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Bio-integrated devices need power sources to operate 1 , 2 . Despite widely used technologies that can provide power to large-scale targets, such as wired energy supplies from batteries or wireless energy transduction 3 , a need to efficiently stimulate cells and tissues on the microscale is still pressing. The ideal miniaturized power source should be biocompatible, mechanically flexible and able to generate an ionic current for biological stimulation, instead of using electron flow as in conventional electronic devices 4 – 6 . One approach is to use soft power sources inspired by the electrical eel 7 , 8 ; however, power sources that combine the required capabilities have not yet been produced, because it is challenging to obtain miniaturized units that both conserve contained energy before usage and are easily triggered to produce an energy output. Here we develop a miniaturized soft power source by depositing lipid-supported networks of nanolitre hydrogel droplets that use internal ion gradients to generate energy. Compared to the original eel-inspired design 7 , our approach can shrink the volume of a power unit by more than 10 5 -fold and it can store energy for longer than 24 h, enabling operation on-demand with a 680-fold greater power density of about 1,300 W m −3 . Our droplet device can serve as a biocompatible and biological ionic current source to modulate neuronal network activity in three-dimensional neural microtissues and in ex vivo mouse brain slices. Ultimately, our soft microscale ionotronic device might be integrated into living organisms. A study describes the development of a miniaturized hydrogel-based soft power source capable of modulating the activity of networks of neuronal cells without the need for metal electrodes.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns 1 . Here we uncover the mechanism by which NPY in sympathetic neurons 2 , 3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY + sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation of mural cells, which are a source of thermogenic adipocytes in both BAT and WAT 4 – 6 . We found that diet-induced obesity leads to neuropathy of NPY + axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapular BAT, reducing its thermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake. We find that, relative to central neuropeptide Y, peripheral neuropeptide Y produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.

Bacteria often live in diverse communities where the spatial arrangement of strains and species is considered critical for their ecology. However, a test of this hypothesis requires manipulation at the fine scales at which spatial structure naturally occurs. Here we develop a droplet-based printing method to arrange bacterial genotypes across a sub-millimetre array. We print strains of the gut bacterium Escherichia coli that naturally compete with one another using protein toxins. Our experiments reveal that toxin-producing strains largely eliminate susceptible non-producers when genotypes are well-mixed. However, printing strains side-by-side creates an ecological refuge where susceptible strains can persist in large numbers. Moving to competitions between toxin producers reveals that spatial structure can make the difference between one strain winning and mutual destruction. Finally, we print different potential barriers between competing strains to understand how ecological refuges form, which shows that cells closest to a toxin producer mop up the toxin and protect their clonemates. Our work provides a method to generate customised bacterial communities with defined spatial distributions, and reveals that micron-scale changes in these distributions can drive major shifts in ecology. The spatial arrangement of bacterial strains and species within microbial communities is considered crucial for their ecology. Here, Krishna Kumar et al. use a droplet-based printing method to arrange different bacterial genotypes across a sub-millimetre array, and show that micron-scale changes in spatial distributions can drive major shifts in ecology.

Objective This study aimed to establish a cell-free fetal DNA (cffDNA) assay using multiplex digital PCR (dPCR) for identifying fetuses at increased risk of 22q11.2 deletion/duplication syndrome. Methods Six detection sites and their corresponding probes were designed for the 22q11.2 recurrent region. A dPCR assay for the noninvasive screening of 22q11.2 deletion/duplication syndrome was established. A total of 130 plasma samples from pregnant women (including 15 samples with fetal 22q11.2 deletion/duplication syndrome) were blindly tested for evaluating the sensitivity and specificity of the established assay. Results DNA with different sizes of 22q11.2 deletion/duplication was detected via dPCR, indicating that the designed probes and detection sites were reasonable and effective. In the retrospective clinical samples, 11 out of 15 samples of pregnant women with 22q11.2 deletion/duplication were detected during the cffDNA assay, and accurate regional localization was achieved. Among the 115 normal samples, 111 were confirmed to be normal. Receiver operating characteristic curves were used for assessing the cut-off values and AUC for these samples. The sensitivity, specificity, and positive as well as negative predictive values were 73.3%, 96.5%, 73.3%, and 96.5%, respectively. Conclusion The cffDNA assay based on dPCR technology for the noninvasive detection of 22q11.2 recurrent copy number variants in fetuses detected most affected cases, including smaller but relatively common nested deletions, with a low false-positive rate. It is a potential, efficient and simple method for the noninvasive screening of 22q11.2 deletion/duplication syndrome.

Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca 2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient’s own induced pluripotent stem cells. Brain injuries can result in significant damage to the cerebral cortex, and restoring the cellular architecture of the tissue remains challenging. Here, the authors use a droplet printing technique to fabricate a simplified human cerebral cortical column and demonstrate its functionality and potential for future personalized therapy approaches.

The energy model of belt conveyors plays a key role in the energy efficiency optimization problem of belt conveyors. However, the existing energy models and parameter identification methods are mainly limited to single-motor-driven belt conveyors and require speed sensors. This paper will present an energy model and a parameter identification method for dual-motor-driven belt conveyors whose speed sensors are not available. Firstly, a new energy model of dual-motor-driven belt conveyors is established by combining the traditional energy model with the dynamic model of a dual-motor-driven system. Then, a parameter identification method based on an extended Kalman filtering algorithm and recursive least square approach is proposed. Finally, the feasibility and effectiveness of the method are demonstrated by simulation experiments.

This paper studies the problems of tip position regulation and vibration suppression of flexible manipulators without using the model. Because of the two-timescale characteristics of flexible manipulators, applying the existing model-free control methods may lead to ill-conditioned numerical problems. In this paper, the dynamics of a flexible manipulator is decomposed into two subsystems which are linear and controllable at different timescales by singular perturbation (SP) theory and a model-free composite controller is designed to alleviate the ill-conditioned numerical problems. To do this, a model-free composite control strategy is constructed which facilitates in designing the controller in slow and fast timescales. In the slow timescale, the slow subsystem controller is designed by adaptive dynamic programming (ADP) based on the measurements of the slow inputs and the position, while the vibration in the slow timescale is estimated by the least square method. In the fast timescale, the vibration is reconstructed based on the measurements of vibration and its estimate in the slow timescale, by which the fast controller is designed using ADP. Stability of the closed-loop system is proved by SP theory. Finally, simulations are given to show the feasibility and effectiveness of the proposed methods.

As a common scheme of image tampering, copy-move forgery plays an important role in image forgery committee. Although several blind methods aimed at detecting replicated regions have been proposed, these methods cannot detect the rotation changes in the duplicated areas efciently. In this paper, a new forensic method is presented to detect the replicated areas rotated by arbitrary angles, even by JPEG compression. To achieve this, overlapping blocks of pixels are decomposed using dual tree complex wavelet transform（DT- CWT）, and then channel energies are extracted from each subband at each decomposition level using the L1 norm. Finally, the anisotropic rotationally invariant features are extracted using magnitudes of discrete Fourier transform for these channel energies. The implementation procedure of the proposed method is described in detail. Extensive experimental results, including a comparative evaluation with existing methods and the special applications in practice, are also presented to demonstrate the robustness and efectiveness of the proposed method.

This paper considers the problems of H ∞ control and ε -bound estimation of discrete-time singularly perturbed systems. A set of well-defined conditions for the existence of state feedback controllers are proposed, under which the resulting closed-loop system is asymptotically stable while satisfying a prescribed H ∞ norm bound when the singular perturbation parameter ε is lower than a pre-defined upper bound. It is shown that the proposed controller design method is less conservative than the existing ones. Furthermore, a method of estimating the ε -bound is proposed, which leads to less conservative results and requires lower computational burden than the existing methods for a wide class of singularly perturbed systems. Finally, examples are given to show the advantages and effectiveness of the obtained results.

. Sensors applied on robot skin have developed rapidly, as various kinds of unique function sensors have been designed to detect circumstances like vision, active touch, thermal sensitivity, etc. Some multi-function containing two or more functions above are proposed which are capable to measure multiple data simultaneously. A novel structure is presented in this article which is able to sense the three-axis force loaded on sensor and the temperature around in a limited area. The structure consists of four sector thin composites; three of them are conductive rubbers to detect three-axis force, another one is thermo-sensitive rubber to sense the temperature. A theoretical model and simulation results show that the novel structure of the sensor is feasible to accomplish the two functions.