Screening for ferroptosis genes related to endometrial carcinoma and predicting of targeted drugs based on bioinformatics.

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

Integrated molybdenum single atom array sensors with multichannels for nitrite detection in foods.

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.

Healthy lifestyles and rapid progression of carotid plaque in population with atherosclerosis: A prospective cohort study in China.

Background: Healthy lifestyles are effective means to reduce major cardiovascular events. However, little is known about the association of healthy lifestyles with development of carotid atherosclerosis at the early stage of cardiovascular diseases (CVDs). Methods: We enrolled participants from Fujian province in the China PEACE MPP project. We calculated a healthy lifestyle score by adherence to non-smoking, sufficient physical activity, healthy diet and healthy body mass index. Cox proportional hazards regression models and restricted cubic splines (RCS) were used to explore the association between the healthy lifestyles and rapid progression of carotid plaque. Results: 8379 participants were included (mean age: 60.6 ± 8.3 years, 54.6 % female), with a median follow-up of 1.2 years (inter quartile range: 1.0-1.6). RCS showed a significant inverse association between the healthy lifestyle score and progression of carotid plaque. Participants with "intermediate" (HR: 0.72 [95 % confidence interval (CI): 0.65-0.80]) or "ideal" (HR: 0.68 [0.59-0.78]) adherence to healthy lifestyles had a lower risk of progression of carotid plaque compared to those with "poor" adherence. Age, sex, occupation, income, residence type and metabolic status were significant factors influencing the relationship. Farmers benefited more in non-smoking and sufficient physical activity compared to non-farmers, and participants with lower income or without dyslipidaemia benefited more in sufficient physical activity and healthy diet compared to their counterparts (p-for-interaction < 0.05). Conclusions: Healthy lifestyles were associated with lower risk of progression of carotid plaque in populations with atherosclerosis. Promotion of healthy lifestyles from the early stage of carotid atherosclerosis could reduce the burden of CVDs in China.

Fully automated deep learning system for osteoporosis screening using chest computed tomography images.

Background: Osteoporosis, a disease stemming from bone metabolism irregularities, affects approximately 200 million people worldwide. Timely detection of osteoporosis is pivotal in grappling with this public health challenge. Deep learning (DL), emerging as a promising methodology in the field of medical imaging, holds considerable potential for the assessment of bone mineral density (BMD). This study aimed to propose an automated DL framework for BMD assessment that integrates localization, segmentation, and ternary classification using various dominant convolutional neural networks (CNNs). Methods: In this retrospective study, a cohort of 2,274 patients underwent chest computed tomography (CT) was enrolled from January 2022 to June 2023 for the development of the integrated DL system. The study unfolded in 2 phases. Initially, 1,025 patients were selected based on specific criteria to develop an automated segmentation model, utilizing 2 VB-Net networks. Subsequently, a distinct cohort of 902 patients was employed for the development and testing of classification models for BMD assessment. Then, 3 distinct DL network architectures, specifically DenseNet, ResNet-18, and ResNet-50, were applied to formulate the 3-classification BMD assessment model. The performance of both phases was evaluated using an independent test set consisting of 347 individuals. Segmentation performance was evaluated using the Dice similarity coefficient; classification performance was appraised using the receiver operating characteristic (ROC) curve. Furthermore, metrics such as the area under the curve (AUC), accuracy, and precision were meticulously calculated. Results: In the first stage, the automatic segmentation model demonstrated excellent segmentation performance, with mean Dice surpassing 0.93 in the independent test set. In the second stage, both the DenseNet and ResNet-18 demonstrated excellent diagnostic performance in detecting bone status. For osteoporosis, and osteopenia, the AUCs were as follows: DenseNet achieved 0.94 [95% confidence interval (CI): 0.91-0.97], and 0.91 (95% CI: 0.87-0.94), respectively; ResNet-18 attained 0.96 (95% CI: 0.92-0.98), and 0.91 (95% CI: 0.87-0.94), respectively. However, the ResNet-50 model exhibited suboptimal diagnostic performance for osteopenia, with an AUC value of only 0.76 (95% CI: 0.69-0.80). Alterations in tube voltage had a more pronounced impact on the performance of the DenseNet. In the independent test set with tube voltage at 100 kVp images, the accuracy and precision of DenseNet decreased on average by approximately 14.29% and 18.82%, respectively, whereas the accuracy and precision of ResNet-18 decreased by about 8.33% and 7.14%, respectively. Conclusions: The state-of-the-art DL framework model offers an effective and efficient approach for opportunistic osteoporosis screening using chest CT, without incurring additional costs or radiation exposure.

A Critical Review of the Effectiveness of Biochar Coupled with Arbuscular Mycorrhizal Fungi in Soil Cadmium Immobilization.

Cadmium-contaminated soil significantly threatens global food security and human health. This scenario gives rise to significant worries regarding widespread environmental pollution. Biochar and arbuscular mycorrhizal fungi (AMF) can effectively immobilize cadmium in the soil in an environmentally friendly way. Existing studies have separately focused on the feasibility of each in remediating polluted soil. However, their association during the remediation of cadmium-polluted soils remains unclear. This review paper aims to elucidate the potential of biochar, in conjunction with AMF, as a strategy to remediate soil contaminated with cadmium. This paper comprehensively analyzes the current understanding of the processes in cadmium immobilization in the soil environment by examining the synergistic interactions between biochar and AMF. Key factors influencing the efficacy of this approach, such as biochar properties, AMF species, and soil conditions, are discussed. The influences of biochar-AMF interactions on plant growth, nutrient uptake, and overall ecosystem health in cadmium-contaminated environments are highlighted. This review indicates that combining biochar and AMF can improve cadmium immobilization. The presence of AMF in the soil can create numerous binding sites on biochar for cadmium ions, effectively immobilizing them in the soil. Insights from this review contribute to a deeper understanding of sustainable and eco-friendly approaches to remediate cadmium-contaminated soils, offering potential applications in agriculture and environmental management.

Development of a multiparametric model for predicting the response to neoadjuvant chemotherapy in breast cancer.

Background: Choosing the appropriate treatment early and predicting the efficacy of neoadjuvant chemotherapy (NAC) for locally advanced breast cancer patients are of particular importance for clinicians. Developing and validating a multiparametric model for predicting NAC would be very meaningful for clinical practice. Methods: This study included 91 patients with locally advanced breast cancer treated from 2016 to 2020. The correlation between multiparametric characteristics and the efficacy of NAC was examined. The data were randomly divided into training and validation sets. A least absolute shrinkage and selection operator (LASSO) regression analysis was used for the variable screening. A multivariable logistic regression analysis was used to construct the model. Calibration and decision curves were used to assess the performance of the established model. Results: Lymph node metastasis, the first standard apparent diffusion coefficient (ADC) at the baseline, the change in the standard ADC at the first follow-up, the change in tumor volume at the first follow-up, and the clinical stage of the tumor at the baseline were selected for inclusion in the model. In the receiver operating characteristic (ROC) analysis, the areas under the curve (AUCs) were 0.984 [95% confidence interval (CI): 0.958-1] and 0.815 (95% CI: 0.509-1) for the primary and validation cohorts, respectively. The utility of the established model was confirmed by calibration and decision curves, and a nomogram was obtained. Conclusions: A multiparametric model based on clinical-pathological-magnetic resonance imaging (MRI) features was established to predict the effect of NAC in patients with locally advanced breast cancer.

Purification, structural characterization, and immunomodulatory activity of two polysaccharides from Portulaca oleracea L.

In present study, two water-soluble polysaccharides designated as POL-1 and POL-2 were purified from purslane and their structural characteristics as well as immunomodulatory activity were investigated. The weight-average molecular weight (Mw) of POL-1 and POL-2 were determined to be 64,100 Da and 21,000 Da, respectively. Comprehensive techniques including UV, IR, GC-MS, and NMR were applied to deduced that POL-1 was a pectin polysaccharide homogalacturonan (HG) consisting of →4)-α-GalpA-(1→ with methyl ester degree of 9.71 % and acetylation degree of 0.34 %, while POL-2 was composed of a 1, 4-linked ß-Galp backbone substituted by short side chain →4)-α-Glcp-(1→ and →6)-α-Glcp-(1→. The →4)-α-Glcp-(1→ was attached at the O-6 position of →4)-ß-Galp-(1→. TEM further revealed that POL-1 was non-branched single chains, while POL-2 was entangled microstructure with side chains. Moreover, POL-2 significantly promoted macrophage phagocytosis as well as the secretion of NO and cytokines (TNF-α, IL-6) through activating NF-κB signaling pathway, thus demonstrating potential immunomodulatory activity. These findings suggested that purslane may be exploited as a potential adjuvant and dietary supplement with immunostimulatory purpose.

MRI combined with clinical features to differentiate ovarian thecoma-fibroma with cystic degeneration from ovary adenofibroma.

OBJECTIVE: To explore the value of magnetic resonance imaging (MRI) and clinical features in identifying ovarian thecoma-fibroma (OTF) with cystic degeneration and ovary adenofibroma (OAF). METHODS: A total of 40 patients with OTF (OTF group) and 28 patients with OAF (OAF group) were included in this retrospective study. Univariable and multivariable analyses were performed on clinical features and MRI between the two groups, and the receiver operating characteristic (ROC) curve was plotted to estimate the optimal threshold and predictive performance. RESULTS: The OTF group had smaller cyst degeneration degree (P < .001), fewer black sponge sign (20% vs. 53.6%, P = .004), lower minimum apparent diffusion coefficient value (ADCmin) (0.986 (0.152) vs. 1.255 (0.370), P < .001), higher age (57.4 ± 14.2 vs. 44.1 ± 15.9, P = .001) and more postmenopausal women (72.5% vs. 28.6%, P < .001) than OAF. The area under the curve of MRI, clinical features and MRI combined with clinical features was 0.870, 0.841, and 0.954, respectively, and MRI combined with clinical features was significantly higher than the other two (P < .05). CONCLUSION: The cyst degeneration degree, black sponge sign, ADCmin, age and menopause were independent factors in identifying OTF with cystic degeneration and OAF. The combination of MRI and clinical features has a good effect on the identification of the two. ADVANCES IN KNOWLEDGE: This is the first time to distinguish OTF with cystic degeneration from OAF by combining MRI and clinical features. It shows the diagnostic performance of MRI, clinical features, and combination of the two. This will facilitate the discriminability and awareness of these two diseases among radiologists and gynaecologists.

Multiple Dimensions of Environmental Justice and Oil and Gas Development in Pennsylvania.

Background: Community socioeconomic deprivation (CSD) may be related to higher oil and natural gas development (OGD) exposure. We tested for distributive and benefit-sharing environmental injustice in Pennsylvania's Marcellus Shale by examining (1) whether OGD and waste disposal occurred disproportionately in more deprived communities and (2) discordance between the location of land leased for OGD and where oil and gas rights owners resided. Materials and Methods: Analyses took place at the county subdivision level and considered OGD wells, waste disposal, and land lease agreement locations from 2005 to 2019. Using 2005-2009 American Community Survey data, we created a CSD index relevant to community vulnerability in suburban/rural areas. Results: In adjusted regression models accounting for spatial dependence, we observed no association between the CSD index and conventional or unconventional drilled well presence. However, a higher CSD index was linearly associated with odds of a subdivision having an OGD waste disposal site and receiving a larger volume of waste. A higher percentage of oil and gas rights owners lived in the same county subdivision as leased land when the community was least versus most deprived (66% vs. 56% in same county subdivision), suggesting that individuals in more deprived communities were less likely to financially benefit from OGD exposure. Discussion and Conclusions: We observed distributive environmental injustice with respect to well waste disposal and benefit-sharing environmental injustice related to oil and rights owner's residential locations across Pennsylvania's Marcellus Shale. These results add evidence of a disparity between exposure and benefits resulting from OGD.

Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging combined with Texture Analysis in Predicting the Histological Grades of Rectal Adenocarcinoma.

PURPOSE: To evaluate the predictive value of 3.0T MRI Intravoxel Incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) combined with texture analysis (TA) in the histological grade of rectal adenocarcinoma. METHODS: Seventy-one patients with rectal adenocarcinoma confirmed by pathology after surgical resection were collected retrospectively. According to pathology, they were divided into a poorly differentiated group (n=23) and a moderately differentiated group (n=48). The IVIM-DWI parameters and TA characteristics of the two groups were compared, and a prediction model was constructed by multivariate logistic regression analysis. ROC curves were plotted for each individual and combined parameter. RESULTS: There were statistically significant differences in D and D* values between the two groups (P < 0.05). The three texture parameters SmallAreaEmphasis, Median, and Maximum had statistically significant differences between groups (P = 0.01, 0.004, 0.009, respectively). The logistic regression prediction model showed that D*, the median, and the maximum value were significant independent predictors, and the AUC of the regression prediction model was 0.860, which was significantly higher than other single parameters. CONCLUSION: 3.0T MRI IVIM-DWI parameters combined with TA can provide valuable information for predicting the histological grades of rectal adenocarcinoma one week before the operation.

Macrophages in the process of osseointegration around the implant and their regulatory strategies.

PURPOSE/AIM OF THE STUDY: To summarize and discuss macrophage properties and their roles and mechanisms in the process of osseointegration in a comprehensive manner, and to provide theoretical support and research direction for future implant surface modification efforts. MATERIALS AND METHODS: Based on relevant high-quality articles, this article reviews the role of macrophages in various stages of osseointegration and methods of implant modification. RESULTS AND CONCLUSIONS: Macrophages not only promote osseointegration through immunomodulation, but also secrete a variety of cytokines, which play a key role in the angiogenic and osteogenic phases of osseointegration. There is no "good" or "bad" difference between the M1 and M2 phenotypes of macrophages, but their timely presence and sequential switching play a crucial role in implant osseointegration. In the implant surface modification strategy, the induction of sequential activation of the M1 and M2 phenotypes of macrophages is a brighter prospect for implant surface modification than inducing the polarization of macrophages to the M1 or M2 phenotypes individually, which is a promising pathway to enhance the effect of osseointegration and increase the success rate of implant surgery.

A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis.

INTRODUCTION: Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3'- and 5'- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. MATERIALS AND METHODS: 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis  predicted binding affinity of circRNA/miRNA/mRNA axis. RESULTS: After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. CONCLUSION: We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.

The Effects of Abdominal Obesity and Sagittal Imbalance on Sacroiliac Joint Pain After Lumbar Fusion.

BACKGROUND: Postoperative sacroiliac joint pain (SIJP) is a common manifestation of failed back surgery syndrome after a posterior lumbar interbody fusion (PLIF). However, there is currently no consensus on the risk factors for SIJP after PLIF. OBJECTIVES: We explored the effects of abdominal obesity and sagittal imbalance on SIJP after PLIF. STUDY DESIGN: This is a prospective observational cohort study. SETTING: This study occurred at the Department of Spinal Surgery at a hospital affiliated with a medical university. METHODS: A total of 401 patients who underwent PLIF from June 2018 to June 2021 were enrolled in this study. 36 patients experienced postoperative SIJP. In contrast, a matched group comprised 72 non-SIJP patients. We used 1:2 propensity score matching to compare obesity features and sagittal spine parameters in the 2 groups. Inflammatory cytokines and visual analog scale (VAS) scores were measured in the SIJP group. RESULTS: A total of 36 patients (8.98%) experienced SIJP during the follow-up. Compared with the non-SIJP group, patients with postoperative SIJP had a higher body mass index (BMI), greater abdominal obesity, a higher incidence of pelvic incidence-lumbar lordosis greater than 10°, and a higher incidence of a sagittal vertical axis greater than 5 cm (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve for waist circumference was greater than that for BMI (0.762 vs. 0.650, P = 0.049). Logistic regression analysis revealed that the risk factors for SIJP were abdominal obesity, a pelvic incidence-lumbar lordosis of greater than 10°, and a sagittal vertical axis greater than 5 cm (P < 0.05). In patients with SIJP, interleukin 6, tumor necrosis factor-α, and VAS scores were higher in the abdominal obesity group than in the non-abdominal obesity group (P < 0.05). LIMITATIONS: There was no uniform diagnosis of SIJP, so the incidence rate of SIJP might not be accurate. CONCLUSIONS: The significant predictors of SIJP were abdominal obesity and sagittal imbalance. Patients with abdominal obesity showed higher levels of inflammatory markers and pain intensity. More attention should be paid to body shape and the angle of correction of lumbar lordosis before lumbar surgery.

Implications of electricity and gas price coupling in US New England region.

The tight coupling between electricity and gas has put the US New England region at constant risk of electricity price spikes due to a shortage of gas supplies, especially in the wake of limited natural gas supply in 2022. Here, we investigate the electricity-gas price couplings in the six states in New England from 2006 to 2022. We found that the price coupling in New England has been high and consistent in the past five years across all states, despite varying levels of gas-fired power generation. Additionally, we anticipate it will remain high even with increasing renewables by 2030. Furthermore, the price coupling exhibits an asymmetrical influence with electricity prices closely tracking gas prices, while gas prices are weakly affected by electricity price variations. Our findings also suggest that promoting electricity-gas cooperations could potentially mitigate the asymmetrical influence and electricity price spikes in New England.

Opportunistic screening for osteoporosis using enhanced images based on dual-energy computed tomography material decomposition: a comparison with quantitative computed tomography.

Background: Many patients with malignant tumors require chemotherapy and radiation therapy, which can result in a decline in physical function and potentially influence bone mineral density (BMD). Furthermore, these treatments necessitate enhanced computed tomography (CT) scans for determining disease staging or treatment outcomes, and opportunistic screening with available imaging data is beneficial for patients at high risk for osteoporosis if existing imaging data can be used. The study aimed to investigate the feasibility of opportunistic screening for osteoporosis using enhanced CT based on a dual-energy CT (DECT) material decomposition technique. Methods: We prospectively enrolled 346 consecutive patients who underwent abdominal unenhanced and triphasic contrast-enhanced CT (arterial, portal venous, and delayed phases) between June 2021 and June 2022. The BMD, and the density of hydroxyapatite (HAP) on HAP-iodine images and calcium (Ca) on Ca-iodine images were measured on the L1-L3 vertebral bodies. The iodine intake was recorded. Pearson analysis was conducted to assess the correlation between iodine intake and the density values in three phases and the correlation between BMD and the densities of HAP and Ca. Furthermore, linear regression was employed for quantitative evaluation. Bland-Altman analysis was used to evaluate the agreement between calculated BMD derived from DECT (BMD-DECT) and reference BMD derived from quantitative CT (BMD-QCT). Receiver operating characteristic (ROC) analysis was applied to assess the diagnostic efficacy. Results: The HAP and Ca density of the L1-L3 vertebral bodies did not differ significantly among the three phases of contrast-enhanced CT (F=0.001-0.049; P>0.05). Significant positive correlations were found between HAP, Ca densities, and BMD (HAP-BMD: r=0.9472, R2=0.8973; Ca-BMD: r=0.9470, R2=0.8968; all P<0.001). Bland-Altman plots showed high agreement between BMD-DECT and BMD-QCT. The area under the curve (AUC) using HAP and Ca measurements was 0.963 [95% confidence interval (CI): 0.937-0.980] and 0.964 (95% CI: 0.939-0.981), respectively, for diagnosing osteoporosis and was 0.951 (95% CI: 0.917-0.973) and 0.950 (95% CI: 0.916-0.973), respectively, for diagnosing osteopenia. Conclusions: The HAP and Ca density measurements generated through the material decomposition technique in DECT have good diagnostic performances in assessing BMD, which offers a new perspective for opportunistic screening of osteoporosis on contrast-enhanced CT.

Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer.

OBJECTIVE: We aim to accurately distinguish ubiquitin-specific proteases (USPs) from other members within the deubiquitinating enzyme families based on protein sequences. Additionally, we seek to elucidate the specific regulatory mechanisms through which USP26 modulates Krüppel-like factor 6 (KLF6) and assess the subsequent effects of this regulation on both the proliferation and migration of cervical cancer cells. METHODS: All the deubiquitinase (DUB) sequences were classified into USPs and non-USPs. Feature vectors, including 188D, n-gram, and 400D dimensions, were extracted from these sequences and subjected to binary classification via the Weka software. Next, thirty human USPs were also analyzed to identify conserved motifs and ascertained evolutionary relationships. Experimentally, more than 90 unique DUB-encoding plasmids were transfected into HeLa cell lines to assess alterations in KLF6 protein levels and to isolate a specific DUB involved in KLF6 regulation. Subsequent experiments utilized both wild-type (WT) USP26 overexpression and shRNA-mediated USP26 knockdown to examine changes in KLF6 protein levels. The half-life experiment was performed to assess the influence of USP26 on KLF6 protein stability. Immunoprecipitation was applied to confirm the USP26-KLF6 interaction, and ubiquitination assays to explore the role of USP26 in KLF6 deubiquitination. Additional cellular assays were conducted to evaluate the effects of USP26 on HeLa cell proliferation and migration. RESULTS: 1. Among the extracted feature vectors of 188D, 400D, and n-gram, all 12 classifiers demonstrated excellent performance. The RandomForest classifier demonstrated superior performance in this assessment. Phylogenetic analysis of 30 human USPs revealed the presence of nine unique motifs, comprising zinc finger and ubiquitin-specific protease domains. 2. Through a systematic screening of the deubiquitinase library, USP26 was identified as the sole DUB associated with KLF6. 3. USP26 positively regulated the protein level of KLF6, as evidenced by the decrease in KLF6 protein expression upon shUSP26 knockdown in both 293T and Hela cell lines. Additionally, half-life experiments demonstrated that USP26 prolonged the stability of KLF6. 4. Immunoprecipitation experiments revealed a strong interaction between USP26 and KLF6. Notably, the functional interaction domain was mapped to amino acids 285-913 of USP26, as opposed to the 1-295 region. 5. WT USP26 was found to attenuate the ubiquitination levels of KLF6. However, the mutant USP26 abrogated its deubiquitination activity. 6. Functional biological assays demonstrated that overexpression of USP26 inhibited both proliferation and migration of HeLa cells. Conversely, knockdown of USP26 was shown to promote these oncogenic properties. CONCLUSIONS: 1. At the protein sequence level, members of the USP family can be effectively differentiated from non-USP proteins. Furthermore, specific functional motifs have been identified within the sequences of human USPs. 2. The deubiquitinating enzyme USP26 has been shown to target KLF6 for deubiquitination, thereby modulating its stability. Importantly, USP26 plays a pivotal role in the modulation of proliferation and migration in cervical cancer cells.

Effect of closed incision negative pressure wound treatment in vascular surgery: A meta-analysis.

The meta-analysis aimed to assess and compare the effect of closed-incision negative pressure wound (NPW) treatment in vascular surgery. Using dichotomous or contentious random or fixed effect models, the outcomes of this meta-analysis were examined, and the odds Ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. Ten examinations from 2017 to 2022 were enrolled for the present meta-analysis, including 2082 personals with vascular surgery. Closed-incision NPW treatment had significantly lower infection rates (OR, 0.39; 95% CI, 0.30-0.51, p < 0.001), grade I infection rates (OR, 0.33; 95% CI, 0.20-0.52, p < 0.001), grade II infection rates (OR, 0.39; 95% CI, 0.21-0.71, p = 0.002), and grade III infection rates (OR, 0.31; 95% CI, 0.13-0.73, p = 0.007), and surgical re-intervention (OR, 0.49; 95% CI, 0.25-0.97, p = 0.04) compared to control in personal with vascular surgery. However, no significant differences were found between closed-incision NPW treatment and control in the 30-day mortality (OR, 0.54; 95% CI, 0.29-1.00, p = 0.05), antibiotic treatment (OR, 0.53; 95% CI, 0.24-1.19, p = 0.12), and length of hospital stay (MD, -0.02; 95% CI, -0.24-0.19, p = 0.83) in personnel with vascular surgery. The examined data revealed that closed-incision NPW treatment had significantly lower infection rates, grade I infection rates, grade II infection rates, and grade III infection rates, surgical re-intervention, however, there were no significant differences in 30-day mortality, antibiotic treatment, or length of hospital stay compared to control group with vascular surgery. Yet, attention should be paid to its values since some comparisons had a low number of selected studies.

Responses of peritubular macrophages and the testis transcriptome profiles of peripubertal and adult rodents exposed to an acute dose of MEHP.

Exposure of rodents to mono-(2-ethylhexyl) phthalate (MEHP) is known to disrupt the blood-testis barrier and cause testicular germ cell apoptosis. Peritubular macrophages (PTMφ) are a newly identified type of testicular macrophage that aggregates near the spermatogonial stem cell niche. We have previously reported that MEHP exposure increased the numbers of PTMφs by 6-fold within the testis of peripubertal rats. The underlying mechanism(s) accounting for this change in PTMφs and its biological significance is unknown. This study investigates if MEHP-induced alterations in PTMφs occur in rodents (PND 75 adult rats and PND 26 peripubertal mice) that are known to be less sensitive to MEHP-induced testicular toxicity. Results show that adult rats have a 2-fold higher basal level of PTMφ numbers than species-matched peripubertal animals, but there was no significant increase in PTMφ numbers after MEHP exposure. Peripubertal mice have a 5-fold higher basal level of PTMφ compared with peripubertal rats but did not exhibit increases in number after MEHP exposure. Further, the interrogation of the testis transcriptome was profiled from both the MEHP-responsive peripubertal rats and the less sensitive rodents via 3' Tag sequencing. Significant changes in gene expression were observed in peripubertal rats after MEHP exposure. However, adult rats showed lesser changes in gene expression, and peripubertal mice showed only minor changes. Collectively, the data show that PTMφ numbers are associated with the sensitivity of rodents to MEHP in an age- and species-dependent manner.

Porcine-derived antimicrobial peptide PR39 alleviates DSS-induced colitis via the NF-κB/MAPK pathway.

PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.