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Purinergic signaling plays an important role in multiple pain processes. P2X3 receptor is considered to be a target in pain therapeutics, and A1 adenosine receptor signaling is essential for analgesia. However, it is still unclear whether there is a link between A1 adenosine receptors and P2X3 receptors in pain process. Herein, we show that the A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) suppressed α,β-methylene-ATP (α,β-meATP)-evoked inward currents mediated by P2X3 receptors in a concentration- dependent and voltage-independent manner in rat dorsal root ganglion (DRG) neurons. CPA shifted the concentration-response curve for α,β-meATP downwards, with a decrease of 38.44 ± 5.87% in the maximal current response of P2X3 receptors to α,β-meATP in the presence of CPA. The CPA-induced suppression was blocked by the A1 adenosine receptor antagonist KW-3902 and prevented by intracellular application of either the Gi/o-protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP. CPA also suppressed the membrane excitability of DRG neurons, with a significant decrease in the amplitude of the depolarization and the number of spikes induced by α,β-meATP in the presence of CPA. Finally, intraplantar pretreatment of CPA dose-dependently relieved α,β-meATP-induced nociceptive responses in rats through peripheral A1 adenosine receptors. These results suggested that CPA suppressed the functional activity of P2X3 receptors in rat primary sensory neurons via A1 adenosine receptor, intracellular Gi/o-proteins and cAMP signaling cascades, suggesting a novel peripheral mechanism underlying its analgesic effect.

Promoting the growth of the lithium battery sector has been a critical aspect of China’s energy policy in terms of achieving carbon neutrality. However, despite significant support on research and development (R&D) investments that have resulted in increasing size, the sector seems to be falling behind in technological areas. To guide future policies and understand proper ways of promoting R&D efficiency, we looked into the lithium battery industry of China. Specifically, data envelopment analysis (DEA) was used as the primary approach based on evidence from 22 listed lithium battery enterprises. The performance of the five leading players was compared with that of the industry as a whole. Results revealed little indication of a meaningful improvement in R&D efficiency throughout our sample from 2010 to 2019. However, during this period, a significant increase in R&D expenditure was witnessed. This finding was supported, as the results showed that the average technical efficiency of the 22 enterprises was 0.442, whereas the average pure technical efficiency was at 0.503, thus suggesting that they were suffering from decreasing returns to scale (DRS). In contrast, the performance of the five leading players seemed superior because their average efficiency scores were higher than the industry’s average. Moreover, they were experiencing increasing scale efficiency (IRS). We draw on these findings to suggest to policymakers that supporting technologically intensive sectors should be more than simply increasing investment scale; rather, it should also encompass assisting businesses in developing efficient managerial processes for R&D.

Gastric cancer (GC) is one of the most common malignancies worldwide. Most patients are diagnosed at advanced stages due to the subtle symptoms of earlier disease and the low rate of regular screening. Systemic therapies for GC, including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. For resectable GC, perioperative chemotherapy has become the standard treatment. Ongoing investigations are exploring the potential benefits of targeted therapy or immunotherapy in the perioperative or adjuvant setting. For metastatic disease, there have been notable advancements in immunotherapy and biomarker-directed therapies recently. Classification based on molecular biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), provides an opportunity to differentiate patients who may benefit from immunotherapy or targeted therapy. Molecular diagnostic techniques have facilitated the characterization of GC genetic profiles and the identification of new potential molecular targets. This review systematically summarizes the main research progress in systemic treatment for GC, discusses current individualized strategies and presents future perspectives.

Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy. Interestingly, global DNA hypomethylation was observed in placental DNA following exposure to DEHP at high concentrations. Bioinformatic analysis confirmed that DNA methylation affected genes related to neurological disorders, such as autism and dementia. These results suggest that maternal exposure to DEHP may predispose offspring to neurological diseases. Given the small sample size in this study, the potential role of DNA methylation as a biomarker to assess the risk of these diseases deserves further investigation.

Background Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac anomaly and can lead to abnormal electrical activity of the heart. The implant of a pacemaker in such patients is more complicated than conventional operations. This case report of an adult with ccTGA who had a leadless pacemaker implant will provide a reference for diagnosing and treating such patients. Case presentation A 50-year-old male patient was admitted to hospital having experienced intermittent vision loss for a month. An electrocardiogram and Holter monitoring showed intermittent third-degree atrioventricular block, and echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging confirmed a diagnosis of ccTGA. A leadless pacemaker was successfully implanted into the patient’s anatomical left ventricle, and the postoperative parameters were stable. Conclusion Implanting a leadless pacemaker into a patient with a rare anatomical and electrophysiological abnormality, such as ccTGA, is feasible and efficacious, but preoperative imaging evaluation is of considerable importance.

To determine the clinical characteristics and prognosis of primary tracheobronchial tumors (PTTs) in children, and to explore the most common tumor identification methods.The medical records of children with PTTs who were hospitalized at the Children's Hospital of Chongqing Medical University from January 1995 to January 2020 were reviewed retrospectively. The clinical features, imaging, treatments, and outcomes of these patients were statistically analyzed. Machine learning techniques such as Gaussian naïve Bayes, support vector machine (SVM) and decision tree models were used to identify mucoepidermoid carcinoma (ME).A total of 16 children were hospitalized with PTTs during the study period. This included 5 (31.3%) children with ME, 3 (18.8%) children with inflammatory myofibroblastic tumors (IMT), 2 children (12.5%) with sarcomas, 2 (12.5%) children with papillomatosis and 1 child (6.3%) each with carcinoid carcinoma, adenoid cystic carcinoma (ACC), hemangioma, and schwannoma, respectively. ME was the most common tumor type and amongst the 3 ME recognition methods, the SVM model showed the best performance. The main clinical symptoms of PPTs were cough (81.3%), breathlessness (50%), wheezing (43.8%), progressive dyspnea (37.5%), hemoptysis (37.5%), and fever (25%). Of the 16 patients, 7 were treated with surgery, 8 underwent bronchoscopic tumor resection, and 1 child died. Of the 11 other children, 3 experienced recurrence, and the last 8 remained disease-free. No deaths were observed during the follow-up period.PTT are very rare in children and the highest percentage of cases is due to ME. The SVM model was highly accurate in identifying ME. Chest CT and bronchoscopy can effectively diagnose PTTs. Surgery and bronchoscopic intervention can both achieve good clinical results and the prognosis of the 11 children that were followed up was good.

Acute lung injury (ALI) is characteristic of the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of pro-inflammatory leukocytes, and intractable hypoxemia, contributing to high mortality. Kindlin-2 is involved in the process of tumor- and wound healing-associated inflammation. However, the effects of kindlin-2 on lipopolysaccharide (LPS)-induced ALI and its mechanisms remain unknown. In this study, we found that the concentration of kindlin-2 was elevated in the lungs of ALI mice. The specific deletion of kindlin-2 by kindlin-2 siRNA attenuated the severity of lung injury, which was demonstrated by the reduced number of pro-inflammatory cells in bronchoalveolar lavage fluid and lung wet/dry weight ratio, and ameliorated pathologic changes in the lungs of ALI mice. Furthermore, kindlin-2 siRNA decreased the mRNA levels of pro-inflammatory factors (IL-1β, IL-6, and TNF-α) and the protein levels of pyroptosis-related proteins. In vitro studies confirmed that LPS + ATP promoted the expressions of pro-inflammatory factors and pyroptosis-related proteins, which was prevented by kindlin-2 siRNA pretreatment in endothelial cells (ECs). In conclusion, inhibition of kindlin-2 developes protective effects against LPS-induced ALI and the cytotoxicity of ECs, which may depend on blocking pyroptosis.