The differential expression of AFF3 in cervical cancer and its correlation with clinicopathological features and prognosis.

BACKGROUND: Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. METHODS: Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with p < 0.01. RESULTS: AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144-7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663-11.607) were identified as independent prognostic risk factors in CC patients. CONCLUSION: Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.

Cervical cancer is a significant health concern worldwide, responsible for over 300,000 deaths annually and ranking as the fourth most common cancer in women. Existing screening methods have limitations, highlighting the need for innovative therapies. In our research, we identified a specific genetic material that varied significantly among cervical cancer patients with varying survival outcomes, detected in tissue samples obtained post-surgery. Our study demonstrates the considerable potential of this marker for accurately predicting outcomes in our study population. By analysing differences in the expression of this genetic marker, we can forecast the prognosis and progression of cervical cancer. These findings offer valuable insights for advancing cervical cancer treatment strategies, potentially improving outcomes for patients. Early detection and targeted treatment based on this genetic marker could extend patients' lives and prevent fatalities by enabling timely medical intervention and management.

Protective Effect of l-Theanine on Cyclophosphamide-Induced Testicular Toxicity in Mice.

l-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of l-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last l-theanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of l-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that l-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of l-theanine on CP-induced testicular toxicity. l-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.

Efficacy and safety of 177Lu-DOTATATE targeted therapy in advanced/metastatic pulmonary neuroendocrine tumors: A systematic review and meta-analysis.

Objective: To perform a meta-analysis of the efficacy and safety about 177Lu-DOTATATE therapy for advanced/metastatic pNETs based on the current clinical evidence. Methods: This systematic review follows the PRISMA guideline. Search PubMed, Medline, EMBASE and CNKI, VIP, Wanfang databases, from establishment to June 2022, on the study of 177Lu-DOTATATE for advanced/metastatic pNETs, the primary endpoint was to evaluate the treatment effect through DRRs and DCRs. Secondary endpoint included assessment of OS, PFS, and treatment-related adverse events across all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using stata16.0 software, and the data were merged and displayed using forest graphs. Results: A total of 5 studies, 174 patients, on 177Lu-DOTATATE for advanced/metastatic pNETs were included. The pools of DRRs and DCRs were 24% (95% CI: 15%~32%) and 77% (95% CI: 62%~92%), respectively. The pool of OS was 48.78 months (95% CI: 41~56.57 months) and the pool of PFS was 21.59 months (95% CI: 17.65~25.53 months). In all studies, the most common side effect of treatment was hematological toxicity. In 174 patients, hematological toxicity of grade III accounted for 4.0% (7/174), and only 4.0% (7/174) and 1.0% (2/174) of patients had mild nephrotoxicity and hepatotoxicity. Gastrointestinal adverse reactions in 3% (6/174), nausea in 2% (3/174), superior vena cava occlusion in 0.5% (1/174). Conclusion: 177Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients' survival, and has low treatment-related toxicity and high safety. However, its efficacy and safety need to be further evaluated in high-quality, multicenter randomized controlled trials in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022344436.

A systematic review of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the diagnostic value of malignant tumor bone metastasis.

Objective: This study aims to perform a systemic analysis of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography (PET)/computerized tomography (CT) and [18F]FDG PET/CT for the diagnosis of malignant tumor bone metastasis based on existing clinical evidence. Methods: This systematic review followed the guidelines of the Preferred Reporting Project (PRISMA) for systematic reviews and meta-analysis. This is a retrospective study of articles published in PubMed. Embase was searched online from the start of May 2022. The main endpoints were the maximum standardized uptake value and the tumor-to-background ratio to determine the examination performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG for bone transfer stoves. Based on the entry and discharge standards, two researchers extracted documents and data and then performed the quality evaluation. Results: A total of eight studies on the metastasis of malignant tumors on bone were included, which involved 358 patients in the final analysis. Conclusion: [68Ga]Ga-DOTA-FAPI-04 showed better detection performance for bone metastasis. The sensitivity of [68Ga]Ga-DOTA-FAPI-04 for the diagnosis of the primary tumor was higher than that of [18F]FDG, whereas the specificity of [18F]FDG was higher than that of [68Ga]Ga-DOTA-FAPI-04. However, further randomized controlled trials and prospective clinical trials are warranted to compare the diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022313019).

An immune-related gene prognostic risk index for pancreatic adenocarcinoma.

Objective: Our goal is to construct an immune-related gene prognostic risk index (IRGPRI) for pancreatic adenocarcinoma (PAAD), and to clarify the immune and molecular features in IRGPRI-defined PAAD subgroups and the benefit of immune checkpoint inhibitors (ICIs) therapy. Method: Through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and univariate Cox regression analysis, 16 immune-related hub genes were identified using the Cancer Genome Atlas (TCGA) PAAD dataset (n = 182) and immune gene set. From these genes, we constructed an IRGPRI with the Cox regression method and the IRGPRI was verified based on the Gene Expression Omnibus (GEO) dataset (n = 45). Then, we analyzed the immune and molecular features and the benefit of ICI therapy in IRGPRI-defined subgroups. Results: Five genes, including S100A16, CD40, VCAM1, TNFRSF4 and TRAF1 were used to construct IRGPRI. As with the results of the GEO cohort, the overall survival (OS) was more favorable in low IRGPRI patients versus high IRGPRI patients. The composite results pointed out that low IRGPRI was associated with immune response-related pathways, high level of CTLA4, low KRAS and TP53 mutation rate, more infiltration of activated memory CD4+ T cells, CD8+ T cells, and more benefits from ICIs therapy. In comparison, high IRGPRI was associated with cancer-related pathways, low expression of CTLA4, high KRAS and TP53 mutation rate, more infiltration of M2 macrophages, and less benefit from ICIs therapies. Conclusion: This IRGPRI is an encouraging biomarker to define the prognosis, immune and molecular features, and benefits from ICIs treatments in PAAD.

Elevated 68 Ga-FAPI Uptake by Primary Benign Intraosseous Meningioma.

ABSTRACT: Intraosseous meningioma is an extremely rare benign tumor. We present the 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT findings of primary intraosseous meningioma in a 71-year-old woman. 68 Ga-FAPI PET/CT revealed an intraosseous mass in the right parietal bone with increased FAPI activity. Primary skull malignancy was suspected. However, pathological examination after resection of the mass in the right parietal bone confirmed the diagnosis of benign meningioma (WHO I). A final diagnosis of benign intraosseous meningioma was made.

Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF-ß/Smad2 signaling.

Ovarian cancer is the most lethal malignancy with depressive 5-year survival rate, mainly due to patients with advanced stages experience tumor recurrence and resistance to the current chemotherapeutic agents. Thus, exploring the underlying molecular mechanisms involved in chemo-resistance is crucial for management of treatment to improve therapeutic outcomes. In the current study, we found overexpression of FAM46A in ovarian cancer patients demonstrated an aggressive phenotype and poor outcome. Furthermore, FAM46A overexpression in ovarian cancer cells induces higher CDDP resistance. However, inhibition of FAM46A sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Mechanically, upregulation of FAM46A activated transforming growth factor-ß (TGF-ß)/Smad signaling and upregulated the levels of nuclear Smad2. Taken together, our results highlight the important oncogenic role of FAM46A in ovarian cancer progression and might provide a potential clinical target for patients with chemo resistant ovarian cancer.

CF1 reduces grain-cadmium levels in rice (Oryza sativa).

Rice (Oryza sativa) is a leading source of dietary cadmium (Cd), a non-essential heavy metal that poses a serious threat to human health. There are significant variations in grain-Cd levels in natural rice populations, which make the breeding of low-Cd rice a cost-effective way to mitigate grain-Cd accumulation. However, the genetic factors that regulate grain-Cd accumulation have yet to be fully established, thereby hindering the development of low-Cd varieties. Here, we reported a low-Cd quantitative trait locus, CF1, that has the potential to reduce Cd accumulation in rice grains. CF1 is allelic to the metal transporter OsYSL2, which transports Fe from the roots to the shoots. However, it is incapable of binding Cd, and thus, reduces grain-Cd levels indirectly rather than directly in the form of upward delivery. Further analysis showed that high expression levels of CF1 improve Fe nutrition in the shoots, subsequently inhibiting Cd uptake by systemically inhibiting expression of the main Cd uptake gene OsNramp5 in the roots. Compared with the CF1 allele from '02428' (CF102428 ), higher expression levels of CF1 from 'TQ' (CF1TQ ) increased the Fe contents and decreased Cd levels in rice grains. In natural rice populations, CF1TQ was found to be a minor allele, while CF102428 is present in most japonica rice, suggesting that CF1TQ could be widely integrated into the japonica rice genome to generate low-Cd varieties. Overall, these results broaden our mechanistic understanding of the natural variation in grain-Cd accumulation, supporting marker-assisted selection of low-Cd rice.

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a meta-analysis of the efficacy and safety of 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer based on existing clinical evidence. METHODS: Search for retrospective studies about 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer from establishment to July 2021 in PubMed and EMBASE. The primary endpoint was 225Ac-PSMA-617 biochemical response evaluation criteria after treatment [any prostate specific antigen (PSA) decrease and PSA decrease >50% from baseline] to evaluate the treatment effect. Secondary endpoints included assessment of overall survival (OS), progression-free survival (PFS), molecular response, and toxicity for all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Use stata16.0 software for analysis, fixed-effects model for data merging and forest plots for display. RESULTS: A total of 6 retrospective studies, namely, 201 patients, were included in the final analysis. The pooled proportions of patients with decreased PSA and PSA decreased by more than 50% were 87.0% (95% confidence interval, 0.820 to 0.920) and 66.1% (95% confidence interval, 0.596 to 0.726), respectively. The pooled proportions of OS and PFS were 12.5 months (95%CI: 6.2-18.8 months) and 9.1 months (95%CI: 2.6-15.7 months). The patients showing molecular responses were 54% (95% confidence interval: 25-84%). In all studies, the most common side effect of 225Ac-PSMA-617 TAT was xerostomia, with any degree of xerostomia occurring in 77.1% (155 out of 201), and grade III only accounted for 3.0%. The second was 30.3% (61 out of 201) anemia of any degree, and grade III accounts for 7.5% (15 out of 201). Grade III leukopenia and thrombocytopenia were 4.5% (9 out of 201) and 5.5% (11 out of 201), respectively. Only 6 (3.0%) of 201 patients had Grade III nephrotoxicity. CONCLUSION: 225Ac-PSMA-617 is an effective and safe treatment option for mCRPC patients, and the toxicity caused by it is relatively low. However, future randomized controlled trials and prospective trials are required in the future to judge the therapeutic effects and survival benefits compared with existing clinical treatments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42021281967.

Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner.

Serpinc1 is a serine protease inhibitor in the coagulation cascade, but its role in tumor biology remains obscure. Here, we report an unexpected role of serpinc1 in suppression of hepatocellular carcinoma (HCC). In HCC patients, the mRNA and protein expression of serpinc1 is upregulated, which is negatively correlated with tumor grade, and has a better prognosis than patients with low serpinc1. In addition, patients with high expression of serpinc1 generally have a better tumor immune microenvironment, accompanied by changes in multiple immune cells and mediators. In particular, tumor-promoting M2 macrophages are negatively correlated with serpinc1 expression and the prognosis of HCC patients. In vitro experiments further show that overexpression of serpinc1 inhibits the growth of HCC cells (HepG2 and SMMC7721) by inducing apoptosis. Accordingly, cell co-culture experiments reveal the direct role of serpinc1-overexpressed HCC cells in inhibiting the formation of M2 macrophages. Subsequent unbiased quantitative proteomic and ubiquitinome analyses identify that multiple poly-ubiquitination of proteins involved in signal pathways (such as autophagy, apoptosis, lactate metabolism, and VEGF signaling) are regulated by serpinc1. Overall, these findings establish a serpinc1-dependent ubiquitin-proteasome system to control apoptosis and antitumor immunity.

Human papillomavirus prevalence among men who have sex with men in China: a systematic review and meta-analysis.

Human papillomavirus (HPV) infection among men who have sex with men (MSM) in China is underreported. We performed a systematic review and meta-analysis to clarify site-specific HPV prevalence among MSM in China. We searched both English and Chinese databases for all studies published before April 1, 2020, that reported HPV prevalence among MSM in China. Random-effects meta-analysis was used to calculate summary estimates. Thirty-four articles were eligible, where 32, 5, and 2 articles reported HPV prevalence at the anus, penis, and oral cavity, respectively. The estimated prevalence of anal HPV among MSM in China was 85.1% (HIV-positive), 53.6% (HIV-negative), and 59.2% (unknown HIV status), with HPV genotypes being predominated by HPV 6, 11, 16, 18, 52, and 58. Any HPV and high-risk (HR) HPV was more common in northern China, while low-risk HPV was more common in southern China. HPV prevalence increased with age among HIV-negative MSM, from 40.5% (aged < 20 years) to 57.2% (aged ≥ 40 years). High prevalence of any HPV (HIV+: 95.1%; HIV-: 97.7%) and multiple infections (HIV+: 75.9%; HIV-: 41.7%) was found in anogenital warts among MSM. HPV is common among MSM in China. MSM living with HIV and/or anogenital warts were at disproportionate risk for HR HPV. Younger MSM were found to have a lower HPV prevalence. HPV vaccines would have prevented the majority of infections if given before sex debut. HPV at anatomical sites other than the anus, incident HPV infection, and the cost-effectiveness of HPV vaccination in this population are worth further investigation.

DNA Framework-Mediated Electrochemical Biosensing Platform for Amplification-Free MicroRNA Analysis.

MicroRNAs (miRNAs) have been explored as biomarkers for early diagnosis of diseases like cancers. However, it remains challenging to detect low-level miRNAs in the total RNA from real samples in a facile approach. In this work, we report a two-phase miRNA biosensing strategy based on a modular framework nucleic acid (FNA) platform, which combines the high efficiency of homogeneous reaction and the convenience of heterogeneous biosensing. In the first phase, free DNA probes bind target miRNAs in a homogeneous solution, forming a DNA-RNA complex with high base stacking energy. Then, at the second phase, the universal FNA interface on the electrode selectively mediated the transition of the complex from the solution onto the interface for electrochemical signal generating and transduction. By applying this method, we detected as few as 1 aM of miR-141, a cancer marker miRNA, without the need for nucleic acid amplification. The dynamic range spans 10 orders of magnitude. We demonstrate multiplex miRNA detection and discrimination of highly homologous miRNAs with mismatches as few as a single base. We also show that this system can detect miR-141 in only 50 ng of total RNA samples from real cells, which allows discrimination of prostate cancer cells with normal cells. We envision this platform may satisfy the need for facile and high-throughput screening of early cancer markers.

A pair-wise meta-analysis highlights circular RNAs as potential biomarkers for colorectal cancer.

BACKGROUND: Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). METHODS: A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. RESULTS: A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P = 0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03-3.50, P = 0.000; X2 = 4.34, P = 0.740, I2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR = 0.30, 95%CI: 0.17-0.53, P = 0.000; X2 = 1.34, P = 0.909, I2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. CONCLUSION: Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.

HPT axis­independent TSHß splice variant regulates the synthesis of thyroid hormone in mice.

Thyroid stimulating hormone (TSH) consists of an α­subunit and a unique ß­subunit. The first in­frame TSHß splice variant produced by the cells of immune system was identified in 2009. The TSHß splice variant and native TSHß exhibit different expression profiles, and research has been conducted to elucidate the role of the TSHß splice variant in different diseases. However, understanding of the fundamental physiological characteristics of the TSHß splice variant is currently limited. To verify whether the TSHß splice variant has the potential to induce thyroid follicular cells to synthesize thyroid hormone, in vivo and in vitro stimulation experiments were conducted in the present study. A total of 60 C57BL/6 mice were divided into control­, 5 and 10 µg TSHß splice variant­treated groups at random. Mice were sacrificed at 0.5, 1 and 4 h after intraperitoneal injection, and serum levels of tri­iodothyronine (T3) and thyroxine (T4) were determined using a radioimmunoassay. Thyroid follicular cells were isolated from the thyroids of mice, and stimulated with 2 µg/ml TSHß splice variant. Supernatants were collected, and the levels of T3 and T4 were detected. The protein expression levels of the sodium­iodide symporter, thyroperoxidase and thyroglobulin in thyroid follicular cells were quantified using western blot analysis. To verify whether the TSHß splice variant expression was regulated by the hypothalamus­pituitary­thyroid (HPT) axis, similar to native TSHß, a total of 60 C57BL/6 mice were equally divided into control, 2 mg/kg T3 intraperitoneal injection and 0.05 mg/kg thyroid­releasing hormone intraperitoneal injection groups at random. Mice were sacrificed at 1 and 4 h after injection. Alterations in the expression of the TSHß splice variant in the pituitary, thyroid, peripheral blood leukocytes and spleen tissues were detected using western blot analysis. The present study demonstrated that the TSHß splice variant is not regulated by the HPT axis and may affect thyroid hormone synthesis. Modifications in the expression of the TSHß splice variant may occur in a uniquely regulated manner to provide peripheral immunological compartments with a source of activated cells, particularly under immune stress.

[Analysis of GDAP1 gene mutation in a pedigree with autosomal dominant Charcot-Marie-Tooth disease].

OBJECTIVE: To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree. METHODS: Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure. RESULTS: A heterozygous missense mutation [c.371A>G (p.Y124C)] was detected in exon 3 of GDAP1 gene of the proband. This heterozygous mutation was also detected in both the proband's mother and her brother, but not in her father. Multiple sequence alignment analysis showed that tyrosine at codon 124 of GDAP1 protein was highly conserved. All the 3 prediction software predicted that the mutation was harmful. Molecular structure simulation showed a weakened interaction force between the amino acid residues at codon 124 and the surrounding amino acid residues to affect the overall stability of the protein. CONCLUSIONS: The mutation of GDAP1 gene may be related to the pathogenesis of autosomal dominant AD-CMT in this pedigree. The newly discovered c.371A>G mutation (p.Y124C) expands the mutation spectrum of GDAP1 gene, but further study is needed to clarify the underlying pathogenesis.

Sensitive and label-free electrochemical lead ion biosensor based on a DNAzyme triggered G-quadruplex/hemin conformation.

Lead ion (Pb2+) is a common environmental contaminant, which causes serious bioaccumulation and toxicity in human body. In this work, we developed a novel Pb2+ electrochemical biosensor using the specific DNAzyme on a DNA tetrahedron probe, in the presence of Pb2+, the substrate strand was cleaved into two parts and released a "G-rich" oligo which subsequently formed a G-quadruplex/hemin complex, generating a detectable catalysis current signal with the assistant of H2O2. The 3-D DNA tetrahedron regulated the density and orientation of the probe and thus improved the DNAzyme reaction, and facilitated the complex DNA conformational change in the confined space of the interface on the electrode surface, Finally, the LOD of our biosensor was proved to be 0.008 nM (3σ), which is 9000 times lower than the safety limit of EPA (15 µg/L or 72 nM), and 6000 times lower than IARC (10 µg/L or 48.26 nM), and more importantly, the specificity and reproducibility of the proposed biosensor was well demonstrated.

PCR-Free Colorimetric DNA Hybridization Detection Using a 3D DNA Nanostructured Reporter Probe.

A "sandwich-like" biosensor was developed on the basis of the magnetic bead platform for sensitive detection of breast cancer 1 (BRCA1) DNA. In the present study, a tetrahedron-structured reporter probe (TSRP) was designed, in which 3 vertices of the tetrahedron were labeled with digoxin (Dig), and the other one was labeled with a detection probe. TSRP here provided accurate enzyme loading and well-organized spatial arrangement for optimized signal amplification. The detection limit of this biosensor was as low as 10 fM, which is at least 4 orders of magnitude lower than that of the single DNA probe (100 pM), and the signal gain was 2 times higher than the analysis using three one-dimensional (1D) reporter probes. We could distinguish DNA sequences with only 1 base mismatch, and the performance of our TSRP biosensor was proven to be equally good in both PCR products and real fetal calf serum (FCS) sample as in buffer. We believe this work provided a novel avenue for the development of signal amplification strategies.

Functional human TSHß splice variant produced by plasma cell may be involved in the immunologic injury of thyroid in the patient with Hashimoto's thyroiditis.

Hashimoto's Thyroiditis (HT) is the most common cause of hypothyroidism in areas of the world where iodine levels are sufficient. However, the pathogenesis of HT has not been completely elucidated. The first functional human TSHß splice variant was supposed to be involved in the pathology of Hashimoto's thyroiditis. The question remains as to which kind of intrathyroid cells expresses functional TSHß splice variant and whether there are expression variations of functional TSHß splice variant in the injured thyroid of patient with HT. For the answer to this question, immune-injured thyroids were obtained from 30 patients with HT. Localization study of functional TSHß splice variant in injured thyroid was done by immunofluorescence double staining. Transcription and translation level of functional TSHß splice variant were detected by using qRT-PCR and semi-quantitative immunohistochemistry method, respectively. The correlation between expression level of functional TSHß splice variant and degree of thyroid follicles damage was assessed. It was firstly identified that functional TSHß splice variant was predominately expressed by plasma cells infiltrated around follicles and germinal center in injured thyroid of patient with HT. Of particular interest, the TSHß splice variant was expressed at significantly higher levels in the thyroid tissues of patients with HT than that in the normal thyroid tissues, furthermore, expression level of TSHß splice variant was positive related with the degree of follicles damage in thyroid of patient with HT. These findings defined the immune-derived functional TSHß splice variant that resided in the thyroid of patient with HT, which exerted the unique effects on the pathogenesis of HT, meanwhile, we considered these findings to have significant implications for understanding immune-endocrine interactions in a number of ways.

Association of p73 G4C14-to-A4T14 polymorphism with lung cancer risk.

Conflicting results were implicated in both single case-control studies and meta-analyses of the correlation between p73 G4C14-to-A4T14 polymorphism and lung cancer risk. We designed this study to further assess the association by meta-analysis. A meta-analysis was performed based on five case-control studies (5,467 subjects) retrieved from PubMed and Embase. Odds ratios (ORs) with 95 % confidence intervals (CIs) were measured for the association using the models of random effects and fixed effects. The results showed no evidence between p73 G4C14-to-A4T14 polymorphism and lung cancer risk in any genetic model (allele model: OR, 1.06, 95 % CI, 0.89-1.26; homozygote genotypes: OR, 1.18, 95 % CI, 0.80-1.73; heterozygote genotypes: OR, 1.04, 95 % CI, 0.89-1.23; dominant model: OR, 1.05, 95 % CI, 0.89-1.24; recessive model: OR, 1.17, 95 % CI, 0.93-1.47). Subgroup analyses according to ethnicity, however, detected significant association in Caucasian population. Our study provides evidence that p73 G4C14-to-A4T14 polymorphism may play a major role in susceptibility to lung cancer in Caucasians.