Displaying publications 21 - 40 of 60 in total

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  1. Chang J, Liang J, Zhang Y, Zhang R, Fang W, Zhang H, et al.
    J Hazard Mater, 2024 May 15;470:134152.
    PMID: 38552398 DOI: 10.1016/j.jhazmat.2024.134152
    Soil contamination by emerging pollutants tetrabromobisphenol A (TBBPA) and microplastics has become a global environmental issue in recent years. However, little is known about the effect of microplastics on degradation of TBBPA in soil, especially aged microplastics. In this study, the effect of aged polystyrene (PS) microplastics on the degradation of TBBPA in soil and the mechanisms were investigated. The results suggested that the aged microplastics exhibited a stronger inhibitory effect on the degradation of TBBPA in soil than the pristine microplastics, and the degradation efficiency of TBBPA decreased by 21.57% at the aged microplastic content of 1%. This might be related to the higher TBBPA adsorption capacity of aged microplastics compared to pristine microplastics. Aged microplastics strongly altered TBBPA-contaminated soil properties, reduced oxidoreductase activity and affected microbial community composition. The decrease in soil oxidoreductase activity and relative abundance of functional microorganisms (e.g., Bacillus, Pseudarthrobacter and Sphingomonas) caused by aged microplastics interfered with metabolic pathways of TBBPA. This study indicated the importance the risk assessment and soil remediation for TBBPA-contaminated soil with aged microplastics.
  2. Katoh TK, Zhang G, Toda MJ, Suwito A, Gao JJ
    Zookeys, 2018.
    PMID: 30271232 DOI: 10.3897/zookeys.781.27354
    The subgenus Dudaica Strand of the genus Drosophila Fallén has been known to comprise only two species: Drosophila (Dudaica) senilis Duda, 1926 (recorded from Indonesia, Philippines, Vietnam, Bhutan, and India) and D.malayana (Takada, 1976) (recorded from Malaysia). In the present study, this subgenus is revised, with D.malayana redescribed and six new species discovered and described from China, Malaysia, and Indonesia: gracilipalpis Katoh & Gao, sp. n., puberula Katoh & Gao, sp. n., albipalpis Katoh, Toda & Gao, sp. n., qiongzhouensis Katoh & Gao, sp. n., orthophallata Katoh, Toda & Gao, sp. n., and dissimilis Katoh & Gao, sp. n. Both morphological and molecular data (DNA barcodes) are used to distinguish the above species. A key to species of this subgenus is provided.
  3. Zhang G, Roslan SNAB, Shafri HZM, Zhao Y, Wang C, Quan L
    Sci Rep, 2024 Jul 13;14(1):16212.
    PMID: 39003342 DOI: 10.1038/s41598-024-67109-3
    To obtain seasonable and precise crop yield information with fine resolution is very important for ensuring the food security. However, the quantity and quality of available images and the selection of prediction variables often limit the performance of yield prediction. In our study, the synthesized images of Landsat and MODIS were used to provide remote sensing (RS) variables, which can fill the missing values of Landsat images well and cover the study area completely. The deep learning (DL) was used to combine different vegetation index (VI) with climate data to build wheat yield prediction model in Hebei Province (HB). The results showed that kernel NDVI (kNDVI) and near-infrared reflectance (NIRv) slightly outperform normalized difference vegetation index (NDVI) in yield prediction. And the regression algorithm had a more prominent effect on yield prediction, while the yield prediction model using Long Short-Term Memory (LSTM) outperformed the yield prediction model using Light Gradient Boosting Machine (LGBM). The model combining LSTM algorithm and NIRv had the best prediction effect and relatively stable performance in single year. The optimal model was then used to generate 30 m resolution wheat yield maps in the past 20 years, with higher overall accuracy. In addition, we can define the optimum prediction time at April, which can consider simultaneously the performance and lead time. In general, we expect that this prediction model can provide important information to understand and ensure food security.
  4. Chu K, Ye F, Sereyvatanak KY, Zhang X, Li Q, Lu Y, et al.
    Sci Total Environ, 2024 Sep 02.
    PMID: 39233071 DOI: 10.1016/j.scitotenv.2024.175997
    Solving the challenges faced during the measurement of the cross-interface transfer of perfluoroalkyl acids (PFAAs) in lakes is crucial for clarifying environmental behaviours of these chemicals and their efficient governance. This study developed a multimedia fugacity model based on the quantitative water-air-sediment interaction (QWASI) covering abiotic/biotic matrices to investigate the cross-interface transfer and fate of PFAAs in Luoma Lake, a typical PFAA-contaminated shallow lake in eastern China. The accuracy and reliability of the established model were confirmed using Percent bias and Monte Carlo simulation, respectively. Using the QWASI model, the multimedia transfer of the PFAAs and their accumulation and persistence in different sub-compartments were described and measured, and the differences among individual PFAAs were explored. The simulation results showed that the sedimentation and resuspension of PFAAs were the most intense cross-interfacial transfers, and the sediments served as a chemical sink in the long term. A significant negative correlation of NC-F (the number of CF bonds) with the relative outflow flux (TW·out-ct) but a positive correlation with the relative net transfer across the interface between water and aquatic plants (Tp-ct) was detected, indicating that the PFAA migration capacity decreased but the bioaccumulation potential increased with the CF bond number. The persistence in water (Pw) of individual PFAAs ranged from 19.65d (PFOA) to 32.22d (PFOS), with an average of 26.15d; their persistence in sediment (Ps) ranged from 432d (PFBA) to 3216d (PFOS), with an average of 1524d, increasing linearly with an increase in NC-F. The water advection flows into and out of the lake (QW·in and QW·out), the PFAA concentration of water inflow (CW·in), and bioconcentration factor of aquatic plants (BCFp) were the primary parameters sensitive to PFAAs in all sub-compartments, which are essential indexes for exploring promising remediation pathways for lacustrine PFAA contamination based on the fugacity model simulation.
  5. Yunus MA, Lin X, Bailey D, Karakasiliotis I, Chaudhry Y, Vashist S, et al.
    J Virol, 2015 Jan 15;89(2):1218-29.
    PMID: 25392209 DOI: 10.1128/JVI.02432-14
    All members of the Caliciviridae family of viruses produce a subgenomic RNA during infection. The subgenomic RNA typically encodes only the major and minor capsid proteins, but in murine norovirus (MNV), the subgenomic RNA also encodes the VF1 protein, which functions to suppress host innate immune responses. To date, the mechanism of norovirus subgenomic RNA synthesis has not been characterized. We have previously described the presence of an evolutionarily conserved RNA stem-loop structure on the negative-sense RNA, the complementary sequence of which codes for the viral RNA-dependent RNA polymerase (NS7). The conserved stem-loop is positioned 6 nucleotides 3' of the start site of the subgenomic RNA in all caliciviruses. We demonstrate that the conserved stem-loop is essential for MNV viability. Mutant MNV RNAs with substitutions in the stem-loop replicated poorly until they accumulated mutations that revert to restore the stem-loop sequence and/or structure. The stem-loop sequence functions in a noncoding context, as it was possible to restore the replication of an MNV mutant by introducing an additional copy of the stem-loop between the NS7- and VP1-coding regions. Finally, in vitro biochemical data suggest that the stem-loop sequence is sufficient for the initiation of viral RNA synthesis by the recombinant MNV RNA-dependent RNA polymerase, confirming that the stem-loop forms the core of the norovirus subgenomic promoter.

    IMPORTANCE: Noroviruses are a significant cause of viral gastroenteritis, and it is important to understand the mechanism of norovirus RNA synthesis. Here we describe the identification of an RNA stem-loop structure that functions as the core of the norovirus subgenomic RNA promoter in cells and in vitro. This work provides new insights into the molecular mechanisms of norovirus RNA synthesis and the sequences that determine the recognition of viral RNA by the RNA-dependent RNA polymerase.

  6. Huang Y, Li J, Xu Y, Xu W, Cheng Z, Liu J, et al.
    Mar Pollut Bull, 2014 Mar 15;80(1-2):194-9.
    PMID: 24462236 DOI: 10.1016/j.marpolbul.2014.01.007
    Nineteen pairs of air and seawater samples collected from the equatorial Indian Ocean onboard the Shiyan I from 4/2011 to 5/2011 were analyzed for PCBs and HCB. Gaseous concentrations of ∑(ICES)PCBs (ICES: International Council for the Exploration of the Seas) and HCB were lower than previous data over the study area. Air samples collected near the coast had higher levels of PCBs relative to those collected in the open ocean, which may be influenced by proximity to source regions and air mass origins. Dissolved concentrations of ∑(ICES)PCBs and HCB were 1.4-14 pg L⁻¹ and 0.94-13 pg L⁻¹, with the highest concentrations in the sample collected from Strait of Malacca. Fugacity fractions suggest volatilization of PCBs and HCB from the seawater to air during the cruise, with fluxes of 0.45-34 ng m⁻² d⁻¹ and 0.36-18 ng m⁻² d⁻¹, respectively.
  7. Mohd-Shamsudin MI, Kang Y, Lili Z, Tan TT, Kwong QB, Liu H, et al.
    PLoS One, 2013;8(5):e60839.
    PMID: 23734171 DOI: 10.1371/journal.pone.0060839
    Gene discovery in the Malaysian giant freshwater prawn (Macrobrachium rosenbergii) has been limited to small scale data collection, despite great interest in various research fields related to the commercial significance of this species. Next generation sequencing technologies that have been developed recently and enabled whole transcriptome sequencing (RNA-seq), have allowed generation of large scale functional genomics data sets in a shorter time than was previously possible. Using this technology, transcriptome sequencing of three tissue types: hepatopancreas, gill and muscle, has been undertaken to generate functional genomics data for M. rosenbergii at a massive scale. De novo assembly of 75-bp paired end Ilumina reads has generated 102,230 unigenes. Sequence homology search and in silico prediction have identified known and novel protein coding candidate genes (∼24%), non-coding RNA, and repetitive elements in the transcriptome. Potential markers consisting of simple sequence repeats associated with known protein coding genes have been successfully identified. Using KEGG pathway enrichment, differentially expressed genes in different tissues were systematically represented. The functions of gill and hepatopancreas in the context of neuroactive regulation, metabolism, reproduction, environmental stress and disease responses are described and support relevant experimental studies conducted previously in M. rosenbergii and other crustaceans. This large scale gene discovery represents the most extensive transcriptome data for freshwater prawn. Comparison with model organisms has paved the path to address the possible conserved biological entities shared between vertebrates and crustaceans. The functional genomics resources generated from this study provide the basis for constructing hypotheses for future molecular research in the freshwater shrimp.
  8. Lau YL, Lee WC, Gudimella R, Zhang G, Ching XT, Razali R, et al.
    PLoS One, 2016;11(6):e0157901.
    PMID: 27355363 DOI: 10.1371/journal.pone.0157901
    Toxoplasmosis is a widespread parasitic infection by Toxoplasma gondii, a parasite with at least three distinct clonal lineages. This article reports the whole genome sequencing and de novo assembly of T. gondii RH (type I representative strain), as well as genome-wide comparison across major T. gondii lineages. Genomic DNA was extracted from tachyzoites of T. gondii RH strain and its identity was verified by PCR and LAMP. Subsequently, whole genome sequencing was performed, followed by sequence filtering, genome assembly, gene annotation assignments, clustering of gene orthologs and phylogenetic tree construction. Genome comparison was done with the already archived genomes of T. gondii. From this study, the genome size of T. gondii RH strain was found to be 69.35Mb, with a mean GC content of 52%. The genome shares high similarity to the archived genomes of T. gondii GT1, ME49 and VEG strains. Nevertheless, 111 genes were found to be unique to T. gondii RH strain. Importantly, unique genes annotated to functions that are potentially critical for T. gondii virulence were found, which may explain the unique phenotypes of this particular strain. This report complements the genomic archive of T. gondii. Data obtained from this study contribute to better understanding of T. gondii and serve as a reference for future studies on this parasite.
  9. Nakamura C, Liu MM, Goo YK, Zhang GH, Jia HL, Kumagai A, et al.
    Trop Biomed, 2020 Dec 01;37(4):1029-1037.
    PMID: 33612755 DOI: 10.47665/tb.37.4.1029
    Previously, we have identified a gene encoding thrombospondin-related anonymous protein of Babesia gibsoni (BgTRAP), and have shown that the antisera raised against recombinant BgTRAP expressed in Escherichia coli inhibited the growth of parasites. In the present study, a recombinant vaccinia virus expressing the BgTRAP (VV/BgTRAP) was constructed. A specific band with a molecular mass of 80 kDa, which is similar to that of native BgTRAP on the merozoites of B. gibsoni, was detected in the supernatant of VV/ BgTRAP-infected RK13 cells. Mice inoculated with VV/BgTRAP produced a specific antiBgTRAP response. The antiserum against VV/BgTRAP showed reactivity against the native BgTRAP on parasites. These results indicated that the recombinant vaccinia virus expressing BgTRAP might be a vaccine candidate against canine B. gibsoni infection.
  10. Chen M, Samuel VP, Wu Y, Dang M, Lin Y, Sriramaneni R, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(2):143-152.
    PMID: 31679277 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029341
    The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.
  11. Vaezzadeh V, Yi X, Rais FR, Bong CW, Thomes MW, Lee CW, et al.
    Mar Pollut Bull, 2021 Nov;172:112871.
    PMID: 34428623 DOI: 10.1016/j.marpolbul.2021.112871
    Concentrations, sources and interactions between black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) were investigated in 42 sediment samples collected from riverine, coastal and shelf areas in Peninsular Malaysia. The concentrations of BC measured by benzene polycarboxylic acid (BPCA) method and PAHs showed broad spatial variations between the relatively pristine environment of the East coast and developed environment of the West and South coast ranging from 0.02 to 0.36% dw and 57.7 ng g-1 dw to 19,300 ng g-1 dw, respectively. Among diagnostic ratios of PAHs, the ratios of Ant/(Ant+Phe) and LMW/HMW drew the clearest distinctions between the East coast versus the West and South coast sediments indicating the predominance of petrogenic sources in the former versus pyrogenic sources in the latter. PAHs significantly correlated with BC and total organic carbon (TOC) in the sediments (p 
  12. Xie W, Yao Z, Yuan Y, Too J, Li F, Wang H, et al.
    Genomics, 2024 Jul 29.
    PMID: 39084477 DOI: 10.1016/j.ygeno.2024.110906
    Enhancers are crucial in gene expression regulation, dictating the specificity and timing of transcriptional activity, which highlights the importance of their identification for unravelling the intricacies of genetic regulation. Therefore, it is critical to identify enhancers and their strengths. Repeated sequences in the genome are repeats of the same or symmetrical fragments. There has been a great deal of evidence that repetitive sequences contain enormous amounts of genetic information. Thus, We introduce the W2V-Repeated Index, designed to identify enhancer sequence fragments and evaluates their strength through the analysis of repeated K-mer sequences in enhancer regions. Utilizing the word2vector algorithm for numerical conversion and Manta Ray Foraging Optimization for feature selection, this method effectively captures the frequency and distribution of K-mer sequences. By concentrating on repeated K-mer sequences, it minimizes computational complexity and facilitates the analysis of larger K values. Experiments indicate that our method performs better than all other advanced methods on almost all indicators.
  13. Hussain I, Syed JH, Kamal A, Iqbal M, Eqani SA, Bong CW, et al.
    Environ Monit Assess, 2016 Jun;188(6):378.
    PMID: 27234513 DOI: 10.1007/s10661-016-5359-3
    Chenab River is one of the most important rivers of Punjab Province (Pakistan) that receives huge input of industrial effluents and municipal sewage from major cities in the Central Punjab, Pakistan. The current study was designed to evaluate the concentration levels and associated ecological risks of USEPA priority polycyclic aromatic hydrocarbons (PAHs) in the surface sediments of Chenab River. Sampling was performed from eight (n = 24) sampling stations of Chenab River and its tributaries. We observed a relatively high abundance of ∑16PAHs during the summer season (i.e. 554 ng g(-1)) versus that in the winter season (i.e. 361 ng g(-1)), with an overall abundance of two-, five- and six-ring PAH congeners. Results also revealed that the nitrate and phosphate contents in the sediments were closely associated with low molecular weight (LMW) and high molecular weight (HMW) PAHs, respectively. Source apportionment results showed that the combustion of fossil fuels appears to be the key source of PAHs in the study area. The risk quotient (RQ) values indicated that seven PAH congeners (i.e. phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)pyrene, chrysene and benzo(a)anthracene) could pose serious threats to the aquatic life of the riverine ecosystem in Pakistan.
  14. Liu J, Andersson A, Zhong G, Geng X, Ding P, Zhu S, et al.
    Sci Total Environ, 2020 Jul 03;744:140359.
    PMID: 32688001 DOI: 10.1016/j.scitotenv.2020.140359
    Black Carbon (BC) deteriorates air quality and contributes to climate warming, yet its regionally- and seasonally-varying emission sources are poorly constrained. Here we employ natural abundance radiocarbon (14C) measurements of BC intercepted at a northern Malaysia regional receptor site, Bachok, to quantify the relative biomass vs. fossil source contributions of atmospheric BC, in a first year-round study for SE Asia (December 2015-December 2016). The annual average 14C signature suggests as large contributions from biomass burning as from fossil fuel combustion. This is similar to findings from analogous measurements at S Asian receptors sites (~50% biomass burning), while E Asia sites are dominated by fossil emission (~20% biomass burning). The 14C-based source fingerprinting of BC in the dry spring season in SE Asia signals an even more elevated biomass burning contribution (~70% or even higher), presumably from forest, shrub and agricultural fires. This is consistent with this period showing also elevated ratio of organic carbon to BC (up from ~5 to 30) and estimates of BC emissions from satellite fire data. Hence, the present study emphasizes the importance of mitigating dry season vegetation fires in SE Asia.
  15. Vaezzadeh V, Thomes MW, Kunisue T, Tue NM, Zhang G, Zakaria MP, et al.
    Chemosphere, 2021 Jan;263:128272.
    PMID: 33297216 DOI: 10.1016/j.chemosphere.2020.128272
    Barnacles are ubiquitous in coastal ecosystems of different geographical regions worldwide. This is the first study attempting to assess the suitability of barnacles as bioindicators of persistent organic pollutants (POPs) in coastal environments. Barnacles were collected from the coasts around Peninsular Malaysia and analyzed for POPs including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Among POPs, PCBs showed the highest concentrations with elevated contributions of CB28 and CB153. As for PBDEs, BDE47 was the most frequently detected congener, while BDE209 was detected in barnacles from two stations in Port Klang and the levels reached up to >70% of total PBDE concentrations. Concentrations of OCPs detected in barnacles were in the order of CHLs > DDTs > HCHs > HCB and 4,4'-DDE and cis- and trans-chlordane were the predominant OCP compounds. A comparison with previous studies in Malaysia showed consistent levels of POPs. Green mussels collected from selected barnacles' habitats, for the sake of a comparison, showed almost similar profiles but lower concentrations of POPs. The spatial distribution of POPs observed in barnacles and comparison of POP levels and profiles with mussels indicated that barnacles can be useful bioindicators for monitoring POPs contamination in the coastal ecosystems.
  16. Du P, Liu X, Zhong G, Zhou Z, Thomes MW, Lee CW, et al.
    PMID: 32023897 DOI: 10.3390/ijerph17030889
    Southeast Asian countries including Malaysia play a major role in global drug trade and abuse. Use of amphetamine-type stimulants has increased in the past decade in Malaysia. This study aimed to apply wastewater-based epidemiology for the first time in Kuala Lumpur, Malaysia, to estimate the consumption of common illicit drugs in urban population. Influent wastewater samples were collected from two wastewater treatment plants in Kuala Lumpur in the summer of 2017. Concentrations of twenty-four drug biomarkers were analyzed for estimating drug consumption. Fourteen drug residues were detected with concentrations of up to 1640 ng/L. Among the monitored illicit drugs, 3,4-methylenedioxy-methamphetamine (MDMA) or ecstasy had the highest estimated per capita consumptions. Consumption and dose of amphetamine-type stimulants (methamphetamine and MDMA) were both an order of magnitude higher than those of opioids (heroin and codeine, methadone and tramadol). Amphetamine-type stimulants were the most prevalent drugs, replacing opioids in the drug market. The prevalence trend measured by wastewater-based epidemiology data reflected the shift to amphetamine-type stimulants as reported by the Association of Southeast Asian Nations Narcotics Cooperation Center. Most of the undetected drug residues were new psychoactive substances (NPSs), suggesting a low prevalence of NPSs in the drug market.
  17. Zhang X, Deng T, Lu J, Zhao P, Chen L, Qian M, et al.
    Transbound Emerg Dis, 2020 May;67(3):1349-1355.
    PMID: 31943814 DOI: 10.1111/tbed.13477
    Infectious bronchitis virus (IBV), an ongoing emergence enveloped virus with a single-stranded positive-sense RNA genome, belongs to the Gammacoronavirus genus in the Coronaviridae family. IBV-associated tracheitis, nephritis, salpingitis, proventriculitis and egg drop have caused devastating economic losses to poultry industry worldwide. Since the end of 2018, a remarkably increasing number of commercial broilers and layers, vaccinated or not, were infected with IBV in China. Here, we described two IB outbreaks with severe respiratory system or kidney injury in IBV-vaccinated commercial poultry farms in central China. Other possible causative viral pathogens, including avian influenza virus (AIV), Newcastle disease virus (NDV) and Kedah fatal kidney syndrome virus (KFKSV), were excluded by reverse transcription-polymerase chain reaction (RT-PCR), and three virulent IBV strains, HeN-1/China/2019, HeN-2/China/2019 and HeN-101/China/2019, were identified. Although the gross pathologic appearance of these two IB outbreaks was different, the newly identified IBV strains were all closely related to the ck/China/I0529/17 strain and grouped into GI-19 genotype clade based on the sequencing and phylogenetic analysis of the complete S1 genes. Moreover, there are still some evolutionary distance between the newly identified IBV strains, HeN-101/China/2019 in particular, and other GI-19 strains, suggesting that Chinese IBV strains constantly emerge and evolve towards different directions. In conclusion, this study provided an insight of the recently emerging IBV outbreaks in IBV-vaccinated commercial poultry farms and identified the genetic characteristics of three virulent GI-19 IBV strains, which shows the need to carry out proper preventive measures and control strategies.
  18. Zhou C, Yu T, Zhu R, Lu J, Ouyang X, Zhang Z, et al.
    Int J Biol Sci, 2023;19(5):1471-1489.
    PMID: 37056925 DOI: 10.7150/ijbs.77979
    Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.
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