Integrated Physiologic and Proteomic Analyses Reveal the Molecular Mechanism of Navicula sp. in Response to Ultraviolet Irradiation Stress.

With the continuous development of space station construction, space ecosystem research has attracted increasing attention. However, the complicated responses of different candidate plants and algae to radiation stress remain unclear. The present study, using integrated physiologic and proteomic analyses, was carried out to reveal the molecular mechanism of Navicula sp. in response to ultraviolet (UV) irradiation stress. Under 12~24 h of high-dose UV irradiation conditions, the contents of chlorophyll and soluble proteins in Navicula sp. cells were significantly higher than those in the control and 4~8 h of low-dose UV irradiation groups. The activity of catalase (CAT) increased with the extension of irradiation time, and the activity of superoxide dismutase (SOD) decreased first and then increased. Furthermore, differential volcano plot analysis of the proteomic data of Navicula sp. samples found only one protein with a significant difference. Differential protein GO analysis unveiled that UV irradiation can activate the antioxidant system of Navicula sp. and further impact photosynthesis by affecting the photoreaction and chlorophyll synthesis of Navicula sp. The most significant differences in KEGG pathway analysis were also associated with photosynthesis. The above results indicate that Navicula sp. has good UV radiation resistance ability by regulating its photosynthetic pigment content, photosynthetic activity, and antioxidant system, making it a potential candidate for the future development of space ecosystems.

Transient Coupling between Infragranular and Subplate Layers to Layer 1 Neurons Before Ear Opening and throughout the Critical Period Depends on Peripheral Activity.

Cortical layer 1 (L1) contains a diverse population of interneurons that can modulate processing in superficial cortical layers, but the intracortical sources of synaptic input to these neurons and how these inputs change over development and with sensory experience is unknown. We here investigated the changing intracortical connectivity to L1 in the primary auditory cortex (A1) of mice of both sexes in in vitro slices across development using laser-scanning photostimulation. Before postnatal day (P)10, L1 cells receive excitatory input from within L1, L2/3, L4, and L5/6 as well as from subplate. Excitatory inputs from all layers increase, especially from L4, and peak during P10-P16, around the peak of the critical period for tonotopy. Inhibitory inputs followed a similar pattern. Functional circuit diversity in L1 emerges after P16. In adults, L1 neurons receive ascending inputs from L2/3 and L5/6, but only few inputs from L4. The transient hyperconnectivity from deep layers but not L2/3 is absent in deaf mice. Our results demonstrate that deep excitatory and superficial inhibitory circuits are tightly linked in early development and might provide a functional scaffold for the layers in between. These results suggest that early thalamically driven spontaneous and sensory activity in subplate can be relayed to L1 from the earliest ages on and shape L1 connectivity from deep layers. Our results also reveal a period of high transient columnar hyperconnectivity after ear opening coinciding with the critical period, suggesting that circuits originating in deep layers might play a key role in this process.SIGNIFICANCE STATEMENT L1 contains a diverse population of interneurons that can modulate processing in superficial cortical layers but the sources of synaptic input to these neurons and how these inputs change over development is unknown. We found that during the critical period a large fraction of excitatory inputs to L1 originated in L5/6 and the cortical subplate. This hyperconnectivity is absent in deaf mice. Our results directly demonstrate that deep excitatory and superficial inhibitory circuits are tightly linked in early development and might provide a functional scaffold for the layers in between.

Loss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex.

For a long time, myelin was thought to be restricted to excitatory neurons, and studies on dysmyelination focused primarily on excitatory cells. Recent evidence showed that axons of inhibitory neurons in the neocortex are also myelinated, but the role of myelin on inhibitory circuits remains unknown. Here we studied the impact of mild hypomyelination on both excitatory and inhibitory connectivity in the primary auditory cortex (A1) with well-characterized mouse models of hypomyelination due to loss of oligodendrocyte ErbB receptor signaling. Using laser-scanning photostimulation, we found that mice with mild hypomyelination have reduced functional inhibitory connections to A1 L2/3 neurons without changes in excitatory connections, resulting in altered excitatory/inhibitory balance. These effects are not associated with altered expression of GABAergic and glutamatergic synaptic components, but with reduced density of parvalbumin-positive (PV+ ) neurons, axons, and synaptic terminals, which reflect reduced PV expression by interneurons rather than PV+ neuronal loss. While immunostaining shows that hypomyelination occurs in both PV+ and PV- axons, there is a strong correlation between MBP and PV expression, suggesting that myelination influences PV expression. Together, the results indicate that mild hypomyelination impacts A1 neuronal networks, reducing inhibitory activity, and shifting networks towards excitation.

An eco-friendly fluorometric assay for high-sensitive meloxicam quantitation in biological matrices.

Meloxicam (Mel), as a powerful and effective anti-inflammatory drug, is commonly employed for the treatment of various inflammatory diseases; however, the use of Mel at high doses or for extended periods could cause severe side effects in human visceral organs. Therefore, a simple, rapid, and reliable method is urgently needed to monitor Mel in biological samples. Herein, novel water-soluble luminescent nano-carbon dots (nano-Cdots) with outstanding physicochemical properties were prepared by a one-pot high-temperature hydrothermal process of ellagic acid and guanidine. The nano-Cdots were further used as an optical probe for the sensitive detection of Mel in serum samples through the cooperative mechanisms of the inner filter effect and photoelectron transfer. By employing this sensor, an excellent linear correlation was achieved between the relative luminescent intensity [(PL0 - PL)/PL0] and the concentration of Mel in the range of 0.1 to 200 µM, with a limit of detection of 34.68 nM (3σ/k). This sensor was effectively employed for the analysis of Mel in real serum samples, implying its potential development prospects for the advancement of drug analysis with carbon-based probes.

Impaired Hearing and Altered Subplate Circuits During the First and Second Postnatal Weeks of Otoferlin-Deficient Mice.

Sensory deprivation from the periphery impacts cortical development. Otoferlin deficiency leads to impaired cochlear synaptic transmission and is associated with progressive hearing loss in adults. However, it remains elusive how sensory deprivation due to otoferlin deficiency impacts the early development of the auditory cortex (ACX) especially before the onset of low threshold hearing. To test that, we performed in vivo imaging of the ACX in awake mice lacking otoferlin (Otof-/-) during the first and second postnatal weeks and found that spontaneous and sound-driven cortical activity were progressively impaired. We then characterized the effects on developing auditory cortical circuits by performing in vitro recordings from subplate neurons (SPN), the first primary targets of thalamocortical inputs. We found that in Otof-/- pups, SPNs received exuberant connections from excitatory and inhibitory neurons. Moreover, as a population, SPNs showed higher similarity with respect to their circuit topology in the absence of otoferlin. Together, our results show that otoferlin deficiency results in impaired hearing and has a powerful influence on cortical connections and spontaneous activity in early development even before complete deafness. Therefore, peripheral activity has the potential to sculpt cortical structures from the earliest ages, even before hearing impairment is diagnosed.

Neonatal Hypoxia-Ischemia Causes Persistent Intracortical Circuit Changes in Layer 4 of Rat Auditory Cortex.

The connection between early brain injury and subsequent development of disorders is unknown. Neonatal hypoxia-ischemia (HI) alters circuits associated with subplate neurons (SPNs). SPNs are among the first maturing cortical neurons, project to thalamorecipient layer 4 (L4), and are required for the development of thalamocortical connections. Thus, early HI might influence L4 and such influence might persist. We investigated functional circuits to L4 neurons in neonatal rat HI models of different severities (mild and moderate) shortly after injury and at adolescence. We used laser-scanning photostimulation in slices of auditory cortex during P5-10 and P18-23. Mild injuries did not initially (P6/P7) alter the convergence of excitatory inputs from L2/3, but hyperconnectivity emerged by P8-10. Inputs from L4 showed initial hypoconnectivity which resolved by P8-10. Moderate injuries resulted in initial hypoconnectivity from both layers which resolved by P8-10 and led to persistent strengthening of connections. Inhibitory inputs to L4 cells showed similar changes. Functional changes were mirrored by reduced dendritic complexity. We also observed a persistent increase in similarity of L4 circuits, suggesting that HI interferes with developmental circuit refinement and diversification. Altogether, our results show that neonatal HI injuries lead to persistent changes in intracortical connections.

Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats.

OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

Echinacoside exerts its protective effects in a type 2 diabetes mellitus injury model via the AKT pathway.

Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.

Reactive Molecular Dynamics Simulations of Polystyrene Pyrolysis.

Polymers' controlled pyrolysis is an economical and environmentally friendly solution to prepare activated carbon. However, due to the experimental difficulty in measuring the dependence between microstructure and pyrolysis parameters at high temperatures, the unknown pyrolysis mechanism hinders access to the target products with desirable morphologies and performances. In this study, we investigate the pyrolysis process of polystyrene (PS) under different heating rates and temperatures employing reactive molecular dynamics (ReaxFF-MD) simulations. A clear profile of the generation of pyrolysis products determined by the temperature and heating rate is constructed. It is found that the heating rate affects the type and amount of pyrolysis intermediates and their timing, and that low-rate heating helps yield more diverse pyrolysis intermediates. While the temperature affects the pyrolytic structure of the final equilibrium products, either too low or too high a target temperature is detrimental to generating large areas of the graphitized structure. The reduced time plots (RTPs) with simulation results predict a PS pyrolytic activation energy of 159.74 kJ/mol. The established theoretical evolution process matches experiments well, thus, contributing to preparing target activated carbons by referring to the regulatory mechanism of pyrolytic microstructure.

Synergism of Photo-Induced Electron Transfer and Aggregation-Induced Quenching Mechanisms for Highly Sensitive Detection of Silver Ion and Captopril.

Carbon-based nanoprobes, with excellent physicochemical performance and biocompatibility, are a kind of ideal nanomaterial for biosensing. Herein, we designed and prepared novel oxygen-doped nitrogen-enrichment carbon nanoribbons (ONCNs) with an excellent optical performance and uniform morphology, which could be used as a dual-mode fluorescence probe for the detection of Ag+ ion and captopril (Ctl) based on the synergism of photo-induced electron transfer and aggregation-induced quenching mechanisms. By recording the changes in fluorescent intensities of ONCNs, the Ag+ ion and Ctl concentrations can be easily tested in real samples. The results displayed that two good linear relationships existed between the change in fluorescent intensity of ONCNs and the concentrations of Ag+ ion and Ctl in the ranges of 3 µM to 30 µM and 1 µM to 30 µM, with the detection limit of 0.78 µM and 74 nM, respectively. The proposed sensing platform has also been successfully applied for the Ctl analysis in commercial tablet samples based on its high selectivity, proving its value in practical applications.

Transient Subgranular Hyperconnectivity to L2/3 and Enhanced Pairwise Correlations During the Critical Period in the Mouse Auditory Cortex.

During the critical period, neuronal connections are shaped by sensory experience. While the basis for this temporarily heightened plasticity remains unclear, shared connections introducing activity correlations likely play a key role. Thus, we investigated the changing intracortical connectivity in primary auditory cortex (A1) over development. In adult, layer 2/3 (L2/3) neurons receive ascending inputs from layer 4 (L4) and also receive few inputs from subgranular layer 5/6 (L5/6). We measured the spatial pattern of intracortical excitatory and inhibitory connections to L2/3 neurons in slices of mouse A1 across development using laser-scanning photostimulation. Before P11, L2/3 cells receive most excitatory input from within L2/3. Excitatory inputs from L2/3 and L4 increase after P5 and peak during P9-16. L5/6 inputs increase after P5 and provide most input during P12-16, the peak of the critical period. Inhibitory inputs followed a similar pattern. Functional circuit diversity in L2/3 emerges after P16. In vivo two-photon imaging shows low pairwise signal correlations in neighboring neurons before P11, which peak at P15-16 and decline after. Our results suggest that the critical period is characterized by high pairwise activity correlations and that transient hyperconnectivity of specific circuits, in particular those originating in L5/6, might play a key role.

A novel benzothiadiazole-based and NIR-emissive fluorescent sensor for detection of Hg2+ and its application in living cell and zebrafish imaging.

The development of a novel near-infrared (NIR) probe for the detection of toxic Hg2+ in organisms with high selectivity and sensitivity is of great interest but remains a great challenge. Hence, in this work, a new NIR fluorescence enhanced sensor (TBBA), which contains a D-A structure as the NIR fluorophore and rhodanine-3-acetic acid as the receptor, has been developed for the detection of Hg2+ with high selectivity, sensitivity, low limit of detection (13.10 nM) and good binding constant (2.37 × 104 M-1). The mechanism of TBBA response to Hg2+ was further proved by 1H NMR titration, HRMS, and theoretical calculations. Furthermore, TBBA is applied as a fluorescent probe for imaging living cells and zebrafish, indicating that it can be potentially applied for Hg2+ sensing in both environmental and biology fields.

Neonatal Hypoxia-Ischemia Causes Functional Circuit Changes in Subplate Neurons.

Neonatal hypoxia-ischemia (HI) in the preterm human results in damage to subcortical developing white matter and cognitive impairments. Subplate neurons (SPNs) are among the first-born cortical neurons and are necessary for normal cerebral development. While moderate or severe HI at P1 in rats leads to SPN loss, it is unclear if HI, esp. forms not associated with overt cell loss lead to altered SPN circuits. Thus, we used two HI models with different severities in P1 rats. Cauterization of the common carotid artery (CCA) causes a largely transient and thus milder ischemia (HI-Caut) while CCA ligation causes more severe ischemia (HI-Lig). While HI-Lig caused subplate damage, HI-Caut did not cause overt histological damage on the light microscopic level. We used laser-scanning photostimulation (LSPS) in acute thalamocortical slices of auditory cortex during P5-10 to study the functional connectivity of SPNs. Both HI categories resulted in hyperconnectivity of excitatory and inhibitory circuits to SPNs. Thus, alterations on the circuit level are present in the absence of cell loss. Our results show that SPN circuits are uniquely susceptible to HI. Given the key developmental role of SPNs, our results suggest that altered SPN circuits might underlie the abnormal development of cortical function after HI.

Lysin cell-binding domain-functionalized magnetic beads for detection of Staphylococcus aureus via inhibition of fluorescence of Amplex Red/hydrogen peroxide assay by intracellular catalase.

Accurate and rapid identification of Staphylococcus aureus (S. aureus) is of great significance for controlling the food poisoning and infectious diseases caused by S. aureus. In this study, a novel strategy that combines lysin cell-binding domain (CBD)-based magnetic separation with fluorescence detection was developed for the specific and sensitive quantification of S. aureus in authentic samples. The S. aureus cells were separated from the sample matrix by lysin CBD-functionalized magnetic beads. Following lysis by lysostaphin, intracellular catalase was released from S. aureus cells and detected by a fluorometric system composed of horseradish peroxidase (HRP), hydrogen peroxide (H2O2), and Amplex Red. S. aureus was quantified via the inhibitory effect of the released intracellular catalase on the fluorometric system since the catalase could decompose the H2O2. Optimized conditions afforded a calibration curve for S. aureus ranging from 1.0 × 102 to 1.0 × 107 CFU mL-1. The detection limit was as low as 78 CFU mL-1 in phosphate-buffered saline (PBS), and the total detection process could be completed in less than 50 min. Other bacteria associated with common food-borne and nosocomial infections negligibly interfered with S. aureus detection, except for Staphylococcus epidermidis, which may have slightly interfered. Moreover, the potential of this proposed method for practical applications has been demonstrated by detection assays of sterilized milk and human serum. Graphical abstract.

Retrospective comparison of stereotactic body radiotherapy versus intensity-modulated radiotherapy for stage III ultra-central squamous non-small-cell lung cancer.

Aim: To analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) versus intensity-modulated radiotherapy (IMRT) in stage III patients with ultra-central squamous non-small-cell lung cancer (sqNSCLC). Methods: Forty-four stage III patients with ultra-central sqNSCLC receiving SBRT (n = 15) or IMRT (n = 29) between December 2014 and August 2017 were reviewed. Results: At a median follow-up of 16.5 months, the 1-year local control rate of SBRT and IMRT was 60.8 and 37.5%, respectively (p = 0.23); the median overall survival was 17 versus 18 months (p = 0.48); ≥3 grade toxicity was 20 versus 24.1% (p = 0.83). Conclusion: SBRT is effective and patient friendly for stage III patients with ultra-central sqNSCLC. Toxicity might be tolerable with a moderate dose five to six fraction regimen. However, more prospective studies are warranted.

Electrochemiluminescent immunoassay for the lung cancer biomarker CYFRA21-1 using MoOx quantum dots.

Molybdenum oxide quantum dots (MoOx QDs) were synthesized by a one-pot method and used as a versatile probe in an electrochemiluminescent (ECL) immunoassay of the non-small cell lung cancer biomarker cytokeratin 19 fragment 21-1 (CYFRA21-1) as a model analyte. The MoOx QDs exhibited stable and strong cathodic green ECL, with an emission peak at 535 nm, in the presence of K2S2O8 within the potential range of -2.0 to 0 V. On exposure to CYFRA21-1, the ECL decreases because of the immunoreaction between CYFRA21-1 and its antibody which generates a barrier for electron transfer. The determination of CYFRA21-1 with favorable analytical performances was successfully realized under the optimal conditions. ECL decreases linearly in the 1 pg mL-1 to 350 ng mL-1 CYFRA21-1 concentration range, and the detection is as low as 0.3 pg mL-1. Excellent recoveries from CYFRA21-1-spiked human serum indicate that the assay can be operated under physiological conditions. Graphical abstractSchematic representation of the fabrication of molybdenum oxide quantum dots (MoOx QDs) and the electrochemiluminescent (ECL) immunoassay based on the use of the MoOx QDs ECL probe for cytokeratin 19 fragment 21-1 (CYFRA21-1).

Sublaminar Subdivision of Mouse Auditory Cortex Layer 2/3 Based on Functional Translaminar Connections.

The cerebral cortex is subdivided into six layers based on morphological features. The supragranular layers 2/3 (L2/3) contain morphologically and genetically diverse populations of neurons, suggesting the existence of discrete classes of cells. In primates and carnivores L2/3 can be subdivided morphologically, but cytoarchitectonic divisions are less clear in rodents. Nevertheless, discrete classes of cells could exist based on their computational requirement, which might be linked to their associated functional microcircuits. Through in vitro slice recordings coupled with laser-scanning photostimulation we investigated whether L2/3 of male mouse auditory cortex contains discrete subpopulations of cells with specific functional microcircuits. We use hierarchical clustering on the laminar connection patterns to reveal the existence of multiple distinct classes of L2/3 neurons. The classes of L2/3 neurons are distinguished by the pattern of their laminar and columnar inputs from within A1 and their location within L2/3. Cells in superficial L2 show more extensive columnar integration than deeper L3 cells. Moreover, L3 cells receive more translaminar input from L4. In vivo imaging in awake mice revealed that L2 cells had higher bandwidth than L3 cells, consistent with the laminar differences in columnar integration. These results suggest that similar to higher mammals, rodent L2/3 is not a homogenous layer but contains several parallel microcircuits.SIGNIFICANCE STATEMENT Layer 2/3 of auditory cortex is functionally diverse. We investigated whether L2/3 cells form classes based on their functional connectivity. We used in vitro whole-cell patch-clamp recordings with laser-scanning photostimulation and performed unsupervised clustering on the resulting excitatory and inhibitory connection patterns. Cells within each class were located in different sublaminae. Superficial cells showed wider integration along the tonotopic axis and the amount of L4 input varied with sublaminar location. To identify whether sensory responses varied with sublaminar location, we performed in vivo Ca2+ imaging and found that L2 cells were less frequency-selective than L3 cells. Our results show that the diversity of receptive fields in L2/3 is likely due to diversity in the underlying functional circuits.

Advancements in Copper Nanowires: Synthesis, Purification, Assemblies, Surface Modification, and Applications.

Copper nanowires (CuNWs) are attracting a myriad of attention due to their preponderant electric conductivity, optoelectronic and mechanical properties, high electrocatalytic efficiency, and large abundance. Recently, great endeavors are undertaken to develop controllable and facile approaches to synthesize CuNWs with high dispersibility, oxidation resistance, and zero defects for future large-scale nano-enabled materials. Herein, this work provides a comprehensive review of current remarkable advancements in CuNWs. The Review starts with a thorough overview of recently developed synthetic strategies and growth mechanisms to achieve single-crystalline CuNWs and fivefold twinned CuNWs by the reduction of Cu(I) and Cu(II) ions, respectively. Following is a discussion of CuNW purification and multidimensional assemblies comprising films, aerogels, and arrays. Next, several effective approaches to protect CuNWs from oxidation are highlighted. The emerging applications of CuNWs in diverse fields are then focused on, with particular emphasis on optoelectronics, energy storage/conversion, catalysis, wearable electronics, and thermal management, followed by a brief comment on the current challenges and future research directions. The central theme of the Review is to provide an intimate correlation among the synthesis, structure, properties, and applications of CuNWs.

Low BMI is correlated with increased TGF-ß and IL-10 mRNA levels in the peripheral blood of breast cancer patients.

Transforming growth factor-ß (TGF-ß), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-ß, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-ß, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF-ß mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (<23), low AGR, and high GLB, respectively, than in their counterparts (P < 0.05). In addition, IL-10 mRNA expression levels in patients with normal BMI (<23) were 2.8-fold and 3.5-fold higher than in those who were overweight (23≤ BMI <25) and obese (BMI ≥ 25), respectively (P < 0.05). In addition, TGF-ß, IL-10, and Foxp3 mRNA levels were significantly higher in patients with breast cancer than in healthy controls (P < 0.05). In summary, our results suggest that nutritional status, especially BMI, may strongly affect systematic immune function in patients with breast cancer. © 2018 IUBMB Life, 70(3):237-245, 2018.

Overexpression of modified human TRß1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Association studies suggest that TRß1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRß1 (m-TRß1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRß1 (TRß1) DBD. Studies confirmed that m-TRß1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TRß1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TRß (m-TRß1 and TRß1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TRß), and then evaluated the effects of the expressed TRß on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-L-triiodothyronine (T3), the expression of TRß in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TRß expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TRß1 was stronger than that of TRß1. These data indicate that m-TRß1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TRß1.