Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women.

Estrogen receptor positive (ER+) breast cancer is the most common subtype of breast cancer and is an age-related disease. The peak incidence of diagnosis occurs around age 70, even though these post-menopausal patients have low circulating levels of estradiol (E2). Despite the hormone sensitivity of age-related tumors, we have a limited understanding of the interplay between systemic and local hormones, chronic inflammation, and immune changes that contribute to the growth and development of these tumors. Here, we show that aged F344 rats treated with the dimethylbenz(a)anthracene / medroxyprogestrone acetate (DMBA/MPA) carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment promotes tumor initiation and impacts growth. Single-nuclei RNA-seq (snRNA-seq) of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with an estrone (E1)-predominant estrogen disposition in the systemic circulation, tumors in older patients increase HSD17B7 expression to convert E1 to E2 in the tumor microenvironment (TME) and have local E2 levels similar to pre-menopausal patients. Concurrently, trackable increases in several chemokines, defined most notably by CCL2, promote a chronically inflamed but immune dysfunctional TME. This unique milieu in the aged TME, characterized by high local E2 and chemokine-enriched chronic inflammation, promotes both accumulation of tumor-associated macrophages (TAMs), which serve as signaling hubs, as well as polarization of TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Pharmacologic targeting of estrogen signaling (either by HSD17B7 inhibition or with fulvestrant) and chemokine inflammation both decrease local E2 and prevent macrophage polarization. Overall, these findings suggest that chronic inflammation and hormonal disposition are critical contributors to the age-related nature of ER+ breast cancer development and growth and offer potential therapeutic insight to treat these patients. Translational Summary: We uncover the unique underpinnings establishing how the systemic host environment contributes to the aged breast tumor microenvironment, characterized by high local estradiol and chronic inflammation with immune dysregulation, and show that targeting avenues of estrogen conversion and chronic inflammation work to restore anti-tumor immunity.

Estimation of skin surface roughness in vivo based on optical coherence tomography combined with convolutional neural network.

The texture of human skin is influenced by both external and internal factors, and changes in wrinkles can most directly reflect the state of the skin. Skin roughness is primarily used to quantify the wrinkle features of the skin. Therefore, effective and accurate quantification of skin roughness is essential in skincare, medical treatment, and product development. This study proposes a method for estimating the skin surface roughness using optical coherence tomography (OCT) combined with a convolutional neural network (CNN). The proposed algorithm is validated through a roughness standard plate. Then, the experimental results revealed that skin surface roughness including arithmetic mean roughness and depth of roughness depends on age and gender. The advantage of the proposed method based on OCT is that it can reduce the effect of the skin surface's natural curvature on roughness. In addition, the method is combined with the epidermal thickness and dermal attenuation coefficient for multi-parameter characterization of skin features. It could be seen as a potential tool for understanding the aging process and developing strategies to maintain and enhance skin health and appearance.

Multi-omics analysis identifies BCAT2 as a potential pan-cancer biomarker for tumor progression and immune microenvironment modulation.

Branched-chain amino acid transaminase 2 (BCAT2) encodes a crucial protein involved in the initial catalysis of branched-chain amino acid (BCAA) catabolism, with emerging evidence suggesting its association with tumor progression. This study explores BCAT2 in a pan-cancer multi-omics context and evaluates its prognostic significance. We utilized a multi-database approach, analyzing cBioPortal for genetic alterations, RNA-Seq data from TCGA and GTEx for expression patterns, and RSEM for transcript analysis. Protein expression and interaction networks were assessed using the Human Protein Atlas, UniProt, and STRING. Prognostic value was determined through Cox regression analysis of TCGA clinical survival data, while immune cell infiltration across various cancers was examined using TCGA data and the TIMER2 platform. Our results revealed that BCAT2 alterations are primarily amplifications and is upregulated in various tumors, correlating with poor survival rates in several tumor types, including GBMLGG, LGG, and UVM. Elevated BCAT2 protein levels were common in pan-cancer, interacting with a range of metabolic enzymes. Additionally, BCAT2 expression significantly influenced CD4+ T cells, CD8+ T cells, and Treg cells infiltration, with varied correlations across cancer types. These findings indicate BCAT2 as a potential biomarker for cancer diagnosis and therapy, potentially regulating key metabolic and immune factors to mediate tumor progression and the microenvironment.

TRIM27 revealing by tumor educated platelet RNA-sequencing, as a potential biomarker for malignant ground-glass opacities diagnosis mediates glycolysis of non-small cell lung cancer cells partially through HOXM1.

Background: Efficient ground-glass opacities (GGOs) diagnosis is challenging. A diagnostic method distinguishing malignant from benign GGOs is warranted. In this study, we sought to construct a noninvasive method based on tumor educated platelet (TEP) RNA profiles for malignant GGOs diagnosis and explore the molecular mechanism of the potential biomarker for the first time. Methods: Based on TEP RNA-sequencing (TEP RNA-seq) in benign and malignant GGOs, a classification model was constructed using differentially expressed genes (DEGs) and was used to evaluate diagnostic performance. High-throughput quantitative polymerase chain reaction (HT-qPCR) verified 23 genes selected from the top 60 DEGs between benign and malignant GGOs. The correlation between 17 verified DEGs and 22 key glycolytic genes was analyzed. Tripartite motif-containing 27 (TRIM27) overexpressing and knockdown (KD) cell models were constructed using A549 and PC-9 cells, respectively in which cell growth, apoptosis, migration and invasion were evaluated. The protein levels of HK-1/2, PKM1/2, LDHA and GLUT1 were evaluated by western blot. Glycolysis was evaluated through adenosine triphosphate (ATP), reactive oxygen species (ROS), lactate acid (LD) production, glucose uptake, and lactate dehydrogenase (LDH) activity assays. RNA-seq was performed in loss-of TRIM27-KD PC-9 cells to clarify the downstream factors of TRIM27 which was verified using western blot and immunofluorescence double staining. Results: In 81 samples, the 1,647-DEG-based classification model exhibited area under the curve (AUC), sensitivity, and specificity values of 0.99 [95% confidence interval (CI): 0.972-1.000], 100%, and 91%, respectively, while the top 60-DEG-based classification model exhibited AUC, sensitivity, and specificity values of 0.986 (95% CI: 0.962-1.000), 98%, and 91%, respectively. TRIM27 achieved AUC of 0.87 in the diagnosis of malignant GGOs, with 83.93% sensitivity, 78.79% specificity, 81.15% accuracy, 77.05% positive predictive value (PPV) and 85.25% negative predictive value (NPV). TRIM27 was highly expressed in non-small cell lung cancer (NSCLC) cells, and accelerated cell migration and invasion. In addition, TRIM27 was found to promote glycolysis in NSCLC cells partially through HMOX1 which was negatively correlated with TRIM27. Conclusions: We constructed a novel TEP RNA-seq based classifier for malignant GGOs diagnosis. TRIM27, an important target discovered, could accelerate migration, invasion and regulate glycolysis partially through HMOX1 in NSCLC cells, thus providing scientific support for TRIM27 as a diagnostic biomarker for malignant GGO diagnosis.

Sodium alginate supramolecular nanofibers in synergy with surface crack engineering to prepare tough and highly sensitive hydrogels.

Soft and wet hydrogels often struggle to achieve both toughness and high sensitivity simultaneously, limiting their usefulness in flexible devices. To tackle this challenge, we devised a strategy that combines supramolecular sodium alginate nanofibers, utilizing Zr4+ as physical crosslinkers, with surface crack engineering via the micro-phase separation of polyaniline, to create a physically and chemically dual crosslinked polyacrylamide (PAM)/sodium alginate (SA)/polyaniline (PANI) hydrogel with exceptional toughness and high sensitivity. Owing to the supramolecular sodium alginate nanofibers, the dual crosslinked hydrogel exhibited a tensile strength of 0.391 MPa, an elongation at break of 568.9 %, and a toughness of 1.020 MJ/m3. The in-situ polymerized polyaniline layer, confined within the dense network, introduced micro-cracks onto the hydrogel surface, resulting in a high gauge factor of 11.4 for the fabricated hydrogel. Furthermore, integrating this hydrogel into a triboelectric nanogenerator transformed it into self-powered sensors capable of detecting external forces and generating various signals without power supply. These findings suggest that the developed hydrogel held great potential in diverse fields, including human motion detection, human-machine interaction, and wearable electronic devices.

Animal modeling for myopia.

Background: Myopia is one of the most common eye diseases globally, and has become an increasingly serious health concern among adolescents. Understanding the factors contributing to the onset of myopia and the strategies to slow its progression is critical to reducing its prevalence. Main text: Animal models are key to understanding of the etiology of human diseases. Various experimental animal models have been developed to mimic human myopia, including chickens, rhesus monkeys, marmosets, mice, tree shrews, guinea pigs and zebrafish. Studies using these animal models have provided evidences and perspectives on the regulation of eye growth and refractive development. This review summarizes the characteristics of these models, the induction methods, common indicators of myopia in animal models, and recent findings on the pathogenic mechanism of myopia. Conclusions: Investigations using experimental animal models have provided valuable information and insights into the pathogenic mechanisms of human myopia and its treatment strategies.

TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.

Mechanical control is fundamental for cellular localization within a tissue, including for tumor-associated macrophages (TAMs). While the innate immune sensing pathways cGAS-STING and RLR-MAVS impact the pathogenesis and therapeutics of malignant diseases, their effects on cell residency and motility remain incompletely understood. Here, we uncovered that TBK1 kinase, activated by cGAS-STING or RLR-MAVS signaling in macrophages, directly phosphorylates and mobilizes Zyxin, a key regulator of actin dynamics. Under pathological conditions and in STING or MAVS signalosomes, TBK1-mediated Zyxin phosphorylation at S143 facilitates rapid recruitment of phospho-Zyxin to focal adhesions, leading to subsequent F-actin reorganization and reduced macrophage migration. Intratumoral STING-TBK1-Zyxin signaling was evident in TAMs and critical in antitumor immunity. Furthermore, myeloid-specific or global disruption of this signaling decreased the population of CD11b+ F4/80+ TAMs and promoted PD-1-mediated antitumor immunotherapy. Thus, our findings identify a new biological function of innate immune sensing pathways by regulating macrophage tissue localization, thus providing insights into context-dependent mitigation of antitumor immunity.

Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by Aß1-42 oligomers.

BACKGROUND: Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aß) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aß plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aß oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. METHODS: Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aß1-42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aß-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aß-treated HEBSCs. RESULTS: Neurotoxicity induced by soluble Aß1-42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aß-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aß neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aß as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aß-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aß-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. CONCLUSION: Microglia are key mediators of both protection and neurodegeneration in response to Aß. Polarizing microglia toward a protective state could be used as a preventative strategy against Aß-induced neurotoxicity.

Knockdown of SMYD3 by RNA Interference Regulates the Expression of Autophagy-Related Proteins and Inhibits Bone Formation in Fluoride-Exposed Osteoblasts.

This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/ß-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/ß-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.

Microglial cGAS-STING signaling underlies glaucoma pathogenesis.

Characterized by progressive degeneration of retinal ganglion cells (RGCs) and vision loss, glaucoma is the primary cause of irreversible blindness, incurable and affecting over 78 million patients. However, pathogenic mechanisms leading to glaucoma-induced RGC loss are incompletely understood. Unexpectedly, we found that cGAS-STING (2'3'-cyclic GMP-AMP-stimulator of interferon genes) signaling, which surveils displaced double-stranded DNA (dsDNA) in the cytosol and initiates innate immune responses, was robustly activated during glaucoma in retinal microglia in distinct murine models. Global or microglial deletion of STING markedly relieved glaucoma symptoms and protected RGC degeneration and vision loss, while mice bearing genetic cGAS-STING supersensitivity aggravated retinal neuroinflammation and RGC loss. Mechanistically, dsDNA from tissue injury activated microglial cGAS-STING signaling, causing deleterious macroglia reactivity in retinas by cytokine-mediated microglia-macroglia interactions, progressively driving apoptotic death of RGCs. Remarkably, preclinical investigations of targeting cGAS-STING signaling by intraocular injection of TBK1i or anti-IFNAR1 antibody prevented glaucoma-induced losses of RGCs and vision. Therefore, we unravel an essential role of cGAS-STING signaling underlying glaucoma pathogenesis and suggest promising therapeutic strategies for treating this devastating disease.

Immune Infiltration Correlates with Transcriptomic Subtypes in Primary ER+ Invasive Lobular Breast Cancer.

Understanding interplay of breast cancer and microenvironment is critical. Here, we identified two transcriptomic subtypes and five immune infiltration patterns from RNA-seq and multiplex immunohistochemistry from 21 ER+/HER2- invasive lobular breast cancers. The proliferative subtype associated with increased immune infiltration especially by immunosuppressive regulatory T-cells and macrophages. We also defined a TAM-Low signature, which associated with lower infiltration of proliferative, pro-inflammatory TAM, and improved outcome in patients with ER+ tumors.

Scaling of development indicators in countries and its origin.

Population-normalized indicators (e.g., GDP per capita), under the assumption of the indicators scaling linearly with population, are ubiquitously used in national development performance comparison. This assumption, however, is not valid because it may ignore agglomeration effect resulting from nonlinear interactions in socioeconomic systems. Here, we present extensive empirical evidence showing the sub-linear scaling rather than the presumed linear scaling between population and multiple indicators of national development performance. We then develop a theoretical framework based on the scaling rule observed in cities to explore the origin of scaling in countries. Finally, we demonstrate that urbanization plays a pivotal role in transforming national development from limited sub-linear growth to unlimited super-linear growth. This underscores the significance of urbanization in achieving sustained growth and elevating human living standards at the national level. Our findings have the potential to inform policies aimed at promoting equitable inter-country comparison and achieving sustainable development in countries.

Simultaneous Extraction of Bone Marrow RNA and DNA from Patients with Hematologic Diseases Using a Combined Magnetic Bead Method within 1 Hour.

BACKGROUND: TRIzolTM is widely used for RNA and DNA extraction. However, this method is laborious and time-consuming. The objective of this study was to validate a time-effective and labor-saving protocol. METHODS: The TRIzol method was used to separate the aqueous phase, protein, and phenol layer of bone marrow samples from 12 patients with hematological diseases. Subsequently, RNA and DNA were extracted from the aqueous layer containing RNA and phenol layer containing DNA, respectively, using magnetic bead extraction kits. The quantity and purity of extracted RNA and DNA were examined using a NanoDrop spectrophotometer. Quantitative fluorescence PCR amplification of the ABL1 gene was performed to verify the effectiveness of the extracted RNA and DNA for downstream experiments. RNA and DNA from another 16 bone marrow samples were extracted to compare the performance of the two methods. RESULTS: Co-extraction of RNA and DNA was completed within 1 h. The data showed that RNA and DNA yield ranged from 13.1 to 204.5 ng/µL and 33.1 to 228.8 ng/µL, respectively. The A260/A280 ratios of RNA and DNA samples ranged from 1.82 to 2.01 and 1.73 to 1.91, respectively. RNA and DNA extracted using this scheme exhibited ideal performance in quantitative fluorescence PCR. The present protocol showed better quality and effectiveness in extracting RNA and DNA compared to the TRIzol method. CONCLUSIONS: This protocol for RNA and DNA co-extraction is fast, labor-saving, and high throughput. It can be adopted for routine molecular biology analyses, particularly for non-reproducible specimens.

Distribution, community structure and assembly patterns of phytoplankton in the northern South China Sea.

A cruise was conducted in the summer of 2023 from the Pearl River Estuary (PRE) to the adjacent waters of the Xisha Islands in the northern South China Sea (NSCS) to investigate the distribution, community structure, and assembly patterns of eukaryotic and prokaryotic phytoplankton using high-throughput sequencing (HTS) and microscopic observation. Dinophyta were the most abundant phylum in the eukaryotic phytoplankton community based on HTS, accounting for 92.17% of the total amplicon sequence variants (ASVs). Syndiniales was the most abundant order among eukaryotic phytoplankton, whereas Prochlorococcus was the most abundant genus within cyanobacteria. The alpha diversity showed the lowest values in the PRE area and decreased gradually with depth, while cyanobacteria exhibited higher alpha diversity indices in the PRE and at depths ranging from 75 m to 750 m. The morphological results were different from the data based on HTS. Diatoms (37 species) dominated the phytoplankton community, with an average abundance of 3.01 × 104 cells L-1, but only six species of dinoflagellate were observed. Spearman correlation analysis and redundancy analysis (RDA) showed that the distribution and community structure of phytoplankton were largely influenced by geographical location and environmental parameters in the NSCS. The neutral community model (NCM) and null model indicated that deterministic processes played a significant role in the assembly of eukaryotic phytoplankton, with heterogeneous selection and homogeneous selection accounting for 47.27 and 29.95%, respectively. However, stochastic processes (over 60%) dominated the assembly of cyanobacteria and undominated processes accounted for 63.44%. In summary, the formation of eukaryotic phytoplankton was mainly influenced by environmental factors and geographic location, but the assembly of cyanobacteria was shaped by both stochastic processes, which accounted for over 60%, and environmental selection in the NSCS.

[Effects of Extreme Environments on Human Sleep]. / æžç«¯çŽ¯å¢ƒå¯¹äººç±»ç¡çœ çš„å½±å“.

Recently, with the rapid growth of the global population and the exhaustion of resources, exploration activities in extreme environments such as the polar regions, the outer space, the deep sea, the deep underground and highlands are becoming increasingly more frequent. This in-depth exploration of the external environment and the consequent dramatic changes in lifestyles impact on sleep, a basic life activity of humans, in ways that cannot be overlooked. the basic life activity of human beings. Sleep, a basic life activity and the result of the evolution of organisms to adapt to their environment, is closely associated with sleep homeostasis and endogenous rhythms. However, external environmental changes and lifestyle shifts in extreme environments have had a significant impact on the patterns and the quality of sleep in humans. Furthermore, this impact can lead to many physiological and psychological problems, posing a great threat to human health. In this review, we delved into the specific effects of different extreme natural environments and enclosed environments on sleep, elaborating on how these environments alter the patterns and the quality of sleep in humans. In addition, we summarized the changes in human sleep under extreme environments to help gain a better understanding of the mechanisms by which these specific environments impact human sleep. It is expected that this review will provide a solid theoretical foundation for optimizing long-term survival strategies in extreme environments and help humans adapt to and overcome the challenges posed by extreme environments more effectively.

Induced Manipulation of Atomically Dispersed Cobalt through S Vacancy for Photocatalytic Water Splitting: Asymmetric Coordination and Dynamic Evolution.

It is still a challenge to construct single-atom level reduction and oxidation sites in single-component photocatalyst by manipulating coordination configuration for photocatalytic water splitting. Herein, the atomically dispersed asymmetric configuration of six-coordinated Co-S2O4 (two exposed S atoms, two OH groups, and two Co─O─Zn bonds) suspending on ZnIn2S4 nanosheets verified by combining experimental analysis with theoretical calculation, is applied into photocatalytic water splitting. The Co-S2O4 site immobilized by Vs acts as oxidation sites to guide electrons transferring to neighboring independent S atom, achieving efficient separation of reduction and oxidation sites. It is worth mentioning that stabilized Co-S2O4 configuration show dynamic structure evolution to highly active Co-S1O4 configuration (one exposed S atom, one OH group, and three Co─O─Zn bonds) in reaction, which lowers energy barrier of transition state for H2O activization. Ultimately, the optimized photocatalyst exhibits excellent photocatalytic activity for water splitting (H2: 80.13 µmol g-1 h-1, O2: 37.81 µmol g-1 h-1) and outstanding stability than that of multicomponent photocatalysts due to dynamic and reversible evolution between stable Co-S2O4 configuration and active Co-S1O4 configuration. This work demonstrates new cognitions on immobilized strategy through vacancy inducing, manipulating coordination configuration, and dynamic evolution mechanism of single-atom level catalytic site in photocatalytic water splitting.

Electronic Health Record-Based Nudge Intervention and Axillary Surgery in Older Women With Breast Cancer: A Nonrandomized Controlled Trial.

Importance: Choosing Wisely recommendations advocate against routine use of axillary staging in older women with early-stage, clinically node-negative (cN0), hormone receptor-positive (HR+), and HER2-negative breast cancer. However, rates of sentinel lymph node biopsy (SLNB) in this population remain persistently high. Objective: To evaluate whether an electronic health record (EHR)-based nudge intervention targeting surgeons in their first outpatient visit with patients meeting Choosing Wisely criteria decreases rates of SLNB. Design, Setting, and Participants: This nonrandomized controlled trial was a hybrid type 1 effectiveness-implementation study with subsequent postintervention semistructured interviews and lasted from October 2021 to October 2023. Data came from EHRs at 8 outpatient clinics within an integrated health care system; participants included 7 breast surgical oncologists. Data were collected for female patients meeting Choosing Wisely criteria for omission of SLNB (aged ≥70 years with cT1 and cT2, cN0, HR+/HER2- breast cancer). The study included a 12-month preintervention control period; baseline surveys assessing perceived acceptability, appropriateness, and feasibility of the designed intervention; and a 12-month intervention period. Intervention: A column nudge was embedded into the surgeon's schedule in the EHR identifying patients meeting Choosing Wisely criteria for potential SLNB omission. Main Outcomes and Measures: The primary outcome was rate of SLNB following nudge deployment into the EHR. Results: Similar baseline demographic and tumor characteristics were observed before (control period, n = 194) and after (intervention period, n = 193) nudge deployment. Patients in both the control and intervention period had a median (IQR) age of 75 (72-79) years. Compared with the control period, unadjusted rates of SLNB decreased by 23.1 percentage points (46.9% SLNB rate prenudge to 23.8% after; 95% CI, -32.9 to -13.8) in the intervention period. An interrupted time series model showed a reduction in the rate of SLNB following nudge deployment (adjusted odds ratio, 0.26; 95% CI, 0.07 to 0.90; P = .03). The participating surgeons scored the intervention highly on acceptability, appropriateness, and feasibility. Dominant themes from semistructured interviews indicated that the intervention helped remind the surgeons of potential Choosing Wisely applicability without the need for additional clicks or actions on the day of the patient visit, which facilitated use. Conclusions and Relevance: This study showed that a nudge intervention in the EHR significantly decreased low-value axillary surgery in older women with early-stage, cN0, HR+/HER2- breast cancer. This user-friendly and easily implementable EHR-based intervention could be a beneficial approach for decreasing low-value care in other practice settings or patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT06006910.

HaMADS3, HaMADS7, and HaMADS8 are involved in petal prolongation and floret symmetry establishment in sunflower (Helianthus annuus L.).

The development of floral organs, crucial for the establishment of floral symmetry and morphology in higher plants, is regulated by MADS-box genes. In sunflower, the capitulum is comprised of ray and disc florets with various floral organs. In the sunflower long petal mutant (lpm), the abnormal disc (ray-like) floret possesses prolongated petals and degenerated stamens, resulting in a transformation from zygomorphic to actinomorphic symmetry. In this study, we investigated the effect of MADS-box genes on floral organs, particularly on petals, using WT and lpm plants as materials. Based on our RNA-seq data, 29 MADS-box candidate genes were identified, and their roles on floral organ development, especially in petals, were explored, by analyzing the expression levels in various tissues in WT and lpm plants through RNA-sequencing and qPCR. The results suggested that HaMADS3, HaMADS7, and HaMADS8 could regulate petal development in sunflower. High levels of HaMADS3 that relieved the inhibition of cell proliferation, together with low levels of HaMADS7 and HaMADS8, promoted petal prolongation and maintained the morphology of ray florets. In contrast, low levels of HaMADS3 and high levels of HaMADS7 and HaMADS8 repressed petal extension and maintained the morphology of disc florets. Their coordination may contribute to the differentiation of disc and ray florets in sunflower and maintain the balance between attracting pollinators and producing offspring. Meanwhile, Pearson correlation analysis between petal length and expression levels of MADS-box genes further indicated their involvement in petal prolongation. Additionally, the analysis of cis-acting elements indicated that these three MADS-box genes may regulate petal development and floral symmetry establishment by regulating the expression activity of HaCYC2c. Our findings can provide some new understanding of the molecular regulatory network of petal development and floral morphology formation, as well as the differentiation of disc and ray florets in sunflower.

Different Effects of Strong-Bonded Water with Different Degrees of Substitution of Sodium Sulfobutylether-ß-cyclodextrin on Encapsulation.

The encapsulation of sodium sulfobutylether-ß-cyclodextrin (SBE-ß-CD) is influenced not only by the degree of substitution (DS) but also by the presence of strong-bonded water (SBW). Guests compete with SBW for positions within the cavity of SBE-ß-CD. However, the correlation between DS and SBW was not clear. This study revealed a positive correlation between DS and SBW utilizing Karl Fischer titration. The mechanism may be attributed to molecular polarizability. To explore the impact of SBW inside SBE-ß-CD with different DS on encapsulation, density functional theory was employed. Throughout the release process, an increase in enthalpy is unfavorable, while an increase in entropy favors spontaneous reaction occurrence. For SBE-ß-CD (DS = 2, 3), enthalpy increase is the primary factor, leading to the retention of SBW within the cavities and consequently hindering guest entry. In contrast, for SBE-ß-CD (DS = 4, 7), the situation differs. For SBE10-ß-CD, the influence of SBW is minimal. This study aims to elucidate the relationship between DS and SBW, as well as the effect of SBW inside SBE-ß-CD with different DS on encapsulation. It is crucial for a comprehensive understanding of the factors affecting the encapsulation of SBE-ß-CD, thereby promoting quality control and functional development of SBE-ß-CD.

Correlation Study between Multi-Scale Structure and In Vitro Digestibility of Starch Modified by Temperature Difference.

Physical techniques are widely applied in the food industry due to their positive impact on food quality and the environment. Temperature differences can effectively modify starch, but the resulting changes in starch structure and quality remain unclear. In this study, the corn starch was processed with high temperature, low temperature, and temperature difference (TD), including high temperature before low temperature (H-L) and low temperature before high temperature (L-H). The results showed that high temperature induced the umbilicus to concave inward shape and sharply decreased the amylose content, while low temperature increased the surface micropores and reduced the A-chain. TD reduced the fluorescence intensity and increased the clearness of the growth ring. TD elevated the relative crystallinity (RC), short-range order, A/B1 chains, hydrolysis parameters, and resistant starch (RS), and reduced amylose content, B2/B3 chains, and viscosity. Moreover, the corn starches treated by H-L had lower amylose content and higher RC, 1047/1022, A-chain, and RS than those treated by L-H. Overall, high temperature degraded the amylose and low temperature destroyed the amylopectin. During the TD, H-L can accelerate the starch molecular rearrangement more than the opposite temperature treatment order. These results will help produce novel starches for better food applications.