Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases.

Erythropoietic protoporphyria (EPP) is a rare inherited disease whose morbidity is about 1:75,000 to 1:200,000. It is caused by the deficiency of porphyrin ferrochelatase (FECH). Liver involvement in EPP is even rarer. The diagnosis of EPP with liver involvement mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing, which is still a huge challenge for both clinicians and pathologists. Here, 5 cases of EPP with liver injury were collected, and the clinicopathological features of these patients were analyzed. The clinical manifestations and laboratory examinations varied from person to person, whereas the liver biopsies showed that there were dark brown deposits within the hepatocytes, Kupffer cells, bile canaliculi and the lumen of bile ducts, which was a constant finding by histopathological examination. Gene tests were conducted in two of the five cases, and the results confirmed the diagnosis. Fully understanding of the diseases can help us reduce the rate of missed diagnosis and provide proper treatment as early as possible.

Rapid expansion of coastal aquaculture ponds in Southeast Asia: Patterns, drivers and impacts.

Aquaculture pond is one of the most important land use types and a main income source in coastal zones in Southeast Asia. However, the fast expansion of aquaculture ponds threatens coastal ecosystems - an issue that Sustainable Development Goals (SDGs)14 seeks to address. Investigating expansion patterns is essential for exploring the drivers and understanding its impacts, and thus the focus of the sustainable management of aquaculture. This study aims to assess the spatio-temporal expansion patterns of aquaculture ponds with multitemporal remote sensing images and geographic information system in the coastal zone of Southeast Asia over a 25-year period (1990-2015), to understanding how globalization and economic policies may have contributed to such changes. The results show that, in 2015, total area of coastal aquaculture ponds was about 23,245 km2, and 79% of coastal aquaculture ponds distributed within 15 km from the coastline. And the amount has expanded about 2.6 times in the past 25 years. Vietnam has the largest area of aquaculture in 2015 and the highest annual increasing rate, accounting for 40.28% and 298.5 km2/y, followed by Indonesia (31.50% and 156.8 km2/y), Thailand (10.79% and 64.8 km2/y), Myanmar (8.76% and 61.1 km2/y). The expansion pattern of aquaculture ponds in the region altered from outlying to edge-expansion from the year of 2000. The main drivers of rapid expansion lie to the intensified local fisher policies as a result of economic globalization. While development of aquaculture has enhanced family income, it has also led to significant reduction of mangrove and coastal water pollution (eutrophication). With the prevailing antagonism between aquaculture expansion and ecosystem conversion, our research call for the local government's attention to sustainable management of aquaculture. This will be the key to reduce food safety risk and simultaneously prevent inevitable damages to coastal ecosystems, as stipulated by SDGs 2 and 14.

Myeloid-derived suppressor cells expansion is closely associated with disease severity and progression in HBV-related acute-on-chronic liver failure.

Dysregulation of the host immune responses induced by host hepatitis B virus (HBV) interactions has been observed in acute-on-chronic liver failure (ACLF). Myeloid-derived suppressor cells (MDSCs), well known for their immunomodulatory properties, can suppress T-cell function by regulating the expression of CD3 ζ chain in cancer and autoimmune/infectious diseases while rarely have been studied in ACLF. In this study, MDSCs, CD4+ /CD8+ T cells, and CD3 ζ chain were analyzed by flow cytometry in peripheral blood mononuclear cells obtained from HBV-related ACLF patients, chronic hepatitis B (CHB) patients and healthy controls. ACLF patients were followed up for dynamic detection of MDSCs and observation of outcomes after treatment. Interestingly, peripheral CD14+ CD33+ CD11b+ HLA-DR-/low MDSCs from ACLF patients were significantly increased compared to those from CHB patients and healthy controls. CD4+ /CD8+ T cell frequency and CD3 ζ chain expression in T cells were decreased in ACLF patients compared to those of healthy controls and were negatively correlated with matched MDSC frequency. Meanwhile, the frequency of MDSCs was closely correlated with biochemical parameters that are relevant for liver injury rather than virological parameters. Moreover, a lower level of MDSCs was correlated with a better short-term prognosis (within 4 weeks but not at 8 weeks), and MDSCs remained high in ACLF patients whose conditions worsened within a 4-week follow-up period after treatment. These results suggest that MDSCs are closely involved in cell-mediated immunity in HBV-related ACLF and that peripheral MDSC expansion is closely associated with disease severity and progression in HBV-related ACLF, which may serve as a predictor of short-term prognosis.

Two-year-supervised resistance training prevented diabetes incidence in people with prediabetes: A randomised control trial.

AIM: The purpose of this study is to explore the long-term effects of aerobic training (AT), resistance training (RT), and combined training (AT + RT) on the prevention of T2D incidence in patients with prediabetes. MATERIALS AND METHODS: In this randomised controlled trial, people with prediabetes (fasting glucose ≥5.6 and <7.0 mmol/L and/or 2-h glucose ≥7.8 and <11.1 mmol/L on the 75-g oral glucose tolerance test and/or haemoglobin A1c ≥5.7% and <6.4%) were randomly assigned to the control group, AT group, RT group, or AT + RT group. Supervised exercise programmes, including AT, RT, and AT + RT, were completed for 60 minutes per day, three non-consecutive days per week for 24 months. The primary outcome was the incidence of T2D; secondary outcomes were blood glucose and lipid levels, including total cholesterol (TC) and standard 2-hour oral glucose tolerance (2hPG). RESULTS: A total of 137 (80%) subjects with a mean age of 59 years (45 men, 92 women) entered the final analysis. After 24 months of intervention, the incidences of T2D adjusted by sex and age were significantly decreased by 74% (95% CI, 38-89), 65% (95% CI, 21-85), and 72% (95% CI, 36-87) in the AT + RT, RT, and AT groups compared with the control group (HR: AT + RT 0.26 [95% CI, 0.11-0.62], RT 0.35 [95% CI, 0.15-0.79], and AT 0.28 [95% CI, 0.13-0.64]). The cumulative T2D incidences were significantly lower in the AT + RT, RT, and AT groups than in the control group (21%, 26%, and 22% vs 69%). The blood glucose and lipid profiles improved more in the AT, RT, and AT + RT groups than in the control group. CONCLUSION: RT and RT plus AT were as effective as isolated AT in preventing progression to T2D.

[Analysis of HEXB gene mutations in an infant with Sandhoff disease].

OBJECTIVE: To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD). METHODS: Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations. RESULTS: The infant was found to carry compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) of the HEXB gene. The c.1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in ß subunit of the Hex protein. The c.1652G>A(p.Cys551Tyr) mutation, unreported previously,was predicted to be probably damaging by Bioinformatic analysis. CONCLUSION: Compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.

[Non-linear rectification of sensor based on immune genetic algorithm].

A non-linear rectification based on immune genetic algorithm (IGA) is proposed in this paper, for the shortcoming of the non-linearity rectification. This algorithm introducing the biologic immune mechanism into the genetic algorithm can restrain the disadvantages that the poor precision, slow convergence speed and early maturity of the genetic algorithm. Computer simulations indicated that the algorithm not only keeps population diversity, but also increases the convergent speed, precision and the stability greatly. The results have shown the correctness and effectiveness of the method.

The flavor substances changes in Fuliang green tea during storage monitoring by GC-MS and GC-IMS.

To study the effect of storage (for 0, 3, 6, and 12 months) on the flavor of green tea (GT), we monitored the volatile organic compounds (VOCs) in GT through gas chromatography (GC) combined with ion mobility spectrometry and headspace solid-phase micro extraction, GC-MS (mass spectrometry). Then, relative odor activity value (ROAV) was applied to analyze the aroma contribution of the VOCs. During storage, the polyphenol and caffeine contents gradually decreased from 22.38 % to 18.51 % and from 4.37 % to 3.74 %, respectively, and the total soluble sugar first increased and then decreased (from 4.89 % to 7.16 % and then 5.02 %). Although the total free amino acid contents showed a fluctuating trend, the content of cysteamine increased gradually. The contents of VOCs with positive contribution to GT aroma, including linalool, geraniol, nonanal, and 6-methyl-5-hepten-2-one, decreased. They also contributed less in the ROAV after storage. The ROAVs of nonanal, linalool, and geraniol decreased from 3.37 to 0.79, from 100 to 38.21, and from 2.98 to 1.8, respectively, after 12 months of storage. Principal component analysis can be used to identify the samples with different storage durations based on these data. Given the increase in amount of cysteamine and decrease in that of linalool oxide, oxidation may be not the only factor responsible for tea quality in storage.

A novel strategy for estimating biomass of submerged aquatic vegetation in lake integrating UAV and Sentinel data.

Submerged aquatic vegetation (SAV) plays a fundamental ecological role in mediating carbon cycling within lakes, and its biomass is essential to assess the carbon sequestration potential of lake ecosystems. Remote sensing (RS) offers a powerful tool for large-scale SAV biomass retrieval. Given the underwater location of SAV, the spectral signal in RS data often exhibits weakness, capturing primarily horizontal structure rather than volumetric information crucial for biomass assessment. Fortunately, easily-measured SAV coverage can serve as an intermediary variable for difficultly-quantified SAV biomass inversion. Nevertheless, obtaining enough SAV coverage samples matching satellite image pixels for robust model development remains problematic. To overcome this challenge, we employed a UAV to acquire high-precision data, thereby replacing manual SAV coverage sample collection. In this study, we proposed an innovative strategy integrating unmanned aerial vehicle (UAV) and satellite data to invert large-scale SAV coverage, and subsequently estimate the biomass of the dominant SAV population (Potamogeton pectinatus) in Ulansuhai Lake. Firstly, a coverage-biomass model (R2 = 0.93, RMSE = 0.8 kg/m2) depicting the relationship between SAV coverage and biomass was developed. Secondly, in a designed experimental area, a high-precision multispectral image was captured by a UAV. Based on the Normalized Difference Water Index (NDWI), the UAV-based image was classified into non-vegetated and vegetated areas, thereby generating an SAV distribution map. Leveraging spatial correspondence between satellite pixels and the UAV-based SAV distribution map, the proportion of SAV within each satellite pixel, referred to as SAV coverage, was computed, and a coverage sample set matched with satellite pixels was obtained. Subsequently, based on the sample set, a satellite-scale SAV coverage estimation model (R2 = 0.78, RMSE = 14.05 %) was constructed with features from Sentinel-1 and Sentinel-2 data by XGBoost algorithm. Finally, integrating the coverage-biomass model with the obtained coverage inversion results, fresh biomass of SAV in Ulansuhai Lake was successfully estimated to be approximately 574,600 tons.

Daily exposure to low concentrations Tetrabromobisphenol A interferes with the thyroid hormone pathway in HepG2 cells.

Tetrabromobisphenol A (TBBPA) is a flame retardant that adversely affects the environment and human health. The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene regulation, mainly related to pathways associated with the endocrine system. The quantitative polymerase chain reaction (qPCR) confirmed that prolonged exposure gradually activated the thyroid hormone and parathyroid hormone signaling pathways. The expression levels of genes related to the thyroid hormone signaling pathway were upregulated (1.15-8.54 times) after five generations of exposure to 1 and 81 nM TBBPA. Furthermore, co-exposure to 81 nM TBBPA and 0.5 nM thyroid hormone receptor antagonist for five generations significantly reduced the expression of thyroid hormone and parathyroid hormone receptors. Meanwhile, 81 nM TBBPA inhibited the activation of the Ras pathway and downregulated Ras gene expression level (3.7 times), indicating the association between the toxic effect and thyroid hormone receptors. Additionally, our experiments revealed that the thyroid hormone pathway regulated the induction of the Ras signaling pathway by TBBPA. The study thus proves that daily exposure to TBBPA interferes with the thyroid hormone signaling pathway and subsequently the endocrine system.

Monitoring Changes in the Volatile Compounds of Tea Made from Summer Tea Leaves by GC-IMS and HS-SPME-GC-MS.

Compared with spring tea, summer tea has the advantages of economy and quantity. However, research on the aroma characteristics of summer tea is currently limited. In this study, summer fresh tea leaves (castanopsis. sinensis, cv. Fuliangzhong) (FTLs) were processed intoblack tea (BT) and green tea (GT). The changes in the volatile compounds during the tea processing were quantified using gas chromatography-ion mobility spectrometry (GC-IMS) and head space-solid phase micro-extraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), and then analyzed on the basis of relative odor activity value (ROAV). Results showed low amounts of flavor compounds, such as linalool oxides, geraniol, and sulcatone, were found in FTLs, but after processing, high amounts of the same in BT and GT. Summer BT and GT contained characteristic compounds similar to spring tea, including linalool, geraniol, (E,E)-2,4-decdienal, ß-ionone, methyl salicylate, geranyl acetone, and decanal. All these compounds have high content and ROAV values, which give the same flavor to summer teas as spring tea. This study confirmed that summer fresh tea leaves were suitable to produce black and green tea with good flavor. Monitoring changes in aroma compounds by GC-IMS coupled with GC-MS, the quality of summer tea is expected to be promoted towards the quality of spring tea by improving processing methods for valuable-tea production.

Low concentration Tetrabromobisphenol A (TBBPA) elevating overall metabolism by inducing activation of the Ras signaling pathway.

Tetrabromobisphenol A (TBBPA), one of the most common flame retardants, affects neurodevelopment, disrupts the endocrine system, and increases the possibility of tumorigenesis. This study investigates the cytotoxic effects, genetic effects, and metabolic effects from exposure to low concentration TBBPA. The cell exposure was measured by mimicking the residual TBBPA concentrations in human plasma, specifically in occupational populations. Our results revealed that long-term TBBPA exposure, especially at 1 nM concentration, significantly promoted the proliferation of HepG2 cells. Furthermore, long-term TBBPA exposure can double the levels of reactive oxygen species (ROS) released from mitochondria, thereby increasing Adenosine Monophosphate activated Protein kinase (AMPK) gene expression level to promote cellular proliferation. However, ROS can also mediate the apoptosis process through the mitochondrial membrane potential (MMP). The RNA-seq analysis confirmed that the Ras signaling pathway was activated by the growth factor to mediate cell detoxification mechanism, increasing lipid and vitamin metabolic rate. Our work uncovers a cellular mechanism by which long-term exposure to low concentration TBBPA can induce the activation of the Ras signaling pathway and demonstrates potential metabolic disorder in the human hepatic cells upon plasma TBBPA exposure.

Phase, microstructure and service character of as-deposited and short-time heat-treated Ni-Mo alloys with mixed state.

Considering the amorphous and nano-crystalline cluster structure and their activity, on the basis of the mixed structure Ni-Mo alloys, the crystallization kinetics of the alloys and the performance of the alloys after heat treatment with different mixed structure were studied. The phase structure and composition were determined by X-ray powder diffraction. The crystallization activation energy of the mixed structure was obtained by differential scanning calorimetry. The electrochemical activity of the mixed structure alloy was determined by electrochemical analysis. The experimental results show that the structural stability of the mixed-structure alloy is better, but the crystallization activation energy is much lower than that of the amorphous alloy. The crystallization process consists of a meta-stable structure transition and a new phase formation. The electrochemical properties of the alloy indicated that the alloy with the mixed structure has higher electrochemical activity, with higher hardness and better corrosion resistance, which results from the large true contact surface and the large number of active centers in this material structure.

Physical activity and fasting glucose in adults with abnormal glucose metabolism: Findings from two independent cross-sectional studies in China.

BACKGROUND: Relationship between physical activity and fasting glucose in people with abnormal glucose metabolism is not well-known. This study was to investigate dose-response association between physical activity (PAT) and fasting glucose from two independent surveys among Chinese adults with abnormal glucose metabolism. METHODS: 9419 adults with abnormal glucose metabolism from two independent surveys among Chinese adults were analyzed. Demographics, level of fasting glucose and PAT (in Met Score) were measured. Dose-response relationship between fasting glucose and PAT was assessed by natural cubic spline model. Certain threshold point was identified, and linear regression models were then used within each threshold interval to assess the liner relationship functions. Models were adjusted for confounding factors and were stratified in subgroup analyses by the main population characteristics including survey site, gender and age-group. RESULTS: Overall the relationship between PAT and fasting glucose was not in a linear association (Linearity test: p < 0.0001). Level of fasting glucose was not associated with amount of PAT until a threshold point (square-rooted Met Score 66.6 (original Met score: 4436 MET-minutes per week), 95% confidence intervals (65.2-69.3 (4,251-4,802 MET-minutes per week)). After this threshold, an inverse association was observed: each increase of every standard deviation of square-rooted Met Score 29.8 (888 MET-minutes per week) was associated with a 0.25 mmol/L decrease in fasting glucose, with adjustment for confounding factors. The patterns of relationship were tested to be consistent in subgroup analyses by survey site, gender and age group. CONCLUSIONS: Our study indicated that among adults with abnormal glucose metabolism the level of fasting glucose was only inversely associated with square-rooted Met Score beyond a certain square-rooted Met Score amount.

A convenient polyculture system that controls a shrimp viral disease with a high transmission rate.

Developing ecological approaches for disease control is critical for future sustainable aquaculture development. White spot syndrome (WSS), caused by white spot syndrome virus (WSSV), is the most severe disease in cultured shrimp production. Culturing specific pathogen-free (SPF) broodstock is an effective and widely used strategy for controlling WSS. However, most small-scale farmers, who predominate shrimp aquaculture in developing countries, cannot cultivate SPF shrimp, as they do not have the required infrastructure and skills. Thus, these producers are more vulnerable to WSS outbreaks than industrial farms. Here we developed a shrimp polyculture system that prevents WSS outbreaks by introducing specific fish species. The system is easy to implement and requires no special biosecurity measures. The promotion of this system in China demonstrated that it allowed small-scale farmers to improve their livelihood through shrimp cultivation by controlling WSS outbreaks and increasing the production of ponds.

Activation of NF-κB pathways mediating the inflammation and pulmonary diseases associated with atmospheric methylamine exposure.

The effects of methylamine on human health have been debated for several years, but the exact adverse outcomes and definite signaling cascades have not been elucidated yet. Herein, a NF-κB signal pathway, a positive regulator of inflammation was identified as the main pathway of methylamine exposure induced adverse effects in bronchial airway cells (16HBE) for the first time. The results indicated that methylamine could stimulate the overproduction of reactive oxygen species (ROS) in cytoplasm and mitochondria of 16HBE cells. Moreover, ROS accelerate the translocation and phosphorylation of NF-κB in nucleic and promote the expression of inflammatory, such as IL-8 and IL-6. As a result, methylamine was found to be increased ROS-mediated NF-κB activation in cells, leading to the production of inflammatory cytokine. Furthermore, the results also showed that methylamine could affect the expression of cytokines related genes, p53, STAT3, Bcl2, c-myc, Cyclin D, Hes1, Mcl-1, TGF-ß2. The breakdown of those cell proliferation and apoptosis related genes were leading to a common toxic mechanism of cell death. In summary, our work uncovers a mechanism by which methylamine can induce the formation of inflammation response and demonstrates potential inflammation and carcinogenesis in human airway cell upon the methylamine inhaled.

Analysis of monocytic and granulocytic myeloid-derived suppressor cells subsets in patients with hepatitis C virus infection and their clinical significance.

Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14(+)HLA-DR(-/low) cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = -2.438, P = 0.015), while there was no statistical difference between the frequency of HLA-DR(-/low)CD33(+)CD11b(+)CD15(+) (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = -2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree.

Expression and clinical significance of myeloid derived suppressor cells in chronic hepatitis B patients.

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/ PBMC median (X(2)=11.877, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/ PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference (X(2)=17.198, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.