor enzyme-like activity and further impede their biomimetic catalysis. Herein, a three-channel electron-engineered Fe-88A@CeO2/carbon dots (Fe-88A@CeO2/CDs) nanozyme is proposed for efficient biomimetic catalysis. Fe-88A@CeO2/CDs nanozyme is prepared by incorporation of CeO2 and CDs into the porosity of Fe-88A. Specifically, the original Fe (II)/Fe (III) and the introduced Ce (III)/Ce (IV) redox couples of the nanozyme constitute a dual electron transfer channel. Furthermore, the presence of CDs produces another electron transfer channel. The three-channel electron engineering strategy for nanozymes can accelerate the electron transfer process accompanied with more active sites, thereby greatly enhancing the oxidase-like activity of Fe-88A@CeO2/CDs for biomimetic catalysis. The nanozyme can efficiently convert oxygen to · O 2 - ${\mathrm{O}}_2^ - $ , oxidizing colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB, and meanwhile the ox-TMB effectively quenches the fluorescence of CDs. As proof of concept, the nanozyme is utilized to construct a colorimetric-fluorescence bimodal immunosensor for monitoring Staphylococcal enterotoxin B with excellent performance. This work provides promising insight into designing excellent nanozymes for effective biomimetic catalysis in various fields.

BACKGROUND:Acinetobacter baumannii (A. baumannii) is a significant global health threat, particularly in hospital environments, where it is often linked to severe infections. As the need for innovative therapeutic approaches grows, fully human monoclonal antibodies (mAbs) have gained attention because of their high specificity, reduced immunogenicity, and enhanced affinity for target antigens, which may improve clinical efficacy. METHODS:Using the Beacon platform, we isolated single B cells from immunized humanized genomic orthologs for antibody development (HUGO-Ab) mice to develop outer membrane protein (OMP)-specific mAbs. The variable regions of the selected mAbs were cloned into mammalian expression vectors containing constant human IgG1 regions to generate fully human mAbs. After identifying mAbs binding to Omp38 via ELISA, their binding ability to LAC-4 and the clinical isolates was further evaluated. Subsequently, the effects of these mAbs on A. baumannii adhesion and biofilm formation were tested, and their protective efficacy was assessed using a lethal infection model. Finally, bioinformatics methods were used to predict the binding conformation of mAb F2 to Omp38. RESULTS:Omp38-specific fully human mAb F2 potently and broadly bound to A. baumannii strains and inhibited bacterial adherence and biofilm formation. Binding modeling and conformational analysis revealed that F2 targets the extracellular region of Omp38 and forms stable hydrogen bonds with different strains, suggesting its potential for broad-spectrum binding to diverse A. baumannii strains. CONCLUSIONS:This study demonstrates the utility of high-throughput single-cell analysis and antibody engineering in developing fully human mAbs against A. baumannii, highlighting the potential of these novel fully human mAbs to advance therapeutic strategies and improve clinical outcomes for A. baumannii infections.

Current treatments for ulcerative colitis (UC) remain limited, highlighting the need for novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti-inflammatory properties. In this study, a dextran sulfate sodium (DSS)-induced animal model is used to investigate the effects of TLB on UC. It is found TLB significantly alleviates DSS-induced UC in mice, as evidenced by a reduction in the disease activity index, an increase in colon length, improvement in histopathological lesions. Furthermore, TLB treatment results in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines. TLB mitigates UC by modulating the intestinal microbiota, particularly Akkermansia, which enhances tryptophan metabolism and upregulates the production of xanthurenic acid (XANA). To confirm the role of TLB-induced microbiota changes, experiments are performed with pseudogerm-free mice and fecal transplantation. It is also identified XANA as a key metabolite that mediates TLB's protective effects. Both TLB and XANA markedly activate the aromatic hydrocarbon receptor (AhR). Administration of an AhR antagonist abrogates their protective effects, thereby confirming the involvement of AhR in the underlying mechanism. In conclusion, the study reveals a novel mechanism through which TLB alleviates UC by correcting microbiota imbalances, regulating tryptophan metabolism, enhancing XANA production, and activating AhR.

Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.

The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production. This study aims to assess the efficacy of plasmid-encoding GM-CSF (pGM-CSF) as an adjuvant to augment the specific humoral and cellular immune response elicited by DNA vaccines based on the receptor-binding domain (RBD) antigen. Compared to the use of plasmid-encoded RBD (pRBD) alone, mice that were immunized with a combination of pRBD and pGM-CSF exhibited significantly elevated levels of RBD-specific antibody titers in serum, BALF, and nasal wash. Furthermore, these mice generated more potent neutralization antibodies against both the wild-type and Omicron pseudovirus, as well as the ancestral virus. In addition, pGM-CSF enhanced pRBD-induced CD4+ and CD8+ T cell responses and promoted central memory T cells storage in the spleen. At the same time, tissue-resident memory T (Trm) cells in the lung also increased significantly, and higher levels of specific responses were maintained 60 days post the final immunization. pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses. In conclusion, pGM-CSF may be an effective adjuvant candidate for the DNA vaccines against SARS-CoV-2.

Objective To compare the immune effects of recombinant PKF protein of Acinetobacter baumannii with different immune modes and different adjuvants. Methods After recombinant PKF protein was obtained by plasmid expression and purification, the protein was then combined with aluminum hydroxide（Al） or with AS03 to immunize mice by intramuscular（im） injection. In another experiment, the combination of PKF and LTK63 or PKF and LP1-34 was adopted to intranasally（in） immunize mice, respectively. The total animals were thus divided into 7 groups: PBS group; PKF group（im）, PKF+Al group（im）, PKF+AS03 group（im）, PKF group（in）, PKF+LTK63 group（in）, and PKF+LP1-34 group（in）. The levels of serum specific IgG and mucosal sIgA in the immunized mice were detected by ELISA. Moreover, the sublethal model of Acinetobacter baumannii pulmonary infection was established, and then the bacterial colonization amount in blood and lung of mice after challenge was measured to evaluate the protective immune efficacy of the recombinant vaccine. Results In the intramuscular immunization group, AS03-assisted PKF produced the highest specific IgG antibody level（P＜0.01）, and in the nasal immunization group, LTK63 significantly increased the level of specific sIgA in the alveolar lavage fluid（P＜0.01）. Bacterial challenge test showed that the bacterial colonization amount was similar in the PKF+AS03（im） group and PKF（im） alone group, while the PKF+LTK63 group（in） obtained remarkably reduced bacterial colonization amount（P＜0.01）. Conclusion LTK63 assists PKF to better protect against Acinetobacter baumannii pulmonary infection, suggesting that vaccine-mediated mucosal immune response may play a more important role in the infection protection.

The epidemic of methicillin-resistant Staphylococcus aureus (MRSA) infections has created a critical health threat. The drug resistance of MRSA makes the development of drugs with new modes of action particularly urgent. In this study, we found that a natural product derivative pyrimirhodomyrtone (PRM) exerted antibacterial activity against S. aureus, including MRSA, both in vitro and in vivo. Genetic and biochemical studies revealed the interaction between PRM and N-acetylglucosamine-6-phosphate deacetylase (NagA) and the inhibitory effect of PRM on its deacetylation activity. We also found that PRM causes depolarization and destroys the integrity of the cell membrane. The elucidation of the antibacterial mechanism will inspire the subsequent development of new anti-MRSA drugs based on PRM.

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 µg/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by real-time reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC. Moreover, Western blot results showed that HL-J6 reduced the secretion level of α-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.

目的 促进药学专业学生的知识与德育协调发展,实现德才兼备、以德为先的培养目标.方法 对药学专业核心课程《生物技术制药》进行思政设计,从正反案例、中华传统文化、道德与伦理等方面深入挖掘各章节知识点的思政元素.结果 《生物技术制药》的思政元素包括文化传承精神,职业精神,遵守法律法规,创新精神,直面困难、坚持科学精神等.通过基因工程制药、动物细胞工程制药、抗体工程制药、酶工程制药、发酵工程制药、蛋白质工程制药等核心章节,设计各章节思政元素的案例和设置点位.带教实践中,树立全员、全过程的《生物技术制药》课程思政新理念,结合背景知识及社会热点将课程教学与爱国主义融合,利用专业知识点背后的经典人文故事将课程教学与职业使命有机联系,以身边典型案例升华思政教学.结论 《生物技术制药》课程的思政设计可实现知识传授、价值引导和能力培养的有机统一,培养出有品德、有能力、有责任的高素质药学人才.

Objectives:The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression.Methods:In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated in vivo after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by in vivo assay.Results:This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity in vitro and in vivo, and delayed antigen release in vivo. The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1β andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice.Conclusions:These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.

Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T-cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.

With the help of the establishment of novel reaction methodology, a series of N-Aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-one conjugates were designed and synthesized in 2-4 steps, and subsequent anticancer activity of these compounds was evaluated. Preliminary results showed that these compounds have moderate to potent activities against human acute leukemia cells K562, human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 2d and 2k were the most potent against K562 cell line with IC50 values of 0.07 and 0.52 µM, respectively, and the toxicity of 2d to the normal of hepatocytes (LO2) cell line was low (the survival rate 81 %). Flow cytometry analysis showed that 2d arrested K562 cells in the G2/M phase potently, even much better than Combretastatin A4 (CA4). In addition, the results demonstrated the involvement of the caspase-dependent or independent pathways of apoptosis, evidenced by the upregulation of FADD, pro-caspase 3, cleaved-caspase 3, HTRA2/Omi, SMAC/Diablo and the ratio of Bax/Bcl-2.The biological effects founding of 2d in this work point to prospective uses against acute leukemia.