Predictive modeling of rice milling degree for three typical Chinese rice varieties using interpretative machine learning methods.

Brown rice over-milling causes high economic and nutrient loss. The rice degree of milling (DOM) detection and prediction remain a challenge for moderate processing. In this study, a self-established grain image acquisition platform was built. Degree of bran layer remaining (DOR) datasets is established with image capturing and processing (grain color, texture, and shape features extraction). The mapping relationship between DOR and the DOM is in-depth analyzed. Rice grain DOR typical machine learning and deep learning prediction models are established. The results indicate that the optimized Catboost model can be established with cross-validation and grid search method, with the best accuracy improving from 84.28% to 91.24%, achieving precision 91.31%, recall 90.89%, and F1-score 91.07%. Shapley additive explanations analysis indicates that color, texture, and shape feature affect Catboost prediction accuracy, the feature importance: color > texture > shape. The YCbCr-Cb_ske and GLCM-Contrast features make the most significant contribution to rice milling quality prediction. The feature importance provides theoretical and practical guidance for grain DOM prediction model. PRACTICAL APPLICATION: Rice milling degree prediction and detection are valuable for rice milling process in practical application. In this paper, image processing and machine learning methods provide an automated, nondestructive, and cost-effective way to predict the quality of rice. The study may serve as a valuable reference for improving rice milling methods, retaining rice nutrition, and reducing broken rice yield.

Evolution and prognostic significance of HER-2 conversion from primary to residual disease in HER-2 negative patients with breast cancer after neoadjuvant chemotherapy.

This study aimed to analyze HER-2 zero or HER-2 low conversion in HER-2 negative patients after neoadjuvant chemotherapy (NAC) and evaluate its prognostic significance. HER-2 negative patients with breast cancer with residual disease after NAC and paired pre- and post-therapeutic HER-2 testing results were analyzed retrospectively. HER-2 low, defined as immunohistochemistry (IHC) scores of 1+ or 2+/in situ hybridization (ISH), were not amplified. HER-2 zero is defined as an IHC score of 0. A total of 571 patients were enrolled, including primary HER-2 zero (n=201, 35.2%) and HER-2 low (n=370, 64.8%). The overall HER-2 change rate was 32.4%. Multivariable logistic regression showed that patients with hormone receptor-positive status before NAC was significantly associated with the conversion of HER-2 zero to low (OR=3.436, P < 0.0001). The median follow-up time was 50.0 months. In patients who are primary HER-2 zero, HER-2 zero to low was significantly associated with better disease-free survival (DFS) than constant HER-2 zero (HR=0.49, P=0.01) after adjustment (4-year DFS 80.1% vs 55.7%, Log-rank P=0.033). Subgroup analysis revealed that among patients who are primary HER-2 zero with hormone receptor-positive, HER-2 zero to low had a significantly better DFS than constant HER-2 zero (Log-rank P=0.037). In contrast, patients with hormone receptor-negative status did not. In conclusion, almost one-third of patients who are HER-2 negative underwent HER-2 zero or HER-2 low conversion after NAC. HER-2 zero to low conversion was associated with better DFS in patients who are HER-2 zero. These results provide a valuable reference for the potential application of anti-HER-2 ADC in an adjuvant setting for patients with residual disease after NAC.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.

Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated ß-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H2O2. Overall, a novel SlipChip-SERS system is developed for single-cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing-related diseases.

Major pathologic response and long-term clinical benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: The majority of HR+/HER2-breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2-breast cancer after neoadjuvant chemotherapy. METHODS: We analyzed HR+/HER2-breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3-5 and positive lymph node ratio of ≤10 %, was used as a pathological evaluation indicator. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. RESULTS: From January 2010 to December 2020, 386 patients were included in the final analysis. 28 patients (7.3 %) achieved pCR and 118 patients (30.6 %) achieved MPR. The median duration of follow-up was 54.4 months,5-year EFS was 87 % in the MPR group vs. 68 % in the non-MPR group. Multivariate analysis showed that low PR expression, high clinical stage, lower Miller-Payne grades and Positive lymph node ratio were independent poor prognostic factors for EFS (all P values < 0.05). The prognostic effect of MPR remained in multivariable models (hazard ratio (HR), 0.45; 95 % confidence interval (CI), 0.26-0.76; P = 0.008), In non-pCR patients, those who achieved MPR exhibited a similar EFS compared with pCR patients (HR, 2.25; 95 % CI, 0.51-9.84; P = 0.28). CONCLUSION: MPR may be a novel pathologic end point in HR+/HER2-breast cancer after neoadjuvant chemotherapy, holding greater applicability in the prognosis evaluation than pCR.

Dynamic changes of respiratory microbiota associated with treatment outcome in drug-sensitive and drug-resistant pulmonary tuberculosis.

BACKGROUND: Respiratory microbiota is closely related to tuberculosis (TB) initiation and progression. However, the dynamic changes of respiratory microbiota during treatment and its association with TB progression remains unclear. METHODS: A total of 16 healthy individuals and 16 TB patients (10 drug-sensitive TB (DS-TB) and 6 drug-resistant TB (DR-TB)) were recruited. Sputum samples were collected at baseline for all anticipants and after anti-TB treatment at Month-6 for TB patients. High throughput 16 S RNA sequencing was used to characterize the respiratory microbiota composition. RESULTS: Compared to the healthy individuals, TB patients exhibited lower respiratory microbiota diversity (p < 0.05). This disruption was alleviated after anti-TB treatment, especially for DS-TB patients. Parvimonas spp. numbers significantly increased after six months of anti-TB treatment in both DS-TB and DR-TB patients (p < 0.05). Rothia spp. increase during treatment was associated with longer sputum-culture conversion time and worse pulmonary lesion absorption (p < 0.05). Besides, Moraxella spp. prevalence was associated with longer sputum-culture conversion time, while Gemella spp. increase was associated with worsening resolving of pulmonary lesions (p < 0.05). CONCLUSION: Dynamic changes of respiratory microbiota during anti-TB treatment is closely related to TB progression. The involvement of critical microorganisms, such as Parvimonas spp., Rothia spp., Moraxella, and Gemella spp., appears to be associated with pulmonary inflammatory conditions, particularly among DR-TB. These microorganisms could potentially serve as biomarkers or even as targets for therapeutic intervention to enhance the prognosis of tuberculosis patients.

Fabrication of 3D Biomimetic Smooth Muscle Using Magnetic Induction and Bioprinting for Tissue Regeneration.

Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe3O4) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe3O4 self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.

Molecular Design of Hole Transport Materials to Immobilize Ion Motion for Photostable Perovskite Solar Cells.

Poor operational stability is a crucial factor limiting the further application of perovskite solar cells (PSCs). Organic semiconductor layers can be a powerful means for reinforcing interfaces and inhibiting ion migration. Herein, two hole-transporting molecules, pDPA-SFX and mDPA-SFX, are synthesized with tuned substituent connection sites. The meta-substituted mDPA-SFX results in a larger dipole moment, more ordered packing, and better charge mobility than pDPA-SFX, accompany with strong interface bonding on perovskite surfaces and suppressed ion motion as well. Importantly, mDPA-SFX-based PSCs exhibit an efficiency that has significantly increased from 22.5% to 24.8% and a module-based efficiency of 19.26% with an active area of 12.95 cm2. The corresponding cell retain 94.8% of its initial efficiency at maximum power point tracking (MPPT) after 1,000 h (T95 = 1,000 h). The MPPT T80 lifetime is as long as 2,238 h. This work illustrates that a small degree of structural variation in organic compounds leaves considerable room for developing new HTMs for light stable PSCs.

atRA Attenuates High Salt-Driven EAE Mainly Through Suppressing Th17-Like Regulatory T Cell Response Mediated by the Inhibition of IL-23R Signaling Pathway.

High salt diet (HSD) is implicated in numerous disorders, which boosts Th17 cell development and weakens immunosuppressive function of regulatory T cells (Treg cells) Treg cells, leading to the exacerbation of EAE. However, little is known regarding the harness of excessive proinflammatory responses evoked by HSD. Here we show that atRA, a key vitamin A metabolite with multifaceted immunoregulatory properties has the potential in inhibiting the proinflammatory reaction of high salt. Treatment with atRA in vivo elicited the Treg generation in cervical and axillary lymph nodes (CALs), and in CNS of experimental autoimmune encephalomyelitis (EAE). Meanwhile, the proportion of Th17-like Treg cells (RORγt-positive or GM-CSF-positive Treg cells) decreased in CALs. atRA also inhibited IL-17A expression in CD4+ effector T cells. In-vitro mechanistic studies showed that atRA inhibit IL-23R but not SGK1 expression in Treg cells and this results in maintained immunosuppressive function of Treg cells even in the presence of IL-6 and high salt. Furthermore, treatment of EAE with anti-IL-23R mAb attenuated HSD-provoked EAE progress. This was associated with a reduction in the number of CNS-infiltrating Th17 cells and an increase of CAL-Treg cells. Mechanically, treatment with atRA significantly promoted LP-CD103+CD11c+ dendritic cells, a subgroup of cells most closely involved in endogenous retinoic acid metabolism, and enhanced intestinal Aldh1a1 and Rdh10 expression from HSD-fed EAE mice. Interestingly, anti-IL-23R mAb administration also reduced IL-23R expression in Treg cells, along with the increased proportion of LP-CD103+CD11c+ dendritic cells and Rdh10 mRNA expression. In conclusion, administration of atRA might be a way to combat the proinflammatory effects of HSD. Meanwhile, systematic inhibition of IL-23R also had a moderate therapeutic potential in inhibiting inflammatory effects of high salt, which may serve as a basis for the identification of novel therapeutic strategies against HSD-driven autoimmune disorders.

ResNeXt-CC: a novel network based on cross-layer deep-feature fusion for white blood cell classification.

Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5-20.43% accuracy, 3.6-23.56% F1-score, 3.5-25.71% AUROC and 8.1-36.98% specificity, respectively.

Effects of High-Hydrostatic-Pressure Treatment on Polyphenols and Volatile Aromatic Compounds in Marselan Wine.

This study investigated the effects of high-hydrostatic-pressure (HHP) treatment of varying intensity (100-600 MPa) and duration (10-30 min) on polyphenols and volatile aromatic compounds in Marselan red wine. The types and concentrations of polyphenols and volatile aromatic compounds were compared before and after HHP treatment; the results indicated that HHP treatment at 300 MPa for 20 min significantly increased the total polyphenol content to 369.70 mg/L, a rise of 35.82%. The contents of key polyphenols, such as resveratrol and protocatechuic acid, were significantly enhanced. Furthermore, while the total content of volatile aromatic compounds did not change significantly under this condition compared to the untreated samples, the concentration of ester compounds significantly increased to 1.81 times that of the untreated group, thereby enriching the floral and fruity aromas of the wine and effectively improving its aromatic profile and sensory quality. Principal component analysis (PCA) further validated the positive impact of HHP treatment on the flavor characteristics of Marselan red wine. These findings provide technical support for the use of HHP in improving wine quality.

Mediating effect of menopausal symptoms between the lifestyle and depressive symptoms.

PURPOSE: This study aimed to explore relationship between lifestyle and depressive symptoms and evaluated the mediating effect of menopausal symptoms. METHODS: This was a secondary analysis of a survey in Hunan Province, China. We selected 3190 women aged 40 to 55 into final analyses. Menopausal and depressive symptoms were assessed by the Kupperman Menopausal Index and the 9-item Patient Health Questionnaire, respectively. A self-administered questionnaire was used to collect demographic and lifestyle information. RESULTS: The prevalence of depressive symptoms was 19.5%. After adjusting for demographic variables, passive smoking, drinking, and intensity of physical activity were positively associated with depressive symptoms. Frequency of exercise was a protective factor for depressive symptoms (AOR = 0.783, 95%CI: 0.446-0.991). Excess or restricted sleep duration was associated with higher probability of having depressive symptoms (AOR = 1.746, 95% CI: 1.324-2.304). Menopausal symptoms partially mediated the relationship between lifestyle and depressive symptoms. CONCLUSION: Findings highlighted the importance of menopausal symptoms in the relationship between the lifestyle and depressive symptoms, and provided a possibility that active lifestyle might improve depression symptoms among women at perimenopause through changes in sex hormones.

Selective excitation of vibrations in a single molecule.

The capability to excite, probe, and manipulate vibrational modes is essential for understanding and controlling chemical reactions at the molecular level. Recent advancements in tip-enhanced Raman spectroscopies have enabled the probing of vibrational fingerprints in a single molecule with Ångström-scale spatial resolution. However, achieving controllable excitation of specific vibrational modes in individual molecules remains challenging. Here, we demonstrate the selective excitation and probing of vibrational modes in single deprotonated phthalocyanine molecules utilizing resonance Raman spectroscopy in a scanning tunneling microscope. Selective excitation is achieved by finely tuning the excitation wavelength of the laser to be resonant with the vibronic transitions between the molecular ground electronic state and the vibrational levels in the excited electronic state, resulting in the state-selective enhancement of the resonance Raman signal. Our approach contributes to setting the stage for steering chemical transformations in molecules on surfaces by selective excitation of molecular vibrations.

Spontaneous water oozing of a soft drain bed via energy-free atmospheric water harvesting.

Atmospheric water harvesting has emerged as an efficient strategy for addressing the global challenge of freshwater scarcity. However, the in being energy-consuming water-collecting process has obstructed its practicality. In this work, a soft drain bed, which was composed of hydrophilic cloth and hygroscopic gel, has been demonstrated to capture atmospheric water effectively, followed by converting it into liquid water spontaneously and sustainably, under all-weather humidity conditions. Under the optimal working condition of 30°C with a relative humidity level of 75%, the bed can provide a spontaneous water oozing ability of 1.25 g (liquid water)/hour within the 8 h of working time. More importantly, after 5 working cycles, 80% of the oozing ability can be reserved, suggesting the high potential for practical freshwater supply application. The proposed design strategy is expected to provide new hints for the development of future energy-saving decentralized freshwater supply systems.

Supplementation with mulberry leaves improves growth performance and meat quality of Xiangdong black goats.

Objective: Mulberry (Morus alba) leaf (ML) is a high-quality feed source for ruminants, while it is unclear whether it can enhance the growth performance and meat quality of Xiangdong black goats. Methods: In this study, we investigated the effects of ML supplementation (0, 5, 10, 15, and 20%) on the growth performance, serum variables, and the profiles of amino acids and fatty acids in the muscle of Xiangdong black goats. Results: Results showed that the final body weight, initial and final dry matter intake, and average daily gain increased linearly and quadratically with the increasing ML content (P < 0.05). The serum concentrations of total antioxidant capacity (T-AOC) increased linearly, while immunoglobulin G (IgG) increased quadratically with the increasing ML content (P < 0.05). Conversely, the saturated fatty acids (SFA) content in meat decreased linearly with the increasing ML content (P < 0.05). Compared to goats without ML supplementation, goats fed with 15% ML showed significant increases in serum concentrations of T-AOC, superoxide dismutase, catalase, and IgG (P < 0.05). Furthermore, goats fed with 20% ML displayed significant decreases in SFA (C18:0) content, compared to goats without ML supplementation (P < 0.05). Conclusion: These results suggest that ML supplementation promotes the growth performance of goats. A diet containing 15% ML showed better effects in promoting antioxidant and immunomodulatory activities, while a diet with 20% ML was more effective in enhancing meat flavor in Xiangdong black goats.

Utilizing radiomics for differential diagnosis of inverted papilloma and chronic rhinosinusitis with polyps based on unenhanced CT scans.

To evaluate whether radiomics models based on unenhanced paranasal sinuses CT images could be a useful tool for differentiating inverted papilloma (IP) from chronic rhinosinusitis with polyps (CRSwNP). This retrospective study recruited 240 patients with CRSwNP and 106 patients with IP from three centers. 253 patients from Qilu Hospital were randomly divided into the training set (n = 151) and the internal validation set (n = 102) with a ratio of 6:4. 93 patients from the other two centers were used as the external validation set. The patients with the unilateral disease (n = 115) from Qilu Hospital were selected to further develop a subgroup analysis. Lesion segmentation was manually delineated in CT images. Least absolute shrinkage and selection operator algorithm was performed for feature reduction and selection. Decision tree, support vector machine, random forest, and adaptive boosting regressor were employed to establish the differential diagnosis models. 43 radiomic features were selected for modeling. Among the models, RF achieved the best results, with an AUC of 0.998, 0.943, and 0.934 in the training set, the internal validation set, and the external validation set, respectively. In the subgroup analysis, RF achieved an AUC of 0.999 in the training set and 0.963 in the internal validation set. The proposed radiomics models offered a non-invasion and accurate differential approach between IP and CRSwNP and has some significance in guiding clinicians determining the best treatment plans, as well as predicting the prognosis.

Targeting transcription factor pu.1 for improving neurologic outcomes after spinal cord injury.

Background: After spinal cord injury (SCI), lipid metabolism dysregulation at the lesion site exacerbates secondary damage. The transcription factor pu.1 has been implicated as a negative regulator of multiple lipid metabolism-related genes and pathways. However, its role in post-SCI lipid metabolism remains unclear. Methods: We employed a mouse model of complete T10 crush SCI. Non-targeted metabolomics and bioinformatics analysis were utilized to investigate lipid metabolism at the lesion site after SCI. Polarized light imaging was used to evaluate the presence of cholesterol crystals. DB1976, a specific inhibitor of pu.1, was administered to examine its impact on local lipid metabolism after SCI. Immunofluorescence staining was performed to assess pu.1 expression and distribution, and to evaluate lipid droplet formation, astrocytic/fibrotic scar development, inflammatory cell infiltration, and tight junctions within the vasculature. Results: Non-targeted metabolomics and bioinformatics analyses revealed significant alterations in lipid metabolism components after SCI. Moreover, immunofluorescence staining and polarized light imaging demonstrated substantial BODIPY+ lipid droplet accumulation and persistent cholesterol crystal formation at the lesion site after SCI. Increased pu.1 expression was predominantly observed within macrophages/microglia at the lesion site after SCI. DB1976 treatment significantly mitigated lipid droplet accumulation and cholesterol crystal formation, reduced CD68+ macrophage/microglial infiltration, and attenuated fibrotic scar formation. Moreover, DB1976 treatment promoted the expression of claudin-5 and zonula occludens-1 between vascular endothelial cells and enhanced GFAP+ glial connectivity after SCI. Conclusion: Our study reveals a significant correlation between lipid metabolism disturbance post-SCI and transcription factor pu.1 upregulation, specifically in macrophages/microglia at the lesion site. Thus, targeted pu.1 modulation has the potential to yield promising results by substantially diminishing the deposition of lipid metabolism byproducts at the lesion site and fostering a milieu conducive to SCI repair.

Prenatal Fish Oil Supplementation, Maternal COX1 Genotype, and Childhood Atopic Dermatitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Eicosanoids have a pathophysiological role in atopic dermatitis (AD), but it is unknown whether this is affected by prenatal ω-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA; ie, fish oil) supplementation and genetic variations in the cyclooxygenase-1 (COX1) pathway. Objective: To explore the association of n-3 LCPUFA supplementation during pregnancy with risk of childhood AD overall and by maternal COX1 genotype. Design, Setting, and Participants: This prespecified secondary analysis of a randomized clinical trial included mother-child pairs from the Danish Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, with prospective follow-up until children were aged 10 years. In the trial, maternal and child COX1 genotypes were determined, and urinary eicosanoids were quantified when the child was 1 year of age. The present study was conducted from January 2019 to December 2021, and data were analyzed from January to September 2023. Intervention: A total of 736 pregnant women at 24 weeks' gestation were randomized 1:1 to 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day until 1 week post partum. Main Outcomes and Measures: Risk of childhood AD until age 10 years overall and by maternal COX1 genotype. Results: At age 10 years, 635 children (91%; 363 [57%] female) completed the clinical follow-up, and these mother-child pairs were included in this study; 321 (51%) were in the intervention group and 314 (49%) in the control group. Pregnancy n-3 LCPUFA supplementation was associated with lower urinary thromboxane A2 metabolites at age 1 year (ß, -0.46; 95% CI, -0.80 to -0.13; P = .006), which was also associated with COX1 rs1330344 genotype (ß per C allele, 0.47; 95% CI, 0.20-0.73; P = .001). Although neither n-3 LCPUFA supplementation (hazard ratio [HR], 1.00; 95% CI, 0.76-1.33; P = .97) nor maternal COX1 genotype (HR, 0.94; 95% CI, 0.74-1.19; P = .60) was associated with risk of childhood AD until age 10 years, there was evidence of an interaction between these variables (P < .001 for interaction). Among mothers with the TT genotype, risk of AD was reduced in the n-3 LCPUFA group compared with the placebo group (390 mother-child pairs [61%]; HR, 0.70; 95% CI, 0.50-0.98; P = .04); there was no association for mothers with the CT genotype (209 [33%]; HR, 1.29; 95% CI, 0.79-2.10; P = .31), and risk was increased among offspring of mothers with the CC genotype (37 [6%]; HR, 5.77; 95% CI, 1.63-20.47; P = .007). There was a significant interaction between n-3 LCPUFA supplementation and child COX1 genotype and development of AD (P = .002 for interaction). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, the association of prenatal n-3 LCPUFA supplementation with risk of childhood AD varied by maternal COX1 genotype. The findings could be used to inform a personalized prevention strategy of providing supplementation only to pregnant individuals with the TT genotype. Trial Registration: ClinicalTrials.gov: NCT00798226.

Highly sensitive microfluidic sensor using integrated optical fiber and real-time single-cell Raman spectroscopy for diagnosis of pancreatic cancer.

Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

[Study on the Experimental Methodology of Plasma Clot Retraction].

OBJECTIVE: To explore the key factors affecting plasma clot retraction and optimize the experimental method of plasma clot retraction, in order to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction. METHODS: The effects of different concentrations of thrombin, Ca2 + and platelets on plasma clot retraction were studied, and the detection system of plasma clot retraction was optimized. The availability of the detection system was then validated by analyzing the regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction. RESULTS: Through the optimization study of multiple factors, platelet rich plasma (PRP) containing 0.5 mmol/L Ca2 + and 40×109/L platelets was treated with 0.2 U/ml thrombin to perform plasma clot retraction analysis. After treatment with thrombin for 15 min, plasma clot retracted significantly. After treatment with thrombin for 30 min, the percentage of plasma clot retraction was more than 50%. The regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction were studied in this detection system. PKC inhibitor Go 6983 exhibited a significant inhibitory effect on plasma clot retraction, while PI3K inhibitor Ly294002 and p38 MAPK inhibitor SB203580 slightly suppressed plasma clot retraction. CONCLUSION: PRP containing 0.5 mmol/L Ca2 + and 40×109/L platelets can be induced with 0.2 U/ml thrombin to conduct plasma clot retraction analysis, which can be used to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.