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"Wang, Xueping"
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The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy
Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies (Abs) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) Abs, are effective for patients with various cancers. However, low response rates to ICI monotherapies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. HPD is a novel pattern of progression, with an unexpected and fast progression in tumor volume and rate, poor survival of patients and early fatality. Considering the limitations of ICI due to HPD incidence, valid biomarkers are urgently needed to predict the occurrence of HPD and the efficacy of ICI. Here, we reviewed and summarized the known biomarkers of HPD, including tumor cell biomarkers, tumor microenvironment biomarkers, laboratory biomarkers and clinical indicators, which provide a potential effective approach for selecting patients sensitive to ICI cancer treatments.
Journal Article
Local and Global Context-Enhanced Lightweight CenterNet for PCB Surface Defect Detection
Printed circuit board (PCB) surface defect detection is an essential part of the PCB manufacturing process. Currently, advanced CCD or CMOS sensors can capture high-resolution PCB images. However, the existing computer vision approaches for PCB surface defect detection require high computing effort, leading to insufficient efficiency. To this end, this article proposes a local and global context-enhanced lightweight CenterNet (LGCL-CenterNet) to detect PCB surface defects in real time. Specifically, we propose a two-branch lightweight vision transformer module with local and global attention, named LGT, as a complement to extract high-dimension features and leverage context-aware local enhancement after the backbone network. In the local branch, we utilize coordinate attention to aggregate more powerful features of PCB defects with different shapes. In the global branch, Bi-Level Routing Attention with pooling is used to capture long-distance pixel interactions with limited computational cost. Furthermore, a Path Aggregation Network (PANet) feature fusion structure is incorporated to mitigate the loss of shallow features caused by the increase in model depth. Then, we design a lightweight prediction head by using depthwise separable convolutions, which further compresses the computational complexity and parameters while maintaining the detection capability of the model. In the experiment, the LGCL-CenterNet increased the mAP@0.5 by 2% and 1.4%, respectively, in comparison to CenterNet-ResNet18 and YOLOv8s. Meanwhile, our approach requires fewer model parameters (0.542M) than existing techniques. The results show that the proposed method improves both detection accuracy and inference speed and indicate that the LGCL-CenterNet has better real-time performance and robustness.
Journal Article
m -Polar Fuzzy Sets: An Extension of Bipolar Fuzzy Sets
Recently, bipolar fuzzy sets have been studied and applied a bit enthusiastically and a bit increasingly. In this paper we prove that bipolar fuzzy sets and 0,1 2 -sets (which have been deeply studied) are actually cryptomorphic mathematical notions. Since researches or modelings on real world problems often involve multi-agent, multi-attribute, multi-object, multi-index, multi-polar information, uncertainty, or/and limit process, we put forward (or highlight) the notion of m -polar fuzzy set (actually, 0,1 m -set which can be seen as a generalization of bipolar fuzzy set, where m is an arbitrary ordinal number) and illustrate how many concepts have been defined based on bipolar fuzzy sets and many results which are related to these concepts can be generalized to the case of m -polar fuzzy sets. We also give examples to show how to apply m -polar fuzzy sets in real world problems.
Journal Article
RNA demethylation increases the yield and biomass of rice and potato plants in field trials
RNA
N
6
-methyladenosine (m
6
A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m
6
A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m
6
A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m
6
A methylation is a promising strategy to dramatically improve plant growth and crop yield.
Rice and potato plants are more productive after epitranscriptome engineering.
Journal Article
Facial Expression Recognition Using Local Sliding Window Attention
There are problems associated with facial expression recognition (FER), such as facial occlusion and head pose variations. These two problems lead to incomplete facial information in images, making feature extraction extremely difficult. Most current methods use prior knowledge or fixed-size patches to perform local cropping, thereby enhancing the ability to acquire fine-grained features. However, the former requires extra data processing work and is prone to errors; the latter destroys the integrity of local features. In this paper, we propose a local Sliding Window Attention Network (SWA-Net) for FER. Specifically, we propose a sliding window strategy for feature-level cropping, which preserves the integrity of local features and does not require complex preprocessing. Moreover, the local feature enhancement module mines fine-grained features with intraclass semantics through a multiscale depth network. The adaptive local feature selection module is introduced to prompt the model to find more essential local features. Extensive experiments demonstrate that our SWA-Net model achieves a comparable performance to that of state-of-the-art methods with scores of 90.03% on RAF-DB, 89.22% on FERPlus, 63.97% on AffectNet.
Journal Article
Metabolomic differentiation of benign vs malignant pulmonary nodules with high specificity via high-resolution mass spectrometry analysis of patient sera
Differential diagnosis of pulmonary nodules detected by computed tomography (CT) remains a challenge in clinical practice. Here, we characterize the global metabolomes of 480 serum samples including healthy controls, benign pulmonary nodules, and stage I lung adenocarcinoma. The adenocarcinoma demonstrates a distinct metabolomic signature, whereas benign nodules and healthy controls share major similarities in metabolomic profiles. A panel of 27 metabolites is identified in the discovery cohort (
n
= 306) to distinguish between benign and malignant nodules. The discriminant model achieves an AUC of 0.915 and 0.945 in the internal validation (
n
= 104) and external validation cohort (
n
= 111), respectively. Pathway analysis reveals elevation in glycolytic metabolites associated with decreased tryptophan in serum of lung adenocarcinoma vs benign nodules and healthy controls, and demonstrates that uptake of tryptophan promotes glycolysis in lung cancer cells. Our study highlights the value of the serum metabolite biomarkers in risk assessment of pulmonary nodules detected by CT screening.
Detection of lung adenocarcinoma through serum sampling could be an alternative to CT scanning. Here, the authors use global metabolomics to create a 27 metabolite signature, which showed accuracy in detection in an external validation cohort.
Journal Article
Microglia-derived TNF-α contributes to RVLM neuronal mitochondrial dysfunction via blocking the AMPK–Sirt3 pathway in stress-induced hypertension
Background
Neuroinflammation in the rostral ventrolateral medulla (RVLM) has been associated with the pathogenesis of stress-induced hypertension (SIH). Neuronal mitochondrial dysfunction is involved in many pathological and physiological processes. However, the impact of neuroinflammation on neuronal mitochondrial homeostasis and the involved signaling pathway in the RVLM during SIH are largely unknown.
Methods
The morphology and phenotype of microglia and the neuronal mitochondrial injury in vivo were analyzed by immunofluorescence, Western blot, RT-qPCR, transmission electron microscopy, and kit detection. The underlying mechanisms of microglia-derived tumor necrosis factor‐α (TNF-α) on neuronal mitochondrial function were investigated through in vitro and in vivo experiments such as immunofluorescence and Western blot. The effect of TNF-α on blood pressure (BP) regulation was determined in vivo via intra-RVLM microinjection of TNF-α receptor antagonist R7050.
Results
The results demonstrated that BP, heart rate (HR), renal sympathetic nerve activity (RSNA), plasma norepinephrine (NE), and electroencephalogram (EEG) power increased in SIH rats. Furthermore, the branching complexity of microglia in the RVLM of SIH rats decreased and polarized into M1 phenotype, accompanied by upregulation of TNF‐α. Increased neuronal mitochondria injury was observed in the RVLM of SIH rats. Mechanistically, Sirtuin 3 (Sirt3) and p-AMPK expression were markedly downregulated in both SIH rats and TNF-α–treated N2a cells. AMPK activator A769662 upregulated AMPK–Sirt3 signaling pathway and consequently reversed TNF-α–induced mitochondrial dysfunction. Microinjection of TNF-α receptor antagonist R7050 into the RVLM of SIH rats significantly inhibited the biological activities of TNF-α, increased p‐AMPK and Sirt3 levels, and alleviated neuronal mitochondrial injury, thereby reducing c-FOS expression, RSNA, plasma NE, and BP.
Conclusions
This study revealed that microglia-derived TNF-α in the RVLM impairs neuronal mitochondrial function in SIH possibly through inhibiting the AMPK–Sirt3 pathway. Therefore, microglia-derived TNF-α in the RVLM may be a possible therapeutic target for the intervention of SIH.
Journal Article