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Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery
摘要： Although new cancer therapeutics are discovered at a rapid pace, lack of effective means of delivery and cancer chemoresistance thwart many of the promising therapeutics. We demonstrate a method that confronts both of these issues with the light-activated delivery of a Bcl-2 functional converting peptide, NuBCP-9, using hollow gold nanoshells. This approach has shown not only to increase the efficacy of the peptide 30-fold in vitro but also has shown to reduce paclitaxel resistant H460 lung xenograft tumor growth by 56.4%.
关键词： Bcl-2,Resistant cancer,Apoptosis,Hollow gold nanoshells,NuBCP,Peptide delivery
更新于2025-11-21 11:08:12
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Antimicrobial-Peptide-Conjugated MoS2 Based Nanoplatform for Multimodal Synergistic Inactivation of Superbugs
摘要： Development of new antibacterial therapeutics material is becoming increasingly urgent due to the huge threat of superbugs, which are responsible for more than half million death each year in this world. Here, we report the development of novel nano-biomaterial based on melittin antimicrobial peptide (AMP) attached transition metal dichalcogenide MoS2 based theranostic nanoplatform. Reported nanoplatform has capability for targeted identification and synergistic inactivation of 100% multidrug-resistant superbugs by combined photo thermal therapy (PTT), photodynamic therapy (PDT) and AMP process. A novel approach for the design of melittin antimicrobial peptide attached MoS2 based nanoplatform is reported, which emits very bright and photo stable fluorescence. It also generates heat as well as reactive oxygen species (ROS) in the presence of 670 nm near infrared light, which allow it to be used as PTT & PDT agent. Due to the presence of AMP, multifunctional AMP exhibits significantly improved antibacterial activity for superbugs via multimodal synergistic killing mechanism. Reported data demonstrate that nanoplatforms are capable of identification of multidrug-resistant superbugs via luminescence imaging. Experimental results show that it is possible to kill only ~45% of superbugs via MoS2 nanopaltform based on PTT & PDT processes together. On the other hand, killing of less than 10% of superbugs is possible using melittin antimicrobial peptide alone. Whereas, 100% Methicillin-resistant Staphylococcus aureus (MRSA), drug resistance Escherichia coli (E. coli) and drug resistance Klebsiella pneumoniae (KPN) superbugs can be killed using antimicrobial peptide attached MoS2 QDs, via synergistic killing mechanism. Mechanisms for possible synergistic killing of multidrug-resistant superbugs have been discussed.
关键词： theranostic transition metal dichalcogenide,photodynamic therapy,multimodal therapy for multidrug-resistant superbugs,Melittin antimicrobial peptide attached MoS2 based nanoplatform,photo thermal therapy
更新于2025-09-23 15:23:52
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Measurement of proton quenching in a LAB-based liquid scintillator
摘要： In this paper, we propose a mathematical model to evaluate the transmission of Tuberculosis with drug-resistant strains and with drug-sensitive strains. Based on the epidemic data from Chinese Center for Disease Control and Prevention, we first estimate the values of parameters in the model. Then the basic reproduction number of TB infection in the mainland China is calculated to be 1.0558. Since the basic reproduction number is greater than 1, Tuberculosis spreads as an endemic in mainland China. Through our investigations, the basic reproduction number associated with drug-sensitive strains is less than 1, but the number of individuals infected by drug-resistant strains will still increase quickly, thus the epidemic is not under control. Moreover, increasing the vaccination coverage rate for newborns is not always beneficial for controlling TB prevalence in China. Whether vaccination effect is positive or negative depends on the relapse rate from the recovered state to the infected state. In summary, improving sanitation conditions, introducing efficient measures to detect the disease, and keeping the public informed about how to lower the chance of being infected and the current epidemic situation are essential in slowing down or eliminating Tuberculosis transmission.
关键词： Tuberculosis Transmission,Drug-Sensitive Strain,The Basic Reproduction Number,Drug-Resistant Strain,Least-Square Method
更新于2025-09-23 15:23:52
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Changes of Intracellular Porphyrin, Reactive Oxygen Species, and Fatty Acids Profiles During Inactivation of Methicillin-Resistant Staphylococcus aureus by Antimicrobial Blue Light
摘要： Antimicrobial blue light (aBL) has attracted increasing interest for its antimicrobial properties. However, the underlying bactericidal mechanism has not yet been verified. One hypothesis is that aBL causes the excitation of intracellular chromophores; leading to the generation of reactive oxygen species (ROS) and the resultant oxidization of various biomolecules. Thus, monitoring the levels of redox-sensitive intracellular biomolecules such as coproporphyrins, as well as singlet oxygen and various ROS may help to uncover the physiological changes induced by aBL and aid in establishing the underlying mechanism of action. Furthermore, the identification of novel targets of ROS, such as fatty acids, is of potential significance from a therapeutic perspective. In this study, we sought to investigate the molecular impact of aBL treatment on methicillin-resistant Staphylococcus aureus (MRSA). The results showed that aBL (5–80 J/cm2) exhibited a bactericidal effect on MRSA, and almost no bacteria survived when 80 J/cm2 had been delivered. Further studies revealed that the concentrations of certain intracellular molecules varied in response to aBL irradiation. Coproporphyrin levels were found to decrease gradually, while ROS levels increased rapidly. Moreover, imaging revealed the emergence and increase of singlet oxygen molecules. Concomitantly, the lipid peroxidation product malondialdehyde (MDA) increased in abundance and intracellular K+ leakage was observed, indicating permeability of the cell membrane. Atomic force microscopy showed that the cell surface exhibited a coarse appearance. Finally, fatty acid profiles at different illumination levels were monitored by GC-MS. The relative amounts of three unsaturated fatty acids (C16:1, C20:1, and C20:4) were decreased in response to aBL irradiation, which likely played a key role in the aforementioned membrane injuries. Collectively, these data suggest that the cell membrane is a major target of ROS during aBL irradiation, causing alterations to membrane lipid profiles, and in particular to the unsaturated fatty acid component.
关键词： membrane injuries,coproporphyrin,lipids,methicillin-resistant Staphylococcus aureus,antimicrobial blue light,unsaturated fatty acids
更新于2025-09-23 15:22:29
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Reduced Graphene Oxide Functionalized with Gold Nanostar Nanocomposites for Synergistically Killing Bacteria through Intrinsic Antimicrobial Activity and Photothermal Ablation
摘要： The exploration of multifunctional photothermal agent is important for antibacterial photothermal lysis, which has emerged as an effective approach to address the problem of pathogenic bacteria infection irrespective of the drug resistant effect. In the present work, a 2D reduced graphene oxide supported Au nanostar nanocomposite (rGO/AuNS) was prepared by the seed mediated growth method for synergistically killing multidrug resistant bacteria. Owing to the prickly and sharp-edge nanostructure, the rGO/AuNS displayed superior antibacterial activity probably due to the damaging of the cell walls or membranes. The cell viability of MRSA was as low as 32% when the MRSA were incubated with rGO/AuNS for 180 min in the absence of light. The 2D structure of the rGO/AuNS facilitated the strong binding affinity towards bacteria. Upon the 808 nm NIR laser irradiation, significant enhancement in bactericidal efficiency (complete death) was obtained due to the localized hyperthermal effect of rGO/AuNS. Moreover, the RGO/AuNS displayed promising biocompatibility. It indicates that the rGO/AuNS can be an alternative and effective dual functional photothermal agent for synergistically killing the multidrug resistant bacteria.
关键词： Reduced Graphene Oxide,Multidrug-resistant bacteria,Antibacterial photothermal lysis,Gold nanostars,Prickly nanostructure
更新于2025-09-23 15:22:29
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Chemically Interconnected Thermotropic Polymers for Transparency-Tunable and Impact-Resistant Windows
摘要： Thermotropic polymers with the capability of thermally tuning transparency are widely applied in smart windows and energy-saving windows, playing a critical role in enhancing comfort level and energy efficiency of indoor spaces. Usually, thermotropic polymer systems are constructed by physically dispersing phase transition materials in transparent hosting materials. However, bad interfaces universally exist in these systems, resulting in poor mechanical properties, weak interfaces to substrates, or bad long-term stability. Herein, we demonstrate a novel chemically interconnected thermotropic polymer, which is obtained by reacting dodecanedioic acid (DDA) with glycerol. In the system, some of DDA molecules were crosslinked to form a polyester network, poly(glycerol-dodecanoate) (PGD). Other grafted but non-crosslinked DDA molecules form semi-crystalline domains which possess a solid-liquid phase transition within the PGD matrix. The phase transition offers the resulting hybrid materials with tunable optical transparency. The PGD-DDA system shows stable performance after 100 heating-cooling cycles. In addition, when applied for window coating, it results in tough interfacial bonding to glass substrates with toughness of > 6910 J m-2 below its transition temperature and > 135 J m-2 above its transition temperature. It increases the impact-resistance of the window by multiple times.
关键词： chemical interconnection,tough interfacial bonding,impact-resistant,smart windows,thermotropic polymers
更新于2025-09-23 15:22:29
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Degradation of Ciprofloxacin and Inactivation of Ciprofloxacin Resistant E. Faecium during UV-LED (275 nm)/Chlorine Process
摘要： Ciprofloxacin and ciprofloxacin-resistant bacteria are emerging concerns that threaten public health due to the heavy use of antibiotics and the development of bacterial resistance in water environments. In this study, we examined an energy-efficient treatment driven by a UV-LED/chlorine reaction with UV-LED chip emitting UV275 nm to remove ciprofloxacin and ciprofloxacin-resistant bacteria in water. Ciprofloxacin degradation during the UV-LED/chlorine reaction followed pseudo-first-order kinetics, and the excessive chlorine dosage has a negative effect on ciprofloxacin removal. Alkaline pH showed the best efficiency for ciprofloxacin removal, and the reactive chlorine species (RCS) played a major role at alkaline pH values. The cleavages of piperazine, cyclopropyl, and quinolone moieties are considered as the principal degradation reactions in the UV-LED/chlorine reaction. Seven byproducts (m/z = 362.9262, 306.1246, 289.0995, 288.1504, 263.0825, 147.0657, and 1183.9977), two chlorinated compounds (chloroform and chlorate) and two anions (formate and nitrate ions) were observed as the identified byproducts. Toxicity of tentatively identified byproducts were estimated by using quantitative structure activity relationship (QSAR). The complete detoxification of D. magna was achieved when applying UV-LED/chlorine process into hospital wastewater containing CIP. The UV-LED/chlorine process showed the best disinfection ability of E. faecium compared to UV-LED photolysis, chlorination, and UV-LED/H2O2 reactions. A significantly lower EE/O value (6.63 × 10-2 kWh/m3/order) during the UV-LED/chlorine reaction was also observed. Our results indicate that the UV-LED/chlorine process can effectively degrade ciprofloxacin and inactivate ciprofloxacin-resistant bacteria.
关键词： toxicity,UV-LED,ciprofloxacin,byproducts,antibiotic-resistant bacteria,Chlorine
更新于2025-09-23 15:21:01
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[IEEE IGARSS 2019 - 2019 IEEE International Geoscience and Remote Sensing Symposium - Yokohama, Japan (2019.7.28-2019.8.2)] IGARSS 2019 - 2019 IEEE International Geoscience and Remote Sensing Symposium - Retrieval of the Forest Leaf Area Index Based on the Laser Penetration Ratio from the GLAS Waveform Lidar Data
摘要： One method of mitigating arc flash hazards associated with medium-voltage switchgear is the installation of active high-speed switch (HSS) systems. These systems are designed to detect and quench a burning internal arc in less than one-third of one electrical cycle. The internal arc is extinguished by the HSS’s action of redirecting the fault current path from arcing through open air back to the intended current path of the switchgear bus. The new low-impedance current path provided by the HSS operation collapses the voltage at the point of the fault to near zero so that the arc is no longer sustainable. The system’s high speed of operation compared to arc quenching via circuit breaker tripping translates directly to lower arc flash incident energy and minimal equipment damage. Another benefit of such active high speed systems could include switchgear compliance to the IEEE C37.20.7 guide for testing arc-resistant metal-enclosed switchgear without any arc by-product venting requirements. This paper explores application considerations of HSS systems relative to other available means of controlling and reducing the hazards of internal arcing faults in medium-voltage switchgear.
关键词： Arc flash incident energy (AFIE),arc resistant,bolted fault,high-speed switch (HSS),X/R ratio,arcing fault
更新于2025-09-23 15:21:01
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The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging and therapy
摘要： A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC.
关键词： Organic anion-transporting polypeptide,Chemotherapy,Castration-resistant prostate cancer,Near-infrared fluorescent dye
更新于2025-09-23 15:21:01
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Impact of interfaces on the radiation response and underlying defect recovery mechanisms in nanostructured Cu-Fe-Ag
摘要： Newest developments in nuclear fission and fusion technology as well as planned long-distance space missions demand novel materials to withstand harsh, irradiative environments. Radiation-induced hardening and embrittlement are a concern that can lead to failure of materials deployed in these applications. Here the underlying mechanisms are accommodation and clustering of lattice defects created by the incident radiation particles. Interfaces, such as free surfaces, phase and grain boundaries, are known for trapping and annihilating defects and therefore preventing these radiation-induced defects from forming clusters. In this work, differently structured nanocomposite materials based on Cu-Fe-Ag were fabricated using a novel solid-state route, combining severe plastic deformation with thermal and electrochemical treatments. The influence of different interface types and spacings on radiation effects in these materials was investigated using nanoindentation. Interface-rich bulk nanocomposites showed a slight decrease in hardness after irradiation, whereas the properties of a nanoporous material remain mostly unchanged. An explanation for this different material behavior and its link to recovery mechanisms at interfaces is attempted in this work, paving a concept towards radiation resistant materials.
关键词： radiation resistant materials,severe plastic deformation,defect-interface interactions,nanostructured materials,nanoindentation
更新于2025-09-23 15:21:01