摘要：
Extracellular polymeric substances (EPS) participate in heavy metal adsorption in the aquatic environments. Extracellular DNA (eDNA) is an essential component of EPS, but its involvement in metal binding remains ambiguous. Herein, the role of eDNA in Cd(II) and Ni(II) adsorption was described using a combination of semi-quantitative and qualitative approaches. EPS were extracted from Burkholderia sp. MBR-1 and eDNA accounted for 6.9% of the total mass of EPS. The eDNA in the extracted EPS was digested using the DNase II to prepare an eDNA-free EPS sample. Potentiometric titration unveiled that the number of total binding sites of the eDNA-free EPS was 19% lower than the untreated EPS. The Cd(II) and Ni(II) adsorption capacity of the eDNA-free EPS was lower than the untreated EPS at the pH range of 4-7. At pH7, the results of batch adsorption experiments showed that removing eDNA from EPS resulted in declines of 12.6% and 15.7% in the adsorption capacities for Cd(II) and Ni(II), respectively. Furthermore, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy unraveled that the phosphoryl groups and purines of eDNA are responsible for Cd(II) and Ni(II) complexation. The results demonstrated that eDNA plays an essential role in heavy metal adsorption.
关键词：
Cascade signal amplification;Convenient operation;Multi-enzyme biosensor;Pesticide;Smartphone-based sensing
摘要：
Monitoring of pesticide residues in food and environmental matrices is undoubtedly crucial to guarantee food safety and ecological health, yet how to realize their sensitive and convenient detection is still challenging. Herein, we propose an all-in-one test strip that elaborately integrates bioenzyme, nanozyme and chromogen together, and achieve the highly sensitive and convenient sensing of pesticide residues assisted by a smartphone. A sequential self-assembly strategy was first explored to acquire an integrative bioenzyme-nanozyme-chromogen assembly, and then the assembly was confined in a biocompatible hydrogel to construct the test strip. Thanks to both the proximity and confinement effects, a ∼1.2-fold improvement of the cascade catalytic efficiency was gained to benefit high-sensitivity detection. More importantly, since all the sensing elements, including target recognition units and signal amplification modules, were rationally integrated in the test strip, detection operation was significantly simplified, making it possible for in-field rapid analysis. Besides, the microenvironment provided by the alginate hydrogel carrier endowed the test strip with an excellent sensing stability. By taking paraoxon as a typical pesticide, high-performance detection of the target was accomplished via the smartphone-assisted all-in-one test strip. Moreover, the test strip was successfully applied for paraoxon detection in various real samples and exhibited good correlations with commercial kits, demonstrating its great prospect for practical applications. Our work not only offers a new tool for the high-sensitivity and convenient monitoring of pesticide residues, but will also inspire the development of efficient multi-enzyme sensing platforms.
通讯机构：
[Song, Fengmei] H;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.
摘要：
Although titanium (Ti)-based nanomaterials (NMs) were traditionally considered as biologically inert materials, it was recently reported that Ti-based NMs induce adverse vascular effects by inhibiting Kruppel-like factor 2 (KLF2) and/or KLF4, vasoprotective KLFs with well-documented regulatory activity in NO signaling. However, the potential roles of other KLFs are not clear. KLF6 was recently identified as an important KLF involved in regulating endothelial dysfunction, inflammation, and angiogenesis, therefore, this study investigated the influence of titanate nanofibers (TiNFs) on KLF6-mediated events. Ingenuity pathway analysis (IPA) showed that TiNFs altered the expression of a panel of KLF6-related genes: KLF6-mediated gene ontology (GO) terms were altered, categories including cytokine-mediated signaling pathways, transcription factor (TF) functions and membrane-bound organelles. Additionally, RT-PCR confirmed that TiNFs increased KLF6 activating transcription factor 3 (ATF3), a TF involved in endoplasmic reticulum (ER) stress, and ELISA confirmed the increase of soluble monocyte chemotactic protein 1 (sMCP-1), a KLF6-related inflammatory cytokine. Interestingly, the activation of klf6, atf3 and C-C motif chemokine ligand 2 (ccl2; mcp-1 encoding gene) was observed in aortas of mice following one-time intravenous injection but not intratracheal instillation of TiNFs (100 μg per mouse), indicating a need for direct contact with NMs to activate klf6-mediated pathways in vivo. In endothelial cells, KLF6 knockdown inhibited the expression of ATF3 but not CCL2, suggesting the regulatory role of KLF6 in ATF3 expression. Overall, this study uncovered a previously unknown role of KLF6 in TiNF-induced vascular effects both in vitro and in vivo.
作者机构：
[Liu, Jinjin; Niu, Xiangheng] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Niu, Xiangheng] Jiangsu Univ, Sch Chem & Chem Engn, Inst Green Chem & Chem Technol, Zhenjiang 212013, Jiangsu, Peoples R China.
通讯机构：
[Xiangheng Niu] S;School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Institute of Green Chemistry and Chemical Technology, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China
摘要：
Abstract: In comparison with bioenzymes, nanozymes exhibit excellent robustness against extreme conditions, a low production cost, and easy-to-adjust properties, as well as potential versatility. These superiorities have attracted abundant interest in the last 15 years, to develop various nanozymes for applications including analytical sensing, environmental engineering, and biomedicine. In particular, for analytical sensing, a lot of nanozyme-involved principles and methods have been explored and applied to clinical diagnosis, environmental monitoring, food safety detection, and forensic analysis. Moreover, rational exploitation and use of nanozyme materials promote the performance of analytical methods. To highlight the latest progress in this attractive field, recent design concepts of nanozymes for advanced biochemical sensing are summarized. The development of single-atom nanozymes, self-cascade nanozymes, structurally biomimetic nanozymes, molecularly imprinted nanozymes, nanozymes breaking the pH limit, and multifunctional nanozymes is discussed in detail, to enhance detection sensitivity and selectivity, as well as expand application scenarios. Finally, some challenges and trends related to nanozyme-based sensors are reported, to satisfy the increasing needs of biochemical analysis with nanozymes. Keywords: nanozyme; rational design; biochemical detection; sensitivity; selectivity; application scenario
作者机构：
[He, Shuya; Liu, Sisi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Song, Yuxin; He, Shuya; Tan, Huaxin; Liu, Sisi; Wang, Junyao] Univ South China, Sch Basic Med, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.
通讯机构：
[Shuya He; Huaxin Tan] D;Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China
摘要：
The rising incidence and severity of malignant tumors threaten human life and health, and the current lagged diagnosis and single treatment in clinical practice are inadequate for tumor management. Gold nanoclusters (AuNCs) are nanomaterials with small dimensions (<= 3 nm) and few atoms exhibiting unique optoelectronic and physicochemical characteristics, such as fluorescence, photothermal effects, radiosensitization, and biocompatibility. Here, the three primary functions that AuNCs play in practical applications, imaging agents, drug transporters, and therapeutic nanosystems, are characterized. Additionally, the promise and remaining limitations of AuNCs for tumor theranostic and combination therapy are discussed. Finally, it is anticipated that the information presented herein will serve as a supply for researchers in this area, leading to new discoveries and ultimately a more widespread use of AuNCs in pharmaceuticals.
通讯机构：
[Yi Cao] H;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Recently, we reported that titanium dioxide (TiO2) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO2 nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.
摘要：
Inhalation of beryllium and its compounds can cause lung injuries, resulting from inflammation and oxidative stress. Multivesicular bodies (MVB), such as exosomes, are membrane vesicles produced by early and late endosomes that mediate intercellular communications. However, the role of exosomes in beryllium toxicity has not been elucidated. This current study aimed to investigate the functional role of exosomes in lung injury resulting from beryllium sulfate (BeSO(4) ). Here, Sprague-Dawley (SD) rats were exposed to 4, 8, and 12 mg/kg BeSO(4) by nonexposed intratracheal instillation. Murine macrophage (RAW 264.7) cells were pretreated with 50 nmol/L rapamycin (an mTOR signaling pathway inhibitor) for 30 min and then cultured for 24 h with 100 μg/mL exosomes, which had been previously isolated from the serum of 12 mg/kg BeSO(4) -treated SD rats. Compared with those of the controls, exposure to BeSO(4) in vivo increased LDH activity, elevated levels of inflammatory cytokines (IL-10, TNF-α, and IFN-γ) alongside inflammation-related proteins expression (COX-2 and iNOS), and enhanced secretion of exosomes from the SD rat's serum. Moreover, the BeSO(4) -Exos-induced upregulation of LDH activity and inflammatory responses in RAW 264.7 cells can be alleviated following pretreatment with rapamycin. Collectively, these results suggest that serum exosomes play an important role in pulmonary inflammation induced by BeSO(4) in RAW 264.7 cells via the mTOR pathway.
通讯机构：
[Hu, CG ; Naranmandura, H ; Hsu, CH ] Z;Zhejiang Univ, Affiliated Hosp 1, Dept Publ Hlth, Sch Med, Hangzhou 310058, Peoples R China.;Zhejiang Univ, Affiliated Hosp 1, Dept Hematol, Sch Med, Hangzhou 310058, Peoples R China.;Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China.;Zhejiang Prov Ctr Dis Control & Prevent, Hangzhou 310051, Peoples R China.
摘要：
Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2.
摘要：
Radioresistance is the predominant cause for radiotherapy failure and disease progression, resulting in increased breast cancer‑associated mortality. Using gene expression signature analysis of the Library of Integrated Network‑Based Cellular Signatures (LINCS) and Gene Expression Omnibus (GEO), the aim of the present study was to systematically identify potential candidate radiosensitizers from known drugs. The similarity of integrated gene expression signatures between irradiated eukaryotic translation initiation factor 4γ1(eIF4G1)‑silenced breast cancer cells and known drugs was measured using enrichment scores(ES). Drugs with positive ES were selected as potential radiosensitizers. The radiosensitizing effects of the candidate drugs were analyzed in breast cancer cell lines (MCF‑7, MX‑1 and MDA‑MB‑231) using CCK‑8 and colony formation assays following exposure to ionizing radiation. Cell apoptosis was measured using flow cytometry. The expression levels of eIF4G1 and DNA damage response (DDR) proteins were analyzed by western blotting. Bosutinib was identified as a promising radiosensitizer, as its administration markedly reduced the dosage required both for the drug and for ionizing radiation, which may be associated with fewer treatment‑associated adverse reactions. Moreover, combined treatment of ionizing radiation and bosutinib significantly increased cell killing in all three cell lines, compared with ionizing radiation or bosutinib alone. Among the three cell lines, MX‑1 cells were identified as the most sensitive to both ionizing radiation and bosutinib. Bosutinib markedly downregulated the expression of eIF4G1 in a dose‑dependent manner and also reduced the expression of DDR proteins (including ATM, XRCC4, ATRIP, and GADD45A). Moreover, eIF4G1 was identified as a key target of bosutinib that may regulate DNA damage induced by ionizing radiation. Thus, bosutinib may serve as a potential candidate radiosensitizer for breast cancer therapy.
作者机构：
[Xu, Shuaishuai; Veerabadhran, Maruthanayagam] Cent South Univ, Xiangya Sch Publ Hlth, Hunan Prov Key Lab Clin Epidemiol, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China.;[Natesan, Sivakumar] Madurai Kamaraj Univ, Sch Biotechnol, Dept Mol Microbiol, Madurai 625021, Tamil Nadu, India.;[MubarakAli, Davoodbasha] BS Abdur Rahman Crescent Inst Sci & Technol, Sch Life Sci, Chennai, Tamil Nadu, India.;[Yang, Fei] Univ South China, Hengyang Med Coll, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haz, Hengyang, Peoples R China.
通讯机构：
[Fei Yang] H;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical College, University of South China, Hengyang, China
期刊：
Toxicology and Industrial Health,2021年37(12):715-726 ISSN：0748-2337
通讯作者：
Yang, Xifei
作者机构：
[Long, Dingxin; Zhang, Kaiqin] Univ South China, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[He, Kaiwu; Nie, Lulin; Liu, Jianjun; Xu, Jia; Yang, Xifei; Zhang, Kaiqin] Shenzhen Ctr Dis Control & Prevent, Key Lab Modern Toxicol Shenzhen, Shenzhen Med Key Discipline Hlth Toxicol, 8 Longyuan Rd, Shenzhen 518055, Peoples R China.;[He, Kaiwu; Li, Shupeng] Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen, Peoples R China.;[Dai, Zhongliang] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Anesthesiol, Shenzhen, Peoples R China.
通讯机构：
[Yang, Xifei] S;Shenzhen Ctr Dis Control & Prevent, Key Lab Modern Toxicol Shenzhen, Shenzhen Med Key Discipline Hlth Toxicol, 8 Longyuan Rd, Shenzhen 518055, Peoples R China.
关键词：
Movement deficit;manganism;signaling pathways;external globus pallidus;rats
摘要：
Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.
摘要：
Deinococcus radiodurans (DR) is highly resistant to ionizing radiation. This study aims to convert dsrA gene into DR to construct radiation-resistant genetically engineered bacteria (Deino-dsrA) with high reducibility, so as to enhance the reducing and enrichment ability of DR. Methods: the recombinant vector pRADK-dsrA was extracted and transformed into DR. 1. Radiation resistant gene engineering bacteria containing dsrA gene were constructed successfully. 2. In the most favorable conditions,contributing to approximately 92.45% U (VI) was removed. 3. Autioxidant enzyme activities in Deino-dsrA is higher than in Deino-pRADK, excepting the content of malondialdehyde. The uranium enrichment ability of the Deino-dsrA is better than the wild DR, and dsrA gene can increase its antioxidation capability by increasing the activity of oxidase.
作者机构：
[Luo, Dan; Zhang, Chengcheng; Shen, Minxue] Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Changsha, Hunan, Peoples R China.;[Shen, Minxue; Chen, Xiang] Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China.;[Zhang, Chengcheng; Guo, Jian; Xu, Shuaishuai; Yi, Xiping; Yang, Fei] Cent South Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha, Hunan, Peoples R China.;[Huang, Zhijun] Cent South Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Changsha, Hunan, Peoples R China.;[He, Meian] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Hubei, Peoples R China.
通讯机构：
[Minxue Shen; Xiang Chen; Dan Luo; Fei Yang] D;Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical College, University of South China, Hengyang 421001, China<&wdkj&>Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
关键词：
Heavy metals;Bayesian kernel machine regression;Intelligence quotient;Children
摘要：
A simple penicillinase functionalized two-dimensional photonic crystal hydrogel (2DPPCH) biosensor was developed for colorimetric detection of penicillin G and penicillinase inhibitors. The penicillinase can specifically recognize penicillin G and catalyze it to produce penicilloic acid, which decreases the pH of the hydrogel microenvironment and shrinks the pH-sensitive hydrogel. The particle spacing decrease of the 2D photonic crystal array induced by the hydrogel shrinkage further causes a blue-shift in the diffraction wavelength. While the hydrolysis reaction is repressed upon treatment with clavulanate potassium (a kind of penicillinase inhibitor), no significant change in the diffraction wavelength is found. The detection of targets can be achieved by measuring the Debye diffraction ring diameter or observing the structural color change in the visible region. The lowest detectable concentrations for penicillin G and clavulanate potassium are 1 μM and 0.1 μM, respectively. Moreover, the 2DPPCH is proved to exhibit high selectivity and an excellent regeneration property, and it shows satisfactory performance for penicillin G analysis in real water samples.
期刊：
International Immunopharmacology,2021年93(2):107411 ISSN：1567-5769
通讯作者：
Hu, Sihai;Long, Dingxin
作者机构：
[Wu, Xiaoxia; Hu, Sihai; Li, Zhenyu; Li, Yumeng; Hou, Yongli; Cao, Hui] Univ South China, Inst Pathogen Biol, Coll Med, Hengyang 421001, Peoples R China.;[Wang, Yan] Univ South China, Hosp 2, Operating Room, Hengyang 421001, Peoples R China.;[Long, Dingxin] Univ South China, Sch Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Long, Dingxin] C;[Hu, Sihai] I;Institute of Pathogenic Biology, Medical College, University of South China, Hengyang 421001, China. Electronic address:;China School of Public Health, University of South China, Hengyang 421001, China. Electronic address:
关键词：
Chitosan nanoparticle;Immunopotentiators;Moucosal vaccine;NMB0315;Neisseria meningitidis serogroup B
摘要：
Neisseria meningitidis (N. meningitidis) is a human-specific pathogen and a major cause of meningitis and septicemia with a high case fatality rate. N. meningitidis may penetrate the nasopharyngeal mucosal membrane and cause severe meningitis, a mucosal immune response plays a key role in the defense against meningococcal infections. Our previous study demonstrated that N. meningitidis serogroup B 0315 (NMB0315) was a vaccine candidate against N. meningitidis serogroup B (NMB) through parenteral immunization. In this study, immunopotentiators (C48/80 or CpG-ODN) were loaded into chitosan nanoparticle (Chi NP) to form combination adjuvants (Chi-CpG NP and Chi-C48/80 NP) and adopted to enhance the immunogenicity of NMB0315 through intranasal immunization. The experimental results have indicated that both Chi-CpG NP and Chi-C48/80 NP are effective mucosal adjuvants for the induction of significantly higher rNMB0315-specific IgG, IgG1, IgG2a and sIgA antibodies. Meanwhile, Chi-CpG NP and Chi-C48/80 NP could change the ratio of IgG1/IgG2a, inducing a more balanced cellular/humoral immune response. Chi-CpG NP and Chi-C48/80 NP also boosted interleukin-4 (IL-4), interferon-γ (IFN-γ) and interleukin-17 A (IL-17A) production by splenocytes. The bactericidal antibodies have been detected in sera from mice immunized with rNMB0315+Chi-CpG NP and rNMB0315+Chi-C48/80 NP. Overall, the combination adjuvants could be applicable to the development of a mucosal vaccine against NMB.
摘要：
Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission. To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1–parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing. We discovered the ethyl acetate extract of the fungus Purpureocillium lilacinum that inhibited Plasmodium falciparum transmission to mosquitoes. Pre-exposure to the extract rendered Anopheles gambiae resistant to Plasmodium infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or “pulixin.” Pulixin prevented FREP1 from binding to P. falciparum-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC50 (the concentration that gave half-maximal response)of 11µM based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage P. falciparum with an EC50 of 47nM. The compound did not show cytotoxic effects at a concentration of 116µM or lower. By targeting the FREP1–Plasmodium interaction, we discovered that Purpureocillium lilacinum extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture.
