Cheng Sun

Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.

PURPOSE: To evaluate the diagnostic value of abdominal ultrasonography after transrectal filling with contrast agent (AU-TFCA) in the local T staging of colon cancer. METHODS: This retrospective study included patients diagnosed with colon cancer at Tianjin Third Central Hospital between April 2022 and July 2023. RESULTS: Eighty-six patients (mean age 68.5 ± 9.5; 49 men) were included. The number of patients in stages T1-T4 based on pathological results was 3, 6, 64, and 13, respectively. Kappa agreement: AU-TFCA versus pathology, T3-4 = 0.585, T4 = 0.793; CECT versus pathology, T3-4 = 0.481, T4 = 0.429. ROC using lesion maximum diameter yielded optimal cutoffs of 3.35 and 4.45. AUC = 0.777 and AUC = 0.807. For detecting T3-4: sensitivity 0.779, specificity 0.778, accuracy 0.779. For T4: sensitivity 0.846, specificity 0.699, accuracy 0.721. CONCLUSIONS: AU-TFCA might have higher sensitivity and specificity in preoperative T staging of colon cancer. AU-TFCA might be a valuable tool for colon cancer preoperative T staging, with a better correlation with pathology for T staging than CECT. Still, results require confirmation due to the small number of early-stage cases and the possibility of selection bias.

Traumatic cranial defects often involve concurrent loss of soft and hard tissues and can progress to chronic defects due to delayed healing associated with infection or other co-morbidities. Despite autologous reconstruction remaining the clinical standard, it requires staged procedures using heterogeneous tissues, increasing operative time, costs, and surgical risks. Moreover, current tissue engineering approaches focus on single tissues or acute tissue defect models, limiting their clinical applications. Herein, we describe an acellular, material-driven 3D-printed composite scaffold designed to regenerate both bone and skin within composite cranial defects. The scaffold integrates controlled copper ion release from both organic and inorganic components with 3D-printed citrate polymer and citrate polymer-ceramic composites. Integrated thermoresponsive citrate-based hydrogels further enable spatially defined dermoconductive and osteoconductive properties, supporting a one-step surgical approach. At 12 weeks post-implantation, our scaffold enhanced keratinocyte organization, collagen deposition, and defect coverage with mature bone, achieving histological outcomes comparable to autografts. Furthermore, the system suppressed bacterial burden. Thus, this acellular platform represents a clinically promising synchronized strategy to address the complex demands of traumatic craniofacial composite defects.

Purpose: Chlamydia psittaci infection can lead to rhabdomyolysis (RM); however, systematic characterization of RM in patients with Chlamydia psittaci pneumonia has not been performed. This study analyzed the clinical characteristics of and risk factors for RM in patients with Chlamydia psittaci pneumonia. Patients and Methods: Clinical data of patients with Chlamydia psittaci pneumonia who were admitted to hospitals in Guangdong Province between January 2020 and December 2025 were retrospectively collected. Serum muscle enzyme activities at admission and factors associated with RM development were investigated. Results: Elevated creatine kinase (CK) levels were observed in 46.8% of patients, and 20.5% developed RM. Compared with the non-severe pneumonia group, the severe pneumonia group included significantly more patients with elevated CK levels and RM ( P < 0.001). Compared with patients without RM, those with RM experienced higher incidences of myalgia, dyspnea, and altered consciousness, and they had a higher Pneumonia Severity Index (PSI), a greater likelihood of acute kidney injury, and longer hospital stays; additionally, they more commonly required mechanical ventilation. Systemic inflammatory markers (such as C-reactive protein [CRP]), skeletal muscle and myocardial injury markers, D-dimer levels, and hepatic and renal dysfunction indicators were substantially escalated in patients with RM; however, their serum sodium and albumin levels were significantly lower ( P < 0.05). High PSI, elevated CRP level, dyspnea, and hyponatremia were considered independent risk factors for RM in patients with Chlamydia psittaci pneumonia. Conclusion: RM is an important complication of Chlamydia psittaci pneumonia. Early monitoring and intervention are warranted to improve the prognosis. Keywords: Chlamydia psittaci , pneumonia, rhabdomyolysis, risk factors

Summer precipitation in Central China (CC) is typically influenced by ocean-atmosphere coupling processes. However, the mechanisms through which land surface processes in surrounding regions affect CC precipitation, particularly those over the Indochina Peninsula (ICP), remain poorly understood. We propose that extreme heat events (TX90P) over the ICP during March–April-May (MAM) enhance June–July-August (JJA) precipitation in CC. ICP MAM TX90P establishes a self-reinforcing feedback loop through energy and moisture exchange processes at the land-atmosphere (L-A) interface, thereby amplifying the intensity of extreme heat events. Extreme heat events are accompanied by high-pressure systems with anomalous subsidence of airflow that suppress precipitation and reduce soil moisture (SM). The resulting dry soil establishes a positive feedback mechanism with precipitation, enabling the anomalous SM reduction to persist into JJA. This soil moisture memory effect-induced drought leads to weakened vertical motion over the ICP, promoting the formation of an anticyclonic circulation pattern spanning the ICP and Western Pacific (WP), which subsequently strengthens southwesterly winds that transport moisture toward CC, resulting in enhanced precipitation. Simulations using a Linear Baroclinic Model (LBM) confirm that ICP extreme heat events generate southwesterly wind anomalies, facilitating northeastward moisture transport to CC. A multiple linear regression model incorporating MAM TX90P, preceding winter El Niño-Southern Oscillation (ENSO), and preceding winter Indian Ocean Dipole (IOD) effectively reproduces observed JJA CC precipitation ( r = 0.62). This result demonstrates that incorporating extreme heat-related land surface processes significantly improves precipitation prediction skill compared to models relying solely on oceanic variability.

Fluorescence scanning laser ophthalmoscopy (SLO) provides high-resolution en face imaging of the retina to investigate retinal ganglion cells (RGCs) in both small animals and humans. Multicolor fluorescence SLO can further extend the anatomical and functional imaging capabilities; however, its in vivo implementation remains challenging due to optical aberrations, limited labeling strategies, and the need for multichannel calibration. In this study, we present a compact two-color fluorescence SLO system designed with registered field-of-views (FOVs) between the two color channels for in vivo imaging of RGCs at single-cell resolution in mice. Using an Eno2-YFP transgenic mouse model with dextran labeling of the RGCs, we demonstrate high-quality two-color imaging across a 1.2×1.2mm 2 FOV. Furthermore, by employing adeno-associated virus (AAV)-mediated co-labeling of RGCs and mitochondria, we achieved high-resolution visualization and image overlay with precise two-channel registration. The two-color fluorescence SLO system holds promise for longitudinal studies of RGCs, with applications in neurodegeneration, glaucoma, and therapeutic development.

High Resolution Image Download MS PowerPoint Slide Volumetric segmentation of Schlemm’s Canal (SC) in optical coherence tomography (OCT) is time-consuming, creating a barrier to experiments studying glaucoma and the anatomy of the trabecular outflow pathways in vivo . To this end, we developed an automated segmentation tool, Schlemm’s Canal-Localization and Semantic Segmentation (SC-LSS), for the volumetric segmentation of SC in in vivo mice eyes from visible-light OCT (vis-OCT). SC-LSS first localizes the boundaries of SC and subsequently determines the boundaries of SC within the localized region. We used 324 B-scans from 16 mouse eyes for training, validation, and testing the model, and 203 additional B-scans to evaluate the model’s accuracy. We found that the Dice coefficient between segmentations generated by SC-LSS and manual expert graders was 0.70 ± 0.20 and that the Dice coefficient between two expert graders was 0.73 ± 0.18 ( p = 0.10). Furthermore, SC-LSS captured decreases in SC size with increasing intraocular pressure, yielding a 51.5% decrease in SC size at 20 mmHg compared to 5 mmHg. SC-LSS also identified a 20.1% increase in SC size following the administration of pilocarpine. We anticipate that SC-LSS will accelerate studies on factors regulating the trabecular outflow pathways and their role in glaucoma development and management.

Abstract Engineering biomaterial scaffolds with hierarchical structures that integrate macroscale architecture with micro/nanoscale features is essential for directing cellular organization and tissue regeneration. However, fabricating such multiscale scaffolds remains a challenge due to the limitations of conventional techniques and the speed‐resolution trade‐off in current 3D printing methods. Here, a multiscale micro‐continuous liquid interface production (MµCLIP) method is presented, combined with polymerization‐induced phase separation, to enable rapid, one‐step 3D printing of centimeter‐scale scaffolds featuring microscale surface topography and nanoscale porosity. MµCLIP achieves unprecedented structural resolution across five orders of magnitude (20 nm–1 cm) at high printing speed of up to 1.85 mm min −1 . As a proof of concept, a 1cm‐long tubular scaffold with interconnected nanopores (20–260 nm) and dual surface topographies: 15 µm circumferential rings on outer surface and 20 µm longitudinal grooves on luminal surface is fabricated. These topographies directed orthogonal alignment of vascular smooth muscle cells and endothelial cells, closely recapitulating the architecture of native arteries. Additionally, surface grooves significantly enhanced endothelial cell migration within scaffolds, suggesting a promising approach for accelerating re‐endothelialization. This study establishes MµCLIP as a versatile platform for integrating distinct topographies into 3D scaffolds, opening new opportunities for regenerative implants and biomimetic tissue models.

South China is located in humid region. Decadal Abrupt Changes (DACs) in regional hydroclimate significantly impact water resources and ecosystem stability. This study investigated a pronounced DAC in summer runoff over South China around 2002 with moving t-test technique, characterized by an abrupt transition to reduced runoff. We explored the teleconnection mechanisms linking this hydrological shift with concurrent Mediterranean Sea surface temperature (SST) rapid warming using comprehensive observational analysis, Random Forest model, and the SPEEDY-Vegas coupled model, supplemented by 16 Atmospheric Model Intercomparison Project (AMIP) model validations. Results revealed a significant summer runoff decreased DAC around 2002 across the region. Concurrent Mediterranean SST exhibited a warming DAC, demonstrating a latent temporal synchronization. Random Forest analysis identified precipitation changes as the primary driver. The SPEEDY-Vegas model experiments successfully reproduced the observed runoff DAC when forced with realistic Mediterranean SST warming patterns. Both model and observational results revealed the physical mechanism: Mediterranean warming triggers an eastward-propagating atmospheric wave train that establishes an anomalous high-pressure system over East Asia, inducing regional moisture divergence and enhanced surface drying. AMIP model ensemble (16 models) further confirmed this teleconnection pathway. This circulation anomaly ultimately drives a reduction in regional moisture convergence, explaining the observed runoff decline. These findings demonstrate a teleconnection pathway through which Mediterranean warming modulates East Asian decadal hydroclimate via atmospheric wave dynamics and land-atmosphere feedbacks. • A decline Decadal Abrupt Change (DAC) in summer runoff occurred over South China around 2002, mainly driven by precipitation. • Concurrent Mediterranean Sea Surface Temperature (SST) DAC triggers the local atmospheric pattern shifts. • Numerical experiment shows Mediterranean warming triggers a wave train establishing anomalous high-pressure over East Asia.

Abstract Volumetric segmentation of Schlemm’s Canal (SC) in optical coherence tomography (OCT) is time-consuming, creating a barrier to experiments studying glaucoma and the anatomy of the trabecular outflow pathways in vivo . To this end, we developed an automated segmentation tool, Schlemm’s Canal-Localization and Semantic Segmentation (SC-LSS), for the volumetric segmentation of SC in in vivo mice eyes from visible-light OCT (vis-OCT). SC-LSS first localizes the boundaries of SC and subsequently determines the boundaries of SC within the localized region. We used 324 B-scans from 16 mouse eyes for training, validation, and testing the model, and 203 additional B-scans from 16 mouse eyes to evaluate the model’s accuracy. We found that the Dice coefficient between segmentations generated by SC-LSS and manual expert graders was 0.70 ± 0.20 and that the Dice coefficient between two expert graders was 0.73 ± 0.18 (p = 0.10). Furthermore, SC-LSS captured decreases in SC size with increasing intraocular pressure, yielding a 51.5% decrease in SC size at 20 mmHg compared to 5 mmHg. SC-LSS also identified a 20.1% increase in SC size following the administration of pilocarpine. We anticipate that SC-LSS will accelerate studies on factors regulating the trabecular outflow pathways and their role in glaucoma development and management.

The clinical impact of non-pathogenic colonizing bacteria in pneumonia remains poorly understood. This retrospective study analyzed the mutual influence of pneumonia and non-pathogenic bacterial flora in the lungs. Bronchoalveolar lavage fluid samples from 483 patients were analyzed using metagenomic next-generation sequencing, and differences in colonizing bacteria in different pneumonia types and their impact on disease prognosis were determined. Patients with bacterial pneumonia exhibited higher and lower colonization rates of Granulicatella adiacens and Streptococcus parasanguinis, respectively, than those without. Fungal pneumonia showed lower and higher colonization rates of Abiotrophia defectiva and Veillonella parvula, respectively; viral pneumonia showed higher colonization rates of Abiotrophia defectiva and Streptococcus mitis. Rothia mucilaginosa was associated with shorter duration of fever, and lower risks of sepsis and multiple organ dysfunction syndrome (MODS). Prevotella melaninogenica was associated with lower risks of sepsis and MODS. These findings suggest that select non-pathogenic bacteria might influence disease severity and also highlight the need for further investigation into microbiome-based therapeutic strategies, potentially guiding personalized pneumonia treatments.

In this paper, we study a second-order approach to policy optimization in reinforcement learning. Existing second-order methods often suffer from suboptimal sample complexity or rely on unrealistic assumptions about importance sampling. To overcome these limitations, we propose VR-CR-PN, a variance-reduced cubic-regularized policy Newton algorithm. To the best of our knowledge, this is the first algorithm that integrates Hessian-aided variance reduction with second-order policy optimization, effectively addressing the distribution shift problem and achieving best-known sample complexity under general nonconvex conditions but without the need for importance sampling. We theoretically establish that VR-CR-PN achieves a sample complexity of $\tilde{\mathcal{O}}(ε^{-3})$ to reach an $ε$-second-order stationary point, significantly improving upon the previous best result of $\tilde{\mathcal{O}}(ε^{-3.5})$ under comparable assumptions. As an additional contribution, we introduce a novel Hessian estimator for the expected return function, which admits a uniform upper bound independent of the horizon length $H$, allowing the algorithm to achieve horizon-independent sample complexity.

Retinal ganglion cell (RGC) soma and axonal damage is a hallmark of optic neuropathies. Visible-light OCT fibergraphy (vis-OCTF) enables non-invasive imaging and quantitative assessment of individual RGC axon bundles; however, validating vis-OCTF using confocal fluorescence imaging of flat-mounted postmortem retina is less accurate due to structural alterations caused by flat-mount preparation and cannot be performed longitudinally. For in vivo vis-OCTF validation, we developed an integrated visible-light optical coherence tomography (vis-OCT) and fluorescence scanning laser ophthalmoscopy (SLO) system. The vis-OCT had a 100 nm bandwidth with a center wavelength of 560 nm, offering an axial resolution of 1.3 µm in the retina. The lateral resolutions of vis-OCT and SLO were 4 µm and 3.5 µm, respectively. In the transgenic Eno2-YFP mice, we showed that vis-OCTF and SLO provide consistent RGC axon bundle imaging results. Measuring 30 axon bundle widths from six mice yielded a Pearson correlation coefficient of 0.991 between SLO and vis-OCTF. Thus, the combined SLO and vis-OCT can potentially achieve multimodal longitudinal in vivo studies of RGC pathologies.

We propose an efficient radiance field rendering algorithm that incorporates a rasterization process on adaptive sparse voxels without neural networks or 3D Gaussians. There are two key contributions coupled with the proposed system. The first is to adaptively and explicitly allocate sparse voxels to different levels of detail within scenes, faithfully reproducing scene details with 65536<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> grid resolution while achieving high rendering frame rates. Second, we customize a rasterizer for efficient adaptive sparse voxels rendering. We render voxels in the correct depth order by using ray direction-dependent Morton ordering, which avoids the well-known popping artifact found in Gaussian splat- ting. Our method improves the previous neural-free voxel model by over 4db PSNR and more than 10x FPS speedup, achieving state-of-the-art comparable novel-view synthesis results. Additionally, our voxel representation is seamlessly compatible with grid-based 3D processing techniques such as Volume Fusion, Voxel Pooling, and Marching Cubes, enabling a wide range of future extensions and applications. Code: github.com/NVlabs/svraster

We demonstrate an electrically tunable metalens that combines hydrogenated amorphous silicon (a-Si:H) meta-atoms with a liquid crystal (LC) layer for rapid polarization-controlled depth sensing and imaging. Two independent focusing profiles for left-circularly polarized (LCP) light and right-circularly polarized (RCP) light are encoded via propagation and geometric phases in a single metasurface. Adjusting the LC voltage and the incident polarization among the LCP, RCP, and their superposition enables millisecond-scale reconfiguration. Under pure circular polarization, the metalens yields a single high-fidelity focal spot or an image. Linearly polarized light produces two rotating images, whose relative orientation encodes object depth. Experiments match theory and confirm a full π rotation of the image during focal scanning. The device offers a compact, real-time platform for imaging and depth sensing in microscopy, holography, and adaptive optics.

Prenatal environmental stress damages fetal testicular development, leading to male infertility. However, the precise mechanisms underlying the impact of gestational environmental stress on fetal testicular development require further investigation. This study demonstrates that gestational environmental stressor cadmium exposure caused placental estradiol synthesis inhibition and fetal testicular dysplasia. Gestational estradiol supplementation restores fetal testicular dysplasia caused by environmental stress-induced placental estradiol synthesis inhibition. Analysis of human placentae and cadmium-stimulated human primary placental trophoblasts confirmed that ER-phagy is associated with the inhibition of estradiol synthesis in placentae. Subsequently, the data reveals that environmental stress significantly activates RTN3L-mediated ER-phagy. RTN3L-deficient cells and placental Rtn3l-specific knockout mice confirm that environmental stress-activated RTN3L-mediated ER-phagy inhibited placental estradiol synthesis. Total N6-methyladenosine level increasing in gestational environmental stress-exposed placentae. METTL3-mediated N6-methyladenosine modification suppression obviously restrains environmental stress-activated RTN3L-dependent ER-phagy. In conclusion, gestational environmental stress activates ER-phagy by increasing placental Rtn3l mRNA N6-methyladenosine modification, inhibiting placental estradiol synthesis, and contributing to fetal testicular dysplasia. The study demonstrates the early prevention and treatment of adult male infertility from the perspective of fetal-derived diseases.

Stray light suppression is a vital component in the development of optomechanical systems, but its complexity and the uncertainty surrounding scattered light require intricate mathematical calculations and a large number of simulation iterations, along with much expertise and time. Consequently, it is time-consuming and challenging to investigate the stray light suppression in optomechanical systems. To validate the feasibility of using reinforcement learning for stray light suppression, this paper adopts a model-based deep reinforcement learning method within a Monte Carlo ray-tracing environment to devise suppression strategies. The experimental results indicate that the model-based deep reinforcement learning method can provide effective stray light suppression measures for various optical system configurations, leading to significant improvements in suppression efficiency.

Flexible ultrasonic detectors can hold promise for continuous real-time, long-term, and high-quality photoacoustic (PA) imaging by conformal contact to samples with non-planar surfaces. Polymer micro-ring resonators (MRRs) have been proven to be one of the most versatile choices for ultrasonic detections, due to their high detection sensitivity over a wide frequency range, optical transparency, and at a significantly miniaturized form-factor. However, polymer MRR ultrasound detectors being reported were all fabricated on rigid substrates. To address this issue, here we report the development of a new process for nanofabricating MRRs on soft polymer substrate. We optimized the nano-fabrication process to better accommodate the added compliance of the soft polymer substrate, while retaining the low-cost nature of the nano-imprinting process. The choice of the materials has also been optimized. Finally, we validate the characteristic performance of the fabricated flexible MRR ultrasound detectors experimentally.

We developed an integrated two-photon and photoacoustic microscopy system for neurovascular imaging in vivo. We demonstrated its performance in GCaMP mice, showing that this new system enables simultaneous imaging of neuronal activity and multi-functional oxygen hemodynamics with high sensitivity and single-neuron single-capillary resolution.

Anesthetized and head-restrained settings for intravital microscopy of the mouse brain affect neurovascular activities and restrict natural behaviors. To overcome these limitations, we have developed a lightweight (1.1 g) head-mounted photoacoustic microscopy device for label-free imaging of the cerebral microvasculature in freely behaving mice. Using a MEMS scanner and a micro-ring resonator-based ultrasonic detector, our device has achieved dynamic monitoring of cerebrovascular function (1 Hz frame rate) at high resolution (3.2 μm laterally, &lt;20 μm axially) over a large field of view (500 μm × 500 μm). This technique opens new possibilities for studying neurovascular dynamics under natural behavior.

Polymer micro-ring resonators (MRRs) are among the most versatile candidates for ultrasonic detections due to their high sensitivity over a wide frequency range, optical transparency, and at a miniaturized form-factor making it an idea point detector. While it is highly desirable to further develop it into an arrayed format, it requires precise control of the resonance mode for individual MRRs within the array so they can be uniquely addressed. Here, we report our recent work on developing a polymer MRR ultrasound detector array through the optimization of the nano-fabrication process, significantly improving dimensional tolerance. As the results, we demonstrated the ability to precisely controlled resonance modes of each of the MRR and thus, enables parallel ultrasound detection.

Poor fitting contact lenses are a common cause of eye irritation, potentially leading to keratitis. We seek to improve custom contact lens manufacturing through integrating visible-light optical coherence tomography (vis-OCT) imaging and 3D printing with micrometer resolution and nanometer surface smoothness. We show that our customized contact lens fits well on various different corneas and improves the quality of OCT imaging of rodent retina.

Visible-light optical coherence tomography (vis-OCT) offers higher resolution and distinct tissue absorption characteristics compared to near-infrared OCT, making it a powerful tool for imaging biological structures. However, vis-OCT faces limitations such as reduced scanning rates and significant roll-off at greater imaging depths, hindering its potential in clinical and research applications. While swept-source OCT is known to address these challenges, no commercial swept source currently exists for the visible-light range. This work introduces a novel broadband visible-light swept source to enhance vis-OCT performance. The system utilizes a fan-out periodically poled lithium niobate (PPLN) crystal to perform second harmonic generation (SHG), converting an amplified near-infrared swept source into the visible-light spectrum. The developed 100-kHz A-line scanning rate visible-light swept source features a 22nm bandwidth with 0.58mW power output and provides a vis-OCT roll-off of 0.32dB/mm, a more than 60% improvement over traditional vis-OCT. This advancement addresses key limitations of spectrometer-based vis-OCT, enabling deeper imaging with less signal degradation, which is critical for clinical applications.

We introduce a four dual wedge prisms (DWPs) design for high-throughput single-molecule spectroscopy in single-molecule localization microscopy (SMLM). This system enhances photon collection and spectral resolution, enabling detailed analysis of dye spectral heterogeneity. Our findings reveal significant spectral variability among fluorophores, critical for molecular diagnostics, biological imaging, and materials science. By characterizing this heterogeneity, we can select stable fluorophores with minimal overlap and explore environmental factors affecting spectral properties, ensuring reliable results. Leveraging this variability also enhances multiplexed imaging and novel sensing mechanisms. This presentation will cover the optical setup, data acquisition, and implications for single-molecule spectroscopy.

To transition additive manufacturing from a rapid-prototyping role to at-scale production, commercial resin-based printers have pushed towards 1 meter-per-hour printing speed by synergizing area projection and continuous stage motion. To push this further, we present a continuous 3D-printing method using a lubricated textured membrane – dubbed TEMPO - to achieve a 100-fold improvement in speed over the current state-of-the-art. These high-speeds have elucidated a breakdown in the traditional working curve model, as the speed-accuracy trade-off shifts from supply-limited to reaction limited. The versatility of the lubricant layer allows the user to tailor TEMPO for printing speeds of up to 3 cm/s, resolutions down to 1.76um for freestanding features, and viscous and scattering, high-performance polymers with minimal considerations to the physical limitations of the printing window.

The tensile property of 3D printed polymers is found to be both process-dependent and size-dependent. And therefore, to accurately characterize hundred-micron features made by stereolithography in applications like vascular stent, miniaturized specimens fabricated at the device-relevant dimensional scale using the same conditions are required. To achieve gage displacement measurement without introducing errors from physical contact, we developed a numerical algorithm based on a 1D mechanical model of the specimen in tensile process to estimate gage displacement from the total displacement measured via grip distance for miniaturized specimen and calculate the whole stain-stress curve from it. The algorithm has been thoroughly tested and validated through both experiment and FEM simulation, shows a maximum relative error under 6%. And the total wall time for each run only takes 3.034 seconds on a normal laptop. Its efficiency and accuracy indicate its potential in rapid characterizing new-developed polymers and help improve fine-feature devices.

The development of visible-light optical coherence tomography (vis-OCT) has revolutionized the precision in measuring 3D anatomic features. When combined with 3D printing, which efficiently converts digital models into tangible objects, both technologies achieve micron-scale resolution. This synergy opens new avenues in designing and creating custom biomedical devices tailored to individual patients. For instance, in the case of contact lenses, vis-OCT is utilized to accurately map the corneal surface topology. This mapping informs the design of the contact lens's inner surface, ensuring an optimal fit. Subsequently, these personalized contact lens designs are produced using advanced, high-resolution 3D printing techniques. Both the fit and optical performance of these 3D-printed contact lenses have been thoroughly tested and validated experimentally

Super-resolution microscopy has enabled studies that probe protein spatial distribution at the nanoscale. This, in turn, has made it possible to study the distribution of post-translational modifications in the nucleus. Cancer is associated with widespread alterations in gene expression. It is of interest to classify the resulting change in the spatial distribution of post-translational modifications. However, there is a lack of studies that examine the interactions of multiple histone modifications in a single nucleus. We quantified the individual distribution and clustering behaviors of H3K27me3 and H3K27ac and classified the level of contact between these histone modifications using spectroscopic single-molecule localization microscopy (sSMLM). We also associated the detected changes in these parameters with degrees of cancer malignancy and with drug-induced perturbations in methylation machinery.

Purpose: To use robotic visible-light optical coherence tomography (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration. Methods: Anterior segment imaging using a robotic vis-OCT to maintain perpendicular laser illumination aimed at SC was performed. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. SC areas and volumes were measured circumferentially. Results: Circumferential vis-OCT provided high-resolution imaging of the AHO pathways. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; P = 0.018). After pilocarpine administration, the SC became larger (pilocarpine, 26.8 ± 5.0% vs. control, 8.9 ± 4.6% volume increase; P = 0.030). However, the pilocarpine alteration was also segmental, with a greater increase observed superior (pilocarpine, 31.6 ± 8.9% vs. control, 1.8 ± 5.7% volume increase; P = 0.023) and nasal (pilocarpine, 41.1 ± 15.3% vs. control, 13.9 ± 4.5% volume increase; P = 0.045). Conclusions: Circumferential noninvasive imaging of the AHO pathways was done in vivo. Segmental SC anatomy was seen, consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was also observed. Segmental glaucoma drug response around the circumference of AHO pathways is an observation that may influence patient response to glaucoma treatments.

High Resolution Image Download MS PowerPoint Slide Highly elastic and 3D-printable degradable elastomers are advantageous for many biomedical applications. Herein, we report the synthesis of a biodegradable citrate rubber poly(tetrahydrofuran- co -citrate- co -hydroxyl telechelic natural rubber) (PTCR) using citric acid, poly(tetrahydrofuran), and hydroxyl telechelic natural rubber. The citrate rubber PTCR is methacrylated to synthesize a prepolymer methacrylated-PTCR (mPTCR) that can be used to fabricate bioresorbable scaffolds via 3D printing using micro-continuous liquid interface production. Polymers were chemically characterized via NMR spectroscopy, FTIR spectroscopy, DSC, and TGA and mechanically characterized via tensile testing and crimping. The addition of rubber improved the elasticity of PTCR (658 ± 68% for dry and 415 ± 45% for swollen films) significantly compared with its nonrubber-based citrate copolymer, i.e., poly(tetrahydrofuran- co -citrate) (PTC) (550 ± 51% for dry and 88 ± 10% for swollen films). Also, the mechanical strength of PTCR reached as high as 0.8 ± 0.06 MPa after the successful addition of rubber into PTC, which had a tensile strength of 0.55 ± 0.04 MPa. Notably, the 3D-printed vascular scaffold of mPTCR demonstrated excellent mechanical competence in crimping and expansion, which is necessary for clinical use. The percent diameter recovery of mPTCR vascular scaffolds (89.4 ± 1.1%) was higher than that of its nonrubber version, i.e., methacrylated-poly(tetrahydrofuran- co -citrate) (mPTC) (77.2 ± 6.7%), illustrating the contribution of rubber in mPTCR. In vitro degradation studies showed rapid hydrolytic degradation of the PTCR elastomer in 6 weeks, whereas 3D-printed scaffolds of mPTCR degraded slowly due to its improved stability after methacrylation. The cytocompatibility and cell attachment on the vascular scaffold surfaces were successfully demonstrated by using L929 mouse myoblasts. To conclude, this study reports a citrate-based rubber that should help meet some of the scaffold mechanical requirements for tissue-engineering applications.

Spectroscopic single-molecule localization microscopy allows multi-color super-resolution images with high spectral sensitivity. While its profile has been steadily growing, it is still under-utilized in biology labs, and the complexity of adoption for existing is prohibitive. In this protocol, we provide essential information for researchers to implement sSMLM in a laboratory setting. We describe how to assemble and optically align the illumination and detection paths of a 3D dual-wedge prism-based sSMLM instrument. We provide detailed step-by-step instructions on performing spectral and axial calibration using fluorescent beads and a nanohole array, respectively. We also discuss using sSMLM to image fluorescently labeled cells and report a new MATLAB package RainbowSTORM v2 to reconstruct super-resolution 3D images. Further, we present representative images as typical anticipated results. By demonstrating an implementation of spectroscopic single-molecule localization microscopy that is simple to implement with commercial microscope systems using freely distributed hardware and by introducing new calibration and image processing user interfaces, we hope to remove some of the barriers to entry that biological labs face when entering the spectroscopic super-resolution field. Ultimately, this protocol will allow users to achieve multi-color super-resolution imaging using a single excitation wavelength.

Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometry. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior chamber but not the posterior chamber. Previous fluorophotometric studies of the aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans. Our goal was to measure anterior and posterior chamber volumes in mice to facilitate better estimates of aqueous inflow rates. Methods: We used standard near-infrared (NIR) optical coherence tomography (OCT) and robotic visible-light OCT (vis-OCT) to visualize, reconstruct, and quantify the volumes of the anterior and posterior chambers of the mouse eye in vivo. We used histology and micro-computed tomography (CT) scans to validate relevant landmarks from ex vivo tissues and facilitate in vivo measurement. Results: Posterior chamber volume is 1.1 times the anterior chamber volume in BALB/cAnNCrl mice, that is, the anterior chamber constitutes about 47% of the total aqueous humor volume, which is very dissimilar to the situation in humans. Anterior chamber volumes in 2-month-old BALB/cAnNCrl and C57BL6/J mice were 1.55 ± 0.36 µL (n = 10) and 2.05 ± 0.25 µL (n = 10), respectively. This implies that previous studies likely overestimated the aqueous inflow rate by approximately twofold. Conclusions: It is necessary to reassess previously reported estimates of aqueous inflow rates and, thus, aqueous humor dynamics in the mouse. For example, we now estimate that only 0% to 15% of aqueous humor drains via the pressure-independent (unconventional) route, similar to that seen in humans and monkeys.

We demonstrate the feasibility of swept-source visible-light optical coherence tomography (SS-vis-OCT). We used a fanout periodically poled lithium niobate (PPLN) crystal for second-harmonic generation (SHG) to convert a commercial near-infrared swept-source (NIR-SS) laser into a visible-light SS laser. To enhance SHG efficiency, we amplified the NIR-SS output with booster optical amplifiers (BOAs) and generated up to 580 µW of power. The SS-vis-OCT achieved a maximum axial resolution of 7.3 µm and an imaging depth of 5 mm in air, corresponding to 5.4 µm and 3.7 mm in tissue (n = 1.35). Compared with spectral-domain vis-OCT, SS-vis-OCT provides a 2.2-fold increased imaging depth and a 2.8-fold improved roll-off. Additionally, we validated SS-vis-OCT performance using a 3D-printed pyramid phantom, with its feature measurements cross-validated by scanning electron microscopy (SEM).

Abstract Surge in global population and shift toward animal‐based diets have accelerated expansion of livestock production, posing various environmental challenges. It requires inventorying localized, activity‐specific, and indicator‐extended multidimensional eco‐environmental burdens and revealing their transfers within interregional trade to inform holistic livestock production management from both production and consumption sides. Herein, we construct a life cycle framework covering multiple livestock species, feeding regimes, and activities to evaluate nine environmental impacts ending up as human health, ecosystem quality and resource scarcity burdens in Chinese provincial regions. Multi‐regional input‐output analysis is then conducted to trace transfers of these burdens embedded within trade associated with livestock production. Results indicate that fine particulate matter formation (mainly by livestock housing) and climate change (mainly by enteric fermentation) contribute greater than 60% and 30% to health burdens. Besides for health burdens, for ecosystem burdens primarily caused by housing, and resource burdens mainly aggravated by high on‐farm energy use, poultry results in the highest level. The main production regions Shandong, Henan and Sichuan lead from perspectives of both production and consumption‐based burdens. Whereas regions with the largest export (Inner Mongolia, 3.87 × 10 4 DALY for health burdens) or import (Guangdong, 3.92 × 10 4 DALY for health burdens) do not necessarily bear greatest burdens. This work provides policy instructions in mitigating various eco‐environmental burdens imposed by livestock production and promoting sustainable agricultural practices.

High Resolution Image Download MS PowerPoint Slide Effective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs). Specifically, we synthesized and characterized methacrylate poly(1,8 octamethylene citrate) (mPOC), mixed it with 0%, 40% or 60% HA (i.e., mPOC-0HA, mPOC-40HA, or mPOC-60HA), and fabricated composite scaffold via micro-continuous liquid interface production (μCLIP). The 3D-printed mPOC-HA composite scaffolds were compatible with human USCs that exhibited high osteogenic activity in vitro upon BMP9 stimulation. Subcutaneous implantation of mPOC-HA scaffolds laden with BMP9-stimulated USCs revealed effective bone formation in all three types of mPOC-HA composite scaffolds. Histologic evaluation revealed that the mPOC-60HA composite scaffold yielded the most mature bone, resembling native bone tissue with extensive scaffold-osteointegration. Collectively, these findings demonstrate that the citrate-based mPOC-60HA composite, human urine stem cells, and the potent osteogenic factor BMP9 constitute a desirable triad for effective bone tissue engineering.