M3^3CS: Multi-Target Masked Point Modeling with Learnable Codebook and Siamese Decoders

Masked point modeling has become a promising scheme of self-supervised pre-training for point clouds. Existing methods reconstruct either the original points or related features as the objective of pre-training. However, considering the diversity of downstream tasks, it is necessary for the model to have both low- and high-level representation modeling capabilities to capture geometric details and semantic contexts during pre-training. To this end, M$^3$CS is proposed to enable the model with the above abilities. Specifically, with masked point cloud as input, M$^3$CS introduces two decoders to predict masked representations and the original points simultaneously. While an extra decoder doubles parameters for the decoding process and may lead to overfitting, we propose siamese decoders to keep the amount of learnable parameters unchanged. Further, we propose an online codebook projecting continuous tokens into discrete ones before reconstructing masked points. In such way, we can enforce the decoder to take effect through the combinations of tokens rather than remembering each token. Comprehensive experiments show that M$^3$CS achieves superior performance at both classification and segmentation tasks, outperforming existing methods

Deletion of Glut1 in early postnatal cartilage reprograms chondrocytes toward enhanced glutamine oxidation

Abstract Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones. On the other hand, articular cartilage (AC) with Glut1 deficiency presents diminished cellularity and loss of proteoglycans, which ultimately progress to cartilage fibrosis. Moreover, predisposition to Glut1 deficiency severely exacerbates injury-induced osteoarthritis. Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions, both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability. However, uncontrolled glutamine flux causes collagen overmodification, thus affecting extracellular matrix remodeling in both cartilage compartments. These results uncover the pivotal and distinct roles of Glut1-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism

Interfacial and emulsifying properties of the electrostatic complex of β-lactoglobulin fibril and gum Arabic (Acacia Seyal)

Formation, interfacial and emulsifying properties of the electrostatic complex of β-lactoglobulin fibril (BLGF) and gum Arabic Acacia Seyal (AS) were investigated. Necklace-like soluble complex could be formed at pH 3.5, and its charge and interfacial properties depended on the BLGF content. With appropriate amount of BLGF (< 9.09 wt.%), the formed complex possessed a good dispersibility and surface activity. When excessive BLGF (9.09∼50 wt.%) existed, surface charge of the complex was gradually neutralized and aggregation occurred. Homogeneous oil-in-water emulsions could be stabilized by the complex and the droplet size decreased with increasing BLGF content. Higher content of BLGF (9.09∼50 wt.%) was detrimental for emulsification due to the aggregation of complex, and the formed emulsion tended to flocculate. Compared with AS, the complex formed emulsions were much more stable against heating (90 ℃, 30 min) and salting (200 mM NaCl) environments, and the emulsions were stable during long-term storage (46 days). Proposed mechanisms for the adsorption of BLGF/AS complex at the oil-water interface. Pure AS (i) could adsorb at the oil-water interface but formed a loose film due to its poor surface activity and insufficient adsorption amount. With addition of a small amount of fibrils (ii), soluble electrostatic complexes are formed and they can be adsorbed at the interface to formed a dense viscoelastic film due to the surface activity of the BLGF. With a higher content of fibrils (iii), surface charge of the complex tended to be neutralized, causing the aggregation. Because the presence of protein fibrils, they could also adsorb at the oil-water interface to produce a viscoelastic film. However, with a bigger size and irregular shape, the aggregates were difficult to array at the interface as densely as the soluble complex

Macular microcirculation changes after repair of rhegmatogenous retinal detachment assessed with optical coherence tomography angiography: A systematic review and meta-analysis

Purpose: The aim of the study was to investigate microcirculation changes in the macula evaluated by optical coherence tomography angiography (OCTA)in patients receiving anatomical repair after surgery for rhegmatogenous retinal detachment (RRD).Methods: A literature search was conducted in PubMed, EMBASE, Web of Science and the Cochrane Library. Studies including patients with macula-on or macula-off RRD and repaired successfully through primary surgery were selected. Foveal avascular zone (FAZ) area and macular vascular density (VD) in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed using RevMan 5.4 software.Results: Twelve studies including 430 RRD eyes and 430 control eyes were selected. In eyes with macula-on RRD, FAZ area, VD in the foveal SCP and DCP, and VD in the parafoveal SCP and DCP were not altered compared with control eyes, after the retina was reattached. In eyes with macula-off RRD that was repaired successfully through surgery, FAZ area in the DCP (0.13 mm2, 95% CI: 0.02 to 0.25, p = 0.02) remained enlarged compared with control eyes. Meanwhile, VD in the foveal DCP was also significantly reduced (−3.12%, 95% CI: −6.15 to −0.09%, p = 0.04), even though retinal reattachment was achieved by surgery in eyes with macula-off RRD.Conclusion: In patients with macula-off rhegmatogenous retinal detachment, foveal avascular zone area in the deep capillary plexuses was enlarged and vascular density in the foveal deep capillary plexus was reduced, even after the retina was successfully reattached through a primary surgery

Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation

An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4 −/− mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias. Keywords: thyroid hormone; erythropoiesis; NCOA4; nuclear receptorUnited States. Defense Advanced Research Projects Agency (Award HR0011-14-2-0005)United States. Department of Defense (Award W81WH-12-1-0449)National Heart, Lung, and Blood Institute (Grant P01 HL032262-25

A knowledge-guided active model method of skull segmentation on T1-weighted MR images

Skull is the anatomic landmark for patient set up of head radiation therapy. Skull is generally segmented from CT images because CT provides better definition of skull than MR imaging. In the mean time, radiation therapy is planned on MR images for soft tissue information. This study utilized a knowledge-guided active model (KAM) method to segmented skull on MR images in order to enable radiation therapy planning with MR images as the primary planning dataset. KAM utilized age-specific skull mesh models that segmented from CT images using a conditional region growing algorithm. Skull models were transformed to given MR images using an affine registration algorithm based on normalized mutual information. The transformed mesh models actively located skull boundaries by minimizing their total energy. The preliminary validation was performed on MR and CT images from five patients. The KAM segmented skulls were compared with those segmented from CT images. The average image similarity (kappa index) was 0.57. The initial validation showed that it was promising to segment skulls directly on MR images using KAM

TcMYC2a, a Basic Helix–Loop–Helix Transcription Factor, Transduces JA-Signals and Regulates Taxol Biosynthesis in Taxus chinensis

The multitherapeutic taxol, which can be obtained from Taxus spp., is the most widely used anticancer drug. Taxol biosynthesis is significantly regulated by jasmonate acid (JA), one of the most important endogenous hormones in land plants. Nevertheless, the JA-inducing mechanism remains poorly understood. MYC2 is one of the key regulators of JA signal transfer and the biosynthesis of various secondary metabolites. Here, TcMYC2a was identified to contain a basic helix–loop–helix (bHLH)-leucine zipper domain, a bHLH-MYC_N domain, and a BIF/ACT-like domain. TcMYC2a was also found to bind with TcJAZ3 in yeast, which was a homolog of Arabidopsis JASMONATE ZIM-domain JAZ proteins, indicating that TcMYC2a had a similar function to AtMYC2 of JA signal transduction. TcMYC2a was able to affect the expression of GUS reporter gene by binding with the T/G-box, G-box, and E-box, which were the key cis-elements of TASY and TcERF12/15 promoter. TcMYC2a overexpression also led to significantly increased expression of TASY, tat, dbtnbt, t13h, and t5h genes. Additionally, TcERF15, which played the positive role to regulate tasy gene, was up-regulated by TcMYC2a. All these results revealed that TcMYC2a can regulate taxol biosynthesis either directly or via ERF regulators depending on JA signaling transduction

Mechanistic Insight Into the Interaction Between Helicobacter pylori Urease Subunit α and Its Molecular Chaperone Hsp60

Helicobacter pylori is the etiologic agent in a variety of gastroduodenal diseases. As its key pathogenic factors, both urease and Hsp60 play important roles in the pathogenesis of H. pylori. Previous studies have suggested that there is close relationship between urease and Hsp60, which implied that Hsp60 may act as a chaperone in urease stabilization and assembly. However, how these two proteins interact remains unclear. In this study, the impact of Hsp60 on urease activity of H. pylori lysate was first detected to confirm the interaction between urease and Hsp60. Pull-down assays further indicated that Hsp60 could bind to UreA subunit but not UreB. Then, the 3D structure of Hsp60 was modeled using I-TASSER to simulate the binding complex with UreA by molecular docking. The results showed that UreA is a perfect fit for the cavity of Hsp60. Analysis of the resulting model demonstrated that at least seven residues of UreA, located on two interfaces, participate in the interaction. Site-directed mutagenesis of these potential residues showed reduced affinity with Hsp60 than the wild type UreA through surface plasmon resonance (SPR) experiments, and D68 appears to have an important role in the affinity. Further analysis also showed that mutation of E25 and K26 caused a more rapid association and dissociation than with wild UreA, implying that they have roles in stabilizing the interaction complex. These affinity comparisons suggested that the interfaces predicted by molecular docking are credible. Our study indicated a direct interaction between Hsp60 and urease and revealed the binding interfaces and key residues involved in the interaction. These results provide further evidence for the chaperone activity of Hsp60 toward urease and lay a foundation to better understand the maturation mechanism of urease in H. pylori