Elevated expression of macrophage MERTK exhibits profibrotic effects and results in defective regulation of efferocytosis function in pulmonary fibrosis.

Increased apoptosis of alveolar epithelial cells is a prominent feature of pulmonary fibrosis. Macrophage efferocytosis, phagocytosis of apoptotic cells by macrophages, is crucial for maintaining tissue homeostasis. Expression of Mer tyrosine kinase (MERTK, an important recognition receptor in efferocytosis) in macrophages is thought to be associated with fibrosis. However, how macrophage MERTK affects pulmonary fibrosis and whether it depends on efferocytosis are not yet clear. Here, we found elevated MERTK expression in lung macrophages from IPF patients and mice with bleomycin-induced pulmonary fibrosis. In vitro experiments showed that macrophages overexpressing MERTK exhibit profibrotic effects and that macrophage efferocytosis abrogates the profibrotic effect of MERTK by downregulating MERTK, forming a negative regulatory loop. In pulmonary fibrosis, this negative regulation is defective, and MERTK mainly exhibits profibrotic effects. Our study reveals a previously unsuspected profibrotic effect of elevated macrophage MERTK in pulmonary fibrosis and defective regulation of efferocytosis function as a result of that elevation, suggesting that targeting MERTK in macrophages may help to attenuate pulmonary fibrosis.

Tracing human life trajectory using gut microbial communities by context-aware deep learning.

The gut microbial communities are highly plastic throughout life, and the human gut microbial communities show spatial-temporal dynamic patterns at different life stages. However, the underlying association between gut microbial communities and time-related factors remains unclear. The lack of context-awareness, insufficient data, and the existence of batch effect are the three major issues, making the life trajection of the host based on gut microbial communities problematic. Here, we used a novel computational approach (microDELTA, microbial-based deep life trajectory) to track longitudinal human gut microbial communities' alterations, which employs transfer learning for context-aware mining of gut microbial community dynamics at different life stages. Using an infant cohort, we demonstrated that microDELTA outperformed Neural Network for accurately predicting the age of infant with different delivery mode, especially for newborn infants of vaginal delivery with the area under the receiver operating characteristic curve of microDELTA and Neural Network at 0.811 and 0.436, respectively. In this context, we have discovered the influence of delivery mode on infant gut microbial communities. Along the human lifespan, we also applied microDELTA to a Chinese traveler cohort, a Hadza hunter-gatherer cohort and an elderly cohort. Results revealed the association between long-term dietary shifts during travel and adult gut microbial communities, the seasonal cycling of gut microbial communities for the Hadza hunter-gatherers, and the distinctive microbial pattern of elderly gut microbial communities. In summary, microDELTA can largely solve the issues in tracing the life trajectory of the human microbial communities and generate accurate and flexible models for a broad spectrum of microbial-based longitudinal researches.

"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways.

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear. Objective: In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways. Materials and Methods: Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca2+ in the striatum was analyzed by a calcium kit. Results: Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca2+/CAM/CAMKII signaling pathways. Conclusion: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.

EXPERT: transfer learning-enabled context-aware microbial community classification.

Microbial community classification enables identification of putative type and source of the microbial community, thus facilitating a better understanding of how the taxonomic and functional structure were developed and maintained. However, previous classification models required a trade-off between speed and accuracy, and faced difficulties to be customized for a variety of contexts, especially less studied contexts. Here, we introduced EXPERT based on transfer learning that enabled the classification model to be adaptable in multiple contexts, with both high efficiency and accuracy. More importantly, we demonstrated that transfer learning can facilitate microbial community classification in diverse contexts, such as classification of microbial communities for multiple diseases with limited number of samples, as well as prediction of the changes in gut microbiome across successive stages of colorectal cancer. Broadly, EXPERT enables accurate and context-aware customized microbial community classification, and potentiates novel microbial knowledge discovery.

Flexible Capacitive Pressure Sensor Based on a Double-Sided Microstructure Porous Dielectric Layer.

In the era of intelligent sensing, there is a huge demand for flexible pressure sensors. High sensitivity is the primary requirement for flexible pressure sensors, whereas pressure response range and resolution, which are also key parameters of sensors, are often ignored, resulting in limited applications of flexible pressure sensors. This paper reports a flexible capacitive pressure sensor based on a double-sided microstructure porous dielectric layer. First, a porous structure was developed in the polymer dielectric layer consisting of silicon rubber (SR)/NaCl/carbon black (CB) using the dissolution method, and then hemisphere microstructures were developed on both sides of the layer by adopting the template method. The synergistic effect of the hemispheric surface microstructure and porous internal structure improves the deformability of the dielectric layer, thus achieving high sensitivity (3.15 kPa-1), wide response range (0-200 kPa), and high resolution (i.e., the minimum pressure detected was 27 Pa). The proposed sensing unit and its array have been demonstrated to be effective in large-area pressure sensing and object recognition. The flexible capacitive pressure sensor developed in this paper is highly promising in applications of robot skin and intelligent prosthetic hands.

Brain Structure Alterations in Hemifacial Spasm: A Diffusion Tensor Imaging Study.

This study examined white matter integrity in patients with left-sided hemifacial spasm (HFS) using diffusion tensor imaging (DTI). Thirty-six patients with left-sided HFS (mean age 53.24 ± 8.16 years) and 36 healthy volunteers (mean age 53.92 ± 7.73 years) were recruited. Tract-based spatial statistics (TBSS) analysis revealed significantly increased fractional anisotropy (FA) of bilateral superior longitudinal fasciculus in HFS patients (P < 0.05, family-wise error corrected), with trends for radial diffusivity to decrease. We inferred that the results may be associated with poor sleep quality, impairment in visuospatial construction, and activity-dependent increases in myelination in HFS patients. Furthermore, the FA value of left superior longitudinal fasciculus showed a positive correlation with HFS duration (r = 0.352, P = .041) and spasm severity (r = 0.416, P = .014). However, the alteration of medial diffusivity and axial diffusivity were not found in bilateral superior longitudinal fasciculus between groups. These findings suggest FA changes of superior longitudinal fasciculus reflected by TBSS analysis may provide valuable insights into the diagnosis of HFS.

Human Motion State Recognition Based on Flexible, Wearable Capacitive Pressure Sensors.

Human motion state recognition technology based on flexible, wearable sensor devices has been widely applied in the fields of human-computer interaction and health monitoring. In this study, a new type of flexible capacitive pressure sensor is designed and applied to the recognition of human motion state. The electrode layers use multi-walled carbon nanotubes (MWCNTs) as conductive materials, and polydimethylsiloxane (PDMS) with microstructures is embedded in the surface as a flexible substrate. A composite film of barium titanate (BaTiO3) with a high dielectric constant and low dielectric loss and PDMS is used as the intermediate dielectric layer. The sensor has the advantages of high sensitivity (2.39 kPa-1), wide pressure range (0-120 kPa), low pressure resolution (6.8 Pa), fast response time (16 ms), fast recovery time (8 ms), lower hysteresis, and stability. The human body motion state recognition system is designed based on a multi-layer back propagation neural network, which can collect, process, and recognize the sensor signals of different motion states (sitting, standing, walking, and running). The results indicate that the overall recognition rate of the system for the human motion state reaches 94%. This proves the feasibility of the human motion state recognition system based on the flexible wearable sensor. Furthermore, the system has high application potential in the field of wearable motion detection.

Reliable and Interpretable Mortality Prediction With Strong Foresight in COVID-19 Patients: An International Study From China and Germany.

Cohort-independent robust mortality prediction model in patients with COVID-19 infection is not yet established. To build up a reliable, interpretable mortality prediction model with strong foresight, we have performed an international, bi-institutional study from China (Wuhan cohort, collected from January to March) and Germany (Würzburg cohort, collected from March to September). A Random Forest-based machine learning approach was applied to 1,352 patients from the Wuhan cohort, generating a mortality prediction model based on their clinical features. The results showed that five clinical features at admission, including lymphocyte (%), neutrophil count, C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase, could be used for mortality prediction of COVID-19 patients with more than 91% accuracy and 99% AUC. Additionally, the time-series analysis revealed that the predictive model based on these clinical features is very robust over time when patients are in the hospital, indicating the strong association of these five clinical features with the progression of treatment as well. Moreover, for different preexisting diseases, this model also demonstrated high predictive power. Finally, the mortality prediction model has been applied to the independent Würzburg cohort, resulting in high prediction accuracy (with above 90% accuracy and 85% AUC) as well, indicating the robustness of the model in different cohorts. In summary, this study has established the mortality prediction model that allowed early classification of COVID-19 patients, not only at admission but also along the treatment timeline, not only cohort-independent but also highly interpretable. This model represents a valuable tool for triaging and optimizing the resources in COVID-19 patients.

Can probiotic supplements improve the symptoms of autism spectrum disorder in children?: A protocol for systematic review and meta analysis.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. The externalizing and internalizing problems among children with ASD often persistent and highly impair functioning of both the child and the family. Children with ASD often develop gut-related comorbidities and dysbiosis can have negative effects on not only the gastrointestinal (GI) tract, but also psychological symptoms. Dietary exclusions and probiotic supplements also have been investigated in the management of ASD symptoms. Especially, there is some anecdotal evidence that probiotics supplements are able to alleviate GI symptoms as well as improve behaviors in children with ASD. METHOD AND ANALYSIS: This review will report on overall studies that include randomized control trials, randomized cross-over studies and cluster-randomized trials designs that consider curative effect in children with ASD by probiotic supplements. We will search 6 databases: MEDLINE, Embase, Scopus, PubMed, The Cochrane Library, and Web of Science and we will perform a manual search the journal Autism and information of ongoing or unpublished studies. The Mixed Methods Appraisal Tool (MMAT) will be used to assess quality of articles and the Jadad scale will be used to assess for bias. Assessment of publication bias will be performed using funnel plots generated by Comprehensive Meta-Analysis (CMA) 3.0 software. Clarifying the evidence in this area will be important for future research directions when reformulating and promoting the therapeutic regime in the field. ETHICS AND DISSEMINATION: There are no human participants, data, or tissue being directly studied for the purposes of the review; therefore, ethics approval and consent to participate are not applicable. The results of this study will be presented at conferences and published in peer-reviewed journals. REGISTRATION AND STATUS: PROSPERO 2019 CRD42019132754.

Mechanism underpinning effects of Shichangpu (Rhizoma Acori Tatarinowii) on attention deficit hyperactivity disorder.

OBJECTIVE: To investigate the mechanism underlying the effects of Shichangpu (Rhizoma Acori Tatarinowii) on attention deficit hyperactivity disorder (ADHD). METHODS: A network pharmacology approach integrating ingredients of Shichangpu (Rhizoma Acori Tatarinowii) and target with ADHD, network construction, molecular function interactions and pathway analysis was used. RESULTS: This approach successfully helped to identify 7 active ingredients of CN, interacting with 21 key targets (ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, CHRM1, CHRM2, CHRM3, PTGS1, SLC6A2, SLC6A3, SLC6A4, DRD1, DRD5, HTR2A, ADRA1D, MAOB, GRIA2, HTR1A). The molecular function interactions among candidate targets mainly consisted of four groups: G-protein coupled amine receptor activity, catecholamine binding, monoamine transmembrane transporter activity and neurotransmitter receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that Shichangpu (Rhizoma Acori Tatarinowii)-regulated pathways were mainly classified into signal transduction and monoamine neurotransmitters. CONCLUSION: Our investigation revealed that Shichangpu (Rhizoma Acori Tatarinowii) could improve the symptoms of ADHD by regulating neurotransmitter, in multiple types of compounds-target-pathway, which may be implicated in the major pathological processes of ADHD.

AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors.

The Animal Transcription Factor DataBase (AnimalTFDB) is a resource aimed to provide the most comprehensive and accurate information for animal transcription factors (TFs) and cofactors. The AnimalTFDB has been maintained and updated for seven years and we will continue to improve it. Recently, we updated the AnimalTFDB to version 3.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/) with more data and functions to improve it. AnimalTFDB contains 125,135 TF genes and 80,060 transcription cofactor genes from 97 animal genomes. Besides the expansion in data quantity, some new features and functions have been added. These new features are: (i) more accurate TF family assignment rules; (ii) classification of transcription cofactors; (iii) TF binding sites information; (iv) the GWAS phenotype related information of human TFs; (v) TF expressions in 22 animal species; (vi) a TF binding site prediction tool to identify potential binding TFs for nucleotide sequences; (vii) a separate human TF database web interface (HumanTFDB) was designed for better utilizing the human TFs. The new version of AnimalTFDB provides a comprehensive annotation and classification of TFs and cofactors, and will be a useful resource for studies of TF and transcription regulation.

Pt-Bi decorated nanoporous gold for high performance direct glucose fuel cell.

Binary PtBi decorated nanoporous gold (NPG-PtBi) electrocatalyst is specially designed and prepared for the anode in direct glucose fuel cells (DGFCs). By using electroless and electrochemical plating methods, a dense Pt layer and scattered Bi particles are sequentially coated on NPG. A simple DGFC with NPG-PtBi as anode and commercial Pt/C as cathode is constructed and operated to study the effect of operating temperatures and concentrations of glucose and NaOH. With an anode noble metal loading of only 0.45 mg cm-2 (Au 0.3 mg and Pt 0.15 mg), an open circuit voltage (OCV) of 0.9 V is obtained with a maximum power density of 8 mW cm-2. Furthermore, the maximum gravimetric power density of NPG-PtBi is 18 mW mg-1, about 4.5 times higher than that of commercial Pt/C.

Long-term quality of life outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with androgen deprivation.

With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.

[Imaging study of lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral disc herniation].

OBJECTIVE: Using regional assignment to forked method to study lumbar intervertebral disc hemiation (bugle, hernia, prolapse) dependablity and reason of lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral disc herniation. METHODS: From March 2005 to October 2006, 120 patients of match condition from orthopaedics dept and rehabilitative dept of the Boai hospital of Longyan were studied. All patients were equally divided into two groups according to whether or not accompany with symptom of lumbar intervertebral disc herniation. There was not statistical difference in sex, age, course of disease, segment of intervertebral disc between two groups. Sixty patients of symptomatic lumbar intervertebral disc herniation were equally divided into three groups according to (bugle, hernia, prolapse) image on CT. Sixty patients of asymptomatic lumbar intervertebral disc herniation were equally divided into three groups according to (bugle, hernia, prolapse) image on CT. The age was 20-59 years old with an average of 38.5 years. Using regional assignment to give a mark respectively for every group. The sagittal diameter index (SI), anterior diastema of flaval ligaments, the width of superior outlet of latero-crypt, anteroposterior diameter of dura sac were respectively measured by sliding caliper. CT value and protrusible areas were respectively evaluated by computer tomography. Adopting mean value to measure three times. RESULTS: (1) There were not statistical difference in SI, CT value, hernia areas, anteroposterior diameter of dura sac between two groups (symptomatic lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral disc herniation). There were statistical difference in the width of superior outlet of latero-crypt, anterior diastema of flaval ligaments between two groups (symptomatic lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral disc herniation). (2) There were statistical difference in protrusible type,protrusible segment between two groups (symptomatic lumbar intervertebral disc herniation and asymptomatic lumbar intervertebral disc herniation). CONCLUSION: There were not necessary relationship between in protrusible size, location, type, compression degree and clinical symptom. This paper may support the mechanism of lumbar intervertebral dise herniation that associated with the following the three aspects: (1) spinal reserve capacity (SRC); (2) involved nerve roots escaping from herniated disc compression and its elastic lengthening function; (3) hypoxia symptosis and anti-ischemia injury compensation of involved nerve roots.