Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus.

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.

Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response.

Post-translational modifications (PTMs) of proteins are crucial to guarantee the proper biological functions in immune responses. Although protein phosphorylation has been extensively studied, our current knowledge of protein pyrophosphorylation, which occurs based on phosphorylation, is very limited. Protein pyrophosphorylation is originally considered to be a non-enzymatic process, and its function in immune signaling is unknown. Here, we identify a metabolic enzyme, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), as a pyrophosphorylase for protein serine pyrophosphorylation, by catalyzing the pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 to promote robust type I interferon (IFN) responses. Uap1 deficiency significantly impairs the activation of both DNA- and RNA-viruse-induced type I IFN pathways, and the Uap1-deficient mice are highly susceptible to lethal viral infection. Our findings demonstrate the function of protein pyrophosphorylation in the regulation of antiviral responses and provide insights into the crosstalk between metabolism and innate immunity.

TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation.

Autophagy is a fundamental cellular process of protein degradation and recycling that regulates immune signaling pathways via multiple mechanisms. However, it remains unclear how autophagy epigenetically regulates the immune response. Here, we identified TRIM14 as an epigenetic regulator that reduces histone H3K9 trimethylation by inhibiting the autophagic degradation of the histone demethylase KDM4D. TRIM14 recruited the deubiquitinases USP14 and BRCC3 to cleave the K63-linked ubiquitin chains of KDM4D, which prevented KDM4D from undergoing optineurin (OPTN)-mediated selective autophagy. Tripartite motif-containing 14 (TRIM14) deficiency in dendritic cells significantly impaired the expression of the KDM4D-directed proinflammatory cytokines interleukin 12 (Il12) and Il23 and protected mice from autoimmune inflammation. Taken together, these findings highlight the cross-talk between epigenetic regulation and autophagy and suggest TRIM14 is a potential target of therapeutic intervention for inflammation-related diseases.

USP38 Inhibits Type I Interferon Signaling by Editing TBK1 Ubiquitination through NLRP4 Signalosome.

TBK1 is a component of the type I interferon (IFN) signaling pathway, yet the mechanisms controlling its activity and degradation remain poorly understood. Here we report that USP38 negatively regulates type I IFN signaling by targeting the active form of TBK1 for degradation in vitro and in vivo. USP38 specifically cleaves K33-linked poly-ubiquitin chains from TBK1 at Lys670, and it allows for subsequent K48-linked ubiquitination at the same position mediated by DTX4 and TRIP. Knockdown or knockout of USP38 increases K33-linked ubiquitination, but it abrogates K48-linked ubiquitination and degradation of TBK1, thus enhancing type I IFN signaling. Our findings identify an essential role for USP38 in negatively regulating type I IFN signaling, and they provide insights into the mechanisms by which USP38 regulates TBK1 ubiquitination through the NLRP4 signalosome.

Artificial neural network-based shelf life prediction approach in the food storage process: A review.

The prediction of food shelf life has become a vital tool for distributors and consumers, enabling them to determine storage and optimal edible time, thus avoiding unexpected food waste. Artificial neural network (ANN) have emerged as an effective, fast and accurate method for modeling, simulating and predicting shelf life in food. ANNs are capable of tackling nonlinear, complex and ill-defined problems between the variables without prior knowledge. ANN model exhibited excellent fit performance evidenced by low root mean squared error and high correlation coefficient. The low relative error between actual values and predicted values from the ANN model demonstrates its high accuracy. This paper describes the modeling of ANN in food quality prediction, encompassing commonly used ANN architectures, ANN simulation techniques, and criteria for evaluating ANN model performance. The review focuses on the application of ANN for modeling nonlinear food quality during storage, including dairy, meat, aquatic, fruits, and vegetables products. The future prospects of ANN development mainly focus on optimal models and learning algorithm selection, multiple model fusion, self-learning and self-correcting shelf-life prediction model development, and the potential utilization of deep learning techniques.

ANN-based food shelf life prediction methods are reviewed.This paper discusses application of ANN in the food storage process.BPNN is the mainstream ANN architecture used for the prediction of food quality.ANNs are useful for prediction of outputs with high accuracy.Future trends of ANN in the agri-supply chain are evaluated.

A Cooperative Hunting Method for Multi-USV Based on the A* Algorithm in an Environment with Obstacles.

A single unmanned surface combatant (USV) has poor mission execution capability, so the cooperation of multiple unmanned surface ships is widely used. Cooperative hunting is an important aspect of multi USV collaborative research. Therefore, this paper proposed a cooperative hunting method for multi-USV based on the A* algorithm in an environment with obstacles. First, based on the traditional A* algorithm, a path smoothing method based on USV minimum turning radius is proposed. At the same time, the post order traversal recursive algorithm in the binary tree method is used to replace the enumeration algorithm to obtain the optimal path, which improves the efficiency of the A* algorithm. Second, a biomimetic multi USV swarm collaborative hunting method is proposed. Multiple USV clusters simulate the hunting strategy of lions to pre-form on the target's path, so multiple USV clusters do not require manual formation. During the hunting process, the formation of multiple USV groups is adjusted to limit the movement and turning of the target, thereby reducing the range of activity of the target and improving the effectiveness of the algorithm. To verify the effectiveness of the algorithm, two sets of simulation experiments were conducted. The results show that the algorithm has good performance in path planning and target search.

Predictive growth kinetic parameters and modelled probabilities of deoxynivalenol production by Fusarium graminearum on wheat during simulated storing conditions.

AIMS: Mathematical models were employed to predict the growth kinetic parameters of Fusarium graminearum and the accumulation of deoxynivalenol (DON) during wheat storage as a function of different moisture contents (MCs) and temperatures. METHODS AND RESULTS: The colony counting method was used to quantify F. graminearum growth under different environmental conditions, and kinetic and probability models were developed to describe the effect of different MCs and temperatures on fungal growth and DON production during wheat storage. Among the employed secondary models (Arrhenius-Davey, Gibson and Cardinal), the general polynomial best predicted the fungal growth rate under varying temperature and MC during wheat storage. According to the logistic model, DON contamination was correctly predicted in 96.5% of cases. CONCLUSIONS: The maximum growth rate of fungi was 0.4889 ± 0.092 Log CFU g-1  day-1 at 25°C and 30% moisture according to the polynomial model. At below 17°C and ≤15% moisture, no fungal growth was observed. The probability model of toxin production showed no toxin production at less than 15% moisture (aw ≤0.76) and below 15°C. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first application of a probability model of DON production during wheat storage, providing a reference for preventing fungal growth and mycotoxin accumulation by F. graminearum during wheat storage and guaranteeing food product safety.

A Hybrid Multi-Target Path Planning Algorithm for Unmanned Cruise Ship in an Unknown Obstacle Environment.

To solve the problem of traversal multi-target path planning for an unmanned cruise ship in an unknown obstacle environment of lakes, this study proposed a hybrid multi-target path planning algorithm. The proposed algorithm can be divided into two parts. First, the multi-target path planning problem was transformed into a traveling salesman problem, and an improved Grey Wolf Optimization (GWO) algorithm was used to calculate the multi-target cruise sequence. The improved GWO algorithm optimized the convergence factor by introducing the Beta function, which can improve the convergence speed of the traditional GWO algorithm. Second, based on the planned target sequence, an improved D* Lite algorithm was used to implement the path planning between every two target points in an unknown obstacle environment. The heuristic function in the D* Lite algorithm was improved to reduce the number of expanded nodes, so the search speed was improved, and the planning path was smoothed. The proposed algorithm was verified by experiments and compared with the other four algorithms in both ordinary and complex environments. The experimental results demonstrated the strong applicability and high effectiveness of the proposed method.

Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development.

BACKGROUND: Very-early-onset inflammatory bowel disease (VEOIBD) is a chronic inflammatory disease of the gastrointestinal tract occurring during infancy or early childhood. NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has emerged as a crucial regulator of intestinal homeostasis; however, whether NLRP3 variants may modify VEOIBD risk is unknown. OBJECTIVE: We sought to investigate whether and how a rare NLRP3 variant, found in 3 patients with gastrointestinal symptoms, contributes to VEOIBD development. METHODS: Whole-exome sequencing and bioinformatic analysis were performed to screen disease-associated NLRP3 variants from a cohort of children with VEOIBD. Inflammasome activation was determined in reconstituted HEK293T human embryonic kidney cells with NLRP3 inflammasome components, doxycycline-inducible NLRP3 macrophages, as well as PBMCs and biopsies from patients with NLRP3 variants. Pathogenesis of the variants was determined using a dextran sulfate sodium-induced acute colitis model. RESULTS: We identified a dominant gain-of-function missense variant of NLRP3, encoded by rs772009059 (R779C), in 3 patients with gastrointestinal symptoms. Functional analysis revealed that R779C increased NLRP3 inflammasome activation and pyroptosis in macrophages. This was mediated by enhanced deubiquitination of NLRP3 via binding with deubiquitinases BRCC3 and JOSD2, which are highly expressed in myeloid cells. In a dextran sulfate sodium-induced acute colitis model, NLRP3-R779C in hematopoietic cells resulted in more severe colitis, which can be ameliorated via knockdown of BRCC3 or JOSD2. CONCLUSIONS: BRCC3 and JOSD2 mediate NLRP3-R779C deubiquitination, which promotes NLRP3 inflammasome activation and the risk of developing VEOIBD.

Fault Detection and Identification Method for Quadcopter Based on Airframe Vibration Signals.

Quadcopters are widely used in a variety of military and civilian mission scenarios. Real-time online detection of the abnormal state of the quadcopter is vital to the safety of aircraft. Existing data-driven fault detection methods generally usually require numerous sensors to collect data. However, quadcopter airframe space is limited. A large number of sensors cannot be loaded, meaning that it is difficult to use additional sensors to capture fault signals for quadcopters. In this paper, without additional sensors, a Fault Detection and Identification (FDI) method for quadcopter blades based on airframe vibration signals is proposed using the airborne acceleration sensor. This method integrates multi-axis data information and effectively detects and identifies quadcopter blade faults through Long and Short-Term Memory (LSTM) network models. Through flight experiments, the quadcopter triaxial accelerometer data are collected for airframe vibration signals at first. Then, the wavelet packet decomposition method is employed to extract data features, and the standard deviations of the wavelet packet coefficients are employed to form the feature vector. Finally, the LSTM-based FDI model is constructed for quadcopter blade FDI. The results show that the method can effectively detect and identify quadcopter blade faults with a better FDI performance and a higher model accuracy compared with the Back Propagation (BP) neural network-based FDI model.

Detoxification of Ochratoxin A by a novel Aspergillus oryzae strain and optimization of its biodegradation.

The mycotoxin Ochratoxin A (OTA) causes serious health risks and is found in food products throughout the world. The most promising method to detoxify this compound is biodegradation. In this study, Aspergillus oryzae strain M30011 was isolated and characterized based on its considerable capacity to degrade OTA. The degradation product (compound I) of A. oryzae-treated OTA was isolated, and its toxicity response was also evaluated. Furthermore, the relationships between three key cultivation condition factors affecting the OTA degradation rate were examined using the response surface methodology (RSM). Compound I was identified as ochratoxin α (C11H9O5Cl), and the toxicity response experiments indicated that A. oryzae detoxified OTA to a great extent. A maximum degradation rate of 94% was observed after 72h. This study demonstrates the potential for using A. oryzae to detoxify OTA and suggests that it could be applied in the food industry to improve food safety and quality.

A Neuron-Based Kalman Filter with Nonlinear Autoregressive Model.

The control effect of various intelligent terminals is affected by the data sensing precision. The filtering method has been the typical soft computing method used to promote the sensing level. Due to the difficult recognition of the practical system and the empirical parameter estimation in the traditional Kalman filter, a neuron-based Kalman filter was proposed in the paper. Firstly, the framework of the improved Kalman filter was designed, in which the neuro units were introduced. Secondly, the functions of the neuro units were excavated with the nonlinear autoregressive model. The neuro units optimized the filtering process to reduce the effect of the unpractical system model and hypothetical parameters. Thirdly, the adaptive filtering algorithm was proposed based on the new Kalman filter. Finally, the filter was verified with the simulation signals and practical measurements. The results proved that the filter was effective in noise elimination within the soft computing solution.

Cooperative standoff tracking of target in non-wide area using multi-UAVs with optical cameras.

In order to achieve the cooperative standoff tracking of target in non-wide area by multiple unmanned aerial vehicles (UAVs) with installed optical cameras, this paper proposes the constrained interacting multiple model (CIMM) filter to estimate the target state, as well as the time optimal guidance vector field (TOGVF) to optimize the UAV trajectory. Firstly, the geographical constraint equation deduced from the non-wide area is introduced into the traditional interacting multiple model, aiming to improve the estimation accuracy of the motion state of moving target measured from the optical cameras. According to the target motion information, the TOGVF method is then adopted to generate the velocity in the vertical plane guiding each UAV to the optimal observation height, as well as the velocity in the horizontal plane with which each UAV will converge to the standoff distance along the tangent of the limit cycle. On this basis, the speed of each UAV is adjusted in order to balance the phase difference and achieve the cooperation among multi-UAVs. The experimental results show that our method is effective in non-wide area. The estimation accuracy of target motion via CIMM increases by more than 30% compared to the single-model based filter, and the UAVs transfer to the limit cycle along the shortest path by TOGVF.

Cloning, expression, purification, antiserum preparation and its characteristics of the truncated UL6 protein of herpes simplex virus 1.

The herpes simplex virus 1 (HSV-1) portal protein UL6 is important for HSV-1 replication, however, its precise functions in the virus life cycle are poorly understood. As we known, a relatively important tool for disclosing these functions is the antiserum specifically detecting UL6 in the HSV-1-infected cell. To this end, a recombinant protein consisting of C-terminal 297-676 amino acids of UL6 fused to His-tag was expressed in E. coli and purified from inclusion body by the Ni(2+)-NTA affinity chromatography under denaturing conditions, which was then refolded and used for the preparation of antiserum in rabbit. As results, western blot and immunofluorescence assay showed that this antiserum could specifically detect the purified truncated UL6 as well as native UL6 in the HSV-1 infected cells, indicating that the prepared antiserum could serve as a valuable tool for further exploring the functions of UL6.

Molecular cloning and characterization of pseudorabies virus EP0 gene.

The pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the exact function of EP0 is not clear. In this study, using polymerase chain reaction, a 1,104 base-pair sequence of the EP0 gene was amplified from the PRV Becker strain genome and identification of the EP0gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV EP0 gene encoded a putative polypeptide with 367 amino acids. The encoded protein, designated as EP0 contained a conserved RING-finger superfamily domain and was found to be closely related with the herpes virus RING-finger superfamily and was highly conserved among the counterparts encoded by RING-finger genes. Multiple nucleic acid sequence and amino-acid sequence alignments suggested that PRV EP0 showed a relatively higher similarity with EP0-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV EP0 had a close evolutionary relationship with members of genus Varicellovirus, especially bovine herpesvirus 1 (BoHV-1) and BoHV-5. Antigen prediction indicated that several potential B-cell epitopes were located in EP0. Also, subcellular localization analysis demonstrated that EP0 was predominantly localized in the nucleus, suggesting that it might function as a nuclear-targeted protein.

[Progress on study of factors influencing the prognosis and complications of surgery for discoid meniscus injury in children].

The discoid meniscus is a common congenital meniscal malformation that is prevalent mainly in Asians and often occurs in the lateral discoid meniscus. Patients with asymptomatic discoid meniscus are usually treated by conservative methods such as observation and injury avoidance, while patients with symptoms and tears need to be treated surgically. Arthroscopic saucerization combined with partial meniscectomy and meniscus repair is the most common surgical approach., and early to mid-term reports are good. The prognostic factors are the patient's age at surgery、follow-up time and type of surgery. Some patients experience complications such as prolonged postoperative knee pain, early osteoarthritis, retears and Osteochondritis dissecans. The incidence of prolonged postoperative knee pain was higher and the incidence of Osteochondritis dissecans was the lowest. Retears of the lateral meniscus is the main reason for reoperation.

A rare case of Baker's cysts with hematoma of the lower calf treated with arthroscopic internal drainage combined with intramuscular dissection.

Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.

Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1.

Immunotherapy has greatly improved cancer treatment in recent years by harnessing the immune system to target cancer cells. The first immunotherapeutic agent approved by the US Food and Drug Administration (FDA) was interferon a (IFNa). Treatment with IFNa can lead to effective immune activation and attenuate tumor immune evasion, but persistent treatment has been shown to elicit immune suppressive effects. Here, we identified an autophagy-dependent mechanism by which IFNa triggers tumor immune evasion by upregulating PD-L1 to suppress the anti-tumor activity of CD8+ T cells. Mechanistically, IFNa increased transcription of TRIM14, which recruited the deubiquitinase USP14 to inhibit the autophagic degradation of PD-L1. USP14 removed K63-linked ubiquitin chains from PD-L1, impairing its recognition by the cargo receptor p62 (also known as SQSTM1) for subsequent autophagic degradation. Combining the USP14 inhibitor IU1 with IFNa and anti-CTLA4 treatment effectively suppressed tumor growth without significant toxicity. This work suggests a strategy for targeting selective autophagy to abolish PD-L1-mediated cancer immune evasion.

Tibial tubercle avulsion fracture following preexisting Osgood-Schlatter disease in an adolescent: a case report.

Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.

Closed-loop seizure modulation via extreme learning machine based extended state observer.

Neuromodulation is a promising way in clinical treatment of epilepsy, but the existing methods cannot adjust stimulations according to patients' real-time reactions. Therefore, it is necessary to acquire a systematic and a scientific regulation method based on patients' real-time reactions. The linear active disturbance rejection control can adapt to complex epileptic dynamics and improve the epilepsy regulation, even if little model information is available, and various uncertainties and external disturbances exist. However, a linear extended state observer estimates the time-varying total disturbance with a steady-state error. To improve regulation, it is crucial to estimate the total disturbance in a more accurate manner. An extreme learning machine is capable of approximating any nonlinear function. Its initial parameter generation is more convenient, adjustable parameters are fewer, and learning speed is faster. Thus, a nonlinear time-varying function can be estimated more timely and accurately. Then, an extreme learning machine based extended state observer is proposed to get a more satisfactory total disturbance estimation and more desired closed-loop regulation. The convergence of the extreme learning machine based extended state observer is verified and the stability of the closed-loop system is analyzed. Numerical results show that the proposed extended state observer is much better than a linear extended state observer in estimating the total disturbance. It guarantees a more satisfied closed-loop neuromodulation.