MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2.

Colorectal cancer (CRC) is the most common malignant tumor occurred in digestive system. However, the prognosis of CRC patients is poor. Therefore, it is urgent to illuminate the mechanism suppressing CRC and explore novel targets or therapies for CRC treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs with a length of 20-23 nucleotides encoded by endogenous genes, which are associated with the development of a variety of cancers, including CRC. Studies have shown that miR-19a is identified as oncogenic miRNA and promotes the proliferation, migration and invasion of CRC cells. However, the relationship between miR-19a and ferroptosis in CRC remains unknown. Here, we reported that iron-responsive element-binding protein 2 (IREB2), as an inducer of ferroptosis, was negatively regulated by miR-19a. IREB2 is a direct target of miR-19a. In addition, ferroptosis was suppressed by miR-19a through inhibiting IREB2. Thus, we proposed a novel mechanism of ferroptosis mediated by miR-19a in CRC cells, which could give rise to a new strategy for the therapy of CRC.

An intrinsic energy conversion mechanism via telescopic extension and retraction of concentric carbon nanotubes.

The conversion of other forms of energy into mechanical work through the geometrical extension and retraction of nanomaterials has a wide variety of potential applications, including for mimicking biomotors. Here, using molecular dynamics simulations, we demonstrate that there exists an intrinsic energy conversion mechanism between thermal energy and mechanical work in the telescopic motions of double-walled carbon nanotubes (DWCNTs). A DWCNT can inherently convert heat into mechanical work in its telescopic extension process, while convert mechanical energy into heat in its telescopic retraction process. These two processes are nearly thermodynamically reversible. The underlying mechanism for this energy conversion is that the configurational entropy changes with the telescopic overlapping length of concentric individual tubes. We also find that the entropy effect enlarges with the decreasing intertube space of DWCNTs. As a result, the spontaneous telescopic motion of a condensed DWCNT can be switched to extrusion by increasing the system temperature above a critical value. These findings are important for fundamentally understanding the mechanical behavior of concentric nanotubes, and may have general implications in the application of DWCNTs as linear motors in nanodevices.

Specific hepatic stellate cell-penetrating peptide targeted delivery of a KLA peptide reduces collagen accumulation by inducing apoptosis.

Liver fibrosis is an aberrant wound-healing process to chronic hepatic inflammation and is characterized by excessive accumulation of extracellular matrix (ECM) that is produced by activated hepatic stellate cells (HSCs). Thus, activated HSCs play a key role in the pathogenesis of liver fibrosis and are a potential target for the treatment of liver fibrosis. Herein, we report that a specific HSC-penetrating peptide reduced collagen accumulation by inducing the apoptosis of HSC-T6 cells. We first screened HSC-specific transduction peptides and identified a novel HSC-targeted cell-penetrating peptide (HTP) that specifically interacted with HSC-T6 cells. A chimeric peptide termed HTPK25 was consequently generated by coupling HTP with the antimicrobial peptide KLA, which is capable of initiating cell apoptosis in mammalian cells. HTPK25 entered cells in a dose-dependent manner, reduced the cell viability and induced apoptosis via the caspase 3 pathway in HSC-T6 cells. Furthermore, HTPK25 inhibited the α-smooth muscle actin and collagen I expression in HSC-T6 cells. Our results demonstrated that the HTP was able to specifically and efficiently deliver the KLA peptide into HSC-T6 cells to induce apoptosis, indicating that HTP-delivered functional agents may present a promising approach for liver fibrosis therapy.

Gas-like adhesion of two-dimensional materials onto solid surfaces.

The adhesion of two-dimensional (2D) materials onto other surfaces is usually considered a solid-solid mechanical contact. Here, we conduct both atomistic simulations and theoretical modeling to show that there in fact exists an energy conversion between heat and mechanical work in the attachment/detachment of two-dimensional materials on/off solid surfaces, indicating two-dimensional materials adhesion is a gas-like adsorption rather than a pure solid-solid mechanical adhesion. We reveal that the underlying mechanism of this intriguing gas-like adhesion is the configurational entropy difference between the freestanding and adhered states of the two-dimensional materials. Both the theoretical modeling and atomistic simulations predict that the adhesion induced entropy difference increases with increasing adhesion energy and decreasing equilibrium binding distance. Our findings provide a fundamental understanding of the adhesion of two-dimensional materials, which is important for designing two-dimensional materials based devices and may have general implications for nanoscale efficient actuators.

Negative Thermophoresis in Concentric Carbon Nanotube Nanodevices.

Positive and negative thermophoresis in fluids has found widespread applications from mass transport to molecule manipulation. In solids, although positive thermophoresis has been recently discovered in both theoretical and experimental studies, negative thermophoresis has never been reported. Here we reveal via molecular dynamics simulations that negative thermophoresis does exist in solids. We consider the motion of a single walled carbon nanotube nested inside of two separate outer tubes held at different temperatures. It is found that a sufficiently long inner tube will undergo negative thermophoresis, whereas positive thermophoresis is favorable for a relatively short inner tube. Mechanisms for the observed positive thermophoresis and negative thermophoresis are shown to be totally different. In positive thermophoresis, the driving force comes mainly from the thermally induced edge force and the interlayer attraction force, whereas the driving force for negative thermophoresis is mainly due to the thermal gradient force. These findings have enriched our knowledge of the fundamental driving mechanisms for thermophoresis in solids and may stimulate its further applications in nanotechnology.

A nanoscale linear-to-linear motion converter of graphene.

Motion conversion plays an irreplaceable role in a variety of machinery. Although many macroscopic motion converters have been widely used, it remains a challenge to convert motion at the nanoscale. Here we propose a nanoscale linear-to-linear motion converter, made of a flake-substrate system of graphene, which can convert the out-of-plane motion of the substrate into the in-plane motion of the flake. The curvature gradient induced van der Waals potential gradient between the flake and the substrate provides the driving force to achieve motion conversion. The proposed motion converter may have general implications for the design of nanomachinery and nanosensors.

Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications.

Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse peptides with 5-30 amino acids. CPPs are divided into cationic, amphipathic and hydrophobic CPPs. They are able to carry small molecules, plasmid DNA, small interfering RNA, proteins, viruses, imaging agents and other various nanoparticles across the cellular membrane, resulting in internalization of the intact cargos. However, the mechanisms of CPP internalization remain to be elucidated. Recently, CPPs have received considerable attention due to their high transduction efficiency and low cytotoxicity. These peptides have a significant potential for diagnostic and therapeutic applications, such as delivery of fluorescent or radioactive compounds for imaging, delivery of peptides and proteins for therapeutic application, and delivery of molecules into induced pluripotent stem cells for directing differentiation. The present study reviews the classifications and transduction mechanisms of CPPs, as well as their potential applications.

[Design and establishment of modern literature database about acupuncture Deqi].

A search on acupuncture Deqi was conducted using four Chinese-language biomedical databases (CNKI, Wan-Fang, VIP and CBM) and PubMed database and using keywords "Deqi" or "needle sensation" "needling feeling" "needle feel" "obtaining qi", etc. Then, a "Modern Literature Database for Acupuncture Deqi" was established by employing Microsoft SQL Server 2005 Express Edition, introducing the contents, data types, information structure and logic constraint of the system table fields. From this Database, detailed inquiries about general information of clinical trials, acupuncturists' experience, ancient medical works, comprehensive literature, etc. can be obtained. The present databank lays a foundation for subsequent evaluation of literature quality about Deqi and data mining of undetected Deqi knowledge.

Nanoscale directional motion towards regions of stiffness.

How to induce nanoscale directional motion via some intrinsic mechanisms pertaining to a nanosystem remains a challenge in nanotechnology. Here we show via molecular dynamics simulations that there exists a fundamental driving force for a nanoscale object to move from a region of lower stiffness toward one of higher stiffness on a substrate. Such nanoscale directional motion is induced by the difference in effective van der Waals potential energy due to the variation in stiffness of the substrate; i.e., all other conditions being equal, a nanoscale object on a stiffer substrate has lower van der Waals potential energy. This fundamental law of nanoscale directional motion could lead to promising routes for nanoscale actuation and energy conversion.

[Progress on research of specificity of acupoint effects during "the 11th five-year"].

With retrieval in CNKI and MEDLINE data base, the articles in Chinese and English that were written by Chinese authors, which were about the specificity of acupoint effects during "the Eleventh Five-Year (2006-2010)", are included. Researchers have studied about the specificity of acupoint effects by cerebral function imaging technique and it turns out that from the perspective of central mechanism, there are differences among aupoint stimulatory effect. The curative effect of acupoints is significantly better than that of nonacupoints, different acupoints have different curative effects, the effect of disease-related acupoints is better than that of unrelated acupoints, those above have intitally proved the existence of specificity of acupoint effects. However, part of the research results need futher summaries, analysis and promotion as well as try to avoid low-level repeat in research design.

[Discussion on the influence of factors related organic on Deqi in acupuncture treatment].

OBJECTIVE: To discuss the influence of factors related organic on deqi in acupuncture treatment and provide scientific evidence for further research on the influencing factors of deqi sensation. METHODS: China National Knowledge Infrastructure (CNKI) database, VIP-Chinese scientific and technological journal database, Chinese biological medical (CBM) database and PubMed database were retrieved. There were 30 articles about the organic influencing factors of deqi and they were analyzed. RESULTS: The organic related factors which includes individual constitution, syndrome classification, physical condition, specificity of acupoint function, tolerance and psychological factors play an important part in deqi in acupancture treatment, which should be brought to the forefront for acupuncture practitioners and researchers. CONCLUSION: The organic factors are influencing the deqi sensation in many ways but most of the present studies are resting on the affirmation of the phenomenon. Further studies about organic related influencing factors on deqi should be carried out and scientific, objective indices of deqi sensation should be explored which may improve the clinical and research level of acupuncture.

[Progression of the study on the acupoints from 2006 to 2010 overseas].

With retrieval of MEDLINE database (from Jan 2006 to Dec 2010) and supplementary search on other important literatures, 29 overseas articles that were in accord with inclusive criteria were included. The results showed that the overseas scholars issued the international standard on human acupoint locations and proposed the localization system of animal acupoint model; discovered the new acupoint structure, characteristic of acupoint microcirculation, the states of the diseases could be specifically reflected through acupoint temperature, electric resistance, pressure and pain threshold, and the specific brainstem reaction could be induced by electroacupuncture at acupoints; verified initially the effect on nausea and vomiting with the related acupuncture methods at acupoints and explained the mechanisms on the local analgesia of acupuncture at acupoints; suggested that a further study should be expected on the low electric resistance property of acupoints and the effect specificity in the treatment of disease. Additionally, they were proposed that the domestic study should focus on the symptom treatment, correct application of logic reasoning, the secondary literature study and international exchange and cooperation. It is indicated that the overseas study has made the great progression on the acupoint locations, morphological structure, biological and physical properties, pathological reaction, stimulation effect, therapeutic effect and mechanism, and it provides the references for the domestic study in terms of study clues and methods.

Truncated active human matrix metalloproteinase-8 delivered by a chimeric adenovirus-hepatitis B virus vector ameliorates rat liver cirrhosis.

BACKGROUND: Liver cirrhosis is a potentially life-threatening disease caused by progressive displacement of functional hepatocytes by fibrous tissue. The underlying fibrosis is often driven by chronic infection with hepatitis B virus (HBV). Matrix metalloproteinases including MMP-8 are crucial for excess collagen degradation. In a rat model of liver cirrhosis, MMP-8 delivery by an adenovirus (Ad) vector achieved significant amelioration of fibrosis but application of Ad vectors in humans is subject to various issues, including a lack of intrinsic liver specificity. METHODS: HBV is highly liver-specific and its principal suitability as liver-specific gene transfer vector is established. HBV vectors have a limited insertion capacity and are replication-defective. Conversely, in an HBV infected cell vector replication may be rescued in trans by the resident virus, allowing conditional vector amplification and spreading. Capitalizing on a resident pathogen to help in its elimination and/or in treating its pathogenic consequences would provide a novel strategy. However, resident HBV may also reduce susceptibility to HBV vector superinfection. Thus a size-compatible truncated MMP-8 (tMMP8) gene was cloned into an HBV vector which was then used to generate a chimeric Ad-HBV shuttle vector that is not subject to superinfection exclusion. Rats with thioacetamide-induced liver cirrhosis were injected with the chimera to evaluate therapeutic efficacy. RESULTS: Our data demonstrate that infectious HBV vector particles can be obtained via trans-complementation by wild-type virus, and that the tMMP8 HBV vector can efficiently be shuttled by an Ad vector into cirrhotic rat livers. There it exerted a comparable beneficial effect on fibrosis and hepatocyte proliferation markers as a conventional full-length MMP-8Ad vector. CONCLUSIONS: Though the rat cirrhosis model does not allow assessing in vivo HBV vector amplification these results advocate the further development of Ad-HBV vectors for liver-specific gene therapy, including and perhaps particularly for HBV-related disease.

Thermal-induced edge barriers and forces in interlayer interaction of concentric carbon nanotubes.

Molecular dynamics simulations reveal that thermal-induced edge barriers and forces can govern the interlayer interaction of double walled carbon nanotubes. As a result, friction in such systems depends on both the area of contact and the length of the contact edges. The latter effect is negligible in macroscopic friction and provides a feasible explanation for the seemingly contradictory laws of interlayer friction, which have been reported in the literature. The temperature-dependent edge forces can be utilized as a driving force in carbon nanotube thermal actuators, and has general implications for nanoscale friction and contact.

Temperature-induced reversible dominoes in carbon nanotubes.

We show by molecular dynamics simulations that there exists a reversible domino process in single walled carbon nanotubes (SWCNTs). SWCNTs with one end collapsed and the other circular are chosen for demonstration. At a low temperature, the collapsed zone spreads over the whole tube, while at a higher temperature, the collapsed zone shrinks, and the circular zone extends along the tube. The reason for the reversible domino process is that the temperature modifies the stable state of the tube. The temperature-induced reversible domino process of SWCNTs provides opportunities for the design of nanoscale heat engines, rechargeable expelling devices, temperature-sensitive devices, mechanical oscillators, and pulse generators, etc.