Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

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microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.

Blocking HIF-1α following radiotherapy to prolong and enhance the immune effects of radiotherapy: a hypothesis.

Tumor local immune escape is one of the "hallmarks" of cancer leading to poor prognosis. The effects of local radiotherapy on tumors are rapidly emerging as opportunities to remodel and enhance immunity against cancer. However, this immunity remodeling and enhancing are not permanent after local radiotherapy. High expression of HIF-1α following local radiotherapy for tumor cell reoxygenation has been confirmed, and recently accumulating evidence shows the tumor immune suppression effects. These research findings suggest a new direction in the investigation of methods to enhance the efficacy of local radiotherapy. We speculate that by blocking HIF-1α, the immune effects of radiotherapy might be prolonged and enhanced.

Prediction and related genes of cancer distant metastasis based on deep learning.

Cancer metastasis is one of the main causes of cancer progression and difficulty in treatment. Genes play a key role in the process of cancer metastasis, as they can influence tumor cell invasiveness, migration ability and fitness. At the same time, there is heterogeneity in the organs of cancer metastasis. Breast cancer, prostate cancer, etc. tend to metastasize in the bone. Previous studies have pointed out that the occurrence of metastasis is closely related to which tissue is transferred to and genes. In this paper, we identified genes associated with cancer metastasis to different tissues based on LASSO and Pearson correlation coefficients. In total, we identified 45 genes associated with bone metastases, 89 genes associated with lung metastases, and 86 genes associated with liver metastases. Through the expression of these genes, we propose a CNN-based model to predict the occurrence of metastasis. We call this method MDCNN, which introduces a modulation mechanism that allows the weights of convolution kernels to be adjusted at different positions and feature maps, thereby adaptively changing the convolution operation at different positions. Experiments have proved that MDCNN has achieved satisfactory prediction accuracy in bone metastasis, lung metastasis and liver metastasis, and is better than other 4 methods of the same kind. We performed enrichment analysis and immune infiltration analysis on bone metastasis-related genes, and found multiple pathways and GO terms related to bone metastasis, and found that the abundance of macrophages and monocytes was the highest in patients with bone metastasis.

Control of ultra-intense single attosecond pulse generation in laser-driven overdense plasmas.

Ultra-intense single attosecond pulse (AP) can be obtained from circularly polarized (CP) laser interacting with overdense plasma. High harmonics are naturally generated in the reflected laser pulses due to the laser-induced one-time drastic oscillation of the plasma boundary. Using two-dimensional (2D) planar particle-in-cell (PIC) simulations and analytical model, we show that multi-dimensional effects have great influence on the generation of AP. Self-focusing and defocusing phenomena occur in front of the compressed plasma boundary, which lead to the dispersion of the generated AP in the far field. We propose to control the reflected high harmonics by employing a density-modulated foil target (DMFT). When the target density distribution fits the laser intensity profile, the intensity of the attosecond pulse generated from the center part of the plasma has a flatten profile within the center range in the transverse direction. It is shown that a single 300 attosecond (1 as = 10(-18)s) pulse with the intensity of 1.4 × 10(21) W cm(-2) can be naturally generated. Further simulations reveal that the reflected high harmonics properties are highly related to the modulated density distribution and the phase offset between laser field and the carrier envelope. The emission direction of the AP generated from the plasma boundary can be controlled in a very wide range in front of the plasma surface by combining the DMFT and a suitable driving laser.

Health risks associated with heavy metals in the drinking water of Swat, northern Pakistan.

The concentrations of heavy metals such as Cd, Cr, Cu, Mn, Ni, Pb and Zn were investigated in drinking water sources (surface and groundwater) collected from Swat valley, Khyber Pakhtunkhwa, Pakistan. The potential health risks of heavy metals to the local population and their possible source apportionment were also studied. Heavy metal concentrations were analysed using atomic absorption spectrometer and compared with permissible limits set by Pakistan Environmental Protection Agency and World Health Organization. The concentrations of Cd, Cr, Ni and Pb were higher than their respective permissible limits, while Cu, Mn and Zn concentrations were observed within their respective limits. Health risk indicators such as chronic daily intake (CDI) and health risk index (HRI) were calculated for adults and children separately. CDIs and HRIs of heavy metals were found in the order of Cr > Mn > Ni > Zn > Cd > Cu > Pb and Cd > Ni > Mn > Cr > Cu > Pb > Zn, respectively. HRIs of selected heavy metals in the drinking water were less than 1, indicating no health risk to the local people. Multivariate and univariate statistical analyses showed that geologic and anthropogenic activities were the possible sources of water contamination with heavy metals in the study area.

Differential Effects on HbA1c Detection by HPLC and Capillary Electrophoresis in Five Types of Hb Variants in China.

OBJECTIVE: Hemoglobin A1c (HbA1c) can be used to evaluate blood glucose control. Its measurement will be affected by many factors, but Hb variation is the most critical factor. This study aimed to explore the types of variants found in routine work and their impact on test results. METHODS: Samples with abnormal HbA1c chromatograms found in routine testing were tested with high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) and then further tested with polymerase chain reaction (PCR) and sequencing. RESULTS: Five recessive heterozygous mutations were identified after PCR and sequencing. Hb Riccarton-II (a mutation in the HBA2 gene), Hb E, Hb G-Coushatta, Hb G-Taipei, and Hb North Manchester (a mutation in the HbB gene) were identified. All HbA1c values of these variants detected by HLC-723 G8 (HPLC method) were lower than those of Sebia Capillarys 2 FP (C2FP, CE method) with P < .0001. CONCLUSION: Five Hb mutations were identified in our routine HbA1c test, and their HPLC detection values were significantly lower than those obtained with the CE method.

Evaluation of the Diagnostic Value of FliD, a Helicobacter pylori Flagellar Protein.

Novel immunodominant antigens are urgently required for the diagnosis and vaccination of Helicobacter pylori (HP). FliD, an important colonization factor, was cloned and expressed (rFliD) to evaluate the levels of specific immunoglobulin G (IgG), IgM, and IgA antibodies in the serum of patients using ELISA. Rabbit anti-rFliD polyclonal antibody (pAb) was obtained by the subcutaneous injection of rFliD. The rFliD-specific IFN-γ and IL-4 levels in peripheral blood mononuclear cells and CD4+ T cells from humans were analyzed using enzyme-linked immunospot and flow cytometry. We found that the levels of rFliD-specific IgG, IgM, and IgA were significantly higher in HP-infected-patients than in healthy controls. IgG, IgM, and IgA had diagnostic sensitivities of 92.6%, 89.8%, and 83.2%; specificities of 91.1%, 88.7%, and 64.6%; and areas under the receiver operating curves of 0.97, 0.96, and 0.92, respectively. Furthermore, rFliD-pAb was used for the immunohistochemical analysis of gastritis and gastric cancer tissues from patients infected with HP. The levels of rFliD-specific IFN-γ and IL-4 were significantly elevated in HP-infected patients and exhibited a dominant T helper type 1-dominant subtype. These findings indicate that rFliD exhibits high validity as a biomarker in HP diagnosis and may also be a potent antigen for vaccine design because of its high cellular and humoral immune responses.

The comparative protective effects of ganoderma spores lipid and fish oil on N-methyl-N-nitrosourea-induced photoreceptor cell lesion in rats.

Purpose. To compare Ganoderma spores lipid (GSL) and fish oil (FO) in inhibiting retinal photoreceptor cell lesions induced by N-methyl-N-nitrosourea (MNU) in rats. Methods. 120 rats were untreated (normal control, NC group) or treated with a single intraperitoneal injection of 40 mg/kg MNU (MNU group) then treated with GSL (GSL group) or FO (FO group). Eyes were obtained at 1, 3, 5, 7, and 10 days. Results. Light microscopy assay demonstrated that GSL and FO alleviated rat retinal photoreceptor cell damage (GSL and FO versus MNU group P < .001) similarly (GSL versus FO group P = .980). Electron microscopy confirmed that GSL and FO reversed damage to photoreceptor segments and photoreceptor cell nuclei. GSL-treated rats showed significantly elevated a-wave and b-wave amplitudes over MNU group (P < .05) but less than NC group (P < .05) and not significantly different from FO group (P > .05). Conclusion. GSL, like FO, alleviates rat retinal photoreceptor cell damage induced by MNU.

A Highly Sensitive Electrochemical Glucose Sensor Based on Room Temperature Exfoliated Graphite-Derived Film Decorated with Dendritic Copper.

An ultrasensitive enzyme-free glucose sensor was facilely prepared by electrodepositing three-dimensional dendritic Cu on a room temperature exfoliated graphite-derived film (RTEG-F). An excellent electrocatalytic performance was demonstrated for glucose by using Cu/RTEG-F as an electrode. In terms of the high conductivity of RTEG-F and the good catalytic activity of the dendritic Cu structures, the sensor demonstrates high sensitivities of 23.237 mA/mM/cm2, R2 = 0.990, and 10.098 mA/mM/cm2, R2 = 0.999, corresponding to the concentration of glucose ranging from 0.025 mM to 1.0 mM and 1.0 mM to 2.7 mM, respectively, and the detection limit is 0.68 µM. In addition, the Cu/RTEG-F electrode demonstrates excellent anti-interference to interfering species and a high stability. Our work provides a new idea for the preparation of high-performance electrochemical enzyme-free glucose sensor.

A Pitfall in HbA1c Testing Caused by Hb Long Island Hemoglobin Variant.

BACKGROUND: Although many factors may interfere with hemoglobin (Hb)A1c measurement, Hb variants are among the most important factors. METHODS: We tested the HbA1c levels of the patient, a 32 year old Manchu Chinese woman, during a routine health check. We used different methods, including high-performance liquid chromatography (HPLC) and capillary electrophoresis, to test specimens from the patient. Next, we tested the specimen further using polymerase chain reaction (PCR) and sequencing. RESULTS: We discovered that our patient, who had an HbA1c value of 0, also has an Hb variant, Hb Long Island, which we found during the HbA1c analysis as part of her routine health check at the Health Management Center in the General Hospital of Tianjin Medical University, Tianjin, China. Also, we discovered that the exon 1 of ß gene contained transversion mutations, with 1 heterozygous and 1 homozygous variant (HBB:c.8A > C, 9T > C). These gene mutations resulted in an amino-acid change (His to Pro) and a decrease in HbA1c value. CONCLUSIONS: When there is no correlation between the clinical signs, glycemic status, and glycated Hb levels of the patient, the chromatogram of HbA1c should be carefully checked to detect possible variants that cause interference in the measurement.

A self-attention based neural architecture for Chinese medical named entity recognition.

The combination of medical field and big data has led to an explosive growth in the volume of electronic medical records (EMRs), in which the information contained has guiding significance for diagnosis. And how to extract these information from EMRs has become a hot research topic. In this paper, we propose an ELMo-ET-CRF model based approach to extract medical named entity from Chinese electronic medical records (CEMRs). Firstly, a domain-specific ELMo model is fine-tuned on a common ELMo model with 4679 raw CEMRs. Then we use the encoder from Transformer (ET) as our model's encoder to alleviate the long context dependency problem, and the CRF is utilized as the decoder. At last, we compare the BiLSTM-CRF and ET-CRF model with word2vec and ELMo embeddings to CEMRs respectively to validate the effectiveness of ELMo-ET-CRF model. With the same training data and test data, the ELMo-ET-CRF outperforms all the other mentioned model architectures in this paper with 85.59% F1-score, which indicates the effectiveness of the proposed model architecture, and the performance is also competitive on the CCKS2019 leaderboard.

Circular RNA circFANCL motivates the glioma progression via the action on the miR-337-3p/HMGB1 signal axis.

BACKGROUND: Circular RNAs (circRNAs) are significant modulatory molecules in the developing process of glioma. Our study will emphasize on exploring the function of circRNA Fanconi anemia group L protein (circFANCL) and the specific mechanism in glioma. METHODS: The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for detecting circFANCL, microRNA-337-3p (miR-337-3p) and high mobility group box-1 (HMGB1). Cell proliferation analysis was assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was applied to determine cell cycle and apoptosis. All protein detection was completed by western blot. Animal experiment was performed to investigate the role of circFANCL in vivo. Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were collectively conducted for analyzing the targeted combination. RESULTS: CircFANCL was signally increased in glioma tissues and cells, and the up-regulated circFANCL could predict poor prognosis in clinical glioma patients. Down-regulated circFANCL induced the proliferation inhibition, cell cycle arrest and apoptosis promotion of glioma cells in vitro, and inhibited tumor growth in vivo. Regarding the mechanism, circFANCL served as a sponge of miR-337-3p that was a tumor suppressor in glioma and circFANCL targeted miR-337-3p to regulate HMGB1 that was a target gene of miR-337-3p. Furthermore, HMGB1 down-regulation was responsible for the repression of glioma progression caused by knockdown of circFANCL. CONCLUSIONS: Through the illustration of oncogenic function of circFANCL in glioma by the miR-337-3p/HMGB1 axis, we believed that circFANCL might be a great target in the early diagnosis and late treatment of glioma.

Enhancement of butanol production in Clostridium acetobutylicum SE25 through accelerating phase shift by different phases pH regulation from cassava flour.

A prominent delay with 12h was encountered in the phase shift from acidogenesis to solventogenesis in butanol production when the substrate-glucose was replaced by cassava flour. To solve this problem, different phase of pH regulation strategies were performed to shorten this delay time. With this effort, the phase shift occurred smoothly and the fermentation time was shortened. Under the optimal conditions, 16.24g/L butanol and 72h fermentation time were achieved, which were 25.3% higher and 14.3% shorter than those in the case of without pH regulation. Additionally, the effect of CaCO3 on "acid crash" and butanol production was also investigated. It was found that organic acids reassimilation would be of benefit to enhance butanol production. These results indicated that the simple but effective approach for acceleration of phase shift is a promising technique for shortening the fermentation time and improvement of butanol production.

Treatment of Intestinal Paralysis Using Revised Major Purgative Decoction Combined with Nasointestinal Decompression: Experience with 31 Patients.

To investigate the feasibility of using a revised major purgative decoction in combination with nasointestinal decompression for the treatment of intestinal paralysis. 31 patients with intestinal paralysis underwent gastrointestinal decompression. A fluoroscopic guided tri-lumen nasointestinal decompression tube was placed, and the patients were randomly divided into two groups: patients in the study group (n = 16) received 100 ml of a revised major purgative decoction infused through the decompression tube, three times daily; and patients in the control group (n = 15) were given neostigmine 0.5 mg by muscle injection, twice daily. The clinical presentations and imaging findings both before and after the treatment were recorded and compared. A significant increase in decompression volumes and a rapid reduction in intra-abdominal pressure (IAP) were observed in all patients undergoing nasointestinal decompression (p < 0.05). Patients in the study group achieved significantly earlier restoration of intestinal function by presenting with earlier restoration of bowel sound, earlier passage of flatus and stools (p < 0.05). The deployment of gastrointestinal decompression using a long tri-lumen nasointestinal decompression tube is effective in reducing IAP and relieve abdominal distension, whereas revised major purgative decoction can enhance the recovery of intestinal function. The joint application of these two strategies is effective and safe in the management of intestinal paralysis and is worthy of adoption in clinical settings.

An intratracheal challenge murine model of asthma: can bronchial inflammation affect the nose?

PURPOSE: Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. METHODS: BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. RESULTS: Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. CONCLUSIONS: In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.

Heavy metals in agricultural soils and crops and their health risks in Swat District, northern Pakistan.

This study assessed the concentrations of heavy metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni) and zinc (Zn) in agricultural soils and crops (fruits, grains and vegetable) and their possible human health risk in Swat District, northern Pakistan. Cd concentration was found higher than the limit (0.05 mg/kg) set by world health organization in 95% fruit and 100% vegetable samples. Moreover, the concentrations of Cr, Cu, Mn, Ni and Zn in the soils were shown significant correlations with those in the crops. The metal transfer factor (MTF) was found highest for Cd followed by Cr>Ni>Zn>Cu>Mn, while the health risk assessment revealed that there was no health risk for most of the heavy metals except Cd, which showed a high level of health risk index (HRI⩾10E-1) that would pose a potential health risk to the consumers.

[Study on expression of Treg cells in attenuated Schistosoma japonicum cercariae immunized BALB/c mice].

OBJECTIVE: To study the expression differences of CD4+CD25+Foxp3+Treg cells between the attenuated cercariae immunized mice and the normal infected mice and discuss the immune protection mechanisms of the mice immunized with attenuated cercariae. METHODS: Forty female BALB/c mice were divided into 2 groups, group A, the attenuated cercariae immunized group (16 mices) and the group B, the normal cercariae infected group (16 mices), and the last 8 ones served as the blank control. The spleen cells and the ratios of PBMC's CD4+CD25+Foxp3+/CD4+CD25+T cells were compared between the attenuated cercariae immunized mice and normal mice injected by FCM and the Foxp3 expression levels in spleens and livers were assayed by IHC. The transcription factor Foxp3 in the peripheral blood was detected by RT-PCR. RESULTS: In group A and group B, CD4+CD25+Foxp3+/ CD4+CD25+T ratios in the PBMC 6 weeks post-infection were (14.15 +/- 2.62)% and (7.92 +/- 2.22)%, respectively (P < 0.05); the ratios in the spleen cells were (14.52 +/- 2.98)% and (8.18 +/- 2.84)%, respectively (P < 0.05); 8 weeks post-infection, the ratios in the PBMC were (15.92 +/- 2.98)% and (13.26 +/- 2.64)%, respectively, (P < 0.05); the ratios of the spleen cells were (16.42 +/- 2.46)% and (13.48 +/- 2.36)%, respectively (P < 0.05); 6 weeks post-infection, the Foxp3 expression levels in livers were "+" and "-", respectively, and those in the spleens were "++" and "+", respectively; 8 weeks post-infection, the Foxp3 expression levels in the livers were "++" and "-" respectively, and those in the spleens were "++" and "+", respectively. CONCLUSIONS: The expression level of attenuated cercariae immunized group's CD4+CD25+Foxp3+Treg cells is higher than that in the control group during the late stages, suggesting that CD4+CD25+Foxp3+Treg in the attenuated cercariae immunized mice may play one of the important roles in its immune protection mechanisms.