Type-I Collagen Polypeptide-Based Composite Nanofiber Membranes for Fast and Efficient Bone Regeneration.

The clinical treatment of bone defects includes allogeneic bone transplantation and autologous bone transplantation. However, they all have their own limitations, and the scope of application is limited. In recent years, bone tissue engineering scaffolds based on a variety of materials have been well developed and achieved good bone regeneration ability. However, most scaffold materials always face problems such as high biotoxicity, leading to inflammation and poor bioactivity, which limits the bone regeneration effect and prolongs the bone regeneration time. In our work, we prepared hydroxyapatite, erythropoietin (EPO), and osteogenic growth peptide (OGP) codoped type-I collagen (Col I) polypeptide nanofiber membranes (NFMs) by electrostatic spinning. In cell experiments, the composite NFMs had low cytotoxicity and promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. Quantitative real-time polymerase chain reaction and alkaline phosphatase staining confirmed the high expression of osteogenic genes, and alizarin red S staining directly confirmed the appearance of calcium nodules. In animal experiments, the loaded hydroxyapatite formed multiple independent mineralization centers in the defect center. Under the promotion of Col I, EPO, and OGP, the bone continued to grow along the mineralization centers as well as inward the defect edge, and the bone defect completely regenerated in about two months. The hematological and histological analyses proved the safety of the experiments. This kind of design to promote bone regeneration by simulating bone composition, introducing mineralization center and signal molecules, can shorten repair time, improve repair effect, and has good practical prospects in the future.

A mucosal vaccine formulation against tuberculosis by exploiting the adjuvant activity of S100A4-A damage-associated molecular pattern molecule.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains one of the top three causes of death. Currently, the only licensed vaccine against TB is the bacillus Calmette-Guerin (BCG), which lacks efficacy in preventing and controlling pulmonary TB in adults. We aimed to evaluate a nasal TB vaccine formulation composed of the Mtb-specific vaccine antigen ESAT-6, an Mtb-associated protein that can trigger protective immune responses, and S100A4, a recently characterized novel mucosal adjuvant. Mice were intranasally given recombinant ESAT-6 in the presence or absence of S100A4 as an adjuvant. We have provided experimental evidence demonstrating that S100A4 admixed to ESAT-6 could induce Mtb-specific adaptive immune responses after intranasal immunization. S100A4 remarkably augmented the levels of anti-ESAT-6 IgG in serum and IgA in mucosal sites, including lung exudates, bronchoalveolar lavage fluid (BALF) and nasal lavage. Furthermore, in both lung and spleen tissues, S100A4 strongly promoted ESAT-6-specific expansion of CD4 T cells. Both CD4 and CD8 T cells from these tissues expressed increased levels of IFN-γ, TNF-α, and IL-17, cytokines critical for antimicrobial activity. Antigen-reencounter-induced T cell proliferative responses, a key vaccine performance indicator, were augmented in the spleen of S100A4-adjuvanted mice. Furthermore, CD8 T cells from the spleen and lung tissues of these mice expressed higher levels of granzyme B upon antigen re-stimulation. S100A4-adjuvanted immunization may predict good mucosal protection against TB.

Abnormality in Peripheral and Brain Iron Contents and the Relationship with Grey Matter Volumes in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of "MCCA+jICA" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the "MCCA+jICA" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from "MCCA+jICA" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.

Maize ZmSRO1e promotes mesocotyl elongation and deep sowing tolerance by inhibiting the activity of ZmbZIP61.

Deep sowing is a traditional method for drought resistance in maize production, and mesocotyl elongation is strongly associated with the ability of maize to germinate from deep soil. However, little is known about the functional genes and mechanisms regulating maize mesocotyl elongation. In the present study, we identified a plant-specific SIMILAR TO RCD-ONE (SRO) protein family member, ZmSRO1e, involved in maize mesocotyl elongation. The expression of ZmSRO1e is strongly inhibited upon transfer from dark to white light. The loss-of-function zmsro1e mutant exhibited a dramatically shorter mesocotyl than the wild-type in both constant light and darkness, while overexpression of ZmSRO1e significantly promoted mesocotyl elongation, indicating that ZmSRO1e positively regulates mesocotyl elongation. We showed that ZmSRO1e physically interacted with ZmbZIP61, an ortholog of Arabidopsis ELONGATED HYPOCOTYL 5 (HY5) and showed a function similar to that of HY5 in regulating photomorphogenesis. We found that ZmSRO1e repressed the transcriptional activity of ZmbZIP61 toward target genes involved in the regulation of cell expansion, such as ZmEXPB4 and ZmEXPB6, by interfering with the binding of ZmbZIP61 to the promoters of target genes. Our results provide a new understanding of the mechanism by which SRO regulates photomorphogenesis and highlight its potential application in deep sowing-resistant breeding.

Barium titanate photocatalysts with silver-manganese dual cocatalyst for carbon dioxide reduction with water.

Titanate photocatalysts with suitable cocatalysts are promising candidates for photocatalytic CO2 reduction, with the use of water as an electron donor. Here, several barium titanates with various compositions were examined, and BaTi4O9 (BT4) was found to be the best photocatalyst with the assistance of an Ag cocatalyst for photocatalytic CO2 reduction to form CO. The photocatalytic activity was further enhanced by the use of MnOx as an additional cocatalyst to construct an Ag-MnOx/BT4 photocatalyst, where Ag and MnOx were selectively deposited at different facets on BT4 crystal and functioned as active sites for CO2 reduction and water oxidation, respectively. As for the oxidative products from water, molecular oxygen (O2) and hydrogen peroxide (H2O2) were obtained.

Self-Assembly Reinforced Alginate Fibers for Enhanced Strength, Toughness, and Bone Regeneration.

Material reinforcement commonly exists in a contradiction between strength and toughness enhancement. Herein, a reinforced strategy through self-assembly is proposed for alginate fibers. Sodium alginate (SA) microstructures with regulated secondary structures are assembled in acidic and ethanol as reinforcing units for alginate fibers. Acidity increases the flexibility of the helix and contributes to enhanced extendibility. Ethanol is responsible for formation of a stiff ß-sheet, which enhances the modulus and strength. The structurally engineered SA assembly exhibits robust mechanical compatibility, and thus reinforced alginate fibers possess an improved tensile strength of 2.1 times, a prolonged elongation of 1.5 times, and an enhanced toughness of 3.0 times compared with SA fibers without reinforcement. The reinforcement through self-assembly provides an understanding of strengthening and toughening mechanism based on secondary structures. Due to a similar modulus with bones, reinforced alginate fibers exhibit good efficacy in accelerating bone regeneration in vivo.

Morphological changes in the cerebellum during aging: evidence from convolutional neural networks and shape analysis.

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20-80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process.

Diffusion-tensor-imaging 1-year-old and 2-year-old infant brain atlases with comprehensive gray and white matter labels.

Human infancy is marked by fastest postnatal brain structural changes. It also coincides with the onset of many neurodevelopmental disorders. Atlas-based automated structure labeling has been widely used for analyzing various neuroimaging data. However, the relatively large and nonlinear neuroanatomical differences between infant and adult brains can lead to significant offsets of the labeled structures in infant brains when adult brain atlas is used. Age-specific 1- and 2-year-old brain atlases covering all major gray and white matter (GM and WM) structures with diffusion tensor imaging (DTI) and structural MRI are critical for precision medicine for infant population yet have not been established. In this study, high-quality DTI and structural MRI data were obtained from 50 healthy children to build up three-dimensional age-specific 1- and 2-year-old brain templates and atlases. Age-specific templates include a single-subject template as well as two population-averaged templates from linear and nonlinear transformation, respectively. Each age-specific atlas consists of 124 comprehensively labeled major GM and WM structures, including 52 cerebral cortical, 10 deep GM, 40 WM, and 22 brainstem and cerebellar structures. When combined with appropriate registration methods, the established atlases can be used for highly accurate automatic labeling of any given infant brain MRI. We demonstrated that one can automatically and effectively delineate deep WM microstructural development from 3 to 38 months by using these age-specific atlases. These established 1- and 2-year-old infant brain DTI atlases can advance our understanding of typical brain development and serve as clinical anatomical references for brain disorders during infancy.

Preterm Birth Alters the Regional Development and Structural Covariance of Cerebellum at Term-Equivalent Age.

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.

An MRI Study of Morphology, Asymmetry, and Sex Differences of Inferior Precentral Sulcus.

Numerous studies utilizing magnetic resonance imaging (MRI) have observed sex and interhemispheric disparities in sulcal morphology, which could potentially underpin certain functional disparities in the human brain. Most of the existing research examines the precentral sulcus comprehensively, with a rare focus on its subsections. To explore the morphology, asymmetry, and sex disparities within the inferior precentral sulcus (IPCS), we acquired 3.0T magnetic resonance images from 92 right-handed Chinese adolescents. Brainvisa was used to reconstruct the IPCS structure and calculate its mean depth (MD). Based on the morphological patterns of IPCS, it was categorized into five distinct types. Additionally, we analyzed four different types of spatial relationships between IPCS and inferior frontal sulcus (IFS). There was a statistically significant sex disparity in the MD of IPCS, primarily observed in the right hemisphere. Females exhibited significantly greater asymmetry in the MD of IPCS compared to males. No statistically significant sex or hemispheric variations were identified in sulcal patterns. Our findings expand the comprehension of inconsistencies in sulcal structure, while also delivering an anatomical foundation for the study of related regions' function.

Hepatocellular carcinoma combined with sarcomatoid hepatocellular carcinoma: A case report.

RATIONALE: Sarcomatoid hepatocellular carcinoma (SHC) is an uncommon variant of hepatocellular carcinoma (HCC), characterized by HCC features combined with sarcomatoid histology and manifestations. The simultaneous occurrence of HCC and hepatosarcomatoid carcinoma is infrequent. This report presents a distinctive instance of HCC coexisting with hepatic sarcomatoid carcinoma in a 56-year-old male. The case exhibits an unusual clinical presentation, diagnosis, treatment, and prognosis. Through the presentation of this case, we aspire to contribute novel concepts to shape forthcoming strategies encompassing SHC diagnosis and treatment. PATIENT CONCERNS: The 56-year-old male patient was admitted to the hospital, due to discovering a hepatic mass lasting for over 2 months. DIAGNOSES: Ultimately, combined hepatocellular and SHC diagnosis was conclusively confirmed through histopathological and imaging examinations. INTERVENTION: In this case, our approach encompassed hepatectomy coupled with ultrasound-guided radiofrequency ablation for HCC. Intraoperative ultrasound localization was employed for accurate tumor identification, followed by postoperative hepatic artery embolization to facilitate meticulous tumor resection. OUTCOMES: He underwent hepatic arteriography chemoembolization treatment and is currently stable, experiencing regular chemotherapy follow-up visits. LESSONS: The presence of distinct tumor types concurrently can influence treatment choices and prognosis. Given the intricate nature of this condition, crafting an optimal treatment strategy necessitates the incorporation of variables such as the patient age, tumor characteristics, liver function, and other pertinent factors.

How inflammation dictates diabetic peripheral neuropathy: An enlightening review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS: This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.

Aging pattern of the brainstem based on volumetric measurement and optimized surface shape analysis.

The brainstem, a small and crucial structure, is connected to the cerebrum, spinal cord, and cerebellum, playing a vital role in regulating autonomic functions, transmitting motor and sensory information, and modulating cognitive processes, emotions, and consciousness. While previous research has indicated that changes in brainstem anatomy can serve as a biomarker for aging and neurodegenerative diseases, the structural changes that occur in the brainstem during normal aging remain unclear. This study aimed to examine the age- and sex-related differences in the global and local structural measures of the brainstem in 187 healthy adults (ranging in age from 18 to 70 years) using structural magnetic resonance imaging. The findings showed a significant negative age effect on the volume of the two major components of the brainstem: the medulla oblongata and midbrain. The shape analysis revealed that atrophy primarily occurs in specific structures, such as the pyramid, cerebral peduncle, superior and inferior colliculi. Surface area and shape analysis showed a trend of flattening in the aging brainstem. There were no significant differences between the sexes or sex-by-age interactions in brainstem structural measures. These findings provide a systematic description of age associations with brainstem structures in healthy adults and may provide a reference for future research on brain aging and neurodegenerative diseases.

TaSRO1 interacts with TaVP1 to modulate seed dormancy and pre-harvest sprouting resistance in wheat.

Dormancy is an adaptive trait which prevents seeds from germinating under unfavorable environmental conditions. Seeds with weak dormancy undergo pre-harvest sprouting (PHS) which decreases grain yield and quality. Understanding the genetic mechanisms that regulate seed dormancy and resistance to PHS is crucial for ensuring global food security. In this study, we illustrated the function and molecular mechanism of TaSRO1 in the regulation of seed dormancy and PHS resistance by suppressing TaVP1. The tasro1 mutants exhibited strong seed dormancy and enhanced resistance to PHS, whereas the mutants of tavp1 displayed weak dormancy. Genetic evidence has shown that TaVP1 is epistatic to TaSRO1. Biochemical evidence has shown that TaSRO1 interacts with TaVP1 and represses the transcriptional activation of the PHS resistance genes TaPHS1 and TaSdr. Furthermore, TaSRO1 undermines the synergistic activation of TaVP1 and TaABI5 in PHS resistance genes. Finally, we highlight the great potential of tasro1 alleles for breeding elite wheat cultivars that are resistant to PHS.

Equivalent Heat Treatments and Mechanical Properties in Cold-Rolled TiNiFe Shape-Memory Alloys.

Heat treatments after cold rolling for TiNiFe shape-memory alloys have been compared. After EBSD analysis and as calculated by the Avrami model and Arrhenius equation, the relationship between the heat-treatment temperature and manufacturing time of TiNiFe alloys is established. Through calculation, it can be found that TiNiFe alloys can obtain similar microstructures under the annealing processes of 823 K for 776 min, 827 K for 37 min, and 923 K for 12.5 min. And the recrystallization fractions are all around 50%. Nevertheless, the tensile properties and recovery stress of the alloys show almost similar values. And based on the feasibility of the annealing process, it is believed that annealing at 873 K for 37 min is the optimal choice to obtain a recrystallization fraction φR = 50%.

Multi-slice computed tomographic analysis and identification of remarkable anatomical types of segmental bronchi in bilateral inferior lobes: based on extensive data.

Background: The progress of interventional respiratory medicine necessitates a comprehensive knowledge of the segmental bronchi because of their complexity in branching patterns. Therefore, based on extensive research data, we aimed to examine the anatomical diversity and sex-related variations of the segmental bronchial branching patterns in the bilateral inferior lobes. Methods: Following the exclusion and inclusion criteria, a total of 10,000 participants who underwent multi-slice computed tomography (MSCT) scans from September 2019 to December 2021 at Cheeloo College of Medicine, Shandong University were enrolled in this retrospective study. The computed tomography (CT) data were utilized to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. The distinct bronchial patterns in the bilateral inferior lobes were then found and categorized using the reconstructed images. The proportions of different types of bronchial branches and their sex-related correlations were analyzed by cross-tabulation and chi-square analysis. Results: Our findings primarily identified four types of bronchial branching patterns in the right inferior lobe (RIL), i.e., (B6, B7, B8, B9+10), 71.44%; (B6, B7, B8+9, B10), 16.06%; (B6, B7+8, B9+10), 7.40%; (B6, B7, B8+9+10), 5.10%; and four types in the left inferior lobe (LIL), i.e., (B6, B7+8, B9+10), 82.89%; (B6, B7+8, B9, B10), 13.53%; (B6, B7, B8+9, B10), 2.88%; (B6, B7, B8+9+10), 0.70%. Besides various research methods and outcomes, this study has revealed the types of bronchial branches that were not seen in previous studies. In addition, the proportion of bronchial branches in the LIL did not differ significantly between males and females (P>0.05). However, there was a significant difference in the proportion of bronchial branches in the RIL between sexes (P<0.05). Conclusions: The current study has validated the segmental bronchial variations in the bilateral inferior lobes. The diagnosis of symptomatic patients as well as the performance of interventions like bronchoscopies, endotracheal intubation, and lung resections may be significantly influenced by our findings in the clinical setting.

Fe(III)-Shikonin supramolecular nanomedicines as immunogenic cell death stimulants and multifunctional immunoadjuvants for tumor vaccination.

Immunoadjuvants, as an indispensable component of tumor vaccines, can observably enhance the magnitude, breadth, and durability of antitumor immunity. However, current immunoadjuvants suffer from different issues such as weak immunogenicity, inadequate cellular internalization, poor circulation time, and mono-functional bioactivity. Methods: Herein, we construct Fe3+-Shikonin metal-phenolic networks (FeShik) nanomedicines as immunogenic cell death (ICD) stimulants and multifunctional immunoadjuvants for tumor vaccination. The multifunctionality of FeShik nanomedicines is investigated by loading ovalbumin (OVA) as the model antigen to construct OVA@FeShik nanovaccines or 4T1 tumor cell fragment (TF) as homologous antigen to construct TF@FeShik nanovaccines. In vitro examinations including GSH responsive, •OH generation, colloid stability, cellular uptake, cytotoxicity mechanism of ferroptosis and necroptosis, ICD effect, the promotion of DC maturation and antigen cross-presentation were studied. In vivo observations including pharmacokinetics and biodistribution, antitumor effect, abscopal effect, immune memory effect, and biosafety were performed. Results: The presence of FeShik nanomedicines can significantly prolong the blood circulation time of antigens, increasing the bioavailability of antigens. Upon phagocytosis by tumor cells, FeShik nanomedicines can disassemble into Fe2+ and Shikonin in response to tumor microenvironments, leading to ICD of tumor cells via ferroptosis and necroptosis. Consequently, ICD-released autologous tumor cell lysates and pro-inflammatory cytokines not only stimulate DC maturation and antigen cross-presentation, but also promote macrophage repolarization and cytotoxic T lymphocyte infiltration, resulting in the activation of adaptive immune responses toward solid tumors. Conclusion: In a word, our FeShik supramolecular nanomedicines integrate bioactivities of ICD stimulants and immunoadjuvants, such as eradicating tumor cells, activating antitumor immune responses, modulating immunosuppressive tumor microenvironments, and biodegradation after immunotherapy. Encouraged by the diversity of polyphenols and metal ions, our research may provide a valuable paradigm to establish a large library for tumor vaccination.

Transforming Passive Employee Engagement Into Active Engagement: Supervisor Development Feedback Valences on Feedback-Seeking Behavior.

Employees' feedback-seeking behavior is an important way to develop and maintain self-awareness and interpersonal acuity, reduce uncertainty, boost creativity and improve innovative behavior and performance. Especially during the COVID-19 pandemic, working from home has become the new normal, supervisor feedback and employees feedback-seeking has an increasingly important impact on team creativity and team innovation performance.In the practice of organizational management, there is frequently a "feedback vacuum" between managers and employees. There is increasing research on feedback-seeking behavior in the field of OBHRM. This paper is the first to evaluate the impact of work meaning and positive attributions on workers' feedback-seeking behavior, and the cross-level effects of supervisor development feedback including variable valence. The paper analyzes supervisor-employee paired data from 158 supervisors and 659 employees using multi-source, multi-temporal data to draw the following conclusions: (1) Positive supervisor development feedback has a significant cross-level positive effect on employee feedback-seeking behavior, whereas negative supervisor development feedback does not affect employee feedback-seeking behavior; (2) Work meaningfulness mediates the cross-level relationship between positive supervisor development feedback and employees' feedback-seeking behaviors, whereas negative supervisor development feedback and employees' feedback-seeking behaviors do not; (3) Positive attributions positively moderate the relationship between positive supervisor development feedback and work meaningfulness; while positively moderating the relationship between negative supervisor development feedback and work meaningfulness; (4) Positive attributions have a moderating effect on supervisor development feedback that influences the indirect relationship to feedback-seeking behavior by work meaningfulness.

Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels.

Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we constructed an imputation reference panel using 1,285 Samoan individuals with whole-genome sequencing, combined with 1000 Genomes (1000G) samples, to create a reference panel that better represents Pacific Islander, specifically Samoan, genetic variation. We compared this panel to 1000G and TOPMed panels based on imputed variants using genotyping array data for 1,834 Samoan participants who were not part of the panels. The 1000G + 1285 Samoan panel yielded up to 2.25-2.76 times more well-imputed (r 2 ≥ 0.80) variants than TOPMed and 1000G. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum, although it was more pronounced for variants with 0.01 ≤ MAF ≤ 0.05. Imputation accuracy (r 2 ) was greater for population-specific variants (high fixation index, F ST ) and those from larger haplotypes (high LD score). The gain in imputation accuracy over TOPMed was largest for small haplotypes (low LD score), reflecting the Samoan panel's ability to capture population-specific variation not well tagged by other panels. We also augmented the 1000G reference panel with varying numbers of Samoan samples and found that panels with 48 or more Samoans included outperformed TOPMed for all variants with MAF ≥ 0.001. This study identifies variants with improved imputation using population-specific reference panels and provides a framework for constructing other population-specific reference panels.

Antibacterial mechanism of areca nut essential oils against Streptococcus mutans by targeting the biofilm and the cell membrane.

Introduction: Dental caries is one of the most common and costly biofilm-dependent oral diseases in the world. Streptococcus mutans is the major cariogenic pathogen of dental caries. S. mutans synthesizes extracellular polysaccharides by autologous glucosyltransferases, which then promotes bacterial adhesion and cariogenic biofilm formation. The S. mutans biofilm is the principal target for caries treatment. This study was designed to explore the antibacterial activity and mechanisms of areca nut essential oil (ANEO) against S. mutans. Methods: The ANEOs were separated by negative pressure hydro-distillation. The Kirby-Bauer method and broth microdilution method were carried out to evaluate the antibacterial activity of different ANEOs. The antibacterial mechanism was revealed by crystal violet staining, XTT reduction, microbial adhesion to hydrocarbon test, extracellular polysaccharide production assay, glucosyltransferase activity assay, lactate dehydrogenase leaking, propidium iodide staining and scanning electron microscopy (SEM). The cytotoxicity of ANEOs was determine by MTT assay. Results: The ANEOs separated at different temperatures exhibited different levels of antibacterial activity against S. mutans, and the ANEO separated at 70°C showed the most prominent bacteriostatic activity. Anti-biofilm experiments showed that the ANEOs attenuated the adhesion ability of S. mutans by decreasing the surface hydrophobicity of the bacteria, prevented S. mutans biofilm formation by inhibiting glucosyltransferase activity, reducing extracellular polysaccharide synthesis, and reducing the total biofilm biomass and activity. SEM further demonstrated the destructive effects of the ANEOs on the S. mutans biofilm. Cell membrane-related experiments indicated that the ANEOs destroyed the integrity of the cell membrane, resulting in the leakage of lactic dehydrogenase and nucleic acids. SEM imaging of S. mutans cell showed the disruption of the cellular morphology by the ANEOs. The cytotoxicity assay suggested that ANEO was non-toxic towards normal oral epithelial cells. Discussion: This study displayed that ANEOs exerted antibacterial activity against S. mutans primarily by affecting the biofilm and disrupting the integrity of the cell membrane. ANEOs has the potential to be developed as an antibacterial agent for preventing dental caries. Additionally, a new method for the separation of essential oil components is presented.