Single-tube, single-strip lateral flow assays utilizing loop-mediated isothermal amplification for simultaneous hepatitis B and C viral detection.

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop-mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point-of-care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources.

Cu-Catalyzed Direct Enantioselective Vinylogous Mannich Reaction between ß,γ-Unsaturated Pyrazoleamides and Ketimines.

A catalytic asymmetric vinylogous Mannich-type reaction between ß,γ-unsaturated amides and ketimines has been developed in excellent regio-, diastereo-, and enantioselectivities. The methodology provides an efficient approach to construct chiral homoallylic amines with a 3-amino-2-oxindole scaffold. Moreover, the transformations of the chiral products, including the removal of the pyrazole group or Boc group, the reduction of the C-C double bond, and Suzuki coupling, have been investigated.

A deep learning framework for identifying and segmenting three vessels in fetal heart ultrasound images.

BACKGROUND: Congenital heart disease (CHD) is one of the most common birth defects in the world. It is the leading cause of infant mortality, necessitating an early diagnosis for timely intervention. Prenatal screening using ultrasound is the primary method for CHD detection. However, its effectiveness is heavily reliant on the expertise of physicians, leading to subjective interpretations and potential underdiagnosis. Therefore, a method for automatic analysis of fetal cardiac ultrasound images is highly desired to assist an objective and effective CHD diagnosis. METHOD: In this study, we propose a deep learning-based framework for the identification and segmentation of the three vessels-the pulmonary artery, aorta, and superior vena cava-in the ultrasound three vessel view (3VV) of the fetal heart. In the first stage of the framework, the object detection model Yolov5 is employed to identify the three vessels and localize the Region of Interest (ROI) within the original full-sized ultrasound images. Subsequently, a modified Deeplabv3 equipped with our novel AMFF (Attentional Multi-scale Feature Fusion) module is applied in the second stage to segment the three vessels within the cropped ROI images. RESULTS: We evaluated our method with a dataset consisting of 511 fetal heart 3VV images. Compared to existing models, our framework exhibits superior performance in the segmentation of all the three vessels, demonstrating the Dice coefficients of 85.55%, 89.12%, and 77.54% for PA, Ao and SVC respectively. CONCLUSIONS: Our experimental results show that our proposed framework can automatically and accurately detect and segment the three vessels in fetal heart 3VV images. This method has the potential to assist sonographers in enhancing the precision of vessel assessment during fetal heart examinations.

Magnetic resonance imaging features for differentiating tuberculous from pyogenic spondylitis: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing the MRI features of tuberculous and pyogenic spondylitis, using histopathological results and/or blood culture as the standard reference. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for English-language studies on the MRI features of tuberculous and pyogenic spondylitis published between January 2010 and February 2023. Risk for bias and concerns regarding applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled MRI features' proportions were calculated using a bivariate random-effects model. RESULTS: Thirty-two studies met the inclusion criteria: 21 for tuberculous spondylitis, three for pyogenic spondylitis, and eight for both. Of the nine informative MRI features comparing tuberculous spondylitis to pyogenic spondylitis, involvement of ≥ 2 vertebral bodies (92% vs. 88%, P = .004), epidural extension (77% vs. 25%, P < .001), paravertebral collection (91% vs. 84%, P < .001), subligamentous spread (93% vs. 24%, P < .001), thin and regular abscess wall (94% vs. 18%, P < .001), vertebral collapse (68% vs. 24%, P < .001), and kyphosis (39% vs. 3%, P < .01) were more suggestive of tuberculous spondylitis, while disc signal change (82% vs. 95%, P < .001) and disc height loss (22% vs. 59%, P < .001) were more suggestive of pyogenic spondylitis. CONCLUSION: Involvement of ≥ 2 vertebral vertebral bodies, soft tissue attribution, thin and regular abscess wall, vertebral collapse, and kyphosis were MRI features more common in tuberculous spondylitis, while disc signal change and height loss were more common in pyogenic spondylitis.

Low polarization-sensitive ultra-broadband anti-reflection coatings with improved reliability.

Broader spectra, lower reflectivity and higher reliability are the performance requirements for broadband antireflective (BBAR) films. In this work, a BBAR film structure was proposed, which maintains extremely low reflectivity, ultra-wide spectra, low polarization sensitivity and practical reliability. The BBAR film consists of a dense multilayer interference stack on the bottom and a nano-grass-like alumina (NGLA) layer with a gradient low refractive index distribution on the top. The film was deposited by atomic layer deposition, while the NGLA layer was formed by means of a hot water bath on Al2O3 layer. The top NGLA layer has extremely high porosity and ultra-low refractive index, along with extremely fragile structure. To surmount the fragility of NGLA layer, a sub-nano layer of SiO2 was grown by atomic layer deposition to solidify its structure and also to adjust the refractive index with different thicknesses of SiO2. Finally, in the wide wavelength range of 400-1100 nm, the average transmittance of the double-sided coated fused quartz reaches 99.2%. The absorption, light scattering, reliability and polarization characteristics of BBAR films were investigated. An optimized BBAR film with low polarization-sensitivity and improved reliability was realized, which should be potentially promising for application in optical systems.

Optimization of optical and structural properties of Al2O3/TiO2 nano-laminates deposited by atomic layer deposition for optical coating.

Optimizing the atomic layer deposition (ALD) process of films is particularly important in preparing multilayer interference films. In this work, a series of Al2O3/TiO2 nano-laminates with a fixed growth cycle ratio of 1:10 were deposited on Si and fused quartz substrates at 300 °C by ALD. The optical properties, crystallization behavior, surface appearance and microstructures of those laminated layers were systematically investigated by spectroscopic ellipsometry, spectrophotometry, X-ray diffraction, atomic force microscope and transmission electron microscopy. By inserting Al2O3 interlayers into TiO2 layers, the crystallization of the TiO2 is reduced and the surface roughness becomes smaller. The TEM images show that excessively dense distribution of Al2O3 intercalation leads to the appearance of TiO2 nodules, which in turn leads to increased roughness. The Al2O3/TiO2 nano-laminate with a cycle ratio 40:400 has relatively small surface roughness. Additionally, oxygen-deficient defects exist at the interface of Al2O3 and TiO2, leading to evident absorption. Using O3 as an oxidant instead of H2O for depositing Al2O3 interlayers was verified to be effective in reducing absorption during broadband antireflective coating experiments.

Determination of bone marrow cell morphology in rat.

The skeletal system of the body is responsible for important functions in the human body. In addition to causing movement, this system also plays a role in the production of blood cells and fat storage. Bone marrow is a spongy or viscous tissue that fills the inside of the body's bones. The basic structure of bone marrow is of two types. Red bone marrow and yellow bone marrow. Red bone marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow bone marrow is made mostly of fat and contains stem cells that can turn into cartilage, fat, or bone cells. Human bone marrow mesenchymal stem cells (HBMSCs) are widely used cell sources for clinical bone regeneration. Achieving a therapeutic effect depends on the osteogenic differentiation potential of the stem cells. The purpose of judging the morphology of bone marrow cells is to diagnose leukemia or bone marrow disorders, determine the cause of severe anemia or thrombocytopenia and low platelet count, identify abnormal chromosomes to prevent hereditary diseases, and plan their treatment. In this study, we examined the morphological characteristics of bone marrow cells, mesenchyme cells, and osteoblasts in a laboratory environment. The results of the morphological investigations showed changes such as the change of the position of the nucleus and the rounding of the cytoplasm in the differentiated cells compared to the mesenchyme cells. Therefore, to identify and diagnose as many of these cells as possible, molecular genetic techniques such as network algorithms and fluorescence staining can be used for hematological and cytomorphological investigations.

How does multiple substrate binding lead to substrate inhibition of CYP2D6 metabolizing dextromethorphan? A theoretical study.

CYP2D6 is one of the most important metalloenzymes involved in the biodegradation of many drug molecules in the human body. It has been found that multiple substrate binding can lead to substrate inhibition of CYP2D6 metabolizing dextromethorphan (DM), but the corresponding theoretical mechanism is rarely reported. Therefore, we chose DM as the probe and performed molecular dynamics simulations and quantum mechanical calculations on CYP2D6-DM systems to investigate the mechanism of how the multiple substrate binding leads to the substrate inhibition of CYP2D6 metabolizing substrates. According to our results, three gate residues (Arg221, Val374, and Phe483) for the catalytic pocket are determined. We also found that the multiple substrate binding can lead to substrate inhibition by reducing the stability of CYP2D6 binding DM and increasing the reactive activation energy of the rate-determining step. Our findings would help to understand the substrate inhibition of CYP2D6 metabolizing the DM and enrich the knowledge of the drug-drug interactions for the cytochrome P450 superfamily.

Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.

A Comparison Between Selective Lobar Bronchial Blockade and Main Bronchial Blockade in Pediatric Thoracoscopic Surgery: A Retrospective Cohort Study.

OBJECTIVE: The primary objective of this study was to assess the effect of selective lobar blockade on the risk of hypoxemia during one-lung ventilation in pediatric patients undergoing thoracoscopic surgery. DESIGN: This was a retrospective matched case-control cohort study. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: A total of 60 pediatric patients who underwent thoracoscopic surgery in the authors' hospital from March 2020 to March 2021 were analyzed. INTERVENTIONS: The authors examined their electronic medical records and found 30 patients in whom selective lobar blockade was used. These patients then were matched to 30 other patients in whom routine main bronchial blockade was performed in the authors' center based on age, weight, sex, side of surgery, and type of surgery. MEASUREMENTS AND MAIN RESULTS: The inclusion criteria were four-fold: (1) pediatric patients with scheduled thoracoscopic resection of the middle and lower lobe lesions; (2) no obvious anesthesia or surgical contraindications; (3) American Society of Anesthesiologists class I to II; and (4) age younger than one year old. The exclusion criteria were as follows: (1) pediatric patients whose trachea was intubated with a size less than 3.0 mm; (2) a difficult airway; (3) changes in ventilation patterns during surgery; and (4) severe pneumonia and respiratory and circulatory system dysfunction. The following patient data were collected: (1) general clinical information; (2) mean arterial blood pressure, heart rate, central venous pressure, airway peak pressure (Ppeak), oxygenation index (PaO2/FIO2 ratio), and alveolar-arterial oxygen differential pressure (AaDO2) at different time points; that is, before one-lung ventilation (OLV) (T1), ten minutes after OLV (T2), and ten minutes after the end of OLV (T3); (3) degree of lung collapse ten minutes after OLV; (4) operative duration; and (5) the prevalence of hypoxemia, the number of adjustments required for intraoperative displacement of the bronchial blocker, and pulmonary atelectasis. A total of 135 patients were selected, and 60 pediatric patients (30 in group S and 30 in group R) were included in this study. There were no significant differences in age, sex, weight, general preoperative data, degree of lung collapse, or operative duration (p > 0.05). The perioperative hemodynamics between the two groups were not statistically significant (p > 0.05). The oxygenation index, AaDO2, and Ppeak were not significantly different between the two groups at the T1 time point (p > 0.05). However, the oxygenation index was higher, and AaDO2 and Ppeak were lower in group S than in group R at the T2 and T3 time points (p < 0.05). The incidence of atelectasis, the prevalence of hypoxemia, and the number of adjustments required for intraoperative displacement of the bronchial blocker in group S were lower than those in group R (p < 0.05). CONCLUSION: Selective lobar bronchial blockade, using a bronchial blocker in pediatric thoracoscopic surgery, may represent an alternative to excluding the main bronchial blockade for patients undergoing middle and lower lobe procedures, which may improve intraoperative oxygenation and reduce postoperative atelectasis.

The Interventricular Septal Hematoma Following Surgical Correction of Ventricular Septal Defect in Infants: A Single-Center Experience.

OBJECTIVE: To review and analyze the cases of interventricular septal hematoma (IVSH) following surgical correction of the ventricular septal defect (VSD) in infants in our center. METHODS: Retrospective analysis was performed on five infants with IVSH after surgical correction of VSD in our center from January 2020 to January 2022. The general preoperative information and intraoperative and postoperative results were collected and analyzed. RESULTS: All five infants with VSD were repaired under cardiopulmonary bypass and occurred IVSH. The cardiac arrest occurred in one patient five hours after return to the intensive care unit (ICU). The patient's hemodynamics were difficult to maintain after cardiopulmonary resuscitation, and the patient died. Two other patients had arrhythmia and unstable hemodynamics during the perioperative period, the hematoma puncture was performed, and the patients' symptoms lessened. Perioperative and postoperative echocardiography showed that the hematoma gradually was shrunk, and the hemodynamics became stable. The hemodynamics were stable in the remaining two infants during the perioperative period. No specific medical intervention was required other than clinical observation in these two patients. Finally, the four infants successfully were discharged with good clinical results. CONCLUSION: IVSH is a rare complication of surgical repair of VSD. Prevention and early detection of IVSH during operation in infants with VSD are essential.

Precisely Tailoring Heterometallic Polyoxotitanium Clusters for the Efficient and Selective Photocatalytic Oxidation of Hydrocarbons.

Photocatalysis is a promising yet challenging approach for the selective oxidation of hydrocarbons to valuable oxygenated chemicals with O2 under mild conditions. In this work, we report an atomically precise material model to address this challenge. The key to our solution is the rational incorporation of Fe species into polyoxotitanium cluster to form a heterometallic Ti4 Fe1 cocrystal. This newly designed cocrystal cluster, which well governs the energy and charge transfer as evidenced by spectroscopic characterizations and theoretical calculations, enables the synergistic process involving C(sp3 )-H bond activation by photogenerated holes and further reactions by singlet oxygen (1 O2 ). Remarkably, the cocrystal Ti4 Fe1 cluster achieves efficient and selective oxidation of hydrocarbons (C5 to C16 ) into aldehydes and ketones with a conversion rate up to 12 860 µmol g-1 h-1 , 5 times higher than that of Fe-doped Ti3 Fe1 cluster. This work provides insights into photocatalyst design at atomic level enabling synergistic catalysis.

Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart.

The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared with controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger-Hamilton stage 19-20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion-size map along the inflow heart tube, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated.NEW & NOTEWORTHY To the best of our knowledge, this is the first study investigating the impact of ethanol exposure on the early cardiac conduction system. Our results showed that ethanol-exposed embryos exhibited abnormally fast atrioventricular conduction. In addition, our findings, in CV measurements and endocardial cushion thickness, reveal regional differences in the AVJ myocardium even at this early stage in heart development, suggesting that the differentiation and maturation at this site are complex and warrant further studies.

Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy.

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.

Double-sided optical coating of strongly curved glass by atomic layer deposition.

A reaction chamber of atomic layer deposition (ALD) was developed for simultaneous coating on the inner and outer surfaces of a large-size and strongly curved glass bowl. The inner surface ALD process was in a showerhead reaction mode and the outer surface ALD process was in a cross-flow reaction mode. Blue reflection (BR) film of 400 nm wavelength and broadband antireflection (BBAR) film of 400-700 nm wavelength were coated on different glass bowls by ALD. The spectral uniformity of both coated bowls was studied. The measured spectra at multiple positions of the glass bowl with the BBAR coating show better spectral uniformity along the circumference than the depth. The spectral deviation is mainly caused by the non-uniformity of the film on the outer surface (<±3%), and the film on the inner surface has good uniformity along both the circumference and the depth (<±0.7%). The growth rate of the outer film was reduced by 10% on average compared to that of the inner film due to the different gas flow mode.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Remifentanil-based fast-track cardiac anesthesia combined with the postoperative serratus anterior plane block for transthoracic device closure of atrial septal defect in pediatric patients.

BACKGROUND: To evaluate the safety and effectiveness of remifentanil-based fast-track cardiac anesthesia (FTCA) combined with the postoperative serratus anterior plane block (SAPB) for transthoracic device closure of atrial septal defect (ASD) in pediatric patients. METHODS: A total of 70 children who underwent transthoracic device closure of ASDs from January 2018 to June 2020 were divided into two groups according to different anesthesia strategies administered, namely group F (fast-track anesthesia, n = 38) and group R (routine anesthesia, n = 32), and relevant clinical data were collected and analyzed. RESULTS: There was no statistically significant difference between the two groups in general preoperative data, intraoperative hemodynamics, and FLACC score 1 h after extubation (p > .05). FLACC score of Group F was significantly lower than that of group R at 4, 8, 12, and 24 h after extubation (p < .05). The number of postoperative PCA press and the dose of PCA infusion in group F were lower than those in group R (p < .05). The mechanical ventilation duration, the length of intensive care unit stay in group F were statistically significantly lower than those in group R (p < .05). CONCLUSION: Remifentanil-based FTCA combined with the postoperative SAPB for transthoracic device closure of ASD in pediatric patients could effectively reduce postoperative pain of the children.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Analysis of Remifentanil-Based Fast-Track Anesthesia Combined with Dexmedetomidine for Transthoracic Device Closure of Atrial Septal Defect in Pediatric Patients.

BACKGROUND: To investigate the safety and efficacy of remifentanil combined with dexmedetomidine in fast-track cardiac anesthesia (FTCA) for transthoracic device closure of atrial septal defect (ASD) in pediatric patients. METHODS: A retrospective analysis was performed on 61 cases of children undergoing ASD closure through a small thoracic incision from January 2018 to January 2020. According to whether FTCA was administered, they were divided into group F (fast-track anesthesia, n = 31) and group R (routine anesthesia, n = 30). RESULTS: There was no significant difference in general preoperative data, perioperative hemodynamics, or postoperative pain scores between the 2 groups (P > .05). The postoperative sedation score of group F was higher than that of group R 1 and 4 hours after extubation. Meanwhile, duration of mechanical ventilation and length of postoperative intensive care unit (ICU) stay of group F were significantly shorter than those of group R (P < .05). No serious anesthesia-related complications occurred. CONCLUSION: Remifentanil combined with dexmedetomidine in FTCA for transthoracic device closure of ASD in pediatric patients is safe and effective, is worthy of clinical promotion, and can benefit more children.

Self-Delivery Nanomedicine for O2-Economized Photodynamic Tumor Therapy.

Tumor hypoxia is the Achilles heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the tumor hypoxia. In this work, an oxidative phosphorylation inhibitor of atovaquone (ATO) and a photosensitizer of chlorine e6 (Ce6)-based self-delivery nanomedicine (designated as ACSN) were prepared via π-π stacking and hydrophobic interaction for O2-economized PDT against hypoxic tumors. Specifically, carrier-free ACSN exhibited an extremely high drug loading rate and avoided the excipient-induced systemic toxicity. Moreover, ACSN not only dramatically improved the solubility and stability of ATO and Ce6 but also enhanced the cellular internalization and intratumoral permeability. Abundant investigations confirmed that ACSN effectively suppressed the oxygen consumption to reverse the tumor hypoxia by inhibiting mitochondrial respiration. Benefiting from the synergistic mechanism, an enhanced PDT effect of ACSN was observed on the inhibition of tumor growth. This self-delivery system for oxygen-economized PDT might be a potential appealing clinical strategy for tumor eradication.