The Metabolic Functional Feature of Gut Microbiota in Mongolian Patients with Type 2 Diabetes.

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. ß-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

3D Directional Assembly of Liquid Crystal Molecules.

The precise construction of hierarchically long-range ordered structures using molecules as fundamental building blocks can fully harness their anisotropy and potential. However, the 3D, high-precision, and single-step directional assembly of molecules is a long-pending challenge. Here, a 3D directional molecular assembly strategy via femtosecond laser direct writing (FsLDW) is proposed and the feasibility of this approach using liquid crystal (LC) molecules as an illustrative example is demonstrated. The physical mechanism for femtosecond (fs) laser-induced assembly of LC molecules is investigated, and precise 3D arbitrary assembly of LC molecules is achieved by defining the discretized laser scanning pathway. Additionally, an LC-based Fresnel zone plate array with polarization selection and colorization imaging functions is fabricated to further illustrate the potential of this method. This study not only introduces a 3D high-resolution alignment method for LC-based functional devices but also establishes a universal protocol for the precise 3D directional assembly of anisotropic molecules.

Predicting T-Cell Lymphoma in Children From 18F-FDG PET-CT Imaging With Multiple Machine Learning Models.

This study aimed to examine the feasibility of utilizing radiomics models derived from 18F-FDG PET/CT imaging to screen for T-cell lymphoma in children with lymphoma. All patients had undergone 18F-FDG PET/CT scans. Lesions were extracted from PET/CT and randomly divided into training and validation sets. Two different types of models were constructed as follows: features that are extracted from standardized uptake values (SUV)-associated parameters, and CT images were used to build SUV/CT-based model. Features that are derived from PET and CT images were used to build PET/CT-based model. Logistic regression (LR), linear support vector machine, support vector machine with the radial basis function kernel, neural networks, and adaptive boosting were performed as classifiers in each model. In the training sets, 77 patients, and 247 lesions were selected for building the models. In the validation sets, PET/CT-based model demonstrated better performance than that of SUV/CT-based model in the prediction of T-cell lymphoma. LR showed highest accuracy with 0.779 [0.697, 0.860], area under the receiver operating characteristic curve (AUC) with 0.863 [0.762, 0.963], and preferable goodness-of-fit in PET/CT-based model at the patient level. LR also showed best performance with accuracy of 0.838 [0.741, 0.936], AUC of 0.907 [0.839, 0.976], and preferable goodness-of-fit in PET/CT-based model at the lesion level. 18F-FDG PET/CT-based radiomics models with different machine learning classifiers were able to screen T-cell lymphoma in children with high accuracy, AUC, and preferable goodness-of-fit, providing incremental value compared with SUV-associated features.

Random Forest for Predicting Treatment Response to Radioiodine and Thyrotropin Suppression Therapy in Patients With Differentiated Thyroid Cancer But Without Structural Disease.

BACKGROUND: We aimed to develop a machine-learning model for predicting treatment response to radioiodine (131I) therapy and thyrotropin (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) but without structural disease, based on pre-treatment information. PATIENTS AND METHODS: Overall, 597 and 326 patients with DTC but without structural disease were randomly assigned to "training" cohorts for predicting treatment response to 131I therapy and TSH suppression therapy, respectively. Six supervised algorithms, including Logistic Regression, Support Vector Machine, Random Forest (RF), Neural Networks, Adaptive Boosting, and Gradient Boost, were used to predict effective response (ER) to 131I therapy and biochemical remission (BR) to TSH suppression therapy. RESULTS: Stimulated and suppressed thyroglobulin (Tg) and radioiodine uptake before the current course of 131I therapy were mostly attributed to ER to 131I therapy, while thyroid remnant available on the post-therapeutic whole-body scan at the last course of 131I therapy and TSH were greatly contributed to Tg decline under TSH suppression therapy. RF showed the best performance among all models. The accuracy and area under the receiver operating characteristic curve (AUC) for segregating ER from non-ER during 131I therapy with RF were 81.3% and 0.896, respectively. The accuracy and AUC for predicting BR to TSH suppression therapy with RF were 78.7% and 0.857, respectively. CONCLUSION: This study demonstrates that machine learning models, especially the RF algorithm are useful tools that may predict treatment response to 131I therapy and TSH suppression therapy in DTC patients without structural disease based on pre-treatment routine clinical variables and biochemical markers.

Time-bin phase-encoding quantum key distribution using Sagnac-based optics and compatible electronics.

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

Dynamic Changes of Regulatory T Cells/CD4⁺ T Cells in Peripheral Blood of Adult Kidney Transplant Recipients: A Comparison of Pediatric and Adult Kidney Donors.

BACKGROUND Inducing transplantation tolerance and monitoring the recipient's immune status to improve allograft survival remains the main goal for kidney transplantation (KTx). MATERIAL AND METHODS A total of 53 renal transplantation patients and 20 healthy individuals were assigned to the post-transplantation and healthy groups, respectively; 10 recipients with stable renal function for 2 years after kidney transplantation were assigned to Group C. Eleven kidney transplantation recipients were hospitalized due to lung infection. Flow cytometry was used to measure levels of Tregs/CD4⁺ T cells. RESULTS The Tregs/CD4⁺ T cells ratio reached homeostasis 6 months after KTx, with no significant difference between Group D (healthy control group) and pre-surgery or Group C (2 years after KTx group). The pediatric donor group and the adult donor group reached immune homeostasis 3 months after the operation. Immune homeostasis is maintaining a balance between immune tolerance and immunogenicity. There was no significant difference in graft function between the pediatric and adult donor groups before surgery, 1 day after surgery, 1 week after surgery, 2 weeks after surgery, and 1 month after surgery; however, graft function was significantly better in the pediatric donor group compared with the adult donor group at 3 mouths (eGFR: 51.7 (40.4-66.2) vs 73.0 (55.7-90.2), P=0.008<0.05) and 6 months (eGFR: 52.2 (37.5-62.8) vs 80.5 (64.1-90.4), P<0.001) after surgery. Pediatric donor kidneys reached immune homeostasis 3 months after surgery, with better graft function at this time compared with adult donor kidneys. The proportion of Tregs/CD4⁺ T cells in recipients with a pulmonary infection after KTx was lower than in those with infection recovery. CONCLUSIONS Expanding the use of pediatric kidneys should be further explored by the transplantation community. The proportion of Tregs/CD4⁺ T cells in recipients with a pulmonary infection after KTx was lower than in those with infection recovery.

MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters.

Background: The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear. Methods: To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites. Results: Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3'-UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter. Conclusion: miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter.

Enhanced Water Resistance and Catalytic Performance of Ru/TiO2 by Regulating Brønsted Acid and Oxygen Vacancy for the Oxidative Removal of 1,2-Dichloroethane and Toluene.

The compositions of volatile organic compounds (VOCs) under actual industrial conditions are often complex; especially, the interaction of intermediate products easily leads to more toxic emissions that are harmful to the atmospheric environment and human health. Herein, we report a comparative investigation on 1,2-dichloroethane (1,2-DCE) and (1,2-DCE + toluene) oxidation over the Ru/TiO2, phosphotungstic acid (HPW)-modified Ru/TiO2, and oxygen vacancy-rich Ru/TiOx catalysts. The doping of HPW successfully introduced the 1,2-DCE adsorption sites to promote its oxidation and exhibited outstanding water resistance. For the mixed VOCs, Ru/HPW-TiO2 promoted the preferential and superfluous adsorption of toluene and resulted in the inhibition of 1,2-DCE degradation. Therefore, HPW modification is a successful strategy in catalytic 1,2-DCE oxidation, but Brønsted acid sites tend to adsorb toluene in the mixed VOC oxidation. The Ru/TiOx catalyst exhibited excellent activity and stability in the oxidation of mixed VOCs and could inhibit the generation of byproducts and Cl2 compared with the Ru/HPW-TiO2 catalyst. Compared with the Brønsted acid modification, the oxygen vacancy-rich catalysts are significantly suitable for the oxidation of multicomponent VOCs.

Self-Formation CoO Nanodots Catalyst in Co(TFSI)2 -Modified Electrolyte for High Efficient Li-O2 Batteries.

The major challenges for Li-O2 batteries are sluggish reaction kinetics and large overpotentials due to the cathode passivation resulting from insulative and insoluble Li2 O2 . Here, a novel nanodot (ND)-modified electrolyte is designed by employing cobalt bis(trifluoromethylsulfonyl)imide (Co(TFSI)2 ) as an electrolyte additive. The Co(TFSI)2 additive can react with discharge intermediate LiO2 and product Li2 O2 to form CoO NDs. The generated CoO NDs are well dispersed in electrolyte, which integrates both the high catalytic activity of solid catalyst and the good wettability of soluble catalyst. Under the catalytis of CoO NDs, Li2 O2 is produced and deposits on the cathode together with them. At the recharge process, these well dispersed CoO NDs help to decompose solid Li2 O2 at a lower overpotential. The Li-O2 cells with Co(TFSI)2 exhibit a long cycle life of 200 cycles at a current density of 200 mA g-1 under a cutoff capacity of 1000 mAh g-1 , as well as a superior reversibility associated with the Li2 O2 formation and decomposition. The study is expected to broaden the range of electrolyte additives and provide a new view to developing highly dispersed NDs-based catalysts for Li-O2 batteries.

Robust Cooperative Optimal Sliding-Mode Control for High-Order Nonlinear Systems: Directed Topologies.

This article is concerned with the robust cooperative optimal control of nonlinear multiagent systems (MASs) with external disturbances and modeling uncertainties. Using the super-twisting algorithm, a continuous sliding-mode control protocol is presented for high-order nonlinear MASs with multiple inputs. The sliding-mode dynamics is modeled by the Takagi-Sugeno fuzzy approach, and the nominal control protocol that guarantees the robust optimization of the cost function is designed. Directed topologies are allowed using the presented protocol, and many assumptions about topologies are removed. Finally, three numerical examples are reported to demonstrate the effectiveness and improved performance of the presented protocol.

Improving the fidelity of CT image colorization based on pseudo-intensity model and tumor metabolism enhancement.

BACKGROUND: Subject to the principle of imaging, most medical images are gray-scale images. Human eyes are more sensitive to color images compared to gray-scale images. The state-of-the-art medical image colorization results are unnatural and unrealistic, especially in some organs, such as the lung field. METHOD: We propose a CT image colorization network that consists of a pseudo-intensity model, tumor metabolic enhancement, and MemoPainter-cGAN colorization network. First, the distributions of both the density of CT images and the intensity of anatomical images are analyzed with the aim of building a pseudo-intensity model. Then, the PET images, which are sensitive to tumor metabolism, are used to highlight the tumor regions. Finally, the MemoPainter-cGAN is used to generate colorized anatomical images. RESULTS: Our experiment verified that the mean structural similarity between the colorized images and the original color images is 0.995, which indicates that the colorized image maintains the features of the original images enormously. The average image information entropy is 6.62, which is 13.4% higher than that of the images before metabolism enhancement and colorization. It indicates that the image fidelity is significantly improved. CONCLUSIONS: Our method can generate vivid and fresh anatomical images based on prior knowledge of tissue or organ intensity. The colorized PET/CT images with abundant anatomical knowledge and high sensitivity of metabolic information provide radiologists with access to a new modality that offers additional reference information.

Learning-Based End-to-End Path Planning for Lunar Rovers with Safety Constraints.

Path planning is an essential technology for lunar rover to achieve safe and efficient autonomous exploration mission, this paper proposes a learning-based end-to-end path planning algorithm for lunar rovers with safety constraints. Firstly, a training environment integrating real lunar surface terrain data was built using the Gazebo simulation environment and a lunar rover simulator was created in it to simulate the real lunar surface environment and the lunar rover system. Then an end-to-end path planning algorithm based on deep reinforcement learning method is designed, including state space, action space, network structure, reward function considering slip behavior, and training method based on proximal policy optimization. In addition, to improve the generalization ability to different lunar surface topography and different scale environments, a variety of training scenarios were set up to train the network model using the idea of curriculum learning. The simulation results show that the proposed planning algorithm can successfully achieve the end-to-end path planning of the lunar rover, and the path generated by the proposed algorithm has a higher safety guarantee compared with the classical path planning algorithm.

A paradox: Fe2+-containing agents decreased ROS and apoptosis induced by CoNPs in vascular endothelial cells by inhibiting HIF-1α.

Cobalt nanoparticles (CoNPs) released from hip joint implants are known to have a toxic effect on several organs probably through increasing reactive oxygen species (ROS). Ferrous ion (Fe2+) is well-known to enhance oxidative stress by catalysing the production of ROS. However, in our pilot study, we found that Fe2+ conversely inhibited the ROS production induced by CoNPs. To elucidate the underlying mechanism, the present study treated vascular endothelial HUVEC and HMEC-1 cells with CoNPs alone or in combination with ferrous lactate [Fe(CH3CHOHCOO)2], ferrous succinate [Fe(CH2COO)2], and ferrous chloride (FeCl2). CoNP toxicity was evaluated by measuring cell viability, rate of apoptosis and lactose dehydrogenase (LDH) release, and intracellular ROS levels. Treatment with CoNPs decreased cell viability, LDH release, and ROS production and increased apoptosis. CoNPs increased hypoxia-inducible factor-1α (HIF-1α) protein level and mRNA levels of vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT1) downstream of HIF-1α signalling. Silencing HIF-1α attenuated CoNP toxicity, as seen by recovery of cell viability, LDH release, and ROS levels and reduced apoptosis. CoNPs caused a pronounced reduction of Fe2+ in cells, but supplementation with Fe(CH3CHOHCOO)2, Fe(CH2COO)2, and FeCl2 restored Fe2+ levels and inhibited HIF-1α activation. Moreover, all three Fe2+-containing agents conferred protection from CoNPs; Fe(CH3CHOHCOO)2 and Fe(CH2COO)2 more effectively than FeCl2. In summary, the present study revealed that CoNPs exert their toxicity on human vascular endothelial cells by depleting intracellular Fe2+ level, which causes activation of HIF-1α signalling. Supplements of Fe2+, especially in the form of Fe(CH3CHOHCOO)2 and Fe(CH2COO)2, mitigated CoNP toxicity.

Supplementation with Fe2+-containing agents mitigated the toxic effect of CoNPs in vascular endothelial cells by inhibiting activation of hypoxia-inducible factor.

Cobalt nanoparticles (CoNPs) released from hip joint implants are known to have a toxic effect on several organs. The aim of this study was to examine the effects of CoNP toxicity on vascular endothelium and to elucidate the underlying mechanisms. Moreover, the role of three ferrous ion (Fe2+)containing agents in conferring resistance to the effects of CoNPs was investigated. Vascular endothelial HUVEC and HMEC-1 cells were cultured in a medium supplemented with CoNPs. Ferrous lactate [Fe(CH3CHOHCOO)2], ferrous succinate [Fe(CH2COO)2], and ferrous chloride (FeCl2) were added to the cells in varying concentrations. CoNP toxicity was evaluated by measuring cell viability, rate of apoptosis and LDH release, and intracellular ROS levels. Treatment with CoNPs decreased cell viability, LDH release, and ROS production and increased apoptosis. CoNPs increased hypoxia-inducible factor-1α (HIF-1α) protein level and mRNA levels of VEGF and GLUT1 downstream of HIF-1α signalling. Silencing HIF-1α attenuated CoNP toxicity, as seen by recovery of cell viability, LDH release, and ROS levels and reduced apoptosis. CoNPs caused a pronounced reduction of Fe2+ in cells, but supplementation with Fe(CH3CHOHCOO)2, Fe(CH2COO)2, and FeCl2 restored Fe2+ levels and inhibited HIF-1α activation. Moreover, all three Fe2+-containing agents conferred protection from CoNPs; Fe(CH3CHOHCOO)2 and Fe(CH2COO)2 more effectively than FeCl2. In summary, this study revealed that CoNPs exert their toxicity on human vascular endothelial cells by depleting intracellular Fe2+ level, which causes activation of HIF-1α signalling. Supplements of Fe2+, especially in the form of Fe(CH3CHOHCOO)2 and Fe(CH2COO)2, mitigated CoNP toxicity.

Circulating Exosomes Derived-miR-146a from Systemic Lupus Erythematosus Patients Regulates Senescence of Mesenchymal Stem Cells.

The senescence of mesenchymal stem cells (MSCs) plays a crucial role in the development and progression of systemic lupus erythematosus (SLE). Exosomes, small spherical bilayer proteolipid vesicles, contribute to the communication between various cells and their microenvironment by transferring information via their cargo, including the proteins, lipids, and RNAs. While exosomal miRNAs participate in various biological activities, correlations of circulating exosomes with senescent signs of BM-MSCs remain unclear. In our study, we aimed at exploring the roles of circulating exosomal miRNAs in the senescence of MSCs. We found that exosomes derived from SLE serum could increase the proportions of SA-ß-gal positive cells, disorganize cytoskeletons, and reduce growth rates. Moreover, the expression of miR-146a declined significantly in serum exosomes of SLE patients compared with healthy controls. miR-146a could be internalized into MSCs via exosomes and participate in MSCs senescence through targeting TRAF6/NF-κB signaling. These results clarified the novel mechanism of MSCs senescence in SLE patients.

MicroRNA-21-5p are involved in apoptosis and invasion of fibroblast-like synoviocytes through PTEN/PI3K/AKT signal.

The function of microRNA-21-5p (miR-21) in fibroblast-like synoviocytes in RA was still unclear. In our study, we used tumor necrosis factor alpha (TNFα) (10 ng/ml) to mimic RA-FLSs and we found that normal FLS stimulated with TNFα caused the increasing expression of miR-21, a disintegrin and metalloproteinase with thrombospondin motifs 5 and matrix metalloproteinase 3, which were in accord with RA-FLSs changes. Our data showed that miR-21 overexpression significantly increased cell invasion and decreased apoptosis in FLSs. Knockdown of miR-21 in FLSs causes the opposite result. However, miR-21 may not affect the proliferation of FLSs. Meanwhile, we showed that miR-21 activated the PI3K/AKT signaling pathway to participate in RA by inhibiting PTEN expression. Taken together, our results suggested that miR-21 may play a positive role in RA and may be a promising new therapeutic target for RA.

New Results on Sliding-Mode Control for Takagi-Sugeno Fuzzy Multiagent Systems.

This paper investigates the sliding-mode control (SMC) problem of Takagi-Sugeno (T-S) fuzzy multiagent systems (MASs). A cooperative fuzzy-based dynamical sliding-mode (SM) controller is designed and the overall closed-loop T-S fuzzy MAS is constructed. A new model transformation method for T-S fuzzy MASs is presented to transform the fuzzy weighting matrix into a set of fuzzy weighting scalars. By applying the method of linear matrix inequality, a general stability analysis approach for T-S fuzzy MASs is proposed. Moreover, the energy-cost constraint problem is studied by using the linear quadratic regulator method. Finally, numerical examples are provided to illustrate the effectiveness of the proposed theoretical approaches and the improved performance compared to existing results.

Exponential stability on stochastic neural networks with discrete interval and distributed delays.

This brief addresses the stability analysis problem for stochastic neural networks (SNNs) with discrete interval and distributed time-varying delays. The interval time-varying delay is assumed to satisfy 0 < d(1)

New passivity criteria for neural networks with time-varying delay.

In this paper, improved criteria for the passivity of neural networks with time delay are proposed. The improvement is achieved by exploiting the finer relationships between the time-varying delay and its size bound which allow the use of more slack variables. It is illustrated via numerical examples that the proposed results are less conservative than those available in the literature.