Exploring the adverse effects of 1,3,6,8-tetrabromo-9H-carbazole in atherosclerotic model mice by metabolomic profiling integrated with mechanism studies in vitro.

Given its wide distribution in the environment and latent toxic effects, 1,3,6,8-tetrabromo-9H-carbazole (1368-BCZ) is an emerging concern that has gained increasing attention globally. 1368-BCZ exposure is reported to have potential cardiovascular toxicity. Although atherosclerosis is a cardiovascular disease and remains a primary cause of mortality worldwide, no evidence has been found regarding the impact of 1368-BCZ on atherosclerosis. Therefore, we aimed to explore the deleterious effects of 1368-BCZ on atherosclerosis and the underlying mechanisms. Serum samples from 1368-BCZ-treated atherosclerotic model mice were subjected to metabolomic profiling to investigate the adverse influence of the pollutant. Subsequently, the molecular mechanism associated with the metabolic pathway of atherosclerotic mice that was identified following 1368-BCZ exposure was validated in vitro. Serum metabolomics analysis revealed that 1368-BCZ significantly altered the tricarboxylic acid cycle, causing a disturbance in energy metabolism. In vitro, we further validated general markers of energy metabolism based on metabolome data: 1368-BCZ dampened adenosine triphosphate (ATP) synthesis and increased reactive oxygen species (ROS) production. Furthermore, blocking the aryl hydrocarbon receptor (AhR) reversed the high production of ROS induced by 1368-BCZ. It is concluded that 1368-BCZ decreased the ATP synthesis by disturbing the energy metabolism, thereby stimulating the AhR-mediated ROS production and presumably causing aggravated atherosclerosis. This is the first comprehensive study on the cardiovascular toxicity and mechanism of 1368-BCZ based on rodent models of atherosclerosis and integrated with in vitro models.

Carbon emission reduction effects of renewable energy technological innovation in China: New insights into the intellectual property rights protection.

Renewable energy technological innovation (RETI) is of great significance in reducing carbon emissions. A deeper understanding of the impact of intellectual property rights (IPR) protection on the carbon reduction effect of RETI can provide policymakers with more specific information. Using the dataset from 30 provinces in China during 2007-2018, we provide a detailed analysis of the moderating role of IPR protection in RETI's impact on carbon emissions. The results suggest that RETI has a significant carbon reduction effect, but this effect is not substantial in hydropower technological innovation. Moreover, we find that IPR protection moderates the impact of RETI on carbon emissions; increased levels of IPR protection can enhance RETI's carbon mitigation effect. Specifically, this positive moderating effect is only evidenced in the high energy self-sufficiency ratio and eastern regions, and it diminishes as carbon emissions increase. However, we do not find any evidence that IPR protection moderates the impact of energy storage technological innovation on carbon emissions.

China's ambitious low-carbon goals require fostering city-level renewable energy transitions.

Cities in China, as elsewhere, are increasingly playing a crucial role in mitigating climate change. We developed a panel dataset on renewable energy transition in Chinese cities, and assessed the CO2 emissions reduction of city-level renewable energy transition. We found that city-level renewable energy transition only reduced 446 million tonnes of CO2 emissions from 2005 to 2019. Moreover, the 2030 carbon peak target will be missed in the business-as-usual scenario. The CO2 emissions reduction of city-level renewable energy transition will significantly increase in the policy constraint scenario and in the technology breakthrough scenario, and the 2030 carbon peak target will likely be reached in both these scenarios, with a range of possible CO2 emissions in 2030 equal to 8.34-10.43 and 8.00-10.07 billion tonnes, respectively. In this study, we were the first to assess the historical contribution and prospective trajectory of CO2 emissions reduction of China's city-level renewable energy transition.

Uncertainty-Aware Contrastive Distillation for Incremental Semantic Segmentation.

A fundamental and challenging problem in deep learning is catastrophic forgetting, i.e., the tendency of neural networks to fail to preserve the knowledge acquired from old tasks when learning new tasks. This problem has been widely investigated in the research community and several Incremental Learning (IL) approaches have been proposed in the past years. While earlier works in computer vision have mostly focused on image classification and object detection, more recently some IL approaches for semantic segmentation have been introduced. These previous works showed that, despite its simplicity, knowledge distillation can be effectively employed to alleviate catastrophic forgetting. In this paper, we follow this research direction and, inspired by recent literature on contrastive learning, we propose a novel distillation framework, Uncertainty-aware Contrastive Distillation (UCD). In a nutshell, UCDis operated by introducing a novel distillation loss that takes into account all the images in a mini-batch, enforcing similarity between features associated to all the pixels from the same classes, and pulling apart those corresponding to pixels from different classes. In order to mitigate catastrophic forgetting, we contrast features of the new model with features extracted by a frozen model learned at the previous incremental step. Our experimental results demonstrate the advantage of the proposed distillation technique, which can be used in synergy with previous IL approaches, and leads to state-of-art performance on three commonly adopted benchmarks for incremental semantic segmentation.

Genomic insights into local adaptation and future climate-induced vulnerability of a keystone forest tree in East Asia.

Rapid global climate change is posing a substantial threat to biodiversity. The assessment of population vulnerability and adaptive capacity under climate change is crucial for informing conservation and mitigation strategies. Here we generate a chromosome-scale genome assembly and re-sequence genomes of 230 individuals collected from 24 populations for Populus koreana, a pioneer and keystone tree species in temperate forests of East Asia. We integrate population genomics and environmental variables to reveal a set of climate-associated single-nucleotide polymorphisms, insertion/deletions and structural variations, especially numerous adaptive non-coding variants distributed across the genome. We incorporate these variants into an environmental modeling scheme to predict a highly spatiotemporal shift of this species in response to future climate change. We further identify the most vulnerable populations that need conservation priority and many candidate genes and variants that may be useful for forest tree breeding with special aims. Our findings highlight the importance of integrating genomic and environmental data to predict adaptive capacity of a key forest to rapid climate change in the future.

Effects of the emerging contaminant 1,3,6,8-tetrabromocarbazole on the NF-κB and correlated mechanism in human hepatocellular carcinoma cells.

1,3,6,8-Tetrabromocarbazole (1368-BCZ) is identified as an emerging contaminant that exerts angiogenic effects. Multiple studies indicated there was a positive correlation between angiogenesis and nuclear factor kappa B (NF-κB) activation. While the role of NF-κB in inflammation and apoptosis has been well known, the potential biological effects of 1368-BCZ on NF-κB signaling and related mechanism remain unclear. We, therefore, explored the possible effects of 1368-BCZ on the NF-κB pathway at the gene and protein levels and confirmed that NF-κB activation by 1368-BCZ exposure caused an augmented phosphorylated protein level, induction of NF-κB response element (κBRE)-driven luciferase activity and upregulation of transcriptional level of downstream responsive genes. Although 1368-BCZ did not produce detectable changes in hepatic fibrosis in vivo, it obviously altered the apoptosis in human hepatocellular carcinoma (HepG2) cells. Furthermore, the induction of apoptosis was confirmed by the increased cleaved caspase-3 level. These data revealed the activating effects of 1368-BCZ on NF-κB and its involvement in the underlying mechanisms, providing additional information for toxicology studies of emerging contaminants and introducing a mechanism-based toxicological evaluation of emerging pollutants.

Comprehensive Evaluation of College Students' Physical Health and Sports Mode Recommendation Model Based on Decision Tree Classification Model.

Nowadays, more and more college students' physical health is getting worse because of their living habits and self-consciousness. In order to improve the physical quality of college students as much as possible, the experiment uses the improved iterative dichotomiser III (ID3) decision tree to make decisions on the physical condition of some college students and the corresponding sports mode recommendation, and compares the results with the traditional ID3 algorithm. In the experimental results, the information entropy ratio of the improved ID3 algorithm is 89.5%, the operation information loss rate is 4.136%, and the accuracy of motion mode decision is 92.58%. The average relative time is 12.7, and the accuracy of physical health decision making is 90.02%. The above two values are not significant compared with the traditional ID3 algorithm. The experimental results show that the improved ID3 algorithm has significant optimization in the stability of information transmission and the accuracy of sports recommendation decision making, and can be applied to the physical health evaluation and sports recommendation of college students in a certain range.

HIF-1alpha/VEGF pathway mediates 1,3,6,8-tetrabromo-9 H-carbazole-induced angiogenesis: a potential vascular toxicity of an emerging contaminant.

The dioxin-like substances polyhalogenated carbazoles (PHCZs) may trigger the aryl hydrocarbon receptor (AhR) signaling pathway. Although the crosstalk between AhR and the hypoxia inducible factor-1 (HIF-1) pathways is generally believed to occur, the exact mechanisms of the HIF-1 pathway in PHCZ toxicity have not been determined. We aimed to elucidate the effect of PHCZs on the HIF-1 pathway and its involvement in the regulation of target genes of HIF-1. Herein, we employed human HepG2 cells transiently transfected with a hypoxia response element (HRE) luciferase reporter to identify PHCZs that could influence HIF-1 pathway. We found that exposure to one of the four selected PHCZs, specifically 1,3,6,8-tetrabromo-9 H-carbazole (1368-BCZ), induced a significant enhancement of the activity of HRE activity. In silico data supported 1368-BCZ-induced HIF-1α activity preferentially. Moreover, 1368-BCZ significantly upregulated the expression of HIF-1 target genes, including endothelial growth factor (VEGF) and erythropoietin. Importantly, the stimulated secretion of VEGF by 1368-BCZ promoted the angiogenesis in human umbilical vein endothelial cells. Therefore, the present experimental and computational studies provide new and direct evidence of 1368-BCZ - HIF-1 interaction, which sheds light on the HIF-mediated cardiovascular toxicity and allows a knowledge-based risk assessment of emerging pollutants.

How does biased technological progress affect haze pollution? Evidence from APEC economies.

Biased technological progress is the act of energy conservation and emission reduction by changing the marginal rate of substitution. In this study, we introduced renewable energy into a production function, and proposed a method of identifying biased characteristics of technological progress, based on marginal productivity theory. A panel dataset for the Asia-Pacific Economic Cooperation (APEC) economies from 2000 to 2017 was analyzed to explore the effect of biased technological progress in reducing particulate matter (PM2.5). We found that input biased technological progress tended to use more non-renewable energy. Input biased technological progress aggravated haze pollution; however, this effect decreased as the PM2.5 concentration increased. Output biased technological progress significantly reduced haze pollution in high-income economies, but increased it in low-income economies. The effect of neutral technological progress on haze pollution was the opposite of the effect from output biased technological progress. We also found that increasing renewable energy consumption and reducing energy intensity were separate effective paths for input and output biased technological progress, respectively, to mitigate haze pollution. For neutral technological progress, improving total factor productivity was an important way to mitigate haze pollution. Finally, several policy recommendations are proposed to mitigate haze pollution in APEC economies.

Variational Structured Attention Networks for Deep Visual Representation Learning.

Convolutional neural networks have enabled major progresses in addressing pixel-level prediction tasks such as semantic segmentation, depth estimation, surface normal prediction and so on, benefiting from their powerful capabilities in visual representation learning. Typically, state of the art models integrate attention mechanisms for improved deep feature representations. Recently, some works have demonstrated the significance of learning and combining both spatial- and channel-wise attentions for deep feature refinement. In this paper, we aim at effectively boosting previous approaches and propose a unified deep framework to jointly learn both spatial attention maps and channel attention vectors in a principled manner so as to structure the resulting attention tensors and model interactions between these two types of attentions. Specifically, we integrate the estimation and the interaction of the attentions within a probabilistic representation learning framework, leading to VarIational STructured Attention networks (VISTA-Net). We implement the inference rules within the neural network, thus allowing for end-to-end learning of the probabilistic and the CNN front-end parameters. As demonstrated by our extensive empirical evaluation on six large-scale datasets for dense visual prediction, VISTA-Net outperforms the state-of-the-art in multiple continuous and discrete prediction tasks, thus confirming the benefit of the proposed approach in joint structured spatial-channel attention estimation for deep representation learning. The code is available at https://github.com/ygjwd12345/VISTA-Net.

Construction of 2D/2D MoS2/g-C3N4 Heterostructures for Photoreduction of Cr (VI).

2D/2D MoS2/g-C3N4 (MCN) surface heterostructures were created by second thermal polymerization of bulk g-C3N4 and the reaction of thiourea and MoO3 at 670 °C. MoS2 networks grew vertically along the (002) facet on superior thin g-C3N4 nanosheets. The layered heterostructures drastically improved the Cr(VI) removal ability. In the dark case, 27% of Cr(VI) was removed within 45 min. The result indicates that the adsorption of Cr(VI) was a chemical adsorption process involving the sharing and transfer of electrons. The equilibrium data indicate that the adsorbent was covered with a monolayer adsorbate, which conformed to the Langmuir isotherm model (R2 = 0.9618). In addition, MCN nanocomposites could convert Cr(VI) into non-toxic Cr(III) by photoreduction under visible light irradiation. With an optimized composition, 100% of Cr(VI) was removed within 30 min, which was ∼10 times quicker compared with Cr(VI) removal under dark conditions. Because g-C3N4 nanosheets (sample CN670) with higher photocurrent density revealed the lowest photoreduction Cr(VI) ability, adsorption plays an important role in Cr(VI) removal. For MoS2/g-C3N4 nanocomposites used in Cr(VI) removal, adsorption and photoreduction were incorporated together to get excellent performance.

Sl-lncRNA15492 interacts with Sl-miR482a and affects Solanum lycopersicum immunity against Phytophthora infestans.

Long non-coding RNAs (lncRNAs) are involved in the resistance of plants to infection by pathogens via interactions with microRNAs (miRNAs). Long non-coding RNAs are cleaved by miRNAs to produce phased small interfering RNAs (phasiRNAs), which, as competing endogenous RNAs (ceRNAs), function as decoys for mature miRNAs, thus inhibiting their expression, and contain pre-miRNA sequences to produce mature miRNAs. However, whether lncRNAs and miRNAs mediate other molecular mechanisms during plant resistance to pathogens is unknown. In this study, as a positive regulator, Sl-lncRNA15492 from tomato (Solanum lycopersicum Zaofen No. 2) plants affected tomato resistance to Phytophthora infestans. Gain- and loss-of-function experiments and RNA ligase-mediated 5'-amplification of cDNA ends (RLM-5' RACE) also revealed that Sl-miR482a was negatively involved in tomato resistance by targeting Sl-NBS-LRR genes and that silencing of Sl-NBS-LRR1 decreased tomato resistance. Sl-lncRNA15492 inhibited the expression of mature Sl-miR482a, whose precursor was located within the antisense sequence of Sl-lncRNA15492. Further degradome analysis and additional RLM-5' RACE experiments verified that mature Sl-miR482a could also cleave Sl-lncRNA15492. These results provide a mechanism by which lncRNAs might inhibit precursor miRNA expression through antisense strands of lncRNAs, and demonstrate that Sl-lncRNA15492 and Sl-miR482a mutually inhibit the maintenance of Sl-NBS-LRR1 homeostasis during tomato resistance to P. infestans.

Does environment-biased technological progress reduce CO2 emissions in APEC economies? Evidence from fossil and clean energy consumption.

Environment-biased technological progress plays a critical role in carbon reduction, while the association among environment-biased technological progress, energy consumption, and carbon emissions has not been paid enough attention. Working with a unique spatial panel dataset of APEC economies spanning the 2000-2017 period, we employed the nonspatial panel model and the spatial panel model to investigate the role of fossil energy (FE) and clean energy (CE) consumption in carbon dioxide (CO2) abatement through environment-biased technological progress (EBTP). We decomposed EBTP into both emission-reducing biased technological progress (ErBTP) and energy-saving biased technological progress (EsBTP). The results show that the direct effect of EBTP on CO2 emissions was significantly negative and that the direct effect of ErBTP was significantly larger than that of EsBTP. EBTP reduced CO2 emissions through CE consumption, whereas it increased CO2 emissions through FE consumption, that is, EBTP had a "backfire effect" on FE consumption. More into detail, ErBTP had a larger effect on CO2 emissions in developing economies, while EsBTP played a more important role in developed economies. Furthermore, the results of the robustness test were consistent with our findings. Finally, several policy options were suggested to reduce CO2 emissions in APEC economies.

Tomato lncRNA23468 functions as a competing endogenous RNA to modulate NBS-LRR genes by decoying miR482b in the tomato-Phytophthora infestans interaction.

Our previous studies indicated that tomato miR482b could negatively regulate the resistance of tomato to Phytophthora infestans and the expression of miR482b was decreased after inoculation with P. infestans. However, the mechanism by which the accumulation of miR482b is suppressed remains unclear. In this study, we wrote a program to identify 89 long noncoding RNA (lncRNA)-originated endogenous target mimics (eTMs) for 46 miRNAs from our RNA-Seq data. Three tomato lncRNAs, lncRNA23468, lncRNA01308 and lncRNA13262, contained conserved eTM sites for miR482b. When lncRNA23468 was overexpressed in tomato, miR482b expression was significantly decreased, and the expression of the target genes, NBS-LRRs, was significantly increased, resulting in enhanced resistance to P. infestans. Silencing lncRNA23468 in tomato led to the increased accumulation of miR482b and decreased accumulation of NBS-LRRs, as well as reduced resistance to P. infestans. In addition, the accumulation of both miR482b and NBS-LRRs was not significantly changed in tomato plants that overexpressed lncRNA23468 with a mutated eTM site. Based on the VIGS system, a target gene of miR482b, Solyc02g036270.2, was silenced. The disease symptoms of the VIGS-Solyc02g036270.2 tomato plants were in accordance with those of tomato plants in which lncRNA23468 was silenced after inoculation with P. infestans. More severe disease symptoms were found in the modified plants than in the control plants. Our results demonstrate that lncRNAs functioning as eTMs may modulate the effects of miRNAs in tomato and provide insight into how the lncRNA23468-miR482b-NBS-LRR module regulates tomato resistance to P. infestans.

LncRNA33732-respiratory burst oxidase module associated with WRKY1 in tomato- Phytophthora infestans interactions.

Our previous studies indicated that tomato WRKY1 transcription factor acts as a positive regulator during tomato resistance to Phytophthora infestans. However, the molecular mechanism of WRKY1-mediated resistance regulation remains unclear. Here, we used a comparative transcriptome analysis between wild-type and WRKY1-overexpressing tomato plants to identify differentially expressed genes (DEGs) and long non-coding RNAs (DELs), and we examined long non-coding RNA (lncRNA)-gene networks. The promoter sequences of the upregulated DEGs and DELs were analyzed. Among 1073 DEGs and 199 DELs, 1 kb 5'-upstream regions of 59 DEGs and 22 DELs contain the W-box, the target sequence of the WRKY1. The results of promoter-ß-glucuronidase (GUS) fusion and yeast one-hybrid assay showed that lncRNA33732 was activated by WRKY1 through sequence-specific interactions with the W-box element in its promoter. The overexpression and silencing analysis of lncRNA33732 in tomato showed that lncRNA33732 acts as a positive regulator and enhanced tomato resistance to P. infestans by induction of the expression of respiratory burst oxidase (RBOH) and increase in the accumulation of H2 O2 . When the expression of RBOH gene was inhibited in tomato plants, H2 O2 accumulation decreased and resistance were impaired. These findings suggest that lncRNA33732 activated by WRKY1 induces RBOH expression to increase H2 O2 accumulation in early defense reaction of tomato to P. infestans attack. Our results provide insights into the WRKY1-lncRNA33732-RBOH module involved in the regulation of H2 O2 accumulation and resistance to P. infestans, as well as provide candidates to enhance broad-spectrum resistance to pathogens in tomato.

Comparative transcriptome analysis shows the defense response networks regulated by miR482b.

KEY MESSAGE: The transcriptomic profile in the leaves of miR482b-overexpressing tomato plants revealed that miR482b may suppress alpha-linolenic acid metabolism, cysteine and methionine metabolism, plant-pathogen interaction, and the MAPK pathway to reduce resistance to Phytophthora infestans. Our previous study showed that tomato miR482b acted as a negative regulator during tomato resistance to Phytophthora infestans by silencing NBS-LRR genes. To investigate pathways related to miR482b, the transcriptomic profile of tomato plants that overexpressed miR482b was constructed. A total of 47,124,670 raw sequence reads from the leaves of miR482b-overexpressing tomato plants were generated by Illumina sequencing. A total of 746 genes in miR482b-overexpressing tomato plants were found to show significantly differential expression relative to those in wild-type tomato plants, including 132 up-regulated genes and 614 down-regulated genes. GO and KEGG enrichment analyses showed that plant-pathogen interaction, the MAPK pathway, and the pathways related to JA and ET biosynthesis were affected by miR482b in tomato. qRT-PCR results showed that all the enriched genes in these pathways were down-regulated in tomato plants that overexpressed miR482b and up-regulated in tomato plants that overexpressed an NBS-LRR gene (Soly02g036270.2, the target gene of miR482b). After P. infestans infection, the expression of the enriched genes showed a time-dependent response, and the genes played different roles between resistant tomato (Solanum pimpinellifolium L3708) and tomato susceptible to P. infestans (S. lycopersicum Zaofen No. 2). Our results have, therefore, demonstrated that miR482b is an important component of defense response network. This will also help to identify candidate genes involved in plant-pathogen interaction.

Tomato MYB49 enhances resistance to Phytophthora infestans and tolerance to water deficit and salt stress.

MAIN CONCLUSION: MYB49-overexpressing tomato plants showed significant resistance to Phytophthora infestans and tolerance to drought and salt stresses. This finding reveals the potential application of tomato MYB49 in future molecular breeding. Biotic and abiotic stresses severely reduce the productivity of tomato worldwide. Therefore, it is necessary to find key genes to simultaneously improve plant resistance to pathogens and tolerance to various abiotic stresses. In this study, based on homologous relationships with Arabidopsis R2R3-MYBs (AtMYBs) involved in responses to biotic and abiotic stresses, we identified a total of 24 R2R3-MYB transcription factors in the tomato genome. Among these tomato R2R3-MYBs, MYB49 (Solyc10g008700.1) was clustered into subgroup 11 by phylogenetic analysis, and its expression level was significantly induced after treatment with P. infestans, NaCl and PEG6000. Overexpression of MYB49 in tomato significantly enhanced the resistance of tomato to P. infestans, as evidenced by decreases in the number of necrotic cells, sizes of lesion, abundance of P. infestans, and disease index. Likewise, MYB49-overexpressing transgenic tomato plants also displayed increased tolerance to drought and salt stresses. Compared to WT plants, the accumulation of reactive oxygen species (ROS), malonaldehyde content, and relative electrolyte leakage was decreased, and peroxidase activity, superoxide dismutase activity, chlorophyll content, and photosynthetic rate were increased in MYB49-overexpressing tomato plants under P. infestans, salt or drought stress. These results suggested that tomato MYB49, as a positive regulator, could enhance the capacity to scavenge ROS, inhibit cell membrane damage and cell death, and protect chloroplasts, resulting in an improvement in resistance to P. infestans and tolerance to salt and drought stresses, and they provide a candidate gene for tomato breeding to enhance biotic stress resistance and abiotic stress tolerance.

The hypoxia-mimetic agent CoCl2 induces chemotherapy resistance in LOVO colorectal cancer cells.

Hypoxia, which is an important factor that mediates tumor progression and poor treatment response, is particularly associated with tumor chemoresistance. However, the molecular mechanisms underlying hypoxia-induced colorectal cancer chemoresistance remain unclear. The present study aimed to explore the mechanism underlying hypoxia­induced chemotherapy resistance in LOVO colorectal cancer cells. LOVO cells were cultured in a hypoxic environment simulated by cobalt chloride (CoCl2), which is a chemical inducer of hypoxia­inducible factor­1α (HIF­1α). HIF­1α is a transcription factor that has an important role in tumor cell adaptation to hypoxia, and controls the expression of several genes. Various CoCl2 concentrations are often used to simulate degrees of hypoxia. In the present study, following treatment with CoCl2, an MTT assay was conducted to determine the growth and drug sensitivity of LOVO cells. Reverse transcription­polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of HIF­1α and factors associated with chemotherapy resistance, including multidrug resistance protein (MRP) and multidrug resistant 1 (MDR1), which encodes the major transmembrane efflux transporter P­glycoprotein (P­gp). In addition, the expression levels of apoptosis­related proteins, including B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein (Bax) and Bcl­2­associated agonist of cell death (Bad) were detected by western blotting. Flow cytometry (FCM) was used to visually observe Adriamycin (ADR) accumulation and retention, thus analyzing intracellular drug transportation in cells under hypoxic and normoxic conditions. CoCl2­simulated hypoxia was able to inhibit tumor cell proliferation, and upregulate the expression levels of HIF­1α, MDR1/P­gp and MRP. In addition, proapoptotic members of the Bcl­2 protein family, Bax and Bad, were downregulated. The anti­apoptotic member Bcl­2 exhibited no significant change in expression, whereas the ratio of Bcl­2/Bax was increased. Results of FCM demonstrated that the intracellular retention of ADR was significantly decreased in the hypoxia group cells. In conclusion, the present study revealed that a CoCl2-simulated hypoxic microenvironment was able to effectively induce chemoresistance and reduce apoptosis in LOVO cells.