Cyano-deficient g-C3N4 for round-the-clock photocatalytic degradation of tetracycline: Mechanism and application prospect evaluation.

Without light at night, the system for photocatalytic degradation of refractory organic pollutants in aquatic environments based on free radicals will fall into a dormant state. Hence, a round-the-clock photocatalyst (CCN@SMSED) was prepared by in situ growth of cyanide-deficient g-C3N4 on the surface of Sr2MgSi2O7:Eu2+,Dy3+ through a simple calcination method. The CCN@SMSED exhibits an outstanding oxidative degradation ability for refractory tetracycline (TC) in water under both light and dark conditions, which is attributed to the synergistic effect of free radical (•O2- and •OH) and non-radical (h+ and 1O2). Electrochemical analyses further indicate that direct electron transfer (DET) is also one of the reasons for the efficient degradation of TC. Remarkably, the continuous working time of the round-the-clock photocatalyst in a dark environment was estimated for the first time (about 2.5 h in this system). The degradation pathways of TC mainly include demethylation, ring opening, deamination and dehydration, and the growth of Staphylococcus aureus shows that the process is biosafe. More importantly, CCN@SMSED holds significant promise for practical application due to its low energy consumption and suitability for removing TC from a variety of complex water bodies. This work provides an energy consumption reference for the practical application of round-the-clock photocatalytic degradation of organic pollutants.

Insight into the effect of UVC-based advanced oxidation processes on the interaction of typical microplastics and their derived disinfection byproducts during disinfection.

The 10 µm polystyrene and polyethylene-terephthalate microplastics (MPs), prevalent in finished drink water, were employed to investigate the effect of normal dosage UVC-based advanced-oxidation-processes (UVC-AOPs) on the interaction between MPs and their derived disinfection-byproducts (DBPs) during subsequent chlorination-disinfection, in the presence of Br-, for the first time. The results indicated that UVC/H2O2 caused higher leaching of microplastic-derived dissolved-organic-matter (MP-DOM), with smaller and narrower molecular-weight-distribution than UVC and UVC/peroxymonosulfate (UVC/PMS). The trihalomethanes (as dominant DBPs) molar-formation-potentials (THMs-MFPs) for MP-DOM leached in different UVC-AOPs followed the order of UVC/H2O2>UVC/PMS>UVC. The adsorption of formed THMs, especially Br-THMs, back on MPs was observed in all MPs suspensions with or without UVC-AOPs pre-treatment. The Cl-THMs adsorption by MPs is more sensitive to UVC-AOPs than Br-THMs. The adsorption experiments showed that UVC-AOPs reduce the capacity but increase the rate of THMs adsorption by MPs, suggesting the halogen and hydrogen bonding forces governed the THMs adsorption rate while hydrophobic interaction determines their adsorption capacity. The UVC-AOPs pre-treatment sharply increased the total yield of THMs via both indirectly inducing MP-DOM leaching and directly increasing the THMs-MFPs of MPs by oxidation. 21.36-41.96% of formed THMs adsorbed back on the UVC-AOPs-pretreated MPs, which might increase the toxicity of MPs.

Transcription profiles and phenotype reveal global response of Staphylococcus aureus exposed to ultrasound and ultraviolet stressors.

Ultrasound and ultraviolet light have good inactivation performance against pathogens in sewage. In this study, the inactivation mechanisms of 60 kHz ultrasound and ultraviolet radiation against Staphylococcus aureus (S. aureus) were studied from the perspectives of cell phenotype and transcriptome for the first time. The results showed that both ultrasound and ultraviolet treatments had adverse impacts on the cellular morphology of S. aureus to varying degrees at cellular level. The transcriptomic analysis revealed that there were 225 and 1077 differentially expressed genes (DEGs) in the ultrasound and ultraviolet treatments, respectively. The result revealed that both ultrasound and ultraviolet could interfere with the expression of the genes involved in ABC transporters, amino acid and fatty acid metabolism to influence the membrane permeability. Besides the membrane permeability, ultraviolet also could disturb the ATP synthesis, DNA replication and cell division through restraining the expression of several genes related to carbohydrate metabolism, peptidoglycan synthesis, DNA-binding/repair protein synthesis. Compared with the single inactivation pathway of ultrasound, ultraviolet inactivation of S. aureus is multi-target and multi-pathway. We believe that the bactericidal mechanisms of ultrasound and ultraviolet radiation presented by this study could provide theoretical guidance for the synergistic inactivation of pathogens in sewage by ultrasound and ultraviolet radiation in the future.

Insight into the synergistic mechanism of sonolysis and sono-induced BiFeO3 nanorods piezocatalysis in atenolol degradation: Ultrasonic parameters, ROS and degradation pathways.

Herein, BiFeO3 nanorods (BFO NRs) was synthesized as the piezoelectric catalyst. The synergistic mechanism of sonolysis and sono-induced BFO-piezocatalysis in atenolol degradation was revealed and the effect of ultrasonic parameters on it was investigated for the first time. The results indicated that 100 kHz was the optimal frequency for the sonolytic and sono-piezocatalytic degradation of atenolol in ultrasound/BFO nanorods (US/BFO NRs) system, with the highest synergistic coefficient of 3.43. The piezoelectric potential differences of BFO NRs by COMSOL Multiphysics simulations further distinguishing that the impact of cavitation shock wave and ultrasonic vibration from sonochemistry reaction (i.e., 2.48, -2.48 and 6.60 V versus 0.008, -0.008 and 0.02 V under tensile, compressive and shear stress at 100 kHz). The latter piezoelectric potentials were insufficient for reactive-oxygen-species (ROS) generation, while the former contributed to 53.93% •OH yield in US/BFO NRs system. Sono-piezocatalysis was found more sensitive to ultrasonic power density than sonolysis. The quenching experiments and ESR tests indicated that the ROS contribution in atenolol degradation followed the order of •OH > 1O2 > h+ > O2•- in US/BFO NRs system and 1O2 generation is exclusively dissolved-oxygen dependent. Four degradation pathways for atenolol in US/BFO NRs system were proposed via products identification and DFT calculation. Toxicity assessment by ECOSAR suggested the toxicity of the degradation products could be controlled.

Modulation of plant development and chilling stress responses by alternative splicing events under control of the spliceosome protein SmEb in Arabidopsis.

Cold stress resulting from chilling and freezing temperatures substantially inhibits plant growth and reduces crop production worldwide. Tremendous research efforts have been focused on elucidating the molecular mechanisms of freezing tolerance in plants. However, little is known about the molecular nature of chilling stress responses in plants. Here we found that two allelic mutants in a spliceosome component gene SmEb (smeb-1 and smeb-2) are defective in development and responses to chilling stress. RNA-seq analysis revealed that SmEb controls the splicing of many pre-messenger RNAs (mRNAs) under chilling stress. Our results suggest that SmEb is important to maintain proper ratio of the two COP1 splicing variants (COP1a/COP1b) to fine tune the level of HY5. In addition, the transcription factor BES1 shows a dramatic defect in pre-mRNA splicing in the smeb mutants. Ectopic expression of the two BES1 splicing variants enhances the chilling sensitivity of the smeb-1 mutant. Furthermore, biochemical and genetic analysis showed that CBFs act as negative upstream regulators of SmEb by directly suppressing its transcription. Together, our results demonstrate that proper alternative splicing of pre-mRNAs controlled by the spliceosome component SmEb is critical for plant development and chilling stress responses.

Sulfidised nanoscale zerovalent iron-modified pitaya peel-derived carbon for enrofloxacin degradation and swine wastewater treatment: Combination of electro-Fenton and bio-electro-Fenton process.

In this study, a new Fenton system combining electro-Fenton and bio-electro-Fenton (EF-BEF) processes was proposed for ENR degradation and swine wastewater treatment, and pitaya peel-derived carbon modified with sulfidised nanoscale zerovalent iron (SnZVI) was developed as a catalyst for the system. The as-prepared PPC-800 carbon displayed a hierarchical porous structure (693.5 m2/g), abundant oxygen-containing groups, and carbon defects, which endowed it with a good adsorption capacity, high H2O2 generation capacity (151.9 ± 10.5 mg/L) during the EF period, and good power production performance (194.3 ± 12.50 mW/m2) during the BEF period. When modified with SnZVI, despite the decrease in the adsorption capacity and power output (102.05 ± 4.05 mW/m2), the SnZVI@PPC-2 exhibited the best ENR removal performance with that of 98.9 ± 0.2% in the EF period and 86.2 ± 5.6% during the BEF period. An increase in the current intensity and air flow rate promoted ENR degradation. Finally, swine wastewater was treated using the SnZVI@PPC-2 EF-BEF system, and 97.9 ± 1.3% of the TOC was removed using the combined system.

Liquid-liquid phase separation of RBGD2/4 is required for heat stress resistance in Arabidopsis.

As sessile organisms, plants are highly sensitive to environmental stresses. In response to stresses, globally repressed translation initiation leads to stress granule (SG) formation. Protein liquid-liquid phase separation (LLPS) contributes to SG formation, but a direct link between protein LLPS and stress resistance has not yet been found in plants. Here, we report that two RNA-binding proteins, RBGD2 and RBGD4, function redundantly to improve heat resistance in Arabidopsis. RBGD2 and RBGD4 undergo LLPS in vitro and condense into heat-induced SGs in vivo via tyrosine residue array (TRA). Importantly, disrupting LLPS by mutating TRA abolishes RBGD2/4 condensation in SGs and impairs their protective function against heat stress (HS). Further study found that upon HS, the RBGD2/4 interaction network expands with additional SG proteins and heat-responsive mRNA. Our work shows a mechanistic basis that underlies protein LLPS in HS response in plants and suggests manipulation of protein LLPS as a general strategy to improve plant stress resistance.

New insight into the regulation mechanism of visible light in naproxen degradation via activation of peroxymonosulfate by MOF derived BiFeO3.

BiFeO3 (BFO) nanocage prepared by metal-organic-framework derivatization (MOF-d) was adopted as activator to first investigate the effect mechanism of visible-light on naproxen-degradation via peroxymonosulfate (PMS) activation. MOF-d BFO expressed more excellent PMS activation ability than hydrothermal-synthetic BFO, due to highly ordered mesopores. A 3.0 times higher pseudo-first-order degradation rate constant was achieved after visible-light introduced. The quenching experiments indicated that the contribution of ROS in naproxen degradation followed the order of SO4•->1O2 ≈ â€¢OH in MOF-d BFO/PMS/dark system, while changed into h+>1O2 > >O2•-≈SO4•-> â€¢OH after visible-light introduced. EPR tests first revealed that visible-light promoted 1O2 yield (non-radical pathway) but suppressed •OH and SO4•- generation (free-radical pathways). N2-purging experiments further proved that 1O2 primarily originates from the reaction between h+ and PMS, equivalently to that between O2 and e--h+ in MOF-d BFO/PMS/vis system. Under visible-light, PMS activation via Fe (III) might be hindered by e- filling on Fe 3d orbital and anion PMS preferred to approach h+ rather than e-, resulting in the decrease of •OH and SO4•- yields. Moreover, PMS faces competition from adsorbed-O2 and oxygen-vacancies for e- capture. The degradation-pathways for naproxen in dark and under visible light were both proposed in MOF-d BFO/PMS system.

SUMO E3 ligase SIZ1 negatively regulates arsenite resistance via depressing GSH biosynthesis in Arabidopsis.

Arsenic is a metalloid toxic to plants, animals and human beings. Small ubiquitin-like modifier (SUMO) conjugation is involved in many biological processes in plants. However, the role of SUMOylation in regulating plant arsenic response is still unclear. In this study, we found that dysfunction of SUMO E3 ligase SIZ1 improves arsenite resistance in Arabidopsis. Overexpression of the dominant-negative SUMO E2 variant resembled the arsenite-resistant phenotype of siz1 mutant, indicating that SUMOylation plays a negative role in plant arsenite detoxification. The siz1 mutant accumulated more glutathione (GSH) than the wild type under arsenite stress, and the arsenite-resistant phenotype of siz1 was depressed by inhibiting GSH biosynthesis. The transcript levels of the genes in the GSH biosynthetic pathway were increased in the siz1 mutant comparing with the wild type in response to arsenite treatment. Taken together, our findings revealed a novel function of SIZ1 in modulating plant arsenite response through regulating the GSH-dependent detoxification.

Characteristics of extracellular organic matters and the formation potential of disinfection by-products during the growth phases of M. aeruginosa and Synedra sp.

Extracellular organic matter (EOM) is an important precursor of disinfection by-products (DBPs). Nowadays, little is known about changes in molecular weight (MW) and hydrophilic (HPI)/hydrophobic (HPO) fractions of EOM during the entire algal growth phase. In this study, a combined approach of fractionation procedure and parallel factor (PARAFAC) analysis was applied to characterize the EOM during the entire growth phase of two algal species (M. aeruginosa and Synedra sp.), and investigated the relationships between fluorescent component and the DBP formation potential (FP) in MW and HPI/HPO fractions. Thereinto, three components (including one protein-like component (C1), one humic-like component (C2), and one fulvic acid-like component (C3)) were identified by the PARAFAC model. For two algae, the HPI and high MW (> 100 kDa) fractions were both the main components of algal EOM in the three growth phases in terms of the dissolved organic carbon. The high MW fraction had more C1 compared with other MW fractions, especially for M. aeruginosa. Besides, the formation risk of EOM-derived DBPs from M. aeruginosa was lower than that from Synedra sp. The result of this study showed the FP of DBPs varied with fluorescent components of algal EOM fractions and also indicated that the humic-like substances were tended to form trichloromethane and the tryptophan-like substances were associated with dichloroacetic acid by canonical correspondence analysis for both two algae.

The comfort assessment in healthy adults during constant-flow mode in noninvasive ventilator.

BACKGROUND: From the point of view of machine construction and hydrodynamics, this paper innovatively proposes that the essence of high-flow nasal cannula (HFNC) is a constant-flow mode in noninvasive ventilator (NIVCFM). This study enrolled healthy adults as study subjects to assess the subjective comfort assessed by visual analog scoring scale of NIVCFM/HFNC and objective comfort measured by the noise level generated by NIVCFM/HFNC, aiming to provide a scientific basis for the rational clinical application of NIVCFM/HFNC. METHODS: Forty-four healthy adults participated in this study. The noise generated by NIVCFM/HFNC is measured, and the comfort is evaluated during NIVCFM delivery at flow rates of 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 L/min. RESULTS: When the ventilator flow rate is 60 L/min, the maximum noise is 65.9 dB, increasing noise by 23.7 dB from a baseline of 42.2 dB at the flow rate of 0 L/min. There was a strong nonlinear positive correlation between the noise level and the flow rates. The median score for dry mouth, nose or throat, dysphagia, sore throat, and other discomfort was 0. The median score for dyspnea was 0 at 0-30 L/min, 1 at 35-55 L/min, and 2 at 60 L/min. CONCLUSIONS: The grater the flow rate, the greater the noise generated by NIVCFM/HFNC (<65.9 dB). The maximum flow rate that most healthy adults can able to tolerate is 30 L/min, and the main discomfort is dyspnea.

Enhanced bezafibrate degradation and power generation via the simultaneous PMS activation in visible light photocatalytic fuel cell.

A collaborative system including peroxymonosulfate (PMS) activation in a photocatalytic fuel cell (PFC) with an BiOI/TiO2 nanotube arrays p-n type heterojunction as photoanode under visible light (PFC(BiOI/TNA)/PMS/vis system) was established. Xenon lamp was used as the light source of visible light. A 4.6 times higher pseudo-first-order bezafibrate (BZF) degradation rate constant was achieved in this system compared with the single PFC(BiOI/TNA)/vis system. The radical quenching experiments revealed that the contribution of reactive oxidative species (ROS) followed the order of 1O2 ≈ h+ >> •OH > SO4•- >>O2•-. The EPR tests demonstrated that PMS addition enlarged the formation of 1O2, •OH and SO4•-, but suppressed O2•- yield. Interestingly, 1O2 was further proved to dominantly originated from the priority reaction between positive photoinduced holes (h+) and negatively charged PMS. Besides, N2-purging tests and density functional theory calculation indicated that PMS probably reacted with residual photoinduced electron (e-) on the more negative conduction band (CB) of BiOI to form •OH and SO4•-, but competed with dissolved oxygen. Other e- transferred to the less negative CB of TNA through p-n junction will efficiently move to cathode through the external circuit. The greatly promoted power generation of PFC system was observed after PMS addition due to extra h+ consumption and efficient e- separation and transfer. Besides, three possible pathways for BZF degradation were proposed including hydroxylation, fibrate chain substituent and amino bond fracture. This study can provide new insights into the mechanisms of PMS assisted photocatalysis and accompanying energy recovery.

Ultrasound-enhanced coagulation for cyanobacterial removal: Effects of ultrasound frequency and energy density on coagulation performance, leakage of intracellular organic matters and toxicity.

Ultrasound-enhanced coagulation is capable of effectively removing algal cells in algae-laden water. However, study differences in ultrasound settings, algal cell conditions and coagulant properties complicate the accurate evaluation of this technique for practical applications. No study has yet compared algae (and algal organic matters) removal among different frequencies of ultrasound in the ultrasound-coagulation process. In this study, the ultrasound at three typical frequencies, 29.4, 470 and 780 kHz, were applied for this purpose. The results showed that high-frequency ultrasound at 470 and 780 kHz had substantially greater improvement of coagulation than low-frequency ultrasound at 29.4 kHz (For example, the turbidity removal at 1 mg-Al/L of polymeric aluminum chloride increased by 204.2%, 571.9% and 563.2% under 29.4, 470 and 780 kHz ultrasound-coagulation, respectively, at 3.42 J/mL). Algal cells exhibited irreversible physical damage and the release of intracellular organic matters (such as odorous compounds) under low-frequency ultrasound with energy densities ≥ 3.42 J/mL, whereas high-frequency ultrasound was characterized by nonviolent impairment, including oxidative degradation and gas vacuole destruction (particularly reversible) resulting from ultrasound-induced radicals and cell resonance, respectively. Avoiding the severe destruction of algal cells is crucial for minimizing the toxicity and secondary pollution of the treated water. To achieve satisfactory removal, protected safety and better economy, the optimal energy density for each frequency was also determined. The findings from the analyses of the laboratory-cultured sample were confirmed via real eutrophic surface water. This study provides new insights and guidance for the ongoing study of harmful algal removal by ultrasound-enhanced coagulation.

The Arabidopsis spliceosomal protein SmEb modulates ABA responses by maintaining proper alternative splicing of HAB1.

Abscisic acid (ABA) signaling is critical for seed germination and abiotic stress responses in terrestrial plants. Pre-mRNA splicing is known to regulate ABA signaling. However, the involvement of canonical spliceosomal components in regulating ABA signaling is poorly understood. Here, we show that the spliceosome component Sm core protein SmEb plays an important role in ABA signaling. SmEb expression is up-regulated by ABA treatment, and analysis of Arabidopsis smeb mutant plants suggest that SmEb modulates the alternative splicing of the ABA signaling component HAB1 by enhancing the HAB1.1 splicing variant while repressing HAB1.2. Overexpression of HAB1.1 but not HAB1.2 rescues the ABA-hypersensitive phenotype of smeb mutants. Mutations in the transcription factor ABI3, 4, or 5 also reduce the ABA hypersensitivity of smeb mutants during seed germination. Our results show that the spliceosomal component SmEb plays an important role in ABA regulation of seed germination and early seedling development.

The Roles of Sono-induced Nitrosation and Nitration in the Sono-degradation of Diphenylamine in Water: Mechanisms, Kinetics and Impact Factors.

The potential risks of sono-induced nitrosation and nitration side reactions and consequent toxic nitrogenous byproducts were first investigated via sono-degradation of diphenylamine (DPhA) in this study. The kinetic models for overall DPhA degradation and the formation of nitrosation byproduct (N-nitrosodiphenylamine, NDPhA) and nitration byproducts (2-nitro-DPhA and 4-nitro-DPhA) were well established and fitted (R2 > 0.98). Nitrosation contributed much more than nitration (namely, 43.3 - 47.3 times) to the sono-degradation of DPhA. The contribution of sono-induced nitrosation ranged from 0.4 to 56.6% at different conditions. The maximum NDPhA formation rate and the contribution of sono-induced nitrosation were obtained at 600 and 200 kHz, respectively, as ultrasonic frequencies at 200 to 800 kHz. Both NDPhA formation rate and the contribution of sono-induced nitrosation increased with increasing power density, while decreased with increasing initial pH and DPhA concentration. PO43-, HCO3-, NH4+ and Fe2+ presented negative impacts on sono-induced nitrosation in order of HCO3- >> Fe2+ > PO43- > NH4+, while Br- exhibited a promoting effect. The mechanism of NDPhA formation via sono-induced nitrosation was first proposed.

[NLS-RARα transports into the nucleus by binding to importin α1/ß2(KPNA2/KPNB1) and inhibits the differentiation of U937 cells].

Objective To investigate the inhibitory effect of abnormal nuclear localization of the nuclear localization signal-retinoic acid receptor α (NLS-RARα) on cell differentiation and its mechanism of nuclear transport. Methods Over-expression of HA-NLS-RARα and empty vector in HEK293T cells and U937 cells were achieved through a lentivirus vector and were assigned as NLS-RARα over-expression (NR) group and negative control (NC) group. Extracted nucleoproteins and cytosolic proteins of NC and NR groups of HEK293T cells and U937 cells were detected by Western blot analysis in order to demonstrate the localization of NLS-RARα. Meanwhile, immunofluorescence assay was performed to explore the localization of NLS-RARα. The real-time quantitative PCR and Western blot analysis were used to detect difference in the mRNA and protein expression of CD11b and CEBPß in the NR cells treated with 1, 25-dihydroxyvitamin D3 (1, 25D3) compared with NC cells treated with 1, 25D3. Mass spectrometric analysis and co-immunoprecipitation were conducted to screen the transport proteins which were associated with NLS-RARα, which was followed by the verification of nuclear accumulation of NLS-RARα by the transfection of transport protein small interfering RNA. Results Western blot assay and immunofluorescence showed that NLS-RARα was mainly located in the nucleus. And the qRT-PCR analysis and western blot assay showed a significant decrease in the mRNA and protein expression of CD11b and CEBPß in the NR group compared with the NC group. It demonstrated that NLS-RARα inhibited cell differentiation. Mass spectrometric analysis and COIP demonstrated that KPNA2 (importin α1) and KPNB1 (importin ß1) interacted with NLS-RARα, and the knockdown of KPNA2/KPNB1 inhibited the nuclear accumulation of NLS-RARα. Conclusion Abnormal localization of NLS-RARα inhibits cell differentiation via binding to KPNA2 and KPNB1 into the nucleus.

Reciprocal regulation between nicotinamide adenine dinucleotide metabolism and abscisic acid and stress response pathways in Arabidopsis.

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme that has emerged as a central hub linking redox equilibrium and signal transduction in living organisms. The homeostasis of NAD is required for plant growth, development, and adaption to environmental cues. In this study, we isolated a chilling hypersensitive Arabidopsis thaliana mutant named qs-2 and identified the causal mutation in the gene encoding quinolinate synthase (QS) critical for NAD biosynthesis. The qs-2 mutant is also hypersensitive to salt stress and abscisic acid (ABA) but resistant to drought stress. The qs-2 mutant accumulates a reduced level of NAD and over-accumulates reactive oxygen species (ROS). The ABA-hypersensitivity of qs-2 can be rescued by supplementation of NAD precursors and by mutations in the ABA signaling components SnRK2s or RBOHF. Furthermore, ABA-induced over-accumulation of ROS in the qs-2 mutant is dependent on the SnRK2s and RBOHF. The expression of QS gene is repressed directly by ABI4, a transcription factor in the ABA response pathway. Together, our findings reveal an unexpected interplay between NAD biosynthesis and ABA and stress signaling, which is critical for our understanding of the regulation of plant growth and stress responses.

NLS-RARα blocks cell differentiation by inhibiting the retinoic acid signalling pathway.

A majority of acute promyelocytic leukaemia (APL) cases are characterized by the PML-RARα fusion gene. Previous studies have shown that neutrophil elastase (NE) can cleave PML-RARα and is important for the development of APL. Here, we demonstrate that one of the cleavage products of PML-RARα, NLS-RARα, can block cell differentiation by repressing the expression of the target genes within the retinoic acid signalling pathway. The results of reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis showed that NLS-RARα depressed the expression of the cell differentiation marker protein, CD11b and CEBPß, as well as the retinoic acid signalling pathway target genes, RARß and CEBPε. Studies have shown that NLS-RARα forms heterodimers with retinoid X receptor α(RXRα) and interacts with SMRT. When treated with all-trans retinoic acid (ATRA), NLS-RARα exhibits diminished transcriptional activity compared to RARα. Moreover, in the presence of high doses of ATRA, NLS-RARα could be degraded along with the consequent transactivation of retinoic acid signalling pathway target genes and cell differentiation induction in a dose- and time-dependent manner. Together, these results indicate that NLS-RARα blocks cell differentiation by inhibiting the retinoic acid signalling pathway.