Role of high-frequency ultrasound in differentiating benign and malignant skin lesions: potential and limitations.

PURPOSE: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. METHODS: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). RESULTS: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. CONCLUSION: In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

A deep learning fusion network trained with clinical and high-frequency ultrasound images in the multi-classification of skin diseases in comparison with dermatologists: a prospective and multicenter study.

Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

EGFR mediates epithelial­mesenchymal transition through the Akt/GSK-3ß/Snail signaling pathway to promote liver cancer proliferation and migration.

Epidermal growth factor receptor (EGFR) is expressed in various types of cancer and is associated with the malignant biological behavior of cancer cells. In the present study, the expression of EGFR in hepatocellular carcinoma (HCC) tissues and liver cancer cells was detected by immunohistochemical staining, western blotting and immunofluorescence. Furthermore, a lentivirus was transduced into HepG2 liver cancer cells to knock down EGFR expression. Cell proliferation and migration, and the expression levels of epithelial-mesenchymal transition (EMT) markers were assessed by EdU staining, Cell Counting Kit-8, colony formation, wound healing and Transwell assays, and western blotting. The results revealed that EGF/EGFR can mediate EMT through the Akt/glycogen synthase kinase-3ß (GSK-3ß)/Snail signaling pathway to promote HepG2 cell proliferation and migration. Inhibition of the activation of the EGFR signaling pathway can help to partially reverse the EMT phenotype, and inhibit the proliferation and migration of HepG2 cells. In conclusion, the EGFR/Akt/GSK-3ß/Snail signaling pathway serves an important role in HCC progression, and inhibition of the activation of the EGFR signaling pathway may be a valuable strategy in liver cancer treatment.

Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

H2O2 negatively regulates aluminum resistance via oxidation and degradation of the transcription factor STOP1.

Aluminum (Al) stress triggers the accumulation of hydrogen peroxide (H2O2) in roots. However, whether H2O2 plays a regulatory role in aluminum resistance remains unclear. In this study, we show that H2O2 plays a crucial role in regulation of Al resistance, which is modulated by the mitochondrion-localized pentatricopeptide repeat protein REGULATION OF ALMT1 EXPRESSION 6 (RAE6). Mutation in RAE6 impairs the activity of complex I of the mitochondrial electron transport chain, resulting in the accumulation of H2O2 and increased sensitivity to Al. Our results suggest that higher H2O2 concentrations promote the oxidation of SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1), an essential transcription factor that promotes Al resistance, thereby promoting its degradation by enhancing the interaction between STOP1 and the F-box protein RAE1. Conversely, decreasing H2O2 levels or blocking the oxidation of STOP1 leads to greater STOP1 stability and increased Al resistance. Moreover, we show that the thioredoxin TRX1 interacts with STOP1 to catalyze its chemical reduction. Thus, our results highlight the importance of H2O2 in Al resistance and regulation of STOP1 stability in Arabidopsis (Arabidopsis thaliana).

Assessment of the Diagnostic Performance of Clinical Examinations and High-Frequency Ultrasound in Patients With Pigmented Skin Tumors.

OBJECTIVES: To investigate whether the integration of high-frequency ultrasound (HFUS) to routine clinical examinations could improve diagnostic performance and management decision for pigmented skin tumors. METHODS: Three general practitioners trained previously and a dermatologist independently assessed pigmented skin tumors and rendered management decision based on clinical examinations alone or clinical examinations integrating HFUS. RESULTS: After integrating HFUS, the diagnostic area under the curve (AUC) (0.658-0.693 versus 0.848, all P < .05) and specificity (46.6-58.6% versus 89.7%, all P < .05) for pigmented skin malignancies were improved for general practitioners, meanwhile unnecessary biopsy rate reduced (42.9-53.6% versus 10.7%, P < .001). To the dermatologist, the diagnostic AUC (0.822 versus 0.949, P < .001), sensitivity (81.7% versus 96.7%, P = .012) and specificity (0.828 versus 0.931, P = .031) improved significantly, meanwhile both missed biopsy rate (14.5% versus 4.8%, P = .031) and unnecessary biopsy rate (19.6% versus 7.1%, P = .016) decreased. Additionally, the diagnostic performance of the general practitioner with integrating HFUS could be comparable with the dermatologist based on clinical examinations alone (all P > .05). CONCLUSIONS: As a complementary tool of clinical examinations, HFUS could help physicians differentiate pigmented skin malignancies and manage decision.

Class-III Hydrate Reservoir Depressurization Production Enhancement by Volume Fracturing and Cyclic N2 Stimulation Combination.

The depressurization effect is limited to class III hydrate reservoir recovery. To improve the depressurization effect, a new method of volume-fracturing and cyclic N2 stimulation combination (VFCS) was proposed. The production performance of this method was investigated by using numerical models based on reservoir parameters of the SH7 hydrate site in the South China Sea. The results show that (1) VFCS can greatly enhance the production performance with the average CH4 production rate being approximately 2.85 times higher than that of pure depressurization. This method combines the effects of volume fracturing and cyclic N2 stimulation by improving the seepage environment and further reducing the CH4 partial pressure in the gas phase. (2) High reservoir permeability, medium hydrate saturation, large volume-fracturing scale, low bottom-hole pressure, and high N2 injection amount can increase CH4 production by VFCS. (3) Although VFCS has the largest CH4 production volume and the highest hydrate dissociation degree among the studied production strategies, the reservoir temperature drop is significant by VFCS and future studies can be focused on the external heat supply to the reservoir to further improve the production.

High-Frequency Ultrasound Imaging to Distinguish High-Risk and Low-Risk Dermatofibromas.

BACKGROUND: Dermatofibroma has various pathological classifications, some of which pose a risk of recurrence and metastasis. Distinguishing these high-risk dermatofibromas based on appearance alone can be challenging. Therefore, high-frequency ultrasound may provide additional internal information on these lesions, helping to identify high-risk and low-risk dermatofibroma early. METHODS: In this retrospective study, 50 lesions were analyzed to explore the correlation between clinical and high-frequency ultrasound features and dermatofibroma risk level. Based on their pathological features, the lesions were divided into high-risk (n = 17) and low-risk (n = 33) groups. Subsequently, an identification model based on significant high-frequency ultrasound features was developed. RESULTS: Significant differences were observed in the thickness, shape, internal echogenicity, stratum basal, and Doppler vascular patterns between the high-risk and low-risk groups. The median lesion thickness for the high-risk dermatofibroma group was 4.1 mm (IQR: 3.2-6.1 mm), while it was 3.1 mm (IQR: 1.3-4.2 mm) for the low-risk dermatofibroma group. In the high-risk dermatofibroma group, irregular morphology was predominant (70.6%, 12/17), the most common being dermis-to-subcutaneous soft tissue penetration (64.7%, 11/17), and heterogenous internal echogenicity was observed in the majority of cases (76.5%, 13/17). On the other hand, regular morphology was more prevalent in the low-risk dermatofibroma group (78.8%, 26/33), primarily limited to the dermis layer (78.8%, 26/33), with homogeneous internal echogenicity also being prevalent in the majority of cases (81.8%, 27/33). Regarding the Doppler vascularity pattern, 69.7% (23/33) of low-risk dermatofibromas had no blood flow, while 64.7% (11/17) of high-risk dermatofibromas had blood flow. CONCLUSION: High-frequency ultrasound is crucial in distinguishing high-risk and low-risk dermatofibromas, making it invaluable for clinical management.

Diagnostic value of high-frequency ultrasound (HFUS) in evaluation of subcutaneous lesions.

BACKGROUND: It is unknown whether high-frequency ultrasound (HFUS) can evaluate invisible subcutaneous lesions. We aimed to investigate the diagnostic value of HFUS in invisible subcutaneous lesions. METHOD: Patients with invisible subcutaneous lesions were prospectively recruited from two centres. Before undergoing biopsy or surgery, each lesion was independently evaluated by two clinicians. One provides a clinical diagnosis by only clinical examination and the other provides an integrated diagnosis by combining clinical examination and HFUS information. Diagnoses were classified as correct, wrong, and indeterminate. A total of 391 lesions from 355 patients were enrolled, including 225 epidermoid cysts, 77 lipomas, 25 pilomatrixomas, 21 haemangiomas, 19 dermatofibromas, 11 dermatofibrosarcoma protuberans (DFSP), 7 neurofibromas, and 6 leiomyomas. Using pathological results as the gold standard, diagnostic performance was compared. RESULTS: The number of correct diagnoses increased from 185 (47.3%) by clinical examination alone to 316 (80.8%) after the addition of HFUS (P < 0.05). Meanwhile, the indeterminate diagnosis rate decreased from 143 (36.6%) to 10 (2.6%). Using HFUS, the accuracy improved significantly for epidermoid cysts (59.6% vs. 86.7%), lipomas (50.6% vs. 94.8%), pilomatrixomas (0% vs. 48.0%), haemangiomas (23.8% vs. 57.1%), and DFSPs (0% vs. 81.8%) (all p < 0.05). However, HFUS did not significantly improve the diagnostic accuracy of dermatofibromas (15.8% vs. 21.1%, p > 0.999), neurofibromas (42.9% vs. 71.4%, p = 0.625), or leiomyomas (16.7% vs. 100%, p = 0.063). CONCLUSION: Combining HFUS and clinical examination can generally improve the diagnostic accuracy and decrease the indeterminacy of invisible subcutaneous lesions, especially epidermoid cysts, lipomas, pilomatrixomas, haemangiomas, and DFSPs. However, for some rare lesions, HFUS cannot provide useful information.

Cell type-specific proteomics uncovers a RAF15-SnRK2.6/OST1 kinase cascade in guard cells.

Multicellular organisms such as plants contain various cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances our understanding of organization and function at the organismal level. Guard cells (GCs) are specialized epidermal cells that regulate the movement of the stomata and gaseous exchange, and provide a model genetic system for analyzing cell fate, signaling, and function. Several proteomics analyses of GC are available, but these are limited in depth. Here we used enzymatic isolation and flow cytometry to enrich GC and mesophyll cell protoplasts and perform in-depth proteomics in these two major cell types in Arabidopsis leaves. We identified approximately 3,000 proteins not previously found in the GC proteome and more than 600 proteins that may be specific to GC. The depth of our proteomics enabled us to uncover a guard cell-specific kinase cascade whereby Raf15 and Snf1-related kinase2.6 (SnRK2.6)/OST1(open stomata 1) mediate abscisic acid (ABA)-induced stomatal closure. RAF15 directly phosphorylated SnRK2.6/OST1 at the conserved Ser175 residue in its activation loop and was sufficient to reactivate the inactive form of SnRK2.6/OST1. ABA-triggered SnRK2.6/OST1 activation and stomatal closure was impaired in raf15 mutants. We also showed enrichment of enzymes and flavone metabolism in GC, and consistent, dramatic accumulation of flavone metabolites. Our study answers the long-standing question of how ABA activates SnRK2.6/OST1 in GCs and represents a resource potentially providing further insights into the molecular basis of GC and mesophyll cell development, metabolism, structure, and function.

Experimental study of 131I-caerin 1.1 and 131I-c(RGD)2 for internal radiation therapy of esophageal cancer xenografts.

OBJECTIVE: The aim of this study was to analyze and compare the therapeutic effects of 131I-caerin 1.1 and 131I-c(RGD)2 on TE-1 esophageal cancer cell xenografts. METHODS: (1) The in vitro antitumor effects of the polypeptides caerin 1.1 and c(RGD)2 were verified by MTT and clonogenic assays. 131I-caerin 1.1 and 131I-c(RGD)2 were prepared by chloramine-T (Ch-T) direct labeling, and their basic properties were measured. The binding and elution of 131I-caerin 1.1, 131I-c(RGD)2, and Na131I (control group) in esophageal cancer TE-1 cells were studied through cell binding and elution assays. (2) The antiproliferative effect and cytotoxicity of 131I-caerin 1.1, 131I-c(RGD)2, Na131I, caerin 1.1 and c(RGD)2 on TE-1 cells were detected by Cell Counting Kit-8 (CCK-8) assay. (3) A nude mouse esophageal cancer (TE-1) xenograft model was established to study and compare the efficacy of 131I-caerin 1.1 and 131I-c(RGD)2 in internal radiation therapy for esophageal cancer. RESULTS: (1) Caerin 1.1 inhibited the in vitro proliferation of TE-1 cells in a concentration-dependent manner, with an IC50 of 13.00 µg/mL. The polypeptide c(RGD)2 had no evident inhibitory effect on the in vitro proliferation of TE-1 cells. Therefore, the antiproliferative effects of caerin 1.1 and c(RGD)2 on esophageal cancer cells were significantly different (P < 0.05). The clonogenic assay showed that the clonal proliferation of TE-1 cells decreased as the concentration of caerin 1.1 increased. Compared with the control group (drug concentration of 0 µg/mL), the caerin 1.1 group showed significantly lower clonal proliferation of TE-1 cells (P < 0.05). (2) The CCK-8 assay showed that 131I-caerin 1.1 inhibited the in vitro proliferation of TE-1 cells, while 131I-c(RGD)2 had no evident inhibitory effect on proliferation. The two polypeptides showed significantly different antiproliferative effects on esophageal cancer cells at higher concentrations (P < 0.05). Cell binding and elution assays showed that 131I-caerin 1.1 stably bound to TE-1 cells. The cell binding rate of 131I-caerin 1.1 was 15.8 % ± 1.09 % at 24 h and 6.95 % ± 0.22 % after 24 h of incubation and elution. The cell binding rate of 131I-c(RGD)2 was 0.06 % ± 0.02 % at 24 h and 0.23 % ± 0.11 % after 24 h of incubation and elution. (3) In the in vivo experiment, 3 days after the last treatment, the tumor sizes of the phosphate-buffered saline (PBS) group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 68.29 ± 2.67 mm3, 61.78 ± 3.58 mm3, 56.67 ± 5.65 mm3, 58.88 ± 1.71 mm3, 14.40 ± 1.38 mm3, and 60.14 ± 0.47 mm3, respectively. Compared with the other treatment groups, the 131I-caerin 1.1 group had significantly smaller tumor sizes (P < 0.001). After treatment, the tumors were isolated and weighed. The tumor weights in the PBS group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 39.50 ± 9.54 mg, 38.25 ± 5.38 mg, 38.35 ± 9.53 mg, 28.25 ± 8.50 mg, 9.50 ± 4.43 mg, and 34.75 ± 8.06 mg, respectively. The tumor weights in the 131I-caerin 1.1 group were significantly lighter than those in the other groups (P < 0.01). CONCLUSION: 131I-caerin 1.1 has tumor-targeting properties, is capable of targeted binding to TE-1 esophageal cancer cells, can be stably retained in tumor cells, and has an evident cytotoxic killing effect, while 131I-c(RGD)2 has no evident cytotoxic effect. 131I-caerin 1.1 better suppressed tumor cell proliferation and tumor growth than pure caerin 1.1, 131I-c(RGD)2, and pure c(RGD)2.

The Value of Ultrasound for Differentiating Trichilemmal Cysts From Epidermoid Cysts.

OBJECTIVES: This study was aimed to evaluate the diagnostic performance of ultrasound (US) in differentiating trichilemmal cysts (TCs) from epidermoid cysts (ECs). METHODS: Based on clinical and ultrasound features, a prediction model was established and validated. 164 cysts in the pilot cohort and another 69 in the validation cohort diagnosed with TCs or ECs histopathologically were evaluated. The same radiologist performed all ultrasound examinations. RESULTS: For clinic features, TCs tended to occur in females compared with ECs (66.7 vs 28.5%; P < .001). In addition, TCs were prone to occur in the hairy area compared with ECs (77.8 vs 13.1%; P < .001). For ultrasound features, the internal hyperechogenicity and cystic change were more likely to appear in TCs in comparison with ECs (92.6 vs 25.5%; P < .001; 70.4 vs 23.4%; P < .001, respectively). Upon the features mentioned above, a prediction model was established with the areas under the receiver operating characteristic curves of 0.936 and 0.864 in the pilot and validation cohorts, respectively. CONCLUSIONS: US is promising for differentiating TCs from ECs and is valuable for their clinical management.

The role of ultrasound in screening subclinical psoriatic arthritis in patients with moderate to severe psoriasis.

OBJECTIVE: To identify patients in the subclinical psoriatic arthritis (Sub-PsA) phase by ultrasound (US) and provide a solution to screen them. METHODS: A total of 490 participants with moderate-to-severe psoriasis were evaluated. Among them, 384 participants without arthritis symptoms were enrolled into the silent psoriasis group and 106 participants with arthritis symptoms, called prodromal/active PsA phase, were enrolled into the clinical PsA group. Another 80 non-psoriasis participants were enrolled into the control group. Each participant received clinical assessments and US examinations of 60 joints, 38 tendons, and 40 entheses. We compared the incidences of synovio-enthesitis, synovitis, tenosynovitis, erosion, and dactylitis detected on US among the three groups. Subsequently, on the basis of significant US findings, we distinguished Sub-PsA from psoriasis alone (PsO) in the silent psoriasis group and analyzed the clinical characteristics, mainly including basic clinical characteristics, body surface area (BSA), and Psoriasis Area and Severity Index (PASI) score. RESULTS: Only synovio-enthesitis significantly differed between the control group and the silent psoriasis group (1.3% vs. 16.1%, p < 0.001). The knee was the most commonly involved site of synovio-enthesitis (79.0%). Taking synovio-enthesitis as the standard, 16.1% of silent psoriasis participants and 12.7% of all psoriasis participants were in the Sub-PsA phase. Furthermore, there were no differences in BSA and PASI among the three phases of PsO, Sub-PsA, and prodromal/active PsA. CONCLUSIONS: Since the psoriasis patients in Sub-PsA phase was as high as 12.7% in all patients with moderate-to-severe psoriasis, US-detected synovio-enthesitis was recommended routinely for screening them regardless of arthritis symptoms, especially in the lower limbs. KEY POINTS: • Synovio-enthesitis on ultrasound was significantly associated with subclinical psoriatic arthritis, especially in the lower limbs. • Routine ultrasound evaluation could help screen psoriasis patients in the subclinical psoriatic arthritis phase, which was as high as 12.7% in all psoriasis patients.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients. METHODS: Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared. RESULTS: BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05). CONCLUSION: LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

Simple N-Glycan Profile Analysis Using Lectin Staining, Mass Spectrometry, and GlycoMaple.

The Golgi apparatus is one of the major sites of protein and lipid glycosylation and processing. Protein N-glycosylation plays critical roles in protein folding, transport, stability, and activity. Various glycosyltransferases and glycoside hydrolases are localized at each cisterna in the Golgi apparatus and synthesize a large variety of N-glycan structures. The biosynthetic pathways of N-glycans are complicated, which hiders the rational design of glycan metabolic pathways. In addition, the analysis of glycan structure requires specialized instruments for analyses such as mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy, which are not familiar to all laboratories. Here, we introduce relatively simple methods for N-glycan analysis, including disruption of genes encoding glycosyltransferases or glycoside hydrolases, glycan structural analysis using lectins and mass spectrometry, and visualization of glycan metabolic pathways in silico.

Contrast-enhanced ultrasound in the assessment of Crohn's disease activity: comparison with computed tomography enterography.

BACKGROUND AND OBJECTIVE: Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD. MATERIALS AND METHODS: Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard. RESULTS: The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE. CONCLUSION: CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.

Switchable and Strain-Releasable Mg-Ion Diffusion Nanohighway Enables High-Capacity and Long-Life Pyrovanadate Cathode.

Rechargeable magnesium batteries (RMBs) suffer from low capacity and poor cyclability of cathode materials, which is due to the sluggish Mg2+ diffusion kinetics and large lattice strain. Here, a layer-interweaving mechanism in lamellar cathode to simultaneously facilitate Mg2+ diffusion and release Mg2+ -insertion strain is reported. In the Cu3 V2 O7 (OH)2 ·2H2 O (CVOH) cathode, Mg2+ diffusion highways are generated by the vertical interweaving of CVOH layers and V6 O13 layers that nucleate in CVOH during discharging, which are switchable by Mg2+ insertion/extraction. These highways enhance the Mg2+ diffusion coefficient by three orders of magnitude and release 50% Mg2+ -insertion strain. This enables CVOH to exhibit a high capacity of 262 mAh g-1 at high current density of 250 mA g-1 in aqua, and extremely low capacity loss of 0.0004% per cycle in the activated carbon//CVOH cell. This work inspires designing the magnesiation phase transformation of electrodes to resolve both kinetic and strain issues for high-performance RMBs.

Programming a Metal-Organic Framework toward Excellent Hypergolicity.

Exploring novel hypergolic fuels for modern space propulsion is highly desired. However, the analysis and understanding of the structure and hypergolic performance at the molecular level are still insufficient. To understand the factors that dictate hypergolicity, we conducted a comparative study on a series of metal-organic frameworks (MOFs) characterized by the same topology but with varied ligand structures. The ignition delay (ID) time trend was found to be imidazole < triazole < tetrazole, and the rapid ID time was 8 ms. By combining experimental studies and density functional theory (DFT) calculations, we found that propargyl and cyanoborohydride groups that functioned as dual hypergolic triggers contributed to the hypergolicity, and a distinct electronic structure was detrimental to ID time. The structure-performance relationships presented herein can potentially provide some fundamental insights into the field of developing high-performance hypergolic fuels.

Ultrasound-Based Drug Delivery System.

Cancer still represents a leading threat to human health worldwide. The effective usage of anti-cancer drugs can reduce patients' clinical symptoms and extend life-span survival time. Current anti-cancer strategies include chemotherapy, traditional Chinese medicine, biopharmaceuticals, and the latest targeted-therapy. However, due to the complexity and heterogeneity of tumor, serious side effects may result from the direct use of anti-cancer drugs. Besides, the current therapeutic strategies failed to effectively alleviate metastasized tumors. Recently, ultrasound-mediated nano-drug delivery system has become an increasingly important treatment strategy. Due to its abilities to enhance the efficacy and reduce toxic and side effects, it has become a research hotspot in the field of biomedicine. In this review, we introduced the latest research progress of the ultrasound-responsive nano-drug delivery systems, and the possible mechanisms of ultrasound acting on the carrier to change the structure or conformation, as well as to realize the controlled release. In addition, the progress in ultrasound responsive nano-drug delivery systems will also be briefly summarized.

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis.

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.