Quantitative Analysis of Whole-Body MRI for Accessing the Degree of Diffuse Infiltration Patterns and Identifying High Risk Cases of Newly Diagnosed Multiple Myeloma.

BACKGROUND: Accurate identification of high-risk multiple myeloma (HRMM) is important for prognostication. The degree of diffuse infiltration patterns on magnetic resonance imaging (MRI) is associated with patient prognosis in multiple myeloma. However, objective indexes to determine the degree of diffuse infiltration patterns are unavailable. PURPOSE: To investigate whether qualitative and quantitative evaluations of diffuse infiltration patterns on MRI could identify HRMM. STUDY TYPE: Retrospective. SUBJECTS: Totally, 180 patients (79 HRMM and 101 standard-risk MM) were assessed. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, and/or p53 mutations was considered to indicate HRMM. FIELD STRENGTH/SEQUENCE: 3.0 T/diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon chemical-shift imaging Quant (mDIXON Quant), and short TI inversion recovery (STIR). ASSESSMENT: Qualitative analysis involved assessing the degree of diffuse marrow infiltration (mild, moderate, or severe), and quantitative analysis involved evaluating apparent diffusion coefficient (ADC), fat fraction (FF), and T2* values. Clinical data such as sex, age, hemoglobin, serum albumin, serum calcium, serum creatinine, serum lactate dehydrogenase, ß2-microglobulin, and bone marrow plasma cells (BMPCs) were also included. STATISTICAL TESTS: Univariate and multivariate analyses, receiver operating characteristic (ROC) curve. P < 0.05 was considered statistically significant. RESULTS: The high-risk group had significantly higher ADC and T2* and lower FF compared with the standard-risk group. Multivariate analysis indicated BMPCs as a significant independent risk factor for HRMM (odds ratio (OR) = 1.019, 95% CI 1.004-1.033), while FF was a significant independent protective factor associated with HRMM (OR = 0.972, 95% CI 0.946-0.999). The combination of BMPCs and FF achieved the highest areas under the curve (AUC) of 0.732, with sensitivity and specificity of 70.9% and 68.3%, respectively. DATA CONCLUSION: Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Preliminary Study of Confounder-Corrected Fat Fraction and R2* Mapping of Bone Marrow in Children With Acute Leukemia.

BACKGROUND: The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. PURPOSE: To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. FIELD STRENGTH/SEQUENCE: 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. ASSESSMENT: BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). STATISTICAL TESTS: Independent sample t-tests, variance analysis, Spearman correlation. RESULTS: BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). DATA CONCLUSION: MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. EVIDENCE LEVEL: 1 Technical Efficacy: 2.

Identifying Key Factors of Hazardous Materials Transportation Accidents Based on Higher-Order and Multilayer Networks.

This paper focuses on the application of higher-order and multilayer networks in identifying critical causes and relationships contributing to hazardous materials transportation accidents. There were 792 accidents of hazardous materials transportation that occurred on the road from 2017 to 2021 which have been investigated. By considering time sequence and dependency of causes, the hazardous materials transportation accidents causation network (HMTACN) was described using the higher-order model. To investigate the structure of HMTACN such as the importance of causes and links, HMTACN was divided into three layers using the weighted k-core decomposition: the core layer, the bridge layer and the peripheral layer. Then causes and links were analyzed in detail. It was found that the core layer was tightly connected and supported most of the causal flows of HMTACN. The results showed that causes should be given hierarchical attention. This study provides an innovative method to analyze complicated accidents, which can be used in identifying major causes and links. And this paper brings new ideas about safety network study and extends the applications of complex network theory.

Differentiation of Diffuse Infiltration Pattern in Multiple Myeloma From Hyperplastic Hematopoietic Bone Marrow: Qualitative and Quantitative Analysis Using Whole-Body MRI.

BACKGROUND: The visual assessment used for diffuse infiltration of multiple myeloma (MM) is inadequate. It can be difficult to differentiate MM from hyperplastic hematopoietic bone marrow (HHBM) because the MRI signal characteristics overlap. PURPOSE: To analyze the bone marrow diffuse signal changes on whole-body MRI caused by MM and HHBM. STUDY TYPE: Retrospective. SUBJECTS: Thirty Four patients with MM (21 men and 13 women), 22 patients with HHBM (9 men and 13 women), and 15 healthy controls (9 men and 6 women). FIELD STRENGTH/SEQUENCE: A 3.0 T MRI; diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon T1 fast field echo, and T2 STIR. ASSESSMENT: Three radiologists analyzed the whole-body MRI alone and in combination with apparent diffusion coefficient (ADC) and fat fraction (FF) with qualitative and quantitative analysis. Normalized T1 and T2 signal intensities (nT1 and nT2) and signal-to-noise ratio (SNR) were obtained. STATISTICAL TESTS: Kruskal-Wallis and chi-square tests. RESULTS: The MM group had significantly higher ADC and significantly lower FF than HHBM and control groups. There was no significant difference in nT1, nT2 or SNR between MM and HHBM (P = 0.932, P = 0.097, and P = 0.110, respectively). Receiver operating characteristic (ROC) analysis using ADC and FF cut-off values of 0.47 × 10-3  mm2 /sec and 20.63%, respectively. The AUC was 0.866 for ADC and 0.886 for FF. The quantitative analysis yielded better specificity (observer 1: 81.8% vs. 27.3%; observer 2: 68.2% vs. 22.7%; and observer 3: 72.7% vs. 18.2%) and a higher diagnostic accuracy (observer 1: 82.1% vs. 51.8%; observer 2: 80.4% vs. 50.0%; observer 3: 76.8% vs. 44.6%) than the qualitative analysis. DATA CONCLUSION: Whole-body MRI combined with DWIBS and mDIXON could be used to differentiate between MM and HHBM. Combining the quantitative ADC and FF with the whole-body MRI improved the specificity and accuracy in differentiating these conditions. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Cerebral blood flow alterations specific to freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) have been associated with deficits in the cortico-basal ganglia-thalamic network. However, the resting-state cerebral blood flow (CBF) alterations specific to FOG in Parkinson's disease (PD) remain unknown. METHODS: In total, sixty PD individuals, including 30 PD with FOG (PD-FOG) and 30 PD without FOG (PD-NFOG), and 30 healthy controls (HC) underwent arterial spin labeling magnetic resonance image. The CBF were voxel-wise compared among the three groups and validated in a different cohort of PD-FOG and PD-NFOG. RESULTS: The results revealed that patients with PD-FOG had increased CBF in bilateral thalamus and the left caudate nucleus and decreased CBF in the left inferior parietal cortex compared to patients with PD-NFOG. The inter-group differences of CBF between PD-FOG and PD-NFOG was confirmed in a different cohort in the validation analysis. Moreover, the CBF in left caudate nucleus was positively correlated with severity of FOG in PD-FOG patients. CONCLUSIONS: Perfusion alterations in both cortical and subcortical regions in the cortico-basal ganglia-thalamic network are related to the development of FOG in PD patients.

Evaluation of serum IgM and IgG antibodies in COVID-19 patients by enzyme linked immunosorbent assay.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sweeping the world since the end of 2019. The titer change of antibodies against SARS-CoV-2 needs to be further clarified, the clinical and preventive value of antibodies still needs to be further investigated. An enzyme-linked immunosorbent assay (ELISA) was established by coating with SARS-CoV-2 recombinant spike protein and used to detect serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 in coronavirus disease 2019 patients to evaluate the pattern of changes of antibodies. The specificity of the ELISA for detection SARS-CoV-2 IgM and IgG were 96% (144/150) and 100% (150/150), respectively. The sensitivity of ELISA was 100% (150/150) for IgM, and 99.3% (149/150) for IgG. SARS-CoV-2-SP-IgM and SP-IgG antibodies could be detected on Day 1 of hospitalization in 12.5% patients, and SP-IgM began to decrease after reaching its peak at around 22-28 days, and become negative at Month 3 in 30% patients and negative at Month 7 in 79% of these patients after onset; IgG reached its peak around Day 22-28 and kept at a high level within the longest observation period for 4 months, it dropped very sharply at 7 months. The positive rates of SP-IgM and SP-IgG were higher than those of reverse transcription-polymerase chain reaction on Day 7 and 4. The established indirect ELISA has good specificity and sensitivity. IgM and IgG against SARS-CoV-2 appeared almost simultaneously in the early stage, and the level of IgG antibodies could not maintain a high plateau in the observation period of 7 months. Our data will help develop the diagnosis and vaccine of SARS-CoV-2.

Role of the Pumilio gene in the reproductive system of Schistosoma japonicum.

The elimination of schistosomiasis, a parasitic disease caused by Schistosoma and a major source of morbidity and mortality in developing countries, faces serious challenges. Although the pumilio protein regulates the reproductive organ development in many species, its role in Schistosoma japonicum is unknown. Thus, this study investigated the function of pumilio in S. japonicum reproduction. The complete coding sequences of S. japonicum Pumilio1 (SjPum1) and SjPum2 genes were cloned and characterized. The full-length open-reading frame SjPum1 (2613 nucleotides) and SjPum2 (4479 nucleotides) genes were obtained. Bioinformatics analysis showed that those genes belonged to the PUF (pumilio and FBF) family. Quantitative polymerase chain reaction analyses revealed that SjPum1 and SjPum2 were differentially expressed throughout the S. japonicum life cycle and were highly expressed in reproductive organs. In situ hybridization results showed that mRNA expression of SjPum2 was higher than that of SjPum1 in the ovary and testis. Knocking down SjPum2 using RNA interference techniques to explore potential reproductive functions showed that compared with the control (untransfected or scrambled mRNA-transfected) worms, the morphology of both male and female reproductive organs was altered, the number of eggs produced by paired females was significantly decreased, and the transcription levels of caspase 3 and caspase 7 genes related to apoptosis were significantly increased. The transcription level of Nanos1 gene which related to reproduction was also significantly increased. Therefore, SjPum2 may play a role in the reproductive development of S. japonicum.

Regional and network properties of white matter function in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract-based spatial statistical analyses of regional activity, patients showed decreased structural-functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post-central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small-worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un-evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.

Potential role of IL-37 signaling pathway in feedback regulation of autoimmune Hashimoto thyroiditis.

IL-37, the anti-inflammatory cytokine of the IL-1 family, plays several key roles in the regulation of autoimmune diseases. Yet, its role in Hashimoto's thyroiditis (HT) is not clear. In the present study, we found that, in tissues from HT patients, most of the follicular epithelial cells were positive for both IL-37 and single Ig IL-1-related receptor (SIGIRR) by immunohistochemical staining, while the infiltrating lymphocytes and other inflammatory cells hardly expressed any. Meanwhile, mRNA expression levels of IL-37 in peripheral blood mononuclear cells (PBMC) of HT patients were significantly higher than those in normal controls measured by quantitative real-time PCR. Finally, we studied the possible role of IL-37 in IFN-γ-stimulated rat FRTL-5 cells. The results showed that IL-1ß, TNF-α, and MCP-1 mRNA levels were significantly decreased, while the expression of IL-4 mRNA was dramatically up-regulated in IFN-γ-stimulated rat thyroid cell line FRTL-5 pre-treated with IL-37. The current study, for the first time, demonstrated that the IL-37 network is involved in Hashimoto's thyroiditis, and IL-37 signaling pathway may ameliorate the excessive autoimmune responses in this chronic lymphocytic thyroiditis.

Value of Apparent Diffusion Coefficient (ADC) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in Differentially Diagnosing Angiomatous Meningiomas and Solitary Fibrous Tumors/Hemangiopericytomas.

BACKGROUND To determine if ADC and DCE-MRI can be used to differentiate angiomatous meningiomas (AMs) from solitary fibrous tumors/hemangiopericytomas (SFT/HPCs). MATERIAL AND METHODS We retrospectively reviewed records of 103 patients from 1 January 1 2014 to 1 November 2018. We enrolled 41 patients who had undergone a 3T MRI, with histologically confirmed AMs in 20 (48.80%) patients, and SFT/HPCs in 21 (51.20%) patients. The ADC and DCE-MRI features were derived and then compared by 2 independent-samples t tests and Wilcoxon rank sum test to obtain the ROC. RESULTS AMs had significantly lower ADC values than did SFT/HPCs, but AMs had significantly higher MCER values than did SFT/HPCs. A threshold value of 1.03×10⁻³ mm²/s for ADC to predict AMs from SFT/HPCs was estimated (AUC=0.902, sensitivity=88.20%, specificity=83.30%). Optimal diagnostic performance (AUC=0.825, sensitivity=84.60%, specificity=81.80%) was obtained when setting MCER=226.7% as the threshold value. CONCLUSIONS The ADC values of AMs were lower than those of SFT/HPCs; the MCER of AMs were greater than those of SFT/HPCs, and ADC was more useful than MCER, and these parameters could help diagnosis.

Histogram Analysis Parameters ADC for Distinguishing Ventricular Neoplasms of Ependymoma, Choroid Plexus Papilloma, and Central Neurocytoma.

BACKGROUND To determine if histograms of ADC can be used to differentiate ventricular ependymomas, choroid plexus papillomas (CPPs), and central neurocytomas (CNCs). MATERIAL AND METHODS We retrospectively reviewed records from 185 patients from 1 January 2014 to 1 November 2018. We finally included a total of 60 patients: 36 (60.00%) had histologically confirmed ependymomas, 10 (16.67%) had CPPs, and 14 (23.33%) had CNCs, as determined by routine MRI scanning at 3.0T. The ADC histogram features were derived and then compared by Kruskal-Wallis test (they were not normally distributed). Bonferroni test was used to compare the 2 groups and then we determined the ROC. RESULTS Ependymomas had significantly higher mean, perc.01%, perc.10%, perc.50%, perc.90%, and perc.99% than CNCs. Ependymomas had significantly lower skewness than CNCs. Histogram metrics derived from mean, perc.01%, perc.10%, perc.50%, and perc.90% were significantly lower in the CNCs group than in the CPPs group. CPPs showed significantly lower skewness than CNCs. A threshold value of 86.50 for perc.50% to predict ependymomas from CNCs was estimated (AUC=0.97, sensitivity=97.20%, specificity=85.70%). Optimal diagnostic performance to predict CPPs from CNCs (AUC=0.96, sensitivity=100.00%, specificity=85.70%) was obtained when setting Perc.50%=84.00 as the threshold value. CONCLUSIONS The ADC histogram analysis may help to discriminate ependymomas, CPPs, and CNCs.

An Efficient Schistosoma japonicum Bivalent Membrane Protein Antigen DNA Vaccine Against Schistosomiasis in Mice.

BACKGROUND Schistosomiasis is one of the most important infectious parasitic diseases in the world. The most important was to control schistosomiasis is through a combination of medical therapy and immunization. The membrane antigens Tsp2 and 29 from Schistosoma are promising anti-schistosomiasis vaccine candidates. MATERIAL AND METHODS In this study, the pcDNA3.1(+)-SjTsp2, pcDNA3.1(+)-Sj29, and pcDNA3.1 (+)-SjTsp2-29 eukaryotic expression vectors were successfully constructed as DNA vaccines, and the protective abilities of these vaccines were evaluated in mice. RESULTS The results showed that vaccination with SjTsp2, Sj29, and SjTsp2-29 reduced parasite burden and hepatic pathology compared to the control group, and the protective effect of the bivalent SjTsp2-29 DNA vaccine was better than that of the univalent SjTsp2 or Sj29 DNA vaccines. We also found high levels of IgG, IgG1, and IgG2a against SjTsp2, Sj29, and SjTsp2-29 DNA vaccines, with high expression of IFN-γ and no IL-4 in the mice. CONCLUSIONS The double-membrane antigen DNA vaccine SjTsp2-29 elicited protection against Schistosoma infection and might serve as a vaccine candidate.

Function of Nanos1 gene in the development of reproductive organs of Schistosoma japonicum.

Nanos is a necessary factor in the differentiation and migration of primordial germ cells. It is closely associated with the development of genitalia in a wide range of species. We questioned whether Nanos was involved in the reproductive organ development of Schistosoma japonicum. Firstly, by in situ hybridization, S. japonicum Nanos1 (SjNanos1) gene was expressed mainly in reproductive organs of S. japonicum. Then, the paired schistosome of 28 days post-infection (dpi) was transfected with SjNanos1 small interfering RNA three times and cultured in vitro for 10 days. SjNanos1 expression suppression in the mRNA and protein levels were confirmed compared to that of the controls. The morphological changes in reproductive organs and egg production were observed after SjNanos1 gene knockdown. The results observed by confocal laser scanning microscopy showed significant changes in the morphology of reproductive organs of parasites, especially the female ovaries, vitellarium, and the male testes, after RNAi. In addition, SjNanos1 silencing also induced the reduction of eggs, and affected the changes of reproduction-related genes, like Pumilio, CNOT6L, and Fs800. Therefore, our findings demonstrate that the SjNanos1 gene is essential in the development of reproductive organs and the egg production of S. japonicum.

Lack of IL-17 signaling decreases liver fibrosis in murine schistosomiasis japonica.

Accumulating evidence has identified the profibrogenic properties of IL-17A in organ fibrosis. However, the role of IL-17A signal in liver fibrosis induced by Schistosoma japonicum infection remains unclear. In this study, we investigated liver fibrosis in wild-type (WT) and IL-17RA(-/-) mice upon S. japonicum infection. Hepatic IL-17A, IL-17C, IL-17E (IL-25), IL-17F, IL-17RA, IL-17RB and IL-17RC transcript levels were determined by RT-PCR. IL-17A(+) cells were analyzed by flow cytometry and confocal microscopy among granuloma cells. Immunostaining of IL-17R was performed on liver sections. Collagen deposition was assessed by Van Gieson's staining. IL-17A, IL-17C, IL-17E, IL-17F, IL-17RA and IL-17RC mRNA levels were dramatically increased in fibrotic livers. Among granuloma cells, CD3(+) and CD3(-) lymphocytes, neutrophils and macrophages were found to express IL-17A. Compared to WT, IL-17RA(-/-) mice displayed attenuated granulomatous inflammation, liver fibrosis, improved liver function and high survival. Meanwhile, α-smooth muscle actin staining and the expression of fibrogenic genes (transforming growth factor ß, IL-13 and collagen-I) as well as IL-17A-induced proinflammatory mediators (IL-1ß, IL-6, tumor necrosis factor α, CXCL1 and CXCL2) and proteinases (MMP3 and TIMP1) involved in fibrosis were markedly reduced in IL-17RA(-/-) mice. In addition, Th2 cytokines IL-4 and IL-17E (IL-25) were also decreased in IL-17RA(-/-) mice. These results indicated that IL-17A signal contributes to the pathogenesis of liver fibrosis in murine schistosomiasis. This effect was induced possibly by activating hepatic stellate cells and stimulating the release of proinflammatory cytokines and chemokines. Furthermore, the Th2 response was also enhanced by IL-17A signals. Our data demonstrate that IL-17A may serve as a promising target for antifibrotic therapy.

Elevated interleukin-1ß in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PURPOSE OF THE STUDY: To explore the relationship between IL-1ß expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). MATERIALS AND METHODS: qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1ß in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. RESULTS: Although no significant differences in IL-1ß levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1ß mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1ß mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1ß levels with the pathogenesis of HT. CONCLUSION: Our study suggests that IL-1ß may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

mTOR regulate EMT through RhoA and Rac1 pathway in prostate cancer.

Recently, an increasing number of studies have suggested that mTOR plays a critical role in the regulation of tumor cell motility, invasion and cancer metastasis. However, little is known about the signaling mechanisms in regulating epithelial-mesenchymal transition (EMT) of prostate cancer. In this study, we found that the expression levels of Raptor and Rictor in prostate cancer tissues were elevated, which may suggest that Raptor and Rictor signaling pathways are associated with prostate cancer progression and metastasis. Inhibition of mTORC1 or mTORC2 by knock down of Raptor or Rictor, respectively, migration and invasion of prostate cancer were attenuated. Furthermore, EMT, a characterized by the changed expression levels of various markers like E-cadherin, ß-catenin, N-cadherin, and vimentin emergend following inhibition of Raptor or Rictor. Finally, the small GTPases (RhoA and Rac1) which were crucial regulatory proteins in cell migration and invasion were inactivited after downregulating Raptor and Rictor. These results suggest that mTOR regulate EMT at least in part by down regulation of RhoA and Rac1 signaling pathways. Our findings provide novel very attractive target strategies that the inhibition of mTOR signaling pathways may retard prostate cancer migration and invasion at early stages.

Preliminary characterization and expression of Vasa-like gene in Schistosoma japonicum.

The Vasa gene is a vital germline marker to study the origin and development of germ cells and gonads in many organisms. Until now, little information was available about the characteristics of the Vasa gene in Schistosoma japonicum (S. japonicum). In this study, we cloned the open reading frame (ORF) of the S. japonicum Vasa-like gene (Sj-Vasa). The expression pattern and tissue localization of Sj-Vasa were also analyzed. Our results showed that Sj-Vasa shared the general feature of DEAD-box family member proteins. Sj-Vasa was transcribed and expressed throughout the S. japonicum life cycle with transcription exhibiting high levels at day 24 in both male and female worms, and the expression level in the female was always higher than that in the male. Sj-Vasa protein was localized in a variety of tissues of adult schistosomes, including the gonads (ovary, vitellarium, and testes), the subtegument, and some cells of the parenchyma. To our knowledge, this is the first report of preliminary characterization and expression of the Vasa-like gene that may play an important role in the development of the worm, especially in reproductive organs of S. japonicum.

Preliminary exploration of amide proton transfer weighted imaging in differentiation between benign and malignant bone tumors.

Purpose: To explore the value of 3D amide proton transfer weighted imaging (APTWI) in the differential diagnosis between benign and malignant bone tumors, and to compare the diagnostic performance of APTWI with traditional diffusion-weighted imaging (DWI). Materials and methods: Patients with bone tumors located in the pelvis or lower limbs confirmed by puncture or surgical pathology were collected from January 2021 to July 2023 in the First Affiliated Hospital of Zhengzhou University. All patients underwent APTWI and DWI examinations. The magnetization transfer ratio with asymmetric analysis at the frequency offset of 3.5 ppm [MTRasym(3.5 ppm)] derived by APTWI and the apparent diffusion coefficient (ADC) derived by DWI for the tumors were measured. The Kolmogorou-Smirnou and Levene normality test was used to confirm the normal distribution of imaging parameters; and the independent sample t test was used to compare the differences in MTRasym(3.5 ppm) and ADC between benign and malignant bone tumors. In addition, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different imaging parameters in differentiation between benign and malignant bone tumors. P<0.05 means statistically significant. Results: Among 85 bone tumor patients, 33 were benign and 52 were malignant. The MTRasym(3.5 ppm) values of malignant bone tumors were significantly higher than those of benign tumors, while the ADC values were significantly lower in benign tumors. ROC analysis shows that MTRasym(3.5 ppm) and ADC values perform well in the differential diagnosis of benign and malignant bone tumors, with the area under the ROC curve (AUC) of 0.798 and 0.780, respectively. Combination of MTRasym(3.5 ppm) and ADC values can further improve the diagnostic performance with the AUC of 0.849 (sensitivity = 84.9% and specificity = 73.1%). Conclusion: MTRasym(3.5 ppm) of malignant bone tumors was significantly higher than that of benign bone tumors, reflecting the abnormal increase of protein synthesis in malignant tumors. APTWI combined with DWI can achieve a high diagnostic efficacy in differentiation between benign and malignant bone tumors.

IL-17 neutralization significantly ameliorates hepatic granulomatous inflammation and liver damage in Schistosoma japonicum infected mice.

IL-17 is a signature cytokine of Th17 cells implicated in the induction and progression of chronic inflammatory diseases. Several studies in C57BL/6 mice, immunized with soluble schistosome egg Ags (SEA) in complete Freund's adjuvant (CFA), and subsequently infected with Schistosoma mansoni (S. mansoni) have shown that severe hepatic granulomatous inflammation is correlated with high levels of IL-17. Here, using a Schistosoma japonicum (S. japonicum) larvae infection model in C57BL/6 mice, we analyzed the dynamic expression of IL-17 in infected livers by RT-qPCR and ELISA. Our results showed that IL-17 expression was elevated during the course of infection. The temporal expression of IL-17 and cytokines/chemokines involved in the induction and effector function of Th17 cells was paralleled with hepatic granulomatous inflammation. Treatment of S. japonicum infected mice with IL-17-neutralizing mAb resulted in significant downmodulation of granulomatous inflammation and hepatocyte necrosis. The protection was associated with lower expression of proinflammatory cytokines/chemokines, such as IL-6, IL-1ß, CXCL1, and CXCL2 and a reduced number of infiltrating neutrophils. Anti-IL-17 mAb significantly ameliorated hepatic granulomatous inflammation, partly through the downregulation of proinflammatory cytokines/chemokines and recruitment of neutrophils. Our data indicate a pathogenic role of Th17/IL-17 in hepatic immunopathology in S. japonicum infected mice.

Schistosoma japonicum: Tsunagi/Y14 protein plays a critical role in the development of the reproductive organs and eggs.

Tsunagi/Y14 is an evolutionarily conserved RNA-binding protein that is required for the maintenance of oogenesis and the masculinization of the germ-line in many animal models. We speculated that Tsunagi/Y14 might also regulate reproductive organ development in Schistosoma japonicum (S. japonicum, Sj). Sj Tsunagi/Y14 and control double-stranded RNAs were introduced into schistosomula by electroporation respectively. These transfected schistosomula were cultured in vitro for 1, 3 or 5 days. The mRNA and protein levels of the target gene in the cultured schistosomula were significantly suppressed compared with those of the control group. Furthermore, BALB/c mice were infected with the transfected schistosomula for 6 weeks and were sacrificed to harvest the adult worms. We found that the silencing of Sj Tsunagi/Y14 led to defects in reproductive organs development in both male and female worms. Moreover, it also affected the size, quantity and activity of the eggs in the mice liver. Our findings indicated that Tsunagi/Y14 plays a critical role in the development of reproductive organs and eggs in S. japonicum.