A pendulum-type electrochemical aptamer-based sensor for continuous, real-time and stable detection of proteins.

Continuous detection of proteins is crucial for health management and biomedical research. Electrochemical aptamer-based (E-AB) sensor that relies on binding affinity between a recognition oligonucleotide and its specific target is a versatile platform to fulfill this purpose. Yet, the vast majority of E-AB sensors are characterized by voltammetric methods, which suffer from signal drifts and low-frequency data acquisition during continuous operations. To overcome these limitations, we developed a novel E-AB sensor empowered by Gold nanoparticle-DNA Pendulum (GDP). Using chronoamperometric interrogation, the developed sensor enabled drift-resistant, high-frequency, and real-time monitoring of vascular endothelial growth factor (VEGF), a vital signaling protein that regulates angiogenesis, endothelial cell proliferation and vasculogenesis. We assembled VEGF aptamer-anchored GDP probes to a reduced graphene modified electrode, where a fast chronoamperometric current transient occurs as the GDP rapidly transport to the electrode surface. In the presence of target molecules, longer and concentration-dependent time decays were observed because of slower motion of the GDP in its bound state. After optimizing several decisive parameters, including composition ratios of GDP, probe density, and incubation time, the GDP empowered E-AB sensor achieves continuous, selective, and reversible monitoring of VEGF in both phosphate buffered saline (PBS) solutions and artificial urine with a wide detection range from 13 fM to 130 nM. Moreover, the developed sensor acquires signals on a millisecond timescale, and remains resistant to signal degradation during operation. This study offers a new approach to designing E-AB architectures for continuous biomolecular monitoring.

Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway.

Argatroban is a synthetic thrombin inhibitor approved by U.S. Food and Drug Administration for the treatment of thrombosis. However, whether it plays a role in the repair of spinal cord injury is unknown. In this study, we established a rat model of T10 moderate spinal cord injury using an NYU Impactor Moder III and performed intraperitoneal injection of argatroban for 3 consecutive days. Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord. RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway, which is involved in astrogliosis and glial scar formation. Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway. Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord. Taken together, these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway, thereby promoting the recovery of neurological function after spinal cord injury.

Compression Property of TPEE-3D Fibrous Material and Its Application in Mattress Structural Layer.

Thermoplastic poly(ether/ester) elastomer (TPEE) has great potential as a mattress material due to its high resilience, breathability, and light weight. This study aimed to evaluate the feasibility of TPEE-3D fibrous material (T3DF), a three-dimensional block material made of TPEE fibers randomly aligned and loop-connected, for mattress application. After testing the compression properties of T3DF, the effects of T3DF structural layers on mattress firmness were investigated. The results showed that T3DF had good energy absorption capacity, broad indentation hardness range (126.94-333.82 N), and high compression deflection coefficient (2.79-4.39). The thickness and density of T3DF were the main factors influencing mattress firmness, and the impact of thickness was more significant (p < 0.05). Owing to the hard and soft segments contained in TPEE, T3DF could be used for both the padding and core layers of the mattress. The hardness value and Dsurface of the mattress with a T3DF padding layer increased with T3DF density but decreased with T3DF thickness. Moreover, the hardness value and Dsurface of the mattress with a T3DF core layer increased with T3DF density, while with T3DF thickness, its Dsurface increased and Dbottom decreased. Therefore, the thick and low-density T3DF padding layer could improve the comfort of the mattress surface, a thin T3DF core layer could satisfy both the softer surface and the firmer bottom of the mattress.

FireFace: Leveraging Internal Function Features for Configuration of Functions on Serverless Edge Platforms.

The emerging serverless computing has become a captivating paradigm for deploying cloud applications, alleviating developers' concerns about infrastructure resource management by configuring necessary parameters such as latency and memory constraints. Existing resource configuration solutions for cloud-based serverless applications can be broadly classified into modeling based on historical data or a combination of sparse measurements and interpolation/modeling. In pursuit of service response and conserving network bandwidth, platforms have progressively expanded from the traditional cloud to the edge. Compared to cloud platforms, serverless edge platforms often lead to more running overhead due to their limited resources, resulting in undesirable financial costs for developers when using the existing solutions. Meanwhile, it is extremely challenging to handle the heterogeneity of edge platforms, characterized by distinct pricing owing to their varying resource preferences. To tackle these challenges, we propose an adaptive and efficient approach called FireFace, consisting of prediction and decision modules. The prediction module extracts the internal features of all functions within the serverless application and uses this information to predict the execution time of the functions under specific configuration schemes. Based on the prediction module, the decision module analyzes the environment information and uses the Adaptive Particle Swarm Optimization algorithm and Genetic Algorithm Operator (APSO-GA) algorithm to select the most suitable configuration plan for each function, including CPU, memory, and edge platforms. In this way, it is possible to effectively minimize the financial overhead while fulfilling the Service Level Objectives (SLOs). Extensive experimental results show that our prediction model obtains optimal results under all three metrics, and the prediction error rate for real-world serverless applications is in the range of 4.25∼9.51%. Our approach can find the optimal resource configuration scheme for each application, which saves 7.2∼44.8% on average compared to other classic algorithms. Moreover, FireFace exhibits rapid adaptability, efficiently adjusting resource allocation schemes in response to dynamic environments.

Successful Treatment of SAM Syndrome With Secukinumab Monotherapy: A Case Report of a 16-Month-Old Infant.

Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a rare congenital skin disease. We report on a 16-month-old infant presenting with severe disseminated dermatitis, characterized by erythema and lichenified plaques. The crucial result of de novo missense mutation in the DSP gene (c.1769T>C, p.F590S) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions and skin pruritus significantly improved after a 4-week treatment with secukinumab.

Rapid discrimination of urine specific gravity using spectroscopy and a modified combination method based on SPA and spectral index.

To achieve high-accuracy urine specific gravity discrimination and guide the design of four-waveband multispectral sensors. A modified combination strategy was attempted to be proposed based on the successive projections algorithm (SPA) and the spectral index (SI) in the present study. First, the SPA was used to select four spectral variables in the full spectra. Secondly, the four spectral variables were mathematically transformed by SI to obtain SI values. Then, SPA gradually fusions the SI values and establishes models to identify USG. The results showed that the SPA can screen out the four characteristic wavelengths related to the measured sample attributes. SIs can be used to improve the performance of constructed prediction models. The best model only involves four spectral variables and 1 SI value, with high accuracy (91.62%), sensitivity (0.9051), and specificity (0.9667). The results reveal that m-SPA-SI can effectively distinguish USG and provide design guidance for 4-wavelength multispectral sensors. This article is protected by copyright. All rights reserved.

Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: Diabetic retinopathy (DR) is currently recognized as one of the most serious diabetic microangiopathies and a major cause of adult blindness. Commonly used clinical approaches include etiological control, microvascular improvement, and surgical intervention, but they are ineffective and have many side effects. Oral Chinese medicine (OCM) has been used for thousands of years to treat DR and is still widely used today, but it is unclear which OCM is more effective for DR. AIM: To estimate relative effectiveness and safety profiles for different classes of OCMs for DR, and provide rankings of the available OCMs. METHODS: The search time frame was from the creation of the database to January 2023. RevMan 5.3 and Stata 14.0 software were used to perform the systematic review and Network meta-analyses (NMA). RESULTS: A total of 107 studies and 9710 patients were included, including 4767 cases in the test group and 4973 cases in the control group. Based on previous studies and clinical reports, and combined with the recommendations of Chinese guidelines for the prevention and treatment of DR, 9 OCMs were finally included in this study, namely Compound Xueshuantong Capsules, Qiming Granules, Compound Danshen Dripping Pills, Hexue Mingmu Tablets (HXMM), Qiju Dihuang Pills (QJDH), Shuangdan Mingmu Capsules (SDMM), Danggui Buxue Decoction (DGBX), Xuefu Zhuyu Decoction and Buyang Huanwu Decoction. When these nine OCMs were analyzed in combination with conventional western medicine treatment (CT) compared with CT alone, the NMA results showed that HXMM + CT has better intervention effect on the overall efficacy of DR patients, HXMM + CT has better effect on improving patients' visual acuity, SDMM + CT has better effect on inhibiting vascular endothelial growth factor, DGBX + CT has better effect on reducing fundus hemorrhage area, HXMM + CT has better effect on reducing fasting blood glucose, and QJDH + CT has better effect on reducing glycated hemoglobin. When there are not enough clinical indicators for reference, SDMM + CT or HXMM + CT treatments can be chosen because they are effective for more indicators and demonstrate multidimensional efficacy. CONCLUSION: This study provides evidence that combining OCMs with CT leads to better outcomes in all aspects of DR compared to using CT alone. Based on the findings, we highly recommend the use of SDMM or HXMM for the treatment of DR. These two OCMs have demonstrated outstanding efficacy across multiple indicators.

Emodin ameliorates matrix degradation and apoptosis in nucleus pulposus cells and attenuates intervertebral disc degeneration through LRP1 in vitro and in vivo.

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.

Anion-induced electronic localization and polarized cobalt clusters for highly efficient water splitting.

It is a promising pathway to use anions to regulate electronic structures, reasonably design and construct highly efficient catalysts for water splitting. Herein, a N-regulated Co cluster catalyst confined in carbon nanotubes, N-Co NCNTs, was constructed successfully. Nitrogen anions played a crucial role in optimizing the electronic structures of Co clusters and enhancing localization of electrons, resulting in polarized cobalt clusters. The N-induced electronic localization and the resulting polarized Co clusters are responsible for the improvement of catalytic activity. N-Co NCNTs exhibited ultra-low overpotentials of 178 mV and 92 mV for the OER and HER to achieve 10 mA cm-2 in an alkaline electrolyte, respectively. Its long-term catalytic durability is mainly attributed to the obstacle to the surface oxidation of Co clusters caused by N-regulation. N-Co NCNTs maintained a stable current density for 160 h at 10 mA cm-2. DFT computations confirmed the decisive role played by nitrogen anions in regulating the electronic structure. This work provides a pathway for understanding and designing highly efficient anion-regulated catalysts.

Comparing the Effect of Spinal and General Anesthesia for Hip Fracture Surgery in Older Patients: A Meta-analysis of Randomized Clinical Trials.

OBJECTIVE: Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta-analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery. METHODS: Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed. RESULTS: Nine articles of methodological quality were included in the meta-analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = -20.94 [-37.50, -4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = -34.38 [-89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p < 0.05). No publication bias was observed in any of the included studies. CONCLUSION: Compared to general anesthesia, spinal anesthesia was associated with a lower risk of intraoperative hypotension and lower doses of ephedrine in older patients undergoing hip fracture surgery.

The safe zone of distal fibula was determined based on the classification of lateral malleolus fossa.

BACKGROUND: Lateral malleolus fractures are very common, and the distal fibular geometry is complex. This study aimed to classify the lateral malleolus fossa (MF) into different types by characterizing the lateral MF imaging morphology and exploring the relationship between the lateral MF and internal fixation position after distal fibula fractures. METHODS: Anteroposterior CT reconstruction was performed on 248 subjects. After reconstruction, the deepest point of the lateral MF was located, and then, the cross-sectional shape of the lateral MF was observed and classified. RESULTS: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C (43.1%), type V (32.2%), and type Flat (24.7%). Type V (3.98 ± 0.82) was significantly longer than type C(2.83 ± 0.54) and type Flat (1.84 ± 0.42) in cd. Similarly, in ∠α, Type Flat(136.31 ± 9.63) was the largest, followed by type C (116.51 ± 8.79), and type V (89.31 ± 9.07) was the smallest. Other measurements were not found any significant differences between the above. CONCLUSION: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C, type V and type Flat. Type V is most likely to be invaded when fixing the distal fibula. Screws less than 9 mm should be selected when fixing, and screws no more than 10 mm should be selected when there are type C and type Flat of MF.

Studying allosteric regulation of chemokines and antagonists using a nanoscale hCCR3 receptor sensor.

CC chemokine receptor-3 (hCCR3), a G protein-coupled receptor (GPCR) expressed predominantly on eosinophils, is an important drug target. However, it was unclear how chemokine ligands, activators and antagonists recognize hCCR3, and quantitative measurements of hCCR3 inhibition or activation were rare. This study constructed a nanogold receptor sensor using hCCR3 as the molecular recognition element and horseradish peroxidase as the signal amplifier. We quantified the kinetic antagonism between chemokines and hCCR3 before and after adding hCCR3 antagonists. A molecular docking study was carried out to investigate how hCCR3 and its ligands work. The study results indicate chemokines interact with hCCR3 at low concentrations, and reversible hCCR3 inhibitors solely inhibit hCCR3, not CCLs. Moreover, a quantitative evaluation of hCCR3 chemokine activators and their antagonists was carried out using a directed weighted network. This offers a novel approach to quantitatively evaluate chemokine-receptor activation and antagonism together. This research could potentially offer new insights into the mechanisms of action of chemokines and drug screening.

singleCellBase: a high-quality manually curated database of cell markers for single cell annotation across multiple species.

Annotating cells in the analysis of single-cell RNA-seq (scRNA-seq) data is one of the most challenging tasks that researchers are actively addressing. Manual cell annotation is generally considered the gold standard method, although it is labor intensive and independent of prior knowledge. At present, the relationship between high-quality, known marker genes and cell types is very limited, especially for a variety of species other than humans and mice. The singleCellBase is a manually curated resource of high-quality cell types and gene markers associations across multiple species. In details, it offers 9,158 entries spanning a total of 1,221 cell types and linking with 8,740 genes (cell markers), covering 464 diseases/status, and 165 types of tissues across 31 species. The singleCellBase provides a user-friendly interface to the scientific community to browse, search, download and submit records of marker genes and cell types. The resource providing ineluctable prior knowledge required by manual cell annotation, which is valuable to interpret scRNA-seq data and elucidate what cell type or cell state that a cell population represents.

SO42- ions as a nucleophilic reagent: straightforward electrochemical access to organosulfates.

An electrooxidation direct difunctionalization of alkynes with sulfonyl hydrazides has been developed for the construction of sulfonyl alkenyl sulfates in the absence of metal catalysts and a stoichiometric amount of oxidants. Notably, it is the first example to verify that SO42- ions can act as a nucleophilic reagent for the preparation of organosulfates.

Enhancing drug-drug interaction prediction by integrating physiologically-based pharmacokinetic model with fraction metabolized by CYP3A4.

BACKGROUND: Enhancing the precision of drug-drug interaction (DDI) prediction is essential for improving drug safety and efficacy. The aim is to identify the most effective the fraction metabolized by CY3A4 (fm) for improving DDI prediction using physiologically based pharmacokinetic (PBPK) models. RESEARCH DESIGN AND METHODS: The fm values were determined for 33 approved drugs using a human liver microsomes for in vitro measurements and the ADMET Predictor software for in silico predictions. Subsequently, these fm values were integrated into PBPK models using the GastroPlus platform. The PBPK models, combined with a ketoconazole model, were utilized to predict AUCR (AUCcombo with ketoconazole/AUCdosing alone), and the accuracy of these predictions was evaluated by comparison with observed AUCR. RESULTS: The integration of in vitro fm method demonstrates superior performance compared to the in silico fm method and fm of 100% method. Under the Guest-limits criteria, the integration of in vitro fm achieves an accuracy of 76%, while the in silico fm and fm of 100% methods achieve accuracies of 67% and 58%, respectively. CONCLUSIONS: Our study highlights the importance of in vitro fm data to improve the accuracy of predicting DDIs and demonstrates the promising potential of in silico fm in predicting DDIs.

The effects of Spinosad on zebrafish larvae and THP-1 cells: Associated with immune cell damage and NF-kappa B signaling pathway activation.

Spinosad is a highly effective macrolide insecticide with a wide range of applications. However, few studies have been reported on the effects of Spinosad on immune cells. The immune system is an important line of defense in the human body and plays an important role in maintaining the normal functioning of the organism. Meanwhile, macrophages, neutrophils and Thymic T cells are an important component of the immune system. We studied the immunotoxicity of Spinosad using zebrafish and THP-1 cells. In vivo, Spinosad (0-20 µM) did not cause developmental toxicity in zebrafish, but induced damage to immune cells. In vitro, Spinosad (0-20 µM) inhibited THP-1 cells viability and induced mitochondrial damage and oxidative stress production. In further studies, it impaired phagocytosis of THP-1 cells and interfered with lipid metabolism. In addition, we found that Spinosad can promote the formation of the inflammatory body NLRP3 (NLR family, pyrin domain-containing 3) and activate the NF-kappa B (NF-κB) signaling pathway. These results suggest that Spinosad has a potential risk for inducing immunotoxicity. This study has drawn attention to Spinosad-induced immunotoxicity.

Isolation of tumor stem-like cells from primary laryngeal squamous cell carcinoma cells (FD-LS-6).

The development of efficient treatments for laryngeal squamous cell carcinoma (LSCC) is hindered by the lack of applicable tumor cell lines and animal models of the disease, especially those related to cancer stem-like cells (CSCs). CSCs play critical roles in tumor propagation and pathogenesis whereas no CSCs lines have been developed to date. In this study, we establish an LSCC cell line (FD-LS-6) from primary LSCC tumor tissue (not experienced single-cell cloning) and adapted a culturing condition for the expansion of potential stem cells (EPSCs) to isolate CSCs from FD-LS-6. We successfully derived novel CSCs and named them as LSCC sphere-forming cells (LSCSCs) which were subsequently characterized for their CSC properties. We showed that LSCSCs shared many properties of CSCs, including CSC marker, robust self-renewal capacity, tumorigenesis ability, potential to generate other cell types such as adipocytes and osteoblasts, and resistance to chemotherapy. Compared to parental cells, LSCSCs were significantly more potent in forming tumors in vivo in mice and more resistant to chemotherapy. LSCSCs have higher expressions of epithelial-mesenchymal transition proteins and chemotherapy resistance factors, and exhibit an activated COX2/PEG2 signaling pathway. Altogether, our work establishes the first CSCs of LSCC (FD-LS-6) and provides a tool to study tumorigenesis and metastasis of LSCC and help the development of anticancer therapies.

Functionalized 3D-Printed PLA Biomimetic Scaffold for Repairing Critical-Size Bone Defects.

The treatment of critical-size bone defects remains a complicated clinical challenge. Recently, bone tissue engineering has emerged as a potential therapeutic approach for defect repair. This study examined the biocompatibility and repair efficacy of hydroxyapatite-mineralized bionic polylactic acid (PLA) scaffolds, which were prepared through a combination of 3D printing technology, plasma modification, collagen coating, and hydroxyapatite mineralization coating techniques. Physicochemical analysis, mechanical testing, and in vitro and animal experiments were conducted to elucidate the impact of structural design and microenvironment on osteogenesis. Results indicated that the PLA scaffold exhibited a porosity of 84.1% and a pore size of 350 µm, and its macrostructure was maintained following functionalization modification. The functionalized scaffold demonstrated favorable hydrophilicity and biocompatibility and promoted cell adhesion, proliferation, and the expression of osteogenic genes such as ALP, OPN, Col-1, OCN, and RUNX2. Moreover, the scaffold was able to effectively repair critical-size bone defects in the rabbit radius, suggesting a novel strategy for the treatment of critical-size bone defects.

An abnormal LPA/LPAR1-NHE1 axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.

In brief: Autophagy is important for trophoblast cells at the maternal-fetal interface during early pregnancy. This study suggests that trophoblast cells can promote the autophagy under a regulation of the LPA/LPAR 1-NHE1 axis. Abstract: The autophagy of trophoblasts is necessary for developing and maintaining a healthy pregnancy. Autophagy dysfunction in trophoblast cells is linked to recurrent spontaneous abortion (RSA). However, the mechanism underlying trophoblast autophagy is unknown. In this study, we investigated the expression of autophagy-related genes in both normal and RSA villi. We also examined the production of LPA and LPAR1 in trophoblast cells during early pregnancy. We found that the activation of the LPA-LPAR1 axis triggered the autophagy of trophoblast cells and increased the expression of NHE1. Inhibition of NHE1 suppressed the autophagy in trophoblast cells and we confirmed that NHE1 regulates LPA production in trophoblast cells. Additionally, we found decreased expression of autophagy-related genes and LPAR1 in villi from RSA patients. These observations indicate that the LPA/LPAR1-NHE1 axis regulates the autophagy of trophoblast cells during pregnancy. Insufficient autophagy and poor expression of LPAR1 in trophoblast cells may result in the dysfunction of the trophoblasts and an increased risk of spontaneous abortion. Overall, our research elucidated that a positive LPA/LPAR1-NHE1 axis can promote the autophagy of trophoblast cells and the abnormal axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.