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DNA is commonly employed as a substrate for the building of artificial logic networks due to its excellent biocompatibility and programmability. Till now, DNA logic circuits are rapidly evolving to accomplish advanced operations. Nonetheless, nowadays, most DNA circuits remain to be disposable and lack of field programmability and thereby limits their practicability. Herein, inspired by the Configurable Logic Block (CLB), the CLB-based erasable field-programmable DNA circuit that uses clip strands as its operation-controlling signals is presented. It enables users to realize diverse functions with limited hardware. CLB-based basic logic gates (OR and AND) are first constructed and demonstrated their erasability and field programmability. Furthermore, by adding the appropriate operation-controlling strands, multiple rounds of programming are achieved among five different logic operations on a two-layer circuit. Subsequently, a circuit is successfully built to implement two fundamental binary calculators: half-adder and half-subtractor, proving that the design can imitate silicon-based binary circuits. Finally, a comprehensive CLB-based circuit is built that enables multiple rounds of switch among seven different logic operations including half-adding and half-subtracting. Overall, the CLB-based erasable field-programmable circuit immensely enhances their practicability. It is believed that design can be widely used in DNA logic networks due to its efficiency and convenience., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial., Methods: In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used., Results: The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr., Conclusion: Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.

Imaging live cells under stable culture conditions is essential to investigate cell physiological activities and proliferation. To achieve this goal, typically, a specialized incubation chamber that creates desired culture conditions needs to be incorporated into a microscopy system to perform cell monitoring. However, such imaging systems are generally large and costly, hampering their wide applications. Recent advances in the field of miniaturized microscopy systems have enabled incubator cell monitoring, providing a hospitable environment for live cells. Although these systems are more cost-effective, they are usually limited in imaging modalities and spatial temporal resolution. Here, we present a dual-mode, image-enhanced, miniaturized microscopy system (termed MiniCube) for direct monitoring of live cells inside incubators. MiniCube enables both bright field imaging and fluorescence imaging with single-cell spatial resolution and sub-second temporal resolution. Moreover, this system can also perform cell monitoring inside the incubator with tunable time scales ranging from a few seconds to days. Meanwhile, automatic cell segmentation and image enhancement are realized by the proposed data analysis pipeline of this system, and the signal-to-noise ratio (SNR) of acquired data is significantly improved using a deep learning based image denoising algorithm. Image data can be acquired with 5 times lower light exposure while maintaining comparable SNR. The versatility of this miniaturized microscopy system lends itself to various applications in biology studies, providing a practical platform and method for studying live cell dynamics within the incubator., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ning Hu reports a relationship with National Natural Science Foundation of China that includes: funding grants. Diming Zhang reports a relationship with Zhejiang Provincial Natural Science Foundation of China that includes: funding grants. Chunlian Qin reports a relationship with National Natural Science Foundation of China that includes: funding grants. Ning Hu reports a relationship with Hangzhou Agricultural Social Development Research Key Project that includes:. Chunlian Qin reports a relationship with China Postdoctoral Science Foundation Funded Project that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanoagents for chemodynamic therapy (CDT) hold a promising future in the field of antimicrobials, especially copper peroxide (CuO 2 ) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply H 2 O 2 . Nevertheless, the poor stability of CuO 2 remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@Fe 3 O 4 with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO 2 -loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO 2 nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@Fe 3 O 4 undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO 2 @Fe 3 O 4 . The released CuO 2 @Fe 3 O 4 then self-supplies H 2 O 2 and generates reactive oxygen species (ROS) within the infected microenvironment through Fenton and Russell effects, to ultimately achieve effective and precise antimicrobial activity. Simultaneously, the magnetic property provided by Fe 3 O 4 allows the substance to be directed towards the infection site. Both in vitro and in vivo tests demonstrated that HA-CP@Fe 3 O 4 exhibited excellent antimicrobial capabilities at low concentration (30 μg mL -1 ), exceptional biocompatibility and the ability to accelerate wound healing. The findings of this work offer a new and promising approach for targeted and precise CDT.

Seesaw circuits are essential for molecular computing and biosensing. However, a notable limitation of seesaw circuits lies in the irreversible depletion of components, precluding the attainment of system recovery and rendering nucleic acid circuits non-reusable. We developed a brand-new method for creating controllable and reusable seesaw circuits. By using the nicking endonucleases Nt.BbvCI and Nt.Alwi, we removed "functional components" while keeping the "skeletal components" for recurrent usage. T-inputs were introduced, increasing the signal-to-noise ratio of AND logic from 2.68 to 11.33 and demonstrating compatibility. We identified the logic switching feature and verified that it does not impair circuit performance. We also built intricate logic circuits, such as OR-AND gate, to demonstrate the versatility of our methodology. This controllable reusability extends the applications of nanotechnology and bioengineering, enhancing the practicality and efficiency of these circuits across various domains., (© 2024. The Author(s).)

The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field., (© 2023 Wiley-VCH GmbH.)

Human gliomas are lethal brain cancers. Emerging evidence revealed the regulatory role of long noncoding RNAs (lncRNAs) in tumors. Here, we performed a comprehensive analysis of the expression profiles of RNAs in histologically lower-grade glioma (LGG). Enrichment analysis revealed that glioma is influenced by immune-related signatures. Survival analysis further established the close correlation between network features and glioma prognosis. Subsequent experiments showed lncRNA RP11-770J1.4 regulates CTXN1 expression through hsa-miR-124-3p. Correlation analysis identified lncRNA RP11-770J1.4 was immune related, specifically involved in the cytosolic DNA sensing pathway. Downregulated lncRNA RP11-770J1.4 resulted in increased spontaneous gene expression of the cGAS-STING pathway. Single-cell RNA sequencing analysis, along with investigations in a glioblastoma stem cell model and patient sample analysis, demonstrated the predominant localization of CTXN1 within tumor cores rather than peripheral regions. Immunohistochemistry staining established a negative correlation between CTXN1 expression and infiltration of CD8 + T cells. In vivo, Ctxn1 knockdown in GL261 cells led to decreased tumor burden and improved survival while increasing infiltration of CD8 + T cells. These findings unveil novel insights into the lncRNA RP11-770J1.4-CTXN1 as a potential immune regulatory axis, highlighting its therapeutic implications for histologically LGGs., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques., (© 2023. The Author(s).)

Immune homeostasis is delicately mediated by the dynamic balance between effector immune cells and regulatory immune cells. Local deviations from immune homeostasis in the microenvironment of bone fractures, caused by an increased ratio of effector to regulatory cues, can lead to excessive inflammatory conditions and hinder bone regeneration. Therefore, achieving effective and localized immunomodulation of bone fractures is crucial for successful bone regeneration. Recent research has focused on developing localized and specific immunomodulatory strategies using local hydrogel-based delivery systems. In this review, we aim to emphasize the significant role of immune homeostasis in bone regeneration, explore local hydrogel-based delivery systems, discuss emerging trends in immunomodulation for enhancing bone regeneration, and address the limitations of current delivery strategies along with the challenges of clinical translation.

Preclinical investigation of drug-induced cardiotoxicity is of importance for drug development. To evaluate such cardiotoxicity, in vitro high-throughput interdigitated electrode-based recording of cardiomyocytes mechanical beating is widely used. To automatically analyze the features from the beating signals for drug-induced cardiotoxicity assessment, artificial neural network analysis is conventionally employed and signals are segmented into cycles and feature points are located in the cycles. However, signal segmentation and location of feature points for different signal shapes require design of specific algorithms. Consequently, this may lower the efficiency of research and the applications of such algorithms in signals with different morphologies are limited. Here, we present a biosensing system that employs nonlinear dynamic analysis-assisted neural network (NDANN) to avoid the signal segmentation process and directly extract features from beating signal time series. By processing beating time series with fixed time duration to avoid the signal segmentation process, this NDANN-based biosensing system can identify drug-induced cardiotoxicity with accuracy over 0.99. The individual drugs were classified with high accuracies over 0.94 and drug-induced cardiotoxicity levels were accurately predicted. We also evaluated the generalization performance of the NDANN-based biosensing system in assessing drug-induced cardiotoxicity through an independent dataset. This system achieved accuracy of 0.85-0.95 for different drug concentrations in identification of drug-induced cardiotoxicity. This result demonstrates that our NDANN-based biosensing system has the capacity of screening newly developed drugs, which is crucial in practical applications. This NDANN-based biosensing system can work as a new screening platform for drug-induced cardiotoxicity and improve the efficiency of bio-signal processing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although many studies have focused on oncology and therapeutics in cancer, cancer remains one of the leading causes of death worldwide. Due to the unclear molecular mechanism and complex in vivo microenvironment of tumors, it is challenging to reveal the nature of cancer and develop effective therapeutics. Therefore, the development of new methods to explore the role of heterogeneous TME in individual patients' cancer drug response is urgently needed and critical for the effective therapeutic management of cancer. The organ-on-chip (OoC) platform, which integrates the technology of 3D cell culture, tissue engineering, and microfluidics, is emerging as a new method to simulate the critical structures of the in vivo tumor microenvironment and functional characteristics. It overcomes the failure of traditional 2D/3D cell culture models and preclinical animal models to completely replicate the complex TME of human tumors. As a brand-new technology, OoC is of great significance for the realization of personalized treatment and the development of new drugs. This review discusses the recent advances of OoC in cancer biology studies. It focuses on the design principles of OoC devices and associated applications in cancer modeling. The challenges for the future development of this field are also summarized in this review. This review displays the broad applications of OoC technique and has reference value for oncology development., Competing Interests: The authors declare no conflicts of interest.

Hypocalcemia is a disease that adversely affects the production and reproduction of dairy cows. A portable device for rapid bovine blood calcium sensing has been growing in demand. Herein, we report a smartphone-based ratiometric fluorescence probe (SRFP) platform as a new way to detect and quantify calcium ions (Ca 2+ ) in blood serum. Specifically, we employed a cost-effective and portable smartphone-based platform coupled with customized software that evaluates the response of Ca 2+ ions to ratiometric fluorescence probe in bovine serum. The platform consists of a three-dimensional (3D) printed housing and low-cost optical components that excite fluorescent probe and selectively transmit fluorescence emissions to smartphones. The customized software is equipped with a calibration model to quantify the acquired fluorescence images and quantify the concentration of Ca 2+ ions. The ratio of the green channel to the red channel bears a highly reproducible relationship with Ca 2+ ions concentration from 10 μM to 40 μM in bovine serum. Our detection system has a limit of detection (LOD) of 1.8 μM in bovine serum samples and the recoveries of real samples ranged from 92.8% to 110.1%, with relative standard deviation (RSD) ranging from 1.72% to 4.89%. The low-cost SRFP platform has the potential to enable campesino to rapidly detect Ca 2+ ions content in bovine serum on-demand in any environmental setting., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Quaternary chalcogenide materials have long been a source of semiconductors for optoelectronic applications. Recent studies on I 2 -II-IV-X 4 (I = Ag, Cu, Li; II = Ba, Sr, Eu, Pb; IV = Si, Ge, Sn; X = S, Se) materials have shown particular versatility and promise among these compounds. These semiconductors take advantage of a diverse bonding scheme and chemical differences among cations to target a degree of antisite defect resistance. Within this set of compounds, the materials containing both Ag and Sr have not been experimentally studied and leave a gap in the full understanding of the family. Here, we have synthesized powders and single crystals of two Ag- and Sr-containing compounds, Ag 2 SrSiS 4 and Ag 2 SrGeS 4 , each found to form in the tetragonal I 4̅2 m structure of Ag 2 BaGeS 4 . During the synthesis targeting the title compounds, two additional materials, Ag 2 Sr 3 Si 2 S 8 and Ag 2 Sr 3 Ge 2 S 8 , have also been identified. These cubic compounds represent impurity phases during the synthesis of Ag 2 SrSiS 4 and Ag 2 SrGeS 4 . We show through hybrid density functional theory calculations that Ag 2 SrSiS 4 and Ag 2 SrGeS 4 have highly dispersive band-edge states and indirect band gaps, experimentally measured as 2.08(1) and 1.73(2) eV, respectively. Second-harmonic generation measurements on Ag 2 SrSiS 4 and Ag 2 SrGeS 4 powders show frequency-doubling capabilities in the near-infrared range.

Single-base mutations are the most common type of mutation in human diseases. Melting curve analysis is currently one of the most commonly used methods to detect single base mutations. However, the existing melting curve analysis cannot possess universality and robust detection performance simultaneously. Therefore, herein, we invented an interlocked DNA cascade system based universal melting curve analysis (ICU-MCA). The strategy is based on the probe dissolution curve method by designing a bridge strand to achieve an ideal distinction between mutant-type DNA and wild-type DNA. What is more, this method can complete multiplexed detection only by changing the bridge sequence, replacing the specific and expensive probe in a traditional probe based melting curve analysis. We performed 6-plex detection on 6 single-base point mutations in BRAC1/2 genes on synthetic single stranded DNA and verified the compatibility of ICU-MCA and PCR and detected BRCA1/c.2082C>T and BRCA2/c.7397T>C mutations in peripheral blood DNA of ovarian cancer patients. Overall, ICU-MCA is one of the best methods in the field of melting curve analysis for detecting single-base mutations.