Low-temperature CO preferential oxidation in H2-rich stream over Indium modified Pd-Cu/Al2O3 catalyst.

The impact of Indium (In) doping upon the catalytic performance of Pd-Cu/Al2O3 for carbon monoxide preferential oxidation (CO-PROX) in hydrogen (H2) rich atmosphere at low temperature has been studied. A series of catalysts with extremely low palladium (Pd) loading (0.06 wt%) are synthesized by the facile co-impregnation method. When the In/copper (Cu) atomic ratio equals 0.25, Pd-Cu-In0.25/Al2O3 can keep 40% CO conversion and 100% carbon dioxide (CO2) selectivity at least 120 min at 30 °C, which is significantly superior to the catalytic performance of Pd-Cu/Al2O3. The elaborate characterization findings reveal that the added In species to Pd-Cu/Al2O3 causes Indium oxide (In2O3) to generate, which produces the interaction of In2O3 with Pd-Cu/Al2O3, further promoting the dispersion of copper chloride hydroxide (Cu2Cl(OH)3). Moreover, the modification of In facilitates the re-oxidation of Pd0 to Pd+ through reducing the formation of palladium hydride (PdHx) during the CO-PROX reaction. Meanwhile, the addition of In leads to the decrease of Cu+ electron cloud density, making it easier to be oxidized to Cu2+. Collectively, the easy re-oxidation of Pd0 and Cu+ is favorable to fulfill the Wacker cycle between Pd and Cu species, thus improving the catalytic performance for CO-PROX.

Effect and Interactions of BRAF on Lymph Node Metastasis in Papillary Thyroid Carcinoma With Hashimoto Thyroiditis.

CONTEXT: The role of B-Raf proto-oncogene (BRAF) in papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) is unknown. OBJECTIVE: We aimed to explore risk factors affecting lymph node (LN) metastasis and interaction effect of BRAF in PTC patients with HT. METHODS: We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital. We analyzed the correlations between preoperative characteristics and LN metastasis in overall, and different BRAFV600E-mutation patients. Logistic regression was applied to analyze the risk factors for LN metastasis. Finally, we performed an interaction effect analysis to identify the interaction effect of BRAF. RESULTS: The overall LN metastasis rate was 52.71% (524/994); the overall BRAF mutation rate was 26.9% (268/994). BRAF mutation rates were significantly different in LN metastasis and nonmetastasis patients (31.7% vs 21.5%; P < .001). In all 994 patients, age, body mass index (BMI), hypertension, tumor maximum diameter, BRAF mutation, tumor location, aspect ratio, calcification, and extrathyroidal invasion were risk factors for LN metastasis (P < .05). In BRAF-mutant patients, smoking, hypertension, maximum diameter, calcification, and multifocality were risk factors for LN metastasis (P < .05). In BRAF wild-type patients, age, BMI, maximum diameter, tumor location, aspect ratio, tumor shape, calcification, and extrathyroidal invasion were risk factors (P < .05). Additionally, we found statistically significant interactions between BRAF and BMI, hypertension, maximum diameter, and calcification (P < .05), suggesting the potential interaction effect of BRAF. CONCLUSION: BRAF is a risk factor for LN metastasis in PTC with HT. Meanwhile, BRAF can interact with age, BMI, hypertension, and calcification, which together influence LN metastasis.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

CONTEXT: Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. OBJECTIVE: This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. METHODS: We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. RESULTS: After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. CONCLUSION: RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

Foam-templated oleogels constructed by whey protein isolate and xanthan gum: Multiple-effect delivery vehicle for Antarctic krill oil.

To address the limitations of Antarctic krill oil (AKO) such as easy oxidation, unacceptable fishy flavor and low bioaccessibility of astaxanthin in it, a multiple-effect delivery vehicle for AKO is needed. In this study, whey protein isolate (WPI) and xanthan gum (XG) were utilized to construct AKO into oleogels by generating foam-templates. The effects of the concentration of XG on the properties of foam, cryogel and the corresponding oleogels were investigated, and the formation mechanism of oleogel was discussed from the perspective of the correlation between foam-cryogel-oleogel. The results demonstrated that with the increase of the concentration of XG, the foam stability was improved, the cryogel after freeze drying had a more uniform network structure and superior oil absorption ability, and the corresponding oleogel had excellent oil holding ability after oil absorption. The AKO oleogels showed superior oxidative stability compared with AKO. The in vitro digestion experiments demonstrated that the bioaccessibility of the astaxanthin in this oleogel was also considerably higher than that in AKO. In addition, this oleogel had masking effect on the odor-presenting substances in AKO, while retaining other flavors of AKO. The foam-templated oleogel can be considered as a multiple-effect vehicle for AKO to facilitate its application in food products. This study provides theoretical basis and data support for the development and utilization of novel vehicle for AKO, broadening the application of AKO in the field of food science.

Characterization of site-specific N-glycosylation signatures of isolated uromodulin from human urine.

Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.

Sensitivities evaluation of five radiopharmaceuticals in four common medullary thyroid carcinoma metastatic sites on PET/CT: a network meta-analysis and systematic review.

OBJECTIVES: Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most effective method in recent years. However, the sensitivity of each radiopharmaceutical varies greatly in different metastatic sites. We aim to investigate and compare five novel and common PET or PET/CT radiopharmaceutical sensitivities at the four most frequent metastatic sites by network meta-analysis. METHODS: We searched for studies evaluating PET/CT radiopharmaceutical sensitivities at different metastatic sites in PubMed, Web of Science, Embase, and Cochrane Library. The risk bias was analyzed, and publication bias was accessed by funnel plot asymmetry tests. We performed both global inconsistency and local inconsistency tests by evaluating the agreement between direct and indirect comparisons. Then, we made pairwise meta-analyses and network meta-analyses for each metastatic site. Finally, we performed the surface under the cumulative ranking curves (SUCRA) and calculated the SUCRA values to rank the probability of each radiopharmaceutical being the most sensitive method. RESULTS: In our results, 243 patients from 9 clinical studies which accessed sensitivities of different radiopharmaceuticals in MTC metastatic sites were included. For lymph nodes and liver, TF2/ 68 Ga-SSM288 showed the highest SUCRA values (0.974 in lymph nodes, 0.979 in liver). The SUCRA values for 18 F-DOPA and 68 Ga-SSA for bone metastatic lesions were nearly identical (0.301 and 0.319, respectively) and were higher than the other three radiopharmaceuticals. For lung lesions, 11 C-methionine had the highest SUCRA value (0.412). CONCLUSION: TF2/ 68 Ga-SSM288 had the best sensitivity in lymph nodes and liver lesions. 11 C-methionine was most sensitive in lung lesions. While 18 F-DOPA and 68 Ga-SSA had familiar sensitivities to be the best two radiopharmaceuticals.

A Swin Transformer-Based Model for Thyroid Nodule Detection in Ultrasound Images.

In recent years, the incidence of thyroid cancer has been increasing. Thyroid nodule detection is critical for both the detection and treatment of thyroid cancer. Convolutional neural networks (CNNs) have achieved good results in thyroid ultrasound image analysis tasks. However, due to the limited valid receptive field of convolutional layers, CNNs fail to capture long-range contextual dependencies, which are important for identifying thyroid nodules in ultrasound images. Transformer networks are effective in capturing long-range contextual information. Inspired by this, we propose a novel thyroid nodule detection method that combines the Swin Transformer backbone and Faster R-CNN. Specifically, an ultrasound image is first projected into a 1D sequence of embeddings, which are then fed into a hierarchical Swin Transformer. The Swin Transformer backbone extracts features at five different scales by utilizing shifted windows for the computation of self-attention. Subsequently, a feature pyramid network (FPN) is used to fuse the features from different scales. Finally, a detection head is used to predict bounding boxes and the corresponding confidence scores. Data collected from 2,680 patients were used to conduct the experiments, and the results showed that this method achieved the best mAP score of 44.8%, outperforming CNN-based baselines. In addition, we gained better sensitivity (90.5%) than the competitors. This indicates that context modeling in this model is effective for thyroid nodule detection.

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery.

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor location and its relation with the capsule, trachea, esophagus, nerves, and blood vessels before operation. This paper introduces an innovative 3D-printed model establishment method based on computerized tomography (CT) DICOM images. We established a personalized 3D-printed model of the cervical thyroid surgery field for each patient who needed thyroid surgery to help clinicians evaluate the key points and difficulties of the surgery and select the operation methods of key parts as a basis. The results showed that this model is conducive to preoperative discussion and the formulation of operation strategies. In particular, as a result of the clear display of the recurrent laryngeal nerve and parathyroid gland locations in the thyroid operation field, injury to them can be avoided during surgery, the difficulty of thyroid surgery reduced, and the incidence of postoperative hypoparathyroidism and complications related to recurrent laryngeal nerve injury reduced too. Moreover, this 3D-printed model is intuitive and aids communication for the signing of informed consent by patients before surgery.

PRAF2 is an oncogene acting to promote the proliferation and invasion of breast cancer cells.

Prenylated rab acceptor 1 domain family member 2 (PRAF2) acts as an oncogene and is closely related to the occurrence and development of various tumors. The present study aimed to clarify the functional relevance of PRAF2 in the biological behaviors of breast cancer by determining the expression of PRAF2 in breast cancer tissues and the corresponding adjacent tissues. The gene phenotypes of PRAF2 in patients with breast cancer in The Cancer Genome Atlas database were predicted using a cancer data online analysis website: The University of Alabama at Birmingham Cancer Data Analaysis Portal (UALCAN). The mRNA and protein expression of PRAF2 was further examined in 37 pairs of fresh frozen breast cancer tissues and adjacent non-tumor tissues by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. High expression of PRAF2 was verified by RT-qPCR in the breast cancer cell line, MCF-7, and small interfering RNA (siRNA) technology was used to silence PRAF2. In the in vitro cell functional experiment, three groups were used: Negative control (NC) group, siRNA-NC group and siRNA-PRAF2 group. Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to analyze the effect of downregulation of PRAF2 on the proliferation of breast cancer cells. Transwell invasion and cell scratch assays were performed to examine the effect of downregulation of PRAF2 on the invasion and migration of breast cancer cells. UALCAN analysis results indicated that PRAF2 expression was upregulated in breast cancer compared with normal tissue samples (P<0.001). High expression of PRAF2 in breast cancer was associated with TNM stage and regional lymph node metastasis. RT-qPCR results showed increased mRNA expression of PRAF2 in clinical tissue samples from 37 patients with breast cancer, compared with normal adjacent tissues (P<0.001). Protein expression of PRAF2 was also shown to be higher in the breast cancer MCF-7 cells than in the MDA-MB-231 cells. Western blotting analysis combined with ImageJ software quantification showed that the relative expression of PRAF2 protein was significantly higher in clinical tissue samples from 37 patients with breast cancer (1.9750±0.0103) than that in normal adjacent tissues (0.9818±0.0140) (P<0.001). Western blotting analysis results indicated that transfection with siRNA PRAF2 in MCF-7 cells decreased PRAF2 expression (P<0.001). The results of CCK-8 and colony formation assays revealed that downregulation of PRAF2 expression suppressed the proliferation of MCF-7 cells (P<0.05 and P<0.001, respectively). In addition, Transwell invasion and cell scratch assay results showed that downregulation of PRAF2 expression in MCF-7 cells repressed invasion and migration of cancer cells (P<0.001). Overall, PRAF2 expression was significantly higher in breast cancer tissues than normal adjacent tissues, and was closely related to TNM stage and regional lymph node metastasis in breast cancer. PRAF2 was found to act as an oncogene that is able to promote breast cancer cell proliferation and invasion. Thus, PRAF2 may be a potential prognostic factor in patients with breast cancer and a potential target for the treatment of breast cancer metastasis.

Application of near-infrared fluorescence imaging in the accurate assessment of surgical margins during breast-conserving surgery.

OBJECTIVE: To evaluate the feasibility and accuracy of near-infrared fluorescence imaging technology for assessing margins during breast-conserving surgery for breast cancer. METHODS: Forty-three breast cancer patients who received surgical treatment at Yijishan Hospital of Wannan Medical College were selected. Before the operation, the patients were administered with an indocyanine green injection of 0.5 mg/kg intravenously 2 h before operation. During and after the operation, all patients underwent surgical margin monitoring with the near-infrared fluorescence imaging system for fluorescence imaging and acquisition of images and quantitative fluorescence intensity. During the operation, the patients' tissue specimens were collected on the upper, lower, inner, outer, apical, and basal sides of the fluorescence boundary of the isolated lesions for pathological examination. RESULTS: Fluorescence was detected in the primary tumor in all patients. The average fluorescence intensities of tumor tissue, peritumoral tissue, and normal tissue were 219.41 ± 32.81, 143.35 ± 17.37, and 105.77 ± 17.79 arbitrary units, respectively (P < 0.05, t test). The signal-to-background ratio of tumor to peritumor tissue and normal tissue was 1.54 ± 0.20 and 2.14 ± 0.60, respectively (P < 0.05, t test). Abnormal indocyanine green fluorescence was detected in 11.6% patients (5/43), including 3 patients with residual infiltrating carcinoma and 2 patients with adenosis with ductal dilatation. CONCLUSION: This study confirms the high sensitivity and specificity of near-infrared fluorescence imaging technology for breast-conserving surgery margin assessment. Near-infrared fluorescence imaging technology can be used as an intraoperative diagnosis and treatment tool to accurately determine the surgical margin and is of important guiding value in breast-conserving surgery for breast cancer.

A multicenter, randomized controlled, non-inferiority trial, comparing nasal continuous positive airway pressure with nasal intermittent positive pressure ventilation as primary support before minimally invasive surfactant administration for preterm infants with respiratory distress syndrome (the NIV-MISA-RDS trial): Study protocol.

Background: Non-invasive ventilation (NIV) treatment has been developed to minimize lung damage and to avoid invasive mechanical ventilation (IMV) in preterm infants, especially in those with a gestational age of <30 weeks. Our hypothesis is that for preterm infants <30 weeks with potential to develop respiratory distress syndrome (RDS), nasal continuous positive airway pressure (NCPAP) is non-inferior to the nasal intermittent positive pressure ventilation (NIPPV) as primary respiratory support before minimal invasive surfactant administration (MISA). Methods and design: The NIV-MISA-RDS trial is planned as an unblinded, multicenter, randomized, non-inferiority trial at 14 tertiary neonatal intensive care units (NICUs) in China. Eligible infants are preterm infants of 24-29+6 weeks of gestational age who have spontaneous breaths at birth and require primary NIV support for RDS. Infants are randomized 1:1 to treatment with either NCPAP or NIPPV once admitted into NICUs. If an infant presents progressively aggravated respiratory distress and is clinically diagnosed as having RDS, pulmonary surfactant will be supplemented by MISA in the first 2 h of life. The primary outcome is NIV treatment failure within 72 h after birth. With a specified non-inferiority margin of 10%, using a two-sided 95% CI and 80% power, the study requires 480 infants per group (in total 960 infants). Discussion: Current evidence shows that NIV and MISA may be the most effective strategy for minimizing IMV in preterm infants with RDS. However, there are few large randomized controlled trials to compare the effectiveness of NCPAP and NIPPV as the primary respiratory support after birth and before surfactant administration. We will conduct this trial to test the hypothesis that NCPAP is not inferior to NIPPV as the initial respiratory support in reducing the use of IMV in premature infants who have spontaneous breaths after birth and who do not require intubation in the first 2 h after birth. The study will provide clinical data for the selection of the initial non-invasive ventilation mode in preterm infants with a gestational age of <30 weeks with spontaneous breaths after birth. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT05137340.

Non-Linear Correlation Between Tumor Size and Survival Outcomes for Parathyroid Carcinoma: A SEER Population-Based Cohort Study.

Background: Parathyroid carcinoma (PC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study captures how independent prognostic factors and tumor size correlate with outcomes in patients with PC. Methods: The Surveillance, Epidemiology, and End Results database was used to perform a retrospective analysis on PC patients from 2000 to 2018. Univariate and multivariable survival analyses were performed to evaluate cancer-specific survival (CSS) and overall survival (OS), to identify independent prognostic factors in the PC patient population. A generalized additive model was applied to conduct smooth curve fitting and to examine the association between tumor size and relative risk of death. Results: A total of 590 patients were included. The 5- and 10-year OS were 80.8% and 67.1%, respectively. 5- and 10-year CSS was estimated to be 93.6% and 92.1%, respectively. The association between tumor size and relative risk of death can be generalized as a U-shaped curve. The mortality risk reaches its lowest point when tumor diameter approaches 2cm. At a tumor diameter cutoff of 3cm for CSS and 4cm for OS, there is an abrupt drop in survival rates. Multivariate Cox analysis revealed age, no surgery, and debulking surgery as consistent predictors of lower OS and CSS. Conclusions: A non-linear correlation between tumor size and death risk has been identified in patients with PC, along with an accurate size threshold at which survival rates sharply decrease. Further investigation is needed to determine if these trends are seen in other malignancies with promising prognoses.

A Signature of Three Apoptosis-Related Genes Predicts Overall Survival in Breast Cancer.

Background: The commonest malignancy in women is known as breast cancer (BC). Numerous studies demonstrated that apoptosis appears to be critical to the management and clinical outcome of BC patients. The purpose of this study is to explore the potential connection between apoptosis and BC and establish the apoptosis-associated gene signature in BC. Methods: The data of BC patient transcripts and related clinical information comes from the Cancer Genome Atlas Database (TCGA), and the genes related to apoptosis come from the Molecular Characterization Database (MSigDB). We identified the abnormally expressed apoptosis-related genes in BC samples. The optimal apoptosis-related genes screened by Cox regression analysis were designed to construct a prognostic model for predicting BC patients. Using the Nom Chart to Predict 1-Year, 3-Year, and 5-Year overall survival for BC patients. The gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). Results: Three genes [alpha subunit of the interleukin 3 receptor (IL3RA), apoptosis-inducing factor mitochondrial-associated 1 (AIFM1), and phosphatidylinositol-3 kinase catalytic alpha (PIK3CA)] correlated with apoptosis were shown to be strongly linked to the overall survival of BC. Survival analysis shows that the risk score is directly proportional to the poor prognosis of BC patients. Risk assessment based on three genetic characteristics (age, pathological stage N, and pathological stage M) can independently predict the prognosis of patients with BC. The Nom chart is most suitable for assessing the long-term survival rate of BC patients. The results of GSEA demonstrated that numerous cell cycle-related pathways were abundant in the high-risk group. Conclusion: We constructed an apoptosis-associated gene signature in BC, which had a potential clinical application prospect for BC patients.

Synthesis and Evaluation of Technetium-99m-Labeled pH (Low) Insertion Peptide Variant 7 for Early Diagnosis of MDA-MB-231 Triple-Negative Breast Cancer by Targeting the Tumor Microenvironment.

Objective: To prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC). Methods: The pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7). Results: The radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7. Conclusion: 99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.

The Sulfinylsulfonation of alkynes for ß-Sulfinyl alkenylsulfone.

Here we report the sulfinylsulfonation of alkynes to afford ß-sulfinyl alkenylsulfone products with a broad substrate scope, excellent functional group compatibility, and high yield. Moreover, the sulfinylsulfonation reaction of enyne can also be realized for constructing functionalized carbo- and heterocycles through a radical cascade cyclization process.

Comparative N-Glycoproteomics Analysis of Clinical Samples Via Different Mass Spectrometry Dissociation Methods.

Site-specific N-glycosylation characterization requires intact N-glycopeptide analysis based on suitable tandem mass spectrometry (MS/MS) method. Electron-transfer/higher-energy collisional dissociation (EThcD), stepped collision energy/higher-energy collisional dissociation (sceHCD), higher-energy collisional dissociation-product-dependent electron-transfer dissociation (HCD-pd-ETD), and a hybrid mass spectrometry fragmentation method EThcD-sceHCD have emerged as valuable approaches for glycoprotein analysis. However, each of them incurs some compromise, necessitating the systematic performance comparisons when applied to the analysis of complex clinical samples (e.g., plasma, urine, cells, and tissues). Herein, we compared the performance of EThcD-sceHCD with those previous approaches (EThcD, sceHCD, HCD-pd-ETD, and sceHCD-pd-ETD) in the intact N-glycopeptide analysis, and determined its applicability for clinical N-glycoproteomic study. The intact N-glycopeptides of distinct samples, namely, plasma from prostate cancer (PCa) patients, urine from immunoglobulin A nephropathy (IgAN) patients, human hepatocarcinoma cell line (HepG2), and thyroid tissues from thyroid cancer (TC) patients were analyzed by these methods. We found that EThcD-sceHCD outperformed other methods in the balance of depth and accuracy of intact N-glycopeptide identification, and sceHCD and EThcD-sceHCD have good complementarity. EThcD-sceHCD holds great potential for biomarker discovery from clinical samples.

Alteration of gut microbiota and metabolomics in critically ill patients by sequential feeding: A pilot study.

BACKGROUND: Sequential feeding (SF) is a new feeding mode for critically ill patients that involves a combination of continuous feeding (CF) in the beginning, rhythmic feeding in the second stage, and oral feeding in the last stage. In this study, we investigated the influence of SF on gut microbiota and metabolomics in critically ill patients. METHODS: Stool specimens from 20 patients (10 patients with the SF group, 10 patients with the CF group) were collected for full-length 16S ribosomal RNA gene sequencing and untargeted metabolomics analysis. RESULTS: The proportion of patients with low bacterial diversity (Shannon index < 4) in the SF group was much lower than that in the CF group, but there was no significant difference in the proportions (20% vs 50%, P = .350). The abundances of Actinobacteria/Actinobacteria (at the phylum and class levels), Pseudomonadaceae/Pseudomonas (at the family and genus levels), and Fusobacteria/Fusobacteriaceae/Fusobacteriales/Fusobacteria/Fusobacterium (at the phylum, class, order, family, and genus levels) were all higher in the SF group than in the CF group. Actinobacteria/Actinobacteria (at the phylum and class levels) were the most influential of these gut flora. Retinoic acid and leucine were upregulated in the SF group and were respectively responsible for the intestinal immune network for immunoglobulin A production and the mammalian target of rapamycin signaling pathway in the enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes database classification. CONCLUSIONS: SF could alter gut microbiota and metabolomics in critically ill patients. Because of the small sample size, further study is required.

Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress.

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.

Recent advances on food-grade oleogels: Fabrication, application and research trends.

In order to improve the nutritional and quality characteristics of food, solid fats are widely used in food formulations. With the continuous improvement of consumers' awareness of health in recent years, substantial attempts have been carried out to find substitutes for solid fats to reduce saturated fatty acid content in foods. Oleogels have drawn increasing attention due to their attractive advantages such as easy fabrication, superior fatty acid composition and safe use in food products to satisfy consumers' demands for healthy products. This review provides the latest information on the diversified oleogel systems. The feasibility of oleogel and oleogel-based system as nutraceutical vehicles is elucidated. The type as well as concentration of oleogelators and the synergistic effect between two or more oleogelators are important factors affecting the properties of obtained oleogel. Oleogels used in nutraceutical delivery have been shown to offer increased loading amount, enhanced bioaccessibility and targeted or controlled release. These nutrients wrapped in oleogels may in turn affect the formation and properties of oleogels. Furthermore, the future perspectives of oleogels are discussed. The feasible research trends of food-grade oleogel include oleogel-based solid lipid particle, essential oil-in-oleogel system, delivery of probiotics, nutraceuticals co-delivery and microencapsulated oleogel.

Convolutional Neural Network-Based Computer-Assisted Diagnosis of Hashimoto's Thyroiditis on Ultrasound.

PURPOSE: This study investigates the efficiency of deep learning models in the automated diagnosis of Hashimoto's thyroiditis (HT) using real-world ultrasound data from ultrasound examinations by computer-assisted diagnosis (CAD) with artificial intelligence. METHODS: We retrospectively collected ultrasound images from patients with and without HT from 2 hospitals in China between September 2008 and February 2018. Images were divided into a training set (80%) and a validation set (20%). We ensembled 9 convolutional neural networks (CNNs) as the final model (CAD-HT) for HT classification. The model's diagnostic performance was validated and compared to 2 hospital validation sets. We also compared the accuracy of CAD-HT against seniors/junior radiologists. Subgroup analysis of CAD-HT performance for different thyroid hormone levels (hyperthyroidism, hypothyroidism, and euthyroidism) was also evaluated. RESULTS: 39 280 ultrasound images from 21 118 patients were included in this study. The accuracy, sensitivity, and specificity of the HT-CAD model were 0.892, 0.890, and 0.895, respectively. HT-CAD performance between 2 hospitals was not significantly different. The HT-CAD model achieved a higher performance (P < 0.001) when compared to senior radiologists, with a nearly 9% accuracy improvement. HT-CAD had almost similar accuracy (range 0.87-0.894) for the 3 subgroups based on thyroid hormone level. CONCLUSION: The HT-CAD strategy based on CNN significantly improved the radiologists' diagnostic accuracy of HT. Our model demonstrates good performance and robustness in different hospitals and for different thyroid hormone levels.