Building a stable and robust anti-interference DNA dissipation system by eliminating the accumulation of systemic specified errors.

BACKGROUND: The emergence of DNA nanotechnology has enabled the systematic design of diverse bionic dissipative behaviors under the precise control of nucleic acid nanodevices. Nevertheless, when compared to the dissipation observed in robust living systems, it is highly desirable to enhance the anti-interference for artificial DNA dissipation to withstand perturbations and facilitate repairs within the complex biological environments. RESULTS: In this study, we introduce strategically designed "trash cans" to facilitate kinetic control over interferences, transforming the stochastic binding of individual components within a homogeneous solution into a competitive binding process. This approach effectively eliminates incorrect binding and the accumulation of systemic interferences while ensuring a consistent pattern of energy fluctuation from response to silence. Remarkably, even in the presence of numerous interferences differing by only one base, we successfully achieve complete system reset through multiple cycles, effectively restoring the energy level to a minimum. SIGNIFICANCE: The system was able to operate stably without any adverse effect under conditions of irregular interference, high-abundance interference, and even multiplex interferences including DNA and RNA crosstalk. This work not only provides an effective paradigm for constructing robust DNA dissipation systems but also greatly broadens the potential of DNA dissipation for applications in high-precision molecular recognition and complex biological reaction networks.

Nanomaterials Regulate Bacterial Quorum Sensing: Applications, Mechanisms, and Optimization Strategies.

Anti-virulence therapy that interferes with bacterial communication, known as "quorum sensing (QS)", is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti-virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in-depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti-virulence therapy. This review provides reference and inspiration for further research on the anti-virulence application of nanomaterials.

Enhancing harmonic brightness near the cutoff region by using laser pulses with a small positive chirp.

Efficient enhancement of harmonic brightness near the cutoff region is achieved by employing laser pulses with a small positive chirp in theory, where the laser intensity and frequency near the peak of the laser pulse are almost unchanged relative to the chirp-free field. The improvement of harmonic brightness is achieved under the condition that the ionization probability is almost unchanged. Through the analysis of the harmonics contributed by the rising and falling parts of the laser pulse, we have uncovered a "frequency compensation" mechanism that leads to an enhanced harmonic brightness near the cutoff region. Under appropriate chirp parameters, the harmonics contributed by the rising and falling parts can be constructively interfered in a smaller frequency range with greater intensity, thereby obtaining harmonics with good monochromaticity and high brightness. This study explains the mechanism of harmonic brightness enhancement from a new perspective, and provides a new idea for harmonic regulation without changing the ionization.

Network pharmacology and experimental verification of the potential mechanism of Er-Xian decoction in aplastic anemia.

To investigate the potential mechanism of Er-Xian decoction (EXD) in treating aplastic anemia (AA), the active components of EXD were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the targets of the components were predicted by the Swiss Target Prediction database. AA targets were collected from the GeneCards, OMIM, DisGeNET, PharmGKB, DrugBank, and TTD databases, the intersection of AA targets and EXD targets was calculated, and an herb-component-target network was constructed by Cytoscape 3.7.2 software. The STRING database was used for protein‒protein interaction (PPI) analysis, and Cytoscape 3.7.2 software was used to construct a PPI network and perform topology analysis. The core targets were imported into the DAVID database for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The molecular docking software AutoDock was used to measure the affinity between active components and key targets. Finally, we established a mouse model of AA and verified the key targets and signaling pathways of EXD by RT‒PCR, ELISA and Western blot analysis. A total of 53 active components were screened from EXD, 2516 AA-related targets were collected, and 195 common targets were obtained. An herb-component-target network and a PPI network were successfully constructed, and 36 core targets were selected from the PPI network. The main active components of EXD include luteolin, kaempferol, berberine, etc., and key targets include PIK3CA, AKT1, STAT3, etc. GO functional enrichment analysis showed that cell components, molecular functions and biological processes with significant correlations were macromolecular complexes, protein serine/threonine/tyrosine kinase activity and protein phosphorylation, respectively. KEGG pathway analysis showed that the pathways with significant correlations included the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. Molecular docking results showed that the tested key targets had good affinity for the corresponding active components. In AA mice, we found that EXD significantly increased white blood cell count, red blood cell count, platelet count and hemoglobin levels, increased mRNA levels of PIK3CA, PIK3CD, AKT1, JAK2, STAT3 and MAPK1, and promoted phosphorylation of PI3K, AKT, ERK1/2 and STAT3. In summary, EXD acts on PI3K, AKT, STAT3 and other targets through berberine, luteolin, quercetin and other components to regulate the PI3K-Akt pathway, JAK-STAT pathway and other pathways, thus exerting its therapeutic effect on AA. This study explained the Chinese medicine theory of treating AA with EXD by tonifying kidney-yang and provides a scientific basis for the use of EXD in treating AA.

Circularly polarized attosecond light generation from OCS molecules irradiated by the combination of linear polarized infrared and orthogonal terahertz fields.

Researching ultrafast dynamics and creating coherent light sources will both benefit significantly from the establishment of polarization control in high-order harmonic generation (HHG). By employing the time-dependent density functional theory method, we investigate HHG of carbonyl sulfide molecules using a combination of a linear polarized infrared (IR) laser and a weaker orthogonal Terahertz (THz) field. Our findings show that by adjusting the amplitude of the THz field, the movement scale of electrons in the THz direction can be tuned, thereby one can control the harmonic intensity in the IR laser direction. This method allows for the creation of near-circularly polarized attosecond pulses. Furthermore, the ellipticity of the attosecond pulse may be changed by modifying the carrier-envelope phase of the IR laser pulse.

Unmodificated stepless regulation of CRISPR/Cas12a multi-performance.

As CRISPR technology is promoted to more fine-divided molecular biology applications, its inherent performance finds it increasingly difficult to cope with diverse needs in these different fields, and how to more accurately control the performance has become a key issue to develop CRISPR technology to a new stage. Herein, we propose a CRISPR/Cas12a regulation strategy based on the powerful programmability of nucleic acid nanotechnology. Unlike previous difficult and rigid regulation of core components Cas nuclease and crRNA, only a simple switch of different external RNA accessories is required to change the reaction kinetics or thermodynamics, thereby finely and almost steplessly regulating multi-performance of CRISPR/Cas12a including activity, speed, specificity, compatibility, programmability and sensitivity. In particular, the significantly improved specificity is expected to mark advance the accuracy of molecular detection and the safety of gene editing. In addition, this strategy was applied to regulate the delayed activation of Cas12a, overcoming the compatibility problem of the one-pot assay without any physical separation or external stimulation, and demonstrating great potential for fine-grained control of CRISPR. This simple but powerful CRISPR regulation strategy without any component modification has pioneering flexibility and versatility, and will unlock the potential for deeper applications of CRISPR technology in many finely divided fields.

Minimum structure of high-order harmonic spectrum from molecular multi-orbital effects involving inner-shell orbitals.

The spectral features of high-order harmonic spectra can provide rich information for probing the structure and dynamics of molecules in intense laser fields. We theoretically study the high harmonic spectrum with the laser polarization direction perpendicular to the N2O molecule and find a minimum structure in the plateau region of the harmonic spectrum. Through analyzing the time-dependent survival probability of different electronic orbitals and the time-dependent wave packet evolution, it is found that this minimum position is caused by the harmonic interference of HOMO a, HOMO-1, and HOMO-3 a orbitals. Moreover, this interference minimum is discovered over a wide frequency range of 0.087 a.u. to 0.093 a.u., as well as a range of driving laser intensities with peak amplitudes between 0.056 a.u. and 0.059 a.u.. This study sheds light on the multi-electron effects and ultrafast dynamics of inner-shell electrons in intense laser pulses, which are crucial for understanding and controlling chemical reactions in molecules.

Design of a Biaxial High-G Piezoresistive Accelerometer with a Tension-Compression Structure.

To meet the measurement needs of multidimensional high-g acceleration in fields such as weapon penetration, aerospace, and explosive shock, a biaxial piezoresistive accelerometer incorporating tension-compression is meticulously designed. This study begins by thoroughly examining the tension-compression measurement mechanism and designing the sensor's sensitive structure. A signal test circuit is developed to effectively mitigate cross-interference, taking into account the stress variation characteristics of the cantilever beam. Subsequently, the signal test circuit of anti-cross-interference is designed according to the stress variation characteristics of the cantilever beam. Next, the finite element method is applied to analyze the structure and obtain the performance indices of the range, vibration modes, and sensitivity of the sensor. Finally, the process flow and packaging scheme of the chip are analyzed. The results show that the sensor has a full range of 200,000 g, a sensitivity of 1.39 µV/g in the X direction and 1.42 µV/g in the Y direction, and natural frequencies of 509.8 kHz and 510.2 kHz in the X and Y directions, respectively.

Universal probe-based SNP genotyping with visual readout: a robust and versatile method.

Detection of single nucleotide polymorphisms (SNPs) is critical for personalized clinical diagnosis, treatment, and medication. Current clinical detection methods suffer from primer dimerization and require the redesigning of reaction systems for different targets, resulting in a time-consuming and laborious process. Here, we present a robust and versatile method for SNP typing by using tailed primers and universal small molecule probes in combination with a visualized lateral flow assay (LFA). This approach enables not only rapid typing of different targets, but also eliminates the interference of primer dimers and enhances the accuracy and reliability of the results. Our proposed universal assay has been successfully applied to the typing of four SNP loci of clinical samples to verify the accuracy and universality, and the results are consistent with those obtained by Sanger sequencing. Therefore, our study establishes a new universal "typing formula" using nucleic acid tags and small molecule probes that provides a powerful genotyping platform for genetic analysis and molecular diagnostics.

Copper-based biological alloys and nanocomposites for enzymatic catalysis and sensing applications.

Copper (Cu) is an inexpensive transition metal on Earth, exhibiting high catalytic activity due to its rich d-electron configuration and variable oxidation states. Cu-based biological alloys and nanocomposites have emerged as a prominent research area. Under specific synthesis conditions, alloys or nanocomposites formed by Cu with other metals demonstrate excellent enzyme-like and sensing activities. These advanced materials offer significant advantages over artificial enzymes in enzymatic applications, including high stability, simple synthesis, flexible catalytic performance, and ease of preservation. In addition, various types of sensors have been designed based on the unique electrochemical properties exhibited by these alloys and nanocomposites as well as their specific reactions with the target substances. These sensors possess advantages such as stability, high efficiency, a broad detection range, low detection limits, and high sensitivity. In this review, we summarize the current research status of Cu-based biological alloys and nanocomposites in enzyme-like applications and sensing applications. Based on this, we introduce the diverse enzyme-like activities exhibited by Cu-based nanozymes prepared under different synthesis conditions and their applications in areas such as biosensing, cancer treatment, and antibacterial therapy. Furthermore, we provide an overview of the applications of Cu-based alloys and nanocomposites in the field of sensing based on their enzyme-like activity or chemical activities. These sensors have been widely employed in biomedical detection, environmental hazardous substance monitoring, and food safety testing. Challenges and prospects faced by Cu-based alloys and nanocomposites are also highlighted for future works.

Effect of pulse duration on the above-threshold ionization of a hydrogen atom irradiated by a 400 nm intense laser.

The photoelectron emission spectra generated by the interaction between ultrashort intense laser pulses and atoms can reveal the ultrafast dynamics of electrons. By using the numerical solution of the time-dependent Schrödinger equation in momentum space, the photoelectron emission spectra of atoms irradiated by 400 nm intense lasers with different durations of the pulse has been investigated. In the photoelectron emission spectrum, in addition to the above-threshold ionization peaks due to ionization interference in multiple cycles and the sideband peaks mainly due to the interference of ionized electrons at different moments along the rising edge of the laser pulse envelope, additional peaks of photoelectron emission whose intensity appears to oscillate with the increasing duration of the laser pulse can also be observed. Based on strong-field approximation and the population's analysis of the bound state, it is found that these photoelectron peaks originate from the ionization of the excited state and the oscillations of these peaks are due to the superposition of their peak energy positions with the sideband energy positions. Furthermore, it is demonstrated that the energy positions of the maximum intensity of the photoelectron emission spectra move towards the higher energy end as the duration of the driving laser pulse extends. This phenomenon can be attributed to the fact that the main moment of ionization of atoms changes with the increasing duration of the driving laser pulse, thus allowing the real-time ionization of atoms to be probed using photoelectron emission spectra.

Development of a Microfluidic Formatted Ultrasound-Controlled Monodisperse Lipid Vesicles' Hydrogel Dressing Combined with Ultrasound for Transdermal Drug Delivery System.

Transdermal drug delivery system (TDDS) has attracted much attention in the pharmaceutical technology area. However, the current methods are difficult to ensure penetration efficiency, controllability, and safety in the dermis, so its widespread clinical use has been limited. This work proposes an ultrasound-controlled monodisperse lipid vesicles (U-CMLVs) hydrogel dressing, which combines with ultrasound to form TDDS. Using microfluidic technology, prepare size controllable U-CMLVs with high drug encapsulation efficiency and quantitative encapsulation of ultrasonic response materials, and even uniform mix them with hydrogel to prepare the required thickness of dressings. The high encapsulation efficiency can ensure sufficient dosage of the drugs and further realize the control of ultrasonic response through quantitative encapsulation of ultrasound-responsive materials. Using high frequency (5 MHz, 0.4 W cm-2 ) and low frequency (60 kHz, 1 W cm-2 ) ultrasound to control the movement and rupture of U-CMLVs, the contents not only penetrate the stratum corneum into the epidermis but also break through the bottleneck of penetration efficiency, and deep into the dermis. These findings provide the groundwork for deep, controllable, efficient, and safe drug delivery through TDDS and lay a foundation for further expanding its application.

Temperature-boosted PAM-less activation of CRISPR-Cas12a combined with selective inhibitors enhances detection of SNVs with VAFs below 0.01.

The precise identification of rare single nucleotide variations (SNVs) concomitant with excess wild-type DNA is a valuable method for minimally invasive disease diagnosis and early prediction of drug responsiveness. Selective enrichment of mutant variants via strand displacement reaction offers an ideal approach of SNVs analysis but fails to differentiate wildtype from mutants with variant allele fraction (VAF) < 0.01%. Here, we demonstrate that integration of PAM-less CRISPR-Cas12a and adjacent mutation-enhanced inhibition of wild-type alleles enables highly sensitive measurement of SNVs well below the 0.01% VAF threshold. Raising the reaction temperature to the upper limit of LbaCas12a helps to boost PAM-less activation of collateral DNase activity, which can be further enhanced using PCR additives, leading to ideal discriminative performance for single point mutations. Along with selective inhibitors bearing additional adjacent mutation, it allowed detection of model EGFR L858R mutants down to 0.001% with high sensitivity and specificity. Preliminary investigation on adulterated genomic samples prepared in two different ways also suggests that it can accurately measure ultralow-abundance SNVs extracted directly from clinical samples. We believe that our design, which combines the superior SNV enrichment capability of strand displacement reaction and unparalleled programmability of CRISPR-Cas12a, has the potential to significantly advance current SNV profiling technologies.

Effect of perioperative cognitive behavioral interventions on pain, anxiety, and sleep quality in elderly patients after sinus floor elevation and immediate implantation: A randomized controlled trial.

BACKGROUND: Sinus floor elevation and immediate dental implantation are commonly performed to treat dentition defects in elderly patients. Targeted cognitive behavioral interventions (CBI) during the perioperative period can reduce pain and anxiety as well as improve sleep quality. This can lead to improvements in patient cooperation during follow-up treatment and enhance the overall efficacy of the surgery. OBJECTIVE: The study aimed to investigate the impact of a cognitive behavioral intervention method on perioperative pain, anxiety, and sleep quality in elderly patients undergoing sinus floor elevation and immediate dental implantation. METHODS: Forty patients who required the treatment at the Stomatology Clinic in our hospital between December 2018 and December 2022 were enrolled in this randomized controlled trial. The patients were randomly divided into two groups: a control group (n= 20), which received conventional treatment and care during the perioperative period, and an intervention group (n= 20), which received comprehensive behavioral intervention in addition to the conventional treatment and care during the perioperative period. The perioperative anxiety, pain, and sleep quality of the patients in both groups were evaluated. Anxiety was assessed using the Self-Rating Anxiety Scale (SAS), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and pain was measured using the visual analog scale (VAS). RESULTS: No statistically significant differences in SAS and PSQI were observed between the two groups at the initial visit; the values were significantly higher than those measured postoperatively. The SAS scores and PSQI of patients on days 0 and 7 post-surgery in the intervention group were significantly lower than those in the control group (P< 0.05). CONCLUSION: Perioperative cognitive behavioral intervention can effectively improve anxiety, postoperative pain and sleep quality in elderly patients who have undergone sinus floor elevation and immediate dental implantation, thereby reducing the incidence of complications.

The effect of motivational interviewing based on the transtheoretical model on oral cleaning behavior of patients with periodontitis who have undergone implant restoration.

BACKGROUND: Implant-restored patients with periodontitis have a higher risk of developing peri-implantitis, and helping them develop oral cleaning habits is significant. OBJECTIVE: To evaluate the effectiveness of motivational interviewing based on the transtheoretical model on the modification of oral cleaning behaviors of implant-restored patients with periodontitis. METHODS: Patients with periodontitis (n= 70) who would receive dental implant treatment were included. And they were randomly divided into two groups: experimental (n= 35) and control (n= 35). Control patients received routine oral hygiene education, and those in the experimental group received motivational interviewing based on the transtheoretical model. Oral cleaning behavior was compared between the two groups before and after intervention. In addition, periodontal health status was compared on the day of implant restoration and three months later. RESULTS: Compared to the control, the experimental group demonstrated significantly better oral hygiene behavior after intervention (P< 0.05). Three months after implant restoration, significantly better results were obtained by the experimental group in terms of mPLI and mSBI (P< 0.05). CONCLUSION: Motivational interviewing based on the transtheoretical model can effectively improve the oral cleaning behavior and periodontal health of implant-restored patients with periodontitis.

Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities.

The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual ß- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 µmol·L-1. The ß-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 µg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 µg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 µmol·L-1, respectively.

A hairpin probe-mediated exponential amplification reaction for highly sensitive and specific detection of microRNAs.

In this work, we propose a hairpin probe-mediated exponential amplification reaction (HEAR) strategy that combines DNA strand displacement with a "who triggers, who gets generated" mode, providing excellent single-base discrimination and a reduced background signal. The detection limit is 19 aM, which is reduced by 3 orders of magnitude compared to traditional exponential amplification approaches. This one-pot strategy also exhibits a wide dynamic range, high specificity and short detection time. It is expected to become a powerful tool for clinical diagnosis.

Phytotoxic meroterpenoids with herbicidal activities from the phytopathogenic fungus Pseudopestalotiopsis theae.

The fungus Pseudopestalotiopsis theae isolated from the fresh leaves of Illigera celebica, has been reported to be a pathogenic fungus that can cause gray blight on tea leaves, a disease characterized by the appearance of necrotic lesions on tea leaves. The pathogenic substances in this fungus have not been clearly identified. Considering the possible involvement of specialized metabolites in symptom appearance, a chemical investigation of specialized metabolites on P. theae was conducted, resulting in the isolation of eight meroterpenoids, including six undescribed biscognienynes G-L and two known ones (biscognienynes B and D). The structures of these new compounds were characterized by extensive NMR spectroscopic and HR-ESI-MS data, and their absolute configurations were elucidated by ECD calculations. Except for biscogniyne L, all the isolated biscognienynes showed different degrees of phytotoxicity to tea in vivo, thereby revealing for the first time the substances in P. theae that cause tea gray blight. Inspired by the fact that phytotoxins produced by pathogenic fungus are an effective resource for designing natural and safe bioherbicides, when assayed the herbicidal activity through Petri dish bioassays, biscognienynes G-J showed phytotoxic effects against seed germination and seedling growth of Setaria viridis, strongly inhibiting seed germination percentage and radicle and germ lengths of seedlings. The results of this study demonstrated the great potential of biscognienynes G-J to be proposed and developed as ecofriendly herbicides.

The renew plans of urban thermal environment optimization for traditional districts in Xi'an, China.

During the process of the high-speed urbanization in Chinese cities, the social, economic, and political status and the interaction between each factor have been more focused on urban traditional district renewal. However, the effects on urban microclimate and the residential living conditions in traditional districts are not well discussed, which is strongly related to the living comfort and citizens' well-being. In this study, two typical traditional districts in Xi'an are selected. According to the original situation of building functions and the community characteristics, two renewal plans are proposed by adding vegetation in open spaces (V), and adding vegetation combined with building redevelopment (V&B), in order to balance the living convenience and thermal environment. Via ENVI-met simulation, the effects of the district renewal plans on thermal environment including wind speed, air temperature, and mean radiant temperature are evaluated. This study provides method of environmental evaluation for traditional district renewal, which contributes to sustainable urban planning in historical districts, and provides recommendations for related policy development.

Detection of rare CTCs by electrochemical biosensor built on quaternary PdPtCuRu nanospheres with mesoporous architectures.

Circulating tumor cells (CTCs) are promising liquid biopsy biomarkers for early cancer detection and anti-cancer therapy evaluation. The ultra-low abundance of CTCs in blood samples requires highly sensitive and accurate detection ways. In this study, we propose the design of a dual-recognition electrochemical biosensor to improve both the specificity and signal response. PdPtCuRu mesoporous nanospheres (PdPtCuRu MNSs) with excellent three dimensions (3D) nanopore structures were synthesized by one-pot method and connected to mucin 1 (MUC1) aptamer to serve as signal amplification probe. Besides, superconductive carbon black, Ketjen Black (KB), and gold nanoparticles (AuNPs) modified organometallic frame (CeMOF-Au) were combined to work as signal transducer. The characteristic branching structure of KB provides abundant contact points to load CeMOF-Au to heighten the interface electron transfer rate. In addition, AuNPs were reduced on the surface of CeMOF, which could effectively bind the capture antibody and further enhance the conductivity. Under the optimized condition, the limit of detection (LOD) of the as-constructed biosensor was less than 10 cells mL-1 for model A549 cells, and showed good specificity and accuracy in spiked serum samples. We envision the as-proposed electrochemical biosensor would alternate as a useful tool for the clinical detection of CTCs for cancer diagnosis.