Aß Induces Neuroinflammation and Microglial M1 Polarization via cGAS-STING-IFITM3 Signaling Pathway in BV-2 Cells.

Microglia, innate immune cells of the brain, constantly monitor the dynamic changes of the brain microenvironment under physiological conditions and respond in time. Growing evidence suggests that microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease. In this study, we investigated that the expression of IFITM3 was significantly upregulated in microglia under the Aß treatment, and knockdown of IFITM3 in vitro suppressed the M1-like polarization of microglia. Moreover, IFITM3 was regulated by cGAS-STING signaling in activated microglia, and inhibition of cGAS-STING signaling reduces IFITM3 expression. Taken together, our findings suggested that the cGAS-STING-IFITM3 axis may be involved in Aß-induced neuroinflammation in microglia.

Performance Enhancement of Biogenetic Sulfidated Zero-Valent Iron for Trichloroethylene Degradation: Role of Extracellular Polymeric Substances.

Chemical sulfidation has been considered as an effective strategy to improve the reactivity of zero-valent iron (S-ZVI). However, sulfidation is a widespread biogeochemical process in nature, which inspired us to explore the biogenetic sulfidation of ZVI (BS-ZVI) with sulfate-reducing bacteria (SRB). BS-ZVI could degrade 96.3% of trichloroethylene (TCE) to acetylene, ethene, ethane, and dichloroethene, comparable to S-ZVI (97.0%) with the same S/Fe ratio (i.e., 0.1). However, S-ZVI (0.21 d-1) exhibited a faster degradation rate than BS-ZVI (0.17 d-1) based on pseudo-first-order kinetic fitting due to extracellular polymeric substances (EPSs) excreted from SRB. Organic components of EPSs, including polysaccharides, humic acid-like substances, and proteins in BS-ZVI, were detected with 3D-EEM spectroscopy and FT-IR analysis. The hemiacetal groups and redox-activated protein in EPS did not affect TCE degradation, while the acetylation degree of EPS increased with the concentration of ZVI and S/Fe, thus inhibiting the TCE degradation. A low concentration of HA-like substances attached to BS-ZVI materials promoted electron transport. However, EPS formed a protective layer on the surface of BS-ZVI materials, reducing its TCE reaction rate. Overall, this study showed a comparable performance enhancement of ZVI toward TCE degradation through biogenetic sulfidation and provided a new alternative method for the sulfidation of ZVI.

Comparison of brain microstructure alterations on diffusion kurtosis imaging among Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals.

Objective: Our study aimed to explore the differences in brain microstructure in patients with Alzheimer's disease (AD) and with mild cognitive impairment (MCI) and in individuals with normal cognition using diffusion kurtosis imaging (DKI) to identify a potential non-invasive biomarker of AD. Materials and methods: A total of 61 subjects were included in our study, including 20 subjects diagnosed with AD, 21 patients diagnosed with amnestic MCI, and 20 cognitively normal individuals. We acquired magnetic resonance imaging (MRI) scans, and DKI images were processed. Twelve regions of interest were drawn, and various parameters were measured and analyzed using SPSS version 11.0 software. Results: Comparative analysis showed that differences in brain regions in terms of mean diffusion (MD) and mean kurtosis (MK) between groups were the most marked. Precuneus MD, temporal MK, precuneus MK, and hippocampal MK were significantly correlated with neuropsychological test scores. Hippocampal MK showed the strongest correlation with the medial temporal lobe atrophy score (r = -0.510), and precuneus MD had the strongest correlation with the Koedam score (r = 0.463). The receiver operating curve analysis revealed that hippocampal MK exhibited better diagnostic efficacy than precuneus MD for comparisons between any group pair. Conclusion: DKI is capable of detecting differences in brain microstructure between patients with AD, patients with MCI, and cognitively normal individuals. Moreover, it compensates for the deficiencies of conventional MRI in detecting pathological changes in microstructure before the appearance of macroscopic atrophy. Hippocampus MK was the most sensitive single parameter map for differentiating patients with AD, patients with MCI, and cognitively normal individuals.

Distinct Responses of Biofilm Carbon Metabolism to Nanoplastics with Different Surface Modifications.

Recently, there is an increasing concern regarding the toxicity of nanoplastics (NPs) on freshwater organisms. However, knowledge about the potential impacts of NPs with different surface modification on freshwater biofilms is still very limited. In this research, biofilms were cultured in lab and exposed to nano polystyrene (PS) beads: non-functionalized PS NPs, PS-COOH NPs, and the carbon source utilization of biofilms were measured by BIOLOG ECO microplates. The results showed that both two types of PS NPs significantly reduced the total carbon metabolic activity of biofilms, compared with the controls, whereas the carbon metabolic rate increased notably, especially for the PS-COOH NPs treatments at day 14. Moreover, results from six categories of carbon sources analysis suggested that PS NPs with different surface chemical properties exhibit distinct effects on the carbon utilization of biofilms, and the divergent changes of the specific carbon source category were observed at day 21 from the two PS NPs treatments. In addition, the metabolic functional diversity of biofilms were not altered by the PS NPs treatments. These findings highlighted that chemical properties of NPs play an important role in the toxic effects on the carbon metabolism activities of the biofilms. This study offers new insights that nanoplastics of different chemical characteristics have the ability to affect the microbial-mediated carbon cycling process in aquatic ecosystems.

Altered Microstructural Changes Detected by Diffusion Kurtosis Imaging in Patients With Cognitive Impairment After Acute Cerebral Infarction.

Objective: To detect the microstructural changes in patients with cognitive impairment after acute cerebral infarction using diffusion kurtosis imaging (DKI). Materials and Methods: A total of 70 patients with acute cerebral infarction were divided into two groups: 35 patients with cognitive impairment (VCI group), and 35 patients without cognitive impairment (N-VCI group), according to mini-mental state examination (MMSE) score. Healthy individuals (n = 36) were selected as the normal control (NORM) group. DKI parameters from 28 different brain regions of interest (ROIs) were selected, measured, and compared. Results: VCI group patients had significantly higher mean diffusion (MD) and significantly lower mean kurtosis (MK) values in most ROIs than those in the N-VCI and NORM groups. DKI parameters in some ROIs correlated significantly with MMSE score. The splenium of corpus callosum MD was most correlated with MMSE score, the correlation coefficient was -0.652, and this parameter had good ability to distinguish patients with VCI from healthy controls; at the optimal cut-off MD value (0.9915), sensitivity was 91.4%, specificity 100%, and the area under the curve value 0.964. Conclusions: Pathological changes in some brain regions may underlie cognitive impairment after acute cerebral infarction, especially the splenium of corpus callosum. These preliminary results suggest that, in patients with VCI, DKI may be useful for assessing microstructural tissue damage.

JNK/c-Jun-driven NLRP3 inflammasome activation in microglia contributed to retinal ganglion cells degeneration induced by indirect traumatic optic neuropathy.

BACKGROUND: Indirect traumatic optic neuropathy (ITON) is a major cause of permanent loss of vision after blunt head trauma. Neuroinflammation plays a crucial role in neurodegenerative diseases. The present study concentrated on JNK/c-Jun-driven NLRP3 inflammasome activation in microglia during the degeneration of retinal ganglion cells (RGCs) in ITON. METHODS: An impact acceleration (IA) model was employed to induce ITON, which could produce significant neurodegeneration in the visual system. Pharmacological approaches were employed to disrupt JNK and to explore whether JNK and the microglial response contribute to RGC death and axonal degeneration. RESULTS: Our results indicated that the ITON model induced significant RGC death and axonal degeneration and activated JNK/c-Jun signaling, which could further induce the microglial response and NLRP3 inflammasome activation. Moreover, JNK disruption is sufficient to suppress NLRP3 inflammasome activation in microglia and to prevent RGC death and axonal degeneration. CONCLUSIONS: ITON could promote JNK/c-Jun signaling, which further activates the NLRP3 inflammasome in microglia and contributes to the degeneration of axons and death of RGCs. JNK inhibition is able to suppress the inflammatory reaction and improve RGC survival. Although further work is needed to determine whether pharmacological inhibition of the NLRP3 inflammasome can prevent ITON, our findings indicated that such intervention could be promising for translational work.

Greater Omentum Imaging-Reporting and Data System: establishing the grade of benign and malignant lesions of the greater omentum using ultrasonography.

OBJECTIVE: To establish Greater Omentum Imaging-Reporting and Data System (GOI-RADS) to evaluate the possibility of omental diseases being malignant. METHOD: A retrospective analysis was made of 883 patients who had undergone biopsy of the greater omentum in our center from October 2009 to October 2019. Twelve parameters of ultrasonographic images were evaluated, and the odds ratio of each group calculated. We assigned scores for the direct signs (omental echo, omental structure, and omental nodules) and indirect signs (separation of ascites, echo of ascites, mesenteric lymph nodes, and thickening of parietal peritoneum) of omental lesions. We created an omental score (OS) for each patient and receiver operating characteristic (ROC) curve to analyze its effectiveness in the differential diagnosis of benign and malignant omental diseases. RESULTS: The OS was divided into ≤5, 6, 7, 8, 9, 10, 11, 12, 13, and ≥ 14 points, and the malignant rate was 0, 1.85, 5.56, 30.36, 37.25, 87.72, 96.72, 98.28, 99.08, and 100%, respectively. The area under the ROC curve (AUC) was 0.976. When taking 10 points as the cutoff value to diagnose benign and malignant omental diseases, the sensitivity and specificity was 93.85 and 98.21%, respectively. A grading system was established: grade 1: omental score ≤ 5, malignant rate 0%; grade 2: omental score 6-7, malignant rate ≤ 5.56%; grade 3: omental score 8--9, malignant rate ≤ 37.25%; grade 4: omental score ≥ 10, malignant rate ≥ 87.72. CONCLUSION: GOI-RADS had high sensitivity and specificity in the differential diagnosis of benign and malignant omental lesions. We believe that GOI-RADS will aid the diagnosis of omental diseases based on objective and accurate interpretation of ultrasound features, and also to promote the ultrasonography of omental diseases in clinical application.

DASAF: An R Package for Deep Sequencing-Based Detection of Fetal Autosomal Abnormalities from Maternal Cell-Free DNA.

Background. With the development of massively parallel sequencing (MPS), noninvasive prenatal diagnosis using maternal cell-free DNA is fast becoming the preferred method of fetal chromosomal abnormality detection, due to its inherent high accuracy and low risk. Typically, MPS data is parsed to calculate a risk score, which is used to predict whether a fetal chromosome is normal or not. Although there are several highly sensitive and specific MPS data-parsing algorithms, there are currently no tools that implement these methods. Results. We developed an R package, detection of autosomal abnormalities for fetus (DASAF), that implements the three most popular trisomy detection methods-the standard Z-score (STDZ) method, the GC correction Z-score (GCCZ) method, and the internal reference Z-score (IRZ) method-together with one subchromosome abnormality identification method (SCAZ). Conclusions. With the cost of DNA sequencing declining and with advances in personalized medicine, the demand for noninvasive prenatal testing will undoubtedly increase, which will in turn trigger an increase in the tools available for subsequent analysis. DASAF is a user-friendly tool, implemented in R, that supports identification of whole-chromosome as well as subchromosome abnormalities, based on maternal cell-free DNA sequencing data after genome mapping.

Ultrasound Elastography for Differentiating Benign from Malignant Thickened Greater Omentum.

OBJECTIVES: To investigate whether ultrasound elastography (UE) is an effective non-invasive diagnostic procedure for evaluating benign and malignant thickened greater omentum. METHODS: Ultrasound elastographic images from 118 patients who underwent ultrasound-guided biopsy for thickened greater omentum from May 2012 to October 2013 were retrospectively analysed. The results were compared with the pathological findings from the biopsies, and evaluated by ROC curve analysis. RESULTS: A total of 93.6% of the benign thickened greater omentum had elasticity scoring of 1 or 2, whereas 93.0% of the malignant thickened greater omentum had elasticity scoring of 3 or 4. The elasticity strain ratios for malignant thickened greater omenta were higher than for benign thickened greater omenta using muscle or fat yielded as reference tissue (P < 0.01). The optimal cut-off point for elasticity strain ratios using fat as reference was 2.6. The sensitivity, specificity, accuracy, and positive and negative predictive values for determining elasticity strain ratios using fat as reference were 83.3%, 90.6%, 86.5%, 92.1%, and 80.6%, respectively, and for elasticity scoring were 95.2%, 96.9%, 95.9%, 97.6%, and 93.9%, respectively. CONCLUSIONS: UE using elasticity scoring or elasticity strain ratios is an effective new non-invasive method for differentiating benign from malignant thickened greater omentum. KEY POINTS: • Elasticity score is an objective method for differentiating greater omentum lesions. • Elasticity strain ratio is another method for differentiating greater omentum lesions. • Fat tissue is better than abdominal wall muscle as reference in elasticity imaging. • UE is a new effective, non-invasive method for diagnosing omental diseases.

Pseudomyxoma peritonei: some different sonographic findings.

OBJECTIVES: The purpose of our study was to assess the sonographic features of pseudomyxoma peritonei (PMP). MATERIALS AND METHODS: All records of peritoneal biopsies under the guidance of ultrasound in our institutional database from April 2007 to June 2011 were retrospectively reviewed. 19 cases of PMP and 279 cases of other peritoneal lesions were included in the study. The sonograms of peritoneum, ascites, and parenchymal organs involved by PMP were evaluated, respectively, and compared with sonograms of other peritoneal lesions. RESULTS: Anechoic areas were found in 89.5% cases of PMP at high frequency of insonation and the sensitivity in indicating PMP was 100%. In the pelvic cavity, echogenic foci in ascites of PMP in 52.6% cases were mobile. The specificity of "starburst" appearance and sensitivity of scalloping of the liver margin were relatively high (82.3 and 88.1%), but the sensitivity and specificity (57.9 and 42.1%) of these two signs were relatively low. CONCLUSION: Anechoic area in the thickened peritoneum was a specific sign in indicating the diagnosis of PMP and high-frequency transducer could reveal these tiny anechoic areas more explicitly. In the pelvic cavity, echogenic foci in ascites of PMP could be observed to be mobile and scalloping of the liver margin and "starburst" appearance also played a significant role in indicating PMP.

Peritoneal metastases: evaluation with contrast-enhanced ultrasound.

OBJECTIVES: The aim of this study is to evaluate the contrast-enhanced ultrasound (CEUS) features of peritoneal metastases. MATERIALS AND METHODS: Unenhanced ultrasound and CEUS were conducted in 25 patients who had confident diagnoses of peritoneal metastases after ultrasound-guided biopsies of peritoneum. B-mode sonograms, color Doppler, CEUS pattern and quantitative analysis of blood perfusion in peritoneal metastases were successively evaluated. RESULTS: Peritoneum became markedly thickened and was well seen as a heterogeneous omental cake at B-mode ultrasound. Color Doppler only detected dotted or strip-like blood flow scattered in the thickened peritoneum and no blood signal was found in any metastatic nodule. At CEUS, the thickened peritoneum enhanced diffusely and parameters of time-intensity curves did not show any significant difference among variant metastases groups. All the metastatic nodules in the peritoneum showed fast radial enhancement and became homogeneous with adjacent parenchyma. These nodules soon became hypoechoic and the contour of the nodule was clearly shown during the wash-out phase. In all the nodules, the time to peak was shorter and peak intensity was higher compared with the peripheral tissue. CONCLUSION: CEUS played a good role in the evaluation of microcirculation and angiogenesis of peritoneal metastases and metastatic nodules in thickened peritoneum.

Nodules in the thickened greater omentum: a good indicator of lesions?

OBJECTIVE: In patients with unclear ascites, a thickened greater omentum with variable nodules is usually encountered with high-frequency insonation. The purpose of our study was to assess the importance of nodules in indicating the origin of ascites. METHODS: In patients suggested for a biopsy of the greater omentum, if nodules were found in the omentum, sonograms of the nodules were recorded, and during the biopsy, 2 passes were made for each procedure in the nodule and the thickest region without nodules, respectively. A biopsy was considered successful if a specific benign or malignant diagnosis was made. RESULTS: In the 258 patients undergoing sonographically guided biopsies of the greater omentum from November 2001 to November 2008, the percentage of definitive diagnoses was 94.57% (244 of 258), and sonography showed nodules in 62 patients. Nodules were found more often by a 10-MHz transducer (62 cases) than by a 3.5-MHz transducer (15 cases). The percentage of definitive diagnoses by sonographically guided biopsies was 100% (62 of 62) at the sites of the nodules and decreased to 87.1% (54 of 62) at the sites without nodules. According to the pathologic results, 48 cases were peritoneal carcinomatosis, and 14 cases were tuberculous peritonitis. The sensitivity and specificity of nodules for indicating malignant ascites were 77.42% and 75.27%, respectively. CONCLUSIONS: Nodules in the greater omentum were good indicators of lesions and were well shown by a high-frequency transducer. A biopsy at the site of a nodule could substantially increase the positive biopsy result rate.

[Correlation between serum thyroglobulin and thyroid stimulating hormone in populations with non-toxic goiter].

OBJECTIVE: To investigate the correlation between serum thyroglobulin (Tg) and thyroid stimulating hormone (TSH) in populations with non-toxic goiter. METHODS: Thyroid ultrasonography was conducted, and determination of serum triiodothyronine (FT3), thyroxin (FT4), Tg, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) and TSH, and urine iodine were carried out among 609 persons with an average age of 35.4 in Panshan county, a mild iodine-deficient area in Liaoning province, and 1136 persons aged 39.1 on average in Zhangwu county, an iodine sufficient area in Liaoning province, totally 2 320 persons. RESULTS: The serum TSH levels of the populations with diffuse and nodular goiter in Panshan county were (0.11 +/- 0.08) mU/L and (0.90 +/- 0.10) mU/L, significantly higher than those of the normal population in the same areas (1.33 +/- 0.04) mU/L, both P < 0.01. The serum TSH levels of the populations with diffuse and nodular goiter in Zhangwu county were (1.29 +/- 0.13) mU/L and (0.89 +/- 0.14) mU/L, significantly higher than those of the normal population in the same areas (1.74 +/- 0.04) mU/L, both P < 0.01. The serum TSH level of normal population in iodine deficient area was significantly lower than that of normal population in iodine sufficient area (P < 0.01). The serum TSH level of the normal population in Panshan County was significantly lower than that of the normal population in Zhangwu County (P < 0.01). The serum Tg level of the populations with diffuse and nodular goiter in Panshan county were (12.0 +/- 1.21) ng/L and (50.1 +/- 12.20) ng/L, significantly higher than that of the normal population in the same area (9.1 +/- 2.44) ng/L, P < 0.05 and P < 0.01. The serum Tg level of the populations with diffuse and nodular goiter in Zhangwu county were (12.4 +/- 2.11) ng/L and (61.2 +/- 11.86) ng/L, significantly higher than that of the normal population in the same area (7.7 +/- 2.3) ng/L, P < 0.05 and P < 0.01. The Tg level of the normal population in Panshan County was significantly higher than that of the normal population in Zhangwu county (P < 0.01). The Tg level was positively correlated with the thyroid volume in the nodular goiter population. CONCLUSION: The occurrence of goiter is not directly related to TSH stimulation in mild iodine deficient area. Nontoxic goiter shows a thyroid autonomic function. The major cause of high serum Tg in nodular goiter may be the leakage of Tg into blood circulation caused by degeneration of large colloid follicles and destruction of follicular architecture, not the volume increase of thyroid and its autonomic function.