Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Human serum albumin-bound paclitaxel nanoparticle inhibits cervical carcinoma cell proliferation and oxidative damage through CYP3A4 and CYP2C8.

Background: Cervical cancer (CC) is currently the most common malignant tumour in the female reproductive tract, and paclitaxel (PTX) is a commonly used chemotherapeutic agent, but tumour cell resistance will seriously affect the therapeutic efficacy of PTX. Nanoparticle human serum albumin-bound paclitaxel (Nano-HSA-PTX) is a novel drug delivery modality that may have superior effects to PTX alone. Objective: To clarify the effect of Nano-HSA-PTX on cervical carcinoma (CC) cells and the underlying mechanisms. Methods: After the preparation of Nano-HSA-PTX, its morphology was observed by electron transmission microscope (TEM), and its entrapment efficiency (EE%) and drug loading rate (DL%) were detected. Nano-HSA-PTX was compared with conventional PTX for drug metabolism. Additionally, CC HeLa and SiHa cells were purchased and divided into three groups to treat with Nano-HSA-PTX, PTX and normal saline, respectively. MTT, cell cloning, Transwell and cell scratch assays were carried out to determine cell proliferation, invasion and migration, flow cytometry and Western blotting were performed to detect apoptosis rate and apoptosis-related protein expression, and PCR was conducted to quantify oxidative damage indicators. Further, CYP3A4 and CYP2C8 expression patterns in CC cells (HeLa and SiHa) and human normal cervical epithelia (End1/E6E7) and the changes of their levels under the intervention of Nano-HSA-PTX were measured. Subsequently, C57BL/6mice were purchased for subcutaneous tumorigenesis experiment to observe the impact of Nano-HSA-PTX on tumor growth. Results: Under TEM, Nano-HSA-PTX was complete and arranged compactly, with a stable structure and markedly higher EE% and DL% than PTX (P < 0.05). Under Nano-HSA-PTX intervention, the proliferation, invasion, migration and oxidative damage of HeLa and SiHa were significantly decreased compared with the control and PTX groups, while the apoptosis was increased (P < 0.05). Besides, elevated CYP3A4 and CYP2C8 levels were observed in CC cells, which were inhibited by Nano-HSA-PTX and PTX (P < 0.05). Finally, tumorigenesis experiments in nude mice revealed that Nano-HSA-PTX could inhibit tumor growth. Conclusion: Compared with PTX, Nano-HSA-PTX has a superior effect of inhibiting CC activity. And this mechanism of action was carried out by inhibiting the expression of CYP3A4 and CYP2C8.

Application of cantharidin, retinoic acid cream and salicylic acidy in multiple palmoplantar warts.

OBJECTIVE: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream. METHODS: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months. RESULTS: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001). CONCLUSION: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise.

Near-zero beam drift laser tracking and measurement system with two-stage compression structures.

This paper introduces a scheme of near-zero beam drift tracking technology with two-stage compression structures for the coordinate accuracy measurement of a laser tracker. The Galileo telescope system, with a magnification of 21.43, is designed to compress the beam drift in a dual-frequency interferometer. The azimuth and pitch of the beam drift are compressed to 2.41 in. and 2.92 in., and the compression rates are 95.0% and 91.9%, respectively. The improved four degrees of freedom position-sensitive detector system is used to further compress the beam drift. The peak-to-peak value of the beam drift is 0.9 in. in the azimuth direction and 2.1 in. in the pitch direction. The standard deviation of azimuth is within 0.15 in, and the pitch is within 0.43 in. The coordinate accuracy of the laser tracker can be improved 6.85 parts per million by simulation. The developed two-stage compression near-zero beam drift system can be used in the laser tracker to realize large-scale precision instrument geometric measurement.

High-velocity measurement method in dual-frequency laser interference tracker based on beam expander and acousto-optic modulator.

The laser tracker, as a new large-scale measuring instrument of combining conventional measurement technology and modern control technology, has the advantages of intelligence, portability, large measurement space, high measurement accuracy and short detection period. However, the laser tracker has strict requirements on the moving speed of the spherically mounted retroreflector. This deficiency not only limits the application of the measuring instrument in the field of high-velocity measurement, but also greatly reduces the measurement efficiency. In this work, we analyze the factors that affect the tracking velocity of the laser tracker, and propose for the first time to use the beam expander device to improve the transverse tracking measurement velocity of the instrument. The experimental results show that the laser tracker miss distance can reach 2.25 mm. The transverse tracking velocity and acceleration can reach 4.34 m/s and 2.4 g, respectively. Additionally, the acousto-optic modulator is used to increase the frequency difference between the reference beam and the measuring beam, so that the value is greater than 19 MHz. The radial tracking measurement velocity can reach 6.2 m/s. The high-velocity laser interference tracker developed by this new method can be used in the field of large-scale space precision measurement such as nuclear power, medical treatment and rail transit.

Prime factorization via localized tile assembly in a DNA origami framework.

Modern cybersecurity built on public-key cryptosystems like Rivest-Shamir-Adleman is compromised upon finding solutions to the prime factorization. Nevertheless, solving the prime factorization problem, given a large N, remains computationally challenging. Here, we design DNA origami frameworks (DOFs) to direct localized assembly of double-crossover (DX) tiles for solving prime factorization with a model consisting of the computing, decision-making, and reporting motifs. The model implementation is based on the sequential assembly of different DX tiles in the DOF cavity that carries overhangs encoding the prime and composite integers. The primes are multiplied and then verified with the composite, and the result is visualized under atomic force microscopy via the presence (success) or absence (failure) of biotin-streptavidin labels on the reporting DX tile. The factorization of semiprimes 6 and 15 is realized with this DOF-based demonstration. Given the potential of massively parallel processing ability of DNA, this strategy opens an avenue to solve complex mathematical puzzles like prime factoring with molecular computing.

Metronidazole-loaded nanoparticulate thermoreversible gel for gynecologic infection of Trichomonas vaginalis.

OBJECTIVE: Trichomoniasis is a common sexually-transmitted disease that is associated with increased perinatal morbidity and human immunodeficiency virus (HIV) transmission. This study aimed to develop a Metronidazole-loaded nanoparticulate thermoreversible gel for gynecological infection of Trichomonas vaginalis (T. vaginalis). METHODS: The optimized nanoparticulate formulation was used in thermoreversible gel and characterized for physico-chemical properties, antiparasitic activity, and in vivo efficacy in the BALB/c mouse model. RESULT: A nearly threefold rise in antiparasitic activity of the optimized formulation was observed as compared to that of regular gel. Formulation F5 successfully cured the trichomoniasis within 3 days, while regular gel and pure Metronidazole (MTDZ) failed to cure this infection (P<0.05). CONCLUSION: The present investigation confirms the ability of thermoreversible gel containing nanoparticulate metronidazole againstthe infection by T. vaginalis. The developed gel could be an alternative to the existing drug delivery system for the treatment of trichomoniasis.

Survey of antibacterial activity and release kinetics of gold-decorated magnetic nanoparticles of Fe0 conjugated with sulfamethoxazole against Escherichia coli and Staphylococcus aureus.

Drug delivery of antibiotics with magnetic nanoparticles improved by coating metals such as gold and silver has recently been studied. This work describe a simple method to synthesize modified magnetic nanoparticles which have high ability to modify the customary formulation of antibiotics such as sulfamethoxazole (SMX) and pursuant study of adsorption-desorption (release) of this drug. These synthesized nanoparticles were characterized by different methods, including field emission scanning electron microscopy, energy dispersive X-ray spectroscopy and mapping, Fourier-transform infrared spectroscopy, X-ray diffraction, vibrating-sample magnetometry, thermogravimetric analysis and zeta potential test. Present assay showed a well correlation with the introduced carrier for the drug. Also the hypothesis were proved by some adsorption isotherm models and drug kinetics studies of carriers with different drug release kinetics models. This study confirmed the adsorption isotherm models and kinetics of drug sorbate are Temkin and Pseudo-First-Order Lagergren models, respectively; the kinetics of drug release from this carrier is based on Zero-Order model. The values of MIC in antibacterial test for pure SMX and SMX conjugated nanoparticles against Escherichia coli were calculated to be 14 and 2.5 µg/mL, respectively, and these values against Staphylococcus aureus were 24 and 1.25 µg/mL, respectively.

Height measurement of microbumps using a white-light triangulation method.

As the electronic interconnection between chips, microbumps are crucial components in advanced packaging for the demand of better performance and higher packaging density. The height and coplanarity of microbumps are critical to ensure the reliability of connections. The poor uniformity in bump height will lead to disconnect or insufficient contact, which will directly result in the failure of the chip's function and a lower yield rate. In this paper, we proposed a height measurement method of microbumps using white-light triangulation combined with geometrical characteristics of bumps. A linear light projection module composed of a lens group and LED light source was set up as well as a high-quality imaging module consisting of a CCD camera and microscope objective group. The projection and imaging model of microbumps illuminated by the light plane at different positions during the scanning process was analyzed. The microbump height is computed from a simple formula based on the geometry of the specimen and the system configuration. The measurement results are compared with that obtained from a commercial optical profiler, and the measurement uncertainty is analyzed in detail.

Metastable Iron Sulfides Gram-Dependently Counteract Resistant Gardnerella Vaginalis for Bacterial Vaginosis Treatment.

Bacterial vaginosis (BV) is the most common vaginal infection found in women in the world. Due to increasing drug-resistance of virulent pathogen such as Gardnerella vaginalis (G. vaginalis), more than half of BV patients suffer recurrence after antibotics treatment. Here, metastable iron sulfides (mFeS) act in a Gram-dependent manner to kill bacteria, with the ability to counteract resistant G. vaginalis for BV treatment. With screening of iron sulfide minerals, metastable Fe3 S4 shows suppressive effect on bacterial growth with an order: Gram-variable G. vaginalis >Gram-negative bacteria>> Gram-positive bacteria. Further studies on mechanism of action (MoA) discover that the polysulfide species released from Fe3 S4 selectively permeate bacteria with thin wall and subsequently interrupt energy metabolism by inhibiting glucokinase in glycolysis, and is further synergized by simultaneously released ferrous iron that induces bactericidal damage. Such multiple MoAs enable Fe3 S4 to counteract G. vaginalis strains with metronidazole-resistance and persisters in biofilm or intracellular vacuole, without developing new drug resistance and killing probiotic bacteria. The Fe3 S4 regimens successfully ameliorate BV with resistant G. vaginalis in mouse models and eliminate pathogens from patients suffering BV. Collectively, mFeS represent an antibacterial alternative with distinct MoA able to treat challenged BV and improve women health.

Ionic Current Fluctuation and Orientation of Tetrahedral DNA Nanostructures in a Solid-State Nanopore.

Understanding the dynamic behavior of a nanostructure translocating through a nanopore is important for various applications. In this paper, the characteristics in ion current traces of tetrahedral DNA nanostructures (TDN) translocating through a solid-state nanopore are examined, by combined experimental and theoretical simulations. The results of finite element analysis reveal the correlation between orientation of TDN and the conductance blockade. The experimentally measured fluctuations in the conductance blockade, expressed as voltage-dependent histogram profiles, are consistent with the simulation, revealing the nature of a random distribution in orientation and weak influence of electrostatic and viscous torques. The step changes in orientation of a TDN during translocation are further explained by the collision with the nanopore, while the gradual changes in orientation illustrate the impact of a weak torque field in the nano-fluidic channel. The results demonstrate a general method and basic understanding in the dynamic behavior of nanostructures translocating through solid-state nanopores.

Remote Photothermal Control of DNA Origami Assembly in Cellular Environments.

In situ synthesis of DNA origami structures in living systems is highly desirable due to its potential in biological applications, which nevertheless is hampered by the requirement of thermal activation procedures. Here, we report a photothermal DNA origami assembly method in near-physiological environments. We find that the use of copper sulfide nanoparticles (CuS NPs) can mediate efficient near-infrared (NIR) photothermal conversion to remotely control the solution temperature. Under a 4 min NIR illumination and subsequent natural cooling, rapid and high-yield (>80%) assembly of various types of DNA origami nanostructures is achieved as revealed by atomic force microscopy and single-molecule fluorescence resonance energy transfer analysis. We further demonstrate the in situ assembly of DNA origami with high location precision in cell lysates and in cell culture environments.

DNA Nanoribbon-Templated Self-Assembly of Ultrasmall Fluorescent Copper Nanoclusters with Enhanced Luminescence.

Fluorescent copper nanoclusters (CuNCs) have been widely used in chemical sensors, biological imaging, and light-emitting devices. However, individual fluorescent CuNCs have limitations in their capabilities arising from poor photostability and weak emission intensities. As one kind of aggregation-induced emission luminogen (AIEgen), the formation of aggregates with high compactness and good order can efficiently improve the emission intensity, stability, and tunability of CuNCs. Here, DNA nanoribbons, containing multiple specific binding sites, serve as a template for in situ synthesis and assembly of ultrasmall CuNCs (0.6 nm). These CuNC self-assemblies exhibit enhanced luminescence and excellent fluorescence stability because of tight and ordered arrangement through DNA nanoribbons templating. Furthermore, the stable and bright CuNC assemblies are demonstrated in the high-sensitivity detection and intracellular fluorescence imaging of biothiols.

Translocation of tetrahedral DNA nanostructures through a solid-state nanopore.

Tetrahedral DNA nanostructures (TDNs) are programmable DNA nanostructures that have great potential in bio-sensing, cell imaging and therapeutic applications. In this study, we investigate the translocation behavior of individual TDNs through solid-state nanopores. Pronounced translocation signals for TDNs are observed that are sensitive to the size of the nanostructures. TDNs bound to linear DNA molecules produce an extra signal in the ionic current traces. Statistical analysis of its relative temporal position reveals distinct features between TDNs bound to the end and those bound to the middle of the linear DNA molecules. A featured current trace for two TDNs bound to the same linear DNA molecule has also been observed. Our study demonstrates the potential of using TDNs as sensitive bio-sensors to detect specific segments of a single DNA molecule in real time, based on solid-state nanopore devices.

DNA origami-based shape IDs for single-molecule nanomechanical genotyping.

Variations on DNA sequences profoundly affect how we develop diseases and respond to pathogens and drugs. Atomic force microscopy (AFM) provides a nanomechanical imaging approach for genetic analysis with nanometre resolution. However, unlike fluorescence imaging that has wavelength-specific fluorophores, the lack of shape-specific labels largely hampers widespread applications of AFM imaging. Here we report the development of a set of differentially shaped, highly hybridizable self-assembled DNA origami nanostructures serving as shape IDs for magnified nanomechanical imaging of single-nucleotide polymorphisms. Using these origami shape IDs, we directly genotype single molecules of human genomic DNA with an ultrahigh resolution of ∼10 nm and the multiplexing ability. Further, we determine three types of disease-associated, long-range haplotypes in samples from the Han Chinese population. Single-molecule analysis allows robust haplotyping even for samples with low labelling efficiency. We expect this generic shape ID-based nanomechanical approach to hold great potential in genetic analysis at the single-molecule level.