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Mycotoxin contamination in agri-food systems has been a serious global concern over the past few decades. Corn is easily contaminated by Ochratoxin A (OTA) and Zearalenone (ZEN), which seriously threaten the survival and health of humans and animals. Herein, a rapid and sensitive method of OTA and ZEN dual quantum dots (QDs) fluorescence immunochromatographic test strip was established in this study. OTA and ZEN fluorescence probes were prepared by carbodiimide. The OTA-OVA, ZEN-BSA and staphylococcal protein A were sprayed on the nitrocellulose filter membrane as the T1 line, T2 line and control line of the dual test strip, which exhibited high sensitivity, accuracy and specificity. For quantitative detection of OTA, the linear regression equation was y = 0.3222x + 0.3834 (R2 = 0.9687), LOD and IC50 were 0.132 ng/mL and 2.296 ng/mL, and the linear detection range was 0.269 ng/mL to 19.588 ng/mL. In addition, for quantitative detection of ZEN, its linear regression equation was y = 0.3077x + 0.3777 (R2 = 0.9648), LOD and IC50 were 0.125 ng/mL and 2.495 ng/mL, and the linear detection range was 0.264 ng/mL to 23.55 ng/mL. Briefly, the OTA and ZEN dual QDs immunochromatographic test strip was favored for the simultaneous detection of OTA and ZEN in corn. [ABSTRACT FROM AUTHOR]

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan–Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial–mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer. [ABSTRACT FROM AUTHOR]

Awareness and uptake of the meningitis vaccine remains low among marginalized groups, such as Latino men who have sex with men (LMSM), potentially due to structural and psychosocial barriers in accessing preventative healthcare. The current study explored awareness and uptake of meningitis vaccines among a group of LMSM (N = 99) living in South Florida. A three-pronged variable selection approach was utilized prior to conducting regression models (linear and logistic). Overall, 48.5% of the participants reported little to no knowledge about meningitis vaccines, and 20.2% reported being vaccinated. Living with HIV (OR = 10.48) and time since outbreak (OR = 1.03) were significant predictors of meningitis vaccine uptake. No significant correlates of meningitis vaccine awareness were identified. More research is needed to identify other important factors associated with meningitis vaccine awareness and uptake among LMSM, a multiple marginalized group. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that delayed [68 Ga]Ga-PSMA PET/CT imaging improves lesion detection compared to early [68 Ga]Ga-PSMA PET/CT in patients with prostate cancer. However, the sole use of delayed [68 Ga]Ga-PSMA PET/CT has been limited due to the insufficient number of photons obtained with standard PET/CT scanners. The combination of early and delayed [68 Ga]Ga-PSMA standard PET/CT may be considered, and it is challenging to incorporate into a high-demand clinical setting. Long field-of-view (LFOV) PET/CT scanners have higher sensitivity compared to standard PET/CT. However, it remains unknown whether the image quality of solitary delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging is adequate to satisfy clinical diagnostic requirements. Therefore, the purpose of this study was to evaluate the image quality of delayed [68 Ga]Ga-PSMA LFOV PET/CT and examine the feasibility of utilizing delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging alone in patients with prostate cancer. Methods: The study sample consisted of 56 prostate cancer patients who underwent [68 Ga]Ga-PSMA-11 LFOV PET/CT scanning between December 2020 and July 2021. All patients were subjected to early LFOV PET/CT imaging at 1-h post-injection as well as delayed LFOV PET/CT imaging at 3-h post-injection using [68 Ga]Ga-PSMA-11. The image quality and diagnostic efficiency of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging was analyzed. Results: The results showed that delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT yielded satisfactory image quality that fulfilled clinical diagnostic benchmarks. Compared to early imaging, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT demonstrated heightened lesion SUVmax values (11.0 [2.3–193.6] vs. 7.0 [2.0–124.3], P < 0.001) and superior tumor-to-background ratios (3.3 [0.5–62.2] vs. 1.7 [0.3–30.7], P < 0.001). Additionally, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT detected supplementary lesions in 14 patients (25%) compared to early imaging, resulting in modifications to disease staging and management plans. Conclusions: In summary, the findings indicate that the image quality of delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT is satisfactory for meeting clinical diagnostic prerequisites. The use of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging in prostate cancer simplifies the examination protocol and improves patient compliance, compared to [68 Ga]Ga-PSMA-11 standard PET/CT which necessitates both early and delayed imaging. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 35-year-old man with a history of uraemia who presented with increased tumor marker levels. The patient underwent both [18F]F-FDG PET/CT and [68 Ga]Ga-FAPI-04 total-body PET/CT scans. The [18F]F-FDG PET/CT showed increased FDG uptake in osteogenic destructive bones and extensive calcification, while the [68 Ga]Ga-FAPI-04 PET/CT revealed FAPI uptake in the same lesions as well as additional abnormal foci. The study suggests that FAPI PET/CT may be superior to FDG PET/CT in diagnosing and assessing kidney fibrosis and related calcium phosphorus metabolism disorders in chronic kidney disease. [Extracted from the article]

Background: Acute myeloid leukemia (AML) and hyperleukocytosis have an unfavorable prognosis, but the impact of hyperleukocytosis on the prognosis of pediatric AML remains uncertain. We investigated the clinical characteristics and prognosis of pediatric AML with hyperleukocytosis, defined as WBC ≥ 50 × 109/L. Methods: A total of 132 patients with newly diagnosed childhood AML with hyperleukocytosis were consecutively enrolled at our center from September 2009 to August 2021 to investigate prognostic factors and clinical outcomes. Results: Hyperleukocytosis occurred in 27.4% of AML patients. Pediatric patients with hyperleukocytosis had similar CR and OS rates to those without hyperleukocytosis, but had a lower EFS rate. In our study, rates of CR1, mortality, relapsed/refractory disease, and HSCT were comparable between AML patients with WBC counts of 50–100 × 109/L and ≥ 100 × 109/L. AML patients with a WBC count of 50–100 × 109/L had a similar 5-year OS rate to patients with a WBC count ≥ 100 × 109/L (74.6% vs. 75.4%, P = 0.921). Among all patients with hyperleukocytosis, the FAB M5 subtype was associated with significantly inferior survival, and the prognosis of CBF-AML was good. Conclusions: Pediatric AML patients with hyperleukocytosis have the similar prognosis regardless of whether their WBC count is 50–100 × 109/L or ≥ 100 × 109/L. [ABSTRACT FROM AUTHOR]

Background: [68Ga]Ga-FAPI-04 (gallium-68-labeled fibroblast activation protein inhibitor-04) PET/CT has been widely used in diagnosing malignant tumors. Total-body PET/CT has a long axial field of view and provides higher sensitivity compared to traditional PET/CT. However, whether the reduced injected dose of [68Ga]Ga-FAPI-04 could obtain qualified imaging has not been evaluated. Purpose: To explore the effect of half-dose [68Ga]Ga-FAPI-04 on image quality and tumor detectability in oncology patients. Methods: A total of twenty-seven patients with tumors or clinically suspected tumors were included, and all patients were scanned with total-body PET/CT after an injected dose of 0.84–1.14 MBq/kg [68Ga]Ga-FAPI-04. All patients obtained superior image quality with 300 s original acquisition time. Images were reconstructed using 180 s, 120 s, 60 s, 40 s, 30 s, 20 s scanning duration by ordered subset expectation maximization algorithm. The subjective image quality of all patients in each time group was scored using 5-point Likert scale. Mediastinal blood pool, liver, spleen, and muscle were analyzed as background using semi-quantitative parameters maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), standard deviation (SD), and signal to noise ratio (SNR). The lesion detection rate, SUVmax, and tumor-to-background ratio (TBR) were calculated for tumors confirmed by pathology. Results: The subjective image quality score decreased with the shortening of scanning time; however, both 180 s and 120 s images met the diagnostic requirements in terms of overall quality, lesion conspicuity, and image noise. The SUVmax of background increased with the reduction of scanning time, while the SUVmean was relatively stable. With the shortening of scanning time, the SD gradually increased, and the SNR gradually decreased, which was consistent with subjective image quality scores. In 180 s and 120 s images, all 11 primary lesions and 79 metastatic lesions were detected. The SUVmax of tumor focus showed an increasing trend as same as the background. Compared with 300 s, the TBR muscle had no statistical difference in 180 s and 120 s. Conclusions: Half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging can shorten the acquisition time to 120 s with acceptable subjective image quality and 100% tumor detection rate. Total-body PET/CT imaging with a half-dose [68Ga]Ga-FAPI-04 and reduced acquisition time can be used in radiation-sensitive and poor tolerant to prolong horizontal positioning and waiting time populations such as children and gravidas. [ABSTRACT FROM AUTHOR]

Background: PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses. Methods: For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18F-FDG PET/CT. Maximum standardised uptake values (SUVmax) were determined. The usefulness of SUVmax for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis. Results: Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUVmax of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUVmax was significantly associated with PD-L1 expression in TCs and TIICs (P < 0.001 and P = 0.018, respectively). Using SUVmax cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively. Conclusion: Higher 18F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC. [ABSTRACT FROM AUTHOR]

Purpose: Multiple myeloma (MM) is a malignant disease characterized by the secretion of monoclonal immunoglobulins and has a high demand for amino acids. [11C]methionine total-body PET is capable of noninvasive dynamic monitoring of radiotracer in vivo, thus providing a way to reveal the dynamic changes of myeloma metabolism. This study aims to analyze the metabolic process of [11C]methionine based on kinetic modeling, and to preliminary reveal its application value in MM. Methods: Dynamic total-body [11C]methionine PET/CT was conducted with uEXPLORER in 12 subjects (9 MM patients and 3 controls). The tissue time activity curves (TACs) of organs and bone marrows were extracted. Model fitting of TACs was operated using PMOD Kinetic Modeling. After validation by Goodness of fit (GOF), the reversible two-tissue compartment model (2T4k) was used to further analysis. R software was used to analyze the correlation between kinetic parameters and clinical indicators. Results: The 2T4k has passed the criterion of GOF and was used to fit the data of 0-20 minutes. The [11C]methionine net uptake rate (Ki) was significantly higher in the MM lesions than in the non-myeloma controls (control: 0.040±0.007 mL/g/min, MM: 0.171±0.108 mL/g/min, p=0.009). The Ki values were found to be correlated with M protein levels in MM patients. MM patients with t(4;14) translocations had an elevated k4 value compared with t(4;14) negative patients. Conclusion: MM lesions have a propensity for uptake of [11C]methionine. The serum levels of M protein are correlated with [11C]methionine uptake rate in myeloma. Metabolic classification based on the k4 value may be a promising strategy for risk stratification in MM. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a gynecological malignancy characterized with increasing death rate in the world. It is clinically reported that chemotherapy against ovarian cancer is still found with poor curative effect and potential side effect. Plumbagin is an emerging anti-cancer compound. Although some experimental findings of plumbagin anti-ovarian cancer activity are described, the pharmacological targets should be further explored. In this study, we aimed to investigate the underlying pharmacological activities and targets of plumbagin against ovarian cancer in vitro. As results, in silico docking analysis suggested plumbagin potently treating ovarian cancer through regulating pharmacological targets, including octamer-binding transcription factor 4 (OCT4) and Kruppel-like factor 4 (KLF4). The preliminary experimental data showed that plumbagin treatment inhibited cell growth and induced apoptosis in cancer cells. In addition, decreased mRNA expressions of intracellular OCT4, PCNA, and elevated KLF4 mRNA activation were detected in plumbagin-treated cancer cells. Furthermore, immunostaining determination showed reduced OCT4-positive cells and increased KLF4-positive cells were observed following plumbagin treatments. To sum up, our current findings have preliminarily showed the anti-ovarian cancer benefits of plumbagin, and the pharmacological targets may be identified as KLF4 and OCT4 pathway. Thus, we conclude that plumbagin may be a bioactive compound for ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin's lymphoma (NHL) and acute leukemia (AL) in particular are lacking. Objective: The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL. Methods: In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia. Results: Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4–100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%. Conclusion: Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL. [ABSTRACT FROM AUTHOR]

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a grave threat to human life and health, it is essential to develop an efficient and sensitive detection method to identify infected individuals. This study described an electrode platform immunosensor to detect SARS-CoV-2-specific spike receptor-binding domain (RBD) protein based on a bare gold electrode modified with Ag-rGO nanocomposites and the biotin-streptavidin interaction system. The Ag-rGO nanocomposites was obtained by chemical synthesis and characterized by electrochemistry and scanning electron microscope (SEM). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to record the electrochemical signals in the electrode modification. The differential pulse voltammetry (DPV) results showed that the limit of detection (LOD) of the immunosensor was 7.2 fg mL−1 and the linear dynamic detection range was 0.015 ~ 158.5 pg mL−1. Furthermore, this sensitive immunosensor accurately detected RBD in artificial saliva with favorable stability, specificity, and reproducibility, indicating that it has the potential to be used as a practical method for the detection of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Purpose: [68 Ga]Ga-FAPI-04 PET/CT has been widely used in oncology patients. The patients need to lie still for 20–30 min during scan after waiting for 60 min post-tracer injection in traditional [68 Ga]Ga-FAPI-04 PET/CT scan. This is difficult for some patients who are intolerant to prolonged horizontal positioning and waiting time. Therefore, we evaluated the diagnostic value of the images obtained in ultra-early and fast scan (5-min p.i., 30-s acquisition time) by the total-body [68 Ga]Ga-FAPI-04 PET/CT and to investigate whether they could meet the requirements of clinical diagnosis. Methods: Total-body [68 Ga]Ga-FAPI-04 PET/CT was conducted in 12 patients at the Renji Hospital. Patients underwent PET with two acquisitions: 5-min p.i. and 30-s acquisition time (ultra-early and fast imaging) and 60-min p.i. and 300-s acquisition time (traditional imaging). Mean [68 Ga]Ga-FAPI-04 injection dose was 1.85 MBq/kg. Results: Forty-four lesions were detected in 12 patients on traditional imaging. All the 44 lesions on conventional imaging could also detected by ultra-early and fast imaging. For all the 12 patients, the tumor stage did not change, as same lesions were visible for every case in both images. There was no statistically significant difference in SUVmax of lesions between ultra-early and fast imaging and traditional imaging (12.5 ± 8.7 vs 13.7 ± 8.5, P = 0.528). Background bloodpool (4.0 ± 0.6 vs 0.9 ± 0.2, P < 0.001)and liver (2.5 ± 0.7 vs 1.0 ± 0.5, P < 0.001)at traditional imaging showed a significant decrease in SUVmean compared to ultra-early and fast imaging. Conclusions: Ultra-early and fast imaging versus traditional [68 Ga]Ga-FAPI-04 imaging resulted in equivalent tumor detection and lesion uptake. Ultra-early and fast total-body [68 Ga]Ga-FAPI-04 PET/CT scan could meet clinical diagnostic requirements for patients with poor tolerant to prolonged horizontal positioning and waiting time. [ABSTRACT FROM AUTHOR]

Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative disease, and newly diagnosed patients frequently cannot tolerate hematopoietic stem cell transplantation (HSCT) at diagnosis due to their poor condition. This retrospective analysis aimed to explore the short-term effect of decitabine-dominant therapy on improving the condition of JMML patients before HSCT. The subjects were 10 JMML patients. All patients were treated with decitabine after low-dose chemotherapy with an interval of 4 weeks before bridging to HSCT. The median treatment course was 3 cycles, and the overall response rate (ORR) was 70.0% after one cycle and 71.4% after three cycles. White blood cell (WBC) and monocyte counts were significantly lower after treatment, and spleen volume was also lower, though not significantly lower. The 12 month progression-free survival rate (PFS) was 80.0 ± 12.6%. Decitabine-dominant therapy was beneficial for reducing tumor burden and improving clinical condition. [ABSTRACT FROM AUTHOR]

Introduction/objectives: To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis. Method: Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls. Results: Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration. Conclusion: Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably. Key Points • Antigen processing and presentation and leukocyte transendothelial migration may play key roles in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN), which is usually generated by Fusarium species, is common contamination of corn. ZEN induces estrogen effects and disrupts the reproductive system of humans and animals. Herein, we established a method of quantum dots (QDs) immunochromatographic test strips for the detection of ZEN. In this method, QDs (Q2605, G2701A) and anti-ZEN monoclonal antibodies were conjugated by carbodiimide. The control line and test line of test strips were sprayed with staphylococcal protein A and ZEN-BSA, respectively. The standard curve equation of quantitative detection was y = 0.3958x + 0.3233 (R2 = 0.9914). The limit of detection and 50% comparative inhibition (IC50) were 0.273 ng/mL and 2.792 ng/mL, respectively. The test strips showed a linear range of detection (0.488–15.996 ng/mL). In the intra-assay, recovery ranged from 85.62 to 98.57% and the coefficient of variation (CV) was less than 5.53%. In the inter-assay, it ranged from 84.43 to 100.54% with a CV lower than 8.79%. Briefly, the test strips were established and could be used as a rapid and sensitive method for the detection of ZEN in corn. [ABSTRACT FROM AUTHOR]

Purpose: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. Methods: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. Results: Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02–1.10, 95% CI range [1.004–1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58–3.28 95% CI range [1.18–4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46–0.64, 95% CI range [0.34–0.86]). Conclusions: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Adenomyosis is a common gynecological disease, but its pathogenesis and treatment options are not yet completely clear. This study aimed to investigate the analgesic effect of berberine on tamoxifen-induced neonatal mouse adenomyosis and its curative effects on the disease. Methods: The mouse adenomyosis model was established in neonatal female mice via oral administration of tamoxifen suspended solution. Adenomyosis mice were given berberine by intraperitoneal injection with the dosage of 5, 10, and 20 mg/kg body weight, respectively, at 17 weeks after birth. The pain sensation of the mice was evaluated by hotplate and tail-flick tests. The mRNA levels of gene expression were detected by RT-qPCR. The protein expression was analyzed by ELISA and Western blot. Results: Berberine reduced the uterine weight, suppressed the myometrial infiltration of ectopic endometrium, improved the hotplate and tail-flick latency of the adenomyosis mice. Mechanistically, berberine downregulated the expression of genes related to pain and inflammation, such as TRPV1, COX-2, VEGF and OTR, impaired the inflammatory response at the DRG site, and inhibited the expression of TLR4 in DRG and uterine tissues. Conclusions: Berberine attenuates hyperalgesia and exhibits analgesic and therapeutic effects on adenomyosis mice. [ABSTRACT FROM AUTHOR]

Ribosomal protein dysfunction causes diverse human diseases, including Diamond–Blackfan anemia (DBA). Despite the universal need for ribosomes in all cell types, the mechanisms underlying ribosomopathies, which are characterized by tissue-specific defects, are still poorly understood. In the present study, we analyzed the transcriptomes of single purified erythroid progenitors isolated from the bone marrow of DBA patients. These patients were categorized into untreated, glucocorticoid (GC)-responsive and GC-non-responsive groups. We found that erythroid progenitors from untreated DBA patients entered S-phase of the cell cycle under considerable duress, resulting in replication stress and the activation of P53 signaling. In contrast, cell cycle progression was inhibited through induction of the type 1 interferon pathway in treated, GC-responsive patients, but not in GC-non-responsive patients. Notably, a low dose of interferon alpha treatment stimulated the production of erythrocytes derived from DBA patients. By linking the innately shorter cell cycle of erythroid progenitors to DBA pathogenesis, we demonstrated that interferon-mediated cell cycle control underlies the clinical efficacy of glucocorticoids. Our study suggests that interferon administration may constitute a new alternative therapeutic strategy for the treatment of DBA. The trial was registered at www.chictr.org.cn as ChiCTR2000038510. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to identify potential key genes and pathways, using bioinformatics, underlying the potentially common molecular mechanisms between endometriosis (EMS) and ovarian cancer (OC). Methods: Two datasets were collected from the Gene Expression Omnibus database, and the limma package identified common differentially expressed genes (DEGs) in the EMS and OC groups compared to controls. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene interaction network, and module analyses identified the enriched pathways associated with DEGs. A protein–protein interaction (PPI) network was then constructed, and the CytoHubba plugin of Cytoscape was used to calculate the degree of connectivity for proteins in the PPI network. Results: A total of 571 overlapping DEGs were identified between EMS and OC (vs. controls). Enriched DEGs were associated with 36 gene ontology terms and 7 Kyoto Encyclopedia of Genes and Genomes pathways, which were mainly associated with deactivation of the p53 signaling pathway. The Kaplan–Meier plotter platform confirmed the expression of the identified hub genes, and survival analysis suggested that CCNB1, CCNB2, BUB1B, CCNA2, KIF2C, and TOP2A are associated with decreased survival and disease-free survival rates of OC. Conclusion: The key pathways identified herein elucidate the possible mechanism by which EMS evolves into OC; further, the identified hub genes may serve as potential biomarkers to predict OC occurrence and prognosis. [ABSTRACT FROM AUTHOR]

Background: 68 Ga-PSMA PET/CT has been widely used in patients with prostate cancer. Due to the limited axial field of view of conventional PET scanners, whole-body dynamic 68 Ga-PSMA PET/CT has not been performed. We investigated the time-activity curves (TACs) of prostate cancer pathological lesions and physiologic bladder activity to determine the optimal 68 Ga-PSMA PET/CT imaging time by total-body (TB) PET/CT. Methods: Dynamic TB-PET performed on 11 patients with prostate cancer was analyzed. TACs were obtained by drawing regions of interest in normal organs and pathological lesions (primary prostate lesions and lymph nodes and bone metastases). We evaluated the 68 Ga-PSMA uptake pattern of normal organs, urinary bladder, and pathological lesions. Results: The urinary bladder TAC increased slowly between 180 and 330 s post-injection and then rapidly between 5.5 and 60.0 min post-injection. The pathological lesion uptake increased rapidly during the first 5 min post-injection and then slowly through the remaining 55 min. Six minutes post-injection was the optimal time with the highest pathological lesion SUVmean values still higher than the urinary bladder activity value. However, these prostate lesion, lymph node metastasis, and bone metastasis SUVmean values were one-third, one-half, and one-half the corresponding values 60 min post-injection, suggesting that early imaging might miss low PSMA uptake lesions. A minimum of 35 min post-injection was required for the pathological lesions to have SUVmean values similar to the corresponding values at 60 min post-injection (all P > 0.05), even though the pathological lesion SUVmean values showed a continuous upward trend through the 60 min. Conclusions: Combining early dynamic 68 Ga-PSMA PET (75–360 s) and conventional static imaging 60 min post-injection could avoid the urinary bladder activity interference to better detect pathological lesions and lesions with relatively low PSMA uptake. The pathological lesion SUVmean values at 35–59 min and 60 min post-injection were similar, so 68 Ga-PSMA PET imaging could also be made at 35–59 min post-injection. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) often results in an inhibitory environment at the injury site. In our previous studies, transplantation of a scaffold combined with stem cells was proven to induce neural regeneration in animal models of complete SCI. Based on these preclinical studies, collagen scaffolds loaded with the patients' own bone marrow mononuclear cells or human umbilical cord mesenchymal stem cells were transplanted into SCI patients. Fifteen patients with acute complete SCI and 51 patients with chronic complete SCI were enrolled and followed up for 2 to 5 years. No serious adverse events related to functional scaffold transplantation were observed. Among the patients with acute SCI, five patients achieved expansion of their sensory positions and six patients recovered sensation in the bowel or bladder. Additionally, four patients regained voluntary walking ability accompanied by reconnection of neural signal transduction. Among patients with chronic SCI, 16 patients achieved expansion of their sensation level and 30 patients experienced enhanced reflexive defecation sensation or increased skin sweating below the injury site. Nearly half of the patients with chronic cervical SCI developed enhanced finger activity. These long-term follow-up results suggest that functional scaffold transplantation may represent a feasible treatment for patients with complete SCI. [ABSTRACT FROM AUTHOR]

Herein, a strategy was put forward for high-sensitive detection of sulfadimethoxine (SDM) using a label-free electrochemical immunosensor. Silver–graphene oxide (Ag-GO) nanocomposites were applied to fabricate the immunosensor. The prepared silver–graphene oxide (Ag-GO) nanocomposites had good biocompatibility and chemical stability. In addition, GO provided large surface area for the assembly of AgNPs with redox activity, which provided a prerequisite for the preparation of the electrochemical immunosensor. Furthermore, gold nanoparticles (AuNPs) were used to immobilize antibodies (anti-SDM) and amplify electrochemical signal, which could further enhance the sensitivity of detection. Under the optimal conditions, the peak current had a linear relationship with the logarithm of the SDM concentration, and the variation range was 0.333 to 100 ng mL−1 with the detection limit of 4 pg mL−1 (S/N = 3). The designed immunosensor demonstrated the advantages of simple preparation, high sensitivity, good selectivity, and acceptable stability. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes the coronavirus disease (COVID-19). It is confirmed that nucleocapsid (N) protein is closely related to viral pathogenesis, modulation of host immune response, RNA transcription, and replication and virus packaging. Therefore, the N protein is a preponderant antigen target for virus detection. The codon-optimized N gene was designed according to the encoding characteristics of insect cells and inserted into pFastBacTM1 vector with 6 × His-tag-fused N protein for expression in insect sf21 cells. Six anti–N mAbs (4G3, 5B3, 12B6, 18C7-A2, 21H10-A3, 21H10-E9) were prepared by recombinant N protein. The mAbs showed high titers, antibody affinity, and reactivity with the SARS-CoV-2 N protein. Then, fourteen overlapped peptides that covered the intact N protein were synthesized (N1-N14). Peptide N14 was identified as the main linear B-cell epitope region via peptide-ELISA and dot-blot assay, and this region was truncated gradually until mapping the peptide 401-DFSKQLQQ-408. Simultaneously, compared with the sequence of variants of concern (VOCs) and variants of interest (VOIs) strains among the several countries, epitope 401-DFSKQLQQ-408 is very conservative among them. The findings provide new guidance for the design and detection of COVID-19 targets. Key points: • The N protein was optimized according to the insect cell codon preference and was highly expressed. • The monoclonal antibodies prepared in this study were shown high antibody titers and high affinity. • Monoclonal antibodies were used to map the epitope 401–408 amino acids of N protein for the first time in this study. [ABSTRACT FROM AUTHOR]

Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/μl, absolute monocyte count (AMC) ≤ 10 cells/μl or absolute lymphocyte count (ALC) ≤ 1000 cells/μl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all P < 0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/μl and ALC ≤ 1000 cells/μl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both P < 0.05). Among patients with minimal residual disease (MRD) < 1% on day 19 of induction therapy, those with ANC ≤ 90 cells/μl had lower EFS than those with ANC > 90 cells/μl (70.8 ± 6.1% vs 86.4 ± 3.1%, P = 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/μl on day 19 of induction therapy also had lower EFS than those with ANC > 90 cells/μl (34.4 ± 25.2% vs 25.0 ± 21.7%, P = 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene. [ABSTRACT FROM AUTHOR]

Purpose: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is rare in China and case reports are varied. We conducted an in-depth analysis of newly diagnosed children with T-ALL from January 1999 to April 2015 in our center, to show the biological differences between Chinese ETP-ALL children and other immune types of T-ALL. Methods: The newly diagnosed children with T-ALL were divided into four groups according to their immunophenotype: ETP-ALL, early non-ETP-ALL, cortical T-ALL and medullary T-ALL. Disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) rates were estimated by the Kaplan–Meier method. The Cox regression model was used for multivariate analysis. Results: A total of 117 newly diagnosed children with T-ALL were enrolled in this study. The 10-year EFS and OS rates for all patients were 59.0 ± 4.7% and 61.0 ± 4.7%, respectively, with a median follow-up of 64 (5–167) months. Univariate analysis showed that ETP-ALL patients had the lowest 10-year DFS rate of 32.1 ± 11.7%, while cortical T-ALL had the highest DFS rate of 81.3 ± 8.5% compared with early non-ETP-ALL (61.6 ± 7.0%) and medullary T-ALL (59.1 ± 10.6%). Multivariate analysis demonstrated that only ETP-ALL and involvement of the central nervous system were independent prognostic factors. Conclusion: Compared with other subtypes, pediatric ETP-ALL had a poor treatment response and high recurrence rate while cortical T-ALL appeared to have much better outcome. Our observations highlight the need for an individualized treatment regime for ETP-ALL. [ABSTRACT FROM AUTHOR]

Purpose: Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs. Methods: By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models. Results: ImmunoPET imaging with [68Ga]Ga-NOTA-Nb1053 specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models. Conclusion: This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a genetic disorder predominantly affecting people of African descent and is associated with significant morbidity and mortality. To improve SCD outcomes, the National Heart Lung and Blood Institute funded eight centers to participate in the SCD Implementation Consortium. Sites were required to each recruit 300 individuals with SCD, over 20 months. We aim to describe recruitment strategies and challenges encountered. Participants aged 15–45 years with confirmed diagnosis of SCD were eligible. Descriptive statistics were used to analyze the effectiveness of each recruitment strategy. A total of 2432 participants were recruited. Majority (95.3%) were African American. Successful strategies were recruitment from clinics (68.1%) and affiliated sites (15.6%). Recruitment at community events, emergency departments and pain centers had the lowest yield. Challenges included saturation of strategies and time constraints. Effective recruitment of participants in multi-site studies requires multiple strategies to achieve adequate sample sizes. [ABSTRACT FROM AUTHOR]

SiO2 aerogel @ carbon nanotube anchored on graphene sheet (SiO2/CNT/GE) has been produced by a mechanical mixing method. The SiO2 nanoparticle and carbon nanotube are dispersed on graphene sheet. When the current density of the SiO2/CNT/GE material is 120 mA g−1 for lithium ion semi-battery, the first discharge and charge capacities are 839.3 mA h g−1 and 303.5 mA h g−1, respectively. After 200 cycles, its discharge capacity retains 624.3 mA h g−1. When the SiO2/CNT/GE material is used as a negative electrode and LiMn2O4 as a positive electrode for a full cell, the first discharge capacity is 732 mA h g−1, and the first coulomb efficiency is 93.18%. After 200 cycles, the discharge capacity can still be maintained at 217.9 mA h g−1, indicating its potential as a negative electrode material for lithium ion battery. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a rare disease among children. A retrospective study was conducted from November 2002 to March 2019 at a single institution in China. A total of 36 pediatric CML patients (25 male and 11 female) were enrolled. Median follow-up time was 51 months (range 8–144), and 5-year overall survival and event-free survival were 95.5 ± 4.4% and 88.9 ± 6.0%, respectively. Among the 25 patients whose response to imatinib mesylate (IM) was regularly monitored, 92.0% achieved complete hematologic response at 3 months, 80.0% achieved complete cytogenetic response at 12 months, and 64.0% achieved major molecular response at 18 months after IM therapy. A higher WBC count at diagnosis was associated with failure to achieve early molecular response (EMR). Height standard deviation score after long-term treatment was significantly and positively correlated with age at diagnosis and at the start of IM therapy. Overall, IM therapy was effective in treating pediatric CML, and WBC count at diagnosis might be an ideal predictor of EMR. Moreover, retardation of height and weight growth due to IM tended to affect patients younger than 9 years old at diagnosis, and longitudinal growth might normalize further into treatment. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a toxic metabolite produced mainly by Aspergillus and Penicillium species. A quantitative method was developed for the rapid, simple, and sensitive detection of OTA in corn by quantum dots–based fluorescent immunochromatographic assay (QDs-ICA). The CdSe/ZnS QDs–labelled anti-OTA monoclonal antibody (mAb) conjugates were designed as the fluorescent signal probe. The QDs-ICA included the designation of test line (T line) and control line (C line), which were sprayed with optimal concentrations of the OTA-OVA and staphylococcal protein-A (SPA), respectively. Under the optimal experimental conditions, the QDs-ICA exhibited excellent specificity and good accuracy and precision. For qualitative detection, the cut-off value for the T line of the visual detection method was 2.5 ng/mL. For quantitative detection, the linear regression equation of the standard curve was y = 0.366x + 0.514 with a reliable correlation coefficient (R2 = 0.992). Moreover, the 50% inhibition value (IC50) of the QDs-ICA was 0.91 ng/mL, the limit of detection (LOD) was 0.07 ng/mL, and the detection range was 0.05 to 10 ng/mL. In addition, the recovery rates ranged from 91.82 to 100.35% with a coefficient of variation (CV) below 3% for intra-assay, whereas the recovery rates for inter-assay changed from 94.29 to 104.62% with a CV below 10%. These results indicate that the QDs-ICA can serve as a potential large-scale preliminary device for rapid determination of OTA. [ABSTRACT FROM AUTHOR]

Soil microorganisms play an important role in determining productivity of agro-ecosystems. This study was conducted to compare diversity, richness, and structure (relative abundance at the phylum level) of soil bacterial communities among three rice-based cropping systems, namely, a winter fallow-rice-rice (FRR), green manure (Chinese milk vetch)-rice-rice (MRR), and oilseed rape-rice-rice (ORR), in which MRR and ORR had significantly higher productivity than FRR. A 16S rRNA gene sequence analysis showed that no significant differences were observed in diversity and richness indices (observed species, Shannon, Simpson, Chao1, abundance-based coverage estimators, and phylogeny-based metrics) of soil bacterial communities among the three cropping systems. However, relative abundances of dominant phyla in soil bacterial communities, including Proteobacteria, Acidobacteria, Nitrospirae, Gemmatimonadetes, and Verrucomicrobia, were significantly different among the three cropping systems. In particular, a significant reduction in the relative abundance of Nitrospirae was observed in both MRR and ORR compared with FRR. These results indicate that bacterial community structure was affected by cropping systems in the tested paddy soils. Based on the results of our studies and existing knowledge bases, we speculate that benefits to rice yield may be obtained by reducing the relative abundance of Nitrospirae and increasing the ratio of abundances of Proteobacteria/Acidobacteria in paddy soils. [ABSTRACT FROM AUTHOR]

Porcine parvovirus (PPV) virus-like particles (VLPs) are a potential vaccine candidate for the prevention of parvovirus-induced reproductive failure in pregnant sows. Currently, the Escherichia coli (E. coli) expression system is the most cost-efficient to express recombinant proteins. To overcome the limitations of protein misfolding and to prepare soluble highly bioactive antigen and high yields of protein, we optimized the PPV-VP2 gene, subcloned it into pET24a, pET26b, pET28a, and pET30a, and transformed it into E. coli BL21(DE3)-Tf16 competent cells. The pET28a plasmid was selected for further manipulations because it expressed high levels of the bioactive PPV-VP2 protein. Under optimal high-density fermenting conditions in a 70-L fermenter, the total yield of wet weight E. coli cells was 124.86 g/L, and PPV-VP2 protein was 2.5 g/L. After large-scale purification with Triton X-114 two-phase extraction as well as activated carbon powder adsorption, hemagglutination (HA) titers in the purified PPV-VP2 protein reached 219 and endotoxin was reduced to 2500 EU/mL. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicated that the purified PPV-VP2 protein self-assembled into VLPs. Immunogenicity assays in guinea pigs and pigs indicated that the ISA-201 VG adjuvanted PPV-VP2 VLP vaccine elicited hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers comparable with PPV commercial inactivated vaccines, whereas viral loads in the spleen and liver of challenged guinea pigs were significantly reduced. In conclusion, our study provides a method for producing the PPV-VLP vaccine against PPV infection in E. coli and may offer a novel strategy for the soluble expression of other vaccine antigens. [ABSTRACT FROM AUTHOR]

Although the B-cell translocation gene 1 (BTG1) plays an important role in apoptosis and negatively regulates cell proliferation, BTG1 expression in skin squamous cell carcinoma (SCC) has not been reported. In this study, we wanted to investigate the significance of BTG1 expression in SCC and adjacent tissues. The expression of BTG1 protein and mRNA in SCC tissues and adjacent tissues were detected by immunohistochemistry technique (IHC), Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). IHC staining showed that the positive expression rate of BTG1 protein in SCC tissues was 54.00%; and the positive rate was 90.50% in the adjacent tissues. Western blot showed that the expression of BTG1 protein in SCC tissues was significantly lower than that in the adjacent tissues (P<0.05). RT-PCR showed that the positive rate of BTG1 mRNA in SCC was 50.50%, which was significantly lower than that in adjacent tissues 89.00% (P<0.05). Both BTG1 mRNA and protein expression are related to tumor diameter, stage, tumor metastasis and the degree of tumor differentiation in SCC. Patients exhibiting lower BTG1 protein expression in the SCC tissues had a significantly shorter disease-specific survival rate. BTG1 protein expression, tumor diameter, tumors site and stage were independent factors affecting the overall survival of postoperative patients. Further, BTG1 overexpression inhibited A431 cell proliferation ability, while BTG silencing enhanced A431 cell proliferation ability. The lower expression of BTG1 in SCC may be associated with the occurrence, development and prognosis of SCC. [ABSTRACT FROM AUTHOR]

Porcine circovirus type 2 (PCV2) is an economically important pathogen in domestic pigs and wild boars all around the world. To understand the molecular epidemiology of PCV2 strains circulating in central China and to provide a potential vaccine candidate strain, we analyzed the genetic variations of 46 PCV2 isolates circulating from 2009 to 2016 in Henan Province (24 detected in the field from 2009-2013 and 22 from 2013-2016) and evaluated the efficacy of an isolate as a vaccine candidate strain in a mouse model. We found that PCV2b was the predominant genotype and PCV2b-1C was the main subtype. The PCV2 isolate DF-1, which had a virus titer of 106.5 TCID50/mL and a stable genome, was selected and used to immunize Kunming mice. Enzyme-linked immunosorbent assay (ELISA), immunoperoxidase monolayer assay (IPMA), and virus neutralization test (VNT) results indicated that the DF-1 vaccine candidate strain could elicit a level of specific antibodies and neutralizing antibodies similar to those induced by a commercial vaccine. Polymerase chain reaction (PCR) detection of virus in vaccinated mice after challenge revealed that DF-1 vaccination was effective in clearing the virus in different tissues. Hence, the PCV2 isolate DF-1, a circulating subtype of PCV2b-1C, might be used as a potential vaccine candidate strain. [ABSTRACT FROM AUTHOR]

Occurrence of 10 antibiotics in the Yuen Long (YLR), Kam Tin (KTR), and Shing Mun (SMR) rivers of Hong Kong and possible influence of livestock activities on the concentrations of antibiotics were investigated. Tetracycline (30-497 ng/L), sulfadiazine (2-80 ng/L), sulfamethoxazole (2-152 ng/L), ofloxacin (5-227 ng/L), and erythromycin (1-315 ng/L) were detected in all the three rivers; chlortetracycline (23-227 ng/L), oxytetracycline (7-104 ng/L), ciprofloxacin (12-68 ng/L), and roxithromycin (1-105 ng/L) were detected in YLR and KTR, whereas norfloxacin (3-34 ng/L) was detected in KTR only. Significant correlation between livestock population and antibiotic contamination was observed in YLR only, indicating the influences of other sources in KTR and SMR. Among the antibiotics, significant correlation was observed between tetracyclines and sulfonamides indicating the major influence of livestock farms, whereas tetracyclines/sulfonamides were negatively correlated with fluoroquinolones/macrolides implying the differential origin of the latter class of antibiotics. Water quality of KTR and YLR were highly influenced by the non-point source pollutions, while of SMR was relatively good. Particularly, Escherichia coli populations of the YLR and KTR were 3-4 logs higher than those of the SMR indicating the involvement of livestock farms and sewerages. Good correlation between tetracyclines (TCs)/sulfonamides (SAs) and number of livestock farms and a negative correlation between TCs/SAs and fluoroquinolones (FQs)/macrolides (MLs) could be used as an indicator to trace the possible source of pollution. [ABSTRACT FROM AUTHOR]

Accumulated evidence suggests that miR-106b played a key role in the promotion of the metastases of cancer; however, little is known about miR-106b in esophageal squamous cell carcinoma (ESCC). To investigate expression level of miR-106b in ESCC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-106b expression in 35 Kazakh's ESCC and paired normal adjacent tissues (NATs). To evaluate the role mediated by miR-106b in the proliferation, migration, and invasion, MTT, wound healing, and transwell assays were employed, respectively. Luciferase reporter assay was used to identify the downstream target through miR-106b. To understand the regulation between miR-106b and Smad 7, qRT-PCR and western blot were performed. The present study showed that miR-106b was pronouncedly upregulated in ESCC relative to paired NAT and that upregulated miR-106b was significantly associated with lymph node metastases. MiR-106b was found to be able to promote proliferation, migration, and invasion of ESCC cells in vitro. Smad 7 was confirmed as a downstream target of miR-106b in our experimental setting. Smad 7 was remarkably downregulated in ESCC compared with paired NAT. In addition, upregulation of miR-106b can promote epithelial mesenchymal transition (EMT) in ESCC cell in vitro. Our results indicated that miR-106b can promote migration and invasion of ESCC cells through enhancing EMT process via downregulation of Smad 7, suggesting that miR-106b can be a potential molecular phenotype in ESCC metastases. [ABSTRACT FROM AUTHOR]

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by a paucity of erythroid progenitors. We summarized the clinical and genetic features of 104 DBA patients in a single-center retrospective study in China. Data of DBA patients who received consultations at our center from 2003 to 2015 were analyzed retrospectively. Genes encoding 10 ribosomal proteins (RPs) and GATA1 were sequenced for mutation detection. Our cohort was composed of 65 males and 39 females. Congenital malformations were observed in 19 patients. Mutations of the RP genes were detected in 58.3 % patients. Twenty different mutations were first reported. Thirty-four patients received prednisone combined with CsA therapy, and improvement was observed in 20 cases. During follow-up for a median 39 months, 33.7 % of the patients achieved remission, 41.3 % of the patients were persistently transfusion independent, 21.7 % of the patients were transfusion dependent, and three patients died. The patient group with detected mutations had a younger age of disease onset, a higher malformation rate, and tended to have a lower remission rate and a higher transfusion-dependence rate. Prednisone in combination with cyclosporine A can be a second-line choice for DBA patients. Differences were detected between DBA patients with and without detectable mutations in the genes studied. [ABSTRACT FROM AUTHOR]

The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, NeuroRegen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5-4.5 cm were surgically resected in five complete chronic spinal cord injury (SCI) patients. The NeuroRegen scaffold along with autologous bone marrow mononuclear cells (BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or NeuroRegen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials (SSEP) from the lower limbs was also detected. The results indicate that scar resection and NeuroRegen scaffold transplantation could be a promising clinical approach to treating SCI. [ABSTRACT FROM AUTHOR]

Objectives: To improve the expression of soluble IBDV VP2 protein by using different tagged vectors in Escherichia coli. Results: Fusion tags, Grifin, MBP, SUMO, thioredoxin, γ-crystallin, ArsC and PpiB, enhanced the expression and solubility of VP2 protein. The fusion proteins were purified by Ni-NTA chromatography, MBP-VP2 showed the highest purity about 90 %. After removing the MBP tag, VP2 self-assembled into virus-like particles, ~25 nm diam. Results from AGP suggested the recombinant IBDV VP2 protein identified by reference serum like IBDV. Conclusion: All the seven tags enhanced the expression and solubility of IBDV VP2 protein. The recombinant protein self-assembly into virus like particles and possess antigenicity as reference IBDV. [ABSTRACT FROM AUTHOR]

In this study, we sought to determine whether resveratrol (RSV), a nonhormonal compound, would suppress the myometrial infiltration, improve pain behavior, lower stress level, improve the expression of some proteins known to be involved in adenomyosis, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, serving as a blank control. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 3 groups: low-dose RSV (2 mg/kg), high-dose RSV (3 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, they were hotplate tested again, their uterine horns and brains were harvested, and a blood sample was taken to measure the plasma corticosterone (CORT) level by enzyme-linked immunosorbent assay. The left uterine horn was used for immunohistochemistry analysis. The brain stem nucleus raphe magnus (NRM) sections were subjected to immunofluorescence staining for glutamic acid decarboxylase isoform 65 (GAD65). The depth of myometrial infiltration and uterine contractility was evaluated. We found that RSV is well tolerated and that it dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility and lowered plasma CORT levels, and improved the expression of some proteins known to be involved in adenomyosis. It also elevated the number of GAD65-expressing neurons in the brain stem NRM, possibly boosting the GABAergic inhibition of pain due to adenomyosis. Therefore, RSV appears to be a promising compound for treating adenomyosis. [ABSTRACT FROM AUTHOR]

We aimed to delineate how pyrrolidine dithiocarbamate (PDTC) affects nuclear factor κB (NF-κB) and to determine its antitumor activity alone and in combination with cisplatin in human cervical cancer SiHa cells. The SiHa cells were treated with various concentrations of PDTC and/or cisplatin at various time intervals. Cell proliferation and apoptosis were determined using a water-soluble tetrazolium salt 8 assay and flow cytometry. Electrophoretic mobility shift assay was used to assess NF-κB activity. Pyrrolidine dithiocarbamate (2.5-100 µmol/L) was found to inhibit the growth of SiHa cell lines. Cisplatin (0.01-20.0 μg/mL) and PDTC (2.5-20.0 µmol/L) combined demonstrated additive inhibitive effects on cell growth and increased the level of apoptosis. In addition, PDTC blocked cisplatin-induced activation of NF-κB, leading to enhanced apoptosis and increased chemosensitivity to cisplatin. Taken together, PDTC has significant potential as a chemotherapy agent, alone or in combination with cisplatin. [ABSTRACT FROM AUTHOR]

We have previously reported that induction of adenomyosis in mice results in progressive hyperalgesia, uterine hyperactivity, and elevated plasma corticosterone levels and that epigallocatechin-3-gallate (EGCG) treatment dose dependently suppressed myometrial infiltration and improved generalized hyperalgesia. In this study, we examined whether adenomyosis induced in mice results in the loss of GABAergic inhibition as manifested by the diminished glutamate decarboxylase (GAD) 65-expressing neurons in the brainstem nucleus raphe magnus (NRM) that could correlate with heightened hyperalgesia. We also evaluated whether EGCG treatment would reverse these changes and also improve the expression of some proteins known to be involved in adenomyosis. Adenomyosis was induced in 28 female ICR mice and additional 12 were used as blank controls, as reported previously. At the 16th week, all mice with induced adenomyosis received low- or high-dose EGCG treatment or untreated. Mice without adenomyosis received no treatment. After 3 weeks of treatment, their uterine horns and brains were harvested. The right uterine horn was used for immunohistochemistry analysis and for counting the number of macrophages infiltrating into the ectopic endometrium. The brainstem NRM sections were subjected to immunofluorescence staining for GAD65. We found that mice with induced adenomyosis had significantly diminished GAD65-expressing neurons, concomitant with heightened hyperalgesia. Treatment with EGCG increased these neurons in conjunction with improved hyperalgesia, reduced the expression of p-p65, cycloxygenase 2, oxytocin receptor, collagen I and IV, and transient receptor potential vanilloid type 1 in ectopic endometrium or myometrium, reduced the number of macrophages infiltrating into the ectopic endometrium while elevated the expression of progesterone receptor isoform B. Thus, adenomyosis-induced pain resembles neuropathic pain in that there is a remarkable central plasticity. [ABSTRACT FROM AUTHOR]

In an effort to search for novel therapeutics for adenomyosis, we sought to determine whether treatment with epigallocatechin-3-gallate (EGCG) would suppress the myometrial infiltration, improve pain behavior, lower stress level, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, which served as a blank control. Starting from 4 weeks after birth, hot plate test was administrated to all mice every 4 weeks. At the 16th week, all mice induced with adenomyosis were randomly divided into 3 groups: low-dose EGCG (5 mg/kg), high-dose EGCG (50 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, the hot plate test was administered again, a blood sample was taken to measure the plasma corticosterone level by enzyme-linked immunosorbent assay, and then all mice were sacrificed. The depth of myometrial infiltration and uterine contractility were also evaluated. We found that the induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and frequency of uterine contractions as well as elevated plasma corticosterone levels. The EGCG treatment dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels. These results suggest that induced adenomyosis causes pain and elevates stress levels in mice. Uterine hyperactivity may contribute to dysmenorrhea in women with adenomyosis who might also have elevated stress level due to pain. The EGCG appears to be a promising compound for treating adenomyosis. [ABSTRACT FROM PUBLISHER]

Non-severe aplastic anemia (NSAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We reviewed clinical and laboratory data of patients diagnosed with transfusion-independent non-severe aplastic anemia (NSAA) from 1996 to 2009 at the Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College, and analyzed the clinical course and outcomes in these patients. NSAA was defined as bone marrow cellularity <50 % and two or three cytopenias that persisted for 6 weeks or more: absolute neutrophil count (ANC) <1.5 × 10/L, absolute reticulocyte count (ARC) <40 × 10/L, platelet count <100 × 10/L, without meeting criteria for SAA (bone marrow cellularity <30 % and two or three cytopenias: ANC <0.5 × 10/L, ARC <20 × 10/L, platelet count <20 × 10/L). All patients were treated with reasonable supportive care, cyclosporine A, and stanozolol (0.1 mg/kg/day). Of a total of 284 patients, 117 (41.2 %) were female, and 167 (58.8 %) were male. With a median follow-up of 43 months (range 2-196 months), 38 patients (13.4 %) progressed to transfusion-dependent NSAA and among them 26 patients (9.2 %) progressed to SAA. One hundred and ninety-eight patients (69.7 %) had persistent NSAA. Forty-eight patients (16.9 %) showed the complete resolution of NSAA. The Kaplan-Meier estimates of all patients for progression-free survival were 86 ± 2.7 % and 66 ± 7.3 % at 60 and 120 months after diagnosis, respectively. Patients with ANC <1.0 × 10/L or female had a higher probability of progression to transfusion-dependent NSAA (18.5 vs. 5.4 %, respectively; p = 0.002, and 17.1 vs. 10.8 %, respectively; p = 0.022). The patients with ARC <60 × 10/L or with ANC <1.0 × 10/L had a higher probability of progression to SAA (11.5 vs. 3.6 %, respectively; p = 0.035, and 12.7 vs. 3.6 %, respectively; p = 0.011). A categorical risk factor analysis showed that patients with ANC <1 × 10/L had a higher probability of progression to SAA ( p = 0.03) and had a higher probability of progression to transfusion-dependent AA ( p = 0.007). NSAA patients may be benefited from early intervention with cyclosporine A and stanozolol. [ABSTRACT FROM AUTHOR]