Non-small cell lung cancer (NSCLC) is a well-known global health concern. TFAP4 has been reported to function as an oncogene. This study sought to investigate the molecular mechanism of TFAP4 in NSCLC development. Significantly highly-expressed gene IGF2BP1 was screened on online databases and its downstream gene TK1 was predicted. IGF2BP1 promoter sequence was identified. The binding site of TFAP4 and IGF2BP1 was predicted. The expression correlations among TFAP4, IGF2BP1, and TK1 were confirmed. The correlations between TFAP4, IGF2BP1, TK1, and NSCLC prognosis were predicted. NSCLC and paracancerous tissues were collected. The expressions of TFAP4, IGF2BP1, and TK1 were detected. NSCLC cell proliferation, migration, invasion, and apoptosis were detected. The binding of TFAP4 to the IGF2BP1 promoter was verified. m6A modification of TK1 mRNA was detected. The correlation between IGF2BP1 and TK1 was confirmed. A subcutaneous tumor xenograft model was established to validate the effect of TFAP4 in vivo. IGF2BP1 was highly expressed in NSCLC tissues and cells. IGF2BP1 knockdown repressed NSCLC cell proliferation, migration, and invasion and facilitated apoptosis. Mechanically, TFAP4 transcriptionally activated IGF2BP1. IGF2BP1 stabilized TK1 expression via m6A modification and promoted NSCLC cell proliferation, migration, and invasion. In vivo experiments confirmed that TFAP4 knockdown suppressed tumor growth by downregulating IGF2BP1/TK1.

The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.

Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non-small-cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P-TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand-induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.

Advances in human neuroimaging has enabled us to study functional connections among various brain regions in pain states. Despite a wealth of studies at high anatomic resolution, the exact neural signals for the timing of pain remain little known. Identifying the onset of pain signals from distributed cortical circuits may reveal the temporal dynamics of pain responses and subsequently provide important feedback for closed-loop neuromodulation for pain.

In this study, an infection screening system was developed to detect patients suffering from infectious diseases. In addition, the system was also designed to deal with the variability in age and gender, which would affect the accuracy of the detection. Furthermore, to enable a low-cost, non-contact and embedded system, multiple vital signs from a medical radar were measured and all algorithms were implemented on a Field Programmable Gate Array, named PYNQ-Z1.

As pain consists of both sensory and affective components, its management by pharmaceutical agents remains difficult. Alternative forms of neuromodulation, such as electrical stimulation, have been studied in recent years as potential pain treatment options. Although electrical stimulation of the brain has shown promise, more research into stimulation frequency and targets is required to support its clinical applications. Here, we studied the effect that stimulation frequency has on pain modulation in the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC) in acute pain models in rats. We found that low-frequency stimulation in the prelimbic region of the PFC (PL-PFC) provides reduction of sensory and affective pain components. Meanwhile, high-frequency stimulation of the ACC, a region involved in processing pain affect, reduces pain aversive behaviors. Our results demonstrate that frequency-dependent neuromodulation of the PFC or ACC has the potential for pain modulation.

The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non-small cell lung cancer (NSCLC). Immunohistochemical staining of 104 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P-TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well-expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin-dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB-1, Claudin-1, ROCK1, MMP-9, and E-cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.

Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.

Long noncoding RNAs (lncRNAs) are critical players during cancer progression. Nevertheless, the effect of most lncRNAs in lung cancer (LC) remains unclear. We aimed to explore the role of LINC01342 in LC development through the microRNA-508-5p (miR-508-5p)/cysteine-rich secretory protein 3 (CRISP3) axis. LINC01342, miR-508-5p, and CRISP3 expression in clinical samples and cell lines were determined, and their correlations in LC were analyzed. The prognostic role of LINC01342 in LC patients was evaluated. LC cells were screened and, respectively, transfected to alter the expression of LINC01342, miR-508-5p, and CRISP3. Then, proliferation, migration, invasion, and apoptosis of transfected LC cells were determined, and the in vivo tumor growth was observed as well. Binding relationships between LINC01342 and miR-508-5p, and between miR-508-5p and CRISP3 were identified. LINC01342 and CRISP3 were upregulated and miR-508-5p was downregulated in LC tissues and cells. High LINC01342 expression indicated a poor prognosis of LC patients. The LINC01342/CRISP3 silencing or miR-508-5p elevation inhibited proliferation, migration, and invasion of LC cells and promoted LC cell apoptosis, and also suppressed the in vivo tumor growth. LINC01342 bound to miR-508-5p and miR-508-5p targeted CRISP3. LINC01342 plays a prognostic role in LC and LINC01342 silencing upregulates miR-508-5p to inhibit the progression of LC by reducing CRISP3.

Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.

Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known. However, the temporal processing of nociceptive inputs in the cortex remains little studied. Here, we took two approaches to examine how nociceptive inputs are processed by the S1 and ACC. We simultaneously recorded local field potentials in both regions, during the application of a brain-computer interface (BCI). First, we compared event related potentials in the S1 and ACC. Next, we used an algorithmic pain decoder enabled by machine-learning to detect the onset of pain which was used during the implementation of the BCI to automatically treat pain. We found that whereas mechanical pain triggered neural activity changes first in the S1, the S1 and ACC processed thermal pain with a reasonably similar time course. These results indicate that the temporal processing of nociceptive information in different regions of the cortex is likely important for the overall pain experience.