[Corrigendum] Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway.

Following the publication of the above article, the authors realized that, in Fig. 1D on p. 7363, the data panel selected for the '0.5 mM Succinate' group was duplicated in Fig. 1B (Control) in another article of theirs published in FASEB J ("α­Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway": doi: 10.1096/fj.201700670R) due to the fact that they had inadvertently confused the layout of the two figures. The authors apologize for this error. Secondly, in terms of the quantification of the blots shown in Fig. 2A, ß­actin was not in fact used as a loading control; the phosphoproteins were normalized against the levels of the relative total protein, and the layout of Fig. 2A has been revised to reflect this (note that the the figure legend for Fig. 2 has also been revised: The last sentence no longer reads, "ß­actin was used as a loading control."). The revised versions of Figs. 1 and 2 are shown on the next page. Note that these errors did not affect the results or the main conclusions reported in the study, and no corrections were required either to the descriptions in the text or to the histograms shown in these figures. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 7361­7366, 2017; DOI: 10.3892/mmr.2017.7554].

A field trial for remediation of multi-metal contaminated soils using the combination of fly ash stabilization and Zanthoxylumbungeanum- Lolium perenne intercropping system.

Insitu stabilization and phytoextraction are considered as two convenient and effective technologies for the remediation of toxic elements (TEs) in soils. However, the effectiveness of these two remediation technologies together on the bioavailability and phytoextraction of TEs in field trials has not been explored yet. Specifically, the remediation potential of fly ash (FA; as stabilizing agent) and ryegrass (as a TE accumulator) intercropped with a target crop for soil polluted with multiple TEs has not been investigated yet, particularly in long-term field trials. Therefore, in this study, a six-month combined remediation field experiment of FA stabilization and/or ryegrass intercropping (IR) was carried out on the farmland soils contaminated with As, Cd, Cr, Cu, Hg, Ni, Pb and Zn where Zanthoxylumbungeanum (ZB) trees as native crops were grown for years. The treatments include soil cultivated alone with ZB untreated- (control) and treated-with FA (FA), produced by burning lignite in Shaanxi Datong power plant, China, soil cultivated with ZB and ryegrass untreated- (IR) and treated-with FA (FA + IR). This was underpinned by a large-scale survey in Daiziying (China), which showed that the topsoils were polluted by Cd, Cu, Hg and Pb, and that Hg and Pb contents in the Zanthoxylumbungeanum fruits exceeded their allowable limits. The TEs contents in the studied FA were lower than their total element contents in the soil. The DTPA-extractable TEs contents of the remediation modes were as follows: FA < FA + IR < IR < control. Notably, TEs contents in the ZB fruits were lowest under the FA + IR treatment, which were decreased by 27.6% for As, 42.3% for Cd, 16.7% for Cr, 30.5% for Cu, 23.1% for Hg, 15.5% for Ni, 33.2% for Pb and 38.1% for Zn compared with the control treatment. Whereas the FA + IR treatment enhanced TEs contents in ryegrass shoots and roots, and the TEs contents in ryegrass shoots were below their regulatory limits for fodder crops. The findings confirmed that the combined remediation strategy, i.e., FA (with low content of TEs) stabilization effect and intercropping of ZB (target crop) and ryegrass (accumulating plant) could provide a prospective approach to produce target plants within safe TEs thresholds with greater economic benefits, while remediating soils polluted with multiple TEs and mitigating the potential ecological and human health risk. Those results are of great applicable concern.

Proband-independent haplotyping based on NGS-based long-read sequencing for detecting pathogenic variant carrier status in preimplantation genetic testing for monogenic diseases.

Preimplantation genetic testing for monogenic diseases (PGT-M) can be used to select embryos that do not develop disease phenotypes or carry disease-causing genes for implantation into the mother's uterus, to block disease transmission to the offspring, and to increase the birth rate of healthy newborns. However, the traditional PGT-M technique has some limitations, such as its time consumption, experimental procedural complexity, and the need for a complete family or reference embryo to construct the haplotype. In this study, proband-independent haplotyping based on NGS-based long-read sequencing (Phbol-seq) was used to effectively construct haplotypes. By targeting the mutation sites of single gene disease point mutations and small fragment deletion carriers, embryos carrying parental disease-causing mutations were successfully identified by linkage analysis. The efficiency of embryo resolution was then verified by classical Sanger sequencing, and it was confirmed that the construction of haplotype and SNP linkage analysis by Phbol-seq could accurately and effectively detect whether embryos carried parental pathogenic mutations. After the embryos confirmed to be nonpathogenic by Phbol-seq-based PGT-M and confirmed to have normal copy number variation by Phbol-seq-based PGT-A were transplanted into the uterus, gene detection in amniotic fluid of the implanted embryos was performed, and the results confirmed that Phbol-seq technology could accurately distinguish normal genotype embryos from genetically modified carrier embryos. Our results suggest that Phbol-seq is an effective strategy for accurately locating mutation sites and accurately distinguishing between embryos that inherit disease-causing genes and normal embryos that do not. This is critical for Phbol-seq-based PGT-M and could help more single-gene disease carriers with incomplete families, de novo mutations or suspected germline mosaicism to have healthy babies with normal phenotypes. It also helps to reduce the transmission of monogenic genetic diseases in the population.

Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency.

Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways.

Downregulation of Claudin5 promotes malignant progression and radioresistance through Beclin1-mediated autophagy in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive cancer with poor treatment outcomes. Despite the critical role of tight junction proteins in tumorigenesis, the involvement of Claudin5 in ESCC remains poorly understood. Thus, this study aimed to investigate the role of Claudin5 in ESCC malignant progression and radioresistance, as well as the underlying regulatory mechanisms. METHODS: The expression of Claudin5 was evaluated in esophageal cancer tissue using both public databases and 123 clinical samples. CCK-8, transwell invasion, wound healing and clonogenic survival assays were used to examine the proliferation, invasion, migration and radiosensitivity of ESCC cells in vitro. Xenograft and animal lung metastasis experiments were conducted to examine the impact of Claudin5 on tumor growth and lung metastasis in vivo. The effect of Claudin5 on autophagy was detected via transmission electron microscopy, western blotting and autophagy flux. Immunohistochemical staining was used to detect Claudin5 expression in ESCC patient samples. The statistical difference was assessed with Student t test or one-way ANOVA. The correlation between Claudin5 expression and radiotherapy response rate was performed by the Chi-square test. The significance of Kaplan-Meier curves was evaluated by the Logrank test. RESULTS: Claudin5 expression was downregulated in ESCC tissues. Downregulation of Claudin5 promoted ESCC cell proliferation, invasion, and migration both in vitro and in vivo. Downregulation of Claudin5 decreased the radiosensitivity of ESCC cells. Moreover, downregulation of Claudin5 promoted autophagy and the expression of Beclin1. Beclin1 knockdown reversed the effect of Claudin5 downregulation on autophagy induction and the promotion of ESCC cell malignant progression and radioresistance. Additionally, low expression of Claudin5 in ESCC cancer tissues was associated with poor radiotherapy response and prognosis. CONCLUSIONS: In summary, these findings suggest that downregulation of Claudin5 promotes ESCC malignant progression and radioresistance via Beclin1-autophagy activation and may serve as a promising biomarker for predicting radiotherapy response and patient outcome in ESCC.

Protective Effect of l-Theanine on Cyclophosphamide-Induced Testicular Toxicity in Mice.

l-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of l-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last l-theanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of l-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that l-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of l-theanine on CP-induced testicular toxicity. l-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.

Graphene-based microfluidic perforated microelectrode arrays for retinal electrophysiological studies.

Perforated microelectrode arrays (pMEAs) have become essential tools for ex vivo retinal electrophysiological studies. pMEAs increase the nutrient supply to the explant and alleviate the accentuated curvature of the retina, allowing for long-term culture and intimate contacts between the retina and electrodes for electrophysiological measurements. However, commercial pMEAs are not compatible with in situ high-resolution optical imaging and lack the capability of controlling the local microenvironment, which are highly desirable features for relating function to anatomy and probing physiological and pathological mechanisms in retina. Here we report on microfluidic pMEAs (µpMEAs) that combine transparent graphene electrodes and the capability of locally delivering chemical stimulation. We demonstrate the potential of µpMEAs by measuring the electrical response of ganglion cells to locally delivered high K+ stimulation under controlled microenvironments. Importantly, the capability for high-resolution confocal imaging of the retina tissue on top of the graphene electrodes allows for further analyses of the electrical signal source. The new capabilities provided by µpMEAs could allow for retinal electrophysiology assays to address key questions in retinal circuitry studies.

Dynamic Observation of Retinal Response to Pressure Elevation in a Microfluidic Chamber.

Dynamic observation of cell and tissue responses to elevated pressure could help our understanding of important physiological and pathological processes related to pressure-induced injury. Here, we report on a microfluidic platform capable of maintaining a wide range of stable operating pressures (30 to 200 mmHg) while using a low flowrate (2-14 µL/h) to limit shear stress. This is achieved by forcing flow through a porous resistance matrix composed of agarose gel downstream of a microfluidic chamber. The flow characteristics were investigated and the permeabilities of the agarose with four different concentrations were extracted, agreeing well with results found in the literature. To demonstrate the capability of the device, we measured the change in intracellular Ca2+ levels of retinal ganglion cells in whole mouse retina in response to pressure. The onset of enhanced pressure results in, on average, an immediate 119.16% increase in the intracellular Ca2+ levels of retinal ganglion cells. The demonstrated microfluidic platform could be widely used to probe cell and tissue responses to elevated pressure.

Sustainable biochar effects on the remediation of contaminated soil: A 2-crop season site practice near a lead-zinc smelter in Feng County, China.

It is of great significance to explore the remediation pattern in actual heavy metal (HM) contaminated sites. The field trial was carried out to research the remediation effect of biochar near a lead-zinc smelter in Feng County, China, under the rotation condition of different crops. This kind of cultivation mode is very representative in northern of China. And the pattern of production and restoration is suitable for scarce land resources and large food demand in China. The changes of soil physiochemical properties with the biochar addition, crop growth and the accumulated HMs by crops were focused on. The results showed the biochar application was excellent in improving soil nutrient elements and crop growth. The contents of TK were more obvious than those of TN and TP, with an increase of 2.6%-28.2% compared with the controls (without the addition of biochar). The yield of first season crops, i.e., soybean and corn, increased by 30%-42% and 34%-61%, respectively, and the second season crops, i.e., rape and wheat, with the increment of 25%-41% and 9%-29%, respectively. The availability forms of Cd and Pb decreased by 1.07-10.0% and 2.92-8.35%, respectively. While the improvement on the status of the HMs accumulated by crops was disappointing. The contents of HMs accumulated by crops increased to varying degrees (e.g., Pb and Zn in root, Cu and Pb in grain, and Cd in stems and leaves). Moreover, the concentrations of HMs in seeds of crops were higher than the limited levels given by the Chinese directive. Considering the results of the study and food safety, it is suggested to change the nature of the land around the smelter into woodland or construction land to prohibit the cultivation of food crops in this area.

Probing Light-Stimulated Activities in the Retina via Transparent Graphene Electrodes.

Graphene has triggered tremendous research due to its superior properties. In particular, the intrinsic high light transmission illustrates the unique advantage in neural biosensing. Here, we combine perforated flexible graphene electrodes with microfluidic platforms to explore real-time extracellular electrical activities of retinal ganglion cells (RGCs). Under light stimulation, the transparent graphene electrodes have demonstrated the capability of recording the electrical activities of stimulated RGCs in direct contact. Different types of RGCs have shown three distinct light induced patterns, ON, OFF, and ON-OFF, which are primarily operated by cone photoreceptors. Moreover, the observed spiking waveforms can be divided into two groups: the biphasic waveform usually occurs at contacts with soma, while the triphasic waveform is likely related to the axon. Under high K+ stimulation, the graphene electrodes exhibit higher electrical sensitivity than gold counterparts with an average 2.5-fold enhancement in spiking amplitude. Furthermore, a strong response has been observed with the firing rate first increasing and then ceasing, which could be due to the potassium-induced neural depolarization. These results show that graphene electrodes can be a promising candidate in the electrophysiology studies of retina and offer a route to engineering future two-dimensional materials-based biosensors.

Earthworms as candidates for remediation of potentially toxic elements contaminated soils and mitigating the environmental and human health risks: A review.

Global concerns towards potentially toxic elements (PTEs) are steadily increasing due to the significant threats that PTEs pose to human health and environmental quality. This calls for immediate, effective and efficient remediation solutions. Earthworms, the 'ecosystem engineers', can modify and improve soil health and enhance plant productivity. Recently, considerable attention has been paid to the potential of earthworms, alone or combined with other soil organisms and/or soil amendments, to remediate PTEs contaminated soils. However, the use of earthworms in the remediation of PTEs contaminated soil (i.e., vermiremediation) has not been thoroughly reviewed to date. Therefore, this review discusses and provides comprehensive insights into the suitability of earthworms as potential candidates for bioremediation of PTEs contaminated soils and mitigating environmental and human health risks. Specifically, we reviewed and discussed: i) the occurrence and abundance of earthworms in PTEs contaminated soils; ii) the influence of PTEs on earthworm communities in contaminated soils; iii) factors affecting earthworm PTEs accumulation and elimination, and iv) the dynamics and fate of PTEs in earthworm amended soils. The technical feasibility, knowledge gaps, and practical challenges have been worked out and critically discussed. Therefore, this review could provide a reference and guidance for bio-restoration of PTEs contaminated soils and shall also help developing innovative and applicable solutions for controlling PTEs bioavailability for the remediation of contaminated soils and the mitigation of the environment and human risks.

Enhanced photocurrent response speed in charge-density-wave phase of TiSe2-metal junctions.

Group IVB transition metal dichalcogenides (TMDCs) have attracted significant attention due to their predicted high charge carrier mobility, large sheet current density, and enhanced thermoelectric power. Here, we investigate the electrical and optoelectronic properties of few-layer titanium diselenide (TiSe2)-metal junctions through spatial-, wavelength-, temperature-, power- and temporal-dependent scanning photocurrent measurements. Strong photocurrent responses have been detected at TiSe2-metal junctions, which is likely attributed to both photovoltaic and photothermoelectric effects. A fast response time of 31 µs has been achieved, which is two orders of magnitude better than HfSe2 based devices. More importantly, our experimental results reveal a significant enhancement in the response speed upon cooling to the charge-density-wave (CDW) phase transition temperature (TCDW = 206 K), which may result from dramatic reduction in carrier scattering that occurs as a result of the switching between the normal and CDW phases of TiSe2. Additionally, the photoresponsivity at 145 K is up to an order of magnitude higher than that obtained at room temperature. These fundamental studies not only offer insight for the photocurrent generation mechanisms of group IVB TMDC materials, but also provide a route to engineering future temperature-dependent, two-dimensional, fast electronic and optoelectronic devices.

Observation of superdiffusive phonon transport in aligned atomic chains.

Fascinating phenomena can occur as charge and/or energy carriers are confined in one dimension1-4. One such example is the divergent thermal conductivity (κ) of one-dimensional lattices, even in the presence of anharmonic interatomic interactions-a direct consequence of the Fermi-Pasta-Ulam-Tsingou paradox proposed in 19555. This length dependence of κ, also known as superdiffusive phonon transport, presents a classical anomaly of continued interest6-9. So far the concept has remained purely theoretical, because isolated single atomic chains of sufficient length have been experimentally unattainable. Here we report on the observation of a length-dependent κ extending over 42.5 µm at room temperature for ultrathin van der Waals crystal NbSe3 nanowires. We found that κ follows a 1/3 power law with wire length, which provides experimental evidence pointing towards superdiffusive phonon transport. Contrary to the classical size effect due to phonon-boundary scattering, the observed κ shows a 25-fold enhancement as the characteristic size of the nanowires decreases from 26 to 6.8 nm while displaying a normal-superdiffusive transition. Our analysis indicates that these intriguing observations stem from the transport of one-dimensional phonons excited as a result of elastic stiffening with a fivefold enhancement of Young's modulus. The persistent divergent trend of the observed thermal conductivity with sample length reveals a real possibility of creating novel van der Waals crystal-based thermal superconductors with κ values higher than those of any known materials.

Retraction Note: Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-72330-x.

Net negative contributions of free electrons to the thermal conductivity of NbSe3 nanowires.

Understanding transport mechanisms of electrons and phonons, two major energy carriers in solids, are crucial for various engineering applications. It is widely believed that more free electrons in a material should correspond to a higher thermal conductivity; however, free electrons also scatter phonons to lower the lattice thermal conductivity. The net contribution of free electrons has been rarely studied because the effects of electron-phonon (e-ph) interactions on lattice thermal conductivity have not been well investigated. Here an experimental study of e-ph scattering in quasi-one-dimensional NbSe3 nanowires is reported, taking advantage of the spontaneous free carrier concentration change during charge density wave (CDW) phase transition. Contrary to the common wisdom that more free electrons would lead to a higher thermal conductivity, results show that during the depinning process of the condensed electrons, while the released electrons enhance the electronic thermal conductivity, the overall thermal conductivity decreases due to the escalated e-ph scattering. This study discloses how competing effects of free electrons result in unexpected trends and provides solid experimental data to dissect the contribution of e-ph scattering on lattice thermal conductivity. Lastly, an active thermal switch design is demonstrated based on tuning electron concentration through electric field.

Ultrafast Photocurrent Response and High Detectivity in Two-Dimensional MoSe2-based Heterojunctions.

Two-dimensional (2D) transition metal dichalcogenide (TMDC) materials have garnered great attention on account of their novel properties and potential to advance modern technology. Recent studies have demonstrated that TMDCs can be utilized to create high-performing heterostructures with combined functionality of the individual layers and new phenomena at these interfaces. Here, we report an ultrafast photoresponse within MoSe2-based heterostructures in which heavily p-doped WSe2 and MoS2 flakes share an undoped MoSe2 channel, allowing us to directly compare the optoelectronic properties of MoSe2-based heterojunctions with different 2D materials. Strong photocurrent signals have been observed in both MoSe2-WSe2 and MoSe2-MoS2 heterojunctions with a photoresponse time constant of ∼16 µs, surmounting previous MoSe2-based devices by three orders of magnitude. Further studies have shown that the fast response is independent of the integrated 2D materials (WSe2 or MoS2) but is likely attributed to the high carrier mobility of 260 cm2 V-1 s-1 in the undoped MoSe2 channel as well as the greatly reduced Schottky barriers and near absence of interface states at MoSe2-WSe2/MoS2 heterojunctions, which lead to reduced carrier transit time and thus short photocurrent response time. Lastly, a high detectivity on the order of ∼1014 Jones has been achieved in MoSe2-based heterojunctions, which supersedes current industry standards. These fundamental studies not only shed light on photocurrent generation mechanisms in MoSe2-based heterojunctions but also open up new avenues for engineering future high-performance 2D optoelectronic devices.

Electrical and Thermal Transport through Silver Nanowires and Their Contacts: Effects of Elastic Stiffening.

Silver nanowires have been widely adopted as nanofillers in composite materials used for various applications. Electrical and thermal properties of these composites are critical for proper device operation, and highly depend on transport through the nanowires and their contacts, yet studies on silver nanowires have been limited to one or two samples and no solid data have been reported for individual contacts. Through systematic measurements of silver nanowires of different sizes, we show that the Lorenz number increases with decreasing wire diameter and has a higher value at wire contacts. Examination of the corresponding electrical and thermal conductivities indicates that these changes are due to contributions of phonons that become more important as a result of elastic stiffening. The derived contact thermal conductance per unit area between silver nanowires is ∼10 times that between carbon nanotubes. This helps to explain the more significant thermal conductivity enhancement of silver nanowires-based composites.

Hsa-miR-140-5p down-regulates LDL receptor and attenuates LDL-C uptake in human hepatocytes.

BACKGROUND AND AIMS: MicroRNAs (miRs) exert important regulatory effects in cholesterol metabolism. Hepatic low density lipoprotein receptor (LDLR) pathway, as the major mechanism for clearing circulating low density lipoprotein cholesterol (LDL-C) in bloodstream, is a pivotal therapeutic target to treat hypercholesterolemia and atherosclerosis. This study aimed to identify novel miRs that regulate LDLR expression. METHODS AND RESULTS: Hsa-miR-140-5p was predicted by bioinformatics analyses to interact with human LDLR mRNA. To evaluate its functional effects in regulating LDLR, hsa-miR-140-5p and anti-miR-140-5p were transfected into human and mouse liver cells, followed by qRT-PCR, western blot, immunofluorescence, flow cytometry, and LDL-C uptake assays. It was observed that hsa-miR-140-5p over-expression dramatically down-regulated LDLR expression and reduced LDL-C uptake, whereas inhibition of hsa-miR-140-5p significantly up-regulated LDLR expression and enhanced LDL-C uptake in human HepG2 and LO2 cells, but not in mouse Hepa1-6 cells. Luciferase reporter assay and site-directed mutagenesis identified that hsa-miR-140-5p interacts with the predicted seed sequence "AAACCACU" in the 3'-UTR of human LDLR mRNA. Hsa-miR-140-5p over-expression attenuated LDL-C uptake and decreased intracellular cholesterol levels in the presence of 50 µg/ml ox-LDL in HepG2 cells. Additionally, palmitic acid and simvastatin suppressed, whereas LDL-C up-regulated the expression of miR-140-5p in HepG2 cells. CONCLUSIONS: Hsa-miR-140-5p is a negative regulator of LDLR expression in human hepatocytes, but not in mouse hepatocytes. Simvastatin inhibits hsa-miR-140-5p expression in human hepatocytes, which is likely to be a novel mechanism for treating hypercholesterolemia with statins in clinic. Antagonism of hsa-miR-140-5p could be a new therapeutic strategy for the treatment of hypercholesterolemia and atherosclerosis.