The role of vitamin D receptor in predentin mineralization and dental repair after injury.

Dentin is a permeable and complex tubular composite formed by the mineralization of predentin that mineralization and repair are of considerable clinical interest during dentin homeostasis. The role of Vdr, a receptor of vitamin D, in dentin homeostasis remains unexplored. The aim of the present study was to assess the impact of Vdr on predentin mineralization and dental repair. Vdr-knockout (Vdr-/-) mice models were constructed; histology and immunohistochemistry analyses were conducted for both WT and Vdr-/- mice. The finding revealed a thicker predentin in Vdr-/- mice, characterized by higher expression of biglycan and decorin. A dental injury model was employed to observe tertiary dentin formation in Vdr-/- mice with dental injuries. Results showed that tertiary dentin was harder to form in Vdr-/- mice with dental injury. Over time, heightened pulp invasion was observed at the injury site in Vdr-/- mice. Expression of biglycan and decorin was reduced in the predentin at the injury site in the Vdr-/- mice by immunohistochemistry. Taken together, our results imply that Vdr plays a regulatory role in predentin mineralization and tertiary dentin formation during dentin homeostasis.

Insect-Scale Biped Robots Based on Asymmetrical Friction Effect Induced by Magnetic Torque.

Multimodal and controllable locomotion in complex terrain is of great importance for practical applications of insect-scale robots. Robust locomotion plays a particularly critical role. In this study, a locomotion mechanism for magnetic robots based on asymmetrical friction effect induced by magnetic torque is revealed and defined. The defined mechanism overcomes the design constraints imposed by both robot and substrate structures, enabling the realization of multimodal locomotion on complex terrains. Drawing inspiration from human walking and running locomotion, a biped robot based on the mechanism is proposed, which not only exhibits rapid locomotion across substrates with varying friction coefficients but also achieves precise locomotion along patterned trajectories through programmed controlling. Furthermore, apart from its exceptional locomotive capabilities, the biped robot demonstrates remarkable robustness in terms of load-carrying and weight-bearing performance. The presented locomotion and mechanism herein introduce a novel concept for designing magnetic robots while offering extensive possibilities for practical applications in insect-scale robotics.

All-Inorganic Perovskite NiTiO3 /Cs3 Sb2 I9 Heterostructure for Photocatalytic CO2 Reduction to CH4 with High Selectivity.

Developing efficient and stable halide perovskite-based photocatalysts for highly selectivity reduction CO2 to valuable fuels remains a significant challenge due to their intrinsic instability. Herein, a novel heterostructure featuring 2D Cs3 Sb2 I9 nanosheets on a 3D flower-like mesoporous NiTiO3 framework using a top-down stepwise membrane fabrication technique is constructed. The unique bilayer heterostructure formed on the 3D mesoporous framework endowed NiTiO3 /Cs3 Sb2 I9 with sufficient and close interface contact, minimizing charge transport distance, and effectively promoting the charge transfer at the interface, thus improving the reaction efficiency of the catalyst surface. As revealed by characterization and calculation, the coupling of Cs3 Sb2 I9 with NiTiO3 facilitates the hydrogenation process during catalytic, directing reaction intermediates toward highly selective CH4 production. Furthermore, the van der Waals forces inherent in the 3D/2D heterostructure with face-to-face contact provide superior stability, ensuring the efficient realization of photocatalytic CO2 reduction to CH4 . Consequently, the optimized 3D/2D NiTiO3 /Cs3 Sb2 I9 heterostructure demonstrates an impressive CH4 yield of 43.4 µmol g-1  h-1 with a selectivity of up to 88.6%, surpassing most reported perovskite-based photocatalysts to date. This investigation contributes to overcoming the challenges of commercializing perovskite-based photocatalysts and paves the way for the development of sustainable and efficient CO2 conversion technologies.

Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery.

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.

An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADA neurons in turn project to the ACC and synapse to the initial ACCGlu neurons to convey feedback information from emotional changes. Thus, an ACCGlu-VTAGABA-VTADA-ACCGlu positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.

tPA-anchored nanorobots for in vivo arterial recanalization at submillimeter-scale segments.

Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects.

Modularized microrobot with lock-and-detachable modules for targeted cell delivery in bile duct.

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design-based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.

Mechanical behavior of an FGM-type frozen soil wall: Theory and numerical analysis.

With a laminate model foundation, we have used the complex variable function method to calculate the boundary displacement and stress of a frozen soil wall in a horizontal connecting passage. Using an actual engineering case, the effects of the number of divided layers of a functionally graded material-type frozen soil wall, the position of the freezing pipe and the section shape of the connecting passage on the displacements and tangential stresses of the frozen soil wall are discussed. The results indicate that the frozen soil wall as a temporary support structure exhibits a good supporting effect. With the increase of layers, the material strength of the frozen soil wall weakens, and the displacements and tangential stresses of the inner boundary increase. When the midline of the freezing pipe moves toward the inner boundary, the tensile area in the frozen soil wall begins to shift, and the displacements and tangential stresses of the inner boundary decrease differently. Thedistributions of internal boundary displacements and tangential stresses are significantly affected by the section shape of the frozen soil wall, and the internal boundary displacements and tangential stresses of the frozen soil wall of the small section are more uniform than those of the frozen soil wall of the large section.

Metabolomic profiling and antidiabetic activity of Callerya speciosa.

Callerya speciosa is a perennial edible and medicinal plant belonging to the family Fabaceae. This study was to reveal the similarities and differences between phytochemicals in different parts of C. speciosa using a combination of ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). In addition, the anti-diabetic activity of C. speciosa extracts was explored. A total of 141 compounds were identified and 34 robustly known chemical markers were marked. PCA and heat map analyses revealed that the stems, leaves and pods had similar phytochemical compounds, while compounds in roots and flowers differed from each other and from those in the above ground parts. In addition, extracts of C. speciosa roots and flowers exhibited anti-diabetic activity, which can be applied to the development of anti-diabetic drugs.

Exploration on dynamics in a ratio-dependent predator-prey bioeconomic model with time delay and additional food supply.

In this manuscript, a novel ratio-dependent predator-prey bioeconomic model with time delay and additional food supply is investigated. We first change the bioeconomic model into a normal version by virtue of the differential-algebraic system theory. The local steady-state of equilibria and Hopf bifurcation could be derived by varying time delay. Later, the formulas of the direction of Hopf bifurcation and the properties of the bifurcating periodic solutions are obtained by the normal form theory and the center manifold theorem. Moreover, employing the Pontryagin's maximum principle and considering the instantaneous annual discount rate, the optimal harvesting problem of the model without time delay is analyzed. Finally, four numeric examples are carried out to verify the rationality of our analytical findings. Our analytical results show that Hopf bifurcation occurs in this model when the value of bifurcation parameter, the time delay of the maturation time of prey, crosses a critical value.

Magnetic Continuum Robot with Intraoperative Magnetic Moment Programming.

Magnetic continuum robots (MCRs), which are free of complicated structural designs for transmission, can be miniaturized and are therefore widely used in the medical field. However, the deformation shapes of different segments, including deflection directions and curvatures, are difficult to control simultaneously under an external programmable magnetic field. This is because the latest MCRs have designs with an invariable magnetic moment combination or profile of one or more actuating units. Therefore, the limited dexterity of the deformation shape causes the existing MCRs to collide readily with their surroundings or makes them unable to approach difficult-to-reach regions. These prolonged collisions are unnecessary or even hazardous, especially for catheters or similar medical devices. In this study, a novel magnetic moment intraoperatively programmable continuum robot (MMPCR) is introduced. By applying the proposed magnetic moment programming method, the MMPCR can deform under three modalities, that is, J, C, and S shapes. Additionally, the deflection directions and curvatures of different segments in the MMPCR can be modulated as desired. Furthermore, the magnetic moment programming and MMPCR kinematics are modeled, numerically simulated, and experimentally validated. The experimental results exhibit a mean deflection angle error of 3.3° and correspond well with simulation results. Comparisons between navigation capacities of the MMPCR and MCR demonstrate that the MMPCR has a higher capacity for dexterous deformation.

Dephasing Dynamics in a Non-Equilibrium Fluctuating Environment.

We performed a theoretical study of the dephasing dynamics of a quantum two-state system under the influences of a non-equilibrium fluctuating environment. The effect of the environmental non-equilibrium fluctuations on the quantum system is described by a generalized random telegraph noise (RTN) process, of which the statistical properties are both non-stationary and non-Markovian. Due to the time-homogeneous property in the master equations for the multi-time probability distribution, the decoherence factor induced by the generalized RTN with a modulatable-type memory kernel can be exactly derived by means of a closed fourth-order differential equation with respect to time. In some special limit cases, the decoherence factor recovers to the expression of the previous ones. We analyzed in detail the environmental effect of memory modulation in the dynamical dephasing in four types of dynamics regimes. The results showed that the dynamical dephasing of the quantum system and the conversion between the Markovian and non-Markovian characters in the dephasing dynamics under the influence of the generalized RTN can be effectively modulated via the environmental memory kernel.

Swarming self-adhesive microgels enabled aneurysm on-demand embolization in physiological blood flow.

The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.

Wirelessly powered deformable electronic stent for noninvasive electrical stimulation of lower esophageal sphincter.

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.

Cocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice.

As a central part of the mammalian brain, the prefrontal cortex (PFC) has been implicated in regulating cocaine-induced behaviors including compulsive seeking and reinstatement. Although dysfunction of the PFC has been reported in animal and human users with chronic cocaine abuse, less is known about how the PFC is involved in cocaine-induced behaviors. By using two-photon Ca2+ imaging to simultaneously record tens of intact individual networking neurons in the frontal association cortex (FrA) in awake male mice, here we report that a systematic acute cocaine exposure decreased the FrA neural activity in mice, while the chemogenetic intervention blocked the cocaine-induced locomotor sensitization. The hypoactivity of FrA neurons was critically dependent on both dopamine transporters and dopamine transmission in the ventromedial PFC (vmPFC). Both dopamine D1R and D2R neurons in the vmPFC projected to and innervated FrA neurons, the manipulation of which changed the cocaine-induced hypoactivity of the FrA and locomotor sensitization. Together, this work demonstrates acute cocaine-induced hypoactivity of FrA neurons in awake mice, which defines a cortico-cortical projection bridging dopamine transmission and cocaine sensitization.

Saliva microbiome alterations in dental fluorosis population.

Background: We aimed to explore saliva microbiome alterations in dental fluorosis population. Methods: The prevalence of dental fluorosis was examined in 957 college students. Dean's fluorosis index was used to evaluate the dental fluorosis status. Changes in the composition of the salivary microbiome were assessed in a subset of these patients (100 healthy controls, 100 dental fluorosis patients). Results: Dental fluorosis affected 47% of the student sample, and incidence was unrelated to gender. Compared with healthy controls, the microbiota of patients with dental fluorosis exhibited increased diversity, with increased abundance of Treponema lecithinolyticum, Vibrio metschnikovii, Cupriavidus pauculus, Pseudomonas, Pseudomonadaceae, Pseudomonadales, and decreased abundance of Streptococcus mutans, Streptococcus sanguinis, Gemella, and Staphylococcales. Function analyses showed increases in arginine biosynthesis in patients affected by dental fluorosis, together with reductions in amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, and starch and sucrose metabolism. Conclusions: These results suggest that there are striking differences in salivary microbiome between healthy controls and dental fluorosis patients. Dental fluorosis may contribute to periodontitis and systemic lung diseases. There is a need for cohort studies to determine whether altering the salivary microbiota in dental fluorosis patients can alter the development of oral or systemic diseases.

Stability of Photocathodes: A Review on Principles, Design, and Strategies.

Photoelectrochemical devices based on semiconductor photoelectrode can directly convert and store solar energy into chemical fuels. Although the efficient photoelectrodes with commercially valuable solar-to-fuel energy conversion efficiency have been reported over past decades, one of the most enormous challenges is the stability of the photoelectrode due to corrosion during operation. Thus, it is of paramount importance for developing a stable photoelectrode to deploy solar-fuel production. This Review commences with a fundamental understanding of thermodynamics for photoelectrochemical reactions and the fundamentals of photocathodes. Then, the commercial application of photoelectrochemical technology is prospected. We specifically focus on recent strategies for designing photocathodes with long-term stability, including energy band alignment, hole transport/storage/blocking layer, spatial decoupling, grafting molecular catalysts, protective/passivation layer, surface element reconstruction, and solvent effects. Based on the insights gained from these effective strategies, we propose an outlook of key aspects that address the challenges for development of stable photoelectrodes in future work.

4D Printing of Overall Radiopaque Customized Bionic Occlusion Devices.

Percutaneous closure of ventricular septal defect (VSD) can effectively occlude abnormal blood flow between ventricles. However, commonly used Nitinol occlusion devices have non-negligible limitations, such as nondegradability leading to life-threatening embolization; limited device size predisposing to displacement and wear; only a few radiopaque markers resulting in inaccurate positioning. Nevertheless, the exploration of customized, biodegradable, and overall radiopaque occluders is still vacant. Here, overall radiopaque, biodegradable, and dynamic reconfigurable 4D printed VSD occluders are developed. Based on wavy bionic structures, various VSD occluders are designed and manufactured to adapt to the position diversity of VSD. The customized configuration, biocompatibility, and biodegradability of the developed 4D printed bionic occluders can eliminate the series of complications caused by traditional occluders. The overall radiopacity of 4D printed VSD occluders is validated ex vivo and in vivo, whereby accurate positioning can be assured. Notably, the preparation strategies for 4D printed occluders are scalable, eliminating the barriers to mass production, and marking a meaningful step in bridging the gap between modeling and clinical application of 4D printed occlusion devices. This work opens attractive perspectives for the rapid manufacturing of customized intelligent medical devices for which overall radiopacity, dynamic reconfigurability, biocompatibility, and biodegradability are sought.

Regulation of Calvin-Benson cycle enzymes under high temperature stress.

The Calvin-Benson cycle (CBC) consists of three critical processes, including fixation of CO2 by Rubisco, reduction of 3-phosphoglycerate (3PGA) to triose phosphate (triose-P) with NADPH and ATP generated by the light reactions, and regeneration of ribulose 1,5-bisphosphate (RuBP) from triose-P. The activities of photosynthesis-related proteins, mainly from the CBC, were found more significantly affected and regulated in plants challenged with high temperature stress, including Rubisco, Rubisco activase (RCA) and the enzymes involved in RuBP regeneration, such as sedoheptulose-1,7-bisphosphatase (SBPase). Over the past years, the regulatory mechanism of CBC, especially for redox-regulation, has attracted major interest, because balancing flux at the various enzymatic reactions and maintaining metabolite levels in a range are of critical importance for the optimal operation of CBC under high temperature stress, providing insights into the genetic manipulation of photosynthesis. Here, we summarize recent progress regarding the identification of various layers of regulation point to the key enzymes of CBC for acclimation to environmental temperature changes along with open questions are also discussed.

3D Printed Bioinspired Stents with Photothermal Effects for Malignant Colorectal Obstruction.

Stent placement is an effective palliation therapy for malignant colorectal obstruction. However, recurrent obstruction is a common severe complication caused by tumor ingrowth into the stent lumen. Conventional covered stents play a part in preventing the tumor from growing inward but at the expense of significantly increasing the risk of stent migration. Therefore, there is an urgent demand to develop stents with sustained antitumor and antimigration abilities. Herein, we propose a facile method for fabricating multifunctional bioinspired colorectal stents using 3D printing technology. Inspired by high-adhesion biological structures (gecko feet, tree frog toe pads, and octopus suckers) in nature, different types of bioinspired colorectal stents are designed to reduce migration. After functionalization with graphene oxide (GO), bioinspired colorectal stents show excellent and controllable photothermal performance, which is validated by effective ablation of colon cancer cells in vitro and tumors in vivo. Besides, the bioinspired colorectal stents demonstrate the feasibility of transanal placement and opening of the obstructed colon. More importantly, the facile manufacturing process of multifunctional bioinspired colorectal stents is appealing for mass production. Hence, the developed multifunctional bioinspired colorectal stents exhibit a highly promising potential in clinical applications.