A novel entropy-driven dual-output mode integrated with DNAzyme for enhanced microRNA detection.

Accurate microRNA (miRNA) detection is pivotal in the diagnosis and monitoring of cancer. Entropy-driven catalysis (EDC) has attracted widespread attention as an enzyme-free, isothermal technique for miRNA detection owing to its inherent simplicity and reliability. However, conventional EDC is a single-output mode, limiting the efficiency of signal amplification. In this study, a novel EDC dual-output mode was employed in conjunction with DNAzyme, resulting in the development of an EDC dual-end DNAzyme (EDC-DED) approach for highly sensitive miRNA detection. In this system, miRNA-21 initiated the EDC reaction, producing a large amount of catalytically active dual-end Mg2+-dependent DNAzyme. The DNAzyme further cleaved the reporter cyclically, generating a notably amplified fluorescence signal. The proposed method achieved a low detection limit of 2 pM. Compared with the traditional EDC single-end DNAzyme (EDC-SED) strategy, the present method exhibited superior amplification efficiency, enhancing detection sensitivity by approximately 46.5-fold. Furthermore, this platform demonstrated ideal specificity, satisfactory reproducibility and acceptable detection capabilities in clinical serum samples. Therefore, the straightforward and convenient strategy is a potential tool for miRNA analysis, which may provide a new perspective for biological analysis and clinical application.

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.

Multifunctional dumbbell probes-based logic circuits: microRNAs logic detection and tumor cells identification.

BACKGROUND: The powerful logic processing capability of DNA logic circuits over multiple input signals perfectly meets the demands of multi-biomarker-based clinical diagnostics. As important biomarkers for cancer diagnosis and treatment, the orthogonal differential expression of microRNAs (miRNAs) in different diseases and different cancer cells makes the precise logical detection of multiple miRNAs particularly critical. RESULTS: Therefore, we constructed two fundamental "AND" and "OR" logic gates and one "AND-OR" logic gate on the basis of our proposed multifunctional dumbbell probes. These logic gates allowed for the logical profiling of multiple cancer-associated miRNAs. In addition, by making simple adjustments to the functional modules of multifunctional dumbbell probes, the three logic gates we proposed could be easily transformed without the use of sophisticated probe design. Remarkably, these logic gates, in particular the "AND-OR" logic gate, were able to compute several miRNAs simultaneously, demonstrating excellent cell identification capabilities. SIGNIFICANCE: Overall, this work provided a new idea for accurately distinguishing multiple cell types and showed great application prospects.

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.

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.

Moiré Lattice in One-Dimensional Synthetic Frequency Dimension.

The moiré lattice has recently attracted broad interest in both solid-state physics and photonics where exotic phenomena in manipulating the quantum states are explored. In this work, we study the one-dimensional (1D) analogs of "moiré" lattices in a synthetic frequency dimension constructed by coupling two resonantly modulated ring resonators with different lengths. Unique features associated with the flatband manipulation as well as the flexible control of localization position inside each unit cell in the frequency dimension have been found, which can be controlled via the choice of flatband. Our work therefore provides insight into simulating moiré physics in 1D synthetic frequency space, which holds important promise for potential applications toward optical information processing.

Direct extraction of topological Zak phase with the synthetic dimension.

Measuring topological invariants is an essential task in characterizing topological phases of matter. They are usually obtained from the number of edge states due to the bulk-edge correspondence or from interference since they are integrals of the geometric phases in the energy band. It is commonly believed that the bulk band structures could not be directly used to obtain the topological invariants. Here, we implement the experimental extraction of Zak phase from the bulk band structures of a Su-Schrieffer-Heeger (SSH) model in the synthetic frequency dimension. Such synthetic SSH lattices are constructed in the frequency axis of light, by controlling the coupling strengths between the symmetric and antisymmetric supermodes of two bichromatically driven rings. We measure the transmission spectra and obtain the projection of the time-resolved band structure on lattice sites, where a strong contrast between the non-trivial and trivial topological phases is observed. The topological Zak phase is naturally encoded in the bulk band structures of the synthetic SSH lattices, which can hence be experimentally extracted from the transmission spectra in a fiber-based modulated ring platform using a laser with telecom wavelength. Our method of extracting topological phases from the bulk band structure can be further extended to characterize topological invariants in higher dimensions, while the exhibited trivial and non-trivial transmission spectra from the topological transition may find future applications in optical communications.

Technologically feasible quasi-edge states and topological Bloch oscillation in the synthetic space.

The dimensionality of a physical system is one of the major parameters defining its physical properties. The recently introduced concept of synthetic dimension has made it possible to arbitrarily manipulate the system of interest and harness light propagation in different ways. It also facilitates the transformative architecture of system-on-a-chip devices enabling far reaching applications such as optical isolation. In this report, a novel architecture based on dynamically-modulated waveguide arrays with the Su-Schrieffer-Heeger configuration in the spatial dimension is proposed and investigated with an eye on a practical implementation. The propagation of light through the one-dimensional waveguide arrays mimics time evolution of the field in a synthetic two-dimensional lattice. The addition of the effective gauge potential leads to an exotic topologically protected one-way transmission along adjacent boundary. A cosine-shape isolated band, which supports the topological Bloch oscillation in the frequency dimension under the effective constant force, appears and is localized at the spatial boundary being robust against small perturbations. This work paves the way to improved light transmission capabilities under topological protections in both spatial and spectral regimes and provides a novel platform based on a technologically feasible lithium niobate platform for optical computing and communication.

Contrasting the primings between English and Chinese: To advance Hoey's theory of lexical priming from the perspective of culture psychology.

The present study demonstrated that Hoey's promising and serviceable theory could serve as one that can describe and explain similarities and differences exhibited between English and Chinese. Three fundamental concepts as defined in the theory (collocation, colligation, and semantic association) were considered. The combinatory profile showed that: (1) different word choices were primed to constitute to a shared semantic association (2) no unique word combination containing the nodes was found, but high or low frequency use of particular clusters and collocates appearing at both sides to the node occurred; (3) it is claimed that the interpretation and explanation of priming similarities and differences between English and Chinese need to be extended to culture psychology.

Cooperative Branch Migration: A Mechanism for Flexible Control of DNA Strand Displacement.

DNA strand displacement plays an essential role in the field of dynamic DNA nanotechnology. However, flexible regulation of strand displacement remains a significant challenge. Most previous regulatory tools focused on controllable activation of toehold and thus limited the design flexibility. Here, we introduce a regulatory tool termed cooperative branch migration (CBM), through which DNA strand displacement can be controlled by regulating the complementarity of branch migration domains. CBM shows perfect compatibility with the majority of existing regulatory tools, and when combined with forked toehold, it permits continuous fine-tuning of the strand displacement rate spanning 5 orders of magnitude. CBM manifests multifunctional regulation ability, including rate fine-tuning, continuous dynamic regulation, reaction resetting, and selective activation. To exemplify the powerful function, we also constructed a nested if-function signal processing system on the basis of cascading CBM reactions. We believe that the proposed regulatory strategy would effectively enrich the DNA strand displacement toolbox and ultimately promote the construction of DNA machines of higher complexity in nucleic acid research and biomedical applications.

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia.

PURPOSE: To explore the clinical significance of plasma pyruvate kinase M2 (PKM2) in assessing the incidence and prognosis of acute leukemia. METHODS: Plasma samples from 56 acute myeloid leukemia (AML) patients, 40 acute lymphoblastic leukemia (ALL) patients, and 66 plasma samples from healthy individuals were collected. The level of plasma PKM2 was detected by enzyme-linked immunosorbent assay. The clinical significance of PKM2 in acute leukemia was assessed by analyzing receiver operating characteristic and survival curves. RESULTS: The plasma levels of PKM2 in AML or ALL patients were significantly higher than those in healthy individuals, respectively. PKM2 can be used as a potential diagnostic index with the AUC of 0.827 for AML and 0.837 for ALL. The level of plasma PKM2 in ALL patients with a BCR/ABL-positive genotype was significantly higher than that in patients with a BCR/ABL-negative genotype (p<0.05). The event-free survival and the overall survival of acute leukemia patients with higher PKM2 expression was worse than those with lower PKM2 expression. CONCLUSION: This study showed that higher levels of PKM2 was negatively correlated with the prognosis of acute leukemia. Therefore, PKM2 can be used as a potential index to assess the incidence and prognosis of acute leukemia.

A Randomized, Double-Blind, and Placebo-Controlled Trial of Chinese Herbal Medicine in the Treatment of Childhood Constipation.

OBJECTIVES: Management of constipation is still challenging in childhood. The pharmacological effect of XiaojiDaozhi Decoction, a prescription of Chinese Herbal Medicine (CHM), has been well described for the treatment of food and Qi stagnation which account for childhood constipation. However, the efficacy and safety of XiaojiDaozhi Decoction in childhood constipation remains unclear. METHODS: A randomized, double-blind, and placebo-controlled trial was conducted to evaluate the efficacy and safety of XiaojiDaozhi Decoction in childhood constipation. Two hundred children were recruited and randomly allocated to the CHM or placebo group to receive their respective interventions. The duration of treatment was 8 weeks, with a 12-week follow-up. Main outcome measures were complete spontaneous bowel movements and satisfaction with bowel function. Safety and adverse effects were evaluated by blood laboratory measurements. RESULTS: At the end of follow-up, the response rates of CHM and placebo were 62% and 31%, respectively (χ2 = 19.315, P < 0.01). At the end of treatment, recurrence was found in 7 cases (10.14%) in CHM and 11 cases (26.19%) in placebo (χ2 = 4.947, P < 0.05). In the main outcome measures, 56 patients (56%) in the CHM group and 25 patients (25%) in the placebo group were satisfied with their bowel movements (χ2 = 19.940, P < 0.05). Increased complete spontaneous bowel movements ≥3 per week from baseline were found in 40 patients (40%) who received CHM and 19 patients (19%) who received placebo (χ2 = 10.602, P < 0.05). No serious adverse effects were found in any of the recruited cases. DISCUSSION: CHM XiaojiDaozhi Decoction is a safe and effective method for the treatment of childhood constipation.

Photon retention in coherently excited nitrogen ions.

Quantum coherence in quantum optics is an essential part of optical information processing and light manipulation. Alkali metal vapors, despite the numerous shortcomings, are traditionally used in quantum optics as a working medium due to convenient near-infrared excitation, strong dipole transitions and long-lived coherence. Here, we proposed and experimentally demonstrated photon retention and subsequent re-emittance with the quantum coherence in a system of coherently excited molecular nitrogen ions (N2+) which are produced using a strong 800 nm femtosecond laser pulse. Such photon retention, facilitated by quantum coherence, keeps releasing directly-unmeasurable coherent photons for tens of picoseconds, but is able to be read out by a time-delayed femtosecond pulse centered at 1580 nm via two-photon resonant absorption, resulting in a strong radiation at 329.3 nm. We reveal a pivotal role of the excited-state population to transmit such extremely weak re-emitted photons in this system. This new finding unveils the nature of the coherent quantum control in N2+ for the potential platform for optical information storage in the remote atmosphere, and facilitates further exploration of fundamental interactions in the quantum optical platform with strong-field ionized molecules..

Tobacco extracts promote PD-L1 expression and enhance malignant biological differences via mTOR in gefitinib-resistant cell lines.

BACKGROUND: The aim of this study was to investigate whether tobacco extracts could regulate PD-L1 expression and enhance malignant biological differences in gefitinib-resistant cell lines. METHODS: We constructed gefitinib-resistant cells and observed the biological differences in gefitinib-resistant cells. The cells were stimulated with medium containing 5% volume of tobacco extract, and the change in PD-L1 expression and the mammalian target of rapamycin (mTOR) and p-mTOR expression in gefitinib-resistant cells treated with tobacco extracts was observed. We discussed the relationship between PD-L1 and mTOR. RESULTS: Tobacco extracts could promote PD-L1 expression in the cell line. Western blot analysis showed that mTOR and p-mTOR were significantly enhanced in gefitinib-resistant cell lines cultured in the tobacco extracts. The mTOR signaling pathway was involved in PD-L1 expression and in regulating the expression of cytokines IL-6 and IL-23. In addition, the tobacco extracts could promote macrophage migration via mTOR/IL-6. CONCLUSIONS: PD-L1 can transmit inhibitory signals and reduce the proliferation of CD8 + T cells in lymph nodes. Tobacco extracts upregulate PD-L1 expression via mTOR/IL-6. These results imply that lung cancer patients should not smoke and stay away from a smoke environment.

Gastroesophageal Reflux Poses a Potential Risk for Late Complications of Bronchopulmonary Dysplasia: A Prospective Cohort Study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder in extremely low birth weight infants. Although most symptoms of BPD improve, some late complications exist, even with regular treatment. Gastroesophageal reflux (GER), also common in extremely premature infants, may be related to many cardiorespiratory symptoms. However, the potential of GER as a risk factor for late complications associated with BPD is still unclear. RESEARCH QUESTION: The goal of this study was to determine if GER increases the risk of late complications of BPD in infants. STUDY DESIGN AND METHODS: A multicenter prospective cohort of 131 infants (79 male subjects, 52 female subjects) with BPD was enrolled. The development of late complications was assessed over an 18-month follow-up period. Twenty-four-hour pH-multichannel intraluminal impedance and gastric sodium concentrations were analyzed in all infants at 36 weeks' postmenstrual age and at the last interview. Prevalence and risk factors of late complications of BPD were analyzed by using forward logistic regression. RESULTS: The prevalence of late complications in BPD infants was 63.79% and included respiratory symptoms (49.14%), vomiting (38.79%), retinopathy of prematurity (25.86%), hypoxic-ischemic injury (3.45%), rehospitalization (26.72%), and sudden death (0.86%). Respiratory diseases constituted the most frequent complication. The prevalence of GER in BPD was 42.24% and included acid GER (18.10%) and duodenogastroesophageal reflux (DGER; 24.14%). Risk factors for respiratory symptoms were gestational age ≤ 30 weeks (OR, 3.213; 95% CI, 1.221-8.460), birth weight < 1,500 g (OR, 2.803; 95% CI, 1.014-7.749), invasive ventilation > 7 days (OR, 4.952; 95% CI, 1.508-16.267), acid GER (OR, 4.630; 95% CI, 1.305-16.420), and DGER (OR, 5.588; 95% CI, 1.770-17.648). Infants with BPD and DGER were more prone to late complications than those with acid GER or no reflux. INTERPRETATION: The prevalence of late complications is high in infants with BPD. GER (and in particular, DGER) poses a tentative risk for these late complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03014453; URL: www.clinicaltrials.gov.

Exchange unknown quantum states with almost invisible photons.

We propose a quasi-counterfactual quantum swap gate for exchanging Alice's unknown photon state and Bob's unknown atomic state under the condition that only Alice's photon may appear in the transmission channel between Alice and Bob, while the probability of the existence of photon in the transmission channel is controllable and can tend to zero. Unlike standard counterfactual quantum communication protocols, quantum states exchange in present scenario is achieved by multiple phase operations, rather than multiple measurements. The total effect of those operations can be considered as a unitary time evolution operator. Therefore, the communication fidelity and efficiency of our protocol are always one if system imperfection and channel noise are not considered. Compared to standard counterfactual communication protocols, our protocol is easy to implement. We also show that it can be easily converted to a standard counterfactual one.

FOXD3/FOXD4 is required for the development of hindgut in the rat model of anorectal malformation.

Congenital anorectal malformation is the most common digestive tract malformation in newborns. It has been reported that FOXD3/FOXD4, a forkhead transcription factor, regulates the generation, migration, and differentiation of neural crest cells. However, whether FOXD3/FOXD4 takes part in anorectal malformation remains unclear. In the present study, we used ethylene thiourea to induce the animal models of anorectal malformation in rat embryos and to interrogate the role of FOXD3/FOXD4 in anorectal malformation pathogenesis. Hindgut samples of the animal models were collected at E15, E17, E19, and E21 days of age. The expression of FOXD3/FOXD4 was detected by immunohistochemistry, western blot, and quantitative real-time fluorescence PCR. By immunohistochemical staining, FOXD3/FOXD4 was observed in epithelial cells of the rectum and the anus both in normal and rat embryos with anorectal malformation. Expression level analysis by western blot indicated that FOXD3/FOXD4 expression increased in ethylene thiourea-induced anorectal malformation groups. mRNA expression as determined by quantitative real-time fluorescence PCR analysis was consistent with the western blot results. Tentative conclusions were drawn that FOXD3/FOXD4 is expressed in the hindgut in rat embryos and is upregulated in anorectal malformation. FOXD3/FOXD4 is required for the development of the hindgut, and its aberrant expression may be an important factor leading to the incidence of anorectal malformation. Impact statement Congenital anorectal malformation (ARM) is the most common digestive tract malformation in newborns. The pathophysiological ground remains unclear. In this study, we used animal models of ARM for the first time to interrogate the role of FOXD3/FOXD4 in ARM pathogenesis. The animal models of ARM were successfully induced by ethylene thiourea (ETU) in rat embryos providing a strong basis for pathogenesis study of this disease. Expression analysis of FOXD3/FOXD4 was carried out in these models, and the results shape a deeper understanding of FOXD3/FOXD4 being required for the normal development of the hindgut. The aberrant expression of FOXD3/FOXD4 may be an important factor leading to ARM incidence.

Efficient single photon emission and collection based on excitation of gap surface plasmons.

Combining the advantages of ultrahigh photon emission rates achievable in the gap surface plasmon polaritons with high extraction decay rates into low-loss nanofibers, we demonstrate theoretically the efficient photon emission of a single dipole emitter and one-dimensional nanoscale guiding in metallic nanorod-coupled nanofilm structures coupled to dielectric nanofibers. We find that total decay rates and surface plasmon polariton channel decay rates orders of magnitude larger than those characteristic of metallic nanofilms alone can be achieved in ultrastrong hot spots of gap plasmons. For the requirement of practical applications, propagating single photons with decay rates of 290γ_{0}-770γ_{0} are guided into the phase-matched low-loss nanofibers. The proposed mechanism promises to have an important impact on metal-based optical cavities, on-chip bright single photon sources and plasmon-based nanolasers.

Radially oscillating and quasi-guided surface plasmon polaritons in cylindrical metallic nanostructures.

We analytically propose radially oscillating and quasi-guided surface plasmon polaritons (SPPs) by designing the outer and core dielectric permittivities ε(a) and ε(c) of a cylindrical metallic nanotube. When the propagation constant satisfies √ε(a)

Polarized linewidth-controllable double-trapping electromagnetically induced transparency spectra in a resonant plasmon nanocavity.

Surface plasmons with ultrasmall optical mode volume and strong near field enhancement can be used to realize nanoscale light-matter interaction. Combining surface plasmons with the quantum system provides the possibility of nanoscale realization of important quantum optical phenomena, including the electromagnetically induced transparency (EIT), which has many applications in nonlinear quantum optics and quantum information processing. Here, using a custom-designed resonant plasmon nanocavity, we demonstrate polarized position-dependent linewidth-controllable EIT spectra at the nanoscale. We analytically obtain the double coherent population trapping conditions in a double-Λ quantum system with crossing damping, which give two transparent points in the EIT spectra. The linewidths of the three peaks are extremely sensitive to the level spacing of the excited states, the Rabi frequencies and detunings of pump fields, and the Purcell factors. In particular the linewidth of the central peak is exceptionally narrow. The hybrid system may have potential applications in ultra-compact plasmon-quantum devices.