Urinary proteomics for noninvasive monitoring of biomarkers of chronic mountain sickness in a young adult population using data-independent acquisition (DIA)-based mass spectrometry.

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SIGNIFICANCE: Our team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

Endothelial nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome regulation in atherosclerosis.

AIMS: The activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant up-regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli up-regulated endothelial PFKFB3 expression via sterol regulatory element-binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent up-regulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSION: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

Identification of Immune Infiltration and Iron Metabolism-Related Subgroups in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a broad spectrum of symptoms and prognoses. Effective therapy requires understanding this variability. ASD children's cognitive and immunological development may depend on iron homoeostasis. This study employs a machine learning model that focuses on iron metabolism hub genes to identify ASD subgroups and describe immune infiltration patterns. A total of 97 control and 148 ASD samples were obtained from the GEO database. Differentially expressed genes (DEGs) and an iron metabolism gene collection achieved the intersection of 25 genes. Unsupervised cluster analysis determined molecular subgroups in individuals with ASD based on 25 genes related to iron metabolism. We assessed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, gene set variation analysis (GSVA), and immune infiltration analysis to compare iron metabolism subtype effects. We employed machine learning to identify subtype-predicting hub genes and utilized both training and validation sets to assess gene subtype prediction accuracy. ASD can be classified into two iron-metabolizing molecular clusters. Metabolic enrichment pathways differed between clusters. Immune infiltration showed that clusters differed immunologically. Cluster 2 had better immunological scores and more immune cells, indicating a stronger immune response. Machine learning screening identified SELENBP1 and CAND1 as important genes in ASD's iron metabolism signaling pathway. These genes express in the brain and have AUC values over 0.8, implying significant predictive power. The present study introduces iron metabolism signaling pathway indicators to predict ASD subtypes. ASD is linked to immune cell infiltration and iron metabolism disorders.

Quantum octets in high mobility pentagonal two-dimensional PdSe2.

Two-dimensional (2D) materials have drawn immense interests in scientific and technological communities, owing to their extraordinary properties and their tunability by gating, proximity, strain and external fields. For electronic applications, an ideal 2D material would have high mobility, air stability, sizable band gap, and be compatible with large scale synthesis. Here we demonstrate air stable field effect transistors using atomically thin few-layer PdSe2 sheets that are sandwiched between hexagonal BN (hBN), with large saturation current > 350 µA/µm, and high field effect mobilities of ~ 700 and 10,000 cm2/Vs at 300 K and 2 K, respectively. At low temperatures, magnetotransport studies reveal unique octets in quantum oscillations that persist at all densities, arising from 2-fold spin and 4-fold valley degeneracies, which can be broken by in-plane and out-of-plane magnetic fields toward quantum Hall spin and orbital ferromagnetism.

Proteomic and metabolomic analyses uncover integrative mechanisms in Sesuvium portulacastrum tolerance to salt stress.

Introduction: Salt stress is a major constraint affecting crop productivity worldwide. Investigation of halophytes could provide valuable information for improving economically important crops to tolerate salt stress and for more effectively using halophytes to remediate saline environments. Sesuvium portulacastrum L. is a halophyte species widely distributed in tropical and subtropical coastal regions and can absorb a large amount of sodium (Na). This study was to analyze S. portulacastrum responses to salt stress at morphological, physiological, proteomic, and metabolomic levels and pursue a better understanding of mechanisms behind its salt tolerance. Methods: The initial experiment evaluated morphological responses of S. portulacastrum to different concentrations of NaCl in a hydroponic system, and subsequent experiments compared physiological, proteomic, and metabolomic changes in S. portulacastrum after being exposed to 0.4 M NaCl for 24 h as immediate salt stress (IS) to 14 days as adaptive salt stress (AS). Through these analyses, a working model to illustrate the integrative responses of S. portulacastrum to salt stress was proposed. Results: Plants grown in 0.4 M NaCl were morphologically comparable to those grown in the control treatment. Physiological changes varied in control, IS, and AS plants based on the measured parameters. Proteomic analysis identified a total of 47 and 248 differentially expressed proteins (DEPs) in leaves and roots, respectively. KEGG analysis showed that DEPs, especially those occurring in roots, were largely related to metabolic pathways. Root metabolomic analysis showed that 292 differentially expressed metabolites (DEMs) occurred in IS plants and 371 in AS plants. Among them, 20.63% of upregulated DEMs were related to phenolic acid metabolism. Discussion: Based on the integrative analysis of proteomics and metabolomics, signal transduction and phenolic acid metabolism appeared to be crucial for S. portulacastrum to tolerate salt stress. Specifically, Ca2+, ABA, and JA signalings coordinately regulated salt tolerance in S. portulacastrum. The stress initially activated phenylpropanoid biosynthesis pathway through Ca2+ signal transduction and increased the content of metabolites, such as coniferin. Meanwhile, the stress inhibited MAPK signaling pathway through ABA and JA signal transduction, which promoted Na sequestration into the vacuole to maintain ROS homeostasis and enhanced S. portulacastrum tolerance to salt stress.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Glycolysis Promotes Angiotensin II-Induced Aortic Remodeling Through Regulating Endothelial-to-Mesenchymal Transition via the Corepressor C-Terminal Binding Protein 1.

BACKGROUND: Endothelial dysfunction plays a crucial role in aortic remodeling. Aerobic glycolysis and endothelial-to-mesenchymal transition (EndoMT) have, respectively, been suggested to contribute to endothelial dysfunction in many cardiovascular diseases. Here, we tested the hypothesis that glycolytic reprogramming is critical for EndoMT induction in aortic remodeling through an epigenetic mechanism mediated by a transcriptional corepressor CtBP1 (C-terminal binding protein 1), a sensor of glycolysis-derived NADH. METHODS: EndoMT program, aortic remodeling, and endothelial expression of the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) were evaluated in Ang (angiotensin) II-infused mice. Mice with endothelial-specific Pfkfb3 deficiency or CtBP1 inactivation, immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assay were employed to elucidate whether and how PFKFB3/CtBP1 epigenetically controls EndoMT. RESULTS: The EndoMT program and increased endothelial PFKFB3 expression were induced in remodeled thoracic aortas. In TGF-ß (transforming growth factor-ß)-treated human endothelial cells, activated SMAD2/3 (SMAD Family Member 2/3) transcriptionally upregulated PFKFB3 expression. In turn, the TGF-ß/SMAD signaling and EndoMT were compromised by silencing or inhibition of PFKFB3. Mechanistic studies revealed that PFKFB3-mediated glycolysis increased NADH content and activated the NADH-sensitive CtBP1. Through interaction with the transcription repressor E2F4 (E2F Transcription Factor 4), CtBP1 enhanced E2F4-mediated transcriptional repression of SMURF2 (SMAD ubiquitin regulatory factor 2), a negative regulator of TGF-ß/SMAD2 signaling. Additionally, EC-specific Pfkfb3 deficiency or CtBP1 inactivation in mice led to attenuated Ang II-induced aortic remodeling. CONCLUSIONS: Our results demonstrate a glycolysis-mediated positive feedback loop of the TGF-ß signaling to induce EndoMT and indicate that therapeutically targeting endothelial PFKFB3 or CtBP1 activity could provide a basis for treating EndoMT-linked aortic remodeling.

Ubiquitination in the regulation of autophagy.

Autophagy, an efficient and effective approach to clear rapidly damaged organelles, macromolecules, and other harmful cellular components, enables the recycling of nutrient materials and supply of nutrients to maintain cellular homeostasis. Ubiquitination plays an important regulatory role in autophagy. This paper summarizes the most recent progress in ubiquitin modification in various stages of autophagy, including initiation, elongation, and termination. Moreover, this paper shows that ubiquitination is an important way through which selective autophagy achieves substrate specificity. Furthermore, we note the distinction between monoubiquitination and polyubiquitination in the regulation of autophagy. Compared with monoubiquitination, polyubiquitination is a more common strategy to regulate the activity of the autophagy molecular machinery. In addition, the role of ubiquitination in the closure and fusion of autophagosomes warrants further study. This article not only clarifies the regulatory mechanism of autophagy but also contributes to a deeper understanding of the importance of ubiquitination modification.

Facile Synthesis of MXene-Ti3C2/Co Nanosheet Hydrogel Sensor with the Assistance of a Smartphone for On-Site Monitoring of Glucose in Beverages.

A one-step cobaltous chloride (CoCl2) molten salt method was employed to prepare multilayer MXene-Ti3C2/Co materials with further ultrasonic treatment to acquire single-layer MXene-Ti3C2/Co nanosheets (NSs). MXene-Ti3C2/Co NSs were characterized, and their enzyme-like activities were investigated. Under the catalysis of MXene-Ti3C2/Co NSs, 3,3',5,5'-tetramethylbenzidine (TMB) could be oxidized by H2O2, with the color changing from colorless to blue. The affinity of MXene-Ti3C2/Co NSs to H2O2 and TMB was better than that of nanozymes reported in previous studies. The MXene-Ti3C2/Co NSs were used for the colorimetric determination of H2O2/glucose, with limits of detection (LODs) of 0.033 mM and 1.7 µM, respectively. MXene-Ti3C2/Co NSs embedded in sodium alginate (SA) hydrogel were used to construct a sensor platform. The digital pictures combined with a smartphone-installed app (color recognizer) could be used to analyze RGB values for colorimetric detection of glucose in beverages. This point-of-care testing platform has the advantages of cost-effectiveness and good transferability, with the potential to realize quick, intelligent and on-site detection.

In vivo real-time assessment of developmental defects in enamel of anti-Act1 mice using optical coherence tomography.

The purpose of this study was to explore the feasibility of using optical coherence tomography (OCT) for real-time and quantitative monitoring of enamel development in gene-edited enamel defect mice. NF-κB activator 1, known as Act1, is associated with many inflammatory diseases. The antisense oligonucleotide of Act1 was inserted after the CD68 gene promoter, which would cover the start region of the Act1 gene and inhibit its transcription. Anti-Act1 mice, gene-edited mice, were successfully constructed and demonstrated amelogenesis imperfecta by scanning electron microscope (SEM) and energy dispersive X-ray (EDX) spectroscopy. Wild-type (WT) mice were used as the control group in this study. WT mice and anti-Act1 mice at 3 weeks old were examined by OCT every week and killed at eight weeks old. Their mandibular bones were dissected and examined by OCT, micro-computed tomography (micro-CT), and SEM. OCT images showed that the outer layer of enamel of anti-Act1 mice was obviously thinner than that of WT mice but no difference in total thickness. When assessing enamel thickness, there was a significant normal linear correlation between these methods. OCT could scan the imperfect developed enamel noninvasively and quickly, providing images of the enamel layers of mouse incisors.

Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. RESULTS: Meta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. CONCLUSIONS: This study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.

Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review.

RATIONALE: Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. PATIENT CONCERNS: A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. DIAGNOSES: TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. INTERVENTIONS: After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. OUTCOMES: After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. LESSONS: Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, ß2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.

Momentum-Resolved Exciton Coupling and Valley Polarization Dynamics in Monolayer WS_{2}.

Using time- and angle-resolved photoemission, we present momentum- and energy-resolved measurements of exciton coupling in monolayer WS_{2}. We observe strong intravalley coupling between the B_{1s} exciton and A_{n>1} states. Our measurements indicate that the dominant valley depolarization mechanism conserves the exciton binding energy and momentum. While this conservation is consistent with Coulomb exchange-driven valley depolarization, we do not observe a momentum or energy dependence to the depolarization rate as would be expected for the exchange-based mechanism.

Pneumocystis pneumonia in a patient with diabetes mellitus: A case report.

RATIONALE: Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review. PATIENT CONCERNS: A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization. DIAGNOSES: The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally. INTERVENTIONS: A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy. OUTCOMES: The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms. LESSONS: The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.

Glycolysis and de novo fatty acid synthesis cooperatively regulate pathological vascular smooth muscle cell phenotypic switching and neointimal hyperplasia.

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a dedifferentiated (proliferative) phenotype contributes to neointima formation, which has been demonstrated to possess a tumor-like nature. Dysregulated glucose and lipid metabolism is recognized as a hallmark of tumors but has not thoroughly been elucidated in neointima formation. Here, we investigated the cooperative role of glycolysis and fatty acid synthesis in vascular injury-induced VSMC dedifferentiation and neointima formation. We found that the expression of hypoxia-inducible factor-1α (HIF-1α) and its target 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), a critical glycolytic enzyme, were induced in the neointimal VSMCs of human stenotic carotid arteries and wire-injured mouse carotid arteries. HIF-1α overexpression led to elevated glycolysis and resulted in a decreased contractile phenotype while promoting VSMC proliferation and activation of the mechanistic target of rapamycin complex 1 (mTORC1). Conversely, silencing Pfkfb3 had the opposite effects. Mechanistic studies demonstrated that glycolysis generates acetyl coenzyme A to fuel de novo fatty acid synthesis and mTORC1 activation. Whole-transcriptome sequencing analysis confirmed the increased expression of PFKFB3 and fatty acid synthetase (FASN) in dedifferentiated VSMCs. More importantly, FASN upregulation was observed in neointimal VSMCs of human stenotic carotid arteries. Finally, interfering with PFKFB3 or FASN suppressed vascular injury-induced mTORC1 activation, VSMC dedifferentiation, and neointima formation. Together, this study demonstrated that PFKFB3-mediated glycolytic reprogramming and FASN-mediated lipid metabolic reprogramming are distinctive features of VSMC phenotypic switching and could be potential therapeutic targets for treating vascular diseases with neointima formation. © 2023 The Pathological Society of Great Britain and Ireland.

Perioperative Risk Factors for Post-operative Pneumonia after Type A Acute Aortic Dissection Surgery.

OBJECTIVE: Type A acute aortic dissection (TAAAD) is a dangerous and complicated condition with a high death rate before hospital treatment. Patients who are fortunate to receive prompt surgical treatment still face high in-hospital mortality. A series of post-operative complications further affects the prognosis. Post-operative pneumonia (POP) also leads to great morbidity and mortality. This study aimed to identify the prevalence as well as the risk factors for POP in TAAAD patients and offer references for clinical decisions to further improve the prognosis of patients who survived the surgical procedure. METHODS: The study enrolled 89 TAAAD patients who underwent surgical treatment in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China from December 2020 to July 2021 and analyzed the perioperative data and outcomes of these patients. Logistic regression analyses were used to identify the risk factors for POP. RESULTS: In the study, 31.5% of patients developed POP. Patients with POP had higher proportions of severe oxygenation damage, pneumothorax, reintubation, tracheotomy, renal replacement therapy, arrhythmia, gastrointestinal bleeding, and longer duration of mechanical ventilation, fever, ICU stay, and length of stay (all with P<0.05). The in-hospital mortality was 2.3%. Smoking, preoperative white blood cells, and intraoperative transfusion were the independent risk factors for POP in TAAAD. CONCLUSION: Patients who underwent TAAAD surgery suffered poorer outcomes when they developed POP. Furthermore, patients with risk factors should be treated with caution.

Gold nanomaterials for oral cancer diagnosis and therapy: Advances, challenges, and prospects.

Early diagnosis and treatment of oral cancer are vital for patient survival. Since the oral cavity accommodates the second largest and most diverse microbiome community after the gut, the diagnostic and therapeutic approaches with low invasiveness and minimal damage to surrounding tissues are keys to preventing clinical intervention-related infections. Gold nanoparticles (AuNPs) are widely used in the research of cancer diagnosis and therapy due to their excellent properties such as surface-enhanced Raman spectroscopy, surface plasma resonance, controlled synthesis, the plasticity of surface morphology, biological safety, and stability. AuNPs had been used in oral cancer detection reagents, tumor-targeted therapy, photothermal therapy, photodynamic therapy, and other combination therapies for oral cancer. AuNPs-based noninvasive diagnosis and precise treatments further reduce the clinical intervention-related infections. This review is focused on the recent advances in research and application of AuNPs for early screening, diagnostic typing, drug delivery, photothermal therapy, radiotherapy sensitivity treatment, and combination therapy of oral cancer. Distinctive reports from the literature are summarized to highlight the latest advances in the development and application of AuNPs in oral cancer diagnosis and therapy. Finally, this review points out the challenges and prospects of possible applications of AuNPs in oral cancer diagnosis and therapy.

Gene-dosage effect of Pfkfb3 on monocyte/macrophage biology in atherosclerosis.

BACKGROUND AND PURPOSE: Macrophage-rich atherosclerotic arteries are highly active in glycolysis. PFKFB3, a key glycolytic enzyme, has emerged as a potential therapeutic target in atherosclerosis. Small-molecule inhibitors of PFKFB3, such as 3PO and PFK158, have demonstrated efficacy in hampering atherogenesis in preclinical models. However, genetic studies elucidating the role of Pfkfb3 in atherogenesis need to be conducted to validate pharmacological findings and to unveil potential pharmacological side effects. EXPERIMENTAL APPROACH: Apoe-/- mice with global heterozygous or myeloid cell-specific Pfkfb3 deficiency were fed a Western diet (WD), after which atherosclerosis development was determined. Monocyte subsets in atherosclerotic mice and patients were examined by flow cytometry. Monocyte infiltration was assayed by a Ly6Chi monocyte-specific latex labelling procedure. In situ efferocytosis was assessed on mouse aortic root sections. Additionally, metabolic status, macrophage motility, efferocytosis, and involved mechanisms were analysed in peritoneal macrophages. KEY RESULTS: Global heterozygous or myeloid cell-specific Pfkfb3 deficiency reduced atherogenesis in Apoe-/- mice. Mechanistic studies showed that PFKFB3 controlled the proliferation and infiltration of proinflammatory monocytes. Moreover, PFKFB3 expression was associated with inflammatory monocyte expansion in patients with atherosclerotic coronary artery disease. Surprisingly, homozygous loss of Pfkfb3 impaired macrophage efferocytosis and exacerbated atherosclerosis in Apoe-/- mice. Mechanistically, PFKFB3-driven glycolysis was shown to be essential for actin polymerization, thus aiding the efferocytotic function of macrophages. CONCLUSION AND IMPLICATIONS: Collectively, these findings suggest the existence of a double-edged sword effect of myeloid PFKFB3 on the pathogenesis of atherosclerosis and highlight the need for caution in developing anti-atherosclerotic strategies that target PFKFB3.

Boron carbon oxynitride quantum dots-based ratio fluorescent nanoprobe assisted with smartphone for visualization detection of phosphate.

A ratio fluorescence nanoprobe was constructed by simple mixing BCNO QDs with 8-hydroxyquinoline-5-sulfonic acid (HQSA), which had an obvious fluorescence peak at 420 nm and a weak fluorescence peak at 500 nm, corresponding to the BCNO QDs and HQSA, respectively. This fluorescence probe takes stable fluorescence of BCNO QDs as an internal standard, based on HQSA chelating enhanced fluorescence and specificity of phosphate in the presence of Mg2+, which realizes a rapid and sensitive detection of phosphate with good linearity in the range 0.3-50 µM and 50-100 µM and a detection limit of 0.073 µM. The recovery is between 94.1 and 111% and the relative standard deviations (RSDs) below 10%. At the same time, we took color photos of the reaction solution under 310-nm UV lamp with smartphones for visual detection through RGB data image analysis, which make the detection easier and faster. The proposed method provides a new strategy for the intelligent online detection of other targets in complex environment samples.