Ang-1 and VEGF: central regulators of angiogenesis.

Angiopoietin-1 (Ang-1) and Vascular Endothelial Growth Factor (VEGF) are central regulators of angiogenesis and are often inactivated in various cardiovascular diseases. VEGF forms complexes with ETS transcription factor family and exerts its action by downregulating multiple genes. Among the target genes of the VEGF-ETS complex, there are a significant number encoding key angiogenic regulators. Phosphorylation of the VEGF-ETS complex releases transcriptional repression on these angiogenic regulators, thereby promoting their expression. Ang-1 interacts with TEK, and this phosphorylation release can be modulated by the Ang-1-TEK signaling pathway. The Ang-1-TEK pathway participates in the transcriptional activation of VEGF genes. In summary, these elements constitute the Ang-1-TEK-VEGF signaling pathway. Additionally, Ang-1 is activated under hypoxic and inflammatory conditions, leading to an upregulation in the expression of TEK. Elevated TEK levels result in the formation of the VEGF-ETS complex, which, in turn, downregulates the expression of numerous angiogenic genes. Hence, the Ang-1-dependent transcriptional repression is indirect. Reduced expression of many target genes can lead to aberrant angiogenesis. A significant overlap exists between the target genes regulated by Ang-1-TEK-VEGF and those under the control of the Ang-1-TEK-TSP-1 signaling pathway. Mechanistically, this can be explained by the replacement of the VEGF-ETS complex with the TSP-1 transcriptional repression complex at the ETS sites on target gene promoters. Furthermore, VEGF possesses non-classical functions unrelated to ETS and DNA binding. Its supportive role in TSP-1 formation may be exerted through the VEGF-CRL5-VHL-HIF-1α-VH032-TGF-ß-TSP-1 axis. This review assesses the regulatory mechanisms of the Ang-1-TEK-VEGF signaling pathway and explores its significant overlap with the Ang-1-TEK-TSP-1 signaling pathway.

Head to head comparison of 68Ga-FAPI PET/CT with 18F-FDG PET/CT in primary and metastatic lesions of gastric tumor: A systematic review and meta-analysis.

OBJECTIVE: Our study aims to head to head compare the application of gallium-68-fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT in primary and metastatic lesions of gastric tumor to determine the superior diagnostic tool. MATERIALS AND METHODS: A systematic search, up to March 31, 2023, across PubMed, Embase, and Cochrane Library databases utilized a data-specific Boolean logic strategy. Sensitivity (SEN) and specificity (SPE) evaluations of 68Ga-FAPI and 18F-FDG PET/CT in gastric cancer lesions were conducted. The quality of the studies was assessed using QUADAS-2, and publication bias was examined through Begg and Egger tests. RESULTS: Analysis involved 141 gastric tumor patients and 2753 metastatic lesions in five studies, with overall satisfactory study quality and no apparent publication bias. Patient-level data showed a combined SEN of 0.95 (95% CI: 0.90-0.98) for 68Ga-FAPI and 0.84 (95% CI: 0.77-0.89) for 18F-FDG. At the lesion level, combined SEN were 0.91 (95% CI: 0.84-0.96) for 68Ga-FAPI and 0.72 (95% CI: 0.63-0.80) for 18F-FDG. The pooled SEN for detecting lymph node metastases was 0.78 (95% CI: 0.74-0.82) for 68Ga-FAPI and 0.35 (95% CI: 0.30-0.39) for 18F-FDG, with pooled SPE values of 0.99 (95% CI: 0.98-0.99) and 0.97 (95% CI: 0.96-0.98), respectively. For detecting distant metastases, pooled SEN values were 0.97 (95% CI: 0.96-0.98) and 0.69 (95% CI: 0.66-0.72) for 68Ga-FAPI and 18F-FDG, with pooled SPE values of 0.86 (95% CI: 0.82-0.89) and 0.64 (95% CI: 0.59-0.68), respectively. CONCLUSION: This meta-analysis concluded that 68Ga-FAPI PET/CT was significantly more sensitive than 18F-FDG PET/CT in assessing primary gastric tumors, lymph nodes, and distant metastases, but the difference in the specificity of lymph node metastasis was not significant.

Generation of a human embryonic stem cell line (SMUDHe010-A-1A) carrying Brainbow cassette in the AAVS1 gene by CRISPR/Cas9-mediated homologous recombination.

Tracking single-cell lineages and their phenotypes longitudinally would help us better study skin development. Brainbow multicolor labeling approach is a genetic cell-labeling technique that tracks individual cells or analyzes cell lineages during development. Hence, we generated a stable Cre-inducible rainbow reporter human embryonic stem cell line (Named SMUDHe010-A-1A) by inserting the fluorescent protein gene (nGFP, YFP, RFP and CFP) at AAVS1 safe harbor locus using CRISPR/Cas9 technology. We verified that SMUDHe010-A-1A expressed the pluripotency markers and showed normal stem cell morphology. Furthermore, SMUDHe010-A-1A preserves normal karyotype and the ability to differentiate toward three germ layers. So the SMUDHe010-A-1A is effective for identifying and track cell populations.

The Influence of Self-Esteem on Sociocultural Adaptation of College Students of Hong Kong, Macao and Taiwan: The Chain Mediating Role of Social Support and School Belonging.

Purpose: Mainland universities have become one of the important choices for students from Hong Kong, Macao and Taiwan, but the maladaptation caused by environmental migration will have a negative impact on the mental health of them. Therefore, it is urgent to explore the psychological mechanism of sociocultural adaptation of Hong Kong, Macao and Taiwan students. Methods: In order to explore the influence of self-esteem on the sociocultural adaptation of college students of Hong Kong, Macao and Taiwan studying in mainland universities, as well as the mechanism of social support and school belonging, a survey was conducted among 1108 college students from Hong Kong, Macao and Taiwan studying in mainland universities, with the help of Rosenberg Self-Esteem Scale, Sociocultural Adaptation Scale, Perceptive Social Support Scale and The Psychological Sense of School belonging Scale. Results: The results show that (1) Different grades of college students of Hong Kong, Macao and Taiwan have differences in school belonging and sociocultural adaptation (P<0.05); (2) Self-esteem, social support, school belonging and sociocultural adaptation were positively correlated (P < 0.01); (3) The mediation model test showed that self-esteem could directly and positively predict sociocultural adaptation with a direct effect size of 0.245; Social support and school belonging played a mediating role between self-esteem and sociocultural adaptation, and the mediating effect sizes were 0.094 and 0.085, respectively. The chain mediating effect of social support and school belonging was also significant, and the mediating effect size was 0.108. Conclusion: Self-esteem can not only directly affect college students' sociocultural adaptation, but also indirectly affect college students' sociocultural adaptation through the chain mediating effect of social support and school belonging. This study further reveals the mechanism of self-esteem on sociocultural adaptation and provides psychological basis for universities to improve the sociocultural adaptation level of different groups of students.

The effects of double-filtration plasmapheresis on coagulation profiles and the risk of bleeding.

BACKGROUND/PURPOSE: Double-filtration plasmapheresis (DFPP) can be used to remove circulating pathogenic molecules. By reclaiming filtered albumin, DFPP reduces the need for albumin and plasma replacement. Large proteins, such as fibrinogen, are removed. Our institution adopts a DFPP treatment protocol consisting of active surveillance of coagulation profiles and prophylactic supplementation of blood products containing fibrinogen. This study aims to investigate the effects of consecutive DFPP treatments on serial coagulation profiles and the risk of bleeding under this protocol. METHODS: Serial laboratory data and bleeding events at a single tertiary medical center were prospectively collected. Prophylactic transfusion of cryoprecipitate or fresh frozen plasma (FFP) was instituted if significant coagulopathy or a clinically evident bleeding event was observed. RESULTS: After the first treatment session, plasma fibrinogen levels decreased from 332 ± 106 mg/dL to 96 ± 44 mg/dL in the 37 study patients. In the following sessions, plasma fibrinogen levels were maintained at around 100 mg/dL under prophylactic transfusion. No major bleeding events were recorded, but five (14%) patients experienced minor bleeding. CONCLUSION: DFPP treatment might be performed safely along with active monitoring of coagulation profiles and prophylactic transfusion of cryoprecipitate or FFP.

Multifaceted Nature of HuR in Atherosclerosis Development.

HuR (Human antigen R) is an RNA binding protein (RBP) that specifically binds to certain RNA sequences, influencing post-transcriptional regulation. HuR is primarily involved in tumor regulation, as well as cell growth, proliferation, inflammation, and angiogenesis. HuR is implicated in endothelial activation, smooth muscle proliferation, inflammatory response, macrophage apoptosis, lipid regulation, and autophagy, playing a crucial regulatory role in atherosclerosis. Accumulating evidence suggests that HuR has dual roles in AS. On the one hand, HuR expedites the development of AS by facilitating endothelial activation, smooth muscle proliferation, and inflammation. On the contrary, it exerts beneficial effects by reducing macrophage apoptosis, regulating lipid efflux, and increasing autophagy. In this review, we aim to provide a comprehensive summary of the role of HuR in the development of AS by examining its involvement in cellular mechanisms, inflammation, autophagy, and apoptosis. Additionally, we discuss the mechanisms of drugs that target HuR, with the goal of offering new perspectives for the treatment of AS.

Hydrogen sulfide donors across time: From origins to cutting-edge applications.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

Involvement of Histone Acetyltransferase 1 (HAT1) in the Spermatogenesis of Non-Condensed Nuclear Sperm in Chinese Mitten Crab, Eriocheir sinensis.

Chinese mitten crab, Eriocheir sinensis, is a decapod crustacean with a special, non-condensated nucleus in the sperm. Studies have shown that the nuclear compact state of male germ cells during the spermatogenesis is closely related to histone modification. To explore the possible role of histone acetyltransferase 1 (HAT1) in the chromatin organization during the E. sinensis spermatogenesis, we took the testis tissues of both adult and juvenile crabs as the materials of study and analyzed the biological functions of HAT1 by whole transcriptome sequencing and bioinformatics, then further analyzed the expression and distribution of HAT1 using the methods of RT-qRCR, western blotting, and immunofluorescence location. The results showed that HAT1 is an alkaline-unstable hydrophilic protein. It was predicted to interact with a variety of histones and chromosome assembly proteins, including Asf1b, Chaf1b, and Hist1h3f, and is involved in many biological functions pertaining to chromatin dynamics such as chromatin organization, DNA dependent nucleosome assembly, DNA conformational changes, and so on. HAT1 was up-regulated in the adult testes compared to the juvenile (n = 3, P < 0.05). HAT1 was mainly located in the nuclei of male germ cells of E. sinensis. As spermatogenesis proceeded, the expression of HAT1 decreased and even disappeared in the nuclei (n = 3, P < 0.05). HAT1 is an important player in histone acetylation, which facilitates chromatin alteration in a three-dimensional conformation. The expression of HAT1 in different male germ cells might indicate the chromatin dynamics at the diversity stages of spermatogenesis. The high expression of HAT1 at the early stages of E. sinensis spermatogenesis hints the active involvement in chromatin organization, while its progressively reduced expression accompanied by the progression of spermatogenesis suggests a relatively gradual stabilization and stereotyping of chromatin. As for the disappearance of HAT1 in mature sperm with non-condensed nuclei, the reduction in histones targeted by HAT1 or histone acetylation may be an important initiator.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

Intramuscular Hemangioma of the Triceps Brachii Muscle: A Case Report.

Introduction: Intramuscular hemangioma (IMH) is a rare type of benign tumor that represents less than 1% of all hemangiomas. Chronic pain and a palpable mass are the most common symptoms. Due to the atypical clinical characteristics of the disease, accurate diagnosis is difficult. Misdiagnosis of IMH as malignancy can occur due to similarities in imaging features between IMH and malignancy. To diagnose IMH accurately, multiple imaging modalities, including X-ray, MRI, CT, and 18F-FDG PET/CT, can be used. However, the final diagnosis of IMH is confirmed through histopathological examination. Case: This case reports a 16-year-old girl diagnosed with IMH in the triceps brachii muscle. Seek medical attention due to pain and discomfort in the left shoulder. Initial imaging with contrast-enhanced MRI and CT suggested synovial sarcomata. The moderate uptake of FDG on positron emission tomography/computed tomography (PET/CT) also raised suspicions of malignancy. The pathological findings revealed an intramuscular hemangioma with thrombosis and thrombus organization. Conclusion: The accurate diagnosis of IMH can be challenging due to the absence of distinct clinical symptoms and imaging findings. When evaluating periarticular intramuscular lesions, IMH should be considered if the MRI shows mixed signals with heterogeneous enhancement. Despite the moderate uptake of FDG seen in some IMH cases, it should not automatically rule out the possibility of IMH. Hence, a combination of imaging modalities and histopathological examination is crucial in ensuring a correct diagnosis of IMH.

Magnetic Resonance Spectroscopy Quantification Aided by Deep Estimations of Imperfection Factors and Macromolecular Signal.

OBJECTIVE: Magnetic Resonance Spectroscopy (MRS) is an important technique for biomedical detection. However, it is challenging to accurately quantify metabolites with proton MRS due to serious overlaps of metabolite signals, imperfections because of non-ideal acquisition conditions, and interference with strong background signals mainly from macromolecules. The most popular method, LCModel, adopts complicated non-linear least square to quantify metabolites and addresses these problems by designing empirical priors such as basis-sets, imperfection factors. However, when the signal-to-noise ratio of MRS signal is low, the solution may have large deviation. METHODS: Linear Least Squares (LLS) is integrated with deep learning to reduce the complexity of solving this overall quantification. First, a neural network is designed to explicitly predict the imperfection factors and the overall signal from macromolecules. Then, metabolite quantification is solved analytically with the introduced LLS. In our Quantification Network (QNet), LLS takes part in the backpropagation of network training, which allows the feedback of the quantification error into metabolite spectrum estimation. This scheme greatly improves the generalization to metabolite concentrations unseen in training compared to the end-to-end deep learning method. RESULTS: Experiments show that compared with LCModel, the proposed QNet, has smaller quantification errors for simulated data, and presents more stable quantification for 20 healthy in vivo data at a wide range of signal-to-noise ratio. QNet also outperforms other end-to-end deep learning methods. CONCLUSION: This study provides an intelligent, reliable and robust MRS quantification. SIGNIFICANCE: QNet is the first LLS quantification aided by deep learning.

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches.

Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.

LncRNA-mediated Modulation of Endothelial Cells: Novel Progress in the Pathogenesis of Coronary Atherosclerotic Disease.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

Genetics of congenital heart disease.

During embryonic development, the cardiovascular system and the central nervous system exhibit a coordinated developmental process through intricate interactions. Congenital heart disease (CHD) refers to structural or functional abnormalities that occur during embryonic or prenatal heart development and is the most common congenital disorder. One of the most common complications in CHD patients is neurodevelopmental disorders (NDD). However, the specific mechanisms, connections, and precise ways in which CHD co-occurs with NDD remain unclear. According to relevant research, both genetic and non-genetic factors are significant contributors to the co-occurrence of sporadic CHD and NDD. Genetic variations, such as chromosomal abnormalities and gene mutations, play a role in the susceptibility to both CHD and NDD. Further research should aim to identify common molecular mechanisms that underlie the co-occurrence of CHD and NDD, possibly originating from shared genetic mutations or shared gene regulation. Therefore, this review article summarizes the current advances in the genetics of CHD co-occurring with NDD, elucidating the application of relevant gene detection techniques. This is done with the aim of exploring the genetic regulatory mechanisms of CHD co-occurring with NDD at the gene level and promoting research and treatment of developmental disorders related to the cardiovascular and central nervous systems.

Generation of a human embryonic stem cell line (SMUDHe010-A-1B) carrying inducible DTA expression cassette in the AAVS1 locus by CRISPR/Cas9-mediated homologous recombination.

Diphtheria toxin A (DTA) is an exotoxin secreted by Corynebacterium diphtheriae. After entering the cell through receptor-mediated manner, DTA can trigger the programmed cell death mechanism and lead to cell death. In 2001, Michiko Saito established a Diphtheria toxin receptor-mediated cell knockout system, which can conditional deplete specific cell type in transgenic mice. This system is not only very useful in the pathogenesis study of human diseases, but also has a wide application prospect in the study of organ development and regeneration. In 2008, David Voehringer described a newly generated mouse strain that encodes DTA under control of a loxP-flanked stop cassette in the ubiquitously expressed ROSA26 locus. Thereby, it can be used in combination with tissue-specific and/or inducible Cre-expressing mouse strains to achieve toxin-mediated cell ablation in vivo. The application of DTA-mediated cell knockout system in mice has been widely reported, but it has rarely been used in human cells. Accordingly, we generated a human embryonic stem cell line (SMUDHe010-A-1B) carrying inducible DTA expression cassette (loxp-stop-loxp-DTA, LSL-DTA) using CRISPR/Cas9-mediated homologous recombination. The cell line preserves normal karyotype, pluripotency and the ability to differentiate into all three germ layers. Moreover, the cell line can be used to prepare human organoid, which may provide a model for achieving conditional cell ablation in human tissues and organs.

miR-124-3p regulates the involvement of Ptpn1 in testicular development and spermatogenesis in mouse.

Testicular development and spermatogenesis in mouse are a complex process in which phosphorylation modifications and regulation of genes by non-coding RNAs play an important role. However, protein tyrosine phosphatase, non-receptor type 1 (Ptpn1) is widely expressed in mammalian tissues. In this study, we analyzed the expression of Ptpn1 mRNA and its encoded proteins in testicular tissues of juvenile and adult mice by using experimental techniques such as biological information, real-time fluorescence quantitative PCR (RT-qPCR), western blot (WB), immunofluorescence (IF) and transfection, and further analyzed the possible target-regulatory relationship and regulatory mechanisms of miR-124-3p and Ptpn1. We found that Ptpn1 mRNA and its encoded protein were up-regulated in adult mouse testis compared to juvenile mouse testis. The expression trend of miR-124-3p was opposite to that of Ptpn1. In other cell types, Ptpn1 protein is localized in cell membrane, cytoplasm, endoplasmic reticulum and cytoplasmic vesicles. Immunofluorescence showed that Ptpn1 protein was mainly localized in the cytoplasm of male germ cells and was expressed at a high level in early-stage cells (spermatogonia) and at a low level in late-stage cells (sperm). Transfection results showed that the expression levels of Ptpn1 mRNA and its protein were significantly down-regulated after miR-124-3p overexpression in mouse spermatogonia. Bioinformatics analysis showed that Ptpn1 can involved in biological processes such as protein kinase inactivation through peptidyl tyrosine dephosphorylation. The reduction of miR-124-3p may be a key factor in promoting the high expression of Ptpn1 in testicular tissues of adult mice. Increased miR-124-3p may be a key factor in suppressing Ptpn1 expression in the mouse spermatogonia mimics group. The differential expression results from the negative regulation of miR-124-3p.

A new metal ion chelator attenuates human tau accumulation-induced neurodegeneration and memory deficits in mice.

Neuronal neurofibrillary tangles containing Tau hyperphosphorylation proteins are a typical pathological marker of Alzheimer's disease (AD). The level of tangles in neurons correlates positively with severe dementia. However, how Tau induces cognitive dysfunction is still unknown, which leads to a lack of effective treatments for AD. Metal ions deposition occurs with tangles in AD brain autopsy. Reduced metal ion can improve the pathology of AD. To explore whether abnormally phosphorylated Tau causes metal ion deposition, we overexpressed human full-length Tau (hTau) in the hippocampal CA3 area of mice and primary cultured hippocampal neurons (CPHN) and found that Tau accumulation induced iron deposition and activated calcineurin (CaN), which dephosphorylates glycogen synthase kinase 3 beta (GSK3ß), mediating Tau hyperphosphorylation. Simultaneous activation of CaN dephosphorylates cyclic-AMP response binding protein (CREB), leading to synaptic deficits and memory impairment, as shown in our previous study; this seems to be a vicious cycle exacerbating tauopathy. In the current study, we developed a new metal ion chelator that displayed a significant inhibitory effect on Tau phosphorylation and memory impairment by chelating iron ions in vivo and in vitro. These findings provide new insight into the mechanism of memory impairment induced by Tau accumulation and develop a novel potential treatment for tauopathy in AD.

Opioid infusions at different times of the day produce varying degrees of opioid-induced hyperalgesia.

BACKGROUND: Opioids are metabolised by enzymes the activities of which vary with the circadian rhythm. We examined whether opioid infusions administered at different times of the day produce varying degrees of opioid-induced hyperalgesia (OIH) in animal experiments and clinical studies. METHODS: Male Sprague-Dawley rats received remifentanil infusions (1 µg kg-1·min-1 for 1 h) at Zeitgeber times (ZT) 0, 4, 8, 12, 16, or 20 h. Rhythmicity of mechanical hypersensitivity was assayed after the infusion. Mechanical hypersensitivity, drug concentration, and metabolic enzyme activity of Wistar rats that received sufentanil (10 µg kg-1; four consecutive i.p. injections at 15-min intervals) or remifentanil infusion at ZT0 or ZT8 were assayed. Sixty patients who underwent abdominal laparoscopic surgery under general anaesthesia received remifentanil infusion (0.15 µg kg-1 min-1) and sufentanil injection (0.2 µg kg-1) at induction and skin incision, respectively. Postoperative pressure pain sensitivity, pain Numeric Rating Scale (NRS), drug concentrations, and nonspecific esterase activity were assessed. RESULTS: Sprague-Dawley rats that received remifentanil infusion exhibited a robust rhythmic paw withdrawal threshold (JTK_CYCLE: P=0.001, Q=0.001, Phase=26). Wistar rats infused with remifentanil or sufentanil at ZT8 exhibited greater OIH (P<0.001) than those infused at ZT0, with higher blood concentrations (P<0.001) and lower metabolic enzyme activities (P=0.026 and P=0.028, respectively). Patients in the afternoon group exhibited higher pressure pain sensitivity at forearm (P=0.002), higher NRS (P<0.05), higher drug concentrations (sufentanil: P=0.037, remifentanil: P=0.005), and lower nonspecific esterase activity (P=0.024) than the morning group. CONCLUSIONS: Opioid infusions administered at different times of day produced varying degrees of OIH, possibly related to circadian rhythms of metabolic enzyme activities. CLINICAL TRIAL REGISTRATION: NCT05234697.

Role of multiple dual-phase 18F-FDG PET/CT metabolic parameters in differentiating adenocarcinomas from squamous cell carcinomas of the lung.

Purpose: To evaluate the ability of multiple dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters to distinguish the histological subtypes of non-small cell lung cancer (NSCLC). Methods: Data from 127 patients with non-small cell lung cancer who underwent preoperative dual-phase 18F-FDG PET/CT scanning at the PET-CT center of our hospital from December 2020 to October 2021 were collected, and the metabolic parameters of their primary lesions were measured and analyzed retrospectively. Intraclass correlation coefficients (ICC) were calculated for consistency between readers. Metabolic parameters in the early (SUVpeak, SUVmean, SUVmin, SUVmax, MTV, and TLG) and delayed phases (dpSUVpeak, dpSUVmean, dpSUVmin, dpSUVmax, dpMTV, and dpTLG) were calculated. We drew receiver operating characteristic (ROC) curves to compare the differences in different metabolic parameters between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) groups and evaluated the ability of different metabolic parameters to distinguish AC from SCC. Results: Inter-reader agreement, as assessed by the intraclass correlation coefficient (ICC), was good (ICC = 0.71, 95% CI:0.60-0.79). The mean MTV, SUVmax, TLG, SUVpeak, SUVmean, dpSUVmax, dpTLG, dpSUVpeak, dpSUVmean, and dpSUVmin of the tumors were significantly higher in SCC lesions than in AC lesions (P = 0.049, < 0.001, 0.016, < 0.001, 0.001, < 0.001, 0.018, < 0.001, 0.001, and 0.001, respectively). The diagnostic efficacy of the metabolic parameters in 18F-FDG PET/CT for differentiating adenocarcinoma from squamous cell carcinoma ranged from high to low as follows: SUVpeak (AUC = 0.727), SUVmax (AUC = 0.708), dpSUVmax (AUC = 0.699), dpSUVpeak (AUC = 0.698), TLG (AUC = 0.695), and dpTLG (AUC = 0.692), SUVmean (AUC = 0.690), dpSUVmean (AUC = 0.687), dpSUVmin (AUC = 0.680), SUVmin (AUC = 0.676), and MTV (AUC = 0.657). Conclusions: Squamous cell carcinoma of the lung had higher mean MTV, SUVmax, TLG, SUVpeak, SUVmean, SUVmin, dpSUVpeak, dpSUVmean, dpSUVmin, dpSUVmax, and dpTLG than AC, which can be helpful tools in differentiating between the two. The metabolic parameters of the delayed phase (2 h after injection) 18F-FDG PET/CT did not improve the diagnostic efficacy in distinguishing lung AC from SCC. Conventional dual-phase 18F-FDG PET/CT is not recommended.

Non-imaging method for angle measurement based on an axicon.

A new non-imaging angle measurement method based on an axicon is proposed in this paper. This method uses an axicon that can form a complex light spot with a clear edge and rich feature information after total internal reflection and refraction on the sloped face compared with convergent lenses, which can only form a blurry edge spot. According to the high sensitivity of the beam transformation of the axicon to the incident angle, light spot images with obvious feature variation can be easily obtained to achieve angle measurement with high accuracy. The method based on an axicon can meet the application requirements of multiple angle measurement ranges, and the structure is simple and compact. In the small-angle measurement experiment combined with a telescope module, the measurement resolution can reach 1 ' ' , the mean absolute error is 0.0010°, and the relative error is within 0.25% in the measurement range of 1.6°.