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Phase Change Material-based Battery Thermal Management System (PCM-based BTMS) has become a current research hotspot due to its high efficiency, thermal stability, and compactness. Regrettably, most existing research on PCM-based BTMS neglects the existence of mechanical vibrations, despite the inevitable involvement of such vibrations in the operating conditions of BTMS in electric vehicles. Therefore, in this study, a PCM-based BTMS is applied to a 6-cell lithium-ion battery (LIB) module, and then numerical simulation is employed to comprehensively evaluate the BTMS's performance in the existence of mechanical vibration. The findings indicate that, under mechanical vibration condition, mechanical vibration's influence on the performance of the BTMS is negligible at lower discharge rates, but becomes significant when the discharge rate surpasses a certain threshold, particularly at extremely fast discharge level, resulting in a decrease of 2.28 K in the LIB module’s maximum temperature and a more uniform temperature distribution upon completion of an 8 C discharge in contrast to its stationary equivalent. Furthermore, mechanical vibration only effectively enhances the BTMS’s thermal absorption capability when the PCM thickness surpasses a certain value, and this vibration also improves the capability of the BTMS to achieve uniform temperature distribution in the LIB module, especially for larger PCM thicknesses. Lastly, the BTMS's performance is able to strengthened by raising vibrational amplitude, but the impact is negligible when the amplitude is equal to or greater than 50 mm, and the thermal absorption capability of the BTMS can be augmented by raising the vibrational frequency, but there exists an enhancement limit. This work promotes the use of PCM-based BTMS in real-world applications and contributes to the advancement of LIB towards higher discharge rates.

IntroductionThe goal of this study is to assess the efficacy and safety of Lacticaseibacillus rhamnosus LRa05, as an adjunct to the treatment of acute watery diarrhea in children.MethodsEligible diarrheal children were randomized into intervention group (IG, n = 57) and control group (CG, n = 54), and given probiotics or placebo, respectively.ResultsThe total duration of diarrhea in the IG (121.4 ± 13.7 h) was significantly shorter than that in the CG (143.9 ± 19.8 h, p

The waveguide chip with a phase measurement function has garnered significant attention in the field of imaging optics, emerging as a crucial component in optical interferometric imaging systems. Enhancing the working bandwidth of these waveguide chips is essential for improving the imaging quality of interferometric systems. However, most existing designs primarily focus on narrow bands, with no reported research on broadband designs. This paper introduces a novel broadband waveguide chip design that incorporates a phase measurement function. We explore the fundamental structure and working principle of this innovative design. Fabricated on a silicon substrate, the chip features a silicon dioxide cladding layer and a germanium-doped silicon dioxide core layer, strategically optimized for performance. Utilizing the Beam Propagation Method (BPM), we conduct detailed simulations to determine the optimal device parameters. The simulation results demonstrate the effectiveness of our design, showing a phase measurement deviation of approximately 5° at a center wavelength of 1550 nm across a 300 nm wavelength range. The loss of the device is approximately 0.8 dB. These findings provide a solid foundation for future experimental implementations and fabrications, offering both a theoretical framework and technical reference for advancing the practical use of broadband waveguide chips with phase measurement functions in optical interferometric imaging.

Loop closure detection is a key technique for robots to minimize the accumulated localization and mapping errors after long-time explorations of simultaneous localization and mapping. However, the requirement for efficiency and accuracy performance for mobile robot applications is not well satisfied. In this article, we propose a fast and accurate loop closure detection method by exploiting both pose-based and appearance-based information in a probabilistic manner, inspired by the complementarity between the pose-based and the appearance-based information. Our approach formulates a probability framework combing the pose-based loop closure detection probability and the appearance-based loop closure detection probability. In the proposed framework, the pose-based loop closure detection model is firstly derived from the nonlinear optimization model of odometry. Then the appearance-based loop similarity and the pose-based loop similarity are combined into a joint framework to improve the loop closure detection performance. We implemented our approach using C++ and ROS and thoroughly tested it on the publicly available datasets. The experiments presented in this article suggest that the proposed method can achieve high efficiency and accuracy performance on loop closure detection.

A plate-fin heat sink is usually used for the hot side of thermoelectric coolers. The plate-fin heat sink should be optimized to improve its heat dissipation capability and eventually elevate the thermoelectric cooler performance. In this paper, a heat dissipation model of the thermoelectric cooler hot side with a plate-fin sink is established, to explore the performances of the plate-fin sink with two types of fins (rectangular and V-type), two convective conditions (lateral and vertical) and three arrangements (single-row, double-row aligned, and double-row staggered). The results show that under vertical jet conditions, double-row aligned rectangular fins have the best heat dissipation capability for the thermoelectric cooler hot side. In order to optimize the fin geometry and maximize its overall performance, a multi-objective optimization of the fins was performed using a machine learning approach based on artificial neural networks (ANN) and non-dominated sorting genetic algorithm (NSGA-ІІ). The corresponding Pareto front is obtained and the technique for order preference by similarity to ideal solution (TOPSIS) method is applied to take the point. Compared with the base case at the same mass flow rate, the fins designed by this method resulted in a 23.3 % reduction in the mean temperature of the hot side.

Objective: The present study aimed to characterize the genotype distribution and clinical characteristics of HCV monoinfected and HCV/HIV coinfected patients in the Liangshan Prefecture, Sichuan Province, China. Methods: All the patients were divided into HCV monoinfection and HCV/HIV coinfection groups according to whether they were complicated with HIV infection. The data from the two groups were collected. Results: In this study, HCV genotype 3 was the most common genotype in both groups, while HCV genotype 6 was significantly higher in the coinfection group than in the monoinfection group ( p = 0.046). The white blood cell count, total bilirubin level, and HCV RNA were significantly higher in the HCV monoinfection group than that in the HCV/HIV coinfection group ( p = 0.031; p

Abstract Background Calcaneal fractures are associated with numerous complications and a poor prognosis with significant long-term quality-of-life issues, regardless of treatment. Therefore, in-depth research into the underlying mechanism of calcaneal fracture is still of great interest, with the goal of improving treatment for patients suffering from this condition. This study aimed to investigate the relationship between the distribution of calcaneal fracture lines and their determinants, especially those related to the internal structure of the calcaneus. This goal was achieved by fracture maps created by copying and stacking fracture lines as viewed from six surfaces of the calcaneus. Methods A total of 210 consecutive patients with 226 calcaneal fractures were retrospectively analyzed. Fracture lines were copied from a reduced 3D calcaneal fracture model and stacked on calcaneal templates to generate fracture maps. The stacked images of six calcaneus surfaces were also converted into spectrograms with MATLAB to highlight the fracture frequency at specific locations. Results There were four concentrated bands of fracture lines and two fracture hot spots on the superior surface. Three dense bands of fractures were observed on the medial surface, and four fracture bands were observed lateral to the calcaneus. Vertical fracture lines dominated the anterior calcaneal fracture map. On the posterior surface, the fracture lines appeared to be centered superiorly. All fracture locations coincided with the interfaces between the trabecular groups. Conclusions The fracture maps showed fracture patterns and recurrent fracture zones on all calcaneal surfaces. The shape of the talus and calcaneus and the architecture within the calcaneus, especially the arrangement of the trabeculae, are essential factors for calcaneal fractures.

Abstract Background Chickens, important food animals and model organisms, are susceptible to many RNA viruses that invade via the nasal cavity. To determine the nasal entry site of the virus and clarify why avians are susceptible to RNA viruses, infectious bursal disease virus (IBDV) was selected because it is a typical avian RNA virus that infects chickens mainly via the nasal route. Results First, we found that IBDV infected the posterior part of the nasal cavity in chickens, which is rich in lymphoid tissue and allows the virus to be easily transferred to the blood. Via the blood circulation, IBDV infected peripheral blood mononuclear cells (PBMCs) and was transferred to the bursa of Fabricius to damage the IgM + B lymphocyte population. Subsequently, the single-cell RNA sequencing (scRNA-seq) results suggested the more detailed response of different bursal cell populations (B cells, epithelial cells, dendritic cells, and fibroblasts) to IBDV. Regarding B cells, IBDV infection greatly decreased the IgM + B cell population but increased the IgA + B cell population in the bursal follicles. In contrast to B cells, bursal epithelial cells, especially basal cells, accumulated a large number of IBDV particles. Furthermore, we found that both innate RNA sensors and interferon-stimulated genes (ISGs) were highly expressed in the IBDV-infected groups, while dicer and ago2 expression was largely blocked by IBDV infection. This result suggests that dicer-related RNA interference (RNAi) might be an effective antiviral strategy for IBDV infection in avian. Conclusion Our study not only comprehensively elaborates on the transmission of airborne IBDV via the intranasal route and establishes the main target cell types for productive IBDV infection but also provides sufficient evidence to explain the cellular antiviral mechanism against IBDV infection. Graphical Abstract

Tumor microenvironment (TME) is intently related to tumor growth, progression and invasion, leading to drug resistance and insufficient therapeutic efficacy. However, remodeling TME and utilizing TME for exploring intelligent nanomaterials that can realize tumor theranostic is still challenging. Nowadays, the theranostic based on chemotherapy exposes some deficiencies, such as low targeting, weak permeability and premature clearance. Furthermore, it is challenging to cure drug-resistant tumors effectively. For the sake of solving these problems, a biomimetic decomposable nano-theranostic (MMV-Au-CDs-DOX) was well-established in this work. The Au-CDs are coated with macrophage-derived microvesicle to realize drug release accurately and enhance the biocompatibility of internal nanoparticles. Furthermore, MMV-Au-CDs-DOX would locate in the inflammation position of tumor, and disintegrate correspondingly into pieces with certain different functions stimulated by TME. Subsequently, the released anti-tumor nanodrugs were used for multimodal therapy, including chemotherapy and hemodynamic therapy. In addition, combined with the ability of Au-CDs to recognize GSH specifically, the off-on fluorescent probe was constructed to monitor the GSH of tumor cells and provided information on chemotherapy resistance.

Planetary, lunar, and deep space exploration has become the frontier of remote sensing science, and three-dimensional (3D) positioning imaging technology is an important part of lunar and deep space exploration. This paper presents a novel passive 3D imaging method based on the photonics integrated interference computational imaging system. This method uses a photonics integrated interference imaging system with a complex lens array. The midpoints of the interference baselines formed by these lenses are not completely overlapped. The distance between the optical axis and the two lenses of the interference baseline are not equal. The system is used to obtain the complex coherence factor of the object space at a limited working distance, and the image evaluation optimization algorithm is used to obtain the clear images and 3D information of the targets of interest. The simulation results show that this method is effective for the working scenes with targets located at single or multiple limited working distances. The sharpness evaluation function of the target presents a good unimodality near its actual distance. The experimental results of the interference of broad-spectrum light show that the theoretical basis of this method is feasible.

Interferometric imagers based on integrated optics have the advantages of miniaturization and low cost compared with traditional telescope imaging systems and are expected to be applied in the field of space target detection. Phase measurement of the complex coherence factor is crucial for the image reconstruction of interferometric imaging technology. This study discovers the effect of the phase of the complex coherence factor on the extrema of the interference fringes in the interferometric imager and proposes a method for calculating the phase difference of the complex coherence factor of two interference signals by comparing the extrema of the interferometric fringes in the area of approximate linear change in the envelope shape to obtain the phase information required for imaging. Experiments using two interferometric signals with a phase difference of π were conducted to verify the validity and feasibility of the phase difference measurement method. Compared with the existing phase measurement methods, this method does not need to calibrate the position of the zero optical path difference and can be applied to the integrated optical interferometric imager using a single-mode fiber, which also allows the imager to work in a more flexible way. The theoretical phase measurement accuracy of this method is higher than 0.05 π, which meets the image reconstruction requirements.

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.

ABSTRACT: Canthaxanthin is widely used as a feed additive to improve skin and yolk color in poultry. It is insoluble in water and sensitive to oxidation, so commercial canthaxanthin is often microencapsulated with wall materials to improve its solubility and stability. The objective of this study was to evaluate the effects of canthaxanthin microencapsulation on yolk color and canthaxanthin deposition in egg yolk of laying hens. A total of 288 Hyline Brown laying hens (48 wk of age) were allocated to 4 groups with 6 replicates of 12 hens each, and fed a basal diet or the basal diet supplemented with 5 mg/kg canthaxanthin microencapsulated with modified starch (CMMS), gelatin (CMG), and sodium lignosulfonate (CMSL), respectively. Canthaxanthin supplementation did not affect laying performance of hens, but improved (P < 0.05) yolk color of fresh, fried, boiled, and stored (4 and 25°C) eggs. The improvement of yolk color of fresh eggs was greatest in the CMSL group and least in the CMG group (P < 0.05). Both CMMS and CMSL resulted in higher (P < 0.05) yolk canthaxanthin concentration than CMG. The CMSL resulted in higher (P < 0.05) yolk color score of fried eggs than CMMS and CMG and higher (P < 0.05) yolk color score of boiled eggs than CMG, but no difference was observed in stored eggs among three canthaxanthin groups. In conclusion, CMMS and CMSL were more effective in yolk pigmentation than CMG, and CMSL was slightly better than CMMS.

Abstract Background Three-dimensional (3D) computed tomography (CT) reconstruction technology has gained attention owing to its potential in locating ground glass nodules in the lung. The 3D printing technology additionally allows the visualisation of the surrounding anatomical structure and variations. However, the clinical utility of these techniques is unknown. This study aimed to establish a lung tumour and an anatomical lung model using 3D printing and 3D chest CT reconstruction and to evaluate the clinical potential of 3D printing technology in uniportal video-assisted thoracoscopic segmentectomy. Methods Eighty-nine patients with ground glass nodules who underwent uniportal video-assisted thoracoscopic segmentectomy were classified into the following groups: group A, lung models for pre-positioning and simulated surgery that were performed with 3D chest CT reconstruction and 3D printing, and group B, patients who underwent chest CT scans with image enhancement for 3D reconstruction. The differences in the surgery approach transfer rate, surgical method conversion rate, operative time, intraoperative blood loss, and postoperative complication rate were compared between the two groups. Results Between groups A and B, there were significant differences in the approach transfer rate (0% vs.10.5%, p = 0.030), operative time (2.07 ± 0.24 h vs. 2.55 ± 0.41 h, p < 0.001), intraoperative blood loss volume (43.25 ± 13.63 mL vs. 96.68 ± 32.82 mL, p < 0.001) and the rate of surgical method conversion to lobectomy (0% vs. 10.5%, p < 0.030). In contrast, there was an insignificant difference in the postoperative complication rate between groups A and B (3.9% vs. 13.2%, p = 0.132). Conclusions 3D printing technology facilitates a more accurate location of nodules by surgeons, as it is based on two-dimensional and 3D image-based findings, and therefore, it can improve surgical accuracy and safety. This technique is worth applying in clinical practice.

Abstract Akkermansia muciniphila, a novel mucin-degrading bacterium, has been demonstrated to prevent the development of obesity and related complications. However, whether it can protect poultry from intestinal mucosal damage by enteropathogens has never been mentioned. In this study, we found that A. muciniphila colonized in the intestine and then relieved intestinal mucosal damage in chicks caused by S. pullorum, including anatomical and morphological damage, alleviation of body weight and intestinal inflammation. The repair process activated by A. muciniphila is accompanied by an increase in the number of goblet cells in the chick’s intestine and an up-regulation of Mucin 2 and trefoil factor 2 (Tff2). In addition, we also demonstrate that A. muciniphila improved colon length, crypt depth, increased the proliferating cell nuclear antigen, with the accelerated proliferation of intestinal epithelium through Wnt/β-catenin signaling pathway, thereby restoring the damaged intestinal mucosa. This study suggests that A. muciniphila activates the proliferation of intestinal cells protecting the intestinal barrier, thus relieving infection with S. pullorum in chickens.

Our previous study found that IL33 repressed the growth of pulmonary adenocarcinoma (PA) via regulation of dendritic cells (DCs). However, the molecular mechanism of DCs in PA is still unclear. The present work showed that CYLD−/− mice have a shorter survival rate of PA, and knockout CYLD in DCs also repress the progression of PA in mice. Subsequently, we found that decreased expression and reduced the nuclear translocation of NF-κB signalling was observed in CYLD knockout DCs, and inhibiting NF-κB pathway repressed DCs-induced proliferation and function of CD4+ T cells. These results indicated that CYLD function as a tumour suppresser in PA via regulates the function of DCs through NF-κB signalling pathway. Our findings support that CYLD serves as a potential target for immunotherapy in PA.

ABSTRACT: Bacillus coagulans (B. coagulans) have proven to be effective in improving the development of gut immunity and microbiome, and offering protection against pathogens, especially in young animals. The newborn chicks are highly vulnerable to the foodborne pathogenic Salmonella infections, leading to high mortality and economic loss. However, whether B. coagulans can protect young chickens from Salmonella-induced intestinal mucosal damage by modulating the development of intestinal epithelium remains unclear. In this study, B. coagulans with excellent anti-Salmonella property was selected and used. The results showed that B. coagulans alleviated the morphological damage, intestinal inflammation and body weight loss caused by Salmonella enteritidis (S. enteritidis) infections. B. coagulans significantly increased the crypt depth. Furthermore, the goblet cell loss and downregulating of mucin 2 induced by S. enteritidis were all relieved by B. coagulans treatment. Consistently, the expression of the related genes of Notch signaling pathway was also upregulated in the S. enteritidis group but inhibited by B. coagulans. In addition, B. coagulans improved the levels of immunoglobulin A, superoxide dismutase, total antioxidant capacity, and avian beta-defensin 2 in the intestinal mucosa. This study demonstrated that B. coagulans could regulate the development of intestinal epithelium, protect the intestinal barrier, thus relieve infections with S. enteritidis in chicks, which can be used as alternatives to antibiotics in poultry feed.

Photo-thermal responsive actuators are attracting increasing attention due to their good light source and wireless remote control. A Ketjen Black (KB)-based sandwich photo-thermal responsive actuator with low cost, simple preparation, and excellent performance was developed, which significantly improved the actuation performance compared to the bilayer ones, with an impressive actuation bending angle of 75°. Meanwhile, the effects of different carbon materials and structural parameters on actuation performance were discussed. The actuation performance of KB-based actuators can be close to that of the CNTs and GO-based actuators when with the sandwich structure. It was found that the optimal structure would be that of PI-PDMS- KB/PDMS. The actuation mechanism was further analyzed by the finite element method. The simulation results showed good conformity to the experiments, which presented the feasibility of predicting the film actuators' photo-thermal responsive performance. The potential of this photo-thermal responsive film actuator to be used in a breathable fabric, mechanical gripper, and bionics robot were also demonstrated.

Ammonia (NH3) is regarded as a promising medium of hydrogen storage, due to its large hydrogen storage density, decent performance on safety and moderate storage conditions. On the user side, NH3 is generally required to decompose into hydrogen for utilization in fuel cells, and therefore it is vital for the NH3-based hydrogen storage technology development to study NH3 decomposition processes and improve the decomposition efficiency. Numerical simulation has become a powerful tool for analyzing the NH3 decomposition processes since it can provide a revealing insight into the heat and mass transfer phenomena and substantial guidance on further improving the decomposition efficiency. This paper reviews the numerical simulations of NH3 decomposition in various application scenarios, including NH3 decomposition in microreactors, coupled combustion chemical reactors, solid oxide fuel cells, and membrane reactors. The models of NH3 decomposition reactions in various scenarios and the heat and mass transport in the reactor are elaborated. The effects of reactor structure and operating conditions on the performance of NH3 decomposition reactor are analyzed. It can be found that NH3 decomposition in microchannel reactors is not limited by heat and mass transfer, and NH3 conversion can be improved by using membrane reactors under the same conditions. Finally, research prospects and opportunities are proposed in terms of model development and reactor performance improvement for NH3 decomposition.

Summary: Fiber supercapacitors have attracted significant attention because of the relevance for textile electronics. However, the key challenge is to achieve high output voltage and performance of fiber supercapacitors while maintaining the high flexibility of the fibers. Here, we present a fiber supercapacitor, based on an overlaid tree topology configuration, by braiding sub-fiber supercapacitor units in an asymmetrical series connection. The tree-like topology-based asymmetric fiber supercapacitors (TTAFSCs) achieve a high energy density (0.022 Wh cm−3 at a power density of 0.444 W cm−3) with an extendable high voltage output (>9.6 V) while maintaining outstanding mechanical properties (>1,000 bending cycles, capable of loading an object of ∼200 g). TTAFSCs of ∼8 cm in length are capable of lighting light-emitting diodes, driving a watch, and powering a display, even in a bent and twisted state.

Intensive farming is prone to induce large-scale outbreaks of infectious diseases, with increasing use of antibiotics, which deviate from the demand of organic farming. The high mortality rate of chickens infected with Salmonella caused huge economic losses; therefore, the promising safe prevention and treatment measures of Salmonella are in urgent need, such as probiotics. Probiotics are becoming an ideal alternative treatment option besides antibiotics, but the effective chicken probiotic strains with clear protective mechanism against Salmonella remain unclear. In this study, we found Enterococcus faecium YQH2 was effective in preventing Salmonella typhimurium infection in chickens. Salmonella typhimurium induced the loss of body weight, and liver and intestinal morphology damage. The inflammatory factor levels increased and intestinal proliferation inhibited. However, after treatment with Enterococcus faecium YQH2, broilers grew normally, the pathological changes of liver and intestine were reduced, and the colonization of Salmonella in the intestine was improved. Not only that, the length of villi and the depth of crypts were relatively normal, and the levels of inflammatory factors such as IL-1β, TNF-α, and IL-8 were reduced. The number of PCNA cells of Enterococcus faecium YQH2 returned to normal under the action of Salmonella typhimurium infection, which was conducive to the normal proliferation of intestinal epithelial cells. The protective effect of Enterococcus faecium YQH2 may be due to the attribution to the activation of hypoxia and then induced the proliferation of intestinal stem cells to repair the damage of intestinal mucosa under Salmonella typhimurium infection. This study demonstrated that Enterococcus faecium YQH2 was effective in preventing Salmonella typhimurium infection, which could be further used in the chicken health breeding.

Reduced imine cage (RCC3) was covalently bonded to the surface of silica spheres, and then the secondary amine group of the molecular cage was embedded in non-polar C10 for modification to prepare a novel RCC3-C10@silica HPLC stationary phase with multiple separation functions. Through infrared spectroscopy, thermogravimetric analysis and nitrogen adsorption–desorption characterization, it was confirmed that RCC3-C10 was successfully bonded to the surface of silica spheres. The resolution of RCC3-C10@silica in reversed-phase separation mode is as high as 2.95, 3.73, 3.27 and 4.09 for p-phenethyl alcohol, 1-phenyl-2-propanol, p-methylphenethyl alcohol and 1-phenyl-1-propanol, indicating that the stationary phase has excellent chiral resolution performance. In reversed-phase and hydrophilic separation modes, RCC3-C10@silica realized the separation and analysis of a total of 70 compounds in 8 classes of Tanaka mixtures, alkylbenzene rings, polyphenyl rings, phenols, anilines, sulfonamides, nucleosides and flavonoids, and the analysis of a variety of chiral and achiral complex mixtures have been completed at the same time. Compared with the traditional C18 commercial column, RCC3-C10@silica exhibits better chromatographic separation selectivity, aromatic selectivity and polar selectivity. The multifunctional separation mechanism exhibited by the stationary phase originates from various synergistic effects such as hydrophobic interaction, π-π interaction, hydrogen bonding and steric interaction provided by RCC3 and C10 groups. This work provides flexible selectivity and application prospects for novel multi-separation functional chromatographic columns.

Most autonomous mobile robots are often equipped with monocular cameras and 3D LiDARs to perform vital tasks such as localization and mapping. In this paper, we present a two-stage extrinsic calibration method as well as a hybrid-residual-based odometry approach for such camera-LiDAR systems. Our extrinsic calibration method can estimate the relative transformation between the camera and the LiDAR with high accuracy, allowing us to better register the image and the point cloud data. After the calibration, our hybrid-residual-based odometry can be used to provide real-time, accurate odometry estimates. Our approach exploits both direct and indirect image features. The sensor motions are estimated by jointly minimizing reprojection residuals and photometric residuals in a nonlinear optimization procedure. Experiments are conducted to show the accuracy and robustness of our extrinsic calibration and odometry algorithms using both public and self-owned real-world datasets. The results suggest that our calibration method can provide accurate extrinsic parameters estimation without using initial values, and our odometry approach can achieve competitive estimation accuracy and robustness.

Patrol missiles are a common type of unmanned aerial vehicle, which can be efficiently used for reconnaissance and sensing. In this work, target detection and the damage assessment of typical mobile ground targets by patrol missiles are studied, and a new method, combining the YOLO v3 with the VGG networks, is proposed for the problem. Specifically, with YOLO v3 as the precursor, the proposed method can detect, classify, and localize ground targets accurately and quickly. Then, the image blocks of detected targets are fed into the lightweight VGG networks, which can evaluate their damage level coarsely. Meanwhile, based on class activation mapping (CAM) and deconvolution, we further analyse the activation intensity of clustered convolution kernels, which helps determine whether the targets’ key components are destroyed. Unlike traditional image change detection methods, which require images before and after a strike for comparison, the proposed method learns the target model through extensive training and can assess the target’s damage status in a timely and online manner. Compared to previous learning-based methods, our detailed analysis with convolutional feature visualization of the damaged targets and their components gives a more interpretable perspective. Finally, Unity simulation experiments prove the proposed method’s effectiveness, which improves the accuracy of damage level assessment by 16.0% and 8.8% compared with traditional image-change-detection-based methods and the two-CNN learning-based method. The convolutional feature clustering method evaluates the status of the targets’ key components with an accuracy of 72%.

In this study, a tunable gourd-shaped ring resonator is demonstrated to generate optical bistability. The system consists of two sub-rings for a gourd shape configuration with a U-shaped wave guiding pathway. The transfer matrix method and FDTD simulation are used to acquire the spectral characteristics of the system. For the fabricated device, the spectra profile and extinction ratio can be effectively tuned by the microheater above the U-shaped waveguide, which matches with the theoretical results. Due to the gourd structure of the resonator, the light waves in two rings can be cross-coupled with each other, and the optical bistability could come out effectively with the change in the input optical power around 6 mW. The presented optical bistability devices have great application potential in optical information processing such as optical storage, switch and logic operation.

This research explores the design of products based on users’ emotional requirements and how students can be stimulated to generate novel ideas in design education. In order to achieve these aims, multiple methods were taught to students during an online course. In the first step, the students utilised interviews, questionnaires, and mixed perspectives to design hill censers according to the users’ emotional requirements. In the second step, the researcher conducted a qualitative thematic analysis to study the students’ collected survey reports. The analytic results were then shared with students to help them quickly obtain better novel design ideas. And then, an emotional design appraisal model was built in the third step. The two main findings are as follows: first, creation in light of the stakeholder’s perspective enabled the students to come up with better design ideas quickly. Second, the ‘design method’ and ‘emotional experience’ themes obtained by the thematic analysis were found to be vital for the designers/students. Notably, the ‘design method’ theme can help students generate novel design ideas, and the students can learn the users’ needs from the ‘emotional experience’ theme.

As a common and frequent clinical disease, peripheral nerve defect has caused a serious social burden, which is characterized by poor curative effect, long course of treatment and high cost. Nerve autografting is first-line treatment of peripheral nerve injuries (PNIs) but can result in loss of function of the donor site, neuroma formation, and prolonged operative time. Nerve guidance conduit (NGC) serves as the most promising alternative to autologous transplantation, but its production process is complicated and it is difficult to effectively combine growth factors and bioactive substances. In recent years, additive manufacturing of NGCs has effectively solved the above problems due to its simple and efficient manufacturing method, and it can be used as the carrier of bioactive substances. This review examines recent advances in additive manufacture of NGCs for PNIs as well as insight into how these approaches could be improved in future studies.

The increasing number of patients with chronic wounds caused by diseases, such as diabetes, malignant tumors, infections, and vasculopathy, has caused severe economic and social burdens. The main clinical treatments for chronic wounds include the systemic use of antibiotics, changing dressings frequently, operative debridement, and flap repair. These routine therapeutic strategies are characterized by a long course of treatment, substantial trauma, and high costs, and fail to produce satisfactory results. Biomaterial dressings targeting the different stages of the pathophysiology of chronic wounds have become an active research topic in recent years. In this review, after providing an overview of the epidemiology of chronic wounds, and the pathophysiological characteristics of chronic wounds, we highlight the functional biomaterials that can enhance chronic wound healing through debridement, anti-infection and antioxidant effects, immunoregulation, angiogenesis, and extracellular matrix remodeling. It is hoped that functional biomaterials will resolve the treatment dilemma for chronic wounds and improve patient quality of life.

High tracking frame rates have been achieved based on traditional tracking methods which however would fail due to drifts of the object template or model, especially when the object disappears from the camera’s field of view. To deal with it, tracking-and-detection-combination has become more and more popular for long-term unknown object tracking, whose detector almost does not drift and can regain the disappeared object when it comes back. However, for online machine learning and multiscale object detection, expensive computing resources and time are required. So it is not a good idea to combine tracking and detection sequentially like Tracking-Learning-Detection algorithm. Inspired from parallel tracking and mapping, this article proposes a framework of parallel tracking and detection for unknown object tracking. The object tracking algorithm is split into two separate tasks—tracking and detection which can be processed in two different threads, respectively. One thread is used to deal with the tracking between consecutive frames with a high processing speed. The other thread runs online learning algorithms to construct a discriminative model for object detection. Using our proposed framework, high tracking frame rates and the ability of correcting and recovering the failed tracker can be combined effectively. Furthermore, our framework provides open interfaces to integrate state-of-the-art object tracking and detection algorithms. We carry out an evaluation of several popular tracking and detection algorithms using the proposed framework. The experimental results show that different tracking and detection algorithms can be integrated and compared effectively by our proposed framework, and robust and fast long-term object tracking can be realized.

Intestinal microbiota is necessary for the guarantee of intestinal mucosal barrier. However, the detailed effect of probiotics on porcine intestinal development, especially in the early life, is still unclear. In this study, we treated 3-day-old newborn piglets with Lactobacillus reuteri (L. reuteri) D8 and observed its beneficial effect on piglets. The body weights, villus height, and crypt depth of jejunum were all significantly increased after L. reuteri treatment in piglets. L. reuteri also significantly increased the proliferation index of PCNA+ cells in the crypt, as well as c-Myc and Tcf4 expressions. Furthermore, L. reuteri also enhanced intestinal mucosal barrier with the increase of goblet cells and antimicrobial peptides (AMPs) expressions of Muc2, Lyz1, and pBD1. The well development of Peyer's patches and increased number of CD3+ T cells, combined with increased expression of IL-4 and IFN-γ, also demonstrated the immune stimulation effect of L. reuteri D8. This study demonstrated that L. reuteri promotes the development of intestine mucosal system and maintains intestinal mucosal barrier in newborn piglets.

Abstract Background Aberrant AKT activation is prevalent across human cancer lineages, providing an important therapeutic target. AKT comprises three isoforms that mediate critical non-redundant, even opposing functions in cancer pathophysiology. Therefore, targeting specific AKT isoforms in particular cancers may be more effective than pan-AKT inhibition while avoiding disadvantages of pan-AKT inhibition. Currently, AKT isoform-specific expression and activation in cancer are not clearly characterized. Methods We systematically characterized AKT isoform-specific expression and activation in 211 cancer cell lines derived from different lineages and genetic backgrounds using a reverse-phase protein array platform. Results We found that phosphorylation, but not expression, of AKT1 and AKT2 was coordinated in most but not all cells. Different cancer lineages displayed differential AKT1 and AKT2 expression and phosphorylation. A PIK3CA hotspot mutation H1047R but not E545K was associated with selective activation of AKT2 but not AKT1. Conclusions Our study identified and validated AKT isoform-specific expression and phosphorylation in certain cell lines and demonstrated that genetic changes can affect AKT isoform-specific activation. These results provide a more precise understanding of AKT isoform-specific signaling and, in addition, facilitate AKT isoform targeting for personalized cancer therapies.

Visual odometry has greatly progressed since non-linear optimization methods were introduced for pose estimation. Furthermore, RGBD visual odometry has become a hot research topic in the robotic and computer vision field with the introduction of RGBD cameras. However, most RGBD-camera-based visual odometry methods are designed by extending monocular visual odometry methods, therein not paying much attention to the integration of the different types of information provided by RGBD images. In this paper, we propose a novel hybrid-residual-based-RGBD visual odometry, where three types of complementary information are integrated into a joint optimization model. The reprojection residuals, the photometric residuals and the depth residuals are minimized together in the non-linear optimization process, where a robust cost function and outlier filtering are employed in the iterative optimization to enhance the robustness of the iteration while simultaneously maintaining the optimality. Experiments on publicly available RGBD data sets validate the advantages of the integration of multiple types of information for RGBD visual odometry. The accuracy and robustness are greatly improved by our method.

Soft robots are those that can move like living organisms and adapt to the surrounding environment. Compared with traditional rigid robots, the advantages of soft robots, in terms of material flexibility, human–computer interaction, and biological adaptability, have received extensive attention. Flexible actuators based on light response are one of the most promising ways to promote the field of cordless soft robots, and they have attracted the attention of scientists in bionic design, actuation implementation, and application. First, the three working principles and the commonly used light-responsive materials for light-responsive actuators are introduced. Then, the characteristics of light-responsive soft actuators are sequentially presented, emphasizing the structure strategy, actuation performance, and emerging applications. Finally, this review is concluded with a perspective on the existing challenges and future opportunities in this nascent research frontier.

The convective heat transfer behavior of supercritical nitrogen (S-N2) has played a significant role in optimizing the design of recently emerging cryogenic cold storage and recovery systems. However, studies on S-N2 heat transfer have been relatively scarce, not to mention that there is a legitimate urge for a robust numerical model to accurately predict and explain S-N2 heat transfer under various working conditions. In this paper, both experimental and numerical studies were conducted for convective heat transfer of S-N2 in a small vertical tube. The results demonstrated that the standard k-ε model performed better for predicting the key heat transfer characteristics of S-N2 than the SST k-ω model. The effects of heat flux and inlet pressure on the heat transfer characteristics under a large mass flux were evaluated. The variation mechanisms of local heat transfer performance were revealed by illustrating radial profiles of thermophysical properties and turbulent parameters of N2. It was found that the local performance variation along the flow direction was mainly determined by the radial profile of specific heat while the variation of the best local performance with the ratio of heat flux to mass flux was mainly determined by the radial profile of turbulent viscosity.

An ultra-compact broadband silicon polarizing beam splitter is proposed based on a tilted nano-grating structure. A light cross coupling can be realized for transverse-magnetic mode, while the transverse-electric light can almost completely output from the through port. The length of the coupling region is only 6.8 μm, while an extinction ratio of 23.76 dB can be realized at a wavelength of 1550 nm. As a proof of concept, the device was fabricated by a commercial silicon photonic foundry. It can realize a 19.84 dB extinction ratio and an 80 nm working bandwidth with an extinction ratio of larger than 10 dB. The presented device also shows a good fabrication tolerance to the structure deviations, which is favorable for its practical applications in silicon photonics.

Immunological memory is a cardinal feature of the immune system. The intestinal mucosa is the primary exposure and entry site of infectious organisms. For an effective and long-lasting safeguard, a robust immune memory system is required, especially by the mucosal immunity. It is well known that tissue-resident memory T cells (Trms) provide a first response against infections reencountered at mucosal tissues surfaces, where they accelerate pathogen clearance. However, their function in intestinal immunization remains to be investigated. Here, we report enhanced local mucosal and systemic immune responses through oral administration of H9N2 influenza whole inactivated virus (H9N2 WIV) plus Bacillus subtilis spores. Subsequently, H9N2 WIV plus spores led to the generation of CD103+ CD69+ Trms, which were independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spores could stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, spore-stimulated adipocyte supernatant also upregulated the expression of intercellular adhesion molecule-1 (ICAM1) in dendritic cells (DCs). Furthermore, the proportion of HA-tetramer+ cells was severely curtailed upon suppressed ICAM1 expression, which also depended on HA-loaded DCs. Taken together, our data demonstrated that spore-promoted H9N2 WIV induced an immune response by enhancing Trms populations, which were associated with the activation of ICAM1 in DCs.

Abstract The spread of Avian influenza virus via animal feces makes the virus difficult to prevent, which causes great threat to human health. Therefore, it is imperative to understand the survival and invasion mechanism of H9N2 virus in the intestinal mucosa. In this study, we used mouse threedimensional intestinal organoids that contained intestinal crypts and villi differentiated from intestinal stem cells to explore interactions between H9N2 avian influenza virus and the intestinal mucosa. The HA, NA, NP and PB1 genes of H9N2 viruses could be detected in intestinal organoids at 1 h, and reached peak levels at 48 h post-infection. Moreover, the HA and NP proteins of H9N2 virus could also be detected in organoids via immunofluorescence. Virus invasion caused damage to intestinal organoids with reduced mRNA transcript expression of Wnt3, Dll1 and Dll4. The abnormal growth of intestinal organoids may be attributed to the loss of Paneth cells, as indicated by the low mRNA transcript levels of lyz1 and defcr1. This present study demonstrates that H9N2 virus could invade intestinal organoids and then cause damage, as well as affect intestinal stem cell proliferation and differentiation, promoting the loss of Paneth cells.

Personalized medicine: Signature-guided cancer therapy Personalized cancer therapy is one of the holy grails of oncology, as the ability to determine what treatment would best benefit a patient would serve not only to improve outcomes, but also mitigate side effects from less effective treatments. Here, we develop algorithms to predict what patients will respond to a given therapeutic modality, as well as ways to specifically target any observed phenotype, by integrating large scale data sets that profile cancer cell line gene expression and sensitivity to hundreds of drugs. Furthermore, we show how these gene expression signatures can be used to predict novel synergizing agents to further enhance the efficacy of these therapeutics. Taken together, this work stands to advance the era of personalized medicine by enabling precision medicine approaches in the clinic.

Emotional design focuses on providing intended users with a positive emotional experience. Thus far, the concept of emotional design has primarily been restricted to the fields of research and industry. Most professionals using emotional design slowly acquired the required skills by experience and without direct education. Teaching emotional design to design students has been overlooked due to its difficulty. This research introduces a new approach to teaching emotional design, which aims to prevent negative influences from being added to the products created by design students. A systematic method is introduced to make it easier for inexperienced design students to grasp emotional design. Students are first taught proper methods of data collection to determine users’ emotional requirements. Students are then taught how to summarize the data, as well as develop feasibility testing strategies to obtain promising ideas. The proposed teaching approach for emotional design has been proven efficient in the case study course conducted in this research. Graduate-level design students learned how to design products according to users’ emotional requirements. The students successfully produced several designs that clearly provided positive user experiences.

The intestine is home to trillions of microorganisms, and the vast diversity within this gut microbiota exists in a balanced state to protect the intestinal mucosal barrier. Research into the association of the intestinal microbiota with health and disease (including diet, nutrition, obesity, inflammatory bowel disease, and cancer) continues to expand, with the field advancing at a rapid rate. Intestinal stem cells (ISCs) are the fundamental component of the mucosal barrier; they undergo continuous proliferation to replace the epithelium, which is also intimately involved in intestinal diseases. The intestinal microbiota, such as Lactobacillus, communicates with ISCs both directly and indirectly to regulate the proliferation and differentiation of ISCs. Moreover, Salmonella infection significantly decreased the expression of intestinal stem cell markers Lgr5 and Bmi1. However, the detailed interaction of intestinal microbiota and ISCs are still unclear. This review considers the progress of research on the model and niches of ISCs, as well as the complex interplay between the gut microbiota and ISCs, which will be crucial for explaining the mechanisms of intestinal diseases related to imbalances in the intestinal microbiota and ISCs.

Deficient mucosal innate immunity is a hallmark of infectious diarrhea, such as Salmonella typhimurium (S. typhimurium)-induced gastroenteritis. Here, we report that oral administration of a 4,4′-diaponeurosporene-producing Bacillus subtilis (B.s-Dia) could improve mice mucosal immunity, as showed by an increased resistance against S. typhimurium infection. Intragastric administration of B.s-Dia for 7 days could increase the secretion of CCL20 by intestinal epithelial cells (IECs) and then recruit more dendritic cells. Meanwhile, the number of CD8αα+ intraepithelial lymphocytes, which play a critical role in downregulating immune responses, was also reduced, probably as a consequence of the decrease of IEC-derived TGFβ. Further study showed that CD36 played a critical role in B.s-Dia-induced immune enhancement, as blocking CD36 signal with a specific antagonist, sulfo-N-succinimidyl oleate, led to the inability of B.s-Dia to enhance mucosal innate immunity.

OBJECTIVE:The nasal mucosa is equipped with abundant lymphatic tissues, serving as the first line of defense against invasion by microorganisms. In this study, we characterized the features of the nasal mucosa of Bama minipigs (Sus scrofa domestica) via histological analysis. METHODS:Five cross sections (I, II, III, IV, and V) were obtained from the distal end of the nasal cavity toward the pharynx (along the cavity axis) and examined. Specifically, CD3+ T cells, immunoglobulin A (IgA)+ cells, and M cells were detected by immunohistochemistry, while dendritic cells (DCs) were detected by immunofluorescence. The distribution of goblet cells was determined by periodic acid-Schiff (PAS) staining. RESULTS:The nasal cavity of Bama minipigs can be divided into three parts: the regio vestibularis (I, II), regio respiratoria (III, IV), and regio olfactoria (V). Lymphoid tissue was present at random locations in the nasal cavity. Abundant lymphoid tissue was located in the roof of the nasopharyngeal meatus and was continuous with the lymphoid tissue of the pharynx. The distribution of CD3+ T cells, IgA+ cells, M cells, and DCs increased distally in the nasal cavity. CONCLUSIONS:The present work comprises a histological study of the nasal cavity of Bama minipigs, and will be beneficial for understanding the mechanisms of immunity in these animals after nasal vaccination.

Probiotics are essential for the prevention of virus invasion and the maintenance of the immune balance. However, the mechanism of competition between probiotics and virus are unknown. The objectives of this study were to isolate the surface layer (S-layer) protein from L. acidophilus ATCC 4356 as a new antiviral material, to evaluate the stimulatory effects of the S-layer protein on mouse dendritic cells (DCs) and to verify its ability to inhibit the invasion of H9N2 avian influenza virus (AIV) in DCs. We found that the S-layer protein induced DCs activation and up-regulated the IL-10 secretion. The invasion and replication of the H9N2 virus in mouse DCs was successfully demonstrated. However, the invasion of H9N2 virus into DCs could be inhibited by treatment with the S-layer protein prior to infection, which was verified by the reduced hemagglutinin (HA) and neuraminidase (NA) mRNA expression, and nucleoprotein (NP) protein expression in the DCs. Furthermore, treatment with the S-layer protein increases the Mx1, Isg15, and Ddx58 mRNA expressions, and remits the inflammatory process to inhibit H9N2 AIV infection. In conclusion, the S-layer protein stimulates the activation of mouse DCs, inhibits H9N2 virus invasion of DCs, and stimulates the IFN-I signalling pathway. Thus, the S-layer protein from Lactobacillus is a promising biological antiviral material for AIV prevention.

The development of genetically engineered animals has brought with it increasing concerns about biosafety issues. We therefore evaluated the risks of growth hormone from transgenic goats, including the probability of horizontal gene transfer and the impact on the microbial community of the goats' gastrointestinal tracts, feces and the surrounding soil. The results showed that neither the GH nor the neoR gene could be detected in the samples. Moreover, there was no significant change in the microbial community of the gastrointestinal tracts, feces and soil, as tested with PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing. Finally, phylogenetic analysis showed that the intestinal content, feces and soil samples all contained the same dominant group of bacteria. These results demonstrated that expression of goat growth hormone in the mammary of GH transgenic goat does not influence the microflora of the intestine, feces and surrounding soil.

Dendritic cells (DCs) play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5), a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS)-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH) and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs)/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1) was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry.

Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 predicted membrane-spanning helices. Goat GLUT1 and GLUT12 each influenced the mRNA expression of the other transporter and increased the glucose consumption and lactose yield in GLUT1- and GLUT12-transfected goat mammary gland epithelial cells, respectively. The overexpression of GLUT1 or GLUT12 also increased the expression of amino acid transporters SLC1A5, SLC3A2 and SLC7A5 and affected genes expressions in GMGE cells. Using immunofluorescence staining, GLUT1 was detected throughout the cytoplasm and localized to the Golgi apparatus around the nuclear membrane, whereas GLUT12 was mainly distributed in the perinuclear region and cytoplasm. This study contributes to the understanding of how GLUT1 and GLUT12 cooperate in the incorporation of nutrient uptake into mammary gland epithelial cells and the promotion of milk synthesis in the goat mammary gland during lactation.

Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised.