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With the development of the gear transmission system towards complexity, multiple transmission types and high reliability, it becomes more and more important to assign the reliability of the gear transmission system quickly and accurately. In this study, aiming at the problems of incomplete consideration factors, inconsistent range of changes in different allocation methods for the same parameter, and inconvenient digital software development in existing reliability allocation methods, an improved advisory group on reliability of electronic equipment (AGREE) allocation method is proposed, the scoring allocation method is extended, and the digital characteristics of reliability allocation method are discussed. The basic reliability model and task reliability model of the complex gear transmission system are established, and the traversal algorithm of the automatic reliability model generation is studied. A digital platform for rapid reliability allocation of fixed axle gear train, planetary gear train and hybrid gear train is developed. Four independent modules, namely input module, calculation module, result display module and output module, are designed. The accuracy of the calculation results of the software is verified by comparing with the results of examples. The parametric modeling and the automatic generation of the example report for the reliability allocation of the gear transmission system are realized, and the accuracy and efficiency of the reliability allocation model are raised.

We experimentally demonstrate the tuning of accidental bound states in the continuum (A-BICs) in silicon nanodisk arrays. The A-BIC emerges of the destructive interference of multipoles, which are the dominating out-of-plane electric dipole and in-plane magnetic dipole, and weak electric quadrupole and magnetic quadrupole. We further show that the spectral and angular position of the A-BIC can be conveniently tuned by varying the nanodisk size or the lattice period. Remarkably, the angular position can be tuned even to 0°, suggesting an interesting transition of the A-BIC from an off-Γ-BIC to an at-Γ-BIC. Our work provides a new strategy for light trapping with high quality factors, and the obtained tunable A-BICs can find potential applications in low-threshold lasing, enhanced nonlinear optics, and optical sensing.

Maintenance of undifferentiated, long-lived, and often quiescent stem cells in the basal compartment is important for homeostasis and regeneration of multiple epithelial tissues, but the molecular mechanisms that coordinately control basal cell fate and stem cell quiescence are elusive. Here, we report an epithelium-intrinsic requirement for Zeb1, a core transcriptional inducer of epithelial-to-mesenchymal transition, for mammary epithelial ductal side branching and for basal cell regenerative capacity. Our findings uncover an evolutionarily conserved role of Zeb1 in promoting basal cell fate over luminal differentiation. We show that Zeb1 loss results in increased basal cell proliferation at the expense of quiescence and self-renewal. Moreover, Zeb1 cooperates with YAP to activate Axin2 expression, and inhibition of Wnt signaling partially restores stem cell function to Zeb1-deficient basal cells. Thus, Zeb1 is a transcriptional regulator that maintains both basal cell fate and stem cell quiescence, and it functions in part through suppressing Wnt signaling.

Breast cancer is a heterogenous disease that can be classified into multiple subtypes including the most aggressive basal-like and triple-negative subtypes. Understanding the heterogeneity within the normal mammary basal epithelial cells holds the key to inform us about basal-like cancer cell differentiation dynamics as well as potential cells of origin. Although it is known that the mammary basal compartment contains small pools of stem cells that fuel normal tissue morphogenesis and regeneration, a comprehensive yet focused analysis of the transcriptional makeup of the basal cells is lacking. We used single-cell RNA-sequencing and multiplexed RNA in-situ hybridization to characterize mammary basal cell heterogeneity. We used bioinformatic and computational pipelines to characterize the molecular features as well as predict differentiation dynamics and cell-cell communications of the newly identified basal cell states. We used genetic cell labeling to map the in vivo fates of cells in one of these states. We identified four major distinct transcriptional states within the mammary basal cells that exhibit gene expression signatures suggestive of different functional activity and metabolic preference. Our in vivo labeling and ex vivo organoid culture data suggest that one of these states, marked by Egr2 expression, represents a dynamic transcriptional state that all basal cells transit through during pubertal mammary morphogenesis. Our study provides a systematic approach to understanding the molecular heterogeneity of mammary basal cells and identifies previously unknown dynamics of basal cell transcriptional states.

Stem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential.

Mammary gland is an outstanding system to study the regulatory mechanisms governing adult epithelial stem cell activity. Stem cells in the basal layer of the mammary gland fuel the morphogenesis and regeneration of a complex epithelial network during development and upon transplantation. The self-renewal of basal stem/progenitor cells is subjected to regulation by both cell-intrinsic and extrinsic mechanisms. Nfatc1 is a transcription factor that regulates breast tumorigenesis and metastasis, but its role in mammary epithelial development and stem cell function has not been investigated. Here we show that Nfatc1 is expressed in a small subset of mammary basal epithelial cells and its epithelial-specific deletion results in mild defects in side branching and basal-luminal cell balance. Moreover, Nfatc1-deficient basal cells exhibit reduced colony forming ability in vitro and somewhat compromised regenerative potential upon transplantation. Thus, our study provides evidence for a detectable yet non-essential role of Nfatc1 in mammary epithelial morphogenesis and basal stem/progenitor cell self-renewal.

Background and objectives: The role of N-methyl-D-aspartate receptor 2B (GRIN2B) single nucleotide polymorphisms (SNPs) in influencing the risk and progression of Parkinson's disease (PD) is still unclear. This study aimed to assess the impact of GRIN2B genotype status on PD susceptibility and symptom progression. Methods: We enrolled 165 individuals with sporadic PD and 154 healthy controls, all of whom had comprehensive clinical data available at the start and during follow-up. We used chi-squared (χ2) analysis to compare the allele and genotype frequency distributions between the patient and control groups. Linear mixed-effect models were employed to investigate the link between the GRIN2B genotype and the progression of motor and cognitive symptoms. Results: The prevalence of the GG + GT genotype and G allele was higher in patients compared to controls (p = 0.032 and p = 0.001, respectively). Subgroup analysis revealed that the GG + GT genotype and G allele were significantly more frequently observed in late-onset PD (LOPD) patients compared to early-onset PD (EOPD) patients (p = 0.014 and p = 0.035, respectively). Notably, individuals with the GG + GT genotype exhibited an estimated annual progression rate of 6.10 points on the Unified Parkinson's Disease Rating Scale (UPDRS), which is significantly higher than that of the TT genotype carriers. Furthermore, the GG + GT carriers showed a markedly rapid progression in rigidity. In addition, the GG + GT carriers demonstrated significantly faster progression rates in rigidity (1.83 points/year) and axial impairment (1.2 points/year) compared to the TT carriers. Notably, the GG genotype carriers exhibited a more rapid decline in recall function. Conclusion: The GRIN2B rs219882 G allele is associated with increased PD susceptibility, particularly in LOPD. The carriers of the GG + GT genotype exhibited more rapid motor symptom progression, with a pronounced impact on rigidity and axial impairment. [ABSTRACT FROM AUTHOR]

C63H63LaO27, trigonal, R3 (no. 146), a = 27.5427(11) Å, c = 7.7330(4) Å, V = 5080.3(5) Å3, Z = 3, R gt(F) = 0.037, wR ref(F 2) = 0.096, T = 100 K.

Objective To investigate the expression of brain expressed X-linked gene 1(Bex1) and nuclear factor-kBp65 (NF-kBp65) in tongue squamous cell carcinoma, and its significance. Methods Immunohistochemistry was used to detect the expression of Bex1 and NF-kBp65 in 60 tongue squamous cell carcinoma (TSCC) tissues and adjacent normal tissues, and the relationships between Bex1, NF-kBp65 and the clinicopathological features and prognosis of patients were analyzed. Results The positive expression rate of Bex1 in TSCC was 48.3% (29/60), which was significantly lower than that in adjacent normal tissues 88.3% (53/60) (x2=22.18, P < 0.01). The positive rate of Bex1 was negatively correlated with TNM stage, and the difference was statistically significant (P < 0.05). The positive rate of 63.3% (38/60) in TSCC was significantly higher than 20% (12/60) in adjacent normal tissues (x2=23.18, P < 0.01), the positive rate of NF-kBp65 was positively correlated with TNM stage, and the difference was statistically significant (P < 0.05). According to the Pearson correlation analysis results, the expression of Bex1 and NF-kBp65 in TSCC tissues was negatively correlated (r=-0.302, P=0.019). Kaplan-Meier survival curves showed that the survival rate of Bex1 positive patients was significantly higher than that of Bex1 negative patients. Conclusion In TSCC tissues, the low positive expression rate of Bex1 and the high positive expression rate of NF-kBp65 may promote tumor invasion and metastasis, and the negative expression of Bex1 may be related to the poor prognosis of patients.

Dynamic covalent polymers (DCPs) that strike a balance between high performance and rapid reconfiguration have been a challenging task. For this purpose, a solution is proposed in the form of a new dynamic covalent supramolecular motif—guanidine urea structure (GUAs). GUAs contain complex and diverse chemical structures as well as unique bonding characteristics, allowing guanidine urea supramolecular polymers to demonstrate advanced physical properties. Noncovalent interaction aggregates (NIAs) have been confirmed to form in GUA‐DCPs through multistage H‐bonding and π‐π stacking, resulting in an extremely high Young's modulus of 14 GPa, suggesting remarkable mechanical strength. Additionally, guanamine urea linkages in GUAs, a new type of dynamic covalent bond, provide resins with excellent malleability and reprocessability. Guanamine urea metathesis is validated using small molecule model compounds, and the temperature dependent infrared and rheological behavior of GUA‐DCPs following the dissociative exchange mechanism. Moreover, the inherent photodynamic antibacterial properties are extensively verified by antibacterial experiments. Even after undergoing three reprocessing cycles, the antibacterial rate of GUA‐DCPs remains above 99% after 24 h, highlighting their long‐lasting antibacterial effectiveness. GUA‐DCPs with dynamic nature, tuneable composition, and unique combination of properties make them promising candidates for various technological advancements. [ABSTRACT FROM AUTHOR]

Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual's quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis. [ABSTRACT FROM AUTHOR]