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Proximity labeling catalyzed by promiscuous enzymes, such as TurboID, have enabled the proteomic analysis of subcellular regions difficult or impossible to access by conventional fractionation-based approaches. Yet some cellular regions, such as organelle contact sites, remain out of reach for current PL methods. To address this limitation, we split the enzyme TurboID into two inactive fragments that recombine when driven together by a protein–protein interaction or membrane–membrane apposition. At endoplasmic reticulum–mitochondria contact sites, reconstituted TurboID catalyzed spatially restricted biotinylation, enabling the enrichment and identification of >100 endogenous proteins, including many not previously linked to endoplasmic reticulum–mitochondria contacts. We validated eight candidates by biochemical fractionation and overexpression imaging. Overall, split-TurboID is a versatile tool for conditional and spatially specific proximity labeling in cells.

Ageing related post-menopausal osteoporosis is a global healthcare problem for orthopaedic clinicians. As age creeps in, the body tends to have an inhibition in the rate of estrogen production that negatively reflects on the bone mineral apposition rate (BMAR). The present study attempts to establish a correlation between the loading parameters such as strain magnitude, frequency, and the number of cycles on BMAR using Machine learning regressors namely Random Forest Regressor, Support Vector Machine Regressor, K-Nearest Neighbours Regressor, and XGBoost Regressor. The present model is trained and validated using the experimental data, which is later used to simulate the feature importance of loading parameters. XGBoost Regressor outperforms during the prediction of BMAR at the periosteal and endosteal surface. A strong correlation of R 2  = 0.945 and 0.98 and mean squared error (MSE) of 0.004 and 0.007 was observed on periosteal and endosteal surfaces, respectively. In addition, Quantile-Quantile (Q-Q) plot showed that the endosteal surface have greater potential than the periosteal surface in accurately estimating BMAR and through the feature importance graphs the frequency is observed to be the most significant factor in BMAR on both surfaces. The conclusion of the present study indicates that the XGBoost Regressor has the highest accuracy while predicting BMAR, while the endosteal surface shows greater potential than the periosteal surface in accurately estimated BMAR.

Human pregnancy depends on the proper development of the embryo prior to implantation and the implantation of the embryo into the uterine wall. During the pre-implantation phase, formation of the morula is followed by internalization of blastomeres that differentiate into the pluripotent inner cell mass lineage, while the cells on the surface undergo polarization and differentiate into the trophectoderm of the blastocyst. The trophectoderm mediates apposition and adhesion of the blastocyst to the uterine epithelium. These processes lead to a stable contact between embryonic and maternal tissues, resulting in the formation of a new organ, the placenta. During implantation, the trophectoderm cells start to differentiate and form the basis for multiple specialized trophoblast subpopulations, all of which fulfilling specific key functions in placentation. They either differentiate into polar cells serving typical epithelial functions, or into apolar invasive cells that adapt the uterine wall to progressing pregnancy. The composition of these trophoblast subpopulations is crucial for human placenta development and alterations are suggested to result in placenta-associated pregnancy pathologies. This review article focuses on what is known about very early processes in human reproduction and emphasizes on morphological and functional aspects of early trophoblast differentiation and subpopulations.

After half a billion years of evolution, arthropods have developed sophisticated compound eyes with extraordinary visual capabilities that have inspired the development of artificial compound eyes. However, the limited 2D nature of most traditional fabrication techniques makes it challenging to directly replicate these natural systems. Here, we present a biomimetic apposition compound eye fabricated using a microfluidic-assisted 3D-printing technique. Each microlens is connected to the bottom planar surface of the eye via intracorporal, zero-crosstalk refractive-index-matched waveguides to mimic the rhabdoms of a natural eye. Full-colour wide-angle panoramic views and position tracking of a point source are realized by placing the fabricated eye directly on top of a commercial imaging sensor. As a biomimetic analogue to naturally occurring compound eyes, the eye’s full-colour 3D to 2D mapping capability has the potential to enable a wide variety of applications from improving endoscopic imaging to enhancing machine vision for facilitating human–robot interactions. Insect-like biomimetic compound eyes have many technological applications. Here, the authors present a facile fabrication scheme involving microfluidics assisted 3D printing that permits to completely separate design, optimization and construction of optical and sensor components.

The pulp is a unique tissue within each tooth that is susceptible to painful inflammation, known as pulpitis, triggered by microbial invasion from carious lesions or trauma that affect many individuals. The host response involves complex immunological processes for pathogen defense and dentin apposition at the site of infection. The interplay of signaling between the immune and non-immune cells via cytokines, chemokines, neuropeptides, proteases, and reactive nitrogen and oxygen species leads to tissue reactions and structural changes in the pulp that escalate beyond a certain threshold to irreversible tissue damage. If left untreated, the inflammation, which is initially localized, can progress to pulpal necrosis, requiring root canal treatment and adversely affecting the prognosis of the tooth. To preserve pulp vitality and dental health, a deeper understanding of the molecular and cellular mechanisms of pulpitis is imperative. In particular, elucidating the links between signaling pathways, clinical symptoms, and spatiotemporal spread is essential to develop novel therapeutic strategies and push the boundaries of vital pulp therapy.

Background Anteromedial cortex-to-cortex reduction is a key parameter for stable reconstruction of the fracture fragments during the intertrochanteric fracture fixation. This paper introduces the oblique fluoroscopic projection as a novel method to evaluate the quality of anteromedial cortical apposition. Methods Three proximal femur specimens were marked with steel wires along five anatomic landmarks: Greater trochanter, Lesser trochanter, Intertrochanteric line, Anterolateral tubercle and the Anteromedial cortical line. After obtaining the standard femoral neck AP and lateral fluoroscopic images, the C-arm was rotated by every 5°increments until a clear tangential view of the antero-medial-inferior corner cortex was observed. 98 cases of intertrochanteric hip fractures were enrolled from April 2018 to October 2019. After fixation with the nails, the intra-operative anteromedial cortex reduction quality was evaluated from the AP, the true lateral, and the new anteromedial oblique fluoroscopic images. The fluoroscopic results were compared with the post-operative 3D-CT reconstruction images. Results The specimen study showed that internal rotation of the C-arm to approximately 30 ° can remove all the obscure shadows and clearly display the antero-medial-inferior cortical tangent line. Clinically,the positive, neutral and negative apposition of different cortices via intra-operative fluoroscopic images showed79, 19 and 0 cases of medial cortical apposition in AP views; 2, 68 and 28 cases of anterior cortices in lateral views;and 22, 51 and 25cases of anteromedial cortical apposition in oblique views respectively. The post-operative 3D-CT reconstruction images revealed that the final anteromedial cortical contact was noted in 62 cases (63.3%), and lost in 36 cases (36.7%). The overall coincidence rate between intra-operative fluoroscopy and post-operative 3D-CT was 63.3% (62/98) in AP view,79.6% (78/98) in lateral view, and 86.7% (85/98) in oblique view( p  < 0.001). Negative cortical apposition in oblique view was highly predictive of a final loss of cortical support on 3D CT (24/25 cases, 96%).And non-negative cortical apposition in oblique view was highly associated with true cortical support on 3D CT images (61/73 cases, 83.6%) ( p  < 0.001). Conclusions Besides the AP and lateral projections, an anteromedial oblique view of 30° certifies to be a very useful means for evaluation of the fracture reduction quality of anteromedial cortical apposition.

Viviparity and the development of a placenta are two of the major reasons for the success of the mammals in colonizing all habitats, both terrestrial and aquatic. The placenta is an apposition of fetal to maternal tissue which serves two main, but competing functions: to maximize oxygen transfer and the acquisition of nutrients from the mother, but to minimize immunological rejection by the maternal immune system. This has resulted in the evolution of four main types differing in the degree of loss of the maternal uterine epithelial (UE) barrier: epitheliochorial, synepitheliochorial, endotheliochorial, and hemochorial, all providing a successful safe balance between the needs of mother and fetus. Epitheliochorial is the least invasive, a simple apposition and microvillar interdigitation of the apices of uterine epithelium and trophoblast. It is suggested to have evolved as a response to the increase in the size of the animal to provide a sufficiently long gestation to produce a single altricial (run/swim-soon-as-born) neonate as in the Cetartiodactyla. The mother needs to have good control of the fetal demands so the UE barrier is maintained. However, in the synepitheliochorial placenta, characteristic of all ruminants, the fetus has evolved a means of increasing, or at least maintaining, demand without the need for invasion. This has been achieved by the development of the trophoblast binucleate cell which, uniquely, can fuse with a UE cell to form fetomaternal hybrid tissue. This can maintain some maternal barrier function but also deliver fetally synthesized immunomodulatory and metabolic messages to the maternal circulation. This review provides the evidence for this remarkable evolutionary step and also considers an alternative explanation for the formation of the structure of the ruminant placenta.

The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (μCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Transport of dietary cholesterol from endocytic organelles to the endoplasmic reticulum (ER) is essential for cholesterol homoeostasis, but the mechanism and regulation of this transport remains poorly defined. Membrane contact sites (MCS), microdomains of close membrane apposition, are gaining attention as important platforms for non-vesicular, inter-organellar communication. Here we investigate the impact of ER-endocytic organelle MCS on cholesterol transport. We report a role for Niemann-Pick type C protein 1 (NPC1) in tethering ER-endocytic organelle MCS where it interacts with the ER-localised sterol transport protein Gramd1b to regulate cholesterol egress. We show that artificially tethering MCS rescues the cholesterol accumulation that characterises NPC1-deficient cells, consistent with direct lysosome to ER cholesterol transport across MCS. Finally, we identify an expanded population of lysosome-mitochondria MCS in cells depleted of NPC1 or Gramd1b that is dependent on the late endosomal sterol-binding protein STARD3, likely underlying the mitochondrial cholesterol accumulation in NPC1-deficient cells. Though endocytosed dietary cholesterol is transferred to the endoplasmic reticulum (ER), how this is regulated is unclear. Here, the authors report a role for Niemann-Pick Type C Protein 1 (NPC1) in tethering endocytic organelles to the ER, which may contribute to interorganelle cholesterol transport.

This randomized, controlled trial showed that, among patients with malignant pleural effusion, the insertion of talc into the pleural space through an indwelling catheter resulted in a higher frequency of successful pleurodesis than placebo.