The principal barrier for the eradication of HIV/AIDS is the virus latency. One of the effective strategies so called “shock and kill” is to use latency-reversing agents (LRAs) to activate the latent ...HIV reservoirs and then combine them with the highly active antiretroviral therapy (HAART) to eradicate the virus. However, most of the current LRAs are too toxic; therefore, they have not been used clinically. Our preliminary data indicated that polyphenols from grape seeds can activate HIV in latently infected Jurkat T cells. Owing to a lot of food containing polyphenols and based on a reasoning whether all of these kinds of polyphenols contain the latency-reversing function, in this study, we screened 22 fruits/vegetables to see whether polyphenols from these can reactivate latent HIV-1 transcription. We finally proved that the polyphenols from grape seeds, apple, pomegranate, and bilberry can reactivate latent HIV-1 transcription. The activation of which can be detected on the level of protein and mRNA. The activation of which is in a dose- and time-dependent manner, while the activated polyphenol extracts have the effects to stimulate Tat-independent HIV-1 transcription. The mechanism shows that polyphenol extracts from grape seeds and apple can stimulate P-TEFb’s release from 7SK snRNP to induce HIV gene transcription. These results indicate that using a few food of high-content polyphenols as latent activators and combining HARRT may be of great use for the treatment of HIV/AIDS in the future.
Recently, more and more SAW sensors have been developed for viscosity sensing, bringing different ways of contacting the liquid with the device. It is important to choose a contact method that ...maximizes the performance of the device. Therefore, this paper describes the development of devices for detecting the viscosity of liquids and the evolution of fluid-device contact methods. And a responsive viscosity sensing system with a flow channel for real-time monitoring is developed in our work. The channel, made of polycarbonate, is responsible for regulating the flow direction and ensures that the sensing area covered by the liquid, the mass, and the morphology of the liquid load on the sensor are the same for each detection. Based on a one-port resonator, the sensor offers a faster response time, lower attenuation, and higher sensitivity of 38.6 kHz/ kg m−2 s−0.5. The real-time detection results also show that changes in flow rate do not affect resonant frequency. In addition, the sensor's frequency response to viscosity-density product has been conducted using glycerol solution to get a standard curve. Then the viscosity of the rinse water can be accessible by the frequency response. For the first time, the rinse solution directly from the washing machine is used to measure the residual detergent concentration. The residual concentrations of detergent in the first and second rinse solutions are 23 ppm and 6 ppm, respectively. The system is more convenient, more responsive, and more accurate.
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●One-port resonator exhibits higher sensitivity and faster response in liquid sensing.●Flow channel ensures even flow in the sensing area, making the result more accurate.●The effect of flow rate on the results is investigated.●The relationship between the liquid property and the frequency shift is revealed.●The system can detect detergent residues less than 10 ppm.
Ozone is a common air pollutant associated with various human diseases. The human ocular surface is frequently exposed to ozone in the troposphere, but the mechanisms by which ozone affects the ...ocular surface health remain unclear. This study aimed to establish a mouse model to investigate the effects of ozone exposure on the ocular surface and the corneal epithelium. The findings revealed that ozone exposure disrupted corneal epithelial homeostasis and differentiation, resulting in corneal squamous metaplasia. Further, ozone exposure induced oxidative damage and cytoplasmic leakage of mitochondrial DNA (mtDNA), thereby activating the cGAS/STING signaling pathway. The activation of the cGAS/STING signaling pathway triggered the activation of downstream NF-κB and TRAF6 signaling pathways, causing corneal inflammation, thereby promoting corneal inflammation and squamous metaplasia. Finally, C-176, a selective STING inhibitor, effectively prevented and treated corneal inflammation and squamous metaplasia caused by ozone exposure. This study revealed the role of mtDNA leakage-mediated cGAS/STING activation in corneal squamous epithelial metaplasia caused by ozone exposure. It also depicted the abnormal expression pattern of corneal epithelial keratin using three-dimensional images, providing new targets and strategies for preventing and treating corneal squamous metaplasia and other ocular surface diseases.
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•Ozone disrupted corneal epithelial homeostasis.•Ozone exposure affected keratin expression patterns.•Ozone induced DNA damage and abnormal mitosis in corneal epithelial cells.•Ozone induced mtDNA leakage and cGAS/STING activation.•cGAS/STING pathway inhibition could treat corneal squamous metaplasia.
Accurate polyp detection is critical for early colorectal cancer diagnosis. Although remarkable progress has been achieved in recent years, the complex colon environment and concealed polyps with ...unclear boundaries still pose severe challenges in this area. Existing methods either involve computationally expensive context aggregation or lack prior modeling of polyps, resulting in poor performance in challenging cases. In this paper, we propose the Enhanced CenterNet with Contrastive Learning (ECC-PolypDet), a two-stage training & end-to-end inference framework that leverages images and bounding box annotations to train a general model and fine-tune it based on the inference score to obtain a final robust model. Specifically, we conduct Box-assisted Contrastive Learning (BCL) during training to minimize the intra-class difference and maximize the inter-class difference between foreground polyps and backgrounds, enabling our model to capture concealed polyps. Moreover, to enhance the recognition of small polyps, we design the Semantic Flow-guided Feature Pyramid Network (SFFPN) to aggregate multi-scale features and the Heatmap Propagation (HP) module to boost the model's attention on polyp targets. In the fine-tuning stage, we introduce the IoU-guided Sample Re-weighting (ISR) mechanism to prioritize hard samples by adaptively adjusting the loss weight for each sample during fine-tuning. Extensive experiments on six large-scale colonoscopy datasets demonstrate the superiority of our model compared with previous state-of-the-art detectors.
Lipid metabolism is related to lymphomagenesis, and is a novel therapeutic target in some hematologic tumors. Apolipoprotein A (ApoA), the major protein of high-density lipoprotein (HDL), plays a ...crucial role in lipid transportation and protecting against cardiovascular disease, and takes effect on anti-inflammation and anti-oxidation. It is correlated with the prognosis of some solid tumors. Yet, there is no investigation involving the role of ApoA plays in chronic lymphocytic leukemia (CLL). Our retrospective study focuses on the prognostic value of ApoA in CLL and its therapeutic potential for CLL patients. Herein, ApoA is a favorable independent prognostic factor for both overall survival (OS) and progression-free survival (PFS) of CLL patients. ApoA is negatively associated with β2-microglobulin (β2-MG) and advanced stage, which are poor prognostic factors in CLL. Age, Rai stage, ApoA, and adenosine deaminase (ADA) are included in a new risk scoring system named
ARAA-score
. It is capable of assessing OS and PFS of CLL patients. Furthermore, cell proliferation assays show that the ApoA-I mimetic L-4F can inhibit the proliferation of CLL cell lines and primary cells. In conclusion, ApoA is of prognostic value in CLL, and is a potential therapy for CLL patients. The
ARAA-score
may optimize the risk stratification of CLL patients.
Melanoma is a human skin malignant tumor with high invasion and poor prognosis. The limited understanding of genomic alterations in melanomas in China impedes the diagnosis and therapeutic strategy ...selection. We conducted comprehensive genomic profiling of melanomas from 39 primary and metastatic formalin-fixed paraffin-embedded (FFPE) samples from 27 patients in China based on an NGS panel of 223 genes. No significant difference in gene alterations was found between primary and metastasis melanomas. The status of germline mutation, CNV, and somatic mutation in our cohort was quite different from that reported in Western populations. We further delineated the mutation patterns of 4 molecular subgroups (BRAF, RAS, NF1, and Triple-WT) of melanoma in our cohort. BRAF mutations were more frequently identified in melanomas without chromic sun-induced damage (non-CSD), while RAS mutations were more likely observed in acral melanomas. NF1 and Triple-WT subgroups were unbiased between melanomas arising in non-CSD and acral skin. BRAF, RAS, and NF1 mutations were significantly associated with lymph node metastasis or presence of ulceration, implying that these cancer driver genes were independent prognostic factors. In summary, our results suggest that mutational profiles of malignant melanomas in China are significantly different from Western countries, and both gene mutation and amplification play an important role in the development and progression of melanomas.
Accurate polyp detection is critical for early colorectal cancer diagnosis. Although remarkable progress has been achieved in recent years, the complex colon environment and concealed polyps with ...unclear boundaries still pose severe challenges in this area. Existing methods either involve computationally expensive context aggregation or lack prior modeling of polyps, resulting in poor performance in challenging cases. In this paper, we propose the Enhanced CenterNet with Contrastive Learning (ECC-PolypDet), a two-stage training \& end-to-end inference framework that leverages images and bounding box annotations to train a general model and fine-tune it based on the inference score to obtain a final robust model. Specifically, we conduct Box-assisted Contrastive Learning (BCL) during training to minimize the intra-class difference and maximize the inter-class difference between foreground polyps and backgrounds, enabling our model to capture concealed polyps. Moreover, to enhance the recognition of small polyps, we design the Semantic Flow-guided Feature Pyramid Network (SFFPN) to aggregate multi-scale features and the Heatmap Propagation (HP) module to boost the model's attention on polyp targets. In the fine-tuning stage, we introduce the IoU-guided Sample Re-weighting (ISR) mechanism to prioritize hard samples by adaptively adjusting the loss weight for each sample during fine-tuning. Extensive experiments on six large-scale colonoscopy datasets demonstrate the superiority of our model compared with previous state-of-the-art detectors.
To further improve the speaking styles of synthesized speeches, current text-to-speech (TTS) synthesis systems commonly employ reference speeches to stylize their outputs instead of just the input ...texts. These reference speeches are obtained by manual selection which is resource-consuming, or selected by semantic features. However, semantic features contain not only style-related information, but also style irrelevant information. The information irrelevant to speaking style in the text could interfere the reference audio selection and result in improper speaking styles. To improve the reference selection, we propose Contrastive Acoustic-Linguistic Module (CALM) to extract the Style-related Text Feature (STF) from the text. CALM optimizes the correlation between the speaking style embedding and the extracted STF with contrastive learning. Thus, a certain number of the most appropriate reference speeches for the input text are selected by retrieving the speeches with the top STF similarities. Then the style embeddings are weighted summarized according to their STF similarities and used to stylize the synthesized speech of TTS. Experiment results demonstrate the effectiveness of our proposed approach, with both objective evaluations and subjective evaluations on the speaking styles of the synthesized speeches outperform a baseline approach with semantic-feature-based reference selection.
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