NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons.

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability, and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor on colonic pain signaling and intestinal permeability were assessed through behavioral, electrophysiological, and cell culture experiments. Intestinal motility studies in rats and humans demonstrated that tenapanor increased luminal sodium and water retention and gastrointestinal transit versus placebo. A significantly reduced visceral motor reflex (VMR) to colonic distension was observed with tenapanor treatment versus vehicle in two rat models of visceral hypersensitivity (neonatal acetic acid sensitization and partial restraint stress; both P < 0.05), returning VMR responses to that of nonsensitized controls. Whole cell voltage patch-clamp recordings of retrogradely labeled colonic dorsal root ganglia (DRG) neurons from sensitized rats found that tenapanor significantly reduced DRG neuron hyperexcitability to capsaicin versus vehicle (P < 0.05), an effect not mediated by epithelial cell secretions. Tenapanor also attenuated increases in intestinal permeability in human colon monolayer cultures caused by incubation with proinflammatory cytokines (P < 0.001) or fecal supernatants from patients with IBS-C (P < 0.005). These results support a model in which tenapanor reduces IBS-related pain by strengthening the intestinal barrier, thereby decreasing permeability to macromolecules and antigens and reducing DRG-mediated pain signaling.NEW & NOTEWORTHY A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.

Molecular Dynamics Simulation of Dual Nanodroplet Impacts on a Cylindrical Surface.

Droplet impact behavior is ubiquitous in various fields. However, the dynamics and spreading mechanisms of micro- and nanoscale droplet impact on curved surfaces, particularly in the case of multiple droplets, have yet to be fully elucidated. In this study, molecular dynamics (MD) methods are employed to investigate the dynamic evolution of double nanodroplet impact on a nano cylindrical wall. The effects of droplet spacing, initial impact velocity, and wall wettability on droplet impact characteristics are analyzed. The results demonstrate that there are five impact modes of nanoscale double-droplet impacts with nanocylinders: spreading-partial wrapping-splitting-complete detachment (SPSC), spreading-complete wrapping-complete attachment (SCC), spreading-partial wrapping-complete attachment (SPC), spreading-partial wrapping-partial attachment (SPP), and spreading-partial wrapping-fragmentation-partial attachment (SPFP). The droplet spacing has an insignificant effect on the impact modes but affects the droplets' spreading shape in both the axial and radial directions. The initial velocity and wall wettability have significant impacts on the droplet impact modes and liquid film spreading characteristics. As the initial velocity increases, the liquid film's radial and axial spreading distances gradually increase. Under hydrophobic conditions, the spreading of the droplet is dominant in the radial direction, while under hydrophilic conditions, the spreading is dominant in the axial direction. Properly reducing the droplet spacing, increasing the impact velocity, and enhancing the wall hydrophobicity can promote detaching the droplet from the cylindrical wall.

Loss of VGLL4 suppresses tumor PD-L1 expression and immune evasion.

Targeting immune checkpoints, such as PD-L1 and its receptor PD-1, has opened a new avenue for treating cancers. Understanding the regulatory mechanism of PD-L1 and PD-1 will improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients and the development of combinatorial strategies. VGLL4 inhibits YAP-induced cell proliferation and tumorigenesis through competition with YAP for binding to TEADs. However, whether VGLL4 has a role in anti-tumor immunity is largely unknown. Here, we found that disruption of Vgll4 results in potent T cell-mediated tumor regression in murine syngeneic models. VGLL4 deficiency reduces PD-L1 expression in tumor cells. VGLL4 interacts with IRF2BP2 and promotes its protein stability through inhibiting proteasome-mediated protein degradation. Loss of IRF2BP2 results in persistent binding of IRF2, a transcriptional repressor, to PD-L1 promoter. In addition, YAP inhibits IFNγ-inducible PD-L1 expression partially through suppressing the expression of VGLL4 and IRF1 by YAP target gene miR-130a. Our study identifies VGLL4 as an important regulator of PD-L1 expression and highlights a central role of VGLL4 and YAP in the regulation of tumor immunity.

Flow and Heat-Transfer Characteristics of Droplet Impingement on Hydrophilic Wires.

It is a common phenomenon that droplets collide with wires in industrial production, and their flow and heat-transfer behavior significantly impact the production efficiency. This article presents an experimental and numerical study on the impact of pure water droplets on hydrophilic stainless-steel wires. The dynamic behavior and solid-liquid heat-transfer law of droplet impacting the wire are emphatically analyzed. The impact position of the droplets has a significant effect on their morphology. Under the condition of low Weber number (We), eccentric impacts tend to cause droplets to separate from the wire. Additionally, both We and wire/droplet size ratio have noticeable effects on the droplet morphology. The smaller the We, the larger the wire/droplet size ratio, and the easier it is for droplets to be captured by wires. Conversely, as We increases and the wire-to-droplet size ratio decreases, some droplets become detached from the wire, primarily exhibiting a single-film falling mode. Furthermore, the impact morphology of droplets is influenced by the Ohnesorge number (Oh). The higher the Oh, the more inclined the droplet to develop a double-film falling mode. There is obvious field synergy in the process of droplet impacting on wire. The maximum heat flux is located at the three-phase contact line, while the minimum heat flux is observed at the bubble interface. The impact position of droplets influences the temperature distribution, although its impact on the magnitude of temperature variation is minimal.

Rh(III)-Catalyzed [4 + 1] Annulation of Sulfoximines with Maleimides: Access to Benzoisothiazole Spiropyrrolidinediones.

Rh(III)-catalyzed synthesis of benzoisothiazole spiropyrrolidinediones using sulfoximine as a directing group under a C-H activation and [4 + 1] annulation strategy with maleimides as a coupling partner is reported. The cyclization reaction was compatible with various substituted sulfoximine and maleimides. The deuterium-labeling studies were performed to investigate the mechanism of the reaction.

Cp*RhIII-Catalyzed Cascade Annulation of Arylimidates with Pyridotriazoles toward Isoquinolin-3-ol Derivatives.

A Cp*RhIII-catalyzed efficient synthesis of isoquinolin-3-ol derivatives bearing a pyridinyl ring using imidate as a directing group under C-H activation strategy with pyridotriazoles as carbene reagents is reported. In this reaction, cascade C-H activation, regioselective cyclization, and elimination occur in one pot. The present methodology featured a good range of functional group tolerance and furnished the target products in moderate-to-excellent yields.

Reducing speckle in anterior segment optical coherence tomography images based on a convolutional neural network.

Speckle noise is ubiquitous in the optical coherence tomography (OCT) image of the anterior segment, which greatly affects the image quality and destroys the relevant structural information. In order to reduce the influence of speckle noise in OCT images, a denoising algorithm based on a convolutional neural network is proposed in this paper. Unlike traditional algorithms that directly obtain denoised images, the algorithm model proposed in this paper learns the speckle noise distribution through the constructed trainable OCT dataset and indirectly obtains the denoised result image. In order to verify the performance of the model, we compare the denoising results of the algorithm proposed in this paper with several state-of-the-art algorithms from three perspectives: qualitative evaluation from the subjective visual perspective, quantitative evaluation from objective parameter indicators, and running time. The experimental results show that the proposed algorithm has a good denoising effect on different OCT images of the anterior segment and has good generalization ability. Besides, it retains the relevant details and texture information in the image, and it has strong edge preserving ability. The image of OCT speckle removal can be obtained within 0.4 s, which meets the time limit requirement of clinical application.

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis.

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

Hepatic loss of Lissencephaly 1 (Lis1) induces fatty liver and accelerates liver tumorigenesis in mice.

The liver is a major organ in lipid metabolism, and its malfunction leads to various diseases. Nonalcoholic fatty liver disease, the most common chronic liver disorder in developed countries, is characterized by the abnormal retention of excess lipid within hepatocytes and predisposes individuals to liver cancer. We previously reported that the levels of Lissencephaly 1 (LIS1, also known as PAFAH1B1) are down-regulated in human hepatocellular carcinoma. Following up on this observation, we found that genetic deletion of Lis1 in the mouse liver increases lipid accumulation and inflammation in this organ. Further analysis revealed that loss of Lis1 triggers endoplasmic reticulum (ER) stress and reduces triglyceride secretion. Attenuation of ER stress by addition of tauroursodeoxycholic acid (TUDCA) diminished lipid accumulation in the Lis1-deficient hepatocytes. Moreover, the Golgi stacks were disorganized in Lis1-deficient liver cells. Of note, the Lis1 liver-knockout mice exhibited increased hepatocyte ploidy and accelerated development of liver cancer after exposure to the liver carcinogen diethylnitrosamine (DEN). Taken together, these findings suggest that reduced Lis1 levels can spur the development of liver diseases from steatosis to liver cancer and provide a useful model for delineating the molecular pathways that lead to these diseases.

Neuronal Transforming Growth Factor beta Signaling via SMAD3 Contributes to Pain in Animal Models of Chronic Pancreatitis.

BACKGROUND & AIMS: Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, associated with increased pancreatic expression of transforming growth factor beta (TGFB). It is not clear how these might contribute to pain. We investigated whether TGFB signaling via SMAD induces sensitization of pancreatic sensory neurons to increase nociception. METHODS: CP was induced in Sprague-Dawley rats by infusion of trinitrobenzene sulfonic acid; some rats were given intrathecal infusions of TGFB1. CP was induced in control mice by administration of cerulein; we also studied ß1glo/Ptf1acre-ER mice, which on induction overexpress TGFB1 in pancreatic acinar cells, and TGFBr1f/f-CGRPcreER mice, which have inducible disruption of TGFBr1 in calcitonin gene-related peptide-positive neurons. Dominant negative forms of human TGFBR2 and SMAD3 were overexpressed from viral vectors in rat pancreas. Some rats were given the SMAD3 inhibitors SIS3 or halofuginone. After induction of CP, mice were analyzed for pain in behavior tests or electrophysiologic studies of sensory neurons. Pancreatic nociceptor excitability was examined by patch-clamp techniques and nociception was measured by Von Frey Filament tests for referred somatic hyperalgesia and behavioral responses to pancreatic electrical stimulation. Pancreata were collected from mice and rats and analyzed histologically and by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Overexpression of TGFB in pancreatic acinar cells of mice and infusion of TGFB1 into rats resulted in sensory neuron hyperexcitability, SMAD3 activation, and increased nociception. This was accompanied by a reduction in the transient A-type current in pancreas-specific sensory neurons in rats, a characteristic of nociceptive sensitization in animal models of CP. Conversely, pancreata from TGFBr1f/f-CGRPcreER mice, rats with pancreatic expression of dominant negative forms of human TGFBR2 or SMAD3, and rats given small molecule inhibitors of SMAD3 had attenuated neuronal sensitization and pain behavior following induction of CP. In contrast to findings from peripheral administration of TGFB1, intrathecal infusion of TGFB1 reduced hyperalgesia in rats with CP. CONCLUSIONS: In pancreata of mice and rats, TGFB promotes peripheral nociceptive sensitization via a direct effect on primary sensory neurons mediated by intra-neuronal SMAD3. This is distinct from the central nervous system, where TGFB reduces nociception. These results provide an explanation for the link between fibrosis and pain in patients with CP. This signaling pathway might be targeted therapeutically to reduce pain in patients with CP.

Performance Sensing Data Prediction for an Aircraft Auxiliary Power Unit Using the Optimized Extreme Learning Machine.

The aircraft auxiliary power unit (APU) is responsible for environmental control in the cabin and the main engines starting the aircraft. The prediction of its performance sensing data is significant for condition-based maintenance. As a complex system, its performance sensing data have a typically nonlinear feature. In order to monitor this process, a model with strong nonlinear fitting ability needs to be formulated. A neural network has advantages of solving a nonlinear problem. Compared with the traditional back propagation neural network algorithm, an extreme learning machine (ELM) has features of a faster learning speed and better generalization performance. To enhance the training of the neural network with a back propagation algorithm, an ELM is employed to predict the performance sensing data of the APU in this study. However, the randomly generated weights and thresholds of the ELM often may result in unstable prediction results. To address this problem, a restricted Boltzmann machine (RBM) is utilized to optimize the ELM. In this way, a stable performance parameter prediction model of the APU can be obtained and better performance parameter prediction results can be achieved. The proposed method is evaluated by the real APU sensing data of China Southern Airlines Company Limited Shenyang Maintenance Base. Experimental results show that the optimized ELM with an RBM is more stable and can obtain more accurate prediction results.

UAV Sensor Fault Detection Using a Classifier without Negative Samples: A Local Density Regulated Optimization Algorithm.

Fault detection for sensors of unmanned aerial vehicles is essential for ensuring flight security, in which the flight control system conducts real-time control for the vehicles relying on the sensing information from sensors, and erroneous sensor data will lead to false flight control commands, causing undesirable consequences. However, because of the scarcity of faulty instances, it still remains a challenging issue for flight sensor fault detection. The one-class support vector machine approach is a favorable classifier without negative samples, however, it is sensitive to outliers that deviate from the center and lacks a mechanism for coping with them. The compactness of its decision boundary is influenced, leading to the degradation of detection rate. To deal with this issue, an optimized one-class support vector machine approach regulated by local density is proposed in this paper, which regulates the tolerance extents of its decision boundary to the outliers according to their extent of abnormality indicated by their local densities. The application scope of the local density theory is narrowed to keep the internal instances unchanged and a rule for assigning the outliers continuous density coefficients is raised. Simulation results on a real flight control system model have proved its effectiveness and superiority.

An Electro-Mechanical Actuator Motor Voltage Estimation Method with a Feature-Aided Kalman Filter.

Electro-Mechanical Actuators (EMA) have attracted growing attention with their increasing incorporation in More Electric Aircraft. The performance degradation assessment of EMA needs to be studied, in which EMA motor voltage is an essential parameter, to ensure its reliability and safety of EMA. However, deviation exists between motor voltage monitoring data and real motor voltage due to electromagnetic interference. To reduce the deviation, EMA motor voltage estimation generally requires an accurate voltage state equation which is difficult to obtain due to the complexity of EMA. To address this problem, a Feature-aided Kalman Filter (FAKF) method is proposed, in which the state equation is substituted by a physical model of current and voltage. Consequently, voltage state data can be obtained through current monitoring data and a current⁻voltage model. Furthermore, voltage estimation can be implemented by utilizing voltage state data and voltage monitoring data. To validate the effectiveness of the FAKF-based estimation method, experiments have been conducted based on the published data set from NASA's Flyable Electro-Mechanical Actuator (FLEA) test stand. The experiment results demonstrate that the proposed method has good performance in EMA motor voltage estimation.

A Survey of Data Mining and Deep Learning in Bioinformatics.

The fields of medicine science and health informatics have made great progress recently and have led to in-depth analytics that is demanded by generation, collection and accumulation of massive data. Meanwhile, we are entering a new period where novel technologies are starting to analyze and explore knowledge from tremendous amount of data, bringing limitless potential for information growth. One fact that cannot be ignored is that the techniques of machine learning and deep learning applications play a more significant role in the success of bioinformatics exploration from biological data point of view, and a linkage is emphasized and established to bridge these two data analytics techniques and bioinformatics in both industry and academia. This survey concentrates on the review of recent researches using data mining and deep learning approaches for analyzing the specific domain knowledge of bioinformatics. The authors give a brief but pithy summarization of numerous data mining algorithms used for preprocessing, classification and clustering as well as various optimized neural network architectures in deep learning methods, and their advantages and disadvantages in the practical applications are also discussed and compared in terms of their industrial usage. It is believed that in this review paper, valuable insights are provided for those who are dedicated to start using data analytics methods in bioinformatics.

Altered gray matter volume and functional connectivity of the motor network in young divers.

BACKGROUND: Motor learning and professional sports training can induce plastic changes in brain structures that are associated with distinct training demands. OBJECTIVE: To testify the hypothesis of that regional gray matter structures in the motor-related cortex and its functional connectivity (FC) are altered in young divers. METHODS: We undertook T1-voxel-based morphometry (VBM) structural and resting-state functional magnetic resonance imaging in groups of diving athletes (DAs) and demographically-matched healthy controls. RESULTS: Gray matter volume was lower in some regions in Das. By selecting the five most reduced regions, i.e. superior frontal gyrus, orbitofrontal cortex (OFC), insula, hippocampus, and cerebellum posterior lobe, as regions of interest (ROIs) for FC analysis, results showed that DAs had greater FC between the inferior temporal gyrus and superior frontal gyrus, OFC and cerebellum posterior lobe. Conversely, the divers had lesser FC between OFC and putamen, superior frontal gyrus and caudate. CONCLUSIONS: VBM differences suggest that diving training entails more effective synaptic and/or neuronal pruning processes in motor structures. Indeed, cortical volumetric decreases in the DAs group are associated with increased FC among certain motor-related regions. We conclude that motor learning in adolescence alters brain structure in association with changes in FC between the relevant cortical and subcortical regions.

Effective Sensor Selection and Data Anomaly Detection for Condition Monitoring of Aircraft Engines.

In a complex system, condition monitoring (CM) can collect the system working status. The condition is mainly sensed by the pre-deployed sensors in/on the system. Most existing works study how to utilize the condition information to predict the upcoming anomalies, faults, or failures. There is also some research which focuses on the faults or anomalies of the sensing element (i.e., sensor) to enhance the system reliability. However, existing approaches ignore the correlation between sensor selecting strategy and data anomaly detection, which can also improve the system reliability. To address this issue, we study a new scheme which includes sensor selection strategy and data anomaly detection by utilizing information theory and Gaussian Process Regression (GPR). The sensors that are more appropriate for the system CM are first selected. Then, mutual information is utilized to weight the correlation among different sensors. The anomaly detection is carried out by using the correlation of sensor data. The sensor data sets that are utilized to carry out the evaluation are provided by National Aeronautics and Space Administration (NASA) Ames Research Center and have been used as Prognostics and Health Management (PHM) challenge data in 2008. By comparing the two different sensor selection strategies, the effectiveness of selection method on data anomaly detection is proved.

Cerebral activation effects of acupuncture using Zusanli (ST36) and Yanglingquan (GB34) points based on Regional Homogeneity indices: A resting-state fMRI study.

OBJECTIVE: This study aimed to observe the cerebral activation effects of acupuncturing the Zusanli (ST36) plusYanglingquan (GB34) points in young healthy volunteers based on Regional Homogeneity (ReHo) indices. METHODS: Ten healthy volunteers were enrolled, including 4 males and 6 females between the ages 20 and 34 years with a median age of 23 years. Magnetic resonance imaging (GE Signa HDxt 3.0T) was performed in four groups: Before acupuncture (Control Group), after acupuncture at Zusanli (ST36 Group), after acupuncture at Yanglingquan (GB34 Group) and after acupuncture at both Zusanli and Yanglingquan (Compatibility Group). Differences in the brain ReHo indices of the 4 groups were analyzed by statistical parametric mapping (SPM8) and ReHo data processing methods. The significantly different brain regions were obtained using a false discovery rate correction (FDR-Corrected). RESULTS: The ReHo indices revealed that the main significant effect was in the Compatibility Group. Compared with the resting state of the Control Group, the ReHo values of the Compatibility Group increased in the right middle frontal gyrus (BA8, 9), left superior temporal areas (BA22), ventral anterior cingulate area (BA24) and right inferior parietal lobe (BA40); in contrast, the ReHo values decreased in the left thalamus, right insular cortex (BA13), left inferior frontal lobe (BA9) and right dorsal anterior cingulate area (BA32). Our analysis showed that the Compatibility Group had higher ReHo values than the left inferior parietal lobule (BA40) and right frontal cortex (BA6) of the ST36 Group and the posterior lobe of the right cerebellum, dorsal anterior cingulate (BA32), left and right middle frontal gyrus (BA46, BA9), left precuneus (BA7), right inferior parietal love (BA40) of the GB34 Group. CONCLUSION: The results of our neuroimaging study suggest that the combination of acupoints could more widely activate areas of the brain compared to a single acupoint. Additionally, the combination of acupoints can activate some new brain areas and generate new curative effects.

Intranasal versus intraperitoneal delivery of human umbilical cord tissue-derived cultured mesenchymal stromal cells in a murine model of neonatal lung injury.

Clinical trials investigating mesenchymal stromal cell (MSC) therapy for bronchopulmonary dysplasia have been initiated; however, the optimal delivery route and functional effects of MSC therapy in newborns remain incompletely established. We studied the morphologic and functional effects of intranasal versus i.p. MSC administration in a rodent model of neonatal lung injury. Cultured human cord tissue MSCs (0.1, 0.5, or 1 × 10(6) cell per pup) were given intranasally or i.p. to newborn severe combined immunodeficiency-beige mice exposed to 90% O2 from birth; sham controls received an equal volume of phosphate-buffered saline. Lung mechanics, engraftment, lung growth, and alveolarization were evaluated 8 weeks after transplantation. High-dose i.p. MSC administration to newborn mice exposed to 90% O2 resulted in the restoration of normal lung compliance, elastance, and pressure-volume loops (tissue recoil). Histologically, high-dose i.p. MSC administration was associated with alveolar septal widening, suggestive of interstitial matrix modification. Intranasal MSC or lower-dose i.p. administration had no significant effects on lung function or alveolar remodeling. Pulmonary engraftment was rare in all the groups. These findings suggest that high-dose systemic administration of human cultured MSCs can restore normal compliance in neonatally injured lungs, possibly by paracrine modulation of the interstitial matrix. Intranasal delivery had no obvious pulmonary effects.

Anatomical and functional characterization of a duodeno-pancreatic neural reflex that can induce acute pancreatitis.

Neural cross talk between visceral organs may play a role in mediating inflammation and pain remote from the site of the insult. We hypothesized such a cross talk exists between the duodenum and pancreas, and further it induces pancreatitis in response to intraduodenal toxins. A dichotomous spinal innervation serving both the duodenum and pancreas was examined, and splanchnic nerve responses to mechanical stimulation of these organs were detected. This pathway was then excited on the duodenal side by exposure to ethanol followed by luminal mustard oil to activate transient receptor potential subfamily A, member 1 (TRPA1). Ninety minutes later, pancreatic inflammation was examined. Ablation of duodenal afferents by resiniferatoxin (RTX) or blocking TRPA1 by Chembridge (CHEM)-5861528 was used to further investigate the duodeno-pancreatic neural reflex via TRPA1. ~40% of dorsal root ganglia (DRG) from the spinal cord originated from both duodenum and pancreas via dichotomous peripheral branches; ~50% splanchnic nerve single units responded to mechanical stimulation of both organs. Ethanol sensitized TRPA1 currents in cultured DRG neurons. Pancreatic edema and myeloperoxidase activity significantly increased after intraduodenal ethanol followed by mustard oil (but not capsaicin) but significantly decreased after ablation of duodenal afferents by using RTX or blocking TRPA1 by CHEM-5861528. We found the existence of a neural cross talk between the duodenum and pancreas that can promote acute pancreatitis in response to intraduodenal chemicals. It also proves a previously unexamined mechanism by which alcohol can induce pancreatitis, which is novel both in terms of the site (duodenum), process (neurogenic), and receptor (TRPA1).

Control strategy and mechanism for satellite droplet reduction.

Satellite droplets accompanying the formation of monodispersed particles have serious negative effects in the fields of medicine and food, especially in pill preparation. Therefore, it is of great significance to study control strategy and mechanism for satellite droplet reduction. This paper proposes a simple and efficient device, Drainage Assisted Dropper (DAD), which adds a stainless-steel needle to the center of General Dropper (GD). Experimental and numerical results show the number and volume of satellite droplets of the dripping formed by DAD are significantly reduced compared to those formed by GD. DAD can reduce the liquid volume of satellite droplets with a reduction rate of 87 %, while reducing the size of the primary droplet and increasing the interval between the adjacent primary droplets. Compared with GD, DAD has a smaller cross-sectional area and a larger wetted area, which results in a smaller downward velocity of the liquid. The drainage assisted needle of DAD changes the dripping flow pattern at the outlet of the dropper near the breaking time, causing the residual liquid to be subjected to a higher additional pressure. Less liquid is replenished to the filament, resulting in the filament with a shorter length and a smaller liquid volume. DAD proposed here has a clear development potential and application value in the fields of pharmaceuticals, food, agriculture, and manufacturing.