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Abstract Receptor-interacting protein kinase 1 (RIPK1) is a therapeutic target in treating neurodegenerative diseases and cancers. RIPK1 has three distinct functional domains, with the center domain containing a receptor-interacting protein homotypic interaction motif (RHIM), which mediates amyloid formation. The functional amyloid formed by RIPK1 and/or RIPK3 is a crucial intermediate in regulating cell necroptosis. In this study, the amyloid structure of mouse RIPK1, formed by an 82-residue sequence centered at RHIM, is presented. It reveals the “N”-shaped folding of the protein subunit in the fibril with four β-strands. The folding pattern is shared by several amyloid structures formed by proteins with RHIM, with the central β-strand formed by the most conserved tetrad sequence I/VQI/VG. However, the solid-state NMR results indicate a structural difference between mouse RIPK1 and mouse RIPK3. A change in the structural rigidity is also suggested by the observation of weakened signals for mouse RIPK3 upon mixing with RIPK1 to form the RIPK1/RIPK3 complex fibrils. Our results provide vital information to understand the interactions between different proteins with RHIM, which will help us further comprehend the regulation mechanism in cell necroptosis.

BackgroundThough the prevalence of diabetes is set to increase, most serious game solutions typically target patient self-management and education. Few games target health care professions education, and even fewer consider the factors that may increase their efficacies. The impact of facilitation, a prominent feature of health professions education, is examined in the context of a rehearsal-based diabetes management serious game. ObjectiveIn this mixed methods, open-label, superiority randomized controlled trial, we compare student performance, attitudes, and perceptions of a rehearsal-based diabetes management game for health care professionals. MethodsStudent participants were randomized into 2 groups to play a diabetes management game. The control group played the game alone, and the intervention group played the same game alongside a facilitator tasked to moderate overall challenge levels and address queries. Both groups were administered the Flow Short Scale, a 13-item measure rated on a 7-point Likert scale ranging from 1 (“not at all”) to 7 (“very much”) immediately after the game. Students were then invited to voluntary focus group discussions to elicit their attitudes and perceptions of the game. Findings were subject to between-group comparisons and inductive thematic analysis respectively. ResultsA total of 48 (26 control, 22 intervention) clinical-year undergraduates from the Lee Kong Chian School of Medicine in Singapore participated in this study, with 18 continuing to the focus group discussions. Flow Short Scale results indicated the superiority of the intervention group for overall flow (t46=–2.17, P=.04) and the absorption subdomain (t46=–2.6, P=.01). Qualitative results indicated students viewed facilitation as helpful and appropriate, and were able to identify improvable elements of the game’s theoretical foundations and overall design. ConclusionsWhile serious games are efficacious means of rehearsing previously learned knowledge, facilitation allows for their efficiency to be greatly increased. Such increases are likely crucial in the coming years with the increased digitization of health care professions education and the prevalence of diabetes. Trial RegistrationClinicalTrials.gov NCT05637749; https://www.clinicaltrials.gov/study/NCT05637749

Abstract Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.

The tooth profiles at different positions of the non-circular gear pitch curve have the characteristics of equal modulus but unequal curvature radius and polar diameter. The distribution characteristics of the envelope curve of each tooth profile formed during the hobbing process are different, which lead to the unequal envelope error of the tooth profile at different positions. Taking the basic linkage model of hobbing as the motion constraint, the geometric simulation scheme of the tooth profile generated by the intermittent cutting of the hob is constructed, and the correlation characteristics between the envelope distribution and the curvature radius of the pitch curve and the polar diameter are analyzed. The concept of equivalent hobs is introduced, the relationship model between envelope error and equivalent gear tooth number and equivalent hob groove number is built, and the calculation and position distribution of the maximum envelope error of different tooth profiles are analyzed. A hobbing model to improve the envelope error is proposed. The model can realize the change of the equivalent hob groove number at different positions of the non-circular curve through the hob shifting method, thereby the maximum value and uneven distribution of the envelope error are improved. This study provides theoretical support for the analysis of the tooth profile envelope error of the non-circular gear hobbing, which can predict the envelope error and guide the formulation of a reasonable machining plan.

The time-varying meshing force caused by the transmission characteristics of non-circular gears has an important influence on gear drive wear. The elliptic gear pair of the key core components in combing machine is taken as the research object, and a calculation model of gear wear based on the time-varying meshing force is established by applying Hertz basic theory and Archard wear formula. The meshing stiffness of non-circular gears is solved by using the equivalent tooth number method, and the dynamic meshing force and wear of single tooth profile are analyzed. On this basis, the effects of order and eccentricity on dynamic meshing force and wear of elliptical gears are studied. The results show that the dynamic meshing force and wear of gear surfaces increase with the increase of eccentricity and order of elliptical gears. The time-varying meshing force changes at the junction of single and double tooth meshing zone. The tooth profile wear is close to zero near the pitch circle, and the wear is larger at the root and the crown. It is found that the root wear at the radial of the smallest section curve is significantly larger than that at the radial of the largest section curve. The results provide a theoretical basis for using the modification method to reduce the dynamic meshing force and wear, thus prolonging the life of gears.

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis.

Type-2 cannabinoid receptor (CB2R) is a member of the G protein-coupled receptor superfamily with various biological activities in pain regulation, anti-inflammation, anti-fibrosis, and bone metabolism regulation. CB2R modulators have been demonstrated to have significant regulatory effects on bone metabolism with no significant psychoactive adverse effects. In this article, we present a comprehensive review of the molecular mechanism of CB2R in regulating bone metabolism and summarize virtual screening and experimental screening methods for CB2R modulators from natural and synthetic products. Knowing that some botanical compounds are CB2R modulators involved in the regulation of bone metabolism, we also review the botanical and synthetic compounds currently known to be potential CB2R and summarize their regulatory effects on bone metabolism based on the results of animal, osteoblasts (OBs) and osteoclasts (OCs) experimental studies presently available, hoping that the findings and conclusions in this review could provide a scientific basis for the discovery of new CB2R regulators and the development of new anti-osteoporosis drugs.

Abstract Background Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria. Methods Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene. Results Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs). Conclusions Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite. Graphical Abstract

The ideal tooth surface in the meshing process of helical gears is an involute helical surface, but in the actual service process, there is a certain deviation between the actual tooth surface and the ideal tooth surface due to the influence of gear load, thermal deformation and support deformation. The tooth surface modification method is usually used to reduce the tooth surface eccentric load and vibration caused by position deviation. The existing modification methods often use the formula method considering the size of the load to calculate the modification amount. Although it can improve the transmission performance to a certain extent, there is still the problem of low design accuracy. Thus, a topological modification tooth surface design method based on the time-varying meshing process of gears is proposed to improve the meshing performance of gear pair transmission. Firstly, Ishikawa formula is improved by dividing the tooth surface along the contact trace of helical gears, and the time-varying stiffness model of helical gear pair tooth surface is established; then, the six-degree-of-freedom dynamic equation is established according to the actual meshing process of the gear pair; finally, according to the comprehensive deformation of the tooth surface calculated by the dynamic equation, the topological modification of the compensated tooth surface is designed, and the dynamic simulation is carried out. Through the simulation comparison with the modified gear designed by the traditional formula method, the effectiveness of the proposed method is verified.

Abstract To develop a simple and general method for improving the circularly polarized luminescence (CPL) performances of materials is of great significance. In this work, two pairs of CPL‐active homochiral metal–organic frameworks (MOFs) P/M‐Et and P/M‐Et(Cd) with eta topology are reported. In comparison to the reported isomorphic Zn‐imidazolate MOFs P‐Me and M‐Me, both luminescence dissymmetry factor (glum) and photoluminescence quantum yields (ΦPL) of P‐Et and M‐Et are largely improved by simply changing the methyl group to an ethyl group of ligands in P‐Et and M‐Et. Furthermore, the |glum| values are significantly amplified up to 0.015 from 0.0057 by introducing the non‐luminescent halogenated aromatics, while an enhanced fluorescence efficiency is observed simultaneously (from 27.2% to 47.3%). The figure of merit value is about 40 times larger than that of P‐Me and M‐Me. Similarly, the CPL performances of P/M‐Et(Cd) are improved by about five times after encapsulating fluorobenzene molecules. This work represents a new and simple method for developing CPL‐active MOF materials.