LHPP promotes the intracellular reactive oxygen species accumulation and sensitivity of gastric cancer to cisplatin via JNK and p38 MAPK pathways

Background. Cisplatin is the first-line chemotherapy drug for the treatment of gastric cancer (GC) patients. However, GC patients who are resistant to cisplatin often do not benefit from it. Therefore, finding a key molecule that affects cisplatin sensitivity is expected to enhance the efficacy of cisplatin in GC treatment. Methods. The human GC cell lines SGC-7901 and BGC-823 were used. The protein chip array was used to screen the cisplatin-resistance genes from the complete response and non-complete response GC patients’ tissues, then, the differential gene expression analysis, GO function annotation analysis, and KEGG pathway enrichment analysis were performed. The GC tissue chip in the GEO database was analyzed to screen the target gene. Flow cytometry, Hoechst 33342 staining assay, Western Blot, MTT, tumor sphere formation, cell cycle, and apoptosis assays were performed to explore the effect of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) on the apoptosis, stemness, and reactive oxygen species (ROS) accumulation of cisplatin-resistant GC cells treated with cisplatin. In vivo, the cisplatin-resistant GC cell lines transfected with pcDNA-LHPP or si-LHPP were injected subcutaneously into mice to construct GC subcutaneous xenograft GC models. Results. Based on protein chip array and bioinformatics analysis, it was found that LHPP is the core molecule in the cisplatin resistance regulatory network in GC, and its expression is down-regulated in GC cisplatin-resistant tissues and cells. In vitro and in vivo experimental results show that the up-regulated expression of LHPP is closely related to the increase in sensitivity of GC to cisplatin. Mechanically, we found that overexpression of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, promote cisplatininduced ROS accumulation, suppress stemness, and enhance the sensitivity of GC to cisplatin. Conclusions. Up-regulation of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, attenuate stemness, and enhance the accumulation of intracellular ROS, thereby promoting cisplatin-mediated GC cell apoptosis and enhancing cisplatin sensitivity

Fuzzy Combination of TOPSIS and RSR for Comprehensively Assessing the Quality of National Essential Public Health Services

BackgroundThe national essential public health services have been implemented since 2009 as a key initiative of the new round of China's healthcare reform. With the development of this service program, the allotted special funds and service items are increasing. Due to large number of indicators involved and wide coverage, it is imperative to explore a method that can assess the services scientifically, objectively and comprehensively.ObjectiveTo explore an appropriate method for comprehensively assessing the quality of national essential public health services, providing a basis for improving relevant policies and the quality of such services.MethodsBy use of multistage and purposive sampling, 24 community (township) health centers were selected from southern, central and northern Z Province from February to April 2019, and qualities of national essential public health services delivered by them in 2018 were comprehensively assessed using the technique for order of preference by similarity to ideal solution (TOPSIS) , rank-sum ratio (RSR) method, and fuzzy combination of TOPSIS and RSR method, respectively. With reference to the 2018 National Basic Public Health Service Project, 12 evaluation indicators were selected.ResultsAccording to the TOPSIS-based assessment, the top three community (township) health centers ranked by Ci value were A (0.917 4) , C (0.875 9) and G (0.787 9) , and the bottom three were I (0.414 2) , W (0.413 7) and N (0.407 7) . In accordance with the RSR method-based assessment, the top three community (township) health centers ranked by RSR value were A (0.890 6) , G (0.765 6) , and C (0.711 8) , and the bottom three were V (0.381 9) , W (0.362 8) , and K (0.357 6) . According to the fuzzy set theory, the top three community (township) health centers ranked by W1Ci+W2RSR values were A, C and G, and the bottom three were I, K and W in accordance with the "majority rule", which was basically consistent with the evaluation results of TOPSIS and RSR.ConclusionThe assessment results by TOPSIS, RSR, and fuzzy combination of these two and associated factors in this study are consistent with those of other studies. Either use of TOPSIS- or RSR-based quality assessment had limitations, but fuzzy combination of the two overcame these limitations, so the combination approach is worthy of promotion as an appropriate method for assessing the quality of essential public health services

The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo

AbstractSupranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo

Team-wise Effective Communication in Multi-Agent Reinforcement Learning

Effective communication is crucial for the success of multi-agent systems, as it promotes collaboration for attaining joint objectives and enhances competitive efforts towards individual goals. In the context of multi-agent reinforcement learning, determining “whom”, “how” and “what” to communicate are crucial factors for developing effective policies. Therefore, we propose TeamComm, a novel framework for multi-agent communication reinforcement learning. First, it introduces a dynamic team reasoning policy, allowing agents to dynamically form teams and adapt their communication partners based on task requirements and environment states in cooperative or competitive scenarios. Second, TeamComm utilizes heterogeneous communication channels consisting of intra- and inter-team to achieve diverse information flow. Lastly, TeamComm leverages the information bottleneck principle to optimize communication content, guiding agents to convey relevant and valuable information. Through experimental evaluations on three popular environments with seven different scenarios, we empirically demonstrate the superior performance of TeamComm compared to existing methods.</p

Identifying and analyzing novel epilepsy-related genes using random walk with restart algorithm.

As a pathological condition, epilepsy is caused by abnormal neuronal discharge in brain which will temporarily disrupt the cerebral functions. Epilepsy is a chronic disease which occurs in all ages and would seriously affect patients' personal lives. Thus, it is highly required to develop effective medicines or instruments to treat the disease. Identifying epilepsy-related genes is essential in order to understand and treat the disease because the corresponding proteins encoded by the epilepsy-related genes are candidates of the potential drug targets. In this study, a pioneering computational workflow was proposed to predict novel epilepsy-related genes using the random walk with restart (RWR) algorithm. As reported in the literature RWR algorithm often produces a number of false positive genes, and in this study a permutation test and functional association tests were implemented to filter the genes identified by RWR algorithm, which greatly reduce the number of suspected genes and result in only thirty-three novel epilepsy genes. Finally, these novel genes were analyzed based upon some recently published literatures. Our findings implicate that all novel genes were closely related to epilepsy. It is believed that the proposed workflow can also be applied to identify genes related to other diseases and deepen our understanding of the mechanisms of these diseases

MRI in the differential diagnosis of primary architectural distortion detected by mammography

PURPOSEWe aimed to evaluate the diagnostic accuracy of a combination of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) values in lesions that manifest with architectural distortion (AD) on mammography.METHODSAll full-field digital mammography (FFDM) images obtained between August 2010 and January 2013 were reviewed retrospectively, and 57 lesions showing AD were included in the study. Two independent radiologists reviewed all mammograms and MRI data and recorded lesion characteristics according to the BI-RADS lexicon. The gold standard was histopathologic results from biopsies or surgical excisions and results of the two-year follow-up. Receiver operating characteristic curve analysis was carried out to define the most effective threshold ADC value to differentiate malignant from benign breast lesions. We investigated the sensitivity and specificity of FFDM, DCE-MRI, FFDM+DCE-MRI, and DCE-MRI+ADC.RESULTSOf the 57 lesions analyzed, 28 were malignant and 29 were benign. The most effective threshold for the normalized ADC (nADC) was 0.61 with 93.1% sensitivity and 75.0% specificity. The sensitivity and specificity of DCE-MRI combined with nADC was 92.9% and 79.3%, respectively. DCE-MRI combined with nADC showed the highest specificity and equal sensitivity compared with other modalities, independent of the presentation of calcification.CONCLUSIONDCE-MRI combined with nADC values was more reliable than mammography in differentiating the nature of disease manifesting as primary AD on mammography

O-PRESS: Boosting OCT axial resolution with Prior guidance, Recurrence, and Equivariant Self-Supervision

Optical coherence tomography (OCT) is a noninvasive technology that enables real-time imaging of tissue microanatomies. The axial resolution of OCT is intrinsically constrained by the spectral bandwidth of the employed light source while maintaining a fixed center wavelength for a specific application. Physically extending this bandwidth faces strong limitations and requires a substantial cost. We present a novel computational approach, called as O-PRESS, for boosting the axial resolution of OCT with Prior Guidance, a Recurrent mechanism, and Equivariant Self-Supervision. Diverging from conventional superresolution methods that rely on physical models or data-driven techniques, our method seamlessly integrates OCT modeling and deep learning, enabling us to achieve real-time axial-resolution enhancement exclusively from measurements without a need for paired images. Our approach solves two primary tasks of resolution enhancement and noise reduction with one treatment. Both tasks are executed in a self-supervised manner, with equivariance imaging and free space priors guiding their respective processes. Experimental evaluations, encompassing both quantitative metrics and visual assessments, consistently verify the efficacy and superiority of our approach, which exhibits performance on par with fully supervised methods. Importantly, the robustness of our model is affirmed, showcasing its dual capability to enhance axial resolution while concurrently improving the signal-to-noise ratio