Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

The Risk of Deep Vein Thrombosis and Optimal Timing of Breast Cancer Surgery After COVID-19 Infection.

PURPOSE: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic." METHODS: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression. RESULTS: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy. CONCLUSION: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

Photomodulation of Charge Transfer through Excited-State Processes: Directing Donor-Acceptor Binding Dynamics.

Modulating charge transfer (CT) interactions between donor and acceptor molecules may give rise to unique dynamic changes in physicochemical properties, exhibiting great importance in supramolecular chemistry and materials science. In this work, we demonstrate the first instance of reversible photomodulation of donor-acceptor (D-A) CT interaction in the solid state.Pyridinium-based chromophore featuring π-conjugated D-A structures can not only function as a good electron acceptor to undergo photoinduced electron transfer (ET) or engage in intermolecular CT interaction, but also exhibit unique dual emission depending on the excitation wavelengths. The rotatable C-C single bonds within D-A pairs enhance the tunability of molecular structure. Through the synergy of a photoinduced ET and an excited-state conformational change, the intermolecular CT interaction can be switched on and off by alternate light irradiation to enables reversibly modulation of the affinity between donor and acceptor molecules, accompanied by visual color switching and fluorescence on-off as feedback signals.

Iatrogenic harm in functional neurological disorder.

Functional Neurological Disorder (FND) is continuing to gain increasing recognition globally as a valid and potentially treatable disorder. Iatrogenic harm towards patients with FND is significant however, and has been around for centuries. Despite advances in our understanding around the aetiology, pathophysiology, and treatment of FND, many aspects of such harm continue to persist. Avoidance of iatrogenic harm has been highlighted by clinicians as one of the most important therapeutic considerations in FND, however, the sources and range of potential harms, or indeed ways to mitigate them, have not been previously summarised. Using a combination of clinical and research experience and scoping review methodology, this review aims to describe the main sources of iatrogenic harm towards patients with FND, including harm from misdiagnosis, delayed diagnosis and treatment, direct harm from professional interactions, other stigma-related harms, harm related to diagnostic overshadowing and over-diagnosis of FND. We also describe some potential ways to address and prevent such harms, such as ways to reduce misdiagnosis with a focus on rule in signs, optimising teaching and communication, ensuring parity of FND with other medical conditions, and continued integration of patient and professional organisations.

UV-driven self-replenishing liquid-infused surface with promising anti-algal adhesion performance.

Slippery liquid-infused porous surfaces (SLIPSs) inspired by Nepenthes have attracted much attention owing to their potential application in various cutting-edge fields. However, the performance of SLIPSs is impeded by surface damage and lubricant depletion, thereby limiting their further application. Herein, a UV-responsive slippery surface (SMEMG) was fabricated by introducing the UV-responsive functional group coumarin into the polymer side chain through random copolymerization, followed by crosslinking, curing and impregnation with vegetable oil. The self-healing ability and lubricant self-replenishing performance of the SMEMG were investigated. The results show that upon exposure to UV light, the damaged surface substrate can be repaired through a reversible photodimerization reaction between coumarin groups. Meanwhile, the lubricant oil within the bulk of the SMEMG substrate can be extruded to the surface during the photodimerization reaction, facilitating the recovery of surface wettability. The SMEMG exhibited excellent self-cleaning and anti-algal properties as well as durability in a harsh environment, demonstrating its promising application in marine anti-fouling.

Hospitalized children with COVID-19 infection during large outbreak of SARS-CoV-2 Omicron strain: a retrospective study in Chaozhou, Guangdong, China.

OBJECTIVE: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022. METHOD: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively. RESULTS: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels. CONCLUSIONS: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

Study of Manipulative Pore Formation upon Polymeric Coating for the Endowment of the Switchable Property between Passive Daytime Radiative Cooling and Heating.

Passive daytime radiative cooling (PDRC) emerges as a promising cooling strategy with an attractive feature of no energy and refrigerant consumption. In the current study, for the purpose of achieving cost-efficient fabrication of a PDRC polymeric material, a microporous polymeric coating is prepared by a novel "inverse emulsion"-"breath figure" (Ie-BF) method using water droplets as pore-formation template, and the porous morphologies of both the surface and bulk layer can be dynamically manipulated by tuning the emulsion composition as well as environmental conditions. Therefore, the solar reflectivity of the Ie-BF coating can be efficiently tuned within a rather wide range (21-91%) by facile modulation of porosity and thickness. The Ie-BF coating with a thickness of only 125 µm exhibits a high solar reflectance of 85.4% and a long-wave infrared emissivity of 96.3%, realizing a subambient radiative cooling of 6.7 °C and a cooling power of ∼76 W m-2 in the open air. Moreover, by employing the reversible feature of in situ pore formation and erasure combined with the additional attachment of a carbon black layer, the composite film could be easily switched between cooling and heating modes by solvent post-treatment. This research establishes a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of porous polymeric PDRC coating.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua, China: Two case reports.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells. BPDCN often involves the skin, lymph nodes, and bone marrow, with rapid clinical progression and a poor prognosis. The BPDCN diagnosis is mainly based on the immunophenotype. CASE SUMMARY: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive. CONCLUSION: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.

WNT1-inducible signaling pathway protein 1 activation through C-X-C motif chemokine ligand 5/C-X-C chemokine receptor type 2/leukemia inhibitory factor/leukemia inhibitory factor receptor signaling promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention.

Insufficient FUNDC1-dependent mitophagy due to early environmental cadmium exposure triggers mitochondrial redox imbalance to aggravate diet-induced lipotoxicity.

Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd2+/kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure.

Investigation of the Crystallographic Evolution Sequence of Nano-Precipitation via HRTEM in Cu-Bearing Ultra-Low Carbon Steel.

The precipitation behavior of Cu-bearing ultra-low carbon steel after step quenching and tempering at 923 K for 0.5-2.5 h was investigated. The size, quantity, and characteristic distribution of nano-precipitates were analyzed using transmission electron microscopy, and the microstructure of B2 (an ordered structure belonging to the body-centered cubic structure), 9R (a special triclinic lattice that has characteristics of rhombohedral structure), 3R (a special triclinic lattice like 9R), and FCT (face-centered tetragonal lattices) were accurately determined. The relationship between nano-precipitates and mechanical properties under different heat treatment processes was obtained, revealing that nano-precipitates effectively enhanced the yield strength of Cu-bearing ultra-low carbon steel. There were two forms of crystal structure evolution sequence of precipitation: B2→multi twin 9R→detwined 9R→FCT→FCC and B2→multi-twin 9R→detwinned 9R→3R→FCT→FCC. The morphology of the precipitated particles during the growth process changed from spherical to ellipsoidal and finally to rod-shaped. It was proven that a stable 3R structure existed due to the coexistence of 9R, 3R, and FCT structures in the same precipitate particle.

Single-cell transcriptome sequencing reveals that Wolbachia induces gene expression changes in Drosophila ovary cells to favor its own maternal transmission.

Wolbachia is an obligate endosymbiont that is maternally inherited and widely distributed in arthropods and nematodes. It remains in the mature eggs of female hosts over generations through multiple strategies and manipulates the reproduction system of the host to enhance its spreading efficiency. However, the transmission of Wolbachia within the host's ovaries and its effects on ovarian cells during oogenesis, have not been extensively studied. We used single-cell RNA sequencing to comparatively analyze cell-typing and gene expression in Drosophila ovaries infected and uninfected with Wolbachia. Our findings indicate that Wolbachia significantly affects the transcription of host genes involved in the extracellular matrix, cytoskeleton organization, and cytomembrane mobility in multiple cell types, which may make host ovarian cells more conducive for the transmission of Wolbachia from extracellular to intracellular. Moreover, the genes nos and orb, which are related to the synthesis of ribonucleoprotein complexes, are specifically upregulated in early germline cells of ovaries infected with Wolbachia, revealing that Wolbachia can increase the possibility of its localization to the host oocytes by enhancing the binding with host ribonucleoprotein-complex processing bodies (P-bodies). All these findings provide novel insights into the maternal transmission of Wolbachia between host ovarian cells.IMPORTANCEWolbachia, an obligate endosymbiont in arthropods, can manipulate the reproduction system of the host to enhance its maternal transmission and reside in the host's eggs for generations. Herein, we performed single-cell RNA sequencing of ovaries from Drosophila melanogaster and observed the effects of Wolbachia (strain wMel) infection on different cell types to discuss the potential mechanism associated with the transmission and retention of Wolbachia within the ovaries of female hosts. It was found that the transcriptions of multiple genes in the ovary samples infected with Wolbachia are significantly altered, which possibly favors the maternal transmission of Wolbachia. Meanwhile, we also discovered that Wolbachia may flexibly regulate the expression level of specific host genes according to their needs rather than rigidly changing the expression level in one direction to achieve a more suitable living environment in the host's ovarian cells. Our findings contribute to a further understanding of the maternal transmission and possible universal effects of Wolbachia within the host.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Aerobic Copper-Catalyzed Oxysulfonylation of Vinylarenes with Sodium Sulfinates under Mild Conditions: A Modular Synthesis of ß-Ketosulfones.

An aerobic copper-catalyzed oxysulfonylation of vinylarenes with sodium sulfinates is described. This protocol features mild reaction conditions, convenient operation, and broad substrate scope with respect to vinylarenes and sodium sulfinates. Notably, the protocol demonstrates excellent tolerance of functional groups such as chloro, bromo, ester, cyano, and nitro groups. Mechanistic investigations indicated that the reaction should undergo radical cascades involving a sulfonyl radical generated from sodium sulfinate with air as the terminal oxidant, addition across alkene to deliver a benzylic radical, and subsequent cross-coupling with air.

The Past, Present, and Future of Perforator Flaps in Head and Neck Surgery.

A perforator is a vessel that travels through muscle and perfuses the skin. Perforator flaps require intramuscular dissection and can be used as pedicled or free flap. With improved understanding of microvasculature, they can be tailored to have multiple skin paddles, multiple components, or shaped to conform to any defect. Reliable perforator flap-based reconstruction is a meticulous microvascular technique, ultimately allowing the surgeon to harvest any flap in a freestyle fashion and transplant to any recipient vessel. New technologies improve the safety and reproducibility of this type of reconstruction.

Wide-range and high-accuracy wireless sensor with self-humidity compensation for real-time ammonia monitoring.

Real-time and accurate biomarker detection is highly desired in point-of-care diagnosis, food freshness monitoring, and hazardous leakage warning. However, achieving such an objective with existing technologies is still challenging. Herein, we demonstrate a wireless inductor-capacitor (LC) chemical sensor based on platinum-doped partially deprotonated-polypyrrole (Pt-PPy+ and PPy0) for real-time and accurate ammonia (NH3) detection. With the chemically wide-range tunability of PPy in conductivity to modulate the impedance, the LC sensor exhibits an up-to-180% improvement in return loss (S11). The Pt-PPy+ and PPy0 shows the p-type semiconductor nature with greatly-manifested adsorption-charge transfer dynamics toward NH3, leading to an unprecedented NH3 sensing range. The S11 and frequency of the Pt-PPy+ and PPy0-based sensor exhibit discriminative response behaviors to humidity and NH3, enabling the without-external-calibration compensation and accurate NH3 detection. A portable system combining the proposed wireless chemical sensor and a handheld instrument is validated, which aids in rationalizing strategies for individuals toward various scenarios.

Association between rheumatoid arthritis and chronic respiratory diseases in a Japanese population: A Mendelian randomization study.

Past observational studies have documented an association between rheumatoid arthritis (RA) and chronic respiratory diseases. Undertaking the approach of Mendelian randomization (MR) analysis, this research aims to delve deeper into the probability of a causal connection between RA and chronic respiratory diseases. Collated genome-wide association study data covering RA with 4199 cases against 208,254 controls, asthma comprising 8216 cases versus 201,592 controls, and chronic obstructive pulmonary disease (COPD) detailing 3315 cases in contrast to 201,592 controls were derived from the repository of the Japanese Biobank. A selection of 10 RA-related, 8 asthma-related, and 4 COPD-related single nucleotide polymorphisms notable for their statistical significance (P < 5 × 10-8) were identified as instrumental variables. The primary analytical technique was the inverse variance-weighted (IVW) method, alongside the MR-Egger protocol, weighted median, and weighted mode to reinforce the validity and solidity of the principal results. For scrutinizing possible implications of horizontal pleiotropy, we harnessed the MR-Egger intercept examination and the Mendelian Randomization Pleiotropy REsidual Sum and Outlier test. Employing the inverse variance-weighted technique, we established a positive correlation between genetic predispositions for RA and actual occurrences of asthma (odds ratios [OR] = 1.14; 95% confidence intervals [CI]: 1.04-1.24; P = .003). This correlation remained strong when testing the results utilizing various methods, including the MR-Egger method (OR = 1.32; 95% CI: 1.09-1.60; P = .023), the weighted median (OR = 1.16; 95% CI: 1.06-1.26; P < .001), and the weighted mode (OR = 1.21; 95% CI: 1.11-1.32; P = .002). Furthermore, our findings from the inverse variance-weighted method also demonstrated a positive association between genetically predicted RA and COPD (OR = 1.12; 95% CI: 1.02-1.29; P = .021). However, no such link was discerned in supplementary analyses. In a shifted perspective-the reverse MR analysis-no correlation was identified between genetically predicted instances of asthma (IVW, P = .717) or COPD (IVW, P = .177) and RA. The findings confirm a causal correlation between genetically predicted RA and an elevated risk of either asthma or COPD. In contrast, our results offer no support to the presumed causal relationship between genetic susceptibility to either asthma or COPD and the subsequent development of RA.

Study of pediatric appendicitis scores and management strategies: A prospective observational feasibility study.

OBJECTIVE: The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED). METHODS: A literature search was conducted to identify potential CPSs and a single-center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5-15 years presenting with acute right-sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician-collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low-risk or high-risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow-up for those discharged directly from ED. RESULTS: Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC-ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86-0.94) and specificity 99.0% (95% CI 96.4%-99.7%) in diagnosing high-risk cases and a misclassification rate of 4.5% for low-risk cases. CONCLUSIONS: The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC-ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings.

Liver-specific delivery of spherical DNA frameworks for alleviation of hepatic ischemic reperfusion injury.

DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures.

Elucidating the role of angiogenesis-related genes in colorectal cancer: a multi-omics analysis.

Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.