Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway.

BACKGROUND: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. AIM: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. METHODS: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant. RESULTS: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group (P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group (P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 (r = 0.823, P < 0.05). CONCLUSION: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

Titanium dioxide nanoparticles oral exposure induce osteoblast apoptosis, inhibit osteogenic ability and increase lipogenesis in mouse.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used in food, paint, coating, cosmetic, and composite orthodontic material. As a common food additive, TiO2-NPs can accumulate in various organs of human body, but the effect and underlying mechanism of bone remain unclear. Here mice were exposed to TiO2-NPs by oral gavage, and histological staining of femoral sections showed that TiO2-NPs reduced bone formation and enhanced osteoclast activity and lipogenesis, contributing to decreased trabecula bone. Transmission electron microscope (TEM) as well as biochemical and flow cytometry analysis of osteoblast exhibited that TiO2-NPs accumulated in osteoblast cytoplasm and impaired mitochondria ultrastructure with increased reactive oxygen species (ROS) and lipid hyperoxide, resulting in osteoblast apoptosis. In terms of mechanism, TiO2-NPs treatment inhibited expression of AKT and then increased pro-apoptotic protein Bax expression which was failure to form heterodimers with decreased anti-apoptotic Bcl-2, activating downstream Caspase-9 and Caspase-3 and inducing apoptosis. Additionally, TiO2-NPs suppressed Wnt3a level and then activated anti-Glycogen synthesis kinase (GSK-3ß) phosphorylation, and ultimately resulted in degradation of ß-catenin which down-regulated Runt-related transcription factor 2 (Runx2) and Osterix, inhibiting expression of osteogenic related proteins. Together, these results revealed that exposure of TiO2-NPs induced apoptosis and inhibited osteoblast differentiation through suppressing PI3K/AKT and Wnt/ß-catenin signaling pathways, resulting in reduction of trabecula bone.

A signal recognition particle-related joint model of LASSO regression, SVM-RFE and artificial neural network for the diagnosis of systemic sclerosis-associated pulmonary hypertension.

Background: Systemic sclerosis-associated pulmonary hypertension (SSc-PH) is one of the most common causes of death in patients with systemic sclerosis (SSc). The complexity of SSc-PH and the heterogeneity of clinical features in SSc-PH patients contribute to the difficulty of diagnosis. Therefore, there is a pressing need to develop and optimize models for the diagnosis of SSc-PH. Signal recognition particle (SRP) deficiency has been found to promote the progression of multiple cancers, but the relationship between SRP and SSc-PH has not been explored. Methods: First, we obtained the GSE19617 and GSE33463 datasets from the Gene Expression Omnibus (GEO) database as the training set, GSE22356 as the test set, and the SRP-related gene set from the MSigDB database. Next, we identified differentially expressed SRP-related genes (DE-SRPGs) and performed unsupervised clustering and gene enrichment analyses. Then, we used least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) to identify SRP-related diagnostic genes (SRP-DGs). We constructed an SRP scoring system and a nomogram model based on the SRP-DGs and established an artificial neural network (ANN) for diagnosis. We used receiver operating characteristic (ROC) curves to identify the SRP-related signature in the training and test sets. Finally, we analyzed immune features, signaling pathways, and drugs associated with SRP and investigated SRP-DGs' functions using single gene batch correlation analysis-based GSEA. Results: We obtained 30 DE-SRPGs and found that they were enriched in functions and pathways such as "protein targeting to ER," "cytosolic ribosome," and "coronavirus disease-COVID-19". Subsequently, we identified seven SRP-DGs whose expression levels and diagnostic efficacy were validated in the test set. As one signature, the area under the ROC curve (AUC) values for seven SRP-DGs were 0.769 and 1.000 in the training and test sets, respectively. Predictions made using the nomogram model are likely beneficial for SSc-PH patients. The AUC values of the ANN were 0.999 and 0.860 in the training and test sets, respectively. Finally, we discovered that some immune cells and pathways, such as activated dendritic cells, complement activation, and heme metabolism, were significantly associated with SRP-DGs and identified ten drugs targeting SRP-DGs. Conclusion: We constructed a reliable SRP-related ANN model for the diagnosis of SSc-PH and investigated the possible role of SRP in the etiopathogenesis of SSc-PH by bioinformatics methods to provide a basis for precision and personalized medicine.

Thumb Stabilization and Assistance in a Robotic Hand Orthosis for Post-Stroke Hemiparesis.

We propose a dual-cable method of stabilizing the thumb in the context of a hand orthosis designed for individuals with upper extremity hemiparesis after stroke. This cable network adds opposition/reposition capabilities to the thumb, and increases the likelihood of forming a hand pose that can successfully manipulate objects. In addition to a passive-thumb version (where both cables are of fixed length), our approach also allows for a single-actuator active-thumb version (where the extension cable is actuated while the abductor remains passive), which allows a range of motion intended to facilitate creating and maintaining grasps. We performed experiments with five chronic stroke survivors consisting of unimanual resistive-pull tasks and bimanual twisting tasks with simulated real-world objects; these explored the effects of thumb assistance on grasp stability and functional range of motion. Our results show that both active- and passive-thumb versions achieved similar performance in terms of improving grasp force generation over a no-device baseline, but active thumb stabilization enabled users to maintain grasps for longer durations.

Adaptive Semi-Supervised Intent Inferral to Control a Powered Hand Orthosis for Stroke.

In order to provide therapy in a functional context, controls for wearable robotic orthoses need to be robust and intuitive. We have previously introduced an intuitive, user-driven, EMG-based method to operate a robotic hand orthosis, but the process of training a control that is robust to concept drift (changes in the input signal) places a substantial burden on the user. In this paper, we explore semi-supervised learning as a paradigm for controlling a powered hand orthosis for stroke subjects. To the best of our knowledge, this is the first use of semi-supervised learning for an orthotic application. Specifically, we propose a disagreement-based semi-supervision algorithm for handling intrasession concept drift based on multimodal ipsilateral sensing. We evaluate the performance of our algorithm on data collected from five stroke subjects. Our results show that the proposed algorithm helps the device adapt to intrasession drift using unlabeled data and reduces the training burden placed on the user. We also validate the feasibility of our proposed algorithm with a functional task; in these experiments, two subjects successfully completed multiple instances of a pick-and-handover task.

Construction of a three commitment points for S phase entry cell cycle model and immune-related ceRNA network to explore novel therapeutic options for psoriasis.

While competing endogenous RNAs (ceRNAs) play pivotal roles in various diseases, the proliferation and differentiation of keratinocytes are becoming a research focus in psoriasis. Therefore, the three commitment points for S phase entry (CP1-3) cell cycle model has pointed to a new research direction in these areas. However, it is unclear what role ceRNA regulatory mechanisms play in the interaction between keratinocytes and the immune system in psoriasis. In addition, the ceRNA network-based screening of potential therapeutic agents for psoriasis has not been explored. Therefore, we used multiple bioinformatics approaches to construct a ceRNA network for psoriasis, identified CTGF as the hub gene, and constructed a ceRNA subnetwork, after which validation datasets authenticated the results' accuracy. Subsequently, we used multiple online databases and the single-sample gene-set enrichment analysis algorithm, including the CP1-3 cell cycle model, to explore the mechanisms accounting for the increased proliferation and differentiation of keratinocytes and the possible roles of the ceRNA subnetwork in psoriasis. Next, we performed cell cycle and cell trajectory analyses based on a single-cell RNA-seq dataset of psoriatic skin biopsies. We also used weighted gene co-expression network analysis and single-gene batch correlation analysis-based gene set enrichment analysis to explore the functions of CTGF. Finally, we used the Connectivity Map to identify MS-275 (entinostat) as a novel treatment for psoriasis, SwissTargetPrediction to predict drug targets, and molecular docking to investigate the minimum binding energy and binding sites of the drug to target proteins.

A Series of Manganese(III) Salen Complexes as a Result of Team-Based Inquiry in a Transnational Education Programme.

The development of a team-based approach to research-led transnational practical chemistry teaching is described in which a team of five Chinese students on an articulated transnational degree programme, supported by a team of academic and technical staff, carried out a study examining the structural chemistry of a series of manganese(III) salen complexes. A series of four crystallographically characterized manganese(III) salen complexes with ancillary carboxylate ligands are reported here. The carboxylate coordination modes range from the bridging syn-anti µ2 -κO : κO' mode observed in the predominant cyclohexanoate and isobutyrate species, to a capping terminal monodentate mode for the adamantanoate species, and an unusual mixture of bridging and terminal coordination modes observed in a second minor phase of the cyclohexanoate species. The variation on extended structures based on the weakly interacting aliphatic backbones may provide a useful basis for further structural studies.

A boron nitride electrode modified with a nanocomposite prepared from an ionic liquid and tungsten disulfide for voltammetric sensing of 4-aminophenol.

Boron nitride (BN) was used as a support and covered with an ionic liquid (IL) and tungsten disulfide (WS2) nanoparticles to obtain an electrode for the determination of 4-aminophenol (4-AP). BN was prepared using a "solvent cutting" method, and the BN-IL-WS2 nanocomposite was obtained by an ultrasonic method. BN and its hybrids were characterized by scanning electron microscopy, transmission electron microscopy and X-ray diffraction. When the BN-IL-WS2 composites were coated on the surface of the electrode, the response to 4-AP was strongly amplified due to the strong synergetic effect between the three materials. The voltammetric response of the modified sensor (with a maximum at 0.29 V vs. Ag/AgCl) in solutions with a pH of 6 is linear in the 0.01-50 µΜ 4-AP concentration range, and the limit of detection is 3 nM. A modified glassy carbon electrode was applied for the determination of 4-AP in seawater and dispersions containing paracetamol tablets. The results were consistent with those obtained by HPLC. Graphical abstract Schematic representation of the voltammetric determination process of 4-aminophenol (4-AP). The electrochemical sensor based on the glassy carbon electrode modified with boron nitride (BN), ionic liquid (IL) and tungsten disulfide (WS2) nanomaterials. They, exhibit an excellent performance compared with other electrodes.