Search

Zero-Shot Sketch-Based Image Retrieval (ZS-SBIR) is a novel cross-modal retrieval task, where abstract sketches are used as queries to retrieve natural images under zero-shot scenario. Most existing methods regard ZS-SBIR as a traditional classification problem and employ a cross-entropy or triplet-based loss to achieve retrieval, which neglect the problems of the domain gap between sketches and natural images and the large intra-class diversity in sketches. Toward this end, we propose a novel Domain-Smoothing Network (DSN) for ZS-SBIR. Specifically, a cross-modal contrastive method is proposed to learn generalized representations to smooth the domain gap by mining relations with additional augmented samples. Furthermore, a category-specific memory bank with sketch features is explored to reduce intra-class diversity in the sketch domain. Extensive experiments demonstrate that our approach notably outperforms the state-of-the-art methods in both Sketchy and TU-Berlin datasets. Our source code is publicly available at https://github.com/haowang1992/DSN., Comment: Accepted to IJCAI 2021

Learning feature embedding directly from images without any human supervision is a very challenging and essential task in the field of computer vision and machine learning. Following the paradigm in supervised manner, most existing unsupervised metric learning approaches mainly focus on binary similarity in Euclidean space. However, these methods cannot achieve promising performance in many practical applications, where the manual information is lacking and data exhibits non-Euclidean latent anatomy. To address this limitation, we propose an Unsupervised Hyperbolic Metric Learning method with Hierarchical Similarity. It considers the natural hierarchies of data by taking advantage of Hyperbolic metric learning and hierarchical clustering, which can effectively excavate richer similarity information beyond binary in modeling. More importantly, we design a new loss function to capture the hierarchical similarity among samples to enhance the stability of the proposed method. Extensive experimental results on benchmark datasets demonstrate that our method achieves state-of-the-art performance compared with current unsupervised deep metric learning approaches.

Xiaolei Liang,1,* Jiexi Yan,2,* Yingwei Lu,3 Shan Liu,4 Xiaojing Chai5 1Key Laboratory for Gynecologic Oncology Gansu Province, Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 2The Precision Medicine Laboratory, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 3Gansu Provincial Center for Disease Control and Prevention, Lanzhou, People’s Republic of China; 4The First Clinical Medicine School, Lanzhou University, Lanzhou, People’s Republic of China; 5The Key Laboratory, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojing ChaiThe Key Laboratory, The First Hospital of Lanzhou University, No. 1, Donggang Road, Lanzhou, People’s Republic of ChinaEmail chaixiaoj@163.comPurpose: Increasingly complex diseases require novel drugs for their treatment. Antimicrobial peptides (AMPs) are promising candidate treatments due to their broad existence and special characteristics. However, the current understanding of AMPs is not sufficient to allow them to be produced commercially for clinical use.Materials and Methods: Melectin, from the venom of the cleptoparasitic bee Melecta albifrons, does not exhibit sequence homology with other wasp venom peptides. To investigate this more deeply, we explored the antibacterial and antitumor activities of Melectin and related mechanisms.Results: Our results demonstrate that Melectin possesses antimicrobial properties against standard sensitive/clinical drug-resistant bacteria strains as well as antitumor activity. It has an α-helix form and exhibits moderate cytotoxicity. Its action mechanisms are involved with membrane interfering and DNA binding. The membrane interfering effect was distinct between different phospholipid compositions.Conclusion: We found that Melectin may serve as a new potential template in the battle against multidrug resistance, and our study indicated that there are promising prospects for medically applicable drugs based on AMPs.Keywords: antimicrobial peptide, melectin, antibacterial, antitumor, action mechanism

Alzheimer's disease (AD) is a severe type of neurodegeneration which worsens human memory, thinking and cognition along a temporal continuum. How to identify the informative phenotypic neuroimaging markers and accurately predict cognitive assessment are crucial for early detection and diagnosis Alzheimer's disease. Regression models are widely used to predict the relationship between imaging biomarkers and cognitive assessment, and identify discriminative neuroimaging markers. Most existing methods use different matrix norms as the similarity measures of the empirical loss or regularization to improve the prediction performance, but ignore the inherent geometry of the cognitive data. To tackle this issue, in this paper we propose a novel robust matrix regression model with imposing Wasserstein distances on both loss function and regularization. It successfully integrate Wasserstein distance into the regression model, which can excavate the latent geometry of cognitive data. We introduce an efficient algorithm to solve the proposed new model with convergence analysis. Empirical results on cognitive data of the ADNI cohort demonstrate the great effectiveness of the proposed method for clinical cognitive predication.

Research question The aim of this study was to investigate how female age affects the predictive effect of sperm DNA fragmentation index (DFI) on clinical outcomes with assisted reproductive technology. Design A total of 2371 patients, comprising 2115 men with a normal DFI (≤30), 256 men with a high DFI (>30) and women of different ages, were recruited and investigated. All patients had normal chromosome karyotypes and were undergoing their first fresh IVF or intracytoplasmic sperm injection (ICSI) cycles. Clinical outcomes were analysed according to the two DFI groups and female age ≤30 and >30 years. Binary logistic regression analysis was performed to identify factors associated with clinical outcome. Results The proportion of couples with at least one good-quality embryo in the DFI ≤30 group was higher than that in the DFI >30 group. When female age exceeded 30 years, clinical pregnancy rate and the proportion of couples with good-quality embryos in the DFI >30 group were lower compared with DFI ≤30; however, there were no differences in outcomes for female age ≤30 years according to DFI. When DFI >30, the cut-off value of female age was 30.5 for detecting clinical pregnancy; the sensitivity was 62.0%, and the specificity was 63.6%. Clinical pregnancy rate and proportion of couples with good-quality embryos were lower in the DFI >30 versus DFI ≤30 group with a female age above 30 years for IVF but not for ICSI. Conclusion Female age has a negative effect and should be considered in predicting the effects of sperm DNA fragmentation on pregnancy outcomes.

Multidrug-resistant bacteria are emerging as a global threat, making the search for alternative compounds urgent. Antimicrobial peptides (AMPs) became a promising hotspot due to their distinct action mechanism and possibility to be used as an alternative or complement to traditional antibiotics. However, gaining a better understanding about the relationship between antimicrobial peptides structure and its bioactivity is crucial for the development of next generation of antimicrobial agents. NK-2, derived from mammalian protein NK-lysin, has potent antitumor and bactericidal abilities. As proline was considered to be an effective α-helix breaker due to its restricted conformation, to better comprehend the effects of proline in the structure-activity relationship of NK-2, we constructed two NK-2 analogs. We examined the biological activities of NK-2 and its proline substitution analogs and analyzed the resulting conformational changes. Our results showed that introducing proline into the primary sequence of NK-2 significantly decreased the antitumor, antibacterial, and cytotoxic effects, as well as DNA binding activity by changing the α-helix content. However, α-helical content was not the only determining factor, the position of proline inserted was also critical. This study will allow for clearer insight into the role of proline in structure and bioactivity of NK-2 and provide a foundation for future studies.

Quercetin is widely known as potent natural antioxidant and scavenger of reactive oxygen species (ROS) and nitric oxide both in vitro and in vivo. Quercetin has a wide range of biological functions and health-promoting effects. There are more and more interests in the addition of this flavonol to various traditional food products. However, the in vitro toxicity of quercetin to mature human sperm remains unknown. In this study, we investigated the in vitro effects of quercetin on human sperm functions. The results showed that the total sperm motility were significantly inhibited compared to the controls following exposure to 100, 200 and 400µM quercetin for 6 and 12h; quercetin did not affect human sperm viability. The acrosome reaction and capacitation induced by progesterone were dose-dependently inhibited by quercetin. Furthermore, quercetin induced a significantly decrease of human sperm [Ca

Hospital-acquired infections caused by multidrug-resistant bacteria pose significant challenges for treatment, which necessitate the development of new antibiotics. Antimicrobial peptides are considered potential alternatives to conventional antibiotics. The skin of Anurans (frogs and toads) amphibians is an extraordinarily rich source of antimicrobial peptides. CPF-C1 is a typical cationic antimicrobial peptide that was originally isolated from the tetraploid frog Xenopus clivii. Our results showed that CPF-C1 has potent antimicrobial activity against both sensitive and multidrug-resistant bacteria. It disrupted the outer and inner membranes of bacterial cells. CPF-C1 induced both propidium iodide uptake into the bacterial cell and the leakage of calcein from large liposome vesicles, which suggests a mode of action that involves membrane disturbance. Scanning electron microscopy and transmission electron microscopy verified the morphologic changes of CPF-C1-treated bacterial cells and large liposome vesicles. The membrane-dependent mode of action signifies that the CPF-C1 peptide functions freely and without regard to conventional resistant mechanisms. Additionally, it is difficult for bacteria to develop resistance against CPF-C1 under this action mode. Other studies indicated that CPF-C1 had low cytotoxicity against mammalian cell. In conclusion, considering the increase in multidrug-resistant bacterial infections, CPF-C1 may offer a new strategy that can be considered a potential therapeutic agent for the treatment of diseases caused by multidrug-resistant bacteria.

With the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes . We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

The extensive use of antibiotics in medicine, the food industry, and agriculture has resulted in the frequent emergence of multidrug-resistant bacteria, which creates an urgent need for new antibiotics. It is now widely recognized that antimicrobial peptides (AMPs) could play a promising role in fighting multidrug-resistant bacteria. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista . In this study, we synthesized polybia-CP and studied its action mode of antibacterial activity. Our results revealed that polybia-CP has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. The results from both the real bacterial membrane and the in vitro model membrane showed that polybia-CP is membrane active and that its action target is the membrane of bacteria. It is difficult for bacteria to develop resistance to polybia-CP, which may thus offer a new strategy for defending against resistant bacteria in medicine and the food and farming industries.

A new single molecule multianalyte sensor, vanillic aldehyde rhodamine 6G hydrazone has been designed for the selective detection of Cu 2+ and Hg 2+ ions. UV/Vis spectroscopy indicates that the sensor is a good chromogenic chemosensor for Cu 2+ in 1:99 (v/v) ethanol–water media. Whereas, other ions, such as Li + , Na + , Mg 2+ , K + , Ca 2+ , Cr 3+ , Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Zn 2+ , Ag + , Cd 2+ , Ba 2+ , Hg 2+ and Pb 2+ failed to generate a distinct response. Fluorescence spectral data reveals that the sensor is an excellent fluorescent chemosensor for Hg 2+ in aqueous ethanol solution and with no fluorescent response toward other ions. The spectroscopic behavior of the sensor in living cells indicated that it can be used for the detection of Cu 2+ and Hg 2+ in environmental and biological systems. Mechanisms for the high selectivity of the sensor to Cu 2+ and Hg 2+ are discussed.

As the increasing emergence of multi-drug resistant tumor cells, there is an urgent need for developing new chemotherapeutic agents. NK-lysin was a novel effector of cytotoxic T cells and natural killer (NK) cells and had broad antimicrobial activity. In this study, we developed a core region of NK-lysin termed NK-18, and studied its antitumor activity and possible action mode. Our results showed that NK-18 (with 18 amino acids) possesses potent antitumor activity against bladder and prostate cancer cells by disrupting the integrity of cell membrane, but has negligible hemolysis activity against mouse erythrocytes. In addition, CD spectra was employed to study its conformation in membrane mimicking environment. NK-18 takes a standard α-helical conformation in membrane mimicking environment, which could be accounted for its more potent antitumor activity compared with its low α-helical content homologous derivatives. These findings together with its shorter amino acid sequence and lower synthesis cost suggest that NK-18 could present an alternative therapeutic strategy to cancer chemotherapy and play a promising role in fighting the multi-drug resistant tumors.

As the frequent emergency of resistant tumor cells during treatment, the development of new agents with new modes of action attracts a great deal of interest. Polybia-MPI was a short cationic alpha-helical amphiphilic peptide that has selective toxicity toward cancer cells but no hemolytic activity. Its target selectivity is based on the binding preference to membranes containing anionic phospholipids by electrostatic driving. Its ability to make PI and trypan blue permeate into tumor cells at the same rate (within minutes), suggests a killing mechanism that involves plasma membrane perturbation. SEM and confocal microscopy experiments verified that the cell died as a result of acute injury and bursting, suggesting necrosis. As compared to the conventional chemotherapy, polybia-MPI targets at the cell membrane rather than enters into the cell to exert its action. So it is difficult for tumor cells to develop resistance to polybia-MPI during treatment and its action is not affected by the common multi-drug resistant mechanism. Although this is an initial study that looked at its in vitro activity rather than the in vivo activity, with the increasing resistance of conventional chemotherapy, polybia-MPI may offer a novel therapeutic strategy in the treatment of multi-drug resistant cancer.

Leu5AMD ([D-Val2, L-MeLeu5]2 AMD) is a novel actinomycin D (AMD) analog, in which both N-methylvalines were replaced by N-methylleucines. In the present study, an attempt has been made to investigate the effects of Leu5AMD on the proliferation of human gastric carcinoma cell line SGC-7901. The results showed that Leu5AMD inhibited the proliferation and induces apoptosis in SGC-7901 cells in a dose-dependent manner. Apoptosis induced by Leu5AMD was further confirmed by annexin V-FITC/PI dual staining assay. After treatment with Leu5AMD, the loss of mitochondrial potential and the decrease of bcl-2 gene expression were observed in apoptotic cells, suggesting that Leu5AMD may be involved in mitochondria and bcl-2 related apoptotic pathway. In addition, the in vivo antitumor effects of Leu5AMD on S-180 bearing mice and the acute toxicity on healthy mice were investigated. Treatment with Leu5AMD markedly suppressed the growth of Sarcoma xenograft. These results suggest that Leu5AMD may be used as a promising chemotherapeutical agent for patients affected by gastric carcinoma and other solid cancer.

The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option.

Hospital-acquired infections caused by multidrug-resistant bacteria pose significant challenges for treatment, which necessitate the development of new antibiotics. Antimicrobial peptides are considered potential alternatives to conventional antibiotics. The skin of Anurans (frogs and toads) amphibians is an extraordinarily rich source of antimicrobial peptides. CPF-C1 is a typical cationic antimicrobial peptide that was originally isolated from the tetraploid frog Xenopus clivii. Our results showed that CPF-C1 has potent antimicrobial activity against both sensitive and multidrug-resistant bacteria. It disrupted the outer and inner membranes of bacterial cells. CPF-C1 induced both propidium iodide uptake into the bacterial cell and the leakage of calcein from large liposome vesicles, which suggests a mode of action that involves membrane disturbance. Scanning electron microscopy and transmission electron microscopy verified the morphologic changes of CPF-C1-treated bacterial cells and large liposome vesicles. The membrane-dependent mode of action signifies that the CPF-C1 peptide functions freely and without regard to conventional resistant mechanisms. Additionally, it is difficult for bacteria to develop resistance against CPF-C1 under this action mode. Other studies indicated that CPF-C1 had low cytotoxicity against mammalian cell. In conclusion, considering the increase in multidrug-resistant bacterial infections, CPF-C1 may offer a new strategy that can be considered a potential therapeutic agent for the treatment of diseases caused by multidrug-resistant bacteria.

With the increasing emergence of resistant fungi, the discovery and development of novel antifungal therapeutics were urgently needed. Compared with conventional antibiotics, the limited propensity of AMPs to induce resistance in pathogens has attracted great interest. In the present study, the antifungal activity and its mechanism-of-action of polybia-MPI, a cationic peptide from the venom of Social wasp Polybia Paulista was investigated. We demonstrated that polybia-MPI could potently inhibit the growth of Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The 50% inhibitory concentrations (IC50) of Polybia-MPI against cancer cells were much higher than the MICs against the tested C. albicans and C. glabrata cells, indicating that polybia-MPI had high selectivity between the fungal and mammalian cells. Our results also indicated that membrane disturbance mechanism was involved in the antifungal activity. Furthermore, polybia-MPI could inhibit the bio film forming of C. glabrata, which was frequently associated with clinically significant biofilm. These results suggest that polybia-MPI has great advantages in the development of antifungal agents.

The extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NK-Lysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity against Escherichia coli and Staphylococcus aureus . According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.

As the frequent emergence of the resistant bacteria, the development of new agents with a new action mode attracts a great deal of interest. It is now widely accepted that antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics. In this study, antimicrobial peptide polybia-MPI and its analogs were synthesized and their antibacterial activity was studied. Our results revealed that polybia-MPI has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Its ability to make PI permeate into bacteria and lead to the leakage of calcein from model membrane LUVs, suggests a killing mechanism involving membrane perturbation. SEM and TEM microscopy experiments verified that the morphology of bacteria was changed greatly under the treatment of polybia-MPI. Compared with the conventional chemotherapy, polybia-MPI targets the cell membrane rather than entering into the cell to exert its antibacterial activity. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. The results indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity and the membrane disturbance by polybia-MPI is a cooperative process. In conclusion, with the increasing resistance to conventional antibiotics, there is no doubt that polybia-MPI could offer a new strategy to defend the resistant bacteria.

The chromene derivative (XVII) shows high antibiotic activity against Staphylococcus aureus.

Function-oriented design and synthesis of chiral small molecules with novel activity is a key goal in modern organic chemistry. As multiple antibiotic-resistant pathogens are emerging and causing serious diseases, the need for practical routes for the development of new types of antibacterial agents is very urgent. Herein, we present a highly efficient process for the synthesis of optically active pyranocoumarins and 2-amino-4H-chromenes through an organocatalytic Knoevenagel/Michael/cyclization sequence, and the preliminary biological studies of these new heterocyclic compounds revealed potent antibacterial activity. This study provides a novel strategy for further research and development of new types of antibacterial agents effective against human pathogens.

Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. It has an amphipathic sequence ILGTILGLLKSL-NH(2) and possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this study we synthesized polybia-CP, studied its cytotoxity on tumor cells and proposed its possible mechanism. Our results revealed that polybia-CP exerts its cytotoxic efficacy by disrupting the integrity of cell membrane. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. Both the MD simulations and the experimental data indicated that polybia-CP takes a standard α-helix conformation in the membrane. These findings together with the other experimental results support a speculation of mechanism similar to the "carpet" model.

Polybia-MPI (MPI), a short cationic α-helical antimicrobial peptide, exhibited excellent anticancer activity and selectivity in vitro in our previous studies. To improve its in vivo application, we synthesized an analog (MPI-1) of MPI by replacing the C terminal amide -[CO-NH(2)] with thioamide -ψ[CS-NH(2)]. Although there is just one atom difference, the MPI-1 exhibited some surprising properties. In vitro studies revealed that MPI-1 exhibited relatively high lytic activity over MPI, whereas its stability to enzymatic degradation in serum was improved remarkably. Despite the enhanced toxicity in vitro, MPI-1 exhibited significantly lower mortality to mice than MPI at 75 mg/kg. Importantly, in vivo anticancer activity study indicated that MPI-1 could remarkably suppress the growth of sarcoma xenograft tumors more efficiently than MPI. Therefore, the significantly improved anticancer activity and predominantly lower in vivo toxicity might allow MPI-1 to be a good candidate for future anticancer treatment.

The actinomycin D (AMD) analogs in which the D-valine residues (the second amino acid residue in the cyclic depsipeptide of AMD) and the N-methyl-L-valine residues (the fifth amino acid residue in the cyclic depsipeptide of AMD) were replaced with D-Phe or l- and D-forms N-methylvalines, N-methylisoleucine, N-methylleucine, N-methylphenylalanine, N-methylalanine, and sarcosine were synthesized. The antimicrobial activity and cytotoxic activities of these compounds in vitro were investigated. The results showed that most D-valine substituted analogs had much lower antimicrobial activity and cytotoxic activities in vitro than AMD itself, but three N-methyl-L-valine substituted analogs had comparable or even more remarkable cytotoxic activities in vitro than AMD. Acute toxicities and antitumor effects of the N-methyl-L-valine substituted analogs in mice were also examined. The result showed that the acute toxicity of compound 4 L-methylleucine(5)-AMD analog is comparable to AMD itself and that of compound 3(L-Methylisoleucine(5)-AMD analog) is slightly more toxic, about 1.25-fold than AMD. However, the acute toxicity of compound 5 D-methylleucine5-AMD analog is about 2-fold lower than AMD. This suggested that the N-methyl-D-amino acid replacement in the cyclic ring might play a vital role in their decreased acute toxicities, and perhaps the N-methyl-D-leucine substituent is more favorable, though there may be a slight loss of antitumor activity. This finding may be helpful for the design and development of more potent antitumor agents together with low acute toxicity, and suggests that the N-methyl-D-leucine substituent has the potential to be used as antitumor drug lead.

A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the social wasp Polybia paulista. It has potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat erythrocytes. To date, there is no report about its antitumor effects on any tumor cell lines. In this study we synthesized polybia-MPI and studied its antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation. It can selectively inhibit the proliferation of prostate and bladder cancer cells, but has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate the structure-activity relationship of polybia-MPI, three analogs in which Leu7, Ala8 or Asp9 replaced by L-Pro were designed and synthesized. L-Pro substitution of Leu7 or Asp9 significantly reduces the content of alpha-helix conformation, and L-Pro substitution of Ala8 can disrupt the alpha-helix conformation thoroughly. The L-Pro substitution induces a significant reduction of antitumor activity, indicating that the alpha-helix conformation of polybia-MPI is important for its antitumor activity. In summary, polybia-MPI may offer a novel therapeutic strategy in the treatment of prostate cancer and bladder cancer, considering its relatively lower cytotoxicity to normal cells.