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Integrating rationally designed DNA molecular walkers and DNA origami platforms is a promising route towards advanced nano-robotics of diverse functions.

Background and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT.Methods This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH).Results Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013).Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

The discovery of RNA interference (RNAi) has created a new platform for cancer therapy applications. This approach utilizes small interfering RNA (siRNA) molecules to regulate the expression of a specific target gene and subsequently suppresses the growth of the cancer cells. However, the formulation of free siRNAs alone is incapable of transfecting cells as they are negatively charged and degrade in biological fluids. For successful siRNA transfection, a biocompatible and functional carrier is needed. In this contribution, we demonstrated the preparation of functionalized single walled carbon nanotubes (SWNTs) as efficient siRNA carriers and utilized the SWNTs/siRNA nanoplex for the in vitro gene therapy of pancreatic cancer. Through fluorescent imaging and quantitative flow cytometric analysis, we observed a high siRNA transfection efficiency mediated by the nanoplex formulation. We demonstrated the successful internalization of the nanoplex by the pancreatic cancer cell and the subsequent release of the siRNAs from the nanoplex, which resulted in a down-regulation of the target gene. In addition, the functionalized SWNTs proved to be highly biocompatible as assessed by cell viability tests. Our results suggest that in the near future the SWNTs may be able to serve as a multifunctional nanoplatform for the in vivo targeted gene therapy of pancreatic cancer.

Transition metal dichalcogenides (TMDCs) are categorized as novel two-dimensional (2D) nanomaterials with unique physical and chemical properties, bearing varied applications in medical and materials sciences. However, only a few works report the application of TMDCs for gene therapy in cancer treatment. Here, we engineer a multi-gene delivery system based on functionalized monolayer MoS2, which can co-deliver HDAC1 and KRAS small interfering RNAs (siRNAs) to Panc-1 cancer cells for combinational cancer therapy. The synergistic effect of gene silencing therapy and NIR phototherapy is demonstrated by inhibition of both genes, in vitro cell growth rate, and in vivo tumor volume growth rate, exemplifying pre-eminent anticancer efficacy. This anti-tumor effect is a result of the photothermal effect of MoS2 induced by NIR excitation and inactivation of HDAC1 and KRAS genes, which consequently bring about apoptosis, inhibit migration, and induce cell cycle arrest in the treated Panc-1 cells. Moreover, good biocompatibility and reduced cytotoxicity of MoS2-based nanocarriers enable their metabolism within in vitro and in vivo mouse models over a prolonged duration without any evident ill-effects. In summary, we demonstrate the promising potential of low-toxicity, functionalized MoS2 nanocarriers as a biocompatible gene delivery system for in vivo pancreatic adenocarcinoma therapy.

INTRODUCTION:Madagascar possesses a land of exceptional endemism for flora and fauna representing 90% of its whole wildlife, which can be considered as one of the highest rates in the world (Annik Schnitzler, 2015). By the splendor of its ecosystem, Madagascar was once called the Green Island. But this name is now changed into the so-called "Red Island' because of the pressure of population on the environment (Bernard Moizo, 2011). One aspect of that pressure is the illegal exploitation of precious wood, rosewood and ebony. The rosewood known under the scientific name Dalbergia of Madagascar (Dalbergia. spp), for decades has become the main target of illegal operations. This rosewood belongs to the rainforest type. Rosewood has a lot of function; among the others, it represents the place where animals like Simpona, Indri Indri and many others dwell. Therefore, it is practically important to protect and preserve it against illegal activities, especially if it is associated with World Heritage areas, namely Marojejy and Masoala National Parks (NPs).Derek S. and Porter P. Lowry II acknowledge an increase rate of illegal logging in the SAVA region, a UNESCO World Heritage Site, where abundant rosewood has been exploited and exported for the last decade ( Derek S. and Porter P. Lowry II, 2009). Confiscated wood has been apprehended in both protected areas of Marojejy and Masoala as suggested by various tangible evidences. (Patel, 2007). Besides, poor local people in the vicinity of the parks as well as several well-organized criminal networks have unceasingly seized on forests exploitation (Derek Schuurman and Porter P. Lowry II, 2009). It is illegal because the illegal logging is defined as the harvest, transport, sale or purchase of timber in contravention to national laws (John Innes, 2010). The Malagasy Law No. 97-017 of 8 August 1997 revising forest legislation has clearly cited in article 17 that, strict nature reserves, national parks, special reserves and protected forests in respect of international conventions as well as land and water areas defined in Article 2 are not likely to distraction (Ministry of Water and Forests, 2015) whereas the logging in question is operated inside the PAs. Environmental Investigation Agency and Global Witness has discovered the illegal harvest of rosewood is about 100 to 200 trees per day in northern Madagascar, according to the survey conducted in 2009 (Global Witness and Environmental Investigation Agency, 2009).This means that these woods are from Marojejy and Masoala, and also from the place around the sites. Thousands of trees are cut illegally, and tons of timbers are exported outside the country in the same way. According to the Ministry of Water and Forest, between 87% of the exploited forests, 60% is for the rosewood only (Brodbeck, 1999 cited in Randriamalala and Zhou). Currently, Madagascar is already suffering serious land degradation due to illegal operations inspite of the presentt laws in vigor governing the protection of forest. Since 2009, rosewood trafficking has never ceased growing. The number of exploiters increases, for instance, in 2009, operators were in total of 13, but in 2012, that number has increased from 19 to 103, or 542% (Hery F. Randriamalala, 2013). The vast majority of rosewood exploitation source, representing 98,5% of them are considered as illegal, according to Rakotondramanga, 2002, while Jerome Ballet et al. 2010, shared the same views emphasizing to an extreme but chaotic illegal exploition of such invaluble wood since the year 2009. Therefore, this present study aimed to, firstly, analyze the reason why the forestry regulation and management policies on rosewood trees are not effective and stop the problems of forest harvesting in Madagascar. Secondly, it proposes recommendations on how to protect the Protected Areas (PAs) of Marojejy and Masoala from illegal logging.MATERIALS AND METHODS:DATA COLLECTION:The data was collected in Madagascar. …

Pancreatic cancer is one of the deadliest cancers throughout the world with rarely efficient therapies currently available. Gene therapy on pancreatic cancer through small interfering RNA (siRNA)-based RNA interference (RNAi) has shown great potential and attracted much attention. However, due to the fragile nature of nucleic acid, the application of RNAi as a safe and efficient carrier faces great challenges. In this contribution, a self-assembly regime, which is based on well-defined cationic polylactides (CPLAs) with tertiary amine groups, has been used to encapsulate and protect siRNAs from fast degradation. CPLA is a safe and degradable formulation that allowed us to deliver siRNAs targeting the proangiogenic chemokine interleukin-8 (IL-8) to pancreatic cancer cells for gene therapy. Stable IL-8 siRNA-CPLA nanoplexes were successfully formed by electrostatic force and high gene transfection efficiencies were shown on two pancreatic cancer cell lines. We did not observe any cytotoxicity from these CPLAs over a large concentration range via cell viability evaluations. More importantly, the silencing of IL-8 gene expression significantly attenuated the proliferation of pancreatic cancer cells. Our preliminary results support the future development of gene therapy that might provide an effective and safe treatment approach towards pancreatic cancer.

Cancer is one of the leading causes of death. Despite the huge progress in the field of cancer drugs and therapies, the treatment outcome is still bleak for most cancer patients. Nanotechnology has revolutionized cancer therapeutics. By using nano‐sized particles as delivery systems, therapeutic biomolecules are transported efficiently to the target sites. Moreover, these particles are designed to carry out multiple cancer treatments simultaneously. Near‐infrared (NIR) light‐responsive nanomaterials have gained much attention as NIR light has a greater penetration depth, minimal phototoxicity, lower autofluorescence, and reduced light scattering. Among the available NIR light‐responsive nanomaterials, gold nanorods, upconversion nanoparticles, carbon dots, transition metal dichalcogenide, metal oxides, black phosphorus, and polymeric nanomaterials have become attractive options owing to their excellent optical properties, ease of synthesis and modification, outstanding photodynamic and photothermal conversion properties, and most importantly, favorable toxicity level and biocompatibility which are prerequisites for biological applications. In this review, the outstanding properties, synthesis, and surface functionalization of the aforementioned NIR light‐responsive nanomaterials are introduced in detail. Recent advances of these nanomaterials for various cancer treatment modalities are summarized to highlight their versatility and potential in cancer theranostics. Finally, a perspective is proposed on future research directions and their clinical translation. Ministry of Education (MOE) Accepted version Y.-H.C., K.K.C., and T.A. contributed equally to this work. This work was supported by the NRF-ANR 2DPS Grant (M4197007.640), Grants Tier 2 MOE2017-T2-2-0022739 (No. M402110000) from Ministry of Education, NTU Start-up Grant M4082109, and the School of Electrical and Electronic Engineering at NTU.

In this work, we propose a new configuration of surface plasmon resonance (SPR) sensor that is based on graphene–MoS2 hybrid structures for ultrasensitive detection of molecules. The proposed system displays a phase-sensitivity enhancement factor of more than 500-fold when compared to the SPR sensing scheme without the graphene–MoS2 coating or with only graphene coating. Our hypothesis is that the monolayer MoS2 has a much higher optical absorption efficiency (∼5%) than that of the graphene layer (∼2.3%). Based on our findings, the electron energy loss of MoS2 layer is comparable to that of graphene and this will allow a successful (∼100%) of light energy transfer to the graphene–MoS2 coated sensing substrate. Such process will lead to a significant enhancement of SPR signals. Our simulation shows that a quasi-dark point of the reflected light can be achieved under this condition and this has resulted in a steep phase jump at the resonance angle of our newly proposed SPR system. More importantly, we found that phase interrogation detection approach of the graphene–MoS2 hybrid structures-based sensing system is more sensitive than that of using the regularly angular interrogation method and our theoretical analysis indicates that 45 nm of Au film thickness and 3 coating layers of MoS2 nanosheet are the optimized parameters needed for the proposed SPR system to achieve the highest detection sensitivity range. Accepted version

One third of all breast cancers are estrogen receptor alpha (ERalpha) negative, carry a poor overall prognosis, and do not respond well to currently available endocrine therapies. New treatment strategies are therefore required. Loss of Wnt-5a has previously been correlated with loss of ERalpha in clinical breast cancer samples, and we sought to investigate this association further. Three breast cancer cell lines (MDA-MB-231, MDA-MB-468, and 4T1) lacking expression of ERalpha and Wnt-5a, and one breast cancer cell line (T47D) expressing both proteins were used in this study. Wnt-5a signaling was generated in ERalpha-negative cell lines via stimulation with either recombinant Wnt-5a protein or a Wnt-5a-derived hexapeptide (Foxy-5) possessing Wnt-5a signaling properties. ERalpha expression was restored at both mRNA and protein level, after treatment with recombinant Wnt-5a or Foxy-5. This restoration of expression occurred in parallel with a reduction in methylation of the ERalpha promoter. Up-regulated ERalpha could be activated, initiate transcription of progesterone receptor and pS2, and activate an estrogen response element reporter construct. Significantly, breast cancer cells re-expressing ERalpha responded to treatment with the selective estrogen receptor modulator tamoxifen, as measured by induction of apoptosis and cell growth inhibition. Finally, Foxy-5 also increased ERalpha expression in an in vivo model of ERalpha-negative breast cancer. This represents the first evidence that Wnt-5a signaling acts to re-establish ERalpha expression in ERalpha-negative breast cancer cells. Our data suggest that combinatorial therapy with Foxy-5 and tamoxifen should be considered as a future treatment possibility for ERalpha-negative breast cancer patients.

A Percoll density gradient was employed for selecting large numbers of viable insulin-producing RINm5F cells. Homogenates of these cells were then subjected to gradient centrifugation and two clearly visible bands were obtained. The light fraction was essentially composed of mitochondria banded at a density of about 1.06 g/ml. The heavier fraction banded at 1.09 to 1.10 g/ml and contained lysosomes and a small number of secretory granules. The distribution of Percoll particles was restricted to the extracellular space and there was no adsorption to any membrane structures. The distribution pattern of marker enzymes for the mitochondria and lysosomes was similar to that of normal pancreatic beta-cells. With the use of a Percoll density gradient it was thus possible to isolate a purified mitochondrial fraction from viable RINm5F cells.