SIRT1 as a potential therapeutic target in pelvic organ prolapse due to protective effects against oxidative stress and cellular senescence in human uterosacral ligament fibroblasts.

INTRODUCTION: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. METHODS: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. RESULTS: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. CONCLUSIONS: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

M2 Macrophage-Derived Extracellular Vesicles Encapsulated in Hyaluronic Acid Alleviate Osteoarthritis by Modulating Macrophage Polarization.

An imbalance between M1 and M2 macrophage polarization is critical in osteoarthritis (OA) development. We investigated the effect of M2 macrophage-derived extracellular vesicles (M2-EVs) to reprogramme macrophages from the M1 to M2 phenotype for OA treatment. M1 macrophages and mouse OA models were treated with M2-EVs. Proteomic analysis was performed to evaluate macrophage polarization in vitro. The OA models were as follows: destabilization of the medial meniscus (DMM) surgery-induced OA and collagenase-induced OA (CIOA). Hyaluronic acid (HA) was used to deliver M2-EVs. M2-EVs decreased macrophage accumulation, repolarized macrophages from the M1 to M2 phenotype, mitigated synovitis, reduced cartilage degradation, alleviated subchondral bone damage, and improved gait abnormalities in the CIOA and DMM models. Moreover, HA increased the retention time of M2-EVs and enhanced the efficiency of M2-EVs in OA treatment. Furthermore, proteomic analysis demonstrated that M2-EVs exhibited a macrophage reprogramming ability similar to IL-4, and the pathways might be the NOD-like receptor (NLR), TNF, NF-κB, and Toll-like receptor (TLR) signaling pathways. M2-EVs reprogrammed macrophages from the M1 to M2 phenotype, which resulted in beneficial effects on cartilage and attenuation of OA severity. In summary, our study indicated that M2-EV-guided reprogramming of macrophages is a promising treatment strategy for OA.

Margin quality analysis for wedge resection of lung cancer and construction of a predictive model.

Background: Insufficient pulmonary wedge resection margin is associated with malignant positive margins and high local recurrence risk for lung cancer. This study aimed to identify the risk factors of insufficient or guideline discordant resection margin distance and establish a predictive model to preoperatively estimate the risk of discordant margin for individual patient. Methods: Guideline discordant resection margin was defined as ratio of resection margin distance to tumor size less than one. Patients who had pulmonary malignancies and underwent wedge resection between April 2014 and February 2023 were enrolled and stratified by quality of resection margin. Multivariable logistic regression analysis was employed to identify risk factors of guideline discordant margin and a predictive model was developed. Data from March 2023 to January 2024 were collected for internal validation. Results: A total of 530 patients were included. The incidence of guideline discordant wedge resection margin was 37.2%. Longer tumor's max distance to pleura and larger tumor size were variables associated with increased risk and included in the final model. Preoperative localization and right-side surgery were protective variables in the predictive model. A nomogram was built based on the predictive model. The model showed satisfying predictive performance with a concordance index of 0.720 for the predictive model, and 0.761 for internal validation. The goodness-if-fit tests were non-significant for both model development and internal validation data set. Conclusions: The preoperative predictive model and nomogram show good predictive performance to estimate the risk of guideline discordant wedge resection margin. Individualized surgical plans or preoperative nodule localization can be made for high-risk patients.

A study on the treatment effects of Crataegus pinnatifida polysaccharide on non-alcoholic fatty liver in mice by modulating gut microbiota.

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.

Home care needs assessment among caregivers of children and adolescents with osteogenesis imperfecta: a cross-sectional study.

BACKGROUND: Children and adolescents with complex medical issues need home care services; however, few studies have provided insight into the unmet home care needs of the families of patients with osteogenesis imperfecta (OI). In this study, we aimed to assess the home care needs of caregivers of children and adolescents with OI and the associated factors. METHODS: A self-administered questionnaire was administered online to 142 caregivers of patients with OI aged 3-17 years between May and October 2022 from 25 provinces in China. The questionnaire comprised 15 questions on demographic variables and 14 questions on home care needs. Chi-square analysis was used to compare group differences for categorical variables. Multivariate binary logistic regression analysis was conducted to examine predictors of caregivers' home care needs. RESULTS: The study findings indicated that 81.5% of caregivers had high home care needs. The three leading types of home care needs were helping the child carry out physical fitness recovery exercises at home (72.5%), understanding precautions regarding treatment drugs (72.5%), and relieving the child's pain (70.4%). OI patients' poor self-care ability (adjusted odds ratio = 5.9, 95% confidence interval = 1.8-19.0) was related to caregivers' high level of home care needs. CONCLUSIONS: The findings of this study suggest that future scientific research and nursing guidance should focus on OI patients' physical training, medication management, pain relief, fracture prevention, and treatment. In addition, caregivers of patients with poor self-care ability should receive special attention in the development of interventions. This study can help with addressing the unmet home care needs of caregivers of children and adolescents with OI. It is vital to develop a personalized intervention plan based on patients' self-care ability.

Impact of glucocorticoids and rapamycin on autophagy in Candida glabrata-infected macrophages from BALB/c mice.

Objective: In the defense against microorganisms like Candida albicans, macrophages recruit LC3(Microtubule-associated protein 1A/1B-light chain 3) to the periplasm, engaging in the elimination process through the formation of a single-membrane phagosome known as LC3-associated phagocytosis (LAP). Building on this, we propose the hypothesis that glucocorticoids may hinder macrophage phagocytosis of Candida glabrata by suppressing LAP, and rapamycin could potentially reverse this inhibitory effect. Methods: RAW264.7 cells were employed for investigating the immune response to Candida glabrata infection. Various reagents, including dexamethasone, rapamycin, and specific antibodies, were utilized in experimental setups. Assays, such as fluorescence microscopy, flow cytometry, ELISA (Enzyme-Linked Immunosorbent Assay), Western blot, and confocal microscopy, were conducted to assess phagocytosis, cytokine levels, protein expression, viability, and autophagy dynamics. Results: Glucocorticoids significantly inhibited macrophage autophagy, impairing the cells' ability to combat Candida glabrata. Conversely, rapamycin exhibited a dual role, initially inhibiting and subsequently promoting phagocytosis of Candida glabrata by macrophages. Glucocorticoids hinder macrophage autophagy in Candida glabrata infection by suppressing the MTOR pathway(mammalian target of rapamycin pathway), while the activation of MTOR pathway by Candida glabrata diminishes over time. Conclusion: Our study elucidates the intricate interplay between glucocorticoids, rapamycin, and macrophage autophagy during Candida glabrata infection. Understanding the implications of these interactions not only sheds light on the host immune response dynamics but also unveils potential therapeutic avenues for managing fungal infections.

Structure-function coupling and hierarchy-specific antidepressant response in major depressive disorder.

BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.

Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid by reducing death risks from noncancer causes: A competing risk analysis of 4641 patients.

BACKGROUND: Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite. METHODS: 4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. RESULTS: Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%). CONCLUSIONS: RAI therapy can improve survival in OCA by reducing noncancer death risks.

Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum.

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

Advances in magnetoelectric composites for promoting bone regeneration: a review.

Repair of large bone defects is one of the clinical problems that have not yet been fully solved. The dynamic balance of bone tissue is regulated by many biological, chemical and physical environmental factors. Simulating the microenvironment of bone tissue in the physiological state through biomimetic materials is an important development direction of tissue engineering in recent years. With the deepening of research, it has been found that when bone tissue is damaged, its surrounding magnetoelectric microenvironment is subsequently destroyed, and providing a magnetoelectric microenvironment in the biomimetic state will be beneficial to promote bone repair. This review describes the piezoelectric effect of natural bone tissue with magnetoelectric stimulation for bone regeneration, provides a detailed account of the historical development of magnetoelectric composites and the current magnetoelectric composites that are most commonly utilized in the field of tissue engineering. Besides, the hypothesized mechanistic pathways through which magnetoelectric composite materials promote bone regeneration are critically examined, including the enhancement of osteogenesis, promotion of cell adhesion and angiogenesis, modulation of bone immunity, and promotion of nerve regeneration.

A socioemotional network perspective on momentary experiences of family conflict in young adults.

Family conflict is an established predictor of psychopathology in youth. Traditional approaches focus on between-family differences in conflict. Daily fluctuations in conflict within families might also impact psychopathology, but more research is needed to understand how and why. Using 21 days of daily diary data and 6-times a day experience-sampling data (N = 77 participants; mean age = 21.18, SD = 1.75; 63 women, 14 men), we captured day-to-day and within-day fluctuations in family conflict, anger, anxiety, and sadness. Using multilevel models, we find that days of higher-than-usual anger are also days of higher-than-usual family conflict. Examining associations between family conflict and emotions within days, we find that moments of higher-than-usual anger predict higher-than-usual family conflict later in the day. We observe substantial between-family differences in these patterns with implications for psychopathology; youth showing the substantial interplay between family conflict and emotions across time had a more perseverative family conflict and greater trait anxiety. Overall, findings indicate the importance of increases in youth anger for experiences of family conflict during young adulthood and demonstrate how intensive repeated measures coupled with network analytic approaches can capture long-theorized notions of reciprocal processes in daily family life.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Assessment of paclitaxel drug-coated balloon angioplasty for intracranial atherosclerotic disease based on high-resolution vessel wall magnetic resonance imaging.

BACKGROUND: To accurately assess the treatment effect of paclitaxel drug-coated balloon (DCB) angioplasty is essential for intracranial atherosclerotic disease (ICAD) patients. This study aimed to investigate the clinical feasibility of high-resolution vessel wall MRI (HR-VWI) in assessing ICAD with DCB angioplasty. METHODS: Forty-five patients with intracranial atherosclerotic stenosis ≥ 70% confirmed by digital subtraction angiography (DSA) underwent HR-VWI before and after DCB angioplasty. Postoperative follow-up was performed after 6 months (±1 month). The differences of pre- and postoperative HR-VWI characteristics, including vessel and lumen area at maximal lumen narrowing (MLN), plaque area and length, degree of stenosis, plaque burden (PB), remodeling index, and plaque enhancement amplitude (PEA) were compared. The relationship between stenotic rate obtained using HR-VWI and DSA was evaluated. Each HR-VWI characteristic and clinical factor before DCB angioplasty was separately evaluated for the association with postoperative restenosis. RESULTS: After six months, lumen area of MLN, plaque length and area, degree of stenosis, PB, and PEA showed a significantly difference relative to the value before DCB angioplasty (all P < 0.05). Spearman correlation coefficients of 0.865 and 0.932 were revealed between DSA and HR-VWI regarding the stenotic rate analysis pre- and post-operation (both P < 0.05). ROC analysis showed PEA, plaque length, and PB before DCB angioplasty separately provided robust prediction of postoperative restenosis (area under the curve = 0.909, 0.814 and 0.743; all P < 0.05). Multivariable analysis revealed that PEA was an independent predictor of prognosis. CONCLUSIONS: The HR-VWI can accurately assess the treatment effect of DCB and robustly predict prognosis.

Association between triglyceride-glucose index and endothelial dysfunction.

BACKGROUND: Triglyceride-glucose (TyG) index, a simple surrogate marker for insulin resistance (IR), has been reported as an independent predictor of arterial structural damage and future cardiovascular events. The association between TyG index and endothelial dysfunction remains uncertain. OBJECTIVE: The purpose of this study was to investigate the association between TyG index and endothelial dysfunction. METHODS: Endothelial dysfunction was measured using flow-mediated dilation (FMD). A total of 840 subjects, who voluntarily accepted FMD measurement at the Health Management Department of Xuanwu Hospital from October 2016 to January 2020, were included in this study. TyG index was calculated as Ln [fasting triglyceride (TG)(mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: The mean age was 59.92 ± 10.28 years and 559 (66.55%) participants were male. The TyG index was correlated with FMD values (P = 0.022). Each unit increment in TyG index was associated with lower FMD values (ß = -0.330, 95%CI -0.609 to -0.052, P = 0.020) after adjusting for covariates. Age (ß = -0.069, 95%CI -0.088 to -0.051, P < 0.001), female (ß = 0.592, 95%CI 0.172 to1.012, P = 0.006), smoking (ß = -0.430, 95%CI -0.859 to -0.002, P = 0.049) and hypertension (ß = -0.741, 95%CI -1.117 to -0.365, P < 0.001) were also independent predictors for endothelial dysfunction. A significant association between the TyG index and endothelial dysfunction was found only in populations younger than 60 years (ß = -0.843, 95%CI -1.371 to -0.316, P = 0.002), females (ß = -0.612, 95%CI -1.147 to -0.077, P = 0.025), and populations without diabetes mellitus (DM) (ß = -0.594, 95%CI -1.042 to -0.147, P = 0.009). CONCLUSIONS: Subjects with an elevated TyG index are more likely to have endothelial dysfunction, particularly in populations without DM.

Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis in Mice.

BACKGROUND: Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism. METHODS: In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis. We also generated Glp1r-/- mice to detect whether GLP-1R is required for angiogenic function of GLP-1(32-36). In in vitro experiments, EPCs isolated from the mouse bone marrow and human umbilical cord blood samples were used to detect GLP-1(32-36)-mediated angiogenic capability under high glucose treatment. RESULTS: We demonstrated that GLP-1(32-36) did not affect insulin secretion but could significantly rescue angiogenic function and blood perfusion in ischemic limb of streptozocin-induced T1DM mice, a function similar to its parental GLP-1. We also found that GLP-1(32-36) promotes angiogenesis in EPCs exposed to high glucose. Specifically, GLP-1(32-36) has a causal role in improving fragile mitochondrial function and metabolism via the GLP-1R-mediated pathway. We further demonstrated that GLP-1(32-36) rescued diabetic ischemic lower limbs by activating the GLP-1R-dependent eNOS (endothelial NO synthase)/cGMP/PKG (protein kinase G) pathway. CONCLUSIONS: Our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming toward glycolytic flux in partnership with GLP-1R for improved angiogenesis in high glucose-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral artery disease. REGISTRATION: URL: www.ebi.ac.uk/metabolights/; Unique identifier: MTBLS9543.

Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation.

Background: The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis. Method: A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Results: Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors. Conclusion: The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

Combination of DCE-MRI and NME-DWI via Deep Neural Network for Predicting Breast Cancer Molecular Subtypes.

BACKGROUND: To explore whether the combination of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and nonmono-exponential (NME) model-based diffusion-weighted imaging (DWI) via deep neural network (DNN) can improve the prediction of breast cancer molecular subtypes compared to either imaging technique used alone. PATIENTS AND METHODS: This prospective study examined 480 breast cancers in 475 patients undergoing DCE-MRI and NME-DWI at 3.0 T. Breast cancers were classified as follows: human epidermal growth factor receptor 2 enriched (HER2-enriched), luminal A, luminal B (HER2-), luminal B (HER2+), and triple-negative subtypes. A total of 20% cases were withheld as an independent test dataset, and the remaining cases were used to train DNN with an 80% to 20% training-validation split and 5-fold cross-validation. The diagnostic accuracies of DNN in 5-way subtype classification between the DCE-MRI, NME-DWI, and their combined multiparametric-MRI datasets were compared using analysis of variance with least significant difference posthoc test. Areas under the receiver-operating characteristic curves were calculated to assess the performances of DNN in binary subtype classification between the 3 datasets. RESULTS: The 5-way classification accuracies of DNN on both DCE-MRI (0.71) and NME-DWI (0.64) were significantly lower (P < .05) than on multiparametric-MRI (0.76), while on DCE-MRI was significantly higher (P < .05) than on NME-DWI. The comparative results of binary classification between the 3 datasets were consistent with the 5-way classification. CONCLUSION: The combination of DCE-MRI and NME-DWI via DNN achieved a significant improvement in breast cancer molecular subtype prediction compared to either imaging technique used alone. Additionally, DCE-MRI outperformed NME-DWI in differentiating subtypes.

Soil amendments reduce CH4 and CO2 but increase N2O and NH3 emissions in saline-alkali paddy fields.

Limited research has been conducted on ammonia (NH3) volatilization and greenhouse gases (GHGs) emissions in saline-alkali paddy fields, along with complex interaction involving various genes (16sRNA, amoA, narG, nirK, nosZ, and nifH). This study employed mesocosm-scale experiment to investigate NH3 volatilization and GHGs emissions, focusing on bacterial communities and genic abundance, in saline-alkali paddy fields with desulfurized gypsum (DG) and organic fertilizer (OF) amendments. Compared to the control (CK) treatment, DG and OF treatments reduced methane (CH4) and carbon dioxide (CO2) emissions by 78.05 % and 26.18 %, and 65.84 % and 11.62 %, respectively. However, these treatments increased NH3 volatilization by 26.26 % and 45.23 %, and nitrous oxide (N2O) emission by 41.00 % and 12.31 %. Notably, NH3 volatilization primarily stemmed from ammonia nitrogen (NH4+-N), rather than total nitrogen (TN) in soil and water. N2O was mainly produced from nitrate nitrogen (NO3--N) in soil and water, as well as NH4+-N in water. The increase in NH3 volatilization and N2O emission in DG and OF treatments, was attributed to the reduced competition among bacterial communities, rather than the increased bacterial activity and genic copies. These findings offer valuable insights for managing nutrient loss and gaseous emissions in saline-alkali paddy fields.

Electrochemical Nickel-Catalyzed Hydrogenation.

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal-catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal-hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well-established HER. Using an inexpensive and bench-stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large-scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre-coordination of the substrate to the nickel center.

Casein-based hydrogels: Advances and prospects.

Casein-based hydrogels (Casein Gels) possess advantageous properties, including mechanical strength, stability, biocompatibility, and even adhesion, conductivity, sensing capabilities, as well as controlled-releasing behavior of drugs. These features are attributed to their gelation methods and functionalization with various polymers. Casein Gels is an important protein-based material in the food industry, in terms of dairy and functional foods, biological and medicine, in terms of carrier for bioactive and sensitive drugs, wound healing, and flexible sensors and wearable devices. Herein, this review aims to highlight the importance of the features mentioned above via a comprehensive investigation of Casein Gels through multiple directions and dimensional applications. Firstly, the composition, structure, and properties of casein, along with the gelation methods employed to create Casein Gels are elaborated, which serves as a foundation for further exploration. Then, the application progresses of Casein Gels in dairy products, functional foods, medicine, flexible sensors and wearable devices, are thoroughly discussed to provide insights into the diverse fields where Casein Gels have shown promise and utility. Lastly, the existing challenges and future research trends are highlighted from an interdisciplinary perspective. We present the latest research advances of Casein Gels and provide references for the development of multifunctional biomass-based hydrogels.