The effects and mechanisms of natural products on Helicobacter pylori eradication.

Helicobacter pylori (H. pylori) eradication is pivotal for alleviating gastric mucosal inflammation and preventing the progression of gastric diseases. While antibiotic-based therapies have achieved significant success in H. pylori eradication, challenges such as antibiotic resistance, drug toxicity, side effects, nonadherence, inapplicability, and disruption of gastrointestinal microflora have emerged. Updated therapies are urgently needed to suppress H. pylori. Nature has provided multitudinous therapeutic agents since ancient times. Natural products can be a potential therapy endowed with H. pylori eradication efficacy. We summarize the basic information, possible mechanisms, and the latest research progress of some representative natural products in H. pylori eradication, highlighting their safety, accessibility, efficiency, and ability to overcome limitations associated with antibiotic application. This review highlights the potential therapeutic advantages of incorporating ethnomedicine into anti-H. pylori regimens. The findings of this review may provide insights into the development of novel natural products and expand the therapeutic options available for H. pylori eradication.

Derivation of aquatic predicted no-effect concentration and ecological risk assessment for triphenyl phosphate and tris(1,3-dichloro-2-propyl) phosphate.

Triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) are common organophosphate esters (OPEs), which are used as additives in various industries. These compounds have been widely detected in aquatic environment, raising concerns about their adverse effects on aquatic organisms. In order to protect aquatic ecosystems, a total of 7 species were selected for acute and chronic toxicity tests in this study. The results indicated that TPhP and TDCIPP exhibited varying degrees of toxicity to aquatic organisms. The 96-h LC50 values ranged from 1.088 mg/L to 1.574 mg/L for TPhP and from 2.027 mg/L to 17.855 mg/L for TDCIPP. The 28-d LC10 values ranged from 0.023 mg/L to 0.177 mg/L for TPhP and from 0.300 mg/L to 1.102 mg/L for TDCIPP. The tested toxicity data, combined with collected toxicity data, were used to investigate the predicted no-effect concentration in water (PNECwater) of TPhP and TDCIPP by species sensitivity distribution (SSD) method. The results revealed PNECwater values of 6.35 and 38.0 µg/L for TPhP and TDCIPP, respectively. Furthermore, the predicted no-effect concentrations in sediment (PNECsed) were derived as 110 µg/kg dry weight (dw) for TPhP and 424 µg/kg dw for TDCIPP using the equilibrium partitioning (EqP) approach. Based on the toxicity data and PNECs, the ecological risk of these two chemicals in surface waters and sediments worldwide over the last decade were evaluated. The results indicated that TDCIPP posed negligible risk in aquatic ecosystems. However, TPhP showed potential risk in sediments, as indicated by the hazard quotients (HQs) exceeding 0.1. The results of joint probability curves (JPC) indicated that the probabilities of exceeding hazardous concentration for 1 % of species for TPhP in water and sediment were 0.33 % and 5.2 %, respectively. Overall, these findings highlight the need for continued monitoring and assessment of the presence and potential impacts of TPhP and TDCIPP in aquatic ecosystems.

Cross-attention learning enables real-time nonuniform rotational distortion correction in OCT.

Nonuniform rotational distortion (NURD) correction is vital for endoscopic optical coherence tomography (OCT) imaging and its functional extensions, such as angiography and elastography. Current NURD correction methods require time-consuming feature tracking/registration or cross-correlation calculations and thus sacrifice temporal resolution. Here we propose a cross-attention learning method for the NURD correction in OCT. Our method is inspired by the recent success of the self-attention mechanism in natural language processing and computer vision. By leveraging its ability to model long-range dependencies, we can directly obtain the spatial correlation between OCT A-lines at any distance, thus accelerating the NURD correction. We develop an end-to-end stacked cross-attention network and design three types of optimization constraints. We compare our method with two traditional feature-based methods and a CNN-based method on two publicly-available endoscopic OCT datasets. We further verify the NURD correction performance of our method on 3D stent reconstruction using a home-built endoscopic OCT system. Our method achieves a ∼3 × speedup to real time (26 ± 3 fps), and superior correction performance.

Annotation-efficient learning for OCT segmentation.

Deep learning has been successfully applied to OCT segmentation. However, for data from different manufacturers and imaging protocols, and for different regions of interest (ROIs), it requires laborious and time-consuming data annotation and training, which is undesirable in many scenarios, such as surgical navigation and multi-center clinical trials. Here we propose an annotation-efficient learning method for OCT segmentation that could significantly reduce annotation costs. Leveraging self-supervised generative learning, we train a Transformer-based model to learn the OCT imagery. Then we connect the trained Transformer-based encoder to a CNN-based decoder, to learn the dense pixel-wise prediction in OCT segmentation. These training phases use open-access data and thus incur no annotation costs, and the pre-trained model can be adapted to different data and ROIs without re-training. Based on the greedy approximation for the k-center problem, we also introduce an algorithm for the selective annotation of the target data. We verified our method on publicly-available and private OCT datasets. Compared to the widely-used U-Net model with 100% training data, our method only requires ∼10% of the data for achieving the same segmentation accuracy, and it speeds the training up to ∼3.5 times. Furthermore, our proposed method outperforms other potential strategies that could improve annotation efficiency. We think this emphasis on learning efficiency may help improve the intelligence and application penetration of OCT-based technologies.

Ecotoxicity stress and bioaccumulation in Eisenia fetida earthworms exposed to vanadium pentoxide in soil.

As an important commercial form of vanadium, vanadium pentoxide (V2O5) is widely used in various modern industries, and its environmental impacts and ecotoxicity have been extensively studied. In this research, the ecotoxicity of V2O5 to earthworms (Eisenia fetida) in soil was tested by exposure to V2O5 at a series of doses, and biochemical response indices, such as the superoxide dismutase (SOD) and catalase (CAT) enzyme activity and malondialdehyde (MDA) content, were analysed to determine the mechanism by which antioxidant enzymes respond to V2O5 exposure. The bioaccumulation factor (BAF) of vanadium pentoxide in the earthworms and soil was also measured to explore the bioaccumulation process of V2O5 in the test period. The results showed that the acute and subchronic lethal toxicity values of V2O5 towards E. fetida were 21.96 mg/kg (LC50, 14 days) and 6.28 mg/kg (LC10, 28 days), respectively. For the antioxidant enzymes, SOD and CAT were synchronously induced or inhibited within the time period, and the enzyme activity had a dose-effect relationship with the V2O5 concentration. MDA analysis indicated that lipid peroxidation in earthworms mainly occurred at the early stage and was eliminated slowly in the later stage during the test time. In addition, the BAFs were much less than 1, which indicated that V2O5 did not easily accumulate in earthworms, and the BAF was positively correlated with the exposure time and negatively linearly correlated with the V2O5 concentration in the soil. These results indicated that the bioconcentration and metabolic mechanism of V2O5 in earthworms differed with the different exposure concentrations, and bioaccumulation became balanced after 14-28 days in earthworms exposed to a relatively lower dose of V2O5. The analysis of the integrated biomarker response (IBR) index indicated that the trends of IBR values were positively related to the changing V2O5 concentration, and the IBR index could reflect the organism's sensitivity to the external stimulus of V2O5. The toxicity of V2O5 is mainly caused by V5+, which is also an important factor in formulating guidelines regarding vanadium levels in soil, and the test earthworm species (Eisenia fetida) is a sensitive biological indicator for risk assessments of vanadium oxidation in the soil.

A New Conformal Penetrating Heating Strategy for Atherosclerotic Plaque.

(1) Background: A combination of radiofrequency (RF) volumetric heating and convection cooling has been proposed to realize plaque ablation while protecting the endothelial layer. However, the depth of the plaque and the thickness of the endothelial layer vary in different atherosclerotic lesions. Current techniques cannot be used to achieve penetrating heating for atherosclerosis with two targets (the specified protection depth and the ablation depth). (2) Methods: A tissue-mimicking phantom heating experiment simulating atherosclerotic plaque ablation was conducted to investigate the effects of the control parameters, the target temperature (Ttarget), the cooling water temperature (Tf), and the cooling water velocity (Vf). To further quantitatively analyze and evaluate the ablation depth and the protection depth of the control parameters, a three-dimensional model was established. In addition, a conformal penetrating heating strategy was proposed based on the numerical results. (3) Results: It was found that Ttarget and Tf were factors that regulated the ablation results, and the temperatures of the plaques varied linearly with Ttarget or Tf. The simulation results showed that the ablation depth increased with the Ttarget while the protection depth decreased correspondently. This relationship reversed with the Tf. When the two parameters Ttarget and Tfwere controlled together, the ablation depth was 0.47 mm-1.43 mm and the protection depth was 0 mm-0.26 mm within 2 min of heating. (4) Conclusions: With the proposed control algorithm, the requirements of both the ablation depth and the endothelium protection depth can be met for most plaques through the simultaneous control of Ttarget and Tf.

A coupled thermal-electrical-structural model for balloon-based thermoplasty treatment of atherosclerosis.

OBJECTIVES: The outcome of balloon-based atherosclerosis thermoplasty is closely related to the temperature/stress distribution during the treatment. For precise prediction of a required thermal lesion in the heterogeneous and thin atherosclerotic vessel, a numerical model incorporating heat-induced tissue expansion or shrinkage and the strain caused by balloon dilation is necessary. METHODS: A fully coupled thermal-electrical-structural new model was established. The model features a heterogeneous structure including eccentric plaque, healthy artery and surrounding tissue. Tissue expansion/shrinkage and hyperelasticity material model were taken into consideration. Different heating strategies and plaque mechanical properties were investigated. The temperature distribution was compared with the traditional thermal-electrical coupled model. The possibility of thermoplasty treatment using balloons with different sizes was also explored. RESULTS: The temperature, the electrical intensity and the stress during the thermoplasty were obtained. Lower stress was found in the heating region where tissue shrinkage occurred. The ablation depth was predicted to be ∼0.42 mm larger without coupling the biomechanical influence. The mechanical properties and input condition significantly affect the temperature and stress distribution considering the small dimensions of the tissue. Besides, with a 12.5% reduction of balloon diameter, the largest Von Mises stress decreases by 25.4%. CONCLUSIONS: It is confirmed that a coupled thermal-electrical-structural model is needed for precise temperature prediction in the balloon-based thermoplasty of the heterogeneous and thin tissue. The model presented may help with future development of optimized treatment planning considering both ablation depth and minimum stress.

Human health ambient water quality criteria and risk assessment of pentachlorophenol in Poyang Lake Basin, China.

Pentachlorophenol (PCP) has been widely used as an insecticide for killing oncomelania (the intermediate host of schistosome) in China and leads to severe environmental contamination. Poyang Lake, as the largest freshwater lake and bird habitat in China, was once a schistosomiasis epidemic area. In this study, the concentrations of PCP in water and aquatic products from Poyang Lake were determined and analyzed, and then the human health ambient water quality criteria (AWQC) was derived based on native parameters of Poyang Lake basin. Finally, a comprehensive analysis of the health risks of drinking water and different types of aquatic products consumption was carried out. The results showed that PCP concentrations were ranged from 0.01 to 0.43 µg/L in surface water and 3.90 to 85.95 µg/kg in aquatic products. Due to the carcinogenicity of PCP, the human health AWQC for PCP are 0.02 µg/L for consumption of water and organisms and 0.03 µg/L for consumption of organisms only. Deterministic and probabilistic risk analysis indicated that the non-carcinogenic risk of PCP were acceptable in Poyang Lake, while the carcinogenic risk cannot be ignored. The health risks of PCP caused by aquatic products consumption were higher than that by drinking water. The percentages of acceptable risk for the population in Poyang Lake Basin were 99.95% at acceptable level of 10-4. Based on the sensitivity analysis, the impact of PCP concentrations on health risk values ranged from 53 to 82%. The study provided valuable information for regional water quality criteria development and water quality assessment.

Synergetic Thermal Therapy for Cancer: State-of-the-Art and the Future.

As a safe and minimal-invasive modality, thermal therapy has become an effective treatment in cancer treatment. Other than killing the tumor cells or destroying the tumor entirely, the thermal modality results in profound molecular, cellular and biological effects on both the targeted tissue, surrounding environments, and even the whole body, which has triggered the combination of the thermal therapy with other traditional therapies as chemotherapy and radiation therapy or new therapies like immunotherapy, gene therapy, etc. The combined treatments have shown encouraging therapeutic effects both in research and clinic. In this review, we have summarized the outcomes of the existing synergistic therapies, the underlying mechanisms that lead to these improvements, and the latest research in the past five years. Limitations and future directions of synergistic thermal therapy are also discussed.

Self-supporting, ultra-thin and highly transparent conducting nickel grids for extremely flexible and stretchable electrochromic devices.

It has been a great challenge to design an extremely flexible and stretchable electrochromic device (ECD), due to the physical deformation and fracture of the conductive materials and supporting substrates after plenty of bending. To solve the aforementioned shortcoming of ECDs, in this paper, a self-supporting metal Ni gird electrode is mentioned, which discarded solid or flexible polymeric substrates, having outstanding features of extremely foldability (bending radius lower 50 µm), stretchability (stretching to 117.6%), excellent conductivity (sheet resistance lower 0.4 Ω/sq), high transmittance (about 90% in full spectra), and ultra-thin thickness (3.7 µm). By assembling the metal electrode, the electrochromic material and the hydrogel, a paper-thin, ultra-flexible, and stretchable ECD with an overall thickness of 113 µm was prepared, which could be attached to the manifold and undulating surface of things and be stretched without compromising the dynamic bleaching and coloration performance. The triple-layered and substrate-free ECD with excellent flexibility and wearability could serve as futuristic electronics used for multiple purposes, like flexible displays, camouflage wearables and medical monitoring, etc.

Freestanding "core-shell" AgNWs/metallic hybrid mesh electrodes for a highly efficient transparent electromagnetic interference shielding film.

We fabricated the freestanding "core-shell" AgNWs/ Ni mesh electrodes by employing AgNWs solution onto the freestanding Ni-mesh. The combination of AgNWs and Ni mesh resulted in higher electrical conductivity, thereby enhancing the electromagnetic interference (EMI) shielding effectiveness (SE). The hybrid freestanding electrode created highly effective transparent and flexible EMI shielding films, featuring an ultrathin thickness (3 µm), the high optical transparency of 93% at 550 nm, and a SE of 41.5 dB in the X-band, which exceeds that of 30 dB for a freestanding Ni-mesh (94%). We showed that the hybrid freestanding AgNWs/Ni-mesh film is a promising high-performance transparent and flexible EMI shielding material that satisfies the requirements for optoelectronic devices.

[Human Health Risk Assessment of Phenol in Poyang Lake Basin].

Phenol is widely used in the production of insulation and thermal insulation materials, adhesives, perfumes, coatings for food containers, paints, and pharmaceutical production, and is also widely detected in the aquatic environment. Long-term exposure to phenol can elicit adverse effects, such as skin burn, liver and central system damage. Here, phenol concentrations in the water and aquatic products of Poyang Lake were investigated. Human health risks from phenol to adults and adolescents were also assessed based on local population exposure parameters. The exposure concentration range of phenol in the studied water and aquatic products was not detected (ND)-556.26 ng·L-1 and 11.98-255.51 µg·kg-1, respectively. Human health risk based on drinking water in different areas ranged from 3.80×10-7-8.46×10-5. Higher human health risks from drinking water was detected in the southern area of Poyang Lake and at the confluence of the Yangtze River to the north. Health risks caused by different types of aquatic products ranges 2.65×10-5-1.47×10-4. In particular, human health risks from the consumption of yellow catfish and catfish are an order of magnitude higher than for other aquatic products. Probabilistic risk assessment was also conducted through Monte Carlo simulation to analyze the health risk to the population in the Poyang Lake Basin and assess its sensitivity of different exposure parameters. The 95th percentile health risk of drinking water and aquatic product consumption in the Poyang Lake Basin was calculated as being acceptable. Overall, the concentrations of phenol had the greatest impact on the calculated health risk values. This study provides valuable information for phenol risk management in the Poyang Lake basin.

Exposure and tiered ecological risk assessment of phthalate esters in the surface water of Poyang Lake, China.

Phthalate esters (PAEs) are a class of endocrine disruptors that are produced and used extensively in China. Given its presence in various products, a great quantity of PAEs flows into different aquatic systems each year. Hence, it is important to study the pollution levels and ecological risk of PAEs. This study investigated the distribution and seasonal variation of six priority PAEs in the surface water of Poyang Lake, the largest freshwater lake in China. In the wet season, the mean concentration of the total PAEs was 0.544 ± 0.173 µg/L, while the dry season concentration (1.003 ± 0.451 µg/L) nearly doubled. The most abundant PAE congeners were di-n-butyl phthalate (DBP), followed by bis (2-ethylhexyl) phthalate (DEHP). To evaluate the ecological risks in Poyang Lake, the predicted no-effect concentrations (PNECs) of four PAEs based on non-lethal effects were derived. For diethyl phthalate (DEP), butyl benzyl phthalate (BBP), DBP, and DEHP, the PNECs were 31.6, 3.30, 2.31, and 0.0210 µg/L, respectively. The tiered ecological risk assessment showed that DEP and BBP posed no risk in Poyang Lake. Meanwhile, DBP posed a potential risk in Poyang Lake, but the risk of DEHP was unacceptable and requires more actions. Specifically, the probabilities of exceeding the threshold for the protection of 95% of the aquatic organisms (HC5) were 3.30% and 4.43% for DEHP in the wet and dry season, respectively. This study provides an appropriate reference for the surface water management of PAE pollution in China.

Embedded flexible and transparent double-layer nickel-mesh for high shielding efficiency.

An efficient approach to obtain high shielding effectiveness (SE) in transparent shielding in an optical window field is proposed and demonstrated by fabricating an embedded double-layer metallic mesh (DLMM) comprised of randomly structured Ni meshes on both sides of a flexible substrate, employing a facile and low-cost double-sided nanoimprinting method. The unique nonperiodic random structure contributes to uniform diffraction and eliminates the Moiré fringe generated by double-layer periodic meshes, ensuring high imaging quality for optical applications. The designed DLMM films simultaneously achieve strong shielding in the X-band and high transmittance in the visible spectrum, demonstrating a high transmittance of 88.7% at the 550-nm wavelength and a SE of 46.9 dB at a frequency of 8.2 GHz. An ultra-high SE of 80 dB is achieved at 64.2% transmittance, which reveals the highest reported SE over a metallic mesh for transparent shielding, indicating the high potential for this transparent electromagnetic interference shielding material for practical optical applications.

Ecological and health risk assessment of perfluorooctane sulfonate in surface and drinking water resources in China.

Perfluorooctane sulfonate (PFOS) is a synthetic substance with a great number of applications. However, it persists in the environment and is potentially toxic to organisms. Although China has been the main manufacturer and consumer for PFOS, the national pollution level and potential risk of this chemical are yet to be determined. This study aimed to provide an overview of PFOS contamination in surface and drinking water across China and to assess the potential ecological and health risks. Available monitoring data for PFOS in surface and drinking water were evaluated. PFOS was found to be ubiquitous in China, but the overall level of contamination was low compared with that in other countries. The southeast coastal area of China, with major PFOS-related companies, was characterized by relatively high PFOS exposure concentrations. The most sensitive effects was screened and applied to assess the ecological risk using the joint probability curve method. The probability of exceeding the growth and development toxicity for 5% of aquatic species was 0.65% in Chinese surface waters, while the highest probability of 0.90% was in Tai Lake in east China. Considering the average daily dose (ADD) for the Chinese population, the health risk posed by PFOS through drinking water ranged from 1.31 × 10-4 to 13.91. Besides the relatively high health risk existed in east China, most health risks in China were acceptable.

A new radiofrequency balloon angioplasty device for atherosclerosis treatment.

BACKGROUND: Restenosis remains a challenge in the treatment of atherosclerosis due to damage to the endothelial layer and induced proliferation of smooth muscle cells. A novel radiofrequency (RF) heating strategy was proposed to selectively ablate atherosclerosis plaque and to thermally inhibit the proliferation of smooth muscle cells while keeping the endothelial cells intact. METHODS: To realize the proposed strategy, a new radiofrequency balloon catheter, consisting of three ports, a three-channel tube, a balloon and an electrode patch, was designed. To evaluate the feasibility of this new design, a phantom experiment with thermocouples measuring temperatures with different voltages applied to the electrodes was conducted. A numerical model was established to obtain the 3D temperature distribution. The heating ability was also evaluated in ex vivo diseased artery samples. RESULTS: The experimental results showed that the highest temperature could be achieved in a distance from the surface of the balloon as designed. The temperature differences between the highest temperature at 0.78 mm and those of the surface reached 9.87 °C, 12.55 °C and 16.00 °C under applied 15 V, 17.5 V and 20 V heating, respectively. In the circumferential direction, the heating region (above 50 °C) spread from the middle of the two electrodes. The numerical results showed that the cooling effect counteracted the electrical energy deposition in the region close to the electrodes. The thermal lesion could be directed to cover the diseased media away from the catheter surface. The ex vivo heating experiment also confirmed the selective heating ability of the device. The temperature at the targeted site quickly reached the set value. The temperature of the external surface was higher than the inner wall surface temperature of the diseased artery lumen. CONCLUSION: Both the experimental and numerical results demonstrated the feasibility of the newly designed RF balloon catheter. The proposed RF microelectrodes heating together with the cooling water convection can realize the desired heating in the deeper site of the blood vessel wall while sparing the thin layer of the endothelium.

Highly flexible electrochromic devices enabled by electroplated nickel grid electrodes and multifunctional hydrogels.

Flexible electronics, as a futuristic technology, is presenting tremendous impact in areas of wearable displaying, energy saving, and adaptive camouflage. In this work, we constructed a simple triple-layered electrochemical device with high flexibility using the electroplated nickel (Ni) grid electrode and the multifunctional hydrogel. The Ni grid electrode with low resistance (0.5 Ω/sq), high optical transparency (84.8%) and good mechanical flexibility, is beneficial for efficient electron injection, while the transparent lithium chloride hydrogel functions simultaneously for ion storage, ion transportation and counter-conducting. The thin polymer poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) film is utilized as the electrochromic (EC) material and it also distributes the electrons evenly for uniform coloration. The triple-layered EC architecture not only simplifies the manufacturing procedures but also improves the device performance in terms of optical contrast and mechanical robustness. The device shows fast response for coloration and bleaching with an absolute transmittance contrast of 40% and a contrast retention over 72% after 2500 bending cycles. The ability of the flexible electrochromic device for conformable attaching was also investigated without obvious performance degradation. The electroplated Ni grid electrode and the multifunctional hydrogel are advantageous in constructing flexible electrochromic devices in terms of the response time, the working stability and the bending capability, paving a way for next-generation flexible electronics.

A New RF Heating Strategy for Thermal Treatment of Atherosclerosis.

OBJECTIVES: Restenosis remains a challenge for the treatment of atherosclerosis due to the damage of the endothelial layer and induced proliferation of the smooth muscle cell. METHODS: A new RF heating strategy was proposed to selectively ablate the atherosclerosis plaque, and to thermally inhibit the proliferation of smooth muscle cells, while keeping the endothelial cells intact. To achieve the goal, an internal cooling agent and distributed electrodes have been integrated in the new designed balloon catheter to focus the shape conformal energy onto the plaque shape. A three-dimensional (3-D) model with experimentally fitted parameters has been established to demonstrate the heating ability of the design and evaluate the microelectrodes configurations for different plaque geometries. RESULTS: The 3-D shape of the lesions resulting from different electrodes settings is obtained. It is found that by individual control of the micro-electrodes, special shapes of the lesions can be formed, which can match the eccentric crescent plaques. Besides, through changing of the polarity of the electrodes, separate lesions can be reached. This suggests the possibility for treatment of disconnected plaques in situ. CONCLUSION: By the control of RF heating and convection coefficient of the internal cooling agent, a targeted heating region away from the inner surface of the blood vessel can be realized. SIGNIFICANCE: This study has illustrated the possibility of achieving a precision thermal treatment of atherosclerosis in favor of inhibiting further restenosis.

Dual Tumor-Targeting Nanocarrier System for siRNA Delivery Based on pRNA and Modified Chitosan.

Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size. To certify the delivering efficiency of this dual system, CNPPs, pRNA dimers alone, chitosan nanoparticles containing siRNA with folate conjugation and PEGylation (CNPS), and chitosan nanoparticles containing pRNA dimers alone (CN) were first prepared. Then, we observed that treatment with CNPPs resulted in increased cellular uptake, higher cell apoptosis, stronger cell cytotoxicity, and more efficacious gene silencing compared to the other three formulations. Higher accumulation of siRNA in the tumor site, stronger tumor inhibition, and longer circulating time were also observed with CNPPs compared to other formulations. In conclusion, this dual nanocarrier system showed high targeting and favorable therapeutic efficacy both in vitro and in vivo. Thereby, a new approach is provided in this study for specific and efficient delivery of siRNA, which lays a foundation for the development of pRNA hexamers, which can simultaneously carry six different substances.

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL) at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic.