Calibration Model Optimization for Strain Metrology of Equal Strength Beams Using Deflection Measurements.

Strain sensors, especially fiber Bragg grating (FBG) sensors, are of great importance in structural health monitoring, mechanical property analysis, and so on. Their metrological accuracy is typically evaluated by equal strength beams. The traditional strain calibration model using the equal strength beams was built based on an approximation method by small deformation theory. However, its measurement accuracy would be decreased while the beams are under the large deformation condition or under high temperature environments. For this reason, an optimized strain calibration model is developed for equal strength beams based on the deflection method. By combining the structural parameters of a specific equal strength beam and finite element analysis method, a correction coefficient is introduced into the traditional model, and an accurate application-oriented optimization formula is obtained for specific projects. The determination method of optimal deflection measurement position is also presented to further improve the strain calibration accuracy by error analysis of the deflection measurement system. Strain calibration experiments of the equal strength beam were carried out, and the error introduced by the calibration device can be reduced from 10 µÎµ to less than 1 µÎµ. Experimental results show that the optimized strain calibration model and the optimum deflection measurement position can be employed successfully under large deformation conditions, and the deformation measurement accuracy is improved greatly. This study is helpful to effectively establish metrological traceability for strain sensors and furthermore improve the measurement accuracy of strain sensors in practical engineering scenarious.

Reproductive toxicity of enrofloxacin in Caenorhabditis elegans involves oxidative stress-induced cell apoptosis.

Fluoroquinolone antibiotics (FQs) that persist and bioaccumulate in the environment have aroused people's great concern. Here, we studied the adverse effects of FQs in soil animals of Caenorhabditis elegans via food-chronically exposure. The result shows C. elegans exposed to FQs exhibited reproductive toxicity with small-brood size and low-egg hatchability. To study the underlying mechanism, we conduct a deep investigation of enrofloxacin (ENR), one of the most frequently detected FQs, on nematodes which is one of commonly used animal indicator of soil sustainability. The concentration-effect curves simulated by the Hill model showed that the half effect concentrations (EC50) of ENR were (494.3 ± 272.9) µmol/kg and (107.4 ± 30.9) µmol/kg for the brood size and the hatchability, respectively. Differential gene expression between the control and the ENR-exposure group enriched with the oxidative stress and cell apoptosis pathways. The results together with the enzyme activity in oxidative stress and the cell corpses suggested that ENR-induced reproductive toxicity was related to germ cell apoptosis under oxidative stress. The risk quotients of some soil and livestock samples were calculated based on the threshold value of EC10 for the egg hatchability (2.65 µmol/kg). The results indicated that there was possible reproductive toxicity on the nematodes in certain agricultural soils for the FQs. This study suggested that chronic exposure to FQs at certain levels in environment would induce reproductive toxicity to the nematodes and might reduce the soil sustainability, alarming the environment risks of antibiotics abuse.

Pd-Catalyzed Aerobic Intermolecular 1,2-Diamination of Conjugated Dienes: Regio- and Chemoselective Synthesis of Piperazines and 2-Piperazinones.

Dinitrogen heterocycles are among the most important molecular structures, and the synthesis of these types of structures through intermolecular 1,2-diamination of olefins is a direct and efficient method. However, the types of nitrogen sources are mostly derived from ureas or arylamines, and nitrogen sources from aliphatic amines are still limited due to their distinct electronic and steric effects. Herein, we report a palladium-catalyzed aerobic intermolecular 1,2-diamination of conjugated dienes, using ethanediamine and α-amino amide derivatives as nitrogen sources respectively, for the synthesis of piperazines and 2-piperazinones in good yields (up to 95 %) and with high regio- and chemoselectivities.

The phosphatidylinositol transfer protein PITP-1 facilitates fast recovery of eating behavior after hypoxia in the nematode Caenorhabditis elegans.

Among the fascinating adaptations to limiting oxygen conditions (hypoxia) is the suppression of food intake and weight loss. In humans, this phenomenon is called high-altitude anorexia and is observed in people suffering from acute mountain syndrome. The high-altitude anorexia appears to be conserved in evolution and has been seen in species across the animal kingdom. However, the mechanism underlying the recovery of eating behavior after hypoxia is still not known. Here, we show that the phosphatidylinositol transfer protein PITP-1 is essential for the fast recovery of eating behavior after hypoxia in the nematode Caenorhabditis elegans. Unlike the neuroglobin GLB-5 that accelerates the recovery of eating behavior through its function in the oxygen (O2 )-sensing neurons, PITP-1 appears to act downstream, in neurons that express the mod-1 serotonin receptor. Indeed, pitp-1 mutants display wild-type-like O2 -evoked-calcium responses in the URX O2 -sensing neuron. Intriguingly, loss-of-function of protein kinase C 1 (PKC-1) rescues pitp-1 mutants' recovery after hypoxia. Increased diacylglycerol (DAG), which activates PKC-1, attenuates the recovery of wild-type worms. Together, these data suggest that PITP-1 enables rapid recovery of eating behavior after hypoxia by limiting DAG's availability, thereby limiting PKC activity in mod-1-expressing neurons.

Reciprocal modulation of 5-HT and octopamine regulates pumping via feedforward and feedback circuits in C. elegans.

Feeding is vital for animal survival and is tightly regulated by the endocrine and nervous systems. To study the mechanisms of humoral regulation of feeding behavior, we investigated serotonin (5-HT) and octopamine (OA) signaling in Caenorhabditis elegans, which uses pharyngeal pumping to ingest bacteria into the gut. We reveal that a cross-modulation mechanism between 5-HT and OA, which convey feeding and fasting signals, respectively, mainly functions in regulating the pumping and secretion of both neuromodulators via ADF/RIC/SIA feedforward neurocircuit (consisting of ADF, RIC, and SIA neurons) and ADF/RIC/AWB/ADF feedback neurocircuit (consisting of ADF, RIC, AWB, and ADF neurons) under conditions of food supply and food deprivation, respectively. Food supply stimulates food-sensing ADFs to release more 5-HT, which augments pumping via inhibiting OA secretion by RIC interneurons and, thus, alleviates pumping suppression by OA-activated SIA interneurons/motoneurons. In contrast, nutrient deprivation stimulates RICs to secrete OA, which suppresses pumping via activating SIAs and maintains basal pumping and 5-HT production activity through excitation of ADFs relayed by AWB sensory neurons. Notably, the feedforward and feedback circuits employ distinct modalities of neurosignal integration, namely, disinhibition and disexcitation, respectively.

Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has infected more than 4 million people within 4 months. There is an urgent need to properly identify high-risk cases that are more likely to deteriorate even if they present mild diseases on admission. METHODS: A multicenter nested case-control study was conducted in four designated hospitals in China enrolling confirmed COVID-19 patients who were mild on admission. Baseline clinical characteristics were compared between patients with stable mild illness (stable mild group) and those who deteriorated from mild to severe illness (progression group). RESULTS: From Jan 17, 2020, to Feb 1, 2020, 85 confirmed COVID-19 patients were enrolled, including 16 in the progression group and 69 in the stable mild group. Compared to stable mild group (n = 69), patients in the progression group (n = 16) were more likely to be older, male, presented with dyspnea, with hypertension, and with higher levels of lactase dehydrogenase and c-reactive protein. In multivariate logistic regression analysis, advanced age (odds ratio [OR], 1.012; 95% confidence interval [CI], 1.020-1.166; P = 0.011) and the higher level of lactase dehydrogenase (OR, 1.012; 95% CI, 1.001-1.024; P = 0.038) were independently associated with exacerbation in mild COVID-19 patients. CONCLUSION: Advanced age and high LDH level are independent risk factors for exacerbation in mild COVID-19 patients. Among the mild patients, clinicians should pay more attention to the elderly patients or those with high LDH levels.

Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir.

The catalytic asymmetric synthesis of the anti-COVID-19 drug Remdesivir has been realized by the coupling of the P-racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 SP :RP ). Mechanistic studies showed that this DyKAT is a first-order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.

An optical method to evaluate both mass and functional competence of pancreatic α- and ß-cells.

Imbalanced glucagon and insulin release leads to the onset of type 2 diabetes. To pinpoint the underlying primary driving force, here we have developed a fast, non-biased optical method to measure ratios of pancreatic α- and ß-cell mass and function simultaneously. We firstly label both primary α- and ß-cells with the red fluorescent probe ZinRhodaLactam-1 (ZRL1), and then highlight α-cells by selectively quenching the ZRL1 signal from ß-cells. Based on the signals before and after quenching, we calculate the ratio of the α-cell to ß-cell mass within live islets, which we found matched the results from immunohistochemistry. From the same islets, glucagon and insulin release capability can be concomitantly measured. Thus, we were able to measure the ratio of α-cell to ß-cell mass and their function in wild-type and diabetic Lepr(db)/Lepr(db) (denoted db/db) mice at different ages. We find that the initial glucose intolerance that appears in 10-week-old db/db mice is associated with further expansion of α-cell mass prior to deterioration in functional ß-cell mass. Our method is extendable to studies of islet mass and function in other type 2 diabetes animal models, which shall benefit mechanistic studies of imbalanced hormone secretion during type 2 diabetes progression.

Pd(ii)-Catalyzed aerobic 1,2-difunctionalization of conjugated dienes: efficient synthesis of morpholines and 2-morpholones.

A novel and efficient methodology concerning the Pd(ii)-catalyzed intermolecular difunctionalization of conjugated dienes is reported to synthesize a series of functionalized morpholines and 2-morpholones. Widely distributed and easily obtained ß-amino alcohols and α-amino acids, as starting nitrogen and oxygen sources, are successfully applied in the difunctionalization of conjugated dienes respectively. The majority of the desired products were obtained in moderate to excellent yields. Oxygen was successfully employed as a terminal oxidant. Further transformation of the generated products allowed for the expansion of structural diversity.

ZNRF3 contributes to the growth of lung carcinoma via inhibiting Wnt/ß-catenin pathway and is regulated by miR-93.

Lung carcinoma is the most common cancer with increasing morbidity, inefficient therapeutic modality, and poor prognosis, due to the lack of understanding of its related molecular mechanism. ZNRF3 is a newly identified negative regulator of Wnt signaling. In this study, we found that ZNRF3 level is reduced in lung carcinoma compared with normal lung tissue and its expression level is positively correlated with the survival of lung cancer patients. Restoration of ZNRF3 suppressed the proliferation and cell cycle progression of lung cancer cell lines. Suppression of ZNRF3 expression in normal lung cells increased the proliferation rates. In an animal model, ZNRF3 was shown to suppress the growth of lung cancer xenografts. ZNRF3 was shown to negatively regulate the activation of Wnt signaling in lung cancerous and normal cells. Further studies revealed that ZNRF3 is a target of miR-93, an oncogenic microRNA (miRNA) for lung cancer progression. Collectively, we found that miR-93/ZNRF3/Wnt/ß-catenin regulatory network contributes to the growth of lung carcinoma. Targeting this pathway may be a promising strategy for lung cancer therapy.

Off-response in ASH neurons evoked by CuSO4 requires the TRP channel OSM-9 in Caenorhabditis elegans.

The off-response of ASH neurons had been overlooked until the microfluidic devices were introduced for in vivo imaging of neuronal activity in Caenorhabditis elegans. The mechanisms of ASH off-response were completely unknown. Here we monitored ASH off-response to CuSO4 stimulation by use of microfluidic device and genetically encoded calcium indicator (GECI) - Case12. We found ASH neurons exhibited a multiphasic response to 10 mM and 50 mM CuSO4 of 30-s stimulation duration. ASH off-responding to Cu(2+) had been dramatically reduced in goa-1, mod-5, trpa-1 and egl-8 mutants. Moreover, in osm-9 mutants ASH off-response was completely eliminated. Neuron-specific rescue of osm-9 in ASH neurons restored the off-response and the normal avoidance behavior in worms.

PKG and NHR-49 signalling co-ordinately regulate short-term fasting-induced lysosomal lipid accumulation in C. elegans.

Lysosomes act as terminal degradation organelles to hydrolyse macromolecules derived from both the extracellular space and the cytoplasm. In Caenorhabditis elegans fasting induces the lysosomal compartment to expand. However, the molecular and cellular mechanisms for this stress response remain largely unclear. In the present study, we find that short-term fasting leads to increased accumulation of polar lipids in lysosomes. The fasting response is co-ordinately regulated by EGL-4, the C. elegans PKG (protein kinase G) orthologue, and nuclear hormone receptor NHR-49. Further results demonstrate that EGL-4 acts in sensory neurons to enhance lysosomal lipid accumulation through inhibiting the DAF-3/SMAD pathway, whereas NHR-49 acts in intestine to inhibit lipids accumulation via activation of IPLA-2 (intracellular membrane-associated calcium-independent phospholipase A2) in cytoplasm and other hydrolases in lysosomes. Remarkably, the lysosomal lipid accumulation is independent of autophagy and RAB-7-mediated endocytosis. Taken together, our results reveal a new mechanism for lysosomal lipid metabolism during the stress response, which may provide new clues for investigations of lysosome function in energy homoeostasis.

Real-time Trajectory Planning and Tracking Control of Bionic Underwater Robot in Dynamic Environment.

In this article, we study the trajectory planning and tracking control of a bionic underwater robot under multiple dynamic obstacles. We first introduce the design of the bionic leopard cabinet underwater robot developed in our lab. Then, we model the trajectory planning problem of the bionic underwater robot by combining its dynamics and physical constraints. Furthermore, we conduct global trajectory planning for bionic underwater robots based on the temporal-spatial Bezier curves. In addition, based on the improved proximal policy optimization, local dynamic obstacle avoidance trajectory replanning is carried out. In addition, we design the fuzzy proportional-integral-derivative controller for tracking control of the planned trajectory. Finally, the effectiveness of the real-time trajectory planning and tracking control method is verified by comparative simulation in dynamic environment and semiphysical simulation of UWSim. Among them, the real-time trajectory planning method has advantages in trajectory length, trajectory smoothness, and planning time. The error of trajectory tracking control method is controlled around 0.2 m.

Adaptive Gait Training of a Lower Limb Rehabilitation Robot Based on Human-Robot Interaction Force Measurement.

The existing fixed gait lower limb rehabilitation robots perform a predetermined walking trajectory for patients, ignoring their residual muscle strength. To enhance patient participation and safety in training, this paper aims to develop a lower limb rehabilitation robot with adaptive gait training capability relying on human-robot interaction force measurement. Firstly, a novel lower limb rehabilitation robot system with several active and passive driven joints is developed, and 2 face-to-face mounted cantilever beam force sensors are employed to measure the human-robot interaction forces. Secondly, a dynamic model of the rehabilitation training robot is constructed to estimate the driven forces of the human lower leg in a completely passive state. Thereafter, based on the theoretical moment from the dynamics and the actual joint interaction force collected by the sensors, an adaptive gait adjustment method is proposed to achieve the goal of adapting to the wearer's movement intention. Finally, interactive experiments are carried out to validate the effectiveness of the developed rehabilitation training robot system. The proposed rehabilitation training robot system with adaptive gaits offers great potential for future high-quality rehabilitation training, e.g., improving participation and safety.

A Fish-like Binocular Vision System for Underwater Perception of Robotic Fish.

Biological fish exhibit a remarkably broad-spectrum visual perception capability. Inspired by the eye arrangement of biological fish, we design a fish-like binocular vision system, thereby endowing underwater bionic robots with an exceptionally broad visual perception capacity. Firstly, based on the design principles of binocular visual field overlap and tangency to streamlined shapes, a fish-like vision system is developed for underwater robots, enabling wide-field underwater perception without a waterproof cover. Secondly, addressing the significant distortion and parallax of the vision system, a visual field stitching algorithm is proposed to merge the binocular fields of view and obtain a complete perception image. Thirdly, an orientation alignment method is proposed that draws scales for yaw and pitch angles in the stitched images to provide a reference for the orientation of objects of interest within the field of view. Finally, underwater experiments evaluate the perception capabilities of the fish-like vision system, confirming the effectiveness of the visual field stitching algorithm and the orientation alignment method. The results show that the constructed vision system, when used underwater, achieves a horizontal field of view of 306.56°. The conducted work advances the visual perception capabilities of underwater robots and presents a novel approach to and insight for fish-inspired visual systems.

Study on the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.

Objective: To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A. Methods: According to a random sequence generated by computer software, 200 patients with confirmed influenza A were divided into a study group and a control group with 100 cases in each group. Group allocation was concealed using sealed envelopes. The study group was treated with oral administration of baloxavir marboxil tablets, 40 mg once. The control group was given oral oseltamivir capsules, 75 mg twice a day, for five consecutive days. The therapeutic effects, symptom disappearance time and adverse drug reactions of the two groups after 5 days of treatment were compared. Results: There was no significant difference in the total effective rate between the two groups (99% vs. 98%, p > 0.05). There was no significant difference in fever subsidence time (1.54 ± 0.66 d vs. 1.67 ± 0.71 d, p > 0.05), cough improvement time (2.26 ± 0.91 d vs. 2.30 ± 0.90 d, p > 0.05) and sore throat improvement time (2.06 ± 0.86 d vs. 2.09 ± 0.83 d, p > 0.05) between the two groups. There was no significant difference in the incidence of adverse drug reactions between the two groups (8% vs. 13%, p > 0.05). Conclusion: Baloxavir marboxil tablets can be effectively used in the treatment of patients with influenza A and have a similar efficacy and safety profile as oseltamivir capsules.

Molecular and circuit mechanisms underlying avoidance of rapid cooling stimuli in C. elegans.

The mechanisms by which animals respond to rapid changes in temperature are largely unknown. Here, we found that polymodal ASH sensory neurons mediate rapid cooling-evoked avoidance behavior within the physiological temperature range in C. elegans. ASH employs multiple parallel circuits that consist of stimulatory circuits (AIZ, RIA, AVA) and disinhibitory circuits (AIB, RIM) to respond to rapid cooling. In the stimulatory circuit, AIZ, which is activated by ASH, releases glutamate to act on both GLR-3 and GLR-6 receptors in RIA neurons to promote reversal, and ASH also directly or indirectly stimulates AVA to promote reversal. In the disinhibitory circuit, AIB is stimulated by ASH through the GLR-1 receptor, releasing glutamate to act on AVR-14 to suppress RIM activity. RIM, an inter/motor neuron, inhibits rapid cooling-evoked reversal, and the loop activities thus equally stimulate reversal. Our findings elucidate the molecular and circuit mechanisms underlying the acute temperature stimuli-evoked avoidance behavior.

GCY-20 signaling controls suppression of Caenorhabditis elegans egg laying by moderate cold.

Organisms sensing environmental cues and internal states and integrating the sensory information to control fecundity are essential for survival and proliferation. The present study finds that a moderate cold temperature of 11°C reduces egg laying in Caenorhabditis elegans. ASEL and AWC neurons sense the cold via GCY-20 signaling and act antagonistically on egg laying through the ASEL and AWC/AIA/HSN circuits. Upon cold stimulation, ASEL and AWC release glutamate to activate and inhibit AIA interneurons by acting on highly and lowly sensitive ionotropic GLR-2 and GLC-3 receptors, respectively. AIA inhibits HSN motor neuron activity via acetylcholinergic ACR-14 receptor signaling and suppresses egg laying. Thus, ASEL and AWC initiate and reduce the cold suppression of egg laying. ASEL's action on AIA and egg laying dominates AWC's action. The biased opposite actions of these neurons on egg laying provide animals with a precise adaptation of reproductive behavior to environmental temperatures.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.

Decoupled Metric Network for Single-Stage Few-Shot Object Detection.

Within the last few years, great efforts have been made to study few-shot learning. Although general object detection is advancing at a rapid pace, few-shot detection remains a very challenging problem. In this work, we propose a novel decoupled metric network (DMNet) for single-stage few-shot object detection. We design a decoupled representation transformation (DRT) and an image-level distance metric learning (IDML) to solve the few-shot detection problem. The DRT can eliminate the adverse effect of handcrafted prior knowledge by predicting objectness and anchor shape. Meanwhile, to alleviate the problem of representation disagreement between classification and location (i.e., translational invariance versus translational variance), the DRT adopts a decoupled manner to generate adaptive representations so that the model is easier to learn from only a few training data. As for a few-shot classification in the detection task, we design an IDML tailored to enhance the generalization ability. This module can perform metric learning for the whole visual feature, so it can be more efficient than traditional DML due to the merit of parallel inference for multiobjects. Based on the DRT and IDML, our DMNet efficiently realizes a novel paradigm for few-shot detection, called single-stage metric detection. Experiments are conducted on the PASCAL VOC dataset and the MS COCO dataset. As a result, our method achieves state-of-the-art performance in few-shot object detection. The codes are available at https://github.com/yrqs/DMNet.