Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Visible-Light-Induced Metal- and Photosensitizer-Free C(sp3)-H Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diphenylphosphine Oxide.

Herein, we report a direct phosphorylation of the C(sp3)-H bond of 3,4-dihydroquinoxalin-2(1H)-ones using oxygen as a green oxidant under visible light at room temperature. This transformation was readily accomplished in the absence of metal and photosensitizer to construct new C(sp3)-P bonds and provide a series of phosphonylated dihydroquinoxalin-2-ones in good to excellent yields. This approach opens straightforward and environmentally friendly access to 3-phosphoryl quinoxalin-2-ones derivatives.

Tocilizumab Treatment in a Patient of Refractory Anti-EJ Positive ASyS: A Case Report.

Anti-synthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of autoantibodies to aminoacyl-tRNA synthetases accompanied with various organ involvements, including the lung, joints, and skin. The ASyS-related interstitial lung disease (ILD) can be seen in the vast majority of patients. The extent of lung involvement has a significant impact on patient prognosis; the occurrence of rapid-progressive ILD could prominently increase mortality. The mainstay of treatment is prednisone in combination with conventional synthetic disease-modifying anti-rheumatic drugs or some biologic disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab (TCZ), a recombinant humanized anti-interleukin (IL)-6 receptor monoclonal antibody, has also been used to treat some systemic autoimmune rheumatic diseases associated with ILD. Although the most recent American College of Rheumatology (ACR) Guideline for the Treatment of Interstitial Lung Disease conditionally recommends against the use of TCZ as a treatment option for people with idiopathic inflammatory myopathy (IIM)-ILD progression despite initial ILD treatment, the treatment effect of TCZ in ASyS patients remains obscure, particularly for refractory cases with anti-non-Jo1 antibodies. This report describes a case of Chinese ASyS patients with anti-EJ-positive antibodies who presented with typical proximal muscle weakness, elevated creatine kinase, and ILD with non-specific interstitial pneumonia (NSIP) pattern, along with typical skin involvement such as mechanic's hand. The patients were resistant to various treatments, including rituximab (RTX), but benefited from TCZ. In this case, TCZ shows good therapeutic efficacy in a fatal acute exacerbation of ILD with a hyperinflammatory status, resulting in a relative remission of the disease flare and full preservation of lung function with a positive long-term treatment outcome.

A separate-dural-incision method of extradural dumbbell spinal schwannoma resection: cumulative experience at a single center.

OBJECTIVE: To present our experience in the surgical management of completely extradural dumbbell spinal schwannomas with a new surgical strategy. METHOD: This study is a case series of patients treated at the Neurosurgery Department of the First Affiliated Hospital of USTC, between January 2018 and June 2021. RESULTS: 24 patients met the inclusion criteria, with cervical and lumbar spines being the most frequent locations. All patients underwent surgical treatment. Total gross resection was accomplished in all patients. Two cases had numbness and no case exhibited motor deficit. There was no postoperative CSF leakage or wound infection. CONCLUSION: Based on a limited number of observations, we conclude that our technique was feasible and effective for the treatment of extradural dumbbell spinal schwannomas. CLINICAL TRIAL: http://www.chictr.org.cn/ , No. ChiCTR2400086171.

An efficient DNAzyme-locked leakless enzyme-free amplification system for alpha-foetoprotein detection in liver cancer and breast cancer.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Poly(3,4-dihydroxyphenylalanine)-modified cellulose paper for the extraction of deoxyribonucleic acid by a laboratory-built automated extraction device.

The success of polymerase chain reaction (PCR) depends on the quality of deoxyribonucleic acid (DNA) templates. This study developed a cost-effective and eco-friendly DNA extraction system utilizing poly(3,4-dihydroxyphenylalanine)-modified cellulose paper (polyDOPA@paper). PolyDOPA@paper was prepared by oxidatively self-polymerizing DOPA under weak alkaline conditions and utilizing the adhesive property of polyDOPA on different materials. Compared to the uncoated cellulose paper, polyDOPA coating significantly enhances DNA adsorption owing to its abundant amino, carboxyl, and hydroxyl moieties. The DNA extraction mechanism using polyDOPA@paper was discussed. The maximum adsorption capacity of polyDOPA@paper for DNA was 20.7 µg cm-2. Moreover, an automated extraction system was designed and fabricated using 3D printing technology. The device simplifies the operation and ensures the reproducibility and consistency of the results. More importantly, it eliminates the need for specialized training of operators. The feasibility of the polyDOPA@paper-based automated extraction system was evaluated by quantitatively detecting Escherichia coli in spiked milk samples via a real-time PCR. The detection limit was 102 cfu mL-1. The results suggest that the system would have significant potential in detecting pathogens.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

N6-methyladenosine-mediated LINC01087 promotes lung adenocarcinoma progression by regulating miR-514a-3p to upregulate centrosome protein 55.

Long noncoding RNAs are key players in the development of lung adenocarcinoma (LUAD). The present study elucidated the role of LINC01087 in LUAD development. Cell vitality and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. The transwell assay was adopted to evaluate cell migration and invasion. Levels of m6A modification of LINC01087 were determined using the methylated RNA binding protein immunoprecipitation assay. The interactions among LINC01087, miR-514a-3p, and centrosome protein 55 (CEP55) were evaluated using dual-luciferase reporter, RNA immunoprecipitation, and RNA-RNA pull-down assays. LINC01087 was highly expressed in LUAD, and its downregulation restrained cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro as well as tumor growth in a xenograft tumor model. Overexpression of miR-514a-3p inhibited malignant phenotypes in LUAD cells by inactivating RhoA/ROCK1 signaling via the suppression of CEP55 expression. Mechanistically, RBM15 increased the expression and mRNA stability of LINC01087 by mediating its m6A modification and LINC01087 induced CEP55 expression by sponging miR-514a-3p. RBM15-induced LINC01087 upregulation accelerated LUAD progression by regulating the miR-514a-3p/CEP55/RhoA/ROCK1 axis, illustrating the potential of LINC01087 as a novel target for LUAD therapy.

[Study on multiple organ injury induced by Haematitum in mice].

Haematitum is a commonly used mineral medicine. It is toxic, as recorded in the second volume of Chinese Materia Medica. Therefore, it should not be taken for a long time. In this study, the effects of Haematitum and calcined Haematitum on multiple organ injuries in mice were investigated, and the mechanism of the toxicity of the related organs was explored by metabolomics. The mice were randomly divided into the control group, Haematitum low-dose group(ZS-L group), Haematitum high-dose group(ZS-H group), and calcined Haematitum high-dose group(DZS-H group), with 12 mice in each group. Haematitum decoction was given by continuous intragastric administration for 10 days. Then the life situation was observed, and samples were taken to detect various indicators. The results showed that the ZS-H group showed obvious toxicity, with different degrees of toxicity damage in the intestinal tract,liver, spleen, and lung. ZS-L group had no toxic reaction. The toxicity of the DZS-H group was significantly reduced, and only the lung was damaged. Metabolomics technology was used to detect the lung tissue of mice in the control group and the ZS-H group, and a total of 15 kinds of significant difference metabolites were detected, mainly involved in choline metabolism in cancer, sphingolipid metabolism, and glycerophospholipid metabolism. Immunohistochemical results showed that the INSIG1 protein expression level in the lung tissue of mice in the ZS-H group was significantly higher than that in the control group. In summary, large doses and long-time use of Haematitum decoction will cause a variety of organ damage, and the same dose of calcined Haematitum is less toxic than Haematitum. In addition, a low dose of Haematitum has no obvious toxic effect. The dysfunction of lipid metabolic pathways such as sphingolipid and glycerophospholipid metabolism may be an important factor in Haematitum-induced pulmonary toxicity. This study provides a reference for further research on the mechanism of Haematitum pulmonary toxicity.

FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper. AIM: To explore the identification of potential biomarkers for STAD disease based on cuproptosis. METHODS: A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas. RESULTS: Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11. CONCLUSION: Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

Acute BRCAness Induction and AR Signaling Blockage through CDK12/7/9 Degradation Enhances PARP Inhibitor Sensitivity in Prostate Cancer.

Current treatments for advanced prostate cancer (PCa) primarily target androgen receptor (AR)-pathways. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR signaling inhibitors (ARSI) remains a significant clinical challenge. This study introduces BSJ-5-63, a novel triple degrader targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, with potential to transform CRPC therapy. BSJ-5-63 effectively downregulates homologous recombination repair (HRR) genes, including BRCA1 and BRCA2, through CDK12 degradation, and attenuates AR signaling through CDK7 and CDK9 degradation, further enhancing its therapeutic impact. Importantly, BSJ-5-63 induces a "BRCAness" state that persists for a significant duration, enabling sequential combination therapy with PARP inhibitors (PARPis) while potentially minimizing drug-related toxicity and resistance. In both in vitro and in vivo studies, BSJ-5-63 exhibited potent antiproliferative effects in both AR-positive and AR-negative CRPC models. This study presents a promising multi-pronged approach for CRPC treatment, addressing both DNA repair mechanisms and AR signaling, with the potential to benefit a wide range of patients regardless of their BRCA1/2 mutational status. SIGNIFICANCE: This study introduces BSJ-5-63, a triple degrader designed to target CDK12, CDK7, and CDK9, making a significant advancement in CRPC therapy. The distinctive mechanism of BSJ-5-63 involves downregulating HRR genes and inhibiting AR signaling, thereby inducing a BRCAness state. This enhances sensitivity to PARP inhibition, effectively addressing ARSI resistance and improving the overall efficacy of treatment. The development of BSJ-5-63 represents a promising therapeutic approach, with the potential to benefit a broad spectrum of CRPC patients.

Fortification of cassava starch edible films with Litsea cubeba essential oil for chicken meat preservation.

Chicken meat is highly perishable and mainly preserved by plastic packaging materials, whereas their widely used have increased environmental burden and threatened human health. Bioactive packaging materials fabricated by biopolymers are promising alternatives for meat preservation. Herein, cassava starch (CS)/sodium carboxymethyl cellulose (CMC) edible films fortified with Litsea cubeba essential oil (LC-EO) were fabricated and characterized. Results showed the textural, mechanical and barrier properties of the CS/CMC edible films were significantly improved after incorporating with LC-EO. Moreover, the composite edible films exhibited potent antibacterial properties, biodegradability, hydrophobicity, and thermal stability. Whereas the water solubility and moisture content was reduced up to 29.68 % and 24.37 %, respectively. The release behavior of LC-EO suggested the suitability of the composite edible films for acidic foods. Comparing with the control group, the pH values of the meat samples packaged with CS/CMC/LCEO-4 mg/mL edible films maintained at around 6.7, and weight loss rate was 15 %. The color and texture changes, and the lipid oxidation of the meat samples with CS/CMC/LCEO-4 mg/mL packaging were also markedly delayed. The microbial growth was retarded at 6.35 log CFU/g after storage for 10 days. These findings suggested the CS/CMC/LCEO-4 mg/mL edible films had great potential for chicken meat preservation.

Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer.

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

Sonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes.

In brief: Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos. Abstract: Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.