Mapping the Mouse Cell Atlas by Microwell-Seq.

Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based "single-cell MCA analysis" pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.

Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

Laser Direct Writing of Flexible Thermal Flow Sensors.

Thin film-based thermal flow sensors afford applications in healthcare and industries owing to their merits in preserving initial flow distributions. However, traditional thermal flow sensors are primarily applied to track flow intensities based on hot-wire or hot-film sensing mechanisms due to their relatively facile device configurations and fabrication strategies. Herein, a calorimetric thermal flow sensor is proposed based on laser direct writing to form laser-induced graphene as heaters and temperature sensors, resulting in monitoring both flow intensities and orientations. Via homogeneously surrounding spiral heaters with multiple temperature sensors, the device exhibits high sensitivity (∼162 K·s/m) at small flows with an extended flow detection range (∼25 m/s). Integrating the device with a data-acquisition board and a dual-mode graphical user interface enables wirelessly and dynamically monitoring respiration and the motion of robotic arms. This versatile flow sensor with facile manufacturing affords potentials in health inspection, remote monitoring, and studying hydrodynamics.

Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3.

BACKGROUND: Intervertebral disc degeneration (IVDD) is the breakdown of the discs supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clinical interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed. METHODS: Nucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms' tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an enzyme-linked immunosorbent assay. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quantitative reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation. RESULTS: The human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1ß (IL-1ß) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p. CONCLUSIONS: The results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.

Changing Epidemiology of Human Brucellosis, China, 1955-2014.

Brucellosis, a zoonotic disease, was made statutorily notifiable in China in 1955. We analyzed the incidence and spatial-temporal distribution of human brucellosis during 1955-2014 in China using notifiable surveillance data: aggregated data for 1955-2003 and individual case data for 2004-2014. A total of 513,034 brucellosis cases were recorded, of which 99.3% were reported in northern China during 1955-2014, and 69.1% (258, 462/374, 141) occurred during February-July in 1990-2014. Incidence remained high during 1955-1978 (interquartile range 0.42-1.0 cases/100,000 residents), then decreased dramatically in 1979-1994. However, brucellosis has reemerged since 1995 (interquartile range 0.11-0.23 in 1995-2003 and 1.48-2.89 in 2004-2014); the historical high occurred in 2014, and the affected area expanded from northern pastureland provinces to the adjacent grassland and agricultural areas, then to southern coastal and southwestern areas. Control strategies in China should be adjusted to account for these changes by adopting a One Health approach.

Thermoplastic Dielectric Elastomer of Triblock Copolymer with High Electromechanical Performance.

Dielectric elastomer (DE) actuators have been shown to have promising applications as soft electromechanical transducers in many emerging technologies. The DE actuators, which are capable of large actuation strain over a wide range of excitation frequencies, are highly desirable. Here, the first single-component DE of a triblock copolymer with attractive electromechanical performance is reported. Symmetric poly(styrene-b-butyl acrylate-b-styrene) (SBAS) is designed and synthesized. The SBAS actuator exhibits about 100% static actuation area strain and excellent dynamic performance, as evidenced by a wide half bandwidth of 300 Hz and a very high specific power of 1.2 W g-1 within the excitation frequency range of 300-800 Hz.

Expansive open-door laminoplasty versus laminectomy and instrumented fusion for cases with cervical ossification of the posterior longitudinal ligament and straight lordosis.

PURPOSE: To identify whether expansive open-door laminoplasty (Lam) is more appropriate than laminectomy and instrumented fusion (LIF) for cases with ossification of the posterior longitudinal ligament (OPLL) and straight cervical lordosis. METHODS: A total of 67 cases were included and divided into Group Lam (n = 32) and Group LIF (n = 35), and the mean follow-up periods were 38 and 42 months, respectively. The cervical lordosis was elevated by C2-7 Cobb angle and cervical sagittal balance by C2-C7 sagittal vertical axis (SVA). Japanese Orthopedic Association (JOA), neurological recovery rate (RR) being calculated by the JOA, visual analog scale (VAS) and neck disability index (NDI) were used to assess clinical outcomes. RESULTS: Differences in general data between two groups were not significant. Total blood loss and operation duration in Group Lam were both significantly less than that in the Group LIF. By the final follow-up, the cervical lordosis significantly decreased in Group Lam and increased in Group LIF, the SVA significantly increased in Group Lam and kept unchanged in Group LIF, and the JOA, VAS, NDI significantly improved in both groups. Although there was no significant difference in RR between the two groups, cases in Group Lam had significantly larger incidence of postoperative kyphosis and kyphotic change rate, and less VAS, NDI and incidence of axial pain than cases in Group LIF. CONCLUSIONS: When compared with the LIF, the Lam is recommended for cases with OPLL and straight cervical lordosis when taking comparable neurological recovery, less axial pain and better neck function improvement into consideration.

The application of a new type of titanium mesh cage in hybrid anterior decompression and fusion technique for the treatment of continuously three-level cervical spondylotic myelopathy.

PURPOSE: To evaluate the efficacy and safety of a new type of titanium mesh cage (NTMC) in hybrid anterior decompression and fusion method (HDF) in treating continuously three-level cervical spondylotic myelopathy (TCSM). METHODS: Ninety-four cases who had TCSM and accepted the HDF from Jan 2007 to Jan 2010 were included. Clinical and radiological outcomes were compared between cases who had the NTMC (Group A, n = 45) and traditional titanium mesh cage (TTMC, Group B, n = 49) after corpectomies. Each case accepted one polyetheretherketone cage (PEEK) after discectomy. RESULTS: Mean follow-up were 74.4 and 77.3 months in Group A and B, respectively (p > 0.05). Differences in cervical lordosis (CL), segmental lordosis (SL), anterior segmental height (ASH) and posterior segmental height (PSH) between two groups were not significant preoperatively, 3-days postoperatively or at final visit. However, losses of the CL, SL, ASH and PSH were all significantly larger in Group B at the final visit, so did incidences of segmental subsidence and severe subsidence. Difference in preoperative Japanese Orthopedic Association (JOA), visual analog scale (VAS), neck disability index (NDI) or SF-36 between two groups was not significant. At the final visit, fusion rate, JOA, and SF-36 were all comparable between two groups, but the VAS and NDI were both significantly greater in Group B. CONCLUSIONS: For cases with TCSM, HDF with the NTMC and TTMC can provide comparable radiological and clinical improvements. But application of the NTMC in HDF is of advantages in decreasing the subsidence incidence, losses of lordosis correction, VAS and NDI.

Nucleation and propagation of voltage-driven wrinkles in an inflated dielectric elastomer balloon.

Dielectric elastomer (DE) transducers frequently undergo voltage-induced large deformation, which may lead to mechanical instabilities. Here, we investigate wrinkle formation and propagation on the surface of a DE membrane mounted on an air chamber and subjected to a step voltage. Our experiments show that the geometric characteristics of the wrinkle morphology and the nucleation sites depend on the inflation pressure and the applied voltage. As the inflation pressure increases, the critical voltage used to nucleate the wrinkle decreases, while the location where the wrinkle nucleates shifts from the center to the boundary of the membrane. Moreover, by increasing the amplitude of the applied voltage, wrinkle morphology changes from stripe-like wrinkles to labyrinth-like wrinkles. Furthermore, we develop an analytical model to validate the experimental observations and map out the various wrinkle morphologies as a function of the applied pressure and voltage. A three dimensional phase diagram is constructed to help design new soft actuators.

Split-Type Magnetic Soft Tactile Sensor with 3D Force Decoupling.

Tactile sensory organs for sensing 3D force, such as human skin and fish lateral lines, are indispensable for organisms. With their sensory properties enhanced by layered structures, typical sensory organs can achieve excellent perception as well as protection under frequent mechanical contact. Here, inspired by these layered structures, a split-type magnetic soft tactile sensor with wireless 3D force sensing and a high accuracy (1.33%) fabricated by developing a centripetal magnetization arrangement and theoretical decoupling model is introduced. The 3D force decoupling capability enables it to achieve a perception close to that of human skin in multiple dimensions without complex calibration. Benefiting from the 3D force decoupling capability and split design with a long effective distance (>20 mm), several sensors are assembled in air and water to achieve delicate robotic operation and water flow-based navigation with an offset <1.03%, illustrating the extensive potential of magnetic tactile sensors in flexible electronics, human-machine interactions, and bionic robots.

The system power control unit based on the on-chip wireless communication system.

Currently, the on-chip wireless communication system (OWCS) includes 2nd-generation (2G), 3rd-generation (3G), and long-term evolution (LTE) communication subsystems. To improve the power consumption of OWCS, a typical architecture design of system power control unit (SPCU) is given in this paper, which can not only make a 2G, a 3G, and an LTE subsystems enter sleep mode, but it can also wake them up from sleep mode via the interrupt. During the sleep mode period, either the real-time sleep timer or the global system for mobile (GSM) communication sleep timer can be used individually to arouse the corresponding subsystem. Compared to previous sole voltage supplies on the OWCS, a 2G, a 3G, or an LTE subsystem can be independently configured with three different voltages and frequencies in normal work mode. In the meantime, the voltage supply monitor, which is an important part in the SPCU, can significantly guard the voltage of OWCS in real time. Finally, the SPCU may implement dynamic voltage and frequency scaling (DVFS) for a 2G, a 3G, or an LTE subsystem, which is automatically accomplished by the hardware.

Tunable Folding Assembly Strategy for Soft Pneumatic Actuators.

With intrinsic compliance, soft pneumatic actuators are widely utilized in delicate tasks. However, complex fabrication approaches and limited tunability are still problems. Here, we propose a tunable folding assembly strategy to design and fabricate soft pneumatic actuators called FASPAs (folding assembly soft pneumatic actuators). A FASPA consists only of a folded silicone tube constrained by rubber bands. By designing local stiffness and folding manner, the FASPA can be designed to achieve four configurations, pure bending, discontinuous-curvature bending, helix, and discontinuous-curvature helix. Analytical models are developed to predict the deformation and the tip trajectory of different configurations. Meanwhile, experiments are performed to verify the models. The stiffness, load capacity, output force, and step response are measured, and fatigue tests are performed. Further, grippers with single, double, and triple fingers are assembled by utilizing different types of FASPAs. As such, objects with different shapes, sizes, and weights can be easily grasped. The folding assembly strategy is a promising method to design and fabricate soft robots with complex configurations to complete tough tasks in harsh environments.

Vision-force-fused curriculum learning for robotic contact-rich assembly tasks.

Contact-rich robotic manipulation tasks such as assembly are widely studied due to their close relevance with social and manufacturing industries. Although the task is highly related to vision and force, current methods lack a unified mechanism to effectively fuse the two sensors. We consider coordinating multimodality from perception to control and propose a vision-force curriculum policy learning scheme to effectively fuse the features and generate policy. Experiments in simulations indicate the priorities of our method, which could insert pegs with 0.1 mm clearance. Furthermore, the system is generalizable to various initial configurations and unseen shapes, and it can be robustly transferred from simulation to reality without fine-tuning, showing the effectiveness and generalization of our proposed method. The experiment videos and code will be available at https://sites.google.com/view/vf-assembly.

Inhibition of Heterogeneous Nucleation in Water by Hydrogel Coating.

Heterogeneous nucleation plays a critical role in the phase transition of water, which can cause damage in various systems. Here, we report that heterogeneous nucleation can be inhibited by utilizing hydrogel coatings to isolate solid surfaces and water. Hydrogels, which contain over 90% water when fully swelled, exhibit a high degree of similarity to water. Due to this similarity, there is a great energy barrier for heterogeneous nucleation along the water-hydrogel interface. Additionally, hydrogel coatings, which possess polymer networks, exhibit higher fracture energy and more robust adhesion to solid surfaces compared to water. This high fracture and adhesion energy acts as a deterrent for fracture nucleation within the hydrogel or along the hydrogel-solid interface. With a hydrogel layer approximately 100 µm thick, the boiling temperature of water under atmospheric pressure can be raised from 100 to 108 °C. Notably, hydrogel coatings also result in remarkable reductions in cavitation pressure on multiple solid surfaces. We have demonstrated the efficacy of hydrogel coatings in preventing damages resulting from acceleration-induced cavitation. Hydrogel coatings have the potential to alter the energy landscape of heterogeneous nucleation on the water-solid interface, making them an exciting avenue for innovation in heat transfer and fluidic systems.

Composite elastomers with on-demand convertible phase separations achieve large and healable electro-actuation.

Phase separation has been widely exploited for fabricating structured functional materials. Generally, after being fabricated, the phase structure in a hybrid material system has been set at a specific length scale and remains unchanged during the lifespan of the material. Herein, we report a strategy to construct on-demand and reversible phase switches among homogenous, nano- and macro-phase separation states in a composite elastomer during its lifespan. We trigger the nanophase separation by super-saturating an elastomer matrix with a carefully selected small-molecule organic compound (SMOC). The nanoparticles of SMOC that precipitate out upon quenching will stretch the elastomer network, yet remain stably arrested in the elastomer matrix at low temperatures for a long time. However, at elevated temperatures, the nano-phase separation will transform into the macro-one. The elastic recovery will drive the SMOC onto the elastomer surface. The phase-separated structures can be reconfigured through the homogeneous solution state at a further elevated temperature. Taking advantage of the reversible phase switches leads to a novel strategy for designing high-performance dielectric elastomers. The in situ formed nanoparticles can boost the electro-actuation performance by eliminating electro-mechanical instability and lead to a very large actuation strain (∼146%). Once the actuator broke down, SMOC could on-demand be driven to the breakdown holes and heal the actuator.

Sustainable Approach for the Synthesis of a Semicrystalline Polymer with a Reversible Shape-Memory Effect.

Shape-memory polymers (SMPs) have demonstrated potential for use in automotive, biomedical, and aerospace industries. However, ensuring the sustainability of these materials remains a challenge. Herein, a sustainable approach to synthesize a semicrystalline polymer using biomass-derivable precursors via catalyst-free polyesterification is presented. The synthesized biodegradable polymer, poly(1,8-octanediol-co-1,12-dodecanedioate-co-citrate) (PODDC), exhibits excellent shape-memory properties, as evidenced by good shape fixity and shape recovery ratios of 98%, along with a large reversible actuation strain of 28%. Without the use of a catalyst, the mild polymerization enables the reconfiguration of the partially cured two-dimensional (2D) film to a three-dimensional (3D) geometric form in the middle process. This study appears to be a step forward in developing sustainable SMPs and a simple way for constructing a 3D structure of a permanent shape.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Bioinspired soft robots for deep-sea exploration.

The deep ocean, Earth's untouched expanse, presents immense challenges for exploration due to its extreme pressure, temperature, and darkness. Unlike traditional marine robots that require specialized metallic vessels for protection, deep-sea species thrive without such cumbersome pressure-resistant designs. Their pressure-adaptive forms, unique propulsion methods, and advanced senses have inspired innovation in designing lightweight, compact soft machines. This perspective addresses challenges, recent strides, and design strategies for bioinspired deep-sea soft robots. Drawing from abyssal life, it explores the actuation, sensing, power, and pressure resilience of multifunctional deep-sea soft robots, offering game-changing solutions for profound exploration and operation in harsh conditions.

Complete genome sequence of Brucella melitensis 133, an isolate of biovar 1 of sequence type 32.

Brucellosis is highly epidemic in China. Of the six classical species, Brucella melitensis and biovar 1 are the most represented species and biovar that cause human brucellosis in China. Here, we report the genome sequence of Brucella melitensis strain 133, a strain of biovar 1 of sequence type 32.