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Combining the linear conjugate tooth profile with the planetary gear transmission with small tooth difference, taking the linear conjugate small tooth difference planetary gear reducer as the research object, the structure natural frequency and vibration mode of the reducer are obtained through finite element modal analysis, which shows the reducer has good structural dynamic characteristics; through the simulation analysis of vibration characteristics, the vibration law of the reducer under typical working conditions is obtained, and the vibration test experiment is carried out. The vibration experiment results are consistent with the simulation results. The vibration characteristics research results show that the input speed has a significant impact on the vibration amplitude and frequency of the linear conjugate small tooth difference planetary gear reducer.

Abstract Poly‐ADP‐ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA‐deficient tumors. However, over 40% of BRCA‐deficient patients fail to respond to PARPi. Here, we report that thioparib, a next‐generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi‐sensitive and ‐resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1‐dependent DNA damage and replication stress, causing S‐phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR‐mediated DNA repair while increasing RAD51 foci formation. Notably, the on‐target inhibition of PARP7 by thioparib‐activated STING/TBK1‐dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome‐scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next‐generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier‐generation PARPi.

Images captured in low-light environments often suffer from various degradations, and numerous effective solutions have been proposed to address these issues. However, current approaches still have problems such as fuzzy details, distorted colors, and insufficient contrast. To enhance the quality of low-light images, we develop a multi-level dynamic feature fusion network combined with a deep supervision mechanism. More specifically, we propose a multi-scale input encoder (MIE) in the feature extraction part, which aims to help the network perceive the scale differences of objects in low-light images, thereby enabling the network to efficiently restore image details. Furthermore, we develop a Multi-level Dynamic Feature Fusion Module (MDFFM) to dynamically fuse features at different levels to complement each other, which helps the network suppress low-light image noise, capture richer color information, and minimize redundant features during the fusion process. When reconstructing images, we utilize multi-level deep supervision in the network, which can solve the vanishing gradients by adding supervision signals in the side outputs, while guiding the network to achieve image enhancement through a stepwise reconstruction manner. Additionally, the output image's contrast is improved by the Contrast Enhancement Module (CEM). Extensive test results show that our method can improve the visual experience of the results and achieve optimal performance across multiple evaluation metrics. [ABSTRACT FROM AUTHOR]

Mucosal immunity plays a critical role in the pathogenesis of inflammatory immune diseases. This study leverages single-cell RNA sequencing, spatial transcriptomics, and spatial proteomics to compare the cellular mechanisms involved in periodontitis between humans and mice, aiming to develop precise strategies to protect the gingival mucosal barrier. We identified key conserved and divergent features in cellular landscapes and transcriptional profiles across the two species, underscoring the complexity of inflammatory responses and immune dynamics in periodontitis. Additionally, we revealed a novel regulatory mechanism by which epithelial cells modulate macrophage behavior and inflammation through the JAG1–Notch pathway. Validation through animal experiments revealed that JAG1 inhibition reduces inflammation in epithelial cells, mitigating periodontitis. Our findings advance the understanding of periodontal disease pathogenesis and highlight the importance of integrating human and animal model data to develop treatments aligned with human physiology, offering potential therapeutic targets for controlling inflammation and enhancing tissue regeneration. [ABSTRACT FROM AUTHOR]

Soluble solids content (SSC) measurements are crucial for managing longan production and post-harvest handling. However, most traditional SSC detection methods are destructive, cumbersome, and unsuitable for field applications. This study proposes a novel field detection model (Brix-back propagation neural network, Brix-BPNN), designed for longan SSC grading based on an improved BP neural network. Initially, nine preprocessing methods were combined with six classification algorithms to develop the longan SSC grading prediction model. Among these, the model preprocessed with Savitzky–Golay smoothing and the first derivative (SG-D1) demonstrated a 7.02% improvement in accuracy compared to the original spectral model. Subsequently, the BP network structure was refined, and the competitive adaptive reweighted sampling (CARS) algorithm was employed for feature wavelength extraction. The results show that the improved Brix-BPNN model, integrated with the CARS, achieves the highest prediction performance, with a 2.84% increase in classification accuracy relative to the original BPNN model. Additionally, the number of wavelengths is reduced by 92% compared to the full spectrum, making this model both lightweight and efficient for rapid field detection. Furthermore, a portable detection device based on visible-near-infrared (Vis-NIR) spectroscopy was developed for longan SSC grading, achieving a prediction accuracy of 83.33% and enabling fast, nondestructive testing in field conditions. [ABSTRACT FROM AUTHOR]

Background/Objectives: Breast cancer survivors often face an elevated risk of developing co-morbid chronic diseases, which may be exacerbated by nutritional inequalities. This study aimed to comprehensively assess the associations between nutrition literacy, dietary quality, and the risk of co-morbidity in breast cancer survivors in China. Methods: A cross-sectional study was conducted among cancer survivors enrolled in the Shanghai Cancer Rehabilitation Club from March to July 2023. The multivariable models of logistic regression, Poisson regression, and mediation analysis were used to explore the relationship between nutrition literacy, dietary quality, and co-morbid chronic diseases among breast cancer survivors in China. Results: The mean age of the 1552 female breast cancer survivors was 64.5 ± 7.02 years. Nutrition literacy was found to be low, with 49.81% of participants scoring above the threshold for adequate nutrition literacy. The median (IQR) diet quality distance, low bound score, and high bound score were 67.0 (55.0, 81.0), −39.0 (−51.0, −28.0), and 25.0 (16.0, 36.0), respectively. Of the total female breast cancer survivors, 67.27% were reported to have at least one comorbid chronic disease. Hypertension (37.32%) was the most common co-morbid chronic disease. Each score increase of 10 in nutrition literacy (AOR 0.88, 95%CI 0.808–0.962) was associated with a significant reduction in co-morbid chronic disease risk among breast cancer survivors. Poisson regression analysis of the number of chronic diseases was conducted, and consistently, an association between higher nutrition literacy levels and fewer chronic diseases was observed (AOR 0.94, 95%CI 0.911–0.971). The indirect effect of nutrition literacy on comorbidity risk through dietary quality was not significant (indirect effect = 0.994, 95%CI = 0.980–1.008). Conclusions: Nutrition literacy is paramount in breast cancer survivors' dietary quality and prognosis. Enhancing nutrition literacy may be a crucial strategy for improving dietary quality and mitigating the risk of comorbid chronic diseases in this vulnerable population. [ABSTRACT FROM AUTHOR]

Ageing-related structural and functional changes are accompanied by polarized imbalance of microglia and astroglia, which enhance neuroinflammation and neurodegeneration. As indispensable components of brain membranes, omega (n)-3 polyunsaturated fatty acids (PUFAs) are parallelly reduced in ageing. However, conflict results have been reported after mixed n-3 PUFA treatments. Thus, this study explored the role of glial phenotypes in ageing-induced memory impairment and compared therapeutic effects of DHA and EPA. Cognitive and spontaneous behaviors were tested in Morris Water Maze (MWM) and “open field”. Then n-3 PUFA profile, glial phenotype markers, and synaptic protein PSD-95 were detected. The results revealed that ageing rats showed memory impairment in MWM, which was improved by both PUFAs, while more effective for DHA than EPA. The imbalance between microglial M1/M2 polarizations, such as up-regulating IBA1, and down-regulating CD206 and ARG-1 were reversed by both n-3 PUFA, while DHA effect on CD206 was better. Similarly, the activation of astrocyte A1 polarization presented increasing S100B and C3, but decreasing S100a10 in ageing rat, which were attenuated by both PUFAs, while DHA was better restored the A2 S100a10 than EPA. Consistently with M1 and A1 activation in ageing rats, the concentration of proinflammatory cytokines TNF-α, interleukin (IL)-1β and IL-6 were significantly elevated accompanied by increasing TLR4 and NLRP3 inflammasome production, while DHA attenuated most cytokine changes, but EPA only suppressed IL-6. In addition, brain-derived neurotrophic factor (BDNF) was decreased in aged rats with increasing pro-BDNF, which was more powerfully down-regulated by DHA than EPA. DHA or EPA supplement increased the DHA or EPA respectively and balanced the n-6/n-3 ratio in the brain. Moreover, ageing decreased the nicotinic acetylcholine receptor (nAChR) β2 and synaptic protein PSD-95 were improved by both, but DHA was better again. In summary, enhanced microglial M1/M2 and astrocytic A1/A2 polarizations may contribute to increased proinflammatory cytokines and dysfunction of BDNF system. DHA was more effective than EPA on alleviating ageing-associated meory impairment.

Abstract Evidence has been emerging of the importance of long non‐coding RNAs (lncRNAs) in genome instability. However, no study has established how to classify such lncRNAs linked to genomic instability, and whether that connection poses a therapeutic significance. Here, we established a computational frame derived from mutator hypothesis by combining profiles of lncRNA expression and those of somatic mutations in a tumor genome, and identified 185 candidate lncRNAs associated with genomic instability in lung adenocarcinoma (LUAD). Through further studies, we established a six lncRNA‐based signature, which assigned patients to the high‐ and low‐risk groups with different prognosis. Further validation of this signature was performed in a number of separate cohorts of LUAD patients. In addition, the signature was found closely linked to genomic mutation rates in patients, indicating it could be a useful way to quantify genomic instability. In summary, this research offered a novel method by through which more studies may explore the function of lncRNAs and presented a possible new way for detecting biomarkers associated with genomic instability in cancers.

Background: Evidence on associations of remnant cholesterol (RC) and its variability with cognitive function is still lacking. Objective: To explore the association of RC and its variability with cognitive function. Methods: Participants were recruited from a population-based cohort, the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed by a standardized questionnaire from CHARLS, with domains of episodic memory and mental intactness. A linear mixed effects model was used to analyze the association of RC with cognitive function, along with its variability (calculated as standard deviation [SD], coefficient of variation [CV], variability independent of the mean [VIM]), with results expressed as β (95%CI). Potential subgroup differences in the association of RC and its variability with cognitive function were also explored. Results: 4234 participants were eventually included, with mean (SD) age of 57.4 (8.0) years. Each 10 mg/dL increase in RC was associated with 0.053 (95%CI: 0.096, 0.009) points, 0.021 (95%CI: 0.042, 0.000) points, 0.032 (95%CI: 0.064, 0.001) points decrease in global cognitive function, episodic memory, and mental intactness scores, respectively. Compared with the first tertile (T1) group of RC variability (calculated as SD, VIM), T3 showed a lower level in global cognition and episodic memory after multivariate adjustment. The potential modification effects of educational level on RC and its variability in relation to cognitive function were also identified. Conclusions: Among Chinese middle-aged and older adults, higher RC level were associated with worse cognitive function. Greater RC variability was also associated with worse cognitive performance, especially in memory function. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) non-layered materials in many aspects differ from their layered counterparts, and the exploration of their physical properties has produced many intriguing findings. However, due to challenges in applying existing experimental techniques to such nanoscale samples, their thermal properties have remained largely uncharacterized, hindering further exploration and device application using this promising material system. Here, we demonstrate an experimental study of thermal conduction in β -In2S3, a typical non-layered 2D material, using a resonant nanoelectromechanical systems (NEMS) platform. We devise a new two-degrees-of-freedom technique, more responsive and sensitive than Raman spectroscopy, to simultaneously determine both the thermal conductivity to be 3.7 W m−1 K−1 and its interfacial thermal conductance with SiO2 as 6.4 MW m−2 K−1. Leveraging such unique thermal properties, we further demonstrate a record-high power-to-frequency responsivity of −447 ppm/μW in β -In2S3 NEMS sensors, the best among drumhead NEMS-based bolometers. Our findings offer an effective approach for studying thermal properties and exploring potential thermal applications of 2D non-layered materials. [ABSTRACT FROM AUTHOR]

Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant‐derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan‐Oxidized Dextran (CMCS‐OD) hydrogel formed via dynamic chemical bonds exhibited self‐healing capabilities and pH‐responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis‐induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis‐induced bone destruction. [ABSTRACT FROM AUTHOR]

To analyze the correlation of carotid stenosis severity, the Plaque Reporting and Data System (RADS) score, arterial transit artifacts (ATAs), and cerebral blood flow (CBF) with clinical cerebral ischemic symptoms in patients with carotid artery stenosis (CAS). Sixty-one patients with unilateral internal carotid artery stenosis or occlusion (≥50% stenosis) diagnosed by ultrasound, Computed Tomography(CT) angiography, or Magnetic Resonance(MR) angiography in Yichang City Central People's Hospital from January 2022 to February 2024 were retrospectively enrolled and divided into two groups according to the presence or absence of symptoms. Both groups underwent MR plaque imaging and arterial spin labeling (ASL)-based 3.0 T MRI to compare the differences in stenosis degree, Plaque-RADS score, ATA grade, and CBF between the two groups. Binary regression analysis was used to identify the parameters with statistically significant differences between the two groups and to evaluate their diagnostic efficacy using the area under the workup curve of the subjects. The Plaque-RADS score, ATA grade, and CBF differences in the anterior cerebral artery(ACA)blood supply region were correlated with symptoms, and the areas under the ROC curves for the CBF differences in the ACA blood supply region, Plaque-RADS score, ATA grade and a joint model that combines all three to predict symptoms in CAS patients were 0.672, 0.796, 0.788 and 0.919, respectively. CBF, Plaque-RADS and ATAs were identified as independent risk factors for symptoms in patients with CAS and have a certain predictive value for symptoms, and the combined predictive value is greater, potentially providing a more effective imaging modality for clinical treatment and evaluation. • Arterial Transit Artifacts were found to be associated with cerebral ischemia symptoms. • The combination of Plaque-RADS and Arterial Transit Artifacts in predicting symptoms has a higher predictive value. • The PLD used for ASL scanning in this study was 2.0 s, further confirming the broad applicability of our results. [ABSTRACT FROM AUTHOR]

The phase diagram serves as a blueprint for designing the structure of a material, offering a comprehensive representation of its different phases under specific conditions, such as temperature and pressure. In the realm of two-dimensional (2D) materials, stacking order can play a crucial role in controlling and inducing phase transitions. However, in studying phase diagrams for 2D materials, the exploration of stacking degree of freedom has largely been overlooked, limiting our understanding and hindering future applications. Here, we experimentally explore the interplay of stacking and pressure degrees of freedom in revealing unique phase transitions in bilayer MoS2 with two different stacking configurations. In AA stacking, interlayer sliding and asymmetric intralayer compressing precede intralayer rotation, while in AB stacking, asymmetric intralayer compressing and intralayer distortion occur simultaneously. Under further elevated pressure, the bilayer system transitions into 1T′ phase before amorphization. Our findings offer valuable insights for creating comprehensive phase diagrams and exploring exotic phases as well as phase transitions of 2D materials in a broader parameter space. [ABSTRACT FROM AUTHOR]

In rice, symbiotic N2 fixation via nodule bacteroids does not take place naturally. Although N2 fixation by endophytic and associative diazotrophs has been reported in rice, the main organs and seasonal regulation for the N2 fixation have not been elucidated. In this study, seasonal changes in nitrogenase (acetylene reduction) activity and carbohydrate contents in elongated culm (EC), unelongated stem (US), and crown root (CR) were investigated in manure compost (MC)- and chemical fertilizer (CF)-applied rice. Nitrogenase activity increased after rooting (June) and reached the highest activity in US of MC-applied rice at panicle initiation (August). The sucrose content in EC continued to increase after rooting regardless of the applied materials, whereas the glucose content in US increased after rooting only in CF-applied rice, suggesting higher consumption of glucose in US of MC-applied rice. There were significant differences among bacterial microbiota in EC, US, and CR at panicle initiation. In addition, Clostridia class anaerobes were more abundant in US of MC-applied rice than in EC and CR of MC-applied rice. Such difference was not observed in US of CF-applied rice. These results suggest the suitability of US of MC-applied rice at panicle initiation as a site of N2 fixation under anaerobic conditions. [ABSTRACT FROM AUTHOR]