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  1. Effects of atmospheric deposition nitrogen flux and its composition on soil solution chemistry from a red soil farmland, southeast China
    Cui J, Zhou J, Peng Y, Chan A, Mao J
    Environ Sci Process Impacts, 2015 Dec;17(12):2082-91.
    PMID: 26515781 DOI: 10.1039/c5em00383k
    A detailed study on the solution chemistry of red soil in South China is presented. Data are collected from two simulated column-leaching experiments with an improved setup to evaluate the effects of atmospheric N deposition (ADN) composition and ADN flux on agricultural soil acidification using a (15)N tracer technique and an in situ soil solution sampler. The results show that solution pH values decline regardless of the increase of the NH4(+)/NO3(-) ratio in the ADN composition or ADN flux, while exchangeable Al(3+), Ca(2+), Mg(2+), and K(+) concentrations increase at different soil depths (20, 40, and 60 cm). Compared with the control, ADN (60 kg per ha per year N, NH4(+)/NO3(-) ratio of 2 : 1) decreases solution pH values, increases solution concentrations of NO3(-)-N, Al(3+), Ca(2+) and Mg(2+) at the middle and lower soil depths, and promotes their removal. NH4(+)-N was not detected in red soil solutions of all the three soil layers, which might be attributed to effects of nitrification, absorption and fixation in farmland red soil. Some of the NO3(-)-N concentrations at 40-60 cm soil depth exceed the safe drinking level of 10 mg L(-1), especially when the ADN flux is beyond 60 kg ha(-1) N. These features are critical for understanding the ADN agro-ecological effects, and for future assessment of ecological critical loads of ADN in red soil farmlands.
  2. Lipidomics insight on differences in lipid profiles and phytosterol compositions of coconut oils extracted by classical and green solvents
    Cui J, Yang Z, Xu Y, Tan CP, Zhang W
    Food Res Int, 2023 Dec;174(Pt 2):113653.
    PMID: 37981374 DOI: 10.1016/j.foodres.2023.113653
    Searching for green and ecofriendly solvents to replace classical solvents for industrial scale extraction of coconut oil is of great interest. To explore these possibilities, this study performed comprehensive comparative analyses of lipid profiles and phytosterol compositions in coconut oils obtained by extraction with n-hexane, absolute ethyl alcohol, deep eutectic solvent/n-hexane, dimethyl carbonate (DME) and cyclopentyl methyl ether (CPME) using a foodomics approach. Results indicated that CPME (64.23 g/100 g dry matter) and DME (65.64 g/100 g dry matter) showed comparable capacity for total lipid extraction of total lipids to classical solvents (63.5-65.66 g/100 g dry matter). Considering the phytosterol yield, CPME (644.26 mg/kg) exhibited higher selectivity than other solvents (535.64-622.13 mg/kg). No significant difference was observed in the fatty acid composition of coconut oil by the different solvents assayed. Additionally, total 468 lipid molecules were identified in the samples. For glycerolipid and sphingolipid, the five solvents showed comparable extraction capabilities. However, CPME exhibited higher extraction efficiency of polar lipids (glycerophospholipid and saccharolipid) than other solvents. Overall, these results may be a useful guide for the application of green solvents in industrial production of coconut oil.
  3. Sources and trends of oxidized and reduced nitrogen wet deposition in a typical medium-sized city of eastern China during 2010-2016
    Cui J, Cui J, Peng Y, Yao D, Chan A, Chen Z, et al.
    Sci Total Environ, 2020 Jun 27;744:140558.
    PMID: 32711301 DOI: 10.1016/j.scitotenv.2020.140558
    Fluxes and composition dynamics of atmospheric nitrogen deposition play key roles in better balancing economic development and ecological environment. However, there are some knowledge gaps and difficulties in urban ecosystems, especially for small and medium-sized cities. In this study, both flux and composition (ratio of NH4+-N to NO3--N, RN) of wet-deposited dissolved inorganic nitrogen (DIN, sum of NO3--N and NH4+-N) were estimated and sources were identified at a long-term urban observation station in Tongling, a typical medium-sized city in eastern China during 2010-2016, respectively. Results showed that wet-deposited DIN fluxes were 33.20 and 28.15 kgN ha-1 yr-1 in Tongling city during 2010-2011 and 2015-2016, respectively. Compared to these two periods, both DIN and NO3--N fluxes decreased by 15.2% and 31.8% for a series of NOx abatement measures applied effectively, respectively. At the same time, the NH4+-N flux remained stable and ranged from 19.53 to 20.62 kgN ha-1 yr-1, and the RN increased from 1.7 to 2.2. Seasonally, winds from the southwest and west-southwest with higher frequencies and speeds in spring and summer brought more NH4+-N and DIN wet deposition from an ammonia plant, which could threaten the safety of regional hydrosphere ecosystems. On the whole, the wet-deposited NH4+-N was threatening regional ecosystems of both the hydrosphere and forest. The wet-deposited DIN including NH4+-N in Tongling city stemmed mainly from a combined source of coal combustion and dust from Cu extraction and smelting, ammonia production, and roads. Therefore, production lines should be updated for Cu extraction and smelting industries, thermal power generations and the ammonia plant, old vehicles should be eliminated, and the use of new energy vehicles should be promoted for regional sustainable development and human health in the medium-sized city.
  4. Distribution and assessment of heavy metal contents in surface sediments of the western Sunda Shelf
    Zhang H, Liu S, Wu K, Cui J, Zhu A, Zhang Y, et al.
    Mar Pollut Bull, 2021 Jul;168:112433.
    PMID: 33962084 DOI: 10.1016/j.marpolbul.2021.112433
    The heavy metal contents (Cr, Cu, Zn, Cd, Pb, Hg, and As) of 88 surface sediment samples from the western Sunda Shelf were analyzed to determine their spatial distribution patterns and contamination status. The results demonstrated that high enrichment regions of heavy metals were focused in the Kelantan, Pahang, and Ambat river estuaries, and deep water regions of the study area. These high enrichment regions were mainly controlled by riverine inputs and their hydrodynamic conditions. The enrichment factor (EF), geoaccumulation index (Igeo), and potential ecological risk index (PERI) were used to assess heavy metal accumulation. The results indicated that the study area was not significantly contaminated overall at the time of the study; however, Cd, As, and Hg were at levels corresponding to moderate contamination at many stations located in the Pahang River estuary, Kelantan River estuary, and north-eastern region of the study area, primarily because of anthropogenic activities.
  5. Seasonal fluxes and sources apportionment of dissolved inorganic nitrogen wet deposition at different land-use sites in the Three Gorges reservoir area
    Cui J, Zhang Y, Yang F, Chang Y, Du K, Chan A, et al.
    Ecotoxicol Environ Saf, 2020 Apr 15;193:110344.
    PMID: 32092583 DOI: 10.1016/j.ecoenv.2020.110344
    To identify seasonal fluxes and sources of dissolved inorganic nitrogen (DIN) wet deposition, concentrations and δ15N signatures of nitrate (NO3-) and ammonium (NH4+) in wet precipitation were measured at four typical land-use types in the Three Gorges reservoir (TGR) area of southwest China for a one-year period. Higher DIN fluxes were recorded in spring and summer and their total fluxes (averaged 7.58 kg N ha-1) were similar to the critical loads in aquatic ecosystems. Significant differences of precipitation δ15N were observed for NH4+-N between town and wetland sites in spring and between urban and rural sites in summer. For NO3--N, significant differences of precipitation δ15N were observed between town and rural sites in spring and between urban and town sites in autumn, respectively. Quantitative results of NO3--N sources showed that both biomass burning and coal combustion had higher fluxes at the urban site especially in winter (0.18 ± 0.09 and 0.19 ± 0.08 kg N ha-1), which were about three times higher than those at the town site. A similar finding was observed for soil emission and vehicle exhausts in winter. On the whole, DIN wet deposition averaged at 12.13 kg N ha-1 yr-1 with the urban site as the hotspot (17.50 kg N ha-1 yr-1) and regional NO3--N fluxes had a seasonal pattern with minimum values in winter. The contribution to NO3--N wet deposition from biomass burning was 26.1 ± 14.1%, which is the second dominant factor lower than coal combustion (26.5 ± 12.6%) in the TGR area during spring and summer. Hence N emission reduction from biomass burning, coal combustion and vehicle exhausts should be strengthened especially in spring and summer to effectively manage DIN pollution for the sustainable development in TGR area.
  6. Functional analysis of Trichinella spiralis serine protease 1.2 by siRNA mediated RNA interference
    Yang F, Guo KX, Yang DQ, Liu RD, Long SR, Zhang X, et al.
    Trop Biomed, 2020 Jun 01;37(2):458-470.
    PMID: 33612815
    A T. spiralis serine protease 1.2 (TsSP1.2) was identified in the muscle larvae (ML) and intestinal larvae surface/excretory-secretory (ES) proteins by immunoproteomics. The aim of this study was to determine the TsSP1.2 function in the process of T. spiralis intrusion, growth and reproduction by using RNA interference (RNAi). RNAi was used to silence the expression of TsSP1.2 mRNA and protein in the nematode. On 2 days after the ML were electroporated with 2 µM of TsSP1.2-specific siRNA 534, TsSP1.2 mRNA and protein expression declined in 56.44 and 84.48%, respectively, compared with untreated ML. Although TsSP1.2 silencing did not impair worm viability, larval intrusion of intestinal epithelium cells (IEC) was suppressed by 57.18% (P < 0.01) and the suppression was siRNA-dose dependent (r = 0.976). Infection of mice with siRNA 534 transfected ML produced a 57.16% reduction of enteral adult burden and 71.46% reduction of muscle larva burden (P < 0.05). Moreover, silencing of TsSP1.2 gene in ML resulted in worm development impediment and reduction of female fertility. The results showed that silencing of TsSP1.2 by RNAi inhibited larval intrusion and development, and reduced female fecundity. TsSP1.2 plays a crucial role for worm invasion and development in T. spiralis life cycle, and is a potential vaccine/drug target against Trichinella infection.
  7. Global genetic diversity of Spirometra tapeworms
    Hong X, Liu SN, Xu FF, Han LL, Jiang P, Wang ZQ, et al.
    Trop Biomed, 2020 Mar 01;37(1):237-250.
    PMID: 33612735
    Spirometra larvae are etiological agents of human sparganosis. However, the systematics of spirometrid cestodes has long been controversial. In order to determine the current knowledge on the evolution and genetic structure of Spirometra, an exhaustive population diversity analysis of spirometrid cestodes using the mitochondrial gene: cytochrome c oxidase subunit 1 (cox1) was performed. All publicly available cox1 sequences available in the GenBank and 127 new sequencing genes from China were used as the dataset. The haplotype identify, network, genetic differentiation and phylogenetic analysis were conducted successively. A total of 488 sequences from 20 host species, representing four spirometrid tapeworms (S. decipiens, S. ranarum, S. erinaceieuropaei and Sparganum proliferum) and several unclassified American and African isolates from 113 geographical locations in 17 countries, identified 45 haplotypes. The genetic analysis revealed that there are four clades of spirometrid cestodes: Clade 1 (Brazil + USA) and Clade 2 (Argentina + Venezuela) included isolates from America, Clade 3 contained African isolates and one Korean sample, and the remainders from Asia and Australia belonged to Clade 4; unclassified Spirometra from America and Africa should be considered the separate species within the genus; and the taxonomy of two Korea isolates (S. erinaceieuropaei KJ599680 and S. decipiens KJ599679) was still ambiguous and needs to be further identified. In addition, the demographical analyses supported population expansion for the total spirometrid population. In summary, four lineages were found in the spirometrid tapeworm, and further investigation with deeper sampling is needed to elucidate the population structure.
  8. Impact of socioeconomic and meteorological factors on reservoirs' air quality: a case in the Three Gorges Reservoir of Chongqing (TGRC), China over a 10-year period
    Peng Y, Zhou F, Cui J, Du K, Leng Q, Yang F, et al.
    Environ Sci Pollut Res Int, 2017 Jul;24(19):16206-16219.
    PMID: 28540543 DOI: 10.1007/s11356-017-9221-0
    The Three Gorges Dam's construction and industrial transfer have resulted in a new air pollution pattern with the potential to threaten the reservoir eco-environment. To assess the impact of socioeconomic factors on the pattern of air quality vairation and economical risks, concentrations of SO2, NO2, and PM10, industry genres, and meteorological conditions were selected in the Three Gorges Reservoir of Chongqing (TGRC) during 2006-2015. Results showed that air quality had improved to some extent, but atmospheric NO2 showed an increased trend during 2011-2015. Spatially, higher atmospheric NO2 extended to the surrounding area. The primary industry, especially for agriculture, had shown to be responsible for the remarkable increase of atmospheric NO2 (p 
  9. Effect of different gelators on the physicochemical properties and microstructure of coconut oleogels
    Yang Z, Cui J, Yun Y, Xu Y, Tan CP, Zhang W
    J Sci Food Agric, 2024 Jan 29.
    PMID: 38284624 DOI: 10.1002/jsfa.13338
    BACKGROUND: The inherent properties of coconut oil (CO), including its elevated saturated fatty acid content and low melting point, make it suitable for application in plastic fat processing. The present study explores the physicochemical characteristics, micromorphology and oxidative stability of oleogels produced from CO using various gelators [ethylcellulose (EC), β-sitosterol/γ-oryzanol (PS) and glyceryl monostearate (MG)] to elucidate the formation mechanisms of coconut oleogels (EC-COO, PS-COO and MG-COO).

    RESULTS: Three oleogel systems exhibited a solid-like behavior, with the formation of crystalline forms dominated by β and β'. Among them, PS-COO exhibited enhanced capability with respect to immobilizing liquid oils, resulting in solidification with high oil-binding capacity, moderate hardness and good elasticity. By contrast, MG-COO demonstrated inferior stability compared to PS-COO and EC-COO. Furthermore, MG-COO and PS-COO demonstrated antioxidant properties against CO oxidation, whereas EC-COO exhibited the opposite effect. PS-COO and EC-COO exhibited superior thermodynamic behavior compared to MG-COO.

    CONCLUSION: Three oleogels based on CO were successfully prepared. The mechanical strength, storage modulus and thermodynamic stability of the CO oleogel exhibited concentration dependence with increasing gelling agent addition. PS-COO demonstrated relatively robust oil-binding capacity and oxidative stability, particularly with a 15% PS addition. This information contributes to a deeper understanding of CO-based oleogels and offers theoretical insights for their application in food products. © 2024 Society of Chemical Industry.

  10. Nonlinear effects of increasing nitrogen deposition on rice growth and heavy metal uptake in a red soil ecosystem of southeastern China
    Wang J, Yi X, Cui J, Chang Y, Yao D, Zhou D, et al.
    Sci Total Environ, 2019 Jun 20;670:1060-1067.
    PMID: 31018421 DOI: 10.1016/j.scitotenv.2019.03.245
    With the population growth, urbanization and industrialization, China has become a hotspot of atmospheric deposition nitrogen (ADN), which is a threat to ecosystem and food safety. However, the impacts of increased ADN on rice growth and grain metal content are little studied. Based on previous long-term ADN studies, greenhouse experiment was conducted with four simulated ADN rates of 0, 30, 60 and 90 kg N ha-1 yr-1 (CK, N1, N2 and N3 as δ15N, respectively) to assess rice growth and metal uptake in a red soil ecosystem of southeast China during 2016-2017. Results showed that simulated ADN could promote rice growth and increase yields by 15.68-24.41% (except N2) and accumulations of cadmium (Cd) or copper (Cu) in organs. However, there was no linear relationship between ADN rate and rice growth or Cd or Cu uptake. The 15N-ADN was mainly accumulated in roots (21.31-67.86%) and grains (25.26-49.35%), while Cd and Cu were primarily accumulated in roots (78.86-93.44% and 90.00-96.24%, respectively). 15N-ADN and Cd accumulations in roots were significantly different between the two growing seasons (p 
  11. Primary assessment of a T. spiralis putative serine protease for early serological detection of experimental trichinellosis
    Sun GG, Lei JJ, Guo KX, Liu RD, Long SR, Zhang X, et al.
    Trop Biomed, 2019 Sep 01;36(3):792-802.
    PMID: 33597500
    A putative serine protease of T. spiralis (TsSP) was expressed in Escherichia coli and its potential as a diagnostic antigen was primarily assessed in this study. Anti-Trichinella IgG in serum samples from T. spiralis different animal hosts (mice, rats, pigs and rabbits) were detected on Western blot analysis with rTsSP. Anti-Trichinella antibodies were detected in 100% (30/30) of experimentally infected mice by rTsSP-ELISA. Cross-reactions of rTsSPELISA were not found with sera from mice infected with other parasites (S. erinaceieuropaei, S. japonicum, C. sinensis, A. cantonensis and T. gondii) and sera from normal mice. There was no statistical difference in antibody detection rate among mice infected with the encapsulated Trichinella species (T. spiralis, T. nativa, T. britovi, and T. nelsoni) (P>0.05). The results of rTsSP-ELISA showed that serum specific antibody IgG in mice infected with 100 or 500 T. spiralis muscle larvae (ML) were detectable early at 7-8 dpi, but not detected by ML ES antigen-ELISA prior to 10-12 dpi. Specific anti-Trichinella IgG was detected in 100% (18/18) of infected pigs by rTsSP-ELISA and ES-ELISA, but no specific antibodies was not detected in 20 conventionally raised normal pigs by two antigens. The results showed the rTsSP had the potential for early serodiagnosis of animal Trichinella infection, however it requires to be assayed with early infection sera of swine infected with Trichinella and other parasites.
  12. Increasing atmospheric deposition nitrogen and ammonium reduced microbial activity and changed the bacterial community composition of red paddy soil
    Zhou F, Cui J, Zhou J, Yang J, Li Y, Leng Q, et al.
    Sci Total Environ, 2018 Aug 15;633:776-784.
    PMID: 29602116 DOI: 10.1016/j.scitotenv.2018.03.217
    Atmospheric deposition nitrogen (ADN) increases the N content in soil and subsequently impacts microbial activity of soil. However, the effects of ADN on paddy soil microbial activity have not been well characterized. In this study, we studied how red paddy soil microbial activity responses to different contents of ADN through a 10-months ADN simulation on well managed pot experiments. Results showed that all tested contents of ADN fluxes (27, 55, and 82kgNha-1 when its ratio of NH4+/NO3--N (RN) was 2:1) enhanced the soil enzyme activity and microbial biomass carbon and nitrogen and 27kgNha-1 ADN had maximum effects while comparing with the fertilizer treatment. Generally, increasing of both ADN flux and RN (1:2, 1:1 and 2:1 with the ADN flux of 55kgNha-1) had similar reduced effects on microbial activity. Furthermore, both ADN flux and RN significantly reduced soil bacterial alpha diversity (p<0.05) and altered bacterial community structure (e.g., the relative abundances of genera Dyella and Rhodoblastus affiliated to Proteobacteria increased). Redundancy analysis demonstrated that ADN flux and RN were the main drivers in shaping paddy soil bacteria community. Overall, the results have indicated that increasing ADN flux and ammonium reduced soil microbial activity and changed the soil bacterial community. The finding highlights how paddy soil microbial community response to ADN and provides information for N management in paddy soil.
  13. A comparison of various approaches used in source apportionments for precipitation nitrogen in a mountain region of southwest China
    Cui J, Zhou F, Gao M, Zhang L, Zhang L, Du K, et al.
    Environ Pollut, 2018 Oct;241:810-820.
    PMID: 29909307 DOI: 10.1016/j.envpol.2018.06.028
    Six different approaches are applied in the present study to apportion the sources of precipitation nitrogen making use of precipitation data of dissolved inorganic nitrogen (DIN, including NO3- and NH4+), dissolved organic nitrogen (DON) and δ15N signatures of DIN collected at six sampling sites in the mountain region of Southwest China. These approaches include one quantitative approach running a Bayesian isotope mixing model (SIAR model) and five qualitative approaches based on in-situ survey (ISS), ratio of NH4+/NO3- (RN), principal component analysis (PCA), canonical-correlation analysis (CCA) and stable isotope approach (SIA). Biomass burning, coal combustion and mobile exhausts in the mountain region are identified as major sources for precipitation DIN while biomass burning and volatilization sources such as animal husbandries are major ones for DON. SIAR model results suggest that mobile exhausts, biomass burning and coal combustion contributed 25.1 ± 14.0%, 26.0 ± 14.1% and 27.0 ± 12.6%, respectively, to NO3- on the regional scale. Higher contributions of both biomass burning and coal combustion appeared at rural and urban sites with a significant difference between Houba (rural) and the wetland site (p 
  14. Effects of Soil Amendments on Microbial Activities in a Typical Cd-Contaminated Purple Field Soil, Southwestern China
    Wang W, Zhou F, Chang Y, Cui J, He D, Du J, et al.
    Bull Environ Contam Toxicol, 2020 Mar;104(3):380-385.
    PMID: 31932904 DOI: 10.1007/s00128-020-02786-0
    In this study, three soil amendments (inorganic, liming, or organic-inorganic materials) were used in a Cd-contaminated purple field soil to investigate their impacts on soil Cd availability, enzyme (urease, catalase, sucrase, and acid phosphatase) activities, microbial biomass (carbon/nitrogen) and type (bacteria, fungi, and actinomycetes) in mustard and corn trials. Results showed that soil amendments generally decreased soil exchangeable Cd, fungi and bacterial populations while increasing the activities of all the four soil enzymes tested, microbial biomass carbon and populations of actinomycetes (p  0.05) whereas stronger effects appeared in soil organic matter and available nutrients (nitrogen, phosphorous and potassium; p 
  15. The development of a novel transforming growth factor-β (TGF-β) inhibitor that disrupts ligand-receptor interactions
    Wu H, Sun Y, Wong WL, Cui J, Li J, You X, et al.
    Eur J Med Chem, 2020 Mar 01;189:112042.
    PMID: 31958737 DOI: 10.1016/j.ejmech.2020.112042
    Transforming growth factor-β (TGF-β) plays an important role in regulating epithelial to mesenchymal transition (EMT) and the TGF-β signaling pathway is a potential target for therapeutic intervention in the development of many diseases, such as fibrosis and cancer. Most currently available inhibitors of TGF-β signaling function as TGF-β receptor I (TβR-I) kinase inhibitors, however, such kinase inhibitors often lack specificity. In the present study, we targeted the extracellular protein binding domain of the TGF-β receptor II (TβR-II) to interfere with the protein-protein interactions (PPIs) between TGF-β and its receptors. One compound, CJJ300, inhibited TGF-β signaling by disrupting the formation of the TGF-β-TβR-I-TβR-II signaling complex. Treatment of A549 cells with CJJ300 resulted in the inhibition of downstream signaling events such as the phosphorylation of key factors along the TGF-β pathway and the induction of EMT markers. Concomitant with these effects, CJJ300 significantly inhibited cell migration. The present study describes for the first time a designed molecule that can regulate TGF-β-induced signaling and EMT by interfering with the PPIs required for the formation of the TGF-β signaling complex. Therefore, CJJ300 can be an important lead compound with which to study TGF-β signaling and to design more potent TGF-β signaling antagonists.
  16. Fulltext Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation
    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.
  17. Fulltext The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure
    Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.
    J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
    PMID: 28938457 DOI: 10.1210/jc.2017-00957
    Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.

    Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.

    Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.

    Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.

    Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

  18. Fulltext Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study
    Li Z, Xia Y, Feng LN, Chen JR, Li HM, Cui J, et al.
    Lancet Oncol, 2016 Sep;17(9):1240-7.
    PMID: 27470079 DOI: 10.1016/S1470-2045(16)30148-6
    BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL.

    METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.

    FINDINGS: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.

    INTERPRETATION: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.

    FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).

  19. Fulltext Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
    Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al.
    Nat Genet, 2022 Nov;54(11):1640-1651.
    PMID: 36333501 DOI: 10.1038/s41588-022-01213-w
    Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P 
  20. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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