Nucleic acid (NA) computation has been widely developed in the past years to solve kinds of logic and mathematic issues in both information technologies and biomedical analysis. However, the ...difficulty to integrate non‐NA molecules limits its power as a universal platform for molecular computation. Here, we report a versatile prototype of hybridized computation integrated with both nucleic acids and non‐NA molecules. Employing the conformationally controlled ligand converters, we demonstrate that non‐NA molecules, including both small molecules and proteins, can be computed as nucleic acid strands to construct the circuitry with increased complexity and scalability, and can be even programmed to solve arithmetical calculations within the computational nucleic acid system. This study opens a new door for molecular computation in which all‐NA circuits can be expanded with integration of various ligands, and meanwhile, ligands can be precisely programmed by the nuclei acid computation.
With utilization of conformationally controlled ligand converters, different kinds of non‐nucleic acid molecules, including both small molecules and proteins, can be integrated into nucleic acid computation to construct circuitries with increased complexity and scalability and to even perform algorithmic calculations. This hybridized system establishes a universal platform for molecular computation.
A passive microfluidic device is reported for continuous microparticle enrichment. The microparticle is enriched based on the inertial effect in a microchannel with contracting‐expanding structures ...on one side where microparticles/cells are subjected to the inertial lift force and the momentum‐change‐induced inertial force induced by highly curved streamlines. Under the combined effect of the two forces, yeast cells and microparticles of different sizes were continuously focused in the present device over a range of Reynolds numbers from 16.7 to 125. ∼68% of the particle‐free liquid was separated from the sample at Re = 66.7, and ∼18 μL particle‐free liquid was fast obtained within 10 s. Results also showed that the geometry of the contracting‐expanding structure significantly influenced the lateral migration of the particle. Structures with a large angle induced strong inertial effect and weak disturbance effect of vortex on the particle, both of which enhanced the microparticle enrichment in microchannel. With simple structure, small footprint (18 × 0.35 mm), easy operation and cell‐friendly property, the present device has great potential in biomedical applications, such as the enrichment of cells and the fast extraction of plasma from blood for disease diagnose and therapy.
The separation of wear microparticles in lubricating oil is crucial for improving the accuracy and throughput of the subsequent detection. However, there are few kinds of research on the separation ...of high‐density metallic microparticles in high‐viscosity lubricating oil. In this paper, a passive method for separating the metallic microparticles in oil is proposed. Gravity sedimentation was adopted to realize three‐dimensional (3D) focusing of the particle by using an inclined capillary. The gravity‐based 3D focusing made the sheath flow no longer responsible for the particle focusing and effectively reduced the sheath flow. Then, the separation of different‐sized metallic microparticles was achieved in a horizontal channel with the aid of a sheath flow based on the different driving forces. The present method solved the problem of nonsynchronous separation of the particle in comparison to the traditional methods. This device has a simple structure with high separation efficiency, and it is easy to integrate with the detection channel. The influence of numerous parameters on the gravity‐based focusing and separation was systematically studied by the numerical simulation and the experiment. The design criteria were established, which is useful in designing and employing the device, expanding its application to other non‐neutral buoyancy particle separation cases, and opening up more prospects for microfluidic technology.
Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory ...syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID‐19). Here, we conducted a prospective, multicenter, open‐label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID‐19. We consecutively recruited 130 COVID‐19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID‐19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID‐19 patients at different disease stages.
The enrichment and focusing of the nano‐/submicroparticle (e.g., 150–1000 nm microvesicle shed from the plasma membrane) in the viscoelastic fluid has great potentials in the biomedical and clinical ...applications such as the disease diagnosis and the prognostic test for liquid biopsy. However, due to the small size and the resulting weak hydrodynamic force, the efficient manipulation of the nano‐/submicroparticle by the passive viscoelastic microfluidic technology remains a major challenge. For instance, a typically long channel length is often required to achieve the focusing or the separation of the nano‐/submicroparticle, which makes it difficult to be integrated in small chip area. In this work, a microchannel with gradually contracted cross‐section and high aspect ratio (the ratio of the height to the average width of channel) is utilized to enhance the hydrodynamic force and change the force direction, eventually leading to the efficient enrichment of nano‐/submicroparticles (500 and 860 nm) in a short channel length (2 cm). The influence of the flow rate, the particle size, the solid concentration, and the channel geometry on the enrichment of the nano‐/submicroparticles are investigated. With simple structure, small footprint, easy operation, and good performance, the present device would be a promising platform for various lab‐chip microvesicle‐related biomedical research and disease diagnosis.
Focusing aerosol particles efficiently is of great significance for high-precision aerosol jet printing and detection of the airborne target. A new method was proposed herein to achieve the efficient ...focusing of aerosol particles in the microchannel by using a reverse external force. Considering the slip at the interface between the gas and the aerosol particle, a numerical model of the particle movement in the microchannel was established and simulations were conducted on the gas-particle two-phase flow in the microchannel under the effect of the reverse external force. The results showed that a suitable reverse external force in a similar order of magnitude to the Stokes force can dramatically increase the velocity difference between the particle and the gas, which significantly enhances the Saffman lift force exerted on the aerosol particle. Eventually, the aerosol particle can be efficiently focused at the center of the microchannel in a short channel length. In addition, the influence of the channel geometry, the magnitude, and the direction of the external force on the particle focusing was also studied. This work is of great significance for the precise detection of aerosol particles and the design of nozzles for aerosol jet printing.
Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and ...algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2–3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor Nature 574, 505 (2019). We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.
A novel method is reported to enhance the focusing of microparticle in the viscoelastic fluid. Gradually contracted geometry is designed in microchannel, which changes the distribution of the elastic ...lift force on the cross section. Additionally, it induces the viscous drag force and the Saffman lift force in the lateral direction. Under the combined effect of these forces, microparticles fast migrate to the center of the channel. In comparison to the channel with constant cross section, the present channel significantly enhances the particle's lateral migration, leading to efficient viscoelastic particle focusing in a short channel length. The influence of flow rate, channel length, particle size and fluid property on the particle focusing is also investigated. With simple structure, small footprint and perfect particle focusing performance, the present device has great potential in the particle focusing processes in various lab‐on‐a‐chip applications.
Recently, cancer-derived exosomes were shown to have pro-metastasis function in cancer, but the mechanism remains unclear. Angiogenesis is essential for tumor progression and is a great promising ...therapeutic target for advanced cervical cancer. Here, we investigated the role of cervical cancer cell-secreted exosomal miR-221-3p in tumor angiogenesis.
miR-221-3p was found to be closely correlated with microvascular density in cervical squamous cell carcinoma (CSCC) by evaluating the microvascular density with immunohistochemistry and miR-221-3p expression with in situ hybridization in clinical specimens. Using the groups of CSCC cell lines (SiHa and C33A) with miR-221-3p overexpression and silencing, the CSCC exosomes were characterized by electron microscopy, western blotting, and fluorescence microscopy. The enrichment of miR-221-3p in CSCC exosomes and its transfer into human umbilical vein endothelial cells (HUVECs) were confirmed by qRT-PCR. CSCC exosomal miR-221-3p promoted angiogenesis in vitro in Matrigel tube formation assay, spheroid sprouting assay, migration assay, and wound healing assay. Then, exosome intratumoral injection indicated that CSCC exosomal miR-221-3p promoted tumor growth in vivo. Thrombospondin-2 (THBS2) was bioinformatically predicted to be a direct target of miR-221-3p, and this was verified by using the in vitro and in vivo experiments described above. Additionally, overexpression of THBS2 in HUVECs rescued the angiogenic function of miR-221-3p.
Our results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression.
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