Cutting Edge: Phagosome-associated Autophagosomes Containing Antigens and Proteasomes Drive TAP-Independent Cross-Presentation.

Activation of naive CD8-positive T lymphocytes is mediated by dendritic cells that cross-present MHC class I (MHC-I)-associated peptides derived from exogenous Ags. The most accepted mechanism involves the translocation of Ags from phagosomes or endolysosomes into the cytosol, where antigenic peptides generated by cytosolic proteasomes are delivered by the transporter associated with Ag processing (TAP) to the endoplasmic reticulum, or an endocytic Ag-loading compartment, where binding to MHC-I occurs. We have described an alternative pathway where cross-presentation is independent of TAP but remains dependent on proteasomes. We provided evidence that active proteasomes found within the lumen of phagosomes and endolysosomal vesicles locally generate antigenic peptides that can be directly loaded onto trafficking MHC-I molecules. However, the mechanism of active proteasome delivery to the endocytic compartments remained unknown. In this study, we demonstrate that phagosome-associated LC3A/B structures deliver proteasomes into subcellular compartments containing exogenous Ags and that autophagy drives TAP-independent, proteasome-dependent cross-presentation.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala.

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal α-synuclein (α-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in α-synucleinopathies. To understand if and how pathologic α-syn impacts the BLA requires animal models of α-syn aggregation. Injection of α-syn pre-formed fibrils (PFFs) into the striatum induces robust α-syn aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if α-syn inclusions in the BLA induce synaptic degeneration and/or morphological changes. In this study, we used C57BL/6 J mice injected bilaterally with PFFs in the dorsal striatum to induce α-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. α-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of α-syn show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that asymmetric synapses in mice with PFF-induced α-syn aggregates have reduced synaptic vesicle intervesicular distances, similar to a recent study showing phospho-serine-129 α-syn increases synaptic vesicle clustering. Thus, pathologic α-syn causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.

Health state utility values for children and adolescents with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most burdensome chronic diseases in the world. Health utility values are an important tool for quantifying this disease burden and conducting cost-utility analyses. This review aimed to derive a reference set of health utility values for children and adolescents with T1DM. METHODS: We searched MEDLINE and Embase from inception to March 2023 for health utility values of T1DM children and adolescents (aged ≤18 years) measured using direct and indirect preference elicitation approaches. Utility estimates were pooled by meta-analyses with subgroup analyses to evaluate differences by populations and elicitation approaches. RESULTS: Six studies involving 1276 participants were included in this study. Meta-analysis showed the overall utility value of children and adolescents with T1DM was 0.91 (95% CI 0.89-0.93). The utility value of T1DM children and adolescents with complications was 0.90 (95% CI 0.88-0.92), which was lower than those without complications (0.96, 95% CI 0.95-0.97). The utility value of children (aged <13 years) was higher than adolescents (aged 13-18 years) (0.90 vs. 0.85). The utility value measured by the EQ-5D-3L (0.91) was higher than the HUI3 (0.89), the SF-6Dv1 (0.83), and the time trade-off (0.81). The parent proxy-reported was similar to the patient self-reported (0.91 vs. 0.91). CONCLUSIONS: This study developed a reference set of pooled utility estimates for children and adolescents with T1DM, which is helpful for understanding the overall health status of T1DM and conducting economic evaluations. Further studies are needed to explore the utilities of T1DM with different types of complications.

An Improved Method for the Synthesis of M2[B12H12] (M = Na, K) and Their Formation Mechanism.

Polyhedral boranes have potential applications in medicine and material science due to their unique structure and stability. However, tedious and low-yield synthetic methods limited their application. Herein, we have developed a facile large-scale synthetic method for M2[B12H12] (M = Na, K) by the reaction of MBH4 with N,N-dipropylaniline borane in diglyme at 120 or 140 °C in up to 88% yield. The mechanistic studies indicated that intermediates, such as [B3H8]- and [B9H14]-, were formed in the formation process of [B12H12]2- anion, similar to previously reported. The formation of B2H6 from the N,N-dipropylaniline borane adducts is most important. The developed method avoided using toxic materials, with high yield, easily scaled up, raw materials are readily available. Additionally, the starting material, N,N-dipropylaniline, could be repeatedly used at least three times with similar yields, which is an economical way to facilitate industrial synthesis. It is believed that this method will support further application of Na2[B12H12] and K2[B12H12] as solid electrolytes for an all-solid-state batteries.

Occlusal trauma aggravates periodontitis through the plasminogen/plasmin system.

OBJECTIVES: Periodontitis is a common oral disease that is aggravated by occlusal trauma. Fibrin is a protein that participates in blood clotting and is involved in several human diseases. The deposition of fibrin in periodontal tissues can induce periodontitis, while mechanical forces may regulate the degradation of fibrin. Our study investigated how occlusal trauma aggravating periodontitis through regulating the plasminogen/plasmin system and fibrin deposition. MATERIALS AND METHODS: This study included 84 C57BL/6 mice in which periodontitis was induced with or without occlusal trauma. Micro-computed tomography was used to assess bone resorption. Fibrin, fibrinogen, plasminogen, plasmin, tissue plasminogen activator (t-PA), and urokinase plasminogen activator (u-PA) levels were measured using Frazer-Lendrum staining, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, immunofluorescence staining, and immunohistochemistry staining. RESULTS: Occlusal trauma aggravated inflammation and bone resorption. The periodontitis group showed significant fibrin deposition. Occlusal trauma increased fibrin deposition and neutrophil aggregation. The periodontitis with occlusal trauma group had decreased fibrinogen, t-PA, and u-PA expression and plasmin and fibrin degradation product levels, as well as increased plasminogen levels. CONCLUSION: Occlusal trauma promotes excessive fibrin deposition by suppressing the plasminogen/plasmin system, thus exacerbating periodontitis.

Network pharmacology to unveil the mechanism of suanzaoren decoction in the treatment of alzheimer's with diabetes.

BACKGROUND: Suanzaoren Decoction (SZRD), a well-known formula from traditional Chinese medicine, has been shown to have reasonable cognitive effects while relaxing and alleviating insomnia. Several studies have demonstrated significant therapeutic effects of SZRD on diabetes and Alzheimer's disease (AD). However, the active ingredients and probable processes of SZRD in treating Alzheimer's with diabetes are unknown. This study aims to preliminarily elucidate the potential mechanisms and potential active ingredients of SZRD in the treatment of Alzheimer's with diabetes. METHODS: The main components and corresponding protein targets of SZRD were searched on the TCMSP database. Differential gene expression analysis for diabetes and Alzheimer's disease was conducted using the Gene Expression Omnibus database, with supplementation from OMIM and genecards databases for differentially expressed genes. The drug-compound-target-disease network was constructed using Cytoscape 3.8.0. Disease and SZRD targets were imported into the STRING database to construct a protein-protein interaction network. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the intersection of genes. Molecular docking and molecular dynamics simulations were conducted on the Hub gene and active compounds. Gene Set Enrichment Analysis was performed to further analyze key genes. RESULTS: Through the Gene Expression Omnibus database, we obtained 1977 diabetes related genes and 622 AD related genes. Among drugs, diabetes and AD, 97 genes were identified. The drug-compound-target-disease network revealed that quercetin, kaempferol, licochalcone a, isorhamnetin, formononetin, and naringenin may be the core components exerting effects. PPI network analysis identified hub genes such as IL6, TNF, IL1B, CXCL8, IL10, CCL2, ICAM1, STAT3, and IL4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that SZRD in the treatment of Alzheimer's with diabetes is mainly involved in biological processes such as response to drug, aging, response to xenobiotic, and enzyme binding; as well as signaling pathways such as Pathways in cancer, Chemical carcinogenesis - receptor activation, and Fluid shear stress and atherosclerosis. Molecular docking results showed that licochalcone a, isorhamnetin, kaempferol, quercetin, and formononetin have high affinity with CXCL8, IL1B, and CCL2. Molecular dynamics simulations also confirmed a strong interaction between CXCL8 and licochalcone a, isorhamnetin, and kaempferol. Gene Set Enrichment Analysis revealed that CXCL8, IL1B, and CCL2 have significant potential in diabetes. CONCLUSION: This study provides, for the first time, insights into the active ingredients and potential molecular mechanisms of SZRD in the treatment of Alzheimer's with diabetes, laying a theoretical foundation for future basic research.

Color and Luminance Separated Enhancement for Low-Light Images with Brightness Guidance.

Existing retinex-based low-light image enhancement strategies focus heavily on crafting complex networks for Retinex decomposition but often result in imprecise estimations. To overcome the limitations of previous methods, we introduce a straightforward yet effective strategy for Retinex decomposition, dividing images into colormaps and graymaps as new estimations for reflectance and illumination maps. The enhancement of these maps is separately conducted using a diffusion model for improved restoration. Furthermore, we address the dual challenge of perturbation removal and brightness adjustment in illumination maps by incorporating brightness guidance. This guidance aids in precisely adjusting the brightness while eliminating disturbances, ensuring a more effective enhancement process. Extensive quantitative and qualitative experimental analyses demonstrate that our proposed method improves the performance by approximately 4.4% on the LOL dataset compared to other state-of-the-art diffusion-based methods, while also validating the model's generalizability across multiple real-world datasets.

Ultrasound-based radiomics for early predicting response to neoadjuvant chemotherapy in patients with breast cancer: a systematic review with meta-analysis.

OBJECTIVE: This study aims to evaluate the diagnostic accuracy of ultrasound imaging (US)-based radiomics for the early prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We comprehensively searched PubMed, Cochrane Library, Embase, and Web of Science databases up to 1 January 2023 for eligible studies. We assessed the methodological quality of the enrolled studies with Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 tools. We performed meta-analyses to summarize the diagnostic efficacy of US-based radiomics in response to NAC in breast cancer patients. RESULTS: Eight studies proved eligible. Eligible studies exhibited an average RQS score of 12.88 (35.8% of the total score), with the RQS score ranging from 8 to 19. In the meta-analyses, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.87 (95% CI 0.81-0.92), 0.78 (95% CI 0.72-0.83), 4.02 (95% CI 3.18-5.08), 0.16 (95% CI 0.10-0.25), and 25.17 (95% CI 15.10-41.95), respectively. Results from subgroup analyses indicated that prospective studies apparently exhibited more optimal sensitivity than retrospective studies. Sensitivity analyses exhibited similar results to the primary analyses. CONCLUSION: US-based radiomics may be a potentially crucial adjuvant method for evaluating the response of breast cancer to NAC. Due to limited data available and low quality of eligible studies, more multicenter prospective studies with rigorous methods are required to confirm our findings.

Common Bean (Phaseolus vulgaris L.) NAC Transcriptional Factor PvNAC52 Enhances Transgenic Arabidopsis Resistance to Salt, Alkali, Osmotic, and ABA Stress by Upregulating Stress-Responsive Genes.

The NAC family of transcription factors includes no apical meristem (NAM), Arabidopsis thaliana transcription activator 1/2 (ATAF1/2), and cup-shaped cotyledon (CUC2) proteins, which are unique to plants, contributing significantly to their adaptation to environmental challenges. In the present study, we observed that the PvNAC52 protein is predominantly expressed in the cell membrane, cytoplasm, and nucleus. Overexpression of PvNAC52 in Arabidopsis strengthened plant resilience to salt, alkali, osmotic, and ABA stresses. PvNAC52 significantly (p < 0.05) reduced the degree of oxidative damage to cell membranes, proline content, and plant water loss by increasing the expression of MSD1, FSD1, CSD1, POD, PRX69, CAT, and P5CS2. Moreover, the expression of genes associated with abiotic stress responses, such as SOS1, P5S1, RD29A, NCED3, ABIs, LEAs, and DREBs, was enhanced by PvNAC52 overexpression. A yeast one-hybrid assay showed that PvNAC52 specifically binds to the cis-acting elements ABRE (abscisic acid-responsive elements, ACGTG) within the promoter. This further suggests that PvNAC52 is responsible for the transcriptional modulation of abiotic stress response genes by identifying the core sequence, ACGTG. These findings provide a theoretical foundation for the further analysis of the targeted cis-acting elements and genes downstream of PvNAC52 in the common bean.

Preparing to Address Social Determinants of Health (SDOH): Approaches to Clinic Transformation.

CONTEXT: Pennsylvanians' health is influenced by numerous social determinants of health (SDOH). Integrating SDOH data into electronic health records (EHRs) is critical to identifying health disparities, informing public health policies, and devising interventions. Nevertheless, challenges remain in its implementation within clinical settings. In 2018, the Pennsylvania Department of Health (PADOH) received the Centers for Disease Control and Prevention's DP18-1815 "Improving the Health of Americans Through Prevention and Management of Diabetes and Heart Disease and Stroke" grant to strengthen SDOH data integration in Pennsylvania practices. IMPLEMENTATION: Quality Insights was contracted by PADOH to provide training tailored to each practice's readiness, an International Classification of Diseases, Tenth Revision (ICD-10) guide for SDOH, Continuing Medical Education on SDOH topics, and introduced the PRAPARE toolkit to streamline SDOH data integration and address disparities. Dissemination efforts included a podcast highlighting success stories and lessons learned from practices. From 2019 to 2022, Quality Insights and the University of Pittsburgh Evaluation Institute for Public Health (Pitt evaluation team) executed a mixed-methods evaluation. FINDINGS: During 2019-2022, Quality Insights supported 100 Pennsylvania practices in integrating SDOH data into EHR systems. Before COVID-19, 82.8% actively collected SDOH data, predominantly using PRAPARE tool (62.7%) and SDOH ICD-10 codes (80.4%). Amidst COVID-19, these statistics shifted to 65.1%, 45.2%, and 42.7%, respectively. Notably, the pandemic highlighted the importance of SDOH assessment and catalyzed some practices' utilization of SDOH data. Progress was evident among practices, with additional contribution to other DP18-1815 objectives. The main challenge was the variable understanding, utilization, and capability of handling SDOH data across practices. Effective strategies involved adaptable EHR systems, persistent efforts by Quality Insights, and the presence of change champions within practices. DISCUSSION: The COVID-19 pandemic strained staffing in many practices, impeding SDOH data integration into EHRs. Addressing the diverse understanding and use of SDOH data requires standardized training and procedures. Customized support and sustained engagement by facilitating organizations are paramount in ensuring practices' efficient SDOH data collection and integration.

Identification and validation of ferroptosis-related gene SLC2A1 as a novel prognostic biomarker in AKI.

BACKGROUND: Emerging evidence reveals the key role of ferroptosis in the pathophysiological process of acute kidney injury (AKI). Our study aimed to investigate the potential ferroptosis-related gene in AKI through bioinformatics and experimental validation. METHODS: The AKI single-cell sequencing dataset was retrieved from the GEO database and ferroptosis-related genes were extracted from the GENECARD website. The potential differentially expressed ferroptosis-related genes of AKI were selected. Functional enrichment analysis was performed. Machine learning algorithms were used to identify key ferroptosis-related genes associated with AKI. A multi-factor Cox regression analysis was used to construct a risk score model. The accuracy of the risk score model was validated using receiver operating characteristic (ROC) curve analysis. We extensively explored the immune landscape of AKI using CIBERSORT tool. Finally, expressions of ferroptosis DEGs were validated in vivo and in vitro by Western blot, ICH and transfection experiments. RESULTS: Three hub genes (BAP1, MDM4, SLC2A1) were identified and validated by constructing drug regulatory network and subsequent screening using experimentally determined interactions. The risk mode showed the low-risk group had significantly better prognosis compared to high-risk group. The risk score was independently associated with overall survival. The ROC curve analysis showed that the prognosis model had good predictive ability. Additionally, CIBERSORT immune infiltration analysis suggest that the hub gene may influence cell recruitment and infiltration in AKI. Validation experiments revealed that SLC2A1 functions by regulating ferroptosis. CONCLUSIONS: In summary, our study not only identifies SLC2A1 as diagnostic biomarker for AKI, but also sheds light on the role of it in AKI progression, providing novel insights for the clinical diagnosis and treatment of AKI.

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway.

Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1ß, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.

New insights into the effect of pyrolysis temperature on the spectroscopy properties of dissolved organic matter in manure-based biochar.

Dissolved organic matter (DOM) derived from biochar takes a crucial role in transport and bioavailability toward contaminants; hence, it is undeniable that a thorough analysis of its properties is important. So far, the effect of pyrolysis temperature on the functional groups, components, and evolutionary sequence of manure-based biochar DOM has not been adequately investigated. Here, DOM was released from two typical livestock manures (cow and pig) at five pyrolysis temperatures (300 ~ 700°C), and it was explored in depth with the aid of moving window 2D correlation spectroscopy (MW-2D-COS) and heterogeneous 2D correlation spectroscopy (hetero-2D-COS). The results demonstrated that the concentration, aromaticity, and hydrophobicity of DOM were greater at high temperatures, and more DOM was liberated from cow manure-based biochar at identical temperature. Protein-like compounds dominated at high temperatures. The pyrolysis temperatures of final configuration transformation points of the fulvic acid-like component and the aromatic ring C=C in DOM were 400°C and 500°C, respectively. Moreover, Fourier transform infrared spectroscopy combined with two-dimensional correlation analysis indicated that the functional group evolution of DOM depends on the pyrolysis temperature and feedstock type. The study provides a new perspective on manure management and environmental applications of biochar.

Investigation of synthetic MRI with quantitative parameters for discriminating axillary lymph nodes status in invasive breast cancer.

OBJECTIVE: To investigate the potential value of quantitative parameters derived from synthetic magnetic resonance imaging (syMRI) for discriminating axillary lymph nodes metastasis (ALNM) in breast cancer patients. MATERIALS AND METHODS: A total of 56 females with histopathologically proven invasive breast cancer who underwent both conventional breast MRI and additional syMRI examinations were enrolled in this study, including 30 patients with ALNM and 26 with non-ALNM. SyMRI has enabled quantification of T1 relaxation time (T1), T2 relaxation time (T2) and proton density (PD). The syMRI quantitative parameters of breast primary tumors before (T1tumor, T2tumor, PDtumor) and after (T1+tumor, T2+tumor, PD+tumor) contrast agent injection were obtained. Similarly, measurements were taken for axillary lymph nodes before (T1LN, T2LN, PDLN) and after (T1+LN, T2+LN, PD+LN) the injection, then theΔT1 (T1-T1+), ΔT2 (T2-T2+), ΔPD (PD-PD+), T1/T2 and T1+/T2+ were calculated. All parameters were compared between ANLM and non-ALNM group. Intraclass correlation coefficient for assessing interobserver agreement. The independent Student's t test or Mann-Whitney U test to determine the relationship between the mean quantitative values and the ALNM. Multivariate logistic regression analyses followed by receiver operating characteristics (ROC) analysis for discriminating ALN status. A P value < 0.05 was considered statistically significant. RESULTS: The short-diameter of lymph nodes (DLN) in ALNM group was significantly longer than that in the non-ALNM group (10.22 ± 3.58 mm vs. 5.28 ± 1.39 mm, P < 0.001). The optimal cutoff value was determined to be 5.78 mm, with an AUC of 0.894 (95 % CI: 0.838-0.939), a sensitivity of 86.7 %, and a specificity of 90.2 %. In syMRI quantitative parameters of breast tumors, T2tumor, ΔT2tumor and ΔPDtumor values showed statistically significant differences between the two groups (P < 0.05). T2tumor value had the best performance in discriminating ALN status (AUC = 0.712), and the optimal cutoff was 90.12 ms, the sensitivity and specificity were 65.0 % and 83.6 % respectively. In terms of syMRI quantitative parameters of lymph nodes, T1LN, T2LN, T1LN/T2LN, T2+LN and ΔT1LN values were significantly different between the two groups (P < 0.05), and their AUCs were 0.785, 0.840, 0.886, 0.702 and 0.754, respectively. Multivariate analyses indicated that the T1LN value was the only independent predictor of ALNM (OR=1.426, 95 % CI: 1.130-1.798, P = 0.039). The diagnostic sensitivity and specificity of T1LN was 86.7 % and 69.4 % respectively at the best cutoff point of 1371.00 ms. The combination of T1LN, T2LN, T1LN/T2LN, ΔT1LN and DLN had better performance for differentiating ALNM and non-ALNM, with AUCs of 0.905, 0.957, 0.964 and 0.897, respectively. CONCLUSION: The quantitative parameters derived from syMRI have certain value for discriminating ALN status in invasive breast cancer, with T2tumor showing the highest diagnostic efficiency among breast lesions parameters. Moreover, T1LN acted as an independent predictor of ALNM.

Executive function performance in children and adolescent patients with narcolepsy type 1.

OBJECTIVE: The executive function profile in patients with narcolepsy type 1 (NT1) has been mentioned; however, limited research exists on children and adolescent patients with NT1.This study aims to assess executive function in children and adolescent patients with NT1 in China, examine potential influencing factors and evaluate the short-term treatment effect on executive function. METHODS: 53 NT1 patients (36 males, age 12.2 ± 3.4 years) and 37 healthy controls (23 males, age 12.2 ± 2.5 years) underwent self-reported measures assessing subjective sleepiness, depression, anxiety and sleep quality. A comprehensive neuropsychological test was administered to assess executive function domains, including processing speed, inhibitory control, cognitive flexibility and working memory. These assessments were repeated in NT1 patients after three-day regular drug treatment. RESULTS: NT1 patients exhibited higher levels of excessive daytime sleepiness, depression, anxiety, and poor sleep quality compared to healthy controls. Patients showed impaired processing speed, inhibitory control and cognitive flexibility (p < 0.05), whereas working memory was unaffected (p > 0.05). Regression analysis revealed that parameters from sleep monitoring, such as sleep efficiency and sleep latency, were correlated with executive function performance after controlling for age, gender, and education years. The short-term treatment led to improvements in inhibitory control, cognitive flexibility, and working memory. CONCLUSION: The findings showed that executive function was impaired among children and adolescent patients with NT1, which was associated with objective sleep parameters. Furthermore, this study emphasizes the necessity of neuropsychological assessments and early interventions among children and adolescent NT1 patients.

An untargeted comparative metabolomics analysis of infants with and without late-onset breast milk jaundice.

BACKGROUND: Late-onset breast milk jaundice (LBMJ) is a common form of hyperbilirubinemia, which can result in serious complications for newborns with persistently high bilirubin levels. The aim of this study was to investigate the differences in fecal metabolites between breastfed infants with and without LBMJ in order to elucidate potential biological mechanisms. METHODS: Biological samples were collected from 12 infants with LBMJ and 12 healthy individuals. Ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was utilized for non-targeted determination of fecal metabolites. Principal components analysis (PCA), cluster analysis, and differential metabolite analysis were performed in both positive ion mode and negative ion mode for the two groups. Additionally, the KEGG database was employed to comprehensively analyze the pathways of differential metabolites. RESULTS: There were no significant differences in maternal and neonatal demographic characteristics between the two groups (p > 0.05). The results of PCA and cluster heat map analysis in both modes showed that there were significant differences in metabolites between the two groups. Among 751 differential metabolites (DMs) detected in positive ion mode, 720 were up-regulated in the case group while 31 were down-regulated. In negative ion mode, 1891 DMs were detected, including 817 up-regulated metabolites and 1074 down-regulated metabolites in the case group. Analysis of differential metabolic pathways showed that the DMs of the two groups were mainly annotated and enriched in Biotin metabolism, N-Glycan biosynthesis, Taurine and hypotaurine metabolism, Pyrimidine metabolism, and Pentose and glucuronate interconversions. CONCLUSION: Significant differences exist in fecal metabolites between LBMJ infants and healthy controls. The study of differential metabolic pathways provides insights into the mechanism of LBMJ.

Formation and reactivity of a unique M⋯C-H interaction stabilized by carborane cages.

Broadening carborane applications has consistently been the goal of chemists in this field. Herein, compared to alkyl or aryl groups, a carborane cage demonstrates an advantage in stabilizing a unique bonding interaction: M⋯C-H interaction. Experimental results and theoretical calculations have revealed the characteristic of this two-center, two-electron bonding interaction, in which the carbon atom in the arene ring provides two electrons to the metal center. The reduced aromaticity of the benzene moiety, long distance between the metal and carbon atom in arene, and the upfield shift of the signal of M⋯C-H in the nuclear magnetic resonance spectrum distinguished this interaction from metal⋯C π interaction and metal-C(H) σ bonds. Control experiments demonstrate the unique electronic effects of carborane in stabilizing the M⋯C-H bonding interaction in organometallic chemistry. Furthermore, the M⋯C-H interaction can convert into C-H bond metallization under acidic conditions or via treatment with t-butyl isocyanide. These findings deepen our understanding regarding the interactions between metal centers and carbon atoms and provide new opportunities for the use of carboranes.

Case of precise full-mouth occlusal reconstruction guided by digital occlusal function analysis.

The clinical demand for occlusal reconstruction increases rapidly with increasing number of patients who have lost their normal occlusion because of tooth wear and dentition defects. Occlusal reconstruction is a special type of restoration defined as a comprehensive restoration of the function of the stomatognathic system by reestablishing a uniform and stable occlusal relationship between the upper and lower dentitions. Occlusal function analysis is an important part of occlusal reconstruction to achieve accurate restoration design and adjustment. Digital occlusal function analysis was conducted to monitor the movement of the mandible and obtain related data for the parameter design of occlusal reconstruction. Preoperative design, intraoperative adjustment, and postoperative verification were achieved, thereby improving the efficiency and accuracy of occlusal reconstruction.

18 F-FDG PET/CT characteristics of IASLC grade 3 invasive adenocarcinoma and the value of 18 F-FDG PET/CT for preoperative prediction: a new prognostication model.

OBJECTIVE: This study is performed to investigate the imaging characteristics of the International Association for the Study of Lung Cancer grade 3 invasive adenocarcinoma (IAC) on PET/CT and the value of PET/CT for preoperative predicting this tumor. MATERIALS AND METHODS: We retrospectively enrolled patients with IAC from August 2015 to September 2022. The clinical characteristics, serum tumor markers, and PET/CT features were analyzed. T test, Mann-Whitney U test, χ 2 test, Logistic regression analysis, and receiver operating characteristic analysis were used to predict grade 3 tumor and evaluate the prediction effectiveness. RESULTS: Grade 3 tumors had a significantly higher maximum standardized uptake value (SUV max ) and consolidation-tumor-ratio (CTR) ( P  < 0.001), while Grade 1 - 2 tumors were prone to present with air bronchogram sign or vacuole sign ( P  < 0.001). A stepwise logistic regression analysis revealed that smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR were useful predictors for Grade 3 tumors. The established prediction model based on the above 5 parameters generated a high AUC (0.869) and negative predictive value (0.919), respectively. CONCLUSION: Our study demonstrates that grade 3 IAC has a unique PET/CT imaging feature. The prognostication model established with smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR can effectively predict grade 3 tumors before the operation.