CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication.

C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.

Secure and Privacy-Preserving Intrusion Detection and Prevention in the Internet of Unmanned Aerial Vehicles.

In smart cities, unmanned aerial vehicles (UAVS) play a vital role in surveillance, monitoring, and data collection. However, the widespread integration of UAVs brings forth a pressing concern: security and privacy vulnerabilities. This study introduces the SP-IoUAV (Secure and Privacy Preserving Intrusion Detection and Prevention for UAVS) model, tailored specifically for the Internet of UAVs ecosystem. The challenge lies in safeguarding UAV operations and ensuring data confidentiality. Our model employs cutting-edge techniques, including federated learning, differential privacy, and secure multi-party computation. These fortify data confidentiality and enhance intrusion detection accuracy. Central to our approach is the integration of deep neural networks (DNNs) like the convolutional neural network-long short-term memory (CNN-LSTM) network, enabling real-time anomaly detection and precise threat identification. This empowers UAVs to make immediate decisions in dynamic environments. To proactively counteract security breaches, we have implemented a real-time decision mechanism triggering alerts and initiating automatic blacklisting. Furthermore, multi-factor authentication (MFA) strengthens access security for the intrusion detection system (IDS) database. The SP-IoUAV model not only establishes a comprehensive machine framework for safeguarding UAV operations but also advocates for secure and privacy-preserving machine learning in UAVS. Our model's effectiveness is validated using the CIC-IDS2017 dataset, and the comparative analysis showcases its superiority over previous approaches like FCL-SBL, RF-RSCV, and RBFNNs, boasting exceptional levels of accuracy (99.98%), precision (99.93%), recall (99.92%), and F-Score (99.92%).

Diagnosing of primary cutaneous amyloidosis using dermoscopy and reflectance confocal microscopy.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is apruritic and potentially disfiguring disorder; this disease is usually diagnosed clinically due to its common occurrence. However, for cases with atypical presentations or for those physicians not familiar with PCA, the diagnosis can be a challenge. OBJECTIVE: To observe the characteristics of PCA under dermoscopy and reflectance confocal microscopy (RCM) in order to gain experience and reference for clinicians to facilitate diagnosis. METHODS: The typical lesions of 110 patients with primary cutaneous amyloidosis were observed by dermoscopy and RCM, and scanning results were recorded. Thirty patients followed by complete excision for histopathological analysis. RESULTS: A total of 110 patients with clinically diagnosed PCA were enrolled. Forty-seven patients had lesions consistent with macular amyloidosis and 63 with lichen amyloidosus. The dermoscopic findings of PCA shared a common feature, each 'macule' was composed of a central hub pattern surrounded by brownish pigmentation, The pattern of the central hub could be brown, white, scar-like and structureless area. RCM features of total patients consisted of dermal papilla present cloud-like agglomerate which are high refractive index. CONCLUSIONS: Dermoscopy and reflectance confocal microscopy can be used in the diagnosis of PCA, which can provide a basis for doctors to diagnose.

lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis.

Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.

An analysis of clinical characteristics and postoperative complications in children craniopharyngioma.

OBJECTIVE: Children treated for craniopharyngioma (CP) experience significant morbidity. We aimed to investigate the clinical characteristics and postoperative complications of pediatric CP and to determine risk factors for complications to provide a theoretical basis for postoperative treatment. METHODS: In this retrospective analysis, we screened clinical data concerning children with CP who had undergone surgery at our hospital from December 2011 to June 2015. We statistically analyzed the relationship between age, sex, disease course, tumor location, extent of tumor resection, and neuroendocrine axis dysfunction. RESULTS: Of 240 patients (males, n = 144; females, n = 96; mean age, 8.33 ± 4.64 years), the main clinical presentations were headache (n = 151, 62.92%), vomiting (n = 84, 35%), vision changes (n = 101, 42.08%), polydipsia and polyuria (n = 47, 19.58%), and growth retardation (n = 42, 17.5%). Hypothalamic-pituitary dysfunction was the most common postoperative complication. There were 216 (90.00%) and 181 (75.42%) patients with pituitary-thyroid and pituitary-adrenal axis injuries, respectively. Being a prepubescent girl was a risk factor for impaired pituitary-thyroid and pituitary-adrenal axis function (P < 0.05). No correlation was found between sex (male), age, disease course, tumor location, extent of tumor resection, and impaired pituitary-thyroid and pituitary-adrenal axis function (P > 0.05). Pituitary-gonad axis injury was observed in 91 (37.92%) patients. Saddle and suprasellar region tumors were risk factors for impaired pituitary-gonad axis function (P < 0.05). No statistically significant correlation was found between sex, disease course, extent of resection, and impaired pituitary-gonad axis function (P > 0.05). CONCLUSIONS: Routine screening for complications during treatment is indicated for children with CP, to optimize the timing of interventions and reduce long-term morbidity.

Cadmium-induced hormesis effect in medicinal herbs improves the efficiency of safe utilization for low cadmium-contaminated farmland soil.

Compared to other soil remediation technologies, Cd-contaminated farmland soil with low cadmium accumulation (LCA) plant-based safe utilization is more catered to developing countries with food in high demand. Hormesis, which describes the fortification of plant growth performance by a low level of environmental stress, can be innovatively used to achieve increases in crop yield and plant functional components, thus amplifying the safe utilization efficiency of low Cd-contaminated soil by LCA plants. In the present study, the growth and physiological responses of Polygonatum sibiricum, a traditional Chinese medicinal herb, were investigated under laboratory conditions of gradient Cd dosage concentrations and times. As a result, the growth performance of P. sibiricum reached the peak of an inverse U-shaped curve of hormesis under e0 mg kg-1 and 9 months of Cd stress, with elevations in tuber biomass (medicinal part), plant height and polysaccharide content (medicinal components) of 143%, 25% and 90%, respectively. Meanwhile, trace Cd accumulation (0.41 mg kg-1) in the tuber guaranteed medicinal edible safety. In addition, Cd-induced hormesis in P. sibiricum was verified to be overcompensated by antioxidation systems. In conclusion, such 'win-win' results, including low Cd accumulation and enhancement of plant pharmaceutical value, provided medicinal herbs with a possibility for safe soil utilization.

Resection of Giant Tumor of Chest Wall under Cardiopulmonary Bypass after Neoadjuvant Chemoradiotherapy: A Case Report.

Osteosarcoma, one of the most common sources of bone malignant tumors, often occurs at the epiphysis, such as in the distal femoral and proximal tibia, but seldom occurs at the costa. Here, we present the case of a 15-year-old girl with giant osteosarcoma on the chest wall. Osteosarcoma is extremely malignant and has a high death rate. We surgically resected the osteosarcoma using cardiopulmonary bypass and administered neoadjuvant chemoradiotherapy.

[Research progress on chemical structures and pharmacological activities of Poria cocos polysaccharide and its derivatives].

Poria cocos is a both medicinal and edible Chinese herb variety, with the effects of diuretic, spleen-enhancing and tranquilizing. P. cocos polysaccharide(PCP) is one of the most important active substances of P. cocos. Pharmacological research shows that PCP has a variety of pharmacological activities such as regulating immunity, anti-inflammatory, anti-oxidation, antitumor, and liver protection, with a huge development and utilization value. By consulting the relevant literature, we systematically summarized the chemical structures and the research progress on pharmacological activities of PCP and its derivatives in recent years to explore the chemical compositions and activities of PCP thoroughly. In addition, the current problems were discussed in this article to provide reference for further exploration of the structure-activity relationship of PCP and its further development and utilization.

Quercetin inhibited mesangial cell proliferation of early diabetic nephropathy through the Hippo pathway.

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and the leading cause of end-stage renal disease. The proliferation of glomerular mesangial cells (MCs) is a common and prominent pathological change of DN, which takes place at the early stage. Quercetin, a bioflavonoid compound, possesses therapeutic efficacy in cardiovascular and kidney diseases via anti-tumour, anti-oxidation, anti-virus, and anti-proliferation effects. However, the mechanism of quercetin in the proliferation of glomerular MCs in early DN has not been reported. In the present study, we investigated the effect of quercetin on the proliferation of glomerular MCs in high glucose-induced mouse glomerular MCs and in db/db mice. On this basis, we tried to clarify the specific mechanisms underlying these effects. The in vitro results showed that the proliferation of glomerular MCs was induced by high glucose, and the Hippo pathway was highly inactivated in high glucose-cultured MCs. Decreased phosphorylation of MST1 and Lats1 promoted expression and nuclear translocation of Yes-associated protein (YAP) and subsequently increased the combination of YAP and TEA/ATS domain (TEAD), which promoted the expression of the downstream target gene such as cyclinE. Quercetin effectively inhibited the high glucose-induced MC proliferation and reactivated the Hippo pathway. In vivo, the proliferation of glomerular MCs was increased, renal function was decreased, and blood fasting glucose was elevated in db/db mice. Furthermore, the Hippo pathway was inactivated in the renal cortex of db/db mice. Eight-week treatment of quercetin retarded MC proliferation, alleviated the renal function, and reactivated Hippo pathway in the renal cortex of db/db mice at 16 weeks. Our previous study clarified that the Hippo pathway was involved in MC proliferation of DN. The results revealed that quercetin inhibited MC proliferation in high glucose-treated mouse glomerular MCs and in DN via reactivation of the Hippo pathway.

Clinical significance of 21-gene recurrence score assay for hormone receptor-positive, lymph node-negative breast cancer in early stage.

OBJECTIVE: To identify the relationship between clinical pathological characteristics and the recurrence score (RS) on a 21-gene expression assay in patients with hormone receptor-positive, node-negative breast cancer, as well as the effect of RS on adjuvant decision-making. METHODS: The retrospective study was conducted among luminal breast cancer patients admitted to Xijing Hospital between October 10, 2016, and September 14, 2018. Real-time PCR was used for 21-genome detection. Based on the calculated RS, participants were classified into low-risk, moderate-risk, and high-risk groups. Single-factor analysis and multiple logistic regression analysis were performed to explore independent predictors of high RS. Moreover, the effect of RS on adjuvant decision-making was studied. RESULTS: Two hundred twenty-two patients with luminal breast cancer, aged 48.3 ±â€¯9.66, were enrolled. Among them, 33.8% had low (13 ±â€¯3.34), 45.5% intermediate (23 ±â€¯3.65), and 20.7% high (37 ±â€¯3.44) RS. According to the single-factor analysis, age, tumor size, Ki-67, molecular subtype, CK5/6 expression, E-cadherin level, and histological grade were positively associated with high RS. Multiple logistic analyses showed that tumor size and histological grade were independent variables that might predict high RS in patients with hormone receptor-positive, node-negative breast cancer. For adjuvant decision-making, the proportion of adjuvant chemotherapy in the intermediate-/high-risk groups was higher than that in the low-risk group, P < 0.001. Compared with the data worldwide, the changes of treatment selection in the present study were similar to those in Japan (23.0% vs. 26%) and America (23.0% vs. 23.0%). Considering the pathology types, 14.3% of patients with invasive breast cancer with lower RS changed treatment recommendations, predominantly from chemo-endocrine to endocrine treatment alone, whereas the percentage in intermediate/high RS groups was 8.1%. CONCLUSIONS: Tumor size and histological grade were independent variables, predicting high risk in patients with hormone receptor-positive, node-negative breast cancer; 21-gene RS assessment was potentially a critical tool in guiding adjuvant decision-making in China.

Three cases of antibody-LGI1 limbic encephalitis and review of literature.

PURPOSE: Antibody-LGI1 limbic encephalitis (LGI1-Ab LE) is an anti-neuronal surface antigen-related autoimmune encephalitis. we report three cases of LGI1-Ab LE, describe the characteristics of clinical manifestation, course of evolution, imaging manifestation and treatment outcomes. METHODS: Data from patients diagnosed with LGI1-Ab LE in the Second Hospital, Hebei Medical University, from June 2016 to July 2017, were retrospectively collected and analyzed. We followed up the patients for 90 days. RESULTS: Two of the three patients were females, the average age of onset is 53 years old. Epilepsy is the most common clinical manifestations, and one of patients developed faciobrachial dystonic seizures (FBDS), which was recently described as a characteristic feature of LGI1-Ab LE. All patients had cognitive impairment in different degrees and abnormal signal of hippocampus in cranial MRI. All serum LGI1 antibodies were positive, whereas one LGI1 antibodies of CSF were negative. All patients accepted first-line immune therapy and had a good outcome. CONCLUSION: LGI1-Ab LE, which is an autoimmune disease, is rare clinically and mostly nonparaneoplastic. We suggest that LGI1-Ab LE be considered in any patient with acute or subacute onset, cognitive dysfunction , various types of seizures, accompanied by mental disorders and hyponatremia, MR showed the involvement of the limbic system. It is necessary to have LE-related antibodies tested. Early immunotherapy can significantly improve the patient's overall prognosis. At the same time, we should also pay attention to the possibility of potential tumors.

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4.

BACKGROUND: MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer. METHODS: We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance. RESULTS: The AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells. CONCLUSIONS: Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance.

Abnormal Connection of the Ductus Venosus to a Dilated Coronary Sinus Imaged by Prenatal Echocardiography: Case Report.

We describe a case of a fetus with an ectopic connection of the ductus venosus to a dilated coronary sinus that was diagnosed at ShengJing Hospital of China Medical University. A dilated coronary sinus was initially detected with prenatal echocardiography. Neither a persistent left superior vena cava nor an anomalous pulmonary venous connection was present. After comprehensive examination, we discovered that the ductus venosus had an abnormal course draining into the coronary sinus. The postnatal outcome of this fetus was good. Once a dilated coronary sinus is confirmed, further ultrasound evaluation should be performed to search for a potential cause.

Evaluation of normal fetal ductus venosus using B-flow imaging with spatiotemporal image correlation and traditional color Doppler echocardiography.

OBJECTIVE: To explore the feasibility of using four-dimensional echocardiography with B-flow and spatiotemporal image correlation (4DBF-STIC) imaging technology to detect fetal ductus venosus (DV), and establish the normal reference range for the ductus venosus diameter at 18-40 weeks gestation. METHODS: This was a prospective observational study to detect the DV in 354 normal fetuses at 18-40 weeks of gestation using color Doppler echocardiography (CDE) and 4DBF-STIC imaging. CDE was performed on an oblique transverse plane of the fetal abdomen, with scanning around the long-axis view of the aortic arch. The DV inlet was measured on a two-dimensional gray-scale image of the long-axis view of the DV. Offline analyses of all datasets were performed. RESULTS: The inlet diameter of the DV increased with increasing gestational age. There were no gender-related differences in the DV diameter. Data revealed that 4DBF-STIC was the best method to detect the DV between 18 and 29 weeks of gestation. The visualization rate was higher when scanning around the long-axis view of the aortic arch with CDE than when scanning around the oblique transverse plane throughout the gestational period. CONCLUSIONS: Scanning around the long-axis view of the aortic arch using CDE was best suited for detecting the DV in clinical practice, whereas 4DBF-STIC was a feasible and promising technology to detect the fetal DV before 29 weeks of gestation.

Unleashing the Neurotherapeutic Potential: The Crucial Role of miR-206-3p in Facilitating Hsp90aa1-Mediated Central Nervous System Injuries During Heat Stroke.

This study aims to explore the molecular mechanisms of miR-206-3p in regulating Hsp90aa1 and its involvement in the central nervous system (CNS) injury in heat stroke. Weighted gene co-expression network analysis (WGCNA) was performed on the GSE64778 dataset of heat stroke to identify module genes most closely associated with disease characteristics. Through the selection of key genes and predicting upstream miRNAs using RNAInter and miRWalk databases, the regulatory relationship between miR-206-3p and Hsp90aa1 was determined. Through in vitro experiments, various methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RIP experiment, and RNA pull-down experiment, were utilized to validate this regulatory relationship. Furthermore, functional experiments, including CCK-8 assay to test neuron cell viability and flow cytometry to assess neuron apoptosis levels, confirmed the role of miR-206-3p. Transmission electron microscopy, real-time quantitative PCR, DCFH-DA staining, and ATP assay were employed to verify neuronal mitochondrial damage. Heat stroke rat models were constructed, and mNSS scoring and cresyl violet staining were utilized to assess neural functional impairment. Biochemical experiments were conducted to evaluate inflammation, brain water content, and histopathological changes in brain tissue using H&E staining. TUNEL staining was applied to detect neuronal apoptosis in brain tissue. RT-qPCR and Western blot were performed to measure gene and protein expression levels, further validating the regulatory relationship in vivo. Bioinformatics analysis indicated that miR-206-3p regulation of Hsp90aa1 may be involved in CNS injury in heat stroke. In vivo, animal experiments demonstrated that miR-206-3p and Hsp90aa1 co-localized in neurons of the rat hippocampal CA3 region, and with prolonged heat stress, the expression of miR-206-3p gradually increased while the expression of Hsp90aa1 gradually decreased. Further in vitro cellular mechanism validation and functional experiments confirmed that miR-206-3p could inhibit neuronal cell viability and promote apoptosis and mitochondrial damage by targeting Hsp90aa1. In vivo, experiments confirmed that miR-206-3p promotes CNS injury in heat stroke. This study revealed the regulatory relationship between miR-206-3p and Hsp90aa1, suggesting that miR-206-3p could regulate the expression of Hsp90aa1, inhibit neuronal cell viability, and promote apoptosis, thereby contributing to CNS injury in heat stroke.

Identification of an 8 HPV-related RNA signature as a novel prognostic biomarker for squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (SCCHN) is a commonly detected cancer worldwide. Human papillomavirus (HPV) is emerging as an important risk factor affecting SCCHN prognosis. Therefore, identification of HPV status is essential for effective therapies in SCCHN. The aim of this study was to investigate the prognostic value of HPV-associated RNA biomarkers for SCCHN. The clinical data, survival data, and RNA-seq data of SCCHN were downloaded from The Cancer Genome Atlas database. Before the differential expression analysis, the heterogeneity between the 2 groups (HPV+ vs HPV-) of samples was analyzed using principal component analysis. The differentially expressed genes (DEGs) between HPV+ and HPV- SCCHN samples were analyzed using the R edgeR package. The Gene Ontology functional annotations, including biological process, molecular function and cellular component (CC), and Kyoto Encyclopedia of Genes And Genomes pathways enriched by the DEGs were analyzed using DAVID. The obtained matrix was analyzed by weighed gene coexpression network analysis. A total of 350 significant DEGs were identified through differential analysis, and these DEGs were significantly enriched in functions associated with keratinization, and the pathway of neuroactive ligand-receptor interaction. Moreover, 72 hub genes were identified through weighed gene coexpression network analysis. After the hub genes and DEGs were combined, we obtained 422 union genes, including 65 survival-associated genes. After regression analysis, a HPV-related prognostic model was established, which consisted of 8 genes, including Clorf105, CGA, CHRNA2, CRIP3, CTAG2, ENPP6, NEFH, and RNF212. The obtained regression model could be expressed by an equation as follows: risk score = 0.065 × Clorf105 + 0.012 × CGA + 0.01 × CHRNA2 + 0.047 × CRIP3 + 0.043 × CTAG2-0.034 × ENPP6 - 0.003 × NEFH - 0.068 × RNF212. CGA interacted with 3 drugs, and CHRNA2 interacted with 11 drugs. We have identified an 8 HPV-RNA signature associated with the prognosis of SCCHN patients. Such prognostic model might serve as possible candidate biomarker and therapeutic target for SCCHN.