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Summary: T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORγt roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORγt/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4+ T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1β, which in turn promotes Ccr6 expression on CD4+ T cells during EAE pathogenesis. Our findings highlight different RORγt-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses.

Choristoneura metasequoiacola Liu, 1983 is an important caterpillar species that specifically infests the leaves and branches of Metasequoia glyptostroboides Hu & W. C. Cheng 1948 with short larval infestations, long-term dormancy, and has a limited distribution in Lichuan, Hubei, China. The complete mitochondria genome of C. metasequoiacola was determined by using Illumina NovaSeq, and analyzed based on previously annotated sibling species. In total, we obtained mitochondria genome with 15,128 bp in length, circular in shape with a double-stranded closed ring structure, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and an AT-rich region. Of which the nucleotide composition was highly A + T biased, accounting for 81.98% of the whole mitogenome. Thirteen protein-coding genes (PCGs) were 11,142 bp; Twenty-two tRNA genes and AT-rich region were 1,472 and 199 bp, respectively. Phylogenetically, the relationship between Choristoneura spp. (containing C. metasequoiacola) and Adoxophyes spp. was closer than any other two genera from Tortricidae, and the relationship between C. metasequoiacola and C.murinana was the closest among nine sibling species from that genus, which helps to explain species evolution within the family Tortricidae.

Highlights Kevlar polyanionic chains induced the formation of highly ordered porous thermoplastic polyurethane foams with adjustable pore sizes. A tiny amount of Ti3C2Tx MXene was performed as reducing agent for the electroless deposition of copper nanoparticles. The conductive foam reinforced by aramid nanofibers exhibited excellent piezoresistive sensing and electromagnetic interference shielding performance.

Dendrolimus houi Lajonquière is one of the most prevalent pine caterpillars in southern China, causing overwhelming forest infestation. It can overcome the negative impact of host shift from the original host, Cryptomeria fortune, to other tree species to complete its life cycle. In this work, D. houi larvae (1st to 3rd instar), originally feeding on C. fortunei needles, were used to determine the changes in the growth and development after they moved to needles of Cupressus funebris and Pinus yunnanensis during their 4th to 5th instar. Metabonomics and transcriptomics were conducted to evaluate the effects of the host shift on metabolite accumulation and gene expression of D. houi larvae. The results showed that the host shift significantly inhibited the pest growth and development by extending developmental duration and minifying the body length, body weight and head shell width. Besides, we found that the host shift influenced steroid hormone biosynthesis in D. houi larvae, which might lead to their abnormal development. The results may help to understand the response of D. houi larvae to host shift, and their adaptation mechanism to different hosts during multiple life cycles, providing a new plantation mode for mixed forests to suppress D. houi as well.

Background: Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. Methods: Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14–3–3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. Results: NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14–3–3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. Conclusions: NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.

Otosclerosis is caused by abnormal bone remodeling in the middle ear, resulting in progressive hearing loss, dizziness, balance problems, and tinnitus. Previous infection, stress fractures of the bony tissue surrounding the inner ear, immune disorders, and genetic factors are believed to contribute to this disease. Currently, no effective drug treatment for otosclerosis is known. Herein, we generated an induced pluripotent stem cell line from the peripheral blood mononuclear cells of an otosclerosis patient. The cell line exhibited normal morphology, karyotype, and pluripotency marker expression. A teratoma assay revealed successful differentiation into all three germ layers.

Robotic bin-picking is a common process in modern manufacturing, logistics, and warehousing that aims to pick-up known or unknown objects with random poses out of a bin by using a robot-camera system. Rapid and accurate object pose estimation pipelines have become an escalating issue for robot picking in recent years. In this paper, a fast 6-DoF (degrees of freedom) pose estimation pipeline for random bin-picking is proposed in which the pipeline is capable of recognizing different types of objects in various cluttered scenarios and uses an adaptive threshold segment strategy to accelerate estimation and matching for the robot picking task. Particularly, our proposed method can be effectively trained with fewer samples by introducing the geometric properties of objects such as contour, normal distribution, and curvature. An experimental setup is designed with a Kinova 6-Dof robot and an Ensenso industrial 3D camera for evaluating our proposed methods with respect to four different objects. The results indicate that our proposed method achieves a 91.25% average success rate and a 0.265s average estimation time, which sufficiently demonstrates that our approach provides competitive results for fast objects pose estimation and can be applied to robotic random bin-picking tasks.

In this study, we investigate the problem of cooperative kinematic control for multiple redundant manipulators under partially known information using recurrent neural network (RNN). The communication among manipulators is modeled as a graph topology network with the information exchange that only occurs at the neighbouring robot nodes. Under partially known information, four objectives are simultaneously achieved, i.e, global cooperation and synchronization among manipulators, joint physical limits compliance, neighbor-to-neighbor communication among robots, and optimality of cost function. We develop a velocity observer for each individual manipulator to help them to obtain the desired motion velocity information. Moreover, a negative feedback term is introduced with a higher tracking precision. Minimizing the joint velocity norm as cost function, the considered cooperative kinematic control is built as a quadratic programming (QP) optimization problem integrating with both joint angle and joint speed limitations, and is solved online by constructing a dynamic RNN. Moreover, global convergence of the developed velocity observer, RNN controller and cooperative tracking error are theoretically derived. Finally, under a fixed and variable communication topology, respectively, application in using a group of iiwa R800 redundant manipulators to transport a payload and comparison with the existing method are conducted. Among the simulative results, the robot group synchronously achieves the desired circle and rhodonea trajectory tracking, with higher tracking precision reaching to zero. When joint angles and joint velocities tend to exceed the setting constraints, respectively, they are constrained into the upper and lower bounds owing to the designed RNN controller.

Learning movement primitive from unstructured demonstrations has become a popular topic in recent years, which provides a natural way to endow human-inspired skills to robots. The main idea of movement primitives is that should suffice to reconstruct a large set of complex manipulation tasks. However, conventional learning methods mostly focus on the kinesthetic variables and ignore those critical introspective capacities in manipulation such as movement generalization and assessment of the sensory signals. In this paper, we investigate the association of generalization, fault detection, fault diagnoses, and task exploration during manipulation task, and call such movement primitives augmented with introspective capacities Introspective Movement Primitives (IMP). With our previous work, this paper mainly addresses how IMPs can be acquired by assessing the quality of multimodal sensory data of unstructured demonstrations and how they can incrementally create manipulation task by reverse execution and human interaction. Experimental evaluation on a human-robot collaborative packaging task with a Rethink Baxter robot, results indicate that our proposed method can effectively increase robustness towards external perturbations and adaptive exploration during robot manipulation task.

Waardenburg syndrome (WS) is an inherited auditory-pigmentary syndrome characterized by deafness and pigment abnormalities. Here, we generated an induced pluripotent stem cell (iPSC) line using episomal plasmid vectors from the fibroblasts of an 8-year-old boy affected with WS, caused by a novel mutation in the SOX10 gene (NM_006941.3: c.937_947del; p.Tyr313Argfs*85), with a concurrent hotspot mutation in the GJB2 gene (NM_004004.5:c.235delC; p.Leu79Cysfs*3). The expression of pluripotency markers of the iPSC cell line was verified at both the mRNA and protein levels and the pluripotency state of the cell line was demonstrated by the capability to differentiate into all three germ layers.

The differentially expressed genes (DEGs), key genes and metabolic pathways of the parasitic beetle, Dastarcus helophoroides (Fairmaire), were compared between the fiftieth commercially reared population and the first natural population to reveal the adaptive mechanism in response to high temperature stress. The high-throughput sequencing technique was employed for transcriptome sequencing of two populations of D. helophoroides. In total, 47,763 non-redundant transcripts with the average length of 989.31 bp and the N50 of 1607 bp were obtained. Under high temperature stress, 1108 DEGs were found in the commercial population; while there were 3946 DEGs in the natural population, which were higher than those in the commercial population (3.56 times). High temperature stress of D. helophoroides promoted the expression of heat shock proteins (HSPs) and metabolism-related genes in both populations, but metabolism synthesis and hydrolysis of natural population was much higher, allowing them to produce more resistant substances (such as HSPs, superoxide dismutase (SOD), peroxiredoxin (Prx), etc.). Therefore, HSPs may play a major role in the high temperature adaptation of a commercial population, while the natural population probably respond to heat stress with more resistant substances (such as HSPs, SOD, Prx, etc.). These results provide a reference to select and domesticate a specific ecotype with stronger adaptability to the high temperature weather in the forest and further improve the efficiency of D. helophoroides as a bio-control factor.

A persistent increase in the number of lung fibroblasts (LFs) is found in the interstitium of the lungs of infants with bronchopulmonary dysplasia (BPD), which leads to lung fibrosis. P16 methylation plays an important role in the pathogenesis of BPD. 5-aza-2′-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. This study investigated the effects of 5-aza-CdR on LFs in vitro from a hyperoxia-induced lung fibrosis model in newborn rats. Methods: Methylation-specific polymerase chain reaction (PCR) and Western blotting were performed to determine P16 gene methylation status and protein expression after LFs were treated with 0 μmol/L, 0.5 μmol/L, 1.0 μmol/L, and 5.0 μmol/L 5-aza-CdR for 120 hours. Proliferation was assessed by an MTT assay after LFs were treated with 0 μmol/L, 0.5 μmol/L, 1.0 μmol/L, and 5.0 μmol/L 5-aza-CdR for 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. At the final time point, cells were also analyzed by flow cytometry to identify any change in their cell cycle profiles. Results: A methylated P16 gene promoter was detected in hyperoxia LFs. Following treatment with 5-aza-CdR, partial methylation and demethylation was detected. The expression protein's level of the P16 gene was significantly higher in the 5.0 μmol/L 5-aza-CdR-treated group compared with that in the control group (p

Robot introspection aids robots to understand what they do and how they do it. Previous robot introspection techniques have often used parametric hidden Markov models or supervised learning techniques, implying that the number of hidden states or classes is defined a priori and fixed through the entire modeling process. Fixed parameterizations limit the modeling power of a process to properly encode the data. Furthermore, first-order Markov models are limited in their ability to model complex data sequences that represent highly dynamic behaviors as they assume observations are conditionally independent given the state. In this work, we contribute a Bayesian nonparametric autoregressive Hidden Markov model for the monitoring of robot contact tasks, which are characterized by complex dynamical data that are hard to model. We used a nonparametric prior that endows our hidden Markov models with an unbounded number of hidden states for a given robot skill (or subtask). We use a hierarchical Dirichlet stochastic process prior to learn an hidden Markov model with a switching vector autoregressive observation model of wrench signatures and end-effector pose for the manipulation contact tasks. The proposed scheme monitors both nominal skill execution and anomalous behaviors. Two contact tasks are used to measure the effectiveness of our approach: (i) a traditional pick-and-place task composed of four skills and (ii) a cantilever snap assembly task (also composed of four skills). The modeling performance or our approach was compared with other methods, and classification accuracy measures were computed for skill and anomaly identification. The hierarchical Dirichlet stochastic process prior to learn an hidden Markov model with a switching vector autoregressive observation model was shown to have excellent process monitoring performance with higher identification rates and monitoring ability.

Robot introspection is expected to greatly aid longer-term autonomy of autonomous manipulation systems. By equipping robots with abilities that allow them to assess the quality of their sensory data, robots can detect and classify anomalies and recover appropriately from common anomalies. This work builds on our previous Sense-Plan-Act-Introspect-Recover (SPAIR) system. We introduce an improved anomaly detector that exploits latent states to monitor anomaly occurrence when robots collaborate with humans in shared workspaces, but also present a multiclass classifier that is activated with anomaly detection. Both implementations are derived from Bayesian non-parametric methods with strong modeling capabilities for learning and inference of multivariate time series with complex and uncertain behavior patterns. In particular, we explore the use of a hierarchical Dirichlet stochastic process prior to learning a Hidden Markov Model (HMM) with a switching vector auto-regressive observation model (sHDP-VAR-HMM). The detector uses a dynamic log-likelihood threshold that varies by latent state for anomaly detection and the anomaly classifier is implemented by calculating the cumulative log-likelihood of testing observation based on trained models. The purpose of our work is to equip the robot with anomaly detection and anomaly classification for the full set of skills associated with a given manipulation task. We consider a human–robot cooperation task to verify our work and measure the robustness and accuracy of each skill. Our improved detector succeeded in detecting 136 common anomalies and 368 nominal executions with a total accuracy of 91.0%. An overall anomaly classification accuracy of 97.1% is derived by performing the anomaly classification on an anomaly dataset that consists of 7 kinds of detected anomalies from a total of 136 anomalies samples.

Background: Depression and smoking decrease health status in Chronic Obstructive Pulmonary Disease (COPD), but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of depression and smoking on the severity of patients with COPD. Methods: A prospective cohort study including 2,268 patients with COPD was conducted in seven rural communities from May 2008 to May 2012. The relationships between the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and depression and nicotine addiction were assessed. The product of depression and smoking was added to the logistic regression model to evaluate the multiplicative interaction and relative excess risk of interaction (RERI). The Attributable Proportion (AP) of interaction and the synergy index (S) was applied to evaluate the additive interaction of two factors. Results: The severity of COPD in patients with depressive symptoms who never smoked was increased 1.74-fold and in smoking patients it increased by 6.08-fold. Highly addicted smokers with depressive symptoms had a nearly 40-fold increase in severity (all P

The quantitative structure-activity relationship (QSAR) of 18 Ti-phenoxy-imine (FI-Ti)-based catalysts was investigated to clarify the role of the structural properties of the catalysts in polyethylene polymerization activity. The electronic properties of the FI-Ti catalysts were analyzed based on density functional theory with the M06L/6-31G** and LANL2DZ basis functions. The analysis results of the QSAR equation with a genetic algorithm showed that the polyethylene catalytic activity mainly depended on the highest occupied molecular orbital energy level and the total charge of the substituent group on phenylimine ring. The QSAR models showed good predictive ability (R2) and R2 cross validation (R2cv) values of greater than 0.927. The design concept is “head-hat”, where the hats are the phenoxy-imine substituents, and the heads are the transition metals. Thus, for the newly designed series, the phenoxy-imine substituents still remained, while the Ti metal was replaced by Zr or Ni transition metals, entitled FI-Zr and FI-Ni, respectively. Consequently, their polyethylene polymerization activities were predicted based on the obtained QSAR of the FI-Ti models, and it is noteworthy that the FI-Ni metallocene catalysts tend to increase the polyethylene catalytic activity more than that of FI-Zr complexes. Therefore, the new designs of the FI-Ni series are proposed as candidate catalysts for polyethylene polymerization, with their predicted activities in the range of 35,000–48,000 kg(PE)/mol(Cat.)·MPa·h. This combined density functional theory and QSAR analysis is useful and straightforward for molecular design or catalyst screening, especially in industrial research.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a novel therapeutic tool to induce a suppression of tinnitus. However, the optimal target sites are unknown. We aimed to determine whether low-frequency rTMS induced lasting suppression of tinnitus by decreasing neural activity in the cortex, navigated by high-density electroencephalogram (EEG) source analysis, and the utility of EEG for targeting treatment.In this controlled three-armed trial, seven normal hearing patients with tonal tinnitus received a 10-day course of 1-Hz rTMS to the cortex, navigated by high-density EEG source analysis, to the left temporoparietal cortex region, and to the left temporoparietal with sham stimulation. The Tinnitus handicap inventory (THI) and a visual analog scale (VAS) were used to assess tinnitus severity and loudness. Measurements were taken before, and immediately, 2 weeks, and 4 weeks after the end of the interventions.Low-frequency rTMS decreased tinnitus significantly after active, but not sham, treatment. Responders in the EEG source analysis-based rTMS group, 71.4% (5/7) patients, experienced a significant reduction in tinnitus loudness, as evidenced by VAS scores. The target site of neuronal generators most consistently associated with a positive response was the frontal lobe in the right hemisphere, sourced using high-density EEG equipment, in the tinnitus patients. After left temporoparietal rTMS stimulation, 42.8% (3/7) patients experienced a decrease in tinnitus loudness.Active EEG source analysis based rTMS resulted in significant suppression in tinnitus loudness, showing the superiority of neuronavigation-guided coil positioning in dealing with tinnitus. Non-auditory areas should be considered in the pathophysiology of tinnitus. This knowledge in turn can contribute to investigate the pathophysiology of tinnitus.