UNSTRUCTURED Traditional medical education is facing significant challenges, particularly since the onset of the COVID-19 pandemic. Extensive research has highlighted the limitations imposed by resource, time, and space constraints, coupled with the often poor relationships between teaching subjects in medical education. This paper presents the architecture of a multimodal teaching interaction model combining both technological phenomenology and multimodal theory and its potential applications. In this study, we successfully constructed a teaching method involving multimodal virtual experience and describe the overall conceptual framework of learning scenarios. Based on the behavioral education model, situational learning, and human-computer interaction theory as the theoretical framework, the model uses the current medical education model as background and combines it with cutting-edge virtual reality, haptic feedback, gesture interaction, and other technologies. This is based on a multi-level application architecture, involving both physical and perceptual layers, and has obvious potential for application in three types of virtual medical education scenarios, namely, "theoretical knowledge learning", "operational skill learning", and "practical experiential learning". This establishes a cross-spatial connection between the virtual and the real using model immersion, collaboration, dynamic feedback, and other characteristics, overcoming the limitations of spatial scenes. If leveraged, the multimodal teaching interaction model (MTIM) will expand the application scenarios of teaching and will effectively enhance the sense of reality and experience of situational teaching, resulting in improved interactive feedback between medical education subjects and meeting teaching and learning needs in the post-epidemic era. Overall, the model proposed in this paper has significant potential for promoting reform in medical education, together with providing feasible ideas and suggestions for the future development of artificial intelligence in medical education.
Additional file 1 Table S1 to S9. Detailed data of results. Table S1: Detailed sequences of all the parts of our designed circuits; Table S2: Raw data for the fluorescence measurement of the protein & promoter; Table S3: Raw data for the fluorescence measurement of the protein & protein interaction of CIII & CII; Table S4: Parameters for tri-stable circuit modelling; Table S5: The variation of pH, β-galactosidase activity and l-lactate dehydrogenase activity in in vitro experiment to confirm the functionality of the circuit; Table S6: The variation of pH of the mice colon in the in vivo experiment to confirm the functionality of the circuit; Table S7: The variation of the β-galactosidase of the mice feces in the in vivo experiment to confirm the functionality of the circuit. Table S8: The experiment design and fecal sample collection of the 21-days in vivo experiment to detect the variation of mice gut microbiota; Table S9: The mean abundance of ASVs in the network and their taxonomic annotations.
Abstract Stimulated Raman scattering (SRS) microscopy is an emerging technology that provides high chemical specificity for endogenous biomolecules and can circumvent common constraints of fluorescence microscopy including limited capabilities to probe small biomolecules and difficulty resolving many colors simultaneously. However, the resolution of SRS microscopy remains governed by the diffraction limit. To overcome this, a new technique called molecule anchorable gel‐enabled nanoscale Imaging of Fluorescence and stimulated Raman scattering microscopy (MAGNIFIERS) that integrates SRS microscopy with expansion microscopy (ExM) is described. MAGNIFIERS offers chemical‐specific nanoscale imaging with sub‐50 nm resolution and has scalable multiplexity when combined with multiplex Raman probes and fluorescent labels. MAGNIFIERS is used to visualize nanoscale features in a label‐free manner with CH vibration of proteins, lipids, and DNA in a broad range of biological specimens, from mouse brain, liver, and kidney to human lung organoid. In addition, MAGNIFIERS is applied to track nanoscale features of protein synthesis in protein aggregates using metabolic labeling of small metabolites. Finally, MAGNIFIERS is used to demonstrate 8‐color nanoscale imaging in an expanded mouse brain section. Overall, MAGNIFIERS is a valuable platform for super‐resolution label‐free chemical imaging, high‐resolution metabolic imaging, and highly multiplexed nanoscale imaging, thus bringing SRS to nanoscopy.
Abstract Background Lactose malabsorption occurs in around 68% of the world populations, causing lactose intolerance (LI) symptoms such as abdominal pain, bloating and diarrhoea. To alleviate LI, previous studies mainly focused on strengthening intestinal β-galactosidase activity but neglected the inconspicuous colon pH drop caused by gut microbes’ fermentation on non-hydrolysed lactose. The colon pH drop will reduce intestinal β-galactosidase activity and influence the intestinal homeostasis. Results Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between expression of β-galactosidase and expression of l-lactate dehydrogenase in respond to intestinal lactose signal and intestinal pH signal. We confirmed the circuit functionality was efficient using 12-hrs in vitro culture at a range of pH levels, as well as 6-hrs in vivo simulations in mice colon. Moreover, another 21-days mice trial indicated that this circuit can recover lactose-effected gut microbiota of mice to the status (enterotypes) similar to that of mice without lactose intake. Conclusions Taken together, the tri-stable-switch circuit can serve as a promising prototype for LI symptoms relief, especially by flexibly adapting to environmental variation, stabilizing colon pH and restoring gut microbiota.
With the development of civil engineering, the demand for suitable cementation materials is increasing rapidly. However, traditional cementation methods are not eco-friendly enough and more sustainable approach such as biobased cementation is required. To meet such demand, Euk.cement, a living eukaryotic cell-based biological autocementation kit, was created in this work. Through the surface display of different silica binding peptides on the fungus Yarrowia lipolytica, Euk.cement cells can immobilize onto any particles with a silica containing surface with variable binding intensity. Meanwhile, recombinant MCFP3 released from the cells will slowly consolidate this binding of cells to particles. The metabolism of immobilized living cells will finally complete the carbonate sedimentation and tightly stick the particles together. The system is designed to be initiated by blue light, making it controllable. This autocementation kit can be utilized for industrial and environmental applications that fit our concerns on making the cementation process eco-friendly.
Abstract Super‐resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. MicroMagnify (µMagnify) is developed, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. The combination of heat denaturation and enzyme cocktails essential is found for robust cell wall digestion and expansion of microbial cells and infected tissues without distortion. µMagnify efficiently retains biomolecules suitable for high‐plex fluorescence imaging with nanoscale precision. It demonstrates up to eightfold expansion with µMagnify on a broad range of pathogen‐containing specimens, including bacterial and fungal biofilms, infected culture cells, fungus‐infected mouse tone, and formalin‐fixed paraffin‐embedded human cornea infected by various pathogens. Additionally, an associated virtual reality tool is developed to facilitate the visualization and navigation of complex 3D images generated by this method in an immersive environment allowing collaborative exploration among researchers worldwide. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables the development of new diagnosis strategies against infectious diseases.
Expansion microscopy (ExM) is a powerful imaging strategy that offers a low-cost solution for interrogating biological systems at the nanoscale using conventional optical microscopes. It achieves this by physically and isotropically magnifying preserved biological specimens embedded in a cross-linked water-swellable hydrogel. However, most reported techniques are unable to preserve endogenous epitopes due to strong protease digestion used to expand samples. In addition, these protocols rely on mechanically fragile hydrogels that only expand by at most 4.5× linearly. We present a new ExM framework, Molecule Anchorable Gel-enabled Nanoscale In-situ Fluorescence MicroscopY (MAGNIFY), that exhibits a broad retention of nucleic acids, proteins, and lipids without the need for a separate anchoring step. By using a mechanically sturdy hydrogel, MAGNIFY is capable of expanding biological specimens up to 11×. This facilitates nanoscale imaging (~25-nm effective resolution) using an ∼280-nm diffraction-limited objective lens on a conventional optical microscope and can be furthered to ~15 nm effective resolution if combined with computational methods such as Super-resolution Optical Fluctuation Imaging (SOFI). Here, we demonstrate that MAGNIFY provides a generalized solution for imaging nanoscale subcellular features of a broad range of biological specimens. We also show that MAGNIFY provides a novel, accessible tool for improving the precision, utility, and generality of nanoscopy.
Large scale campus resembles a small 'semi-open community', harboring disturbances from the exchanges of people and vehicles, wherein stressors such as temperature and population density differ among the ground surfaces of functional partitions. Therefore, it represents a special ecological niche for the study on microbial ecology in the process of urbanization. In this study, we investigated outdoor microbial communities in four campuses in Wuhan, China. We obtained 284 samples from 55 sampling sites over 6 seasons, as well as their matching climatic and environmental records. The structure of campus outdoor microbial communities which influenced by multiple climatic factors featured seasonality. The dispersal influence of human activities on microbial communities also contributed to this seasonal pattern non-negligibly. However, despite the microbial composition alteration in response to multiple stressors, the overall predicted function of campus outdoor microbial communities remained stable across campuses. The spatial-temporal dynamic patterns on campus outdoor microbial communities and its predicted functions have bridged the gap between microbial and macro-level ecosystems, and provided hints towards a better understanding of the effects of climatic factors and human activities on campus micro-environments.
Abstract Background Lactose malabsorption occurs in around 68% of the world’s population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis. Results Here, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of β-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and β-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. Conclusions Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain β-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.
ABSTRACT Locomotion has a global impact on circuit function throughout the cortex, including regulation of spatiotemporal dynamics in primary visual cortex (V1). The mechanisms driving state-changes in V1 result in a 2-3 fold gain of responsiveness to visual stimuli. To determine whether locomotion-mediated increases in response gain improve the perception of spatial acuity we developed a head-fixed task in which mice were free to run or sit still during acuity testing. Spatial acuity, ranging from 0.1 to 0.7 cycles/°, was assessed before and after 3-4 weeks of reward-based training in adult mice. Training on vertical orientations once a day improved the average performance across mice by 22.5 ± 0.05%. Improvement transferred to non-trained orientations presented at 45°, indicating that the improvement in acuity generalized. Furthermore we designed a second closed-loop task in which acuity threshold could be directly assessed in a single session. Using this design, we established that acuity threshold matched the upper limit of the trained spatial frequency; in two mice spatial acuity threshold reached as high as 1.5 cycles/°. During the 3-4 weeks of training we collected a sufficient number of stimulus trials in which mice performed above chance but below 100% accuracy. Using this subset of stimulus trials, we found that perceptual acuity was not enhanced on trials in which mice were running compared to trials in which mice were still. Our results demonstrate that perception of spatial acuity is not improved by locomotion.
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