EPIC: Emotion Perception by Spatio-Temporal Interaction Context of Gait.

Recently, psychophysiological computing has received considerable attention. Due to easy acquisition at a distance and less conscious initiation, gait-based emotion recognition is considered as a valuable research branch in the field of psychophysiological computing. However, most existing methods rarely explore the spatio-temporal context of gait, which limits the ability to capture the higher-order relationship between emotion and gait. In this paper, we utilize a range of research, including psychophysiological computing and artificial intelligence, to propose an integrated emotion perception framework called EPIC, which can find novel joint topology and generate thousands of synthetic gaits by spatio-temporal interaction context. First, we analyze the joint coupling among non-adjacent joints by calculating Phase Lag Index (PLI), which can discover the latent connection among body joints. Second, to synthesize more sophisticated and accurate gait sequences, we explore the effect of spatio-temporal constraints, and propose a new loss function that utilizes the Dynamic Time Warping (DTW) algorithm and pseudo-velocity curve to constrain the output of Gated Recurrent Units (GRU). Finally, Spatial Temporal Graph Convolution Networks (ST-GCN) is used to classify emotions using the generation and the real data. Experimental results demonstrate our approach achieves the accuracy of 89.66%, and outperforms the state-of-the-art methods on Emotion-Gait dataset.

IFI6 Downregulation Reverses Oxaliplatin Resistance of Colorectal Cancer Cells by Activating the ROS-Induced p38MAPK Signaling Pathway.

Oxaliplatin (OXA) is a usual chemotherapeutic agent applied in the colorectal cancer (CRC) clinical treatment. Interferon-alpha inducible protein 6 (IFI6) has been proved to promote proliferation and suppress apoptosis in several tumor cells, while the impacts of IFI6 on OXA resistance in CRC still need exploration. HCT116 and SW620 cells were used as the parental to obtain OXA-resistant cells. The influence of IFI6 on OXA sensitivity, cell proliferation and apoptosis were evaluated by overexpression or knockdown IFI6 in cells. In this work, we found that the level of IFI6 was significantly enhanced in HCT116/OXA and SW620/OXA cells as compared to the parental cells. Overexpression of IFI6 decreased the sensitivity of HCT116 and SW620 cells to OXA. However, knockdown of IFI6 enhanced the sensitivity of HCT116/OXA and SW620/OXA cells to OXA. And upregulated IFI6 promoted the proliferation and repressed apoptosis in HCT116 cells, while suppressed IFI6 markedly reduced proliferation and increased apoptosis in HCT116/OXA cells. Additionally, IFI6 suppressed the phosphorylation level of p38, and silenced IFI6 enhanced it. The addition of the p38 kinase inhibitor, SB203580, alleviated the decreased cell proliferation and increased apoptosis in HCT116/OXA cells. Suppressed IFI6 enhanced the reactive oxygen species (ROS) level in HCT116/OXA cells, and blockade of ROS with N-acetyl-L-cysteine (NAC) decreased the enhancement level of ROS and the phosphorylation level of the p38, which was induced by IFI6 down-regulation. We, therefore, implied that suppressed IFI6 reverses OXA-resistance of CRC cells via promoting the ROS-induced p38 mitogen-activated protein kinase (MAPK) signaling pathway.

Identification of volatile organic compounds in muscle tissues of different species based on Headspace-Gas-Chromatography Ion-Mobility spectrometry.

Species identification of unknown biological samples is crucial for forensic applications, especially in cases of explosion, disaster accidents, and body mutilation after murdering, as well as poaching, illegal trade in endangered animals, and meat food fraud. In this study, we identified 60 volatile organic compounds (VOCs) in fresh skeletal muscle tissues of seven different animal species (cattle, sheep, pigs, rabbits, rats, chickens and carp) and a human dead body by headspace-gas-chromatography ion-mobility spectrometry (HS-GC-IMS), and compared their differences by retention time, drift time and molecular weight. The results showed that these VOCs formed different gallery plot fingerprints in the skeletal muscle tissues of the human dead body and seven animal species. Principal component analysis (PCA) showed significantly different fingerprints between these species, and these fingerprints maintained good stability between the species and within the same species. Some VOCs have high species specificity, while VOCs of human fresh muscle tissues from different individual sources have little difference, demonstrating that all tested muscle tissue samples could be distinguished based on different VOCs. HS-GC-IMS has proved to be a rapid, high-throughput, highly sensitive and specific species identification method, which can be used for forensic species identification in criminal cases and disaster accidents, as well as detection in the field of food safety, such as meat fraud and adulteration.

Obese Individuals With and Without Phlegm-Dampness Constitution Show Different Gut Microbial Composition Associated With Risk of Metabolic Disorders.

Background: Obesity is conventionally considered a risk factor for multiple metabolic diseases, such as dyslipidemia, type 2 diabetes, hypertension, and cardiovascular disease (CVD). However, not every obese patient will progress to metabolic disease. Phlegm-dampness constitution (PDC), one of the nine TCM constitutions, is considered a high-risk factor for obesity and its complications. Alterations in the gut microbiota have been shown to drive the development and progression of obesity and metabolic disease, however, key microbial changes in obese patients with PDC have a higher risk for metabolic disorders remain elusive. Methods: We carried out fecal 16S rRNA gene sequencing in the present study, including 30 obese subjects with PDC (PDC), 30 individuals without PDC (non-PDC), and 30 healthy controls with balanced constitution (BC). Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt. Results: Obese individuals with PDC had higher BMI, waist circumference, hip circumference, and altered composition of their gut microbiota compared to non-PDC obese individuals. At the phylum level, the gut microbiota was characterized by increased abundance of Bacteroidetes and decreased levels of Firmicutes and Firmicutes/Bacteroidetes ratio. At the genus level, Faecalibacterium, producing short-chain fatty acid, achieving anti-inflammatory effects and strengthening intestinal barrier functions, was depleted in the PDC group, instead, Prevotella was enriched. Most PDC-associated bacteria had a stronger correlation with clinical indicators of metabolic disorders rather than more severe obesity. The PICRUSt analysis demonstrated 70 significantly different microbiome community functions between the two groups, which were mainly involved in carbohydrate and amino acid metabolism, such as promoting Arachidonic acid metabolism, mineral absorption, and Lipopolysaccharide biosynthesis, reducing Arginine and proline metabolism, flavone and flavonol biosynthesis, Glycolysis/Gluconeogenesis, and primary bile acid biosynthesis. Furthermore, a disease classifier based on microbiota was constructed to accurately discriminate PDC individuals from all obese people. Conclusion: Our study shows that obese individuals with PDC can be distinguished from non-PDC obese individuals based on gut microbial characteristics. The composition of the gut microbiome altered in obese with PDC may be responsible for their high risk of metabolic diseases.

Hsa_circ_0005100 regulates tumorigenicity of colorectal carcinoma via miR-145-5p/MACC1 axis.

BACKGROUND: Circular RNAs (circRNAs) are a kind of RNA molecules involved in the regulation of cancer progression, including colorectal carcinoma (CRC); nevertheless, their regulation mode is blurry. In the present work, we attempted to reveal the characteristics of hsa_hsa_circ_0005100 in CRC. METHODS: Differential expressions of hsa_circ_0005100, FMN2 mRNA, microRNA-145-5p (miR-145-5p), and MACC1 were indicated by qRT-PCR and Western blot. The capacities of cell growth and motility were validated by the MTT assay, flow cytometry assay, EdU assay, colony formation assay, and transwell assay. Moreover, the targeted relationship of miR-145-5p and hsa_circ_0005100 or MACC1 was distinguished by dual-luciferase reporter assay. The animal experiment was implemented to confirm the influence of hsa_circ_0005100 on tumorigenesis in vivo. RESULTS: Hsa_circ_0005100 and MACC1 expression levels were increased, but miR-145-5p expression level was diminished in CRC. Hsa_circ_0005100 knockdown repressed cell proliferation, cell cycle, migration, and invasion, while expedited cell apoptosis in CRC cells. Furthermore, miR-145-5p was disclosed to block CRC via overturning MACC1. Hsa_circ_0005100 targeted miR-145-5p to modulate MACC1. Additionally, hsa_circ_0005100 knockdown also attenuated tumorigenesis in vivo. CONCLUSION: Hsa_circ_0005100 was a vital regulator in the development of CRC by miR-145-5p/MACC1 axis, which deepened the understanding of CRC pathogenesis from circRNA insights.

Hua-Tan-Sheng-Jing Decoction Treats Obesity With Oligoasthenozoospermia by Up-Regulating the PI3K-AKT and Down-Regulating the JNK MAPK Signaling Pathways: At the Crossroad of Obesity and Oligoasthenozoospermia.

Background: Oligoasthenozoospermia is the leading cause of male infertility, seriously affecting men's health and increasing the societal medical burden. In recent years, obesity-related oligoasthenozoospermia has attracted increased attention from researchers to find a cure. This study aimed to evaluate the efficacy of Hua-Tan-Sheng-Jing decoction (HTSJD) in treating obesity with oligoasthenozoospermia, determine its active ingredients and identify its mechanism of action. Methods: The ingredients of HTSJD were determined by combining the ultra-performance liquid chromatography with mass spectrometry (UPLC-MS/MS) and systems pharmacology approach. The common pathogenesis of obesity and oligoasthenozoospermia and the potential mechanism of HTSJD against obesity with oligoasthenozoospermia were obtained through target fishing, network construction, and enrichment analyses. Further, molecular docking of the key ingredients with the upstream receptors of the key signaling pathways of the potential mechanism was used to predict their affinity. Finally, high-fat-induced obesity with oligoasthenozoospermia rat model was constructed to determine the effects of HTSJD on semen concentration, sperm motility, body weight, and serum lipid metabolism. The key proteins were validated by immunohistochemistry (IHC). Results: A total of 70 effective components and 847 potential targets of HTSJD (H targets) were identified, of which 743 were common targets related to obesity and oligoasthenozoospermia (O-O targets) mainly enriched in the pathways related to inflammation, oxidative stress and hormone regulation. Finally, 143 common targets (H-O-O targets) for HTSJD against obesity with oligoasthenozoospermia were obtained. Combining the hub genes and the results of Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of H-O-O targets, PI3K-AKT and MAPK signaling pathways were identified as the key pathways. Molecular docking results showed that Diosgenin, Kaempferol, Quercetin, Hederagenin, Isorhamnetin may act on the related pathways by docking EGFR, IGF1R and INSR. The animal-based in vivo experiments confirmed that HTSJD improves the sperm quality of high-fat diet-fed rats by reducing their body weight and blood lipid levels, influencing the PI3K-AKT and MAPK signaling pathways and altering the corresponding protein expressions. Conclusion: HTSJD treats obesity with oligoasthenozoospermia by up-regulating the PI3K-AKT signaling pathway and down-regulating the MAPK signaling pathway, which are at the crossroad of obesity and oligoasthenozoospermia.

LncRNA HOXC-AS3 overexpression inhibits TGF-ß2-induced colorectal cancer cell migration and invasion by sponging miR-1269.

OBJECTIVE: Long non-coding RNA (lncRNA) HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown. METHODS: The expression of HOXC-AS3 and TGF-ß2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-ß2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-ß2 in regulating CRC cell invasion and migration. RESULTS: HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-ß2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-ß2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-ß2, while the expression of HOXC-AS3 was not affected by TGF-ß2. Transwell migration and invasion assay showed that overexpression of TGF-ß2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-ß2. MiR-1269 increased the expression of TGF-ß2. HOXC-AS3 directly interacted with miR-1269 in CRC cells. CONCLUSIONS: Upregulation of HOXC-AS3 inhibited TGF-ß2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.

Development and verification of a microsatellite instability-related risk signature for predicting survival and therapy effectiveness in gastric cancer.

Background: Gastric cancer (GC) is one of is one of the most common malignancy among digestive system cancers worldwide. Increasing evidence has revealed that microsatellite instability (MSI) status can affect the survival in various cancers. However, the role of MSI status in GC remains uncertain. Methods: The RNA-seq and clinicopathological features and mutation data of GC was obtained from The Cancer Genome Atlas (TCGA). Different bioinformatic and statistical methods were combined to construct a robust MSI-related gene signature for prognosis. Gene set enrichment analysis was conducted to explore Kyoto Encyclopedia of Genes and Genomes pathways associated with the MSI-related risk signature. Moreover, Kaplan-Meier (K-M) survival and receiver operating characteristic (ROC) analyses evaluate that the MSI-related risk signature. Immune-associated miRNAs were identified using immune scores calculated by the ssGSEA. In addition, 'pRRophetic' R package was used to assess the chemotherapeutic response by the GDSC website. Results: We firstly analyzed the influence of MSI status to GC survival based on the data from the TCGA database. GC patients in the TCGA database were divided into MSI-H and MSI-L/MSS groups. We counted the survival conditions of GC patients in these two groups. In addition, we also calculated the difference of TMB between these two groups and found that MSI-H group had a relatively high survival rate. Next, we identified 99 highly mutated genes in MSI-H group and constructed a MSI-related risk signature based on 10 robust genes for predicting the overall survival (OS) of GC patients. Moreover, analyses indicated that the MSI-related risk signature can accurately predict 1-, 3- and 5-year OS of GC patients. Furthermore, enrichment analysis suggested that genes between the high- and low-risk groups mainly involved in mutation and DNA repair related pathways. Finally, we also found that the MSI-related risk signature can affect the TME immune cell infiltration in GC and can be used to predict the clinical response to immunotherapy. Conclusions: In the present study, we develop a MSI-related risk signature for predicting the survival and therapy of GC, which may contribute to the clinical treatment of GC.

Neonatal sudden death caused by a novel heterozygous mutation in SLC25A20 gene: A case report and brief literature review.

Carnitine-acylcarnitine translocase deficiency (CACTD) is a rare and life-threatening autosomal recessive disorder of fatty acid ß-oxidation (FAO). Most patients with CACTD develop severe metabolic decompensation which deteriorates progressively and rapidly, causing death in infancy or childhood. As CACTD in some patients is asymptomatic or only with some nonspecific symptoms, the diagnosis is easy to be ignored, resulting in sudden death, which often triggers medical disputes. Herein, we report a case of neonatal sudden death with CACTD. The neonate showed a series of severe metabolic crisis, deteriorated rapidly and eventually died 3 days after delivery. Tandem mass spectrometry (MS-MS) screening of dry blood spots before death showed that the level of long-chain acylcarnitines, especially C12-C18 acylcarnitine, was increased significantly, and therefore a diagnosis of inherited metabolic disease (IMD) was suspected. Autopsy and histopathological results demonstrated that there were diffuse vacuoles in the heart and liver of the deceased. Mutation analysis revealed that the patient was a compound heterozygote with c.199-10 T > G and a novel c.1A > T mutation in the SLC25A20 gene. Pathological changes such as heart failure, arrhythmia and cardiac arrest related to mitochondrial FAO disorders are the direct cause of death, while gene mutation is the underlying cause of death.

The analgesic activities of total alkaloids of the ethnic medicine Cynanchum komarovii Al. Iljinski.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. AIM OF THE STUDY: To clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. MATERIALS AND METHODS: TACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. RESULTS: Acute toxicity experiments showed that the LD50 of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. CONCLUSION: TACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators.

MicroRNA-133a-3p inhibits cell proliferation, migration and invasion in colorectal cancer by targeting AQP1.

Recently, miR-133a-3p has been identified as a marker for human colorectal cancer (CRC) and the association between miR-133a-3p and aquaporin 1 (AQP1) has been described in endothelial cells. However, the regulatory functions of the miR-133a-3p/AQP1 axis remain unclear in CRC. The present study analyzed the expression of miR-133a-3p and AQP1 in CRC tissues (n=56) and cell lines using reverse transcription-quantitative PCR and western blot analysis. The χ2 test was used to assess the associations between miR-133a-3p/AQP1 and clinicopathological features of patients with CRC. Next, the functional role of miR-133a-3p/AQP1 in CRC was evaluated in vitro by performing Cell Counting Kit-8 and Transwell assays. Moreover, the online software tool TargetScan7.1 was used to predict AQP1 as the target gene of miR-133a-3p, followed by validation using a luciferase reporter assay. The results showed that miR-133a-3p was significantly downregulated, while AQP1 was upregulated in CRC tissues and cell lines compared with corresponding controls. Clinically, it was demonstrated that miR-133a-3p/AQP1 expression was significantly associated with tumor TNM stage (P=0.020). Functional experiments indicated that miR-133a-3p-overexpression remarkably suppressed, while knockdown promoted, cell proliferation, migration and invasion in CRC cells. Mechanically, AQP1 was identified and validated as a target gene of miR-133a-3p in CRC cells. The expression level of AQP1 mRNA was not correlated with miR-133a-3p expression in CRC tissues. Furthermore, AQP1-knockdown induced, while overexpression reversed, the suppressive effects of miR-133a-3p on CRC cells. Taken together, these findings suggested that miR-133a-3p might be a tumor suppressor by suppressing cell proliferation, migration and invasion via targeting AQP1.

Novel gain-of-function mutation of TRPC6 Q134P contributes to late onset focal segmental glomerulosclerosis in a Chinese pedigree.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS, OMIM®#603 965) is an overriding cause that leads to end-stage renal disease (ESRD). As a member of TRP superfamily, mutations of TRPC6 gene are closely linked to FSGS. By now, 20 missense mutations have been reported, among them, nine gain-of-function (GOF), and five loss-of-function (LOF) mutations have been recognized according to the effect on TRPC6 channel activity. Systematic investigations of functional mutations will provide valuable evidences for understanding the pathophysiology of TRPC6 involved in FSGS. The aim of this study is to investigate the pathogenicity of a novel TRPC6 mutation p.Q134P in FSGS. METHODS: High-throughput sequencing was performed to analyse 436 genes which are associated with hereditary kidney diseases in a Chinese pedigree. Then we constructed TRPC6 expression plasmids of wide type and variant. Immunofluorescence, cell-surface biotinylation assays and electrophysiology were used to analyse the localization, cell surface expression, and calcium transport activity of TRPC6. RESULTS: A novel variant c.401A>C (p.Q134P) in exon 2 of TRPC6 gene was found. There was no significant difference between the expression levels of p.Q134P mutant and WT TRPC6 protein in the whole cell lysate and cell-surface fraction. Q134P mutant-bearing TRPC6 elicited much higher Ca+ current amplitude than WT. CONCLUSION: We identified a novel GOF mutation p.Q134P of TRPC6 which contributed to late-onset FSGS. Our study expands the mutational spectrum of TRPC6 associated with FSGS and furtherly supports the hypothesis of calcium dose-response dependency that a moderate increased calcium influx elicited a mild FSGS phenotype.

LncRNA FEZF1-AS1 promotes colorectal cancer progression through regulating the miR-363-3p/PRRX1 pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in the development of many cancers, including colorectal cancer (CRC). FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) is a key lncRNA in the regulation of CRC progression, but its potential molecular mechanisms need to be further explored. OBJECTIVES: To investigate the mechanism of lncRNA FEZF1-AS1 in the progression of CRC. MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure FEZF1-AS1 and miR-363-3p expression. Cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 (CCK-8) and transwell assays. Protein expression of epithelial-mesenchymal transformation (EMT)-related markers and paired-related homeobox 1 (PRRX1) were determined using western blot analysis. The interactions among FEZF1-AS1, miR-363-3p and PRRX1 were verified with dual-luciferase reporter assay. A xenograft model was constructed in vivo to confirm the role of FEZF1-AS1 in CRC tumor growth. RESULTS: We demonstrated that FEZF1-AS1 expression was upregulated in CRC, and its silencing reduced CRC cell proliferation, migration, invasion, and EMT. MiR-363-3p could be inhibited by FEZF1-AS1, which inhibitor could reverse the suppressive effect of FEZF1-AS1 silencing on CRC progression. Paired-related homeobox 1 could be targeted by miR-363-3p, and the inhibitory effect of FEZF1-AS1 knockdown on CRC progression could also be eliminated by PRRX1 overexpression. Furthermore, interference of FEZF1-AS1 reduced the tumor growth of CRC in vivo. CONCLUSIONS: Our data demonstrate that FEZF1-AS1 regulated PRRX1 expression to promote CRC progression via inhibition of miR-363-3p.

ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer.

BACKGROUND: Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. MATERIAL AND METHODS: The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. RESULTS: ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. CONCLUSIONS: Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

Low expression of miR-138 inhibit the proliferation, migration and invasion of colorectal cancer and affect patient survival by targeting SIRT1.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world, resulting in about 600,000 deaths every year. It is urgent to explore the molecular mechanism and find new effective therapy. Abnormal molecular expression in cancer is considered as a screening biomarker and therapeutic target for tumors, MicroRNA (miRNA) as one of the important molecules, plays an important role in the regulation of tumorigenesis. METHODS: In this study, we aimed to elucidate the molecular mechanism by which mir-138 regulates the development and progression of CRC, and to find new molecular targets for the diagnosis and therapy of CRC. We have used qRT-PCR to study the expression of miR-138 and SIRT1 in CRC cells and tissues, CCK8 assay was used to test the proliferation ability of CRC cells, and invasion and migration ability of CRC cells in vitro were studied by Transwell assay. RESULTS: We found that miR-138 was significantly decreased in CRC tissues and cell lines by qRT-PCR, the level of miR-138 was significantly correlated with lymph node metastasis and distant metastasis, the CRC patients with high miR-138 level whose overall survival and disease-free survival were significantly longer. We also found that the level of SIRT1 in CRC tissues and cell lines is higher, and through Dual-luciferase reporter assay, we found that SIRT1 is a new target of miR-138 in CRC, and SIRT1 knockdown could inhibit CRC proliferation, migration and invasion in vitro. CONCLUSIONS: Thus, we found that miR-138 could inhibit CRC cell proliferation, migration and invasion by targeting SIRT1 firstly, and that will provide a new idea for the therapy of CRC.

Alzheimer's Disease Classification With a Cascade Neural Network.

Classification of Alzheimer's Disease (AD) has been becoming a hot issue along with the rapidly increasing number of patients. This task remains tremendously challenging due to the limited data and the difficulties in detecting mild cognitive impairment (MCI). Existing methods use gait [or EEG (electroencephalogram)] data only to tackle this task. Although the gait data acquisition procedure is cheap and simple, the methods relying on gait data often fail to detect the slight difference between MCI and AD. The methods that use EEG data can detect the difference more precisely, but collecting EEG data from both HC (health controls) and patients is very time-consuming. More critically, these methods often convert EEG records into the frequency domain and thus inevitably lose the spatial and temporal information, which is essential to capture the connectivity and synchronization among different brain regions. This paper proposes a cascade neural network with two steps to achieve a faster and more accurate AD classification by exploiting gait and EEG data simultaneously. In the first step, we propose attention-based spatial temporal graph convolutional networks to extract the features from the skeleton sequences (i.e., gait) captured by Kinect (a commonly used sensor) to distinguish between HC and patients. In the second step, we propose spatial temporal convolutional networks to fully exploit the spatial and temporal information of EEG data and classify the patients into MCI or AD eventually. We collect gait and EEG data from 35 cognitively health controls, 35 MCI, and 17 AD patients to evaluate our proposed method. Experimental results show that our method significantly outperforms other AD diagnosis methods (91.07 vs. 68.18%) in the three-way AD classification task (HC, MCI, and AD). Moreover, we empirically found that the lower body and right upper limb are more important for the early diagnosis of AD than other body parts. We believe this interesting finding can be helpful for clinical researches.

Polygala tenuifolia: a source for anti-Alzheimer's disease drugs.

Context: Alzheimer's disease (AD) is a chronic neurodegenerative disease that originates from central nervous system lesions or recessions. Current estimates suggest that this disease affects over 35 million people worldwide. However, lacking effective drugs is the biggest handicap in treating AD. In traditional Chinese medicine (TCM), Polygala tenuifolia Willd. (Polygalaceae) is generally used to treat insomnia, memory dysfunction and neurasthenia.Objective: This review article explores the role of P. tenuifolia and its active components in anti-Alzheimer's disease.Methods: Literature for the last ten years was obtained through a search on PubMed, SciFinder, CNKI, Google Scholar, Web of Science, Science Direct and China Knowledge Resource Integrated with the following keywords: Polygala tenuifolia, polygalasaponin XXXII (PGS 32), tenuifolin, polygalacic acid, senegenin, tenuigenin, Alzheimer's disease.Results: Polygala tenuifolia and its active components have multiplex neuroprotective potential associated with AD, such as anti-Aß aggregation, anti-Tau protein, anti-inflammation, antioxidant, anti-neuronal apoptosis, enhancing central cholinergic system and promote neuronal proliferation.Conclusions: Polygala tenuifolia and its active components exhibit multiple neuroprotective effects. Hence, P. tenuifolia is a potential drug against Alzheimer's disease, especially in terms of prevention.

Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L., which is called Kudouzi in China, is a medicinal plant distributed in Western and Central Asia, especially in China, and has been used for decades to treat fever, bacterial infection, heart disease, rheumatism, and gastrointestinal diseases. AIM OF THE REVIEW: This review aims to provide up-to-date information on S. alopecuroides, including its botanical characterization, medicinal resources, traditional uses, phytochemistry, pharmacological research, and toxicology, in exploring future therapeutic and scientific potentials. MATERIALS AND METHODS: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations, and other web sources, such as the official website of Flora of China and Yao Zhi website (https://db.yaozh.com/). RESULTS: A total of 128 compounds, such as alkaloids, flavonoids, steroids, and polysaccharides, were isolated from S. alopecuroides. Among these compounds, the effects of alkaloids, such as matrine and oxymatrine, were extensively studied and developed into new drugs. S. alopecuroides and its active components had a wide range of pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, analgesic, and neuroprotective functions, as well as protective properties against pulmonary fibrosis and cardiac fibroblast proliferation. CONCLUSIONS: As an important traditional Chinese medicine, modern pharmacological studies have demonstrated that S. alopecuroides has prominent bioactivities, especially on gynecological inflammation and hepatitis B, and anticancer activities. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the comprehensive evaluation, quality control, understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of S. alopecuroides require further detailed research.

Aberrantly Expressed Genes and miRNAs in Slow Transit Constipation Based on RNA-Seq Analysis.

BACKGROUND: This study aims to identify the key genes and miRNAs in slow transit constipation (STC). METHODS: MRNA and miRNA expression profiling were obtained. Differentially expressed genes (DEGs) and miRNAs were identified followed by the regulatory network construction. Functional annotation analysis and protein-protein interaction (PPI) network were conducted. The electronic validation was performed. RESULTS: Hsa-miR-2116-3p, hsa-miR-3622a-5p, hsa-miR-424-5p, and hsa-miR-1273-3p covered most DEGs. HLA-DRB1, HLA-DRB5, C3, and ICAM were significantly involved in staphylococcus aureus infection. The PPI network generated several hub proteins including ZBTB16, FBN1, CCNF, and CDK1. Electronic validation of HLA-DRB1, PTGDR, MKI67, BIRC5, CCNF, and CDK1 was consistent with the RNA-sequencing analysis. CONCLUSION: Our study might be helpful in understanding the pathology of STC at the molecular level.

miRNA Expression Profile of Saliva in Subjects of Yang Deficiency Constitution and Yin Deficiency Constitution.

BACKGROUND/AIMS: Based on the theory of constitution in Traditional Chinese Medicine (TCM), the Chinese Han population has been classified into nine constitutions. Of these, Yang deficiency constitution mainly exhibit cold intolerance while Yin deficiency constitution mainly exhibit heat intolerance. Some studies have been carried out to explore the modern genetic and biological basis of such constitution classification, but more remains to be done. MicroRNA (miRNA) serves as post-transcriptional regulators of gene expression and may play a role in the classification process. Here, we examined miRNA expression profile of saliva to further improve the comprehensiveness of constitution classification. METHODS: Saliva was collected from Chinese Han individuals with Yang deficiency, Yin deficiency and Balanced constitutions (n=5 each), and miRNA expression profile was determined using the Human miRNA OneArray®v7. Based on 1.5 Fold change, means log2|Ratio|≥0.585 and P-value< 0.05, differentially expressed miRNA was screened. Target genes were predicted using DIANA-TarBasev7.0 and analysis of KEGG pathway was carried out using DIANA-mirPathv.3. RESULTS: We found that 81 and 98 differentially expressed miRNAs were screened in Yang deficiency and Yin deficiency constitution, respectively. Among them, 16 miRNAs were identical and the others were unique. In addition, the target genes that are regulated by the unique miRNAs were significantly enriched in 27 and 20 signaling pathways in Yang deficiency and Yin deficiency constitution, respectively. Thyroid hormone signaling pathway is present in both constitutions. These unique miRNAs that regulated target genes of thyroid hormone signaling pathway may be associated with cold intolerance or heat intolerance. CONCLUSION: The results of our study show that Yang deficiency and Yin deficiency constitutions exhibit systematic differences in miRNA expression profile. Moreover, the distinct characteristics of TCM constitution may be explained, in part, by differentially expressed miRNAs.