Revealing the mechanism of flavor improvement of fermented goat milk based on lipid changes.

The mechanism of goat milk (GM) flavor improvement based on lipid changes requires understanding. According to sensory evaluation results, the texture, taste, appearance, aroma, and overall acceptability score of Guishan fermented goat milk (GMF) were higher than those of GM. In total, 779 lipid molecules and 121 volatile compounds were formed from the metabolite-lipid level in the GM and GMF, as determined through lipidomics and gas chromatography-mass spectrometry. The key volatile flavor compounds in the GMF were (E,E)-2,4-decadienal, ethyl acetate, acetoin, 2,3-pentanedione, acetic acid, and 2,3-butanedione. Of them, 60 lipids significantly contributed to the flavor profiles of the GMF, based on the correlation analysis. The triacylglycerides (TAGs) 12:0_14:0_16:0 and 13:0_13:0_18:2 contributed to aroma retention, while TAG and phosphatidylethanolamine were identified as key substrates for flavor compound formation during fermentation. Lipids associated with glycerophospholipid and linoleic acid metabolism pathways significantly affected volatile compound formation in the GMF. This study provides an in-depth understanding of the lipids and flavors of the GMF, and this information will be useful for the development of specific GMF products.

Evaluating Virtual Contrast-enhanced MRI (VCE-MRI) in Nasopharyngeal Carcinoma Radiotherapy: A Retrospective Analysis for Primary Gross Tumor Delineation.

PURPOSE: To investigate the potential of virtual contrast-enhanced MRI (VCE-MRI) for gross-tumor-volume (GTV) delineation of nasopharyngeal carcinoma (NPC) using multi-institutional data. METHODS AND MATERIALS: This study retrospectively retrieved T1-weighted (T1w), T2-weighted (T2w) MRI, gadolinium-based contrast-enhanced MRI (CE-MRI) and planning CT of 348 biopsy-proven NPC patients from three oncology centers. A multimodality-guided synergistic neural network (MMgSN-Net) was trained using 288 patients to leverage complementary features in T1w and T2w MRI for VCE-MRI synthesis, which was independently evaluated using 60 patients. Three board-certified radiation oncologists and two medical physicists participated in clinical evaluations in three aspects: image quality assessment of the synthetic VCE-MRI, VCE-MRI in assisting target volume delineation, and effectiveness of VCE-MRI-based contours in treatment planning. The image quality assessment includes distinguishability between VCE-MRI and CE-MRI, clarity of tumor-to-normal tissue interface and veracity of contrast enhancement in tumor invasion risk areas. Primary tumor delineation and treatment planning were manually performed by radiation oncologists and medical physicists, respectively. RESULTS: The mean accuracy to distinguish VCE-MRI from CE-MRI was 31.67%; no significant difference was observed in the clarity of tumor-to-normal tissue interface between VCE-MRI and CE-MRI; for the veracity of contrast enhancement in tumor invasion risk areas, an accuracy of 85.8% was obtained. The image quality assessment results suggest that the image quality of VCE-MRI is highly similar to real CE-MRI. The mean dosimetric difference of planning target volumes were less than 1Gy. CONCLUSIONS: The VCE-MRI is highly promising to replace the use of gadolinium-based CE-MRI in tumor delineation of NPC patients.

The efficacy of lumbar erector spinae plane block for postoperative analgesia management in patients undergoing lumbar unilateral bi-portal endoscopic surgery: a prospective randomized controlled trial.

BACKGROUND: The efficacy and reliability of erector spinae plane block (ESPB) in posterior open lumbar spine surgery has been demonstrated; however, few randomized controlled trials of lumbar ESPB (L-ESPB) in lumbar unilateral bi-portal endoscopic (UBE) surgery have been reported. METHODS: A total of 120 patients, aged 18 to 65 (who underwent elective lumbar UBE surgery under general anesthesia and exhibited an American Society of Anesthesiologists physical status of I to III) were randomly assigned in a 1:1 ratio to the ESPB group and the Control group. Ultrasound(US)-guided unilateral single-shot 0.25% ropivacaine L-ESPB was performed in the ESPB group, but not in the control group. Postoperative analgesic strategy for all patients: patient controlled intravenous analgesia (PCIA, diluted and dosed with fentanyl alone) was initiated immediately after surgery combined with oral compound codeine phosphate and ibuprofen sustained release tablets (1 tablet containing ibuprofen 200 mg and codeine 13 mg, 1 tablet/q12h) commenced 6 h postoperatively. We collected and compared patient-centred correlates intraoperatively and 48 h postoperatively. The primary outcomes were intraoperative and postoperative opioid consumption and postoperative quality of recovery-15 (QoR-15) scores. RESULTS: Compared to the control group (n = 56), the ESPB group (n = 58) significantly reduced intraoperative remifentanil consumption (estimated median difference - 280 mcg, 95% confidence interval [CI] - 360 to - 200, p < 0.001, power = 100%); significantly reduced fentanyl consumption at 24 h postoperatively (estimated median difference - 80mcg, 95%[CI] - 128 to - 32, p = 0.001, power = 90%); and significantly enhanced the QoR-15 score at 24 h postoperatively (estimated median difference 11, 95%[CI] 8 to 14, p < 0.001, power = 100%). Compared to the control group, the ESPB group enhanced the resting numeric rating scale (NRS) score up to 8 h postoperatively, and the active movement NRS score up to 4 h postoperatively. The incidence of postoperative nausea and vomiting (PONV) (p = 0.015, power = 70%), abdominal distension (p = 0.024, power = 64%), and muscular calf vein thrombosis (MCVT) (p = 0.033, power = 58%) was lower in the ESPB group than in the control group. Moreover, the occurrence of L-ESPB related adverse reactions was not found herein. CONCLUSION: US-guided L-ESPB reduces intraoperative and 24 h postoperative opioid consumption and improves patients' QoR-15 scores at 24 h postoperatively. L-ESPB can be safely and effectively utilized in lumbar UBE surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061908 , date of registration: 10/07/2022. Registry URL.

Highly Efficient Low-loaded PdOx/AlSiOx for Ethylene Dimerization.

Ethylene dimerization is an industrial process that is currently carried out using homogeneous catalysts. Here we present a highly active heterogeneous catalyst containing minute amounts of atomically dispersed Pd. It requires no co-catalyst(s) or activator(s) and significantly outperforms previously reported catalysts tested under similar reaction conditions. The selectivity to C4- and C6-hydrocarbons was about 80% and 10% at 42% ethylene conversion at 200°C using an industrially relevant feed containing 50 vol% ethylene, respectively. Our kinetic and catalyst characterization experiments complemented by density functional theory calculations provide molecular insights into the local environment of isolated Pd(II)Ox species and their role in achieving high activity in the target reaction. When the developed catalyst was rationally integrated with a Mo-containing olefin metathesis catalyst in the same reactor, the formed butenes reacted with ethylene to propylene with a selectivity of 98% at about 24% ethylene conversion.

Polymyxins: recent advances and challenges.

Antibiotic resistance is a pressing global health challenge, and polymyxins have emerged as the last line of defense against multidrug-resistant Gram-negative (MDR-GRN) bacterial infections. Despite the longstanding utility of colistin, the complexities surrounding polymyxins in terms of resistance mechanisms and pharmacological properties warrant critical attention. This review consolidates current literature, focusing on polymyxins antibacterial mechanisms, resistance pathways, and innovative strategies to mitigate resistance. We are also investigating the pharmacokinetics of polymyxins to elucidate factors that influence their in vivo behavior. A comprehensive understanding of these aspects is pivotal for developing next-generation antimicrobials and optimizing therapeutic regimens. We underscore the urgent need for advancing research on polymyxins to ensure their continued efficacy against formidable bacterial challenges.

Insights into the Acidic Site in Manganese Oxide in Terms of the Sulfur and Water Tolerance of Low-Temperature NH3 Selective Catalytic Reduction.

A critical constraint impeding the utilization of Mn-based oxide catalysts in NH3 selective catalytic reduction (NH3-SCR) is their inadequate resistance to water and sulfur. This vulnerability primarily arises from the propensity of SO2 to bind to the acidic site in manganese oxide, resulting in the formation of metal sulfate and leading to the irreversible deactivation of the catalyst. Therefore, gaining a comprehensive understanding of the detrimental impact of SO2 on the acidic sites and elucidating the underlying mechanism of this toxicity are of paramount importance for the effective application of Mn-based catalysts in NH3-SCR. Herein, we strategically modulate the acidity of the manganese oxide catalyst surface through the incorporation of Ce and Nb. Comprehensive analyses, including thermogravimetry, NH3 temperature-programmed desorption, in situ diffused reflectance infrared Fourier transform spectroscopy, and density functional theory calculations, reveal that SO2 exhibits a propensity for adsorption at strongly acidic sites. This mechanistic understanding underscores the pivotal role of surface acidity in governing the sulfur resistance of manganese oxide.

Association of coagulase-negative staphylococci with orthopedic infections detected by in-house multiplex real-time PCR.

Introduction: Clinical significance of coagulase-negative staphylococci (CoNS) has been gradually acknowledged in both healthcare and clinical research, but approaches for their precise discrimination at the species level remain scarce. The current study aimed to evaluate the association of CoNS with orthopedic infections, where accurate and prompt identification of etiology is crucial for appropriate diagnosis and treatment decision-making. Methods: A 16S rRNA-based quantitative PCR (qPCR) assay was developed for the detection of Staphylococcus genus and two panels of 3-plex qPCR assays for further differentiation of six CoNS species with remarkable clinical significance, including S. epidermidis, S. haemolyticus, S. simulans, S. hominis, S. capitis, and S. caprae. All the assays exhibited excellent analytical performance. ΔCq (quantification cycle) between 16S rRNA and CoNS species-specific targets was established to determine the primary CoNS. These methods were applied to detect CoNS in wound samples from orthopedic patients with and without infection. Results and discussion: Overall, CoNS were detected in 17.8% (21/118) of patients with clinically suspected infection and in 9.8% (12/123) of patients without any infection symptom (p < 0.05). Moreover, the association with infection was found to be bacterial quantity dependent. S. epidermidis was identified as the predominant species, followed by S. simulans, S. haemolyticus, and S. hominis. Male sex, open injury, trauma, and lower extremity were determined as risk factors for CoNS infections. CoNS-positive patients had significantly longer hospitalization duration (20 days (15, 33) versus 13 days (7, 22) for Staphylococcus-negative patients, p = 0.003), which could be a considerable burden for healthcare and individual patients. Considering the complex characteristics and devastating consequences of orthopedic infections, further expanding the detection scope for CoNS may be pursued to better understand the etiology of orthopedic infections and to improve therapeutic strategies.

Analyzing Large-Scale Single-Cell RNA-Seq Data Using Coreset.

The recent boom in single-cell sequencing technologies provides valuable insights into the transcriptomes of individual cells. Through single-cell data analyses, a number of biological discoveries, such as novel cell types, developmental cell lineage trajectories, and gene regulatory networks, have been uncovered. However, the massive and increasingly accumulated single-cell datasets have also posed a seriously computational and analytical challenge for researchers. To address this issue, one typically applies dimensionality reduction approaches to reduce the large-scale datasets. However, these approaches are generally computationally infeasible for tall matrices. In addition, the downstream data analysis tasks such as clustering still take a large time complexity even on the dimension-reduced datasets. We present single-cell Coreset (scCoreset), a data summarization framework that extracts a small weighted subset of cells from a huge sparse single-cell RNA-seq data to facilitate the downstream data analysis tasks. Single-cell data analyses run on the extracted subset yield similar results to those derived from the original uncompressed data. Tests on various single-cell datasets show that scCoreset outperforms the existing data summarization approaches for common downstream tasks such as visualization and clustering. We believe that scCoreset can serve as a useful plug-in tool to improve the efficiency of current single-cell RNA-seq data analyses.

Sustainable chitosan-based materials as heterogeneous catalyst for application in wastewater treatment and water purification: An up-to-date review.

Water pollution is one of serious environmental issues due to the rapid development of industrial and agricultural sectors, and clean water resources have been receiving increasing attention. Recently, more and more studies have witnessed significant development of catalysts (metal oxides, metal sulfides, metal-organic frameworks, zero-valent metal, etc.) for wastewater treatment and water purification. Sustainable and clean catalysts immobilized into chitosan-based materials (Cat@CSbMs) are considered one of the most appealing subclasses of functional materials due to their high catalytic activity, high adsorption capacities, non-toxicity and relative stability. This review provides a summary of various upgrading renewable Cat@CSbMs (such as cocatalyst, photocatalyst, and Fenton-like reagent, etc.). As for engineering applications, further researches of Cat@CSbMs should focus on treating complex wastewater containing both heavy metals and organic pollutants, as well as developing continuous flow treatment methods for industrial wastewater using Cat@CSbMs. In conclusion, this review abridges the gap between different approaches for upgrading renewable and clean Cat@CSbMs and their future applications. This will contribute to the development of cleaner and sustainable Cat@CSbMs for wastewater treatment and water purification.

Aqueous degradation of tioxazafen: Kinetics, products, pathways, and toxicity.

Tioxazafen (TXF) is the first 1,2,4-oxadiazole nematicide. In the present study, the aqueous degradation of TXF was investigated in terms of hydrolysis and photolysis. Under the irradiation of simulated sunlight, TXF degraded very fast in ultrapure water and buffers with half-lives (t1/2s) <8.3 min. A sole photoproduct (PP) PP228a was isolated, and identified by spectroscopic means (UV, IR, HRMS, and 1H NMR) to be the thiophen-3-yl isomer converted from its thiophen-2-yl parent. Comparing with TXF, PP228a had quite extended t1/2s ranging from 6.9 to 7.9 d. The photolysis kinetics of TXF and PP228a showed no pH-dependence, and varied for each individual compound as affected by nitrate, fulvic acid, and humic acid. Besides, both compounds were hydrolytically stable. 6 PPs of PP228a were identified, with two of them being its isomers. The mechanisms involved in the process included the biradical photosensitization, photoinduced electron transfer, and ring contraction-ring expansion reactions. The 48 h-EC50 to Daphnia magna was 0.808 mg/L for PP228a comparing to >1.12 mg/L for TXF, while the results of Vibrio fischeri assays indicated that one or more PPs of PP228a might have higher toxicity.

Will greenhouse gas emissions increase with mining depth in coal mines? An analysis of gas occurrence under varying in-situ stress conditions.

The rapid development of the economy leads to the high demand for deep coal resources, which further poses the potential problem of deep gas (or methane) emissions. The clarification of deep gas occurrence law for coal mines provides theoretical and data support for methane emission predictions, and assists industrial and mining enterprises in planning targeted emission reduction measures. This study defined and verified the existence of a critical depth for the deep gas occurrence in coal mines based on a multiple-scale case study of how the gas occurrence is associated with depth and stress status changes in the Pingdingshan No.8 Coal Mine. In addition, 882 sets of gas content data from 7 major mining areas in China were collected and their gas content distributions among various depths were statistically analyzed to prove the universal existence of critical depth. The results show that the critical depth of Pingdingshan No.8 Coal Mine is 509 m, and the critical depth of other Chinese areas is about 400 to 1000 m. Significant differences were observed in the pore space, surface, and gas desorption characteristics for coal samples with different depths and stress states. The pore structure in the critical depth area is relatively developed, and gas is easily accumulated. The gas occurrence of both normal and abnormal gas gradually increases with the depth's increase in areas above the critical depth, whereas the gas occurrence gradually decreases for areas below the critical depth, showing that the existence of critical depth lead to significant deviations in gas emission predictions. The results provide a fundamental reference for gas emission prediction, greenhouse effect assessment, and carbon emission factor calculation and indicate that using the traditional linear method may be misleading for evaluating deep gas occurrence and emission.

A Bayesian network for estimating hypertension risk due to occupational aluminum exposure.

Background: The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN). Methods: In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN. Results: The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%. Conclusions: The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation.

BACKGROUND: Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. AIMS: The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. MATERIALS AND METHODS: We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co-immunoprecipitation and western blotting. RESULTS: TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. DISCUSSION: TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. CONCLUSION: TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

E3 ligase FBXO22 is not significant for spermatogenesis and male fertility in mice.

BACKGROUND: F-box-only protein 22 (FBXO22), an important substrate receptor of the SKP1-Cullin-F-box (SCF) ubiquitin ligases, has been reported to be involved in many biological processes, including tumorigenesis, neurological disorders, cellular senescence, and DNA damage. However, the specific role of FBXO22 during spermatogenesis is poorly understood. METHODS: We produced Fbxo22 conditional knockout (cKO) and global knockout (KO) mice and assessed their sperm masurements using a computer-assisted sperm analysis (CASA) system. Additionally, we conducted histologic staining and immunostaining to examine the impact of Fbxo22 loss on spermatogenesis. RESULTS: Our results revealed that there were no notable differences in semen quality, fertility test results, or histologic findings in Fbxo22-KO and Fbxo22-cKO mice compared to the control group. CONCLUSIONS: Our study demonstrated that Fbxo22 is not significant for spermatogenesis or male fertility in mice. These findings will help researchers avoid redundant efforts and serve as a foundational resource for genetic studies on human fertility.

Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Strain Effect on Dielectricity of Elastic Thermoplastic Polyurethanes.

Dielectric elastomers, such as thermoplastic polyurethanes (TPUs), are widely used as the dielectric layer, encapsulation layer, and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become urgent to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This study reports a device for the in situ measurement of the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.02 ± 0.01 to 2.88 ± 0.25 (at 1 MHz). In addition, combined Fourier-transform infrared spectroscopy, the X-ray scattering technique, and atomic force microscopy were utilized to characterize the evolution of the microstructure under strain. The investigation under tensile strain reveals a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction in the measured dielectric constant in TPU.

Deep convolutional neural network model ResNeSt for discrimination of papillary thyroid carcinomas and benign nodules in thyroid nodules diagnosed as atypia of undetermined significance.

Background: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy. Methods: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test. Results: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones. Conclusions: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; Epub ahead of print.