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077; p = 0.631), while it was negatively correlated with the McGill test (r=-0.650; p = 0.000).

The lack of correlation between the FMS score and the McGill test implies that one's level of core endurance may not influence their functional movement patterns. In contrast, the lumbar lordosis angle might impact one's core muscle endurance but not their functional movement patterns.

The lack of correlation between the FMS score and the McGill test implies that one's level of core endurance may not influence their functional movement patterns. In contrast, the lumbar lordosis angle might impact one's core muscle endurance but not their functional movement patterns.Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the macrophage activation and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. Macrophage recruitment and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 macrophage activation and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD. Video abstract.Arteriovenous malformation (AVM) is a tangle of arteries and veins, rupture of which can result in catastrophic hemorrhage in vulnerable sites such as the brain. Cerebral AVM is associated with a high mortality rate in humans. The causative factor or the stimulus at the artery-venous junction and the molecular basis of the development and progression of cerebral AVM remain unknown. While it is known that aberrant hemodynamic forces in the artery-vein junction contribute to the development of AVMs, the mechanistic pathways are unclear. Given that various environmental stimuli modulate epigenetic modifications on the chromatin of cells, we speculated that misregulated DNA methylome could lead to cerebral AVM development. To identify the aberrant epigenetic signatures, we used AVM nidus tissues and analyzed the global DNA methylome using the Infinium DNA methylome array. We observed significant alterations of DNA methylation in the genes associated with the vascular developmental pathway. Further, we validated the DNA hypermethylation by DNA bisulfite sequencing analysis of selected genes from human cerebral AVM nidus. Taken together, we provide the first experimental evidence for aberrant epigenetic signatures on the genes of vascular development pathway, in human cerebral AVM nidus.

EGFR mutations in non-small cell lung cancer (NSCLC) are associated with a poor response to immune checkpoint inhibitors (ICIs), and only 20% of NSCLC patients harboring EGFR mutations benefit from immunotherapy. Novel biomarkers or therapeutics are needed to predict NSCLC prognosis and enhance the efficacy of ICIs in NSCLC patients harboring EGFR mutations, especially lung adenocarcinoma (LUAD) patients, who account for approximately 40-50% of all NSCLC cases.

An ARID1A-knockdown (ARID1A-KD) EGFR-mutant LUAD cell line was constructed using lentivirus. RNA-seq and mass spectrometry were performed. Western blotting and IHC were used for protein expression evaluation. Effects of 3-MA and rapamycin on cells were explored. Immunofluorescence assays were used for immune cell infiltration examination.

ARID1A expression was negatively associated with immune cell infiltration and immune scores for ICIs in LUAD with EGFR mutations. In vitro experiments suggested that ARID1A-KD activates the EGFR/PI3K/Akt/mTOR pathway and inhibits autophagy, which attenuates the inhibition of Rig-I-like receptor pathway activity and type I interferon production in EGFR-mutant LUAD cells. In addition, 3-MA upregulated production of type I interferon in EGFR-mutant LUAD cells, with an similar effect to ARID1A-KD. On the other hand, rapamycin attenuated the enhanced production of type I interferon in ARID1A-KD EGFR-mutant LUAD cells. ARID1A function appears to influence the tumor immune microenvironment and response to ICIs.

ARID1A deficiency reverses response to ICIs in EGFR-mutant LUAD by enhancing autophagy-inhibited type I interferon production. Video Abstract.

ARID1A deficiency reverses response to ICIs in EGFR-mutant LUAD by enhancing autophagy-inhibited type I interferon production. Video Abstract.

Adenosine is a potent immunosuppressant whose levels in the tumor microenvironment (TME) are often much higher than those in normal tissues. Binding of adenosine to its receptor A2aR activates a cascade of genes and leads to immunosuppression. In addition, immune checkpoint blockage markedly increases A2aR expression in T cells, which could dampen their anti-tumor response. Several A2aR antagonists are under clinical development, but with limited clinical benefit reported so far. These A2aR antagonists showed much diminished activity at high adenosine levels found in TME, which may explain their clinical underperformance. Inflamm inhibitor We report the discovery and early clinical development of DZD2269, a novel A2aR antagonist which can fully block A2aR mediated immunosuppression commonly found in TME. Adenosine stimulates phosphorylation of cyclic AMP response element binding protein (CREB) in T cells and inhibits anti-tumor cytokine secretion in PBMCs in a dose-dependent manner. DZD2269 was able to reverse the immunosupp these animal models. In the phase 1 clinical study, downregulation of pCREB was detected in human T cells, consistent with preclinical prediction.

DZD2269 is a novel A2aR antagonist which can fully block A2aR mediated immunosuppression commonly found in TME. Clinical development of DZD2269 in patients with cancer is warranted (NCT04634344).

DZD2269 is a novel A2aR antagonist which can fully block A2aR mediated immunosuppression commonly found in TME. Clinical development of DZD2269 in patients with cancer is warranted (NCT04634344).

This study aimed to establish a deep learning method based on convolutional networks for the preliminary study of the pathological diagnosis of prosthetic joint infections (PJI).

We enrolled 20 revision patients after joint replacement from the Department of Orthopedics, the First Medical Center, General Hospital of the People's Liberation Army, from January 2021 to January 2022 (10 of whom were confirmed to be infected against 2018 ICM criteria, and the remaining 10 were verified to be non-infected), and classified high-power field images according to 2018 ICM criteria. Then, we inputted 576 positive images and 576 negative images into a neural network by employing a resNET model, used to select 461 positive images and 461 negative images as training sets, 57 positive images and 31 negative images as internal verification sets, 115 positive images and 115 negative images as external test sets.

The resNET model classification was used to analyze the pathological sections of PJI patients under high magnional network deep learning before it is applied to clinical practice.

This study used the convolutional neural network deep learning to identify high-magnification images from pathological sections of soft tissues around joints, against the diagnostic criteria for acute infection, and a high precision and a high recall rate were accomplished. The results of this technique confirmed that better results could be achieved by comparing the new method with the standard strategies in terms of diagnostic accuracy. Continuous upgrading of extended training sets is needed to improve the diagnostic accuracy of the convolutional network deep learning before it is applied to clinical practice.

Capacitively coupled electrode (CC electrode), as a non-contact and unobtrusive technology for measuring physiological signals, has been widely applied in sleep monitoring scenarios. The most common implementation is capacitive electrocardiogram (cECG) that could provide useful clinical information for assessing cardiac function and detecting cardiovascular diseases. In the current study, we sought to explore another potential application of cECG in sleep monitoring, i.e., sleep postures recognition.

Two sets of experiments, the short-term experiment, and the overnight experiment, were conducted. The cECG signals were measured by a smart mattress based on flexible CC electrodes and sleep postures were recorded simultaneously. Then, a classifier model based on a deep recurrent neural network (RNN) was proposed to distinguish sleep postures (supine, left lateral and right lateral). To verify the reliability of the proposed model, leave-one-subject-out cross-validation was introduced.

In the short-term experiment, the overall accuracy of 96.2% was achieved based on 30-s segment, while the overall accuracy was 88.8% using one heart beat segment. For the unconstrained overnight experiment, the accuracy of 91.0% was achieved based on 30-s segment, while the accuracy was 81.4% using one heart beat segment.

The results suggest that cECG could render valuable information about sleep postures detection and potentially be helpful for sleep disorder diagnosis.

The results suggest that cECG could render valuable information about sleep postures detection and potentially be helpful for sleep disorder diagnosis.

Metabolically healthy obesity (MHO), has been recognized as a transient phenotype with few cardiometabolic diseases; however, little is known regarding the development of hypertension in subjects with an absence of cardiometabolic abnormalities and general obesity evaluated by body mass index (BMI) or abdominal obesity evaluated by waist circumference (WC).

A total of 4764 participants were enrolled from the China Health and Nutrition Survey and followed up from 2009 to 2015, whose fasting blood samples were collected in 2009. Obesity was classified as abdominal obesity (WC ≥ 90cm in men and ≥ 80cm in women) and general obesity (BMI ≥ 25.0kg/m

). Logistic regression was used to analyze the relationship between MHO and prehypertension (120 < SBP < 140 mmHg or 80 < DBP < 90 mmHg) and hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg). The age- and sex-specific impacts were further analyzed.

There were 412 (37.9%) participants with prehypertension and 446 (41.0%) participants with hypertension and metaincident hypertension in both men and women. These findings can guide the establishment of risk-stratified obesity treatments.

The MHO phenotype, regardless of the presence of general or abdominal obesity, showed a worse effect on the development of prehypertension and hypertension, particularly in young adults. Abdominal adiposity with a healthy metabolic state is significantly associated with incident hypertension in both men and women. These findings can guide the establishment of risk-stratified obesity treatments.