Late-onset renal TMA and tubular injury in cobalamin C disease: a report of three cases and literature review.

BACKGROUND: Mutation of MMACHC gene causes cobalamin C disease (cblC), an inherited metabolic disorder, which presents as combined methylmalonic aciduria (MMA-uria) and hyperhomocysteinaemia in clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported. This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists. CASE PRESENTATION: Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical presentation. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealing elevated serum and urine homocysteine, renal biopsy showing TMA and tubular injury, along with genetic testing showing heterogeneous compound mutations in MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them got improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered. CONCLUSIONS: The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease. CLINICAL TRIAL NUMBER: Not applicable.

Recognition method for the bionic camouflage click communication trains modulated by time delay difference.

Bionic camouflage covert underwater acoustic communication has recently attracted great attention. However, we have not found relevant methods or literature to recognize these bionic camouflage communication signals (BCCSs) in the area of anti-reconnaissance. Focused on recognizing the BCCSs, this article proposes a recognition method based on the statistics of inter-click intervals to recognize the camouflaged click communication train (CCCT), which is modulated by time delay difference (TDD). We first analyze the characteristics of TDD distributions of CCCT and real click train (RCT). According to the coding principle, the TDDs of CCCTs present a ladder-like distribution with a fixed time step, and the TDDs are equal to the integral multiple of the fixed time step. On the contrary, the TDDs of RCTs are approximately random distribution within a certain time range. Therefore, based on the different TDD distributions, this article classifies CCCTs and RCTs by utilizing the statistical property of TDD distributions. To measure the TDDs of diverse cetacean clicks accurately, a new click location scheme based on the dynamic window energy ratio is proposed. Next, based on the statistics of TDD distribution, the influences of the TDDs that are caused by multipath interferences are eliminated by iteration. Simulations demonstrate the accuracy of the recognition method under different conditions.

An automated piecewise synthesis method for cetacean tonal sounds based on time-frequency spectrogram.

Bionic signal waveform design plays an important role in biological research, as well as bionic underwater acoustic detection and communication. Most conventional methods cannot construct high-similarity bionic waveforms to match complex cetacean sounds or easily modify the time-frequency structure of the synthesized bionic signals. In our previous work, we proposed a synthesis and modification method for cetacean tonal sounds, but it requires a lot of manpower to construct each bionic signal segment to match the tonal sound contour. To solve these problems, an automated piecewise synthesis method is proposed. First, based on the time-frequency spectrogram of each tonal sound, the fundamental contour and each harmonic contour of the tonal sound is automatically recognized and extracted. Then, based on the extracted contours, four sub power frequency modulation bionic signal models are combined to match cetacean sound contours. Finally, combining the envelopes of the fundamental frequency and each harmonic, the synthesized bionic signal is obtained. Experimental results show that the Pearson correlation coefficient (PCC) between all true cetacean sounds and their corresponding bionic signals are higher than 0.95, demonstrating that the proposed method can automatically imitate all kinds of simple and complex cetacean tonal sounds with high similarity.

Modeling and Experimental Testing of an Unmanned Surface Vehicle with Rudderless Double Thrusters.

Motion control of unmanned surface vehicles (USVs) is a crucial issue in sailing performance and navigation costs. The actuators of USVs currently available are mostly a combination of thrusters and rudders. The modeling for USVs with rudderless double thrusters is rarely studied. In this paper, the three degrees of freedom (DOFs) dynamic model and propeller thrust model of this kind of USV were derived and combined. The unknown parameters of the propeller thrust model were reduced from six to two. In the three-DOF model, the propulsion of the USV was completely provided by the resultant force generated by double thrusters and the rotational moment was related to the differential thrust. It combined the propeller thrust model to represent the thrust in more detail. We performed a series of tests for a 1.5 m long, 50 kg USV, in order to obtain the model parameters through system identification. Then, the accuracy of the modeling and identification results was verified by experimental testing. Finally, based on the established model and the proportional derivative+line of sight (PD+LOS) control algorithm, the path-following control of the USV was achieved through simulations and experiments. All these demonstrated the validity and practical value of the established model.

Self-Contained High-SNR Underwater Acoustic Signal Acquisition Node and Synchronization Sampling Method for Multiple Distributed Nodes.

Aiming at the application demand in underwater noise monitoring, observation of marine animal, antisubmarine and underwater target localization, a high-SNR underwater acoustic signal acquisition (UASA) node that combines a self-contained acquisition system and floating platform is designed to improve the acquisition performance of a single UASA node, and a high-accuracy synchronization sampling method among multiple distributed UASA nodes based on master-slave dual phase-locked loops (MSDPLL) is proposed to improve the synchronization sampling accuracy. According to the equivalent model of hydrophone and application requirements, low noise signal conditioning circuit and large-capacity data storage modules are designed. Based on the long-term monitoring requirements for underwater acoustic signal and distributed positioning requirements for underwater targets, the structure of a single UASA node is designed and MSDPLL is developed for high-accuracy synchronization sampling among multiple UASA nodes. Related experimental results verified the performance of the UASA node and the synchronization sampling method.

Bio-Inspired Covert Active Sonar Strategy.

The covertness of the active sonar is a very important issue and the sonar signal waveform design problem was studied to improve covertness of the system. Many marine mammals produce call pulses for communication and echolocation, and existing interception systems normally classify these biological signals as ocean noise and filter them out. Based on this, a bio-inspired covert active sonar strategy was proposed. The true, rather than man-made sperm whale, call pulses were used to serve as sonar waveforms so as to ensure the camouflage ability of sonar waveforms. A range and velocity measurement combination (RVMC) was designed by using two true sperm whale call pulses which had excellent range resolution (RR) and large Doppler tolerance (DT). The range and velocity estimation methods were developed based on the RVMC. In the sonar receiver, the correlation technology was used to confirm the start and end time of sonar signals and their echoes, and then based on the developed range and velocity estimation method, the range and velocity of the underwater target were obtained. Then, the RVMC was embedded into the true sperm whale call-train to improve the camouflage ability of the sonar signal-train. Finally, experiment results were provided to verify the performance of the proposed method.

Erratum: Sandeep P., et al. An Efficient Biometric-Based Algorithm Using Heart Rate Variability for Securing Body Sensor Networks. Sensors 2015, 15, 15067-15089.

n/a.

Guided-Mode-Leaky-Mode-Guided-Mode Fiber Interferometer and Its High Sensitivity Refractive Index Sensing Technology.

A cascaded symmetrical dual-taper Mach-Zehnder interferometer structure based on guided-mode and leaky-mode interference is proposed in this paper. Firstly, the interference spectrum characteristics of interferometer has been analyzed by the Finite Difference-Beam Propagation Method (FD-BPM). When the diameter of taper waist is 20 µm-30 µm, dual-taper length is 1 mm and taper distance is 4 cm-6 cm, the spectral contrast is higher, which is suitable for sensing. Secondly, experimental research on refractive index sensitivity is carried out. A refractive index sensitivity of 62.78 nm/RIU (refractive index unit) can achieved in the RI range of 1.3333-1.3792 (0%~25% NaCl solution), when the sensor structure parameters meet the following conditions: diameter of taper waist is 24 µm, dual-taper length is 837 µm and taper distance is 5.5 cm. The spectrum contrast is 0.8 and measurement resolution is 1.6 × 10(-5) RIU. The simulation analysis is highly consistent with experimental results. Research shows that the sensor has promising application in low RI fields where high-precision measurement is required due to its high sensitivity and stability.

An Efficient Biometric-Based Algorithm Using Heart Rate Variability for Securing Body Sensor Networks.

Body Sensor Network (BSN) is a network of several associated sensor nodes on, inside or around the human body to monitor vital signals, such as, Electroencephalogram (EEG), Photoplethysmography (PPG), Electrocardiogram (ECG), etc. Each sensor node in BSN delivers major information; therefore, it is very significant to provide data confidentiality and security. All existing approaches to secure BSN are based on complex cryptographic key generation procedures, which not only demands high resource utilization and computation time, but also consumes large amount of energy, power and memory during data transmission. However, it is indispensable to put forward energy efficient and computationally less complex authentication technique for BSN. In this paper, a novel biometric-based algorithm is proposed, which utilizes Heart Rate Variability (HRV) for simple key generation process to secure BSN. Our proposed algorithm is compared with three data authentication techniques, namely Physiological Signal based Key Agreement (PSKA), Data Encryption Standard (DES) and Rivest Shamir Adleman (RSA). Simulation is performed in Matlab and results suggest that proposed algorithm is quite efficient in terms of transmission time utilization, average remaining energy and total power consumption.

Crescentic Glomerulonephritis and Portal Hypertension with Chronic Q Fever: A Case Report and Comprehensive Literature Review.

Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient's renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.

Effect of dietary supplementation with recombinant human lysozyme on growth performance, antioxidative characteristics, and intestinal health in broiler chickens.

Lysozyme is often used as a feed additive to act as an antibacterial protein that boosts the immune system of livestock and poultry while protecting against pathogens. To investigate the effects of recombinant human lysozyme (rhLYZ) from Pichia pastoris and chlortetracycline on broiler chicken's production performance, antioxidant characteristics, and intestinal microbiota, a total of 200, 1-d-old male Arbor Acres broiler chickens (46.53 ±â€…0.42 g) were selected for a 42-d experiment. Dietary treatments included a basal diet of corn-soybean meal supplemented with either 0 mg/kg (CON), 50 mg/kg aureomycin (ANT), 20 mg/kg rhLYZ (LOW), 60 mg/kg rhLYZ (MEDIUM), or 180 mg/kg rhLYZ (HIGH). Compared with CON, MEDIUM diet increased (P < 0.05) average daily gain (67.40 g) of broilers from day 22 to 42. In the early (1.29) and overall phases (1.69), MEDIUM led to a reduction (P < 0.05) in the feed conversion ratio of broiler chickens. Furthermore, in comparison to the CON and ANT, MEDIUM exhibited reduced (P < 0.05) levels of INF-γ and tumor necrosis factor-α in the serum. In the cecum, the abundance of Monoglobus and Family_XIII_AD3011_group was lower (P < 0.05) in the MEDIUM treatment compared to CON. Overall, supplementation of 60 mg/kg of rhLYZ improved growth performance, nutrient utilization efficiency, and serum immune function, while also influencing the composition of intestinal microbiota. This suggests lysozyme's potential to replace antibiotic additives in feed.

The aim of this study was to explore the effects of recombinant human lysozyme (rhLYZ) produced from Pichia pastoris and chlortetracycline on broiler chicken performance, antioxidant properties, and gut microbiota. A 42-d experiment was conducted, involving 200 1-d-old male Arbor Acres broiler chickens. We provided different diets: a standard diet (CON), a diet with 50 mg/kg aureomycin (ANT), a diet with 20 mg/kg rhLYZ (LOW), a diet with 60 mg/kg rhLYZ (MEDIUM), or a diet with 180 mg/kg rhLYZ (HIGH). The results showed that, compared to the control group, the MEDIUM group significantly increased the average daily gain of broilers to 67.40 g from day 22 to 42. Additionally, the MEDIUM group exhibited a reduced feed conversion ratio during both the early and overall growth stages of the chickens. Furthermore, serum levels of INF-γ and tumor necrosis factor-α were lower in the MEDIUM group compared to both the CON and ANT groups. In the cecum, the abundance of Monoglobus and Family_XIII_AD3011_group was also lower in the MEDIUM treatment compared to the CON group. Overall, supplementation with 60 mg/kg of rhLYZ improved growth performance, nutrient utilization efficiency, and serum immune function in broiler chickens while also influencing the composition of their intestinal microbiota. This suggests the potential of lysozyme as a replacement for antibiotic additives in feed.

Hypothalamic-hindbrain circuit for consumption-induced fear regulation.

To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.

Distinct Circuits From the Central Lateral Amygdala to the Ventral Part of the Bed Nucleus of Stria Terminalis Regulate Different Fear Memory.

BACKGROUND: The ability to differentiate stimuli that predict fear is critical for survival; however, the underlying molecular and circuit mechanisms remain poorly understood. METHODS: We combined transgenic mice, in vivo transsynaptic circuit-dissecting anatomical approaches, optogenetics, pharmacological methods, and electrophysiological recording to investigate the involvement of specific extended amygdala circuits in different fear memory. RESULTS: We identified the projections from central lateral amygdala (CeL) protein kinase C δ (PKCδ)-positive neurons and somatostatin (SST)-positive neurons to GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons in the ventral part of the bed nucleus of stria terminalis (vBNST). Prolonged optogenetic activation or inhibition of the PKCδCeL-vBNST pathway specifically reduced context fear memory, whereas the SSTCeL-vBNST pathway mainly reduced tone fear memory. Intriguingly, optogenetic manipulation of vBNST neurons that received the projection from PKCδCeL neurons exerted bidirectional regulation of context fear, whereas manipulation of vBNST neurons that received the projection from SSTCeL neurons could bidirectionally regulate both context and tone fear memory. We subsequently demonstrated the presence of δ and κ opioid receptor protein expression within the CeL-vBNST circuits, potentially accounting for the discrepancy between prolonged activation of GABAergic circuits and inhibition of downstream vBNST neurons. Finally, administration of an opioid receptor antagonist cocktail on the PKCδCeL-vBNST or SSTCeL-vBNST pathway successfully restored context or tone fear memory reduction induced by prolonged activation of the circuits. CONCLUSIONS: Together, these findings establish a functional role for distinct CeL-vBNST circuits in the differential regulation and appropriate maintenance of fear.

Stage-specificity of STING activation in intrahepatic cholangiocarcinoma determines the efficacy of its agonism.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with an extremely poor prognosis, and new treatment options are needed. Recently, immunotherapy has emerged as an efficient treatment against malignant tumors, but less effective in iCCA. Activation of stimulator of interferon genes (STING) signaling could reignite immunologically inert tumors, but the expression and role of STING in iCCA remains to be determined. Here, we show STING is expressed in iCCA, and patients with high expression of STING in early-stage iCCA have a longer overall survival than those have low expression. Increased immune cell infiltration in early-stage iCCA corresponds to elevated STING expression. In mice iCCA models, treatment with the STING agonist MSA-2 show stage-specific inhibitory effects on tumors, with beneficial effects in early-stage tumors but not with advanced-stage cancer. This discrepancy was associated with greater programmed cell death ligand 1 (PD-L1) expression in advanced-stage tumors. Combination therapy targeting PD-L1 and MSA-2 strikingly reduced tumor burden in such tumors compared to either monotherapy. Cumulatively, these data demonstrate that STING agonism monotherapy improves the immune landscape of the tumor microenvironment in early-stage iCCA, while combination therapy ameliorates advanced-stage iCCA.

Expression and characterization of α-L-arabinofuranosidase derived from Aspergillus awamori and its enzymatic degradation of corn byproducts with xylanase.

In this study, α-L-arabinofuranosidase (AF) from Aspergillus awamori was heterologously expressed in Pichia pastoris X33, with a 1-fold increase in AF activity after codon and vector optimization. AF remained stable at 60-65 °C and displayed a broad pH stability range of 2.5-8.0. It also demonstrated considerable resistance to pepsin and trypsin. Furthermore, compared with xylanase alone, AF with xylanase exhibited a marked synergistic effect in the degradation of expanded corn bran, corn bran, and corn distillers' dried grains with solubles, reducing sugars by 3.6-fold, 1.4-fold, and 6.5-fold, respectively, with the degree of synergy increasing to 4.61, 2.44, and 5.4, respectively, while in vitro dry matter digestibility values were 17.6%, 5.2%, and 8.8%, respectively. After enzymatic saccharification, corn byproducts were converted to prebiotic xylo-oligosaccharides and arabinoses, thereby demonstrating the favorable properties of AF in the degradation of corn biomass and its byproducts.

Molecular and cellular evolution of the amygdala across species analyzed by single-nucleus transcriptome profiling.

The amygdala, or an amygdala-like structure, is found in the brains of all vertebrates and plays a critical role in survival and reproduction. However, the cellular architecture of the amygdala and how it has evolved remain elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in the amygdala of humans, macaques, mice, and chickens. Abundant neuronal cell types from different amygdala subnuclei were identified in all datasets. Cross-species analysis revealed that inhibitory neurons and inhibitory neuron-enriched subnuclei of the amygdala were well-conserved in cellular composition and marker gene expression, whereas excitatory neuron-enriched subnuclei were relatively divergent. Furthermore, LAMP5+ interneurons were much more abundant in primates, while DRD2+ inhibitory neurons and LAMP5+SATB2+ excitatory neurons were dominant in the human central amygdalar nucleus (CEA) and basolateral amygdalar complex (BLA), respectively. We also identified CEA-like neurons and their species-specific distribution patterns in chickens. This study highlights the extreme cell-type diversity in the amygdala and reveals the conservation and divergence of cell types and gene expression patterns across species that may contribute to species-specific adaptations.

Optimization of Compound Ratio of Exogenous Xylanase and Debranching Enzymes Supplemented in Corn-Based Broiler Diets Using In Vitro Simulated Gastrointestinal Digestion and Response Surface Methodology.

This experiment aimed to explore the zymogram of endo-xylanase (EX) and debranching enzymes (arabinofuranosidase [EA] and ferulic acid esterase [EF]) supplemented in the corn−soybean meal-based diet of broilers. An in vitro simulated gastrointestinal digestion model was adopted. According to single-factor, completely random design, the optimal supplemental levels of individual carbohydrase were determined by reducing sugars (RS) and in vitro dry matter digestibility (IVDMD). Response surface method (RSM) was used to predict the proper compound ratio of three carbohydrases. Results showed that shifts were different for feedstuffs such as corn−soybean meal−distillers dried grains with solubles, corn hull, and wheat bran, revealing that the net increase of RS or IVDMD distinctly dropped when degrading corn and related by-products by EX (p < 0.05). There was a significant quadratic relationship between the above response metrics and addition levels of each enzyme (p < 0.05). The determined dosage was 54 U/g EX, 5.0 U/g EA, and 0.4 U/g of EF, respectively. The optimistic zymogram of carbohydrases in corn basal substrates was judged by the IVDMD screening (R2 = 0.9089, p < 0.001). Conclusively, the in vitro assay and RSM were convenient and rapid methods for the optimization of xylan-degrading zymogram, and also testified asthenic hydrolysis of corn arabinoxylan by EX, thus highlighting the synergistic combinations with debranching enzymes.

Representation learning in the artificial and biological neural networks underlying sensorimotor integration.

The integration of deep learning and theories of reinforcement learning (RL) is a promising avenue to explore novel hypotheses on reward-based learning and decision-making in humans and other animals. Here, we trained deep RL agents and mice in the same sensorimotor task with high-dimensional state and action space and studied representation learning in their respective neural networks. Evaluation of thousands of neural network models with extensive hyperparameter search revealed that learning-dependent enrichment of state-value and policy representations of the task-performance-optimized deep RL agent closely resembled neural activity of the posterior parietal cortex (PPC). These representations were critical for the task performance in both systems. PPC neurons also exhibited representations of the internally defined subgoal, a feature of deep RL algorithms postulated to improve sample efficiency. Such striking resemblance between the artificial and biological networks and their functional convergence in sensorimotor integration offers new opportunities to better understand respective intelligent systems.

A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior.

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2+) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST+), but not protein kinase C-δ-expressing (PKC-δ+), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2+ neurons. The SST+ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST+ GABAergic neurons, but not PKC-δ+ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeASST-DpMeVGLUT2 circuit that regulates licking behavior and promotes water intake.

The Effect of Continuous Passive Motion in Patients Treated With Total Knee Arthroplasty for Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of the study was to identify the effectiveness of the continuous passive motion application on clinical outcomes after total knee arthroplasty, based on evidence from recently published high-quality randomized controlled trials. DESIGN: Two reviewers retrieved platforms of PubMed, Embase, and CENTRAL independently, for identifying eligible randomized controlled trials evaluating the effect of continuous passive motion applied after total knee arthroplasty for knee osteoarthritis. Subgroup meta-analyses were performed for all syntheses based on the follow-up intervals. RESULTS: A total of 10 randomized controlled trials, involving 841 patients, were finally included. Data were available for 15 different outcomes (including active/passive knee extension/flexion/full range of motion, Western Ontario and McMaster Universities Osteoarthritis Index-pain/physical function/stiffness/total score, visual analogue scale, time up and go, knee girth, Knee Society Scale-function/knee score), at several time points. In general, most of the pools demonstrated similar outcome between continuous passive motion and noncontinuous passive motion groups. Exclusively, the active knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.5-5.5, P = 0.019*), passive knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.28-5.72, P = 0.031*), and 3 mos (mean difference = 3.00, 95% confidence interval = 0.5-5.5, P = 0.019*) were shown to be significantly slightly different between two groups. CONCLUSIONS: This study demonstrated a limited role of continuous passive motion in patients operated with total knee arthroplasty. Thus, there is at this stage no indication for continuous passive motion procedures in patients operated with total knee arthroplasty as a standard postoperative care.