[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease.

Nobiletin (NOB), a flavonoid with significant antioxidant potential, holds promise for treating nonalcoholic fatty liver disease (NAFLD). In this work, we aim to assess the effects and investigate the molecular mechanisms of NOB on NAFLD. After using a methionine choline-deficient diet to induce C57BL/6J mice, as well as oleic acid to induce HepG2 and L02 cells, we administered NOB as an intervention. The results indicated that the NOB significantly ameliorated lipid deposition, oxidative stress, and inflammation in NAFLD in both models. Its mechanism may involve the Nrf2, SREBP-1c, and NF-κB signaling pathways. Furthermore, Nrf2 is not only a direct target for NOB to improve oxidative damage but also indirectly involved in lipid-lowering and anti-inflammatory processes in NAFLD. By inhibiting Nrf2, we found that the regulatory role of Nrf2 in lipid metabolism is not related to SREBP-1c but is closely associated with NF-κB in terms of inflammation. Our results suggest that Nrf2 is one of the most critical targets for NOB against NAFLD in multiple aspects.

Mode division multiplexing chaotic encryption scheme based on key intertwining and accompanying transmission.

A mode division multiplexing (MDM) chaotic encryption scheme based on key intertwining and accompanying transmission is proposed in this paper. Based on the weakly coupled few-mode fiber (FMF), data and time-varying keys can be accompanied by transmission in two modes, LP01 and LP11, respectively. In order to generate a new key, the current key is XORed with all of the keys from all the preceding moments, one by one. To implement chaotic masking in the digital domain, the three chaotic sequences corresponding to the new key are adopted to encrypt the data at the constellation phase, data symbol block, and subcarrier levels. An 8.89 Gb/s encrypted 16QAM-OFDM signal transmission over 1 km weakly-coupled FMF is experimentally demonstrated. The receiver with the correct key can recover the data normally, while the BER of the illegal receiver remains around 0.5. In the case of the key transmission bit rate of 1 Gb/s, the cracking efficiency threshold of the time-varying key encryption scheme is 5.21 × 106 times that of the time-invariant key encryption scheme, which suggests that the proposed work is a promising candidate for future physical layer security.

High-security SCMA-OFDM multi-core fiber transmission system based on a regular hexagon chaotic codebook.

Sparse code multiple access (SCMA), a new code-domain non-orthogonal technology in the fifth-generation mobile communication (5G), can be modulated by orthogonal frequency division multiplexing (OFDM) to improve the link quality of a single user. In this paper, a high-security SCMA-OFDM multi-core fiber transmission system based on a regular hexagonal chaotic codebook is proposed for next-generation passive optical network (PON). The whole encryption process consists of a regular hexagon chaotic codebook design and frequency domain block scrambling. In designing the regular hexagon chaotic codebook, the optimization of constellation points on orthogonal resources are considered as the starting point. Firstly, the chaos factor generated by the four-dimensional Rossler chaos model is deployed to disturb the mother constellation, and then the corresponding chaotic book is formed by rotating the mother constellation and multiplying the sparse matrix. The designed codebook logically avoids the degradation of transmission performance caused by the rough scrambling of codebook constellation, to find a balance between codebook disturbance and bit error rate (BER). The security and reliability of the transmission system have been verified by performing 42 Gb/s encrypted SCMA-OFDM data transmission experiments in a 2km multi-core fiber. The key space of the encryption scheme can reach 10178, which effectively ensures the security of the transmission system. Furthermore, the performance of the transmission system with a regular hexagon chaotic codebook is improved by 2.5 dB compared with the traditional codebook when the BER is 1 × 10-3. Moreover, the SCMA-OFDM-based transmission architecture and the detection effects of different multi-user detection algorithms in the SCMA-OFDM multi-core fiber transmission system are also studied.

Correlations Between Phenotypes and Biological Process Ontologies in Monogenic Human Diseases.

A substantial body of research is focused to improve the understanding of the relationship between genotypes and phenotypes. Genotype-phenotype studies have shown promise in improving disease diagnosis in humans and identification of specific clinical phenotypes may be helpful in developing more effective therapeutic and diagnostic strategies. To expand on the existing paradigm of evaluating genotypes and phenotypes, we present an investigation of the correlation between biological processes as represented by genomic information and phenotypes in human disease. We focus on monogenic diseases and link biological process and phenotype utilizing information from the Online Mendelian Inheritance in Man, the Gene Ontology, and the Human Phenotype Ontology comprehensive genomic, phenotypic, and disease information resources. Our study uncovers 4661 statistically significant associations and identifies novel correlations between biological processes and phenotypes. We find new relationships between unique phenotype-genotype pairs related to cardiovascular diseases and hypertelorism, which suggests that differences between certain phenotype-genotype association may be the key to the divergence of corresponding phenotypes. Although the application of correlating genotype, phenotype, and biological processes may help to guide diagnosis and treatment of diseases, further investigation and more specific gene ontology descriptions are still required to elucidate mechanisms of action.

Study on the characteristics and mechanisms of nicosulfuron biodegradation by Bacillus velezensis CF57.

Nicosulfuron is one of the main sulfonylurea herbicides that have been widely used to protect maize crops. A total of 10 nicosulfuron-degrading strains were isolated from the intestine tract of earthworm Eisenia foetida. Among them, Bacillus velezensis CF57 with the highest degradation efficiency was selected and studied in detail. The degradation characteristics of CF57 showed that it was able to effectively degrade nicosulfuron in a wide range of temperature, pH, and a low inoculation amount, and the response surface analysis revealed that the optimum degradation conditions were 30.8 °C, pH 6.31, and inoculation amount 3.04%. Meanwhile, CF57 could degrade high-concentration nicosulfuron efficiently and posed a broad degradation spectrum of other sulfonylurea herbicides. Furthermore, the localization of degradation enzyme indicated that the nicosulfuron-degrading enzyme was an extracellular fraction. By analyzing the metabolites of nicosulfuron, it could be further determined that the degradation of nicosulfuron by strain CF57 was mainly through the extracellular enzyme, and its possible degradation pathway was mainly derived from the cleavage of the C-N bond of the sulfonylurea bridge. These results may provide new insights into bioremediation of nicosulfuron-contaminated environments and enrich the resources of degrading bacteria of sulfonylurea herbicides.

The sbv IMPROVER Systems Toxicology Computational Challenge: Identification of Human and Species-Independent Blood Response Markers as Predictors of Smoking Exposure and Cessation Status.

Cigarette smoking entails chronic exposure to a mixture of harmful chemicals that trigger molecular changes over time, and is known to increase the risk of developing diseases. Risk assessment in the context of 21st century toxicology relies on the elucidation of mechanisms of toxicity and the identification of exposure response markers, usually from high-throughput data, using advanced computational methodologies. The sbv IMPROVER Systems Toxicology computational challenge (Fall 2015-Spring 2016) aimed to evaluate whether robust and sparse (≤40 genes) human (sub-challenge 1, SC1) and species-independent (sub-challenge 2, SC2) exposure response markers (so called gene signatures) could be extracted from human and mouse blood transcriptomics data of current (S), former (FS) and never (NS) smoke-exposed subjects as predictors of smoking and cessation status. Best-performing computational methods were identified by scoring anonymized participants' predictions. Worldwide participation resulted in 12 (SC1) and six (SC2) final submissions qualified for scoring. The results showed that blood gene expression data were informative to predict smoking exposure (i.e. discriminating smoker versus never or former smokers) status in human and across species with a high level of accuracy. By contrast, the prediction of cessation status (i.e. distinguishing FS from NS) remained challenging, as reflected by lower classification performances. Participants successfully developed inductive predictive models and extracted human and species-independent gene signatures, including genes with high consensus across teams. Post-challenge analyses highlighted "feature selection" as a key step in the process of building a classifier and confirmed the importance of testing a gene signature in independent cohorts to ensure the generalized applicability of a predictive model at a population-based level. In conclusion, the Systems Toxicology challenge demonstrated the feasibility of extracting a consistent blood-based smoke exposure response gene signature and further stressed the importance of independent and unbiased data and method evaluations to provide confidence in systems toxicology-based scientific conclusions.

Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients: updated follow-up data from NATT study.

OBJECTIVE: A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide (TC) regimen was inferior to docetaxel, anthracycline and cyclophosphamide (TAC) in neoadjuvant treatment of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated. METHODS: TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission (pCR). Secondary endpoints included clinical response rate, event-free survival (EFS), and overall survival (OS). RESULTS: A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of 53 (range, 8-76) months, the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR (P<0.05). TAC treatment resulted in consistently better EFS than TC treatment: the estimated 5-year EFS was 66.1% vs. 29.8% (P=0.002). Moreover, the estimated 5-year OS was also in favor of TAC: 88.4% vs. 51.6% (P<0.001). Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.26-0.90; P=0.021] and OS (HR, 0.20; 95% CI, 0.08-0.60; P=0.003). CONCLUSIONS: The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.

Superior outcome after neoadjuvant chemotherapy with docetaxel, anthracycline, and cyclophosphamide versus docetaxel plus cyclophosphamide: results from the NATT trial in triple negative or HER2 positive breast cancer.

The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide(TC) compared with docetaxel, anthracycline, and cyclophosphamide(TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3­36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event free survival (adjusted hazard ratio [HR] 2.42; 95 % CI1.11­5.30) and disease-free survival (HR 2.85; 95 % CI1.21­6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation.

Thyroid gland metastasis arising from breast cancer: A case report.

The thyroid gland is an uncommon site for metastasis to develop and thus metastases arising from breast cancer are rarely observed. In the present study, we describe a case of a 45-year-old female with a three-year history of breast cancer who presented with a thyroid mass that was diagnosed as metastatic breast carcinoma by histopathological analysis of the subtotal thyroidectomy specimen. To ascertain the diagnosis of metastatic breast cancer, we evaluated two types of markers; those that possessed a similar expression status in the original and metastatic lesions [ER, PR and CerbB-2 (HER2/neu)], and those that are capable of differentiating between metastatic lesions and the surrounding thyroid components (TG and TTF-1). The results showed that ER, PR and CerbB-2 demonstrated a similar expression pattern in primary breast carcinoma and thyroid lesions. Meanwhile, in the thyroid lesions, the malignant cells showed negative staining for TG and TTF-1, which confirmed that lesions were not thyroid in origin. This case may prompt clinicians that although thyroid gland are uncommon metastatic site, a diagnosis of metastatic disease should be considered when new aggregates are identified in the thyroid glands and histopathological analysis may aid the diagnosis.

Precise method for modifying birefringence of stress-induced high-birefringence fiber.

A precise method for modifying the birefringence of stress-induced high-birefringence (Hi-Bi) fiber is demonstrated by side polishing a Panda-type fiber with a maximum polished length of at least 14 cm. The polishing depth is controlled with an accuracy of 0.1 microm by piezoelectric ceramic microdisplacement. The accuracy of the birefringence is of the order of 10(-6). This method allows high-quality Hi-Bi fiber segments to be conveniently implemented with low loss at any desired birefringence between 3.17 x 10(-4) and 7.5 x 10(-5) in our experiment from one stress-induced Hi-Bi fiber and without changing the directions of the stress axes. The finite-element method is used to simulate the procedure, and the numerical results agree with the experiment.

Observation of the ovary development and its blood vessels in 185 fetuses at different ages.

OBJECTIVE: To collect evidences for selecting the donors and optimal approaches for ovary transplantation. METHODS: Fetal ovaries were sliced for microscopic examination and the number of primary oocytes and primordial follicles therein was observed. The volume of the ovaries and the external diameter of their vessels were measured and the origin of the vessels also observed. RESULTS: Primary oocytes and primordial follicles were observed in almost equal abundance in the ovaries of the fetuses 21 weeks or older of age. The diameter of the vessels supplying the ovaries were less than 2 mm, and in 40.54% of the cases, both of the ovary vessels originated from the renal artery, with 35.14% from the aorta; in the 24.32% cases left, the vessels supplying the right ovaries started from the aorta and the other from the renal artery. CONCLUSION: The ovaries of the fetuses 21 weeks or older of age can be used as donors for transplantation, preferentially for implantation, but the vessels are too thin for uneventful anastomosis.