Secure multi-path routing for Internet of Things based on trust evaluation.

In the realm of the Internet of Things (IoT), ensuring the security of communication links and evaluating the safety of nodes within these links remains a significant challenge. The continuous threat of anomalous links, harboring malicious switch nodes, poses risks to data transmission between edge nodes and between edge nodes and cloud data centers. To address this critical issue, we propose a novel trust evaluation based secure multi-path routing (TESM) approach for IoT. Leveraging the software-defined networking (SDN) architecture in the data transmission process between edge nodes, TESM incorporates a controller comprising a security verification module, a multi-path routing module, and an anomaly handling module. The security verification module ensures the ongoing security validation of data packets, deriving trust scores for nodes. Subsequently, the multi-path routing module employs multi-objective reinforcement learning to dynamically generate secure multiple paths based on node trust scores. The anomaly handling module is tasked with handling malicious switch nodes and anomalous paths. Our proposed solution is validated through simulation using the Ryu controller and P4 switches in an SDN environment constructed with Mininet. The results affirm that TESM excels in achieving secure data forwarding, malicious node localization, and the secure selection and updating of transmission paths. Notably, TESM introduces a minimal 12.4% additional forwarding delay and a 5.46% throughput loss compared to traditional networks, establishing itself as a lightweight yet robust IoT security defense solution.

Glucose-independent insulin and glucagon secreted from ventral pancreas sharing a similar pattern in healthy adult rat.

Elevated blood glucose concentration due to food intake will trigger insulin secretion from the dorsal pancreas has been extensively studied. This increased intracellular insulin level can stimulate glucagon release from intra-islets. However, the interaction between glucagon and insulin under a fasting state is unknown. To explore the relationship, we partially removed the ventral and dorsal pancreas on wild-type adult rats. The glucose tolerance test was conducted to measure influence of the surgery on the integrity function of the pancreas. The fasting insulin/glucagon level before and after surgery were measured by the ELISA kit. The statistical analyses indicated that the ventral removal of the pancreas had higher fasting glucose than that of dorsal removal. And only the ventral removal group showed significantly increased basal insulin and basal glucagon levels. Our findings showed differential role of the ventral pancreas in response to a glucose-free stimulus and also provided the possible in vitro target for developing the anti-hyperglycemic drugs.

Circular RNA circ_0005835 promotes promoted neural stem cells proliferation and differentiate to neuron and inhibits inflammatory cytokines levels through miR-576-3p in Alzheimer's disease.

Alzheimer's disease (AD) is the most frequent neurodegenerative disease and it is difficult to have an effective and simple method for AD early diagnosis. CircRNAs (circular RNAs) are novel discovered non-coding endogenous RNAs that affect cell apoptosis, differentiation, growth, metabolism, and metastasis. Recently, it has reported that circ_0005835 was one upregulated circRNA in the AD patients. However, the function role of circ_0005835 remains unknown. In our study, we found that circ_0005835 was upregulated in AD patients and cell models. Knockdown of circ_0005835 could downregulate neuroinflammation in BV2 cells. Moreover, knockdown of circ_0005835 promoted neural stem cells (NSC) proliferation and differentiate to neuron. These data mean that circ_0005835 plays important role in the development of AD. The miR-576-3p expression in serum was downregulated in the AD group compared to the health control group. Consistently, the level of circ_0005835 was overexpressed in the Aß-treated in both SH-SY5Y and BV2 cells. Moreover, the expression of miR-576-3p was negatively correlated with circ_0005835 in AD patients. In addition, we performed the rescued experiments to show that knockdown of circ_0005835 could downregulate neuroinflammation through sponging miR-576-3p in BV2 cells. Inhibition of circ_0005835 promoted NSC proliferation and differentiate to neuron via sponging miR-576-3p. These data suggested that circ_0005835 promoted AD development through regulating miR-576-3p expression.

Prognostic value of preoperative modified Glasgow prognostic score in surgical non-small cell lung cancer: A meta-analysis.

Background and purpose: The predictive role of modified Glasgow prognostic score (mGPS) for long-term survival in several types of cancers has been well manifested. We supposed that preoperative mGPS might also be associated with long-term survival of operated non-small cell lung cancer (NSCLC) patients. The aim of this meta-analysis was to identify the prognostic value of preoperative mGPS in surgical NSCLC patients. Methods: The PubMed, Web of Science, EMBASE and CNKI databases were searched for relevant studies up to November 7, 2022. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. Results: A total of 3,803 patients from 11 studies were enrolled and analyzed. The combined results demonstrated elevated preoperative mGPS was significantly related to poorer OS (HR = 2.11, 95% CI: 1.83-2.44, P < 0.001) and DFS (HR = 1.70, 95% CI: 1.42-2.03, P < 0.001). Subgroup analysis for the OS further identified the predictive role of elevated preoperative mGPS for worse OS in NSCLC. Conclusion: Preoperative mGPS was significantly associated with prognosis in NSCLC and patients with elevated preoperative mGPS experienced poorer long-term survival.

A Novel Application of Non-Negative Matrix Factorization to the Prediction of the Health Status of Undocumented Immigrants.

Introduction: Undocumented immigrants (UIs) in the United States are less likely to be able to afford health insurance. As a result, UIs often lack family doctors and are rarely involved in annual screening programs, which makes estimating their health status remarkably challenging. This is especially true if the laboratory results from limited screening programs fail to provide sufficient clinical information. Methods: To address this issue, we have developed a machine learning model based on the non-negative matrix factorization technique. The data set we used for model training and testing was obtained from the 2004 cost-free hepatitis B screening program at the Omni Health Center located in Plano, Texas. Total 300 people were involved, with 199 identified as UIs. Results: People in the UIs group have higher cholesterol (219.6 mg/dL, p=0.038) and triglycerides (173.2 mg/dL, p=0.03) level. They also have a lower hepatitis B vaccination rate (38%, p=0.0247). No significant difference in hepatitis B(+) was found (p=0.8823). Using 16 individual clinical measurements as training features, our newly developed model has a 67.56% accuracy in predicting the ratio of cholesterol to high-density lipoprotein; in addition, this newly developed model performs 9.1% better than a comparable multiclass logistic regression model. Conclusions: Elderly UIs have poorer health status compared with permanent residents and citizens in the United States. Our newly developed machine learning model demonstrates a powerful support tool for designing health intervention programs that target UIs in the United States.

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy.

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo. Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway.

The present study analyzed the change of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) expression in focal cerebral ischemia-reperfusion injury model. A sample of 36 Sprague-Dawley rats were randomly selected and divided into sham operation group (group S), control group (group C) and Chrysanthemum ester group (NF-κB inhibitor, group CE), each group consisted of 12 rats. The rat model of focal cerebral ischemia-reperfusion was established. The physiological indexes and neurological severity score of rats was recorded by a double-blind method. The cerebral infarction area was evaluated by triphenyltetrazole oxide (TTC) staining on brain slices. Apoptosis was evaluated by TUNEL staining. Semi-quantitative PCR and western blot analysis was used to measure the expression of TLR4 and NF-κB. The neurological severity score of rats in group C and CE were found to be significantly lower than group S (P<0.01). The TTC staining results showed that group C and CE had different levels of cerebral infarction but the area of infarction in group CE was significantly lower than group C (P<0.01). In addition, the number of TUNEL positive cells in group CE was significantly lower than group C (P<0.01). Semi-quantitative PCR and westernblot analysis results showed that the expression of NF-κB and TLR4 of group S was significantly lower than that of group C and group CE (P<0.01), the relative expression of NF-κB and TLR4 of group CE was significantly lower than that of group C (P<0.01). Moreover, the expression of NF-κB p65/p50 of group CE and group C was significantly higher than that of group S (P<0.01). This study concludes that the focal cerebral ischemia-reperfusion injury in rats can cause brain damage and cell apoptosis. This effect might be associated to the increased expression of NF-κB and TLR4, and the activation of TLR4/NF-κB signaling pathway.