Protein-Controlled Split DNAzyme to Enhance Catalytic Activity: Design and Performance.

In this study, we utilized proteins to control the assembly of split DNAzyme to establish protein-controlled split DNAzymes (Pc SD), with the aim of enhancing its catalytic activity. To achieve this, simultaneous recognition of protein by affinity ligands at both ends of split DNAzyme fragments induced an increased local concentration of each split fragment, leading to reassembly of the split catalytic core with a rigid conformation and higher affinity to its cofactor. As a result, under protein control, Pc SD exhibits unexpected cleavage efficiency compared to free split DNAzyme. To further explore the catalytic features, we then systematically positioned split sites within the catalytic core of three popular DNAzyme-based Pc SDs, thus revealing the important nucleic acids that influence Pc SDs activity. Based on the excellent analytical performance of Pc SD for streptavidin (with a LOD of 0.1 pM in buffer),we equipped Pc SD with antibodies as rapid diagnostic tools for inpatient care (AFP as biomarker) with a minimized workflow (with a LOD of 2 pM in 5% human serum). The results of this study offer fundamental insights into external factors for boosting DNAzyme catalysis and will be promising for applications that utilize split DNAzymes.

Preoperative in-hospital delay increases postoperative morbidity and mortality in patients with acute appendicitis: A meta-analysis.

BACKGROUND: Complicated appendicitis is associated with high morbidity, mortality, and healthcare costs. However, the relationship of preoperative in-hospital delay >24 hours with complicated appendicitis and postoperative morbidity remains unclear. This meta-analysis investigated the effects of preoperative in-hospital delay on complicated appendicitis and postoperative morbidity in patients with acute appendicitis. MATERIALS AND METHODS: This study adheres to the PRISMA 2020 and AMSTAR 2 guidelines. The PubMed, Embase, Cochrane Library, and Web of Science databases up to October 14, 2023 (updated on March 16, 2024) were searched for randomized controlled trials (RCTs) and observational studies that evaluated the effect of preoperative in-hospital delays of >24 hours on acute appendicitis. Odds ratios (OR) and 95% confidence intervals were also determined. RESULTS: We yielded 18,130 records, of which 28 studies (512,881 patients) were included in the meta-analysis. The risk of bias was considered serious, moderate, and low for 24, 3, and 1 study, respectively. Although preoperative in-hospital delays of >24 hours were not associated with a higher risk of surgical site infection (OR 1.04, 95% CI 0.97, 1.12, P=0.25), in-hospital delays of >24 hours was a risk factor for complicated appendicitis (OR 1.60, 95% CI 1.25, 2.05, P=0.0002), and postoperative complications (OR 1.51, 95% CI 1.30, 1.75, P<0.00001). In addition, an in-hospital delay of >24 hours before surgery increased the OR of postoperative mortality (OR 1.81, 95% CI 1.33, 2.45, P=0.0001). The sensitivity analyses also confirmed the robustness of our results. CONCLUSIONS: An in-hospital delay of >24 hours is a risk factor for complicated appendicitis, postoperative complications, and mortality. Given the subsequent adverse outcomes of in-hospital delays, appendectomy should not be delayed for >24 hours.

Comparison of short-term outcomes of robotic versus open Pancreaticoduodenectomy: A Meta-Analysis of randomized controlled trials and Propensity-Score-Matched studies.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is used more commonly, but this surge is mostly based on observational data. This meta-analysis aimed to compare the short-term outcomes between RPD and open pancreaticoduodenectomy (OPD) using data collected from randomized controlled trials (RCTs) and propensity score-matched (PSM) studies. MATERIALS AND METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases for RCTs and PSM studies comparing RPD and OPD. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Twenty-four studies, encompassing two RCTs and 22 PSM studies, were included, with a total of 9393 patients (RPD group: 3919 patients; OPD group: 5474 patients). Although RPD was associated with a longer operative time (MD, 61.61 min), patients may benefit from reduced blood loss (MD, -154.05 mL), shorter length of stay (MD, -1.60 d), lower blood transfusion rate (RR, 0.85), and wound infection rate (RR, 0.61). There were no significant differences observed in 30-day readmission (RR, 0.99), 90-day mortality (RR, 0.97), overall morbidity (RR, 0.88), major complications (RR, 1.01), reoperation (RR, 1.08), bile leak (RR, 1.01), chylous leak (RR, 0.98), postoperative pancreatic fistula (RR, 0.97), postpancreatectomy hemorrhage (RR, 1.15), delayed gastric emptying (RR, 0.88), number of harvested lymph nodes (MD, -0.12), and R0 resection (RR, 1.01) between the groups. CONCLUSIONS: Although some short-term outcomes were similar between RPD and OPD, RPD exhibited reduced intraoperative blood loss, shorter hospital stays, lower wound infection, and blood transfusion rates. In the future, RPD may become a safe and effective alternative to OPD.

Construction of a streptavidin-based dual-localized DNAzyme walker for disease biomarker detection.

A dual-localized DNAzyme walker (dlDW) was constructed by utilizing multiple split DNAzymes with probes, and their substrates are separately localized on streptavidin and AuNPs, serving as walking pedals and tracks, respectively. Based on dlDW, biosensing platform was successfully constructed and showed great potential application in clinical disease diagnosis.

Advances in Adjoint Functions of Connection Number in Water Resources Complex Systems: A Systematic Review.

The adjoint function of connection number has unique advantages in solving uncertainty problems of water resource complex systems, and has become an important frontier and research hotspot in the uncertainty research of water resource complex problems. However, in the rapid evolution of the adjoint function, some problems greatly limit the application of the adjoint function in the research of water resources. Therefore, based on bibliometric analysis, development, practical application issues, and prospects of the hot directions are analyzed. It is found that the development of the connection number of water resource set pair analysis can be divided into three stages: (1) relatively sluggish development before 2005, (2) a period of rapid advancement in adjoint function research spanning from 2005 to 2017, and (3) a subsequent surge post-2018. The introduction of the adjoint function of connection number promotes the continuous development of set pair analysis of water resources. Set pair potential and partial connection number are the crucial research directions of the adjoint function. Subtractive set pair potential has rapidly developed into a relatively independent and important trajectory. The research on connection entropy is comparatively less, which needs to be further strengthened, while that on adjacent connection number is even less. The adjoint function of set pair potential can be divided into three major categories: division set pair potential, exponential set pair potential, and subtraction set pair potential. The subtraction set pair potential, which retains the original dimension and quantity variation range of the connection number, is widely used in water resources and other fields. Coupled with the partial connection number, a series of new connection number adjoint functions have been developed. The partial connection number can be mainly divided into two categories: total partial connection number, and semi-partial connection number. Among these, the calculation expression and connotation of total partial connection numbers have not yet reached a consensus, accompanied by the slow development of high-order partial connection numbers. Semi-partial connection number can describe the mutual migration movement between different components of the connection number, which develops rapidly. With the limitations and current situation described above, promoting the exploration and application of the adjoint function of connection number in the field of water resources and other fields of complex systems has become the focus of future research.

A Portable Nucleic Acid Testing Platform with Photosensitization, a Three-Dimensionally Printed Multipiece Chip, and Digital Color Sensing.

Portable nucleic acid testing (NAT) holds great promise for point-of-care disease diagnosis and field-based applications but remains difficult to achieve. Herein, we describe a portable NAT that streamlines loop-mediated isothermal amplification with photosensitization-based color development in a fully sealed 3D-printed multipiece chip. Using a smartphone accessory and an APP, we also introduce a calibration-free quantification approach via digital color sensing and library matching. With these innovative approaches, our detection platform is highly accessible, allowing for rapid and sensitive NAT without requiring sophisticated instruments and well-trained personnel. The field applicability of our NAT platform was demonstrated by detecting tuberculosis infections in clinical sputum samples and food adulteration in commercial salmon meat products.

Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.

BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1. RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect. CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.

Hypothermic oxygenated perfusion in liver transplantation: a meta-analysis of randomized controlled trials and matched studies.

BACKGROUND: Hypothermic oxygenated machine perfusion (HOPE) is a novel organ-preservation technology designed to optimize organ quality. However, the effects of HOPE on morbidity and mortality after liver transplantation remain unclear. This meta-analysis evaluated the potential benefits of HOPE in liver transplantation. MATERIALS AND METHODS: The Embase, Web of Science, PubMed, Cochrane Library, and Scopus databases were searched for articles published up to 15 June 2023 (updated on 12 August 2023). Mean differences (MDs), risk ratios (RRs), and 95% confidence intervals were calculated. RESULTS: Eleven studies encompassing five randomized controlled trials and six matched studies were included, with a total of 1000 patients. HOPE did not reduce the incidence of major postoperative complications (RR 0.80), primary non-function (PNF) (RR 0.54), reperfusion syndrome (RR 0.92), hepatic artery thrombosis (RR 0.92), renal replacement therapy (RR 0.98), length of hospital stay (MD, -1.38 days), 1-year recipient death (RR 0.67), or intensive care unit stay (MD, 0.19 days) after liver transplantation. HOPE reduced the incidence of biliary complications (RR 0.74), non-anastomotic biliary strictures (NAS) (RR 0.34), early allograft dysfunction (EAD) (RR 0.54), and acute rejection (RR 0.54). In addition, HOPE improved the retransplantation (RR 0.42) and 1-year graft loss rates (RR 0.38). CONCLUSIONS: Compared with static cold storage (SCS), HOPE can reduce the incidence of biliary complications, NAS, EAD, and acute rejection and retransplantation rate after liver transplantation and improve the 1-year graft loss rate. These findings suggest that HOPE, when compared to SCS, can contribute to minimizing complications and enhancing graft survival in liver transplantation. Further research is needed to investigate long-term outcomes and confirm the promising advantages of HOPE in liver transplantation settings.

Fabrication of 3D printed PCL/PEG artificial bile ducts as supportive scaffolds to promote regeneration of extrahepatic bile ducts in a canine biliary defect model.

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

Connection number based model for coordination development evaluation of regional water resources, social economy and ecological environment complex system.

The development of social economy often requires a large consumption of water resources, and will also discharge a large amount of pollutants to the environment. Currently, the rapid development of regional water resources, social economy and ecological environment (WSE) complex system encounters significant challenges, and the coordination development of WSE complex system becomes important and necessary condition of regional sustainable development. Therefore, to scientifically evaluate the coordination development state of WSE system, based on the establishment of evaluation index system, the connection number and distance coordination model coupling approach for the coordination development evaluation of WSE complex system was proposed in this manuscript. The application results of the proposed method in Anhui Province, China indicate that, during 2011-2020, the coordination level of Anhui province is relatively high, and the coordination grade of most cities are in grade I or II. The coordination development degree of Anhui province presented a distinct improving trend with time, from most cities in grade IV or V in 2011 to most cities in grade II in 2020, from the worst 0.0580 in 2011 to the best 0.9200 in 2020. In terms of space, the coordinated development level of southern Anhui is higher than that of northern Anhui. Meanwhile, the coordination development status of the 16 cities in Anhui province can be divided into three patterns according to its historical variation characteristics, i.e., coordination development mode, ecological environment backward mode, and social and economic backward mode. Compared with the commonly used coordination evaluation method, the method of this paper can solve the problem of homogenization, and its calculation results are more reasonable and practical.

Lanthanide Encoded Logically Gated Micromachine for Simultaneous Detection of Nucleic Acids and Proteins by Elemental Mass Spectrometry.

DNA-based logic computing potentially for analysis of biomarker inputs and generation of oligonucleotide signal outputs is of great interest to scientists in diverse areas. However, its practical use for sensing of multiple biomarkers is limited by the universality and robustness. Based on a proximity assay, a lanthanide encoded logically gated micromachine (LGM-Ln) was constructed in this work, which is capable of responding to multiplex inputs in biological matrices. Under the logic function controls triggered by inputs and a Boolean "AND" algorithm, it is followed by an amplified "ON" signal to indicate the analytes (inputs). In this logically gated sensing system, the whole computational process does not involve strand displacement in an intermolecular reaction, and a threshold-free design is employed to generate the 0 and 1 computation via intraparticle cleavage, which facilitates the computation units and makes the "computed values" more reliable. By simply altering the affinity ligands for inputs' biorecognition, LGM-Ln can also be extended to multi-inputs mode and produce the robust lanthanide encoded outputs in the whole human serum for sensing nucleic acids (with the detection limit of 10 pM) and proteins (with the detection limit of 20 pM). Compared with a logically gated micromachine encoded with fluorophores, the LGM-Ln has higher resolution and no spectral overlaps for multiple inputs, thus holding great promise in multiplex analyses and clinical diagnosis.

Biomolecule-guided co-localization of intermolecular G-rich strands for the construction of a tetramolecular G-quadruplex sensing strategy.

We herein introduce the principle of proximity assay into tetramolecular G-quadruplexes guided by various biomolecules for the construction of a sensing strategy. Our strategy is based on the co-localization of intermolecular G-rich strands guided by a recognition event of a specific biomolecule to its corresponding affinity ligand. In such case, the local concentration among intermolecular strands is significantly increased to trigger the following self-assembly that served as the peroxidase-mimicking activity. This strategy is versatile, homogenous and adaptable to different types of biomolecules.

Coordination evaluation and obstacle factors recognition analysis of water resource spatial equilibrium system.

The comprehensive evaluation analysis of water resource spatial equilibrium (WRSE) system is a fundamental and crucial facet to construct national water resource network system and implement socio-economy equilibrium development strategy in China. To clearly understanding of the structural relationship of WRSE system, we firstly proposed the definition of WRSE system from the perspective of coordination variation between water resource carrying pressure and support force subsystems in this study, then, the multi-dimensional connection cloud and coupling coordination degree approaches were applied to construct integrated evaluation model (MCCD) of WRSE system, and finally, the obstacle degree model was utilized as well to recognize the primary influence factors which resulted in the variation of WRSE system. Eventually, it can be revealed from the application results of MCCD model that, the overall situation of WRSE system in Anhui Province, China was improved obviously during the past 10 years, with the average coupling coordination degree (CCD) increased from 0.58 in 2011 to 0.68 in 2018. In addition, water resources availability per capita (S1) and agricultural irrigation quota (P8) were the two primary indicators causing the variation of water resource carrying support and pressure force subsystems. The above application analysis results were reliable and consistent with the evolution trend of actual historical observed statistics, and could also provide scientific decision-making basis for the implementation of prediction and regulation schemes of WRSE system.

Protein-Recognition-Initiated Exponential Amplification Reaction (PRIEAR) and Its Application in Clinical Diagnosis.

Isothermal exponential amplification technology has rarely been fabricated as a universal sensing platform for the detection of proteins. To broaden their application, we have developed a strategy, named protein-recognition-initiated exponential amplification reaction (PRIEAR) using protein recognition to induce DNA assembly, which converts protein recognition events into ssDNA amplicons and combines two-stage amplification to achieve exponential amplification. Taking advantage of this principle, diverse biomarkers can be quantified at sub-picomolar concentrations in a homogenous manner, making PRIEAR suitable for clinical settings. Therefore, this strategy can expand the powerful isothermal exponential amplification technology to protein targets and thus provide a new toolbox in clinical and biomedical applications.

Advances in the DNA Nanotechnology for the Cancer Biomarkers Analysis: Attributes and Applications.

The most commonly used clinical methods are enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR) in which ELISA was applied for the detection of protein biomarkers and qPCR was especially applied for nucleic acid biomarker analysis. Although these constructed methods have been applied in wide range, they also showed some inherent shortcomings such as low sensitivity, large sample volume and complex operations. At present, many methods have been successfully constructed on the basis of DNA nanotechnology with the merits of high accuracy, rapid and simple operation for cancer biomarkers assay. In this review, we summarized the bioassay strategies based on DNA nanotechnology from the perspective of the analytical attributes for the first time and discussed and the feasibility of the reported strategies for clinical application in the future.

Stimuli-Responsive Three-Dimensional DNA Nanomachines Engineered by Controlling Dynamic Interactions at Biomolecule-Nanoparticle Interfaces.

Stimuli-responsive nanomachines are attractive tools for biosensing, imaging, and drug delivery. Herein, we demonstrate that the orientation of macromolecules and subsequent dynamic interactions at the biomolecule-nanoparticle (bio-nano) interfaces can be rationally controlled to engineer stimuli-responsive DNA nanomachines. The success of this design principle was demonstrated by engineering a series of antibody-responsive DNA walkers capable of moving persistently on a three-dimensional track made of DNA functionalized gold nanoparticles. We show that drastically different responses to antibodies could be achieved using DNA walkers of identical sequences but with varying number or sites of modifications. We also show that multiple interfacial factors could be combined to engineer stimuli-responsive DNA nanomachines with high sensitivity and modularity. The potential of our strategy for practical uses was finally demonstrated for the amplified detection of antibodies and small molecules in both buffer and human serum samples. Unlike many DNA-based nanomachines, the performance of which could be significantly hindered by the matrix of serum, our system shows a matrix-enhanced sensitivity as a result of the engineering approach at the bio-nano interface.