Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

Chronopotentiometric Nanopore Sensor Based on a Stimulus-Responsive Molecularly Imprinted Polymer for Label-Free Dual-Biomarker Detection.

The development of sensors for detection of biomarkers exhibits an exciting potential in diagnosis of diseases. Herein, we propose a novel electrochemical sensing strategy for label-free dual-biomarker detection, which is based on the combination of stimulus-responsive molecularly imprinted polymer (MIP)-modified nanopores and a polymeric membrane chronopotentiometric sensor. The ion fluxes galvanostatically imposed on the sensing membrane surface can be blocked by the recognition reaction between the target biomarker in the sample solution and the stimulus-responsive MIP receptor in the nanopores, thus causing a potential change. By using two external stimuli (i.e., pH and temperature), the recognition abilities of the stimulus-responsive MIP receptor can be effectively modulated so that dual-biomarker label-free chronopotentiometric detection can be achieved. Using alpha fetoprotein (AFP) and prostate-specific antigen (PSA) as model biomarkers, the proposed sensor offers detection limits of 0.17 and 0.42 ng/mL for AFP and PSA, respectively.

Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.

Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2-/- zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2-/- zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2-/- zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.

Regulatory Mechanisms of Quorum Sensing System of Bacteria in Response to Chlorine and Ozone Disinfection.

Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and metabolisms. However, the responses and regulatory mechanisms of bacteria to various disinfection technologies through quorum sensing are still unclear. This study examines the inactivation effect of chlorination and ozonation on biofilms and planktonic cells of QS signaling-deficient mutants of Pseudomonas aeruginosa. Cell counting and viability assessment revealed that the combined disinfection of chlorine and ozone was the most effective for inactivating planktonic P. aeruginosa within 10 min of exposure. Additionally, microfluidic chip culture demonstrated that the secretion of quinolone signals escalated biofilms' disinfection resistance. Disinfection exposure significantly altered the gene expression of wild-type strains and QS signaling-deficient mutants. Moreover, the QS system triggered multilayered gene expression programs as a responsive protection to disinfectant exposure, including oxidative stress, ribosome synthesis, and the nutrient absorption of bacteria. These insights broaden our understanding of bacterial QS in response to disinfection, promising potential strategies toward efficient disinfection processes.

Sustainable efficient utilization of magnetic porous biochar for adsorption of orange G and tetracycline: Inherent roles of adsorption and mechanisms.

Iron-doped biochar has been widely used as an adsorbent to remove contaminants due to the high adsorption performance, but it still suffers from complicated preparation methods, unstable iron loading, unsatisfactory specific surface area, and uneven distribution of active sites. Here, a novel magnetic porous biochar (FeCS800) with nanostructure on surface was synthesized by one-pot pyrolysis method of corn straw with K2FeO4, and used in orange G (OG) and tetracycline (TC) adsorption. FeCS800 exhibited outstanding adsorption capacities for OG and TC after K2FeO4 activation and the adsorption data were fitted satisfactorily to Langmuir isotherm and Pseudo-second-order kinetic model. The maximum adsorption capacities of FeCS800 for OG and TC were around 303.03 mg/g and 322.58 mg/g, respectively, at 25 °C and pH 7.0, which were 16.27 and 24.61 times higher than that before modification. Thermodynamic studies showed that the adsorption of OG/TC by FeCS800 were thermodynamically favorable and highly spontaneous. And the adsorption capacity of OG and TC by FeCS800 remained 77% and 81% after 5 cycles, respectively, indicating that FeCS800 had good stability. The outstanding adsorption properties and remarkable reusability of FeCS800 show its great potential to be an economic and environmental adsorbent in contaminants removal.

EPA and DHA promote cell proliferation and enhance activity of the Akt-TOR-S6K anabolic signaling pathway in primary muscle cells of turbot (Scophthalmus maximus L.).

Fish growth and health are predominantly governed by dietary nutrient supply. Although the beneficial effects of omega-3 polyunsaturated fatty acids supplementation have been shown in a number of fish species, the underlying mechanisms are still mostly unknown. In this study, we conducted an investigation into the effects of EPA and DHA on cell proliferation, nutrient sensing signaling, and branched-chain amino acids (BCAA) transporting in primary turbot muscle cells. The findings revealed that EPA and DHA could stimulate cell proliferation, promote protein synthesis and inhibit protein degradation through activation of target of rapamycin (TOR) signaling pathway, a pivotal nutrient-sensing signaling cascade. While downregulating the expression of myogenin and myostatin, EPA and DHA increased the level of myogenic regulatory factors, such as myoD and follistatin. Furthermore, we observed a significant increase in the concentrations of intracellular BCAAs following treatment with EPA or DHA, accompanied by an upregulation of the associated amino acid transporters. Our study providing valuable insights into the mechanisms underlying the growth-promoting effects of omega-3 fatty acids in fish.

Effects of dietary chloroquine on fish growth, hepatic intermediary metabolism, antioxidant and inflammatory responses in turbot.

Autophagy is a conserved cellular self-digestion process and is essential for individual growth, cellular metabolism and inflammatory responses. It was responsive to starvation, pathogens infection and environmental stress. However, the information on the regulation of autophagy in fish hepatic intermediary metabolism, antioxidant system, and immune responses were limited. In the present study, turbot with inhibited autophagy flux was built by dietary chloroquine. The hepatic metabolic response, antioxidant enzymes and immune responses were explored. Results showed that dietary chloroquine induced the expression of Beclin 1, SQSTM and LC-3II, and effectively inhibited autophagy flux. Autophagy dysfunction depressed fish growth and feed utilization, while it induced clusters of liver lipid droplets. The genes involved in lipolysis and fatty acid ß-oxidation, as well as the lipogenesis-related genes in chloroquine group were depressed. The phosphorylation of AMPK was activated in chloroquine group, and the genes involved in glycolysis were induced. The hepatic content of malonyldialdehyde and the activities of SOD and CAT were induced when autophagy was inhibited. The content of Complement 3, Complement 4 and Immunoglobulin M, as well as the activity of lysozyme in plasma were depressed in chloroquine group. Dietary chloroquine induced the expression of toll-like receptors and stimulated the expression of myd88 and nf-κb p65, as well as the pro-inflammatory cytokines, such as tnf-α and il-1ß. The expression of anti-inflammatory cytokine tgf-ß was depressed in the chloroquine group. Our results would extend the knowledge on the role of autophagy in teleost and assist in improving fishery production.

Comprehensive study on the effect of dietary leucine supplementation on intestinal physiology, TOR signaling and microbiota in juvenile turbot (Scophthalmus maximus L.).

Intestinal damage and inflammation are major health and welfare issues in aquaculture. Considerable efforts have been devoted to enhancing intestinal health, with a specific emphasis on dietary additives. Branch chain amino acids, particularly leucine, have been reported to enhance growth performance in various studies. However, few studies have focused on the effect of leucine on the intestinal function and its underlying molecular mechanism is far from fully illuminated. In the present study, we comprehensively evaluated the effect of dietary leucine supplementation on intestinal physiology, signaling transduction and microbiota in fish. Juvenile turbot (Scophthalmus maximus L.) (10.13 ± 0.01g) were fed with control diet (Con diet) and leucine supplementation diet (Leu diet) for 10 weeks. The findings revealed significant improvements in intestinal morphology and function in the turbot fed with Leu diet. Leucine supplementation also resulted in a significant increase in mRNA expression levels of mucosal barrier genes, indicating enhanced intestinal integrity. The transcriptional levels of pro-inflammatory factors il-1ß, tnf-α and irf-1 was decreased in response to leucine supplementation. Conversely, the level of anti-inflammatory factors tgf-ß, il-10 and nf-κb were up-regulated by leucine supplementation. Dietary leucine supplementation led to an increase in intestinal complement (C3 and C4) and immunoglobulin M (IgM) levels, along with elevated antioxidant activity. Moreover, dietary leucine supplementation significantly enhanced the postprandial phosphorylation level of the target of rapamycin (TOR) signaling pathway in the intestine. Finally, intestinal bacterial richness and diversity were modified and intestinal bacterial composition was re-shaped by leucine supplementation. Overall, these results provide new insights into the beneficial role of leucine supplementation in promoting intestinal health in turbot, offering potential implications for the use of leucine as a nutritional supplement in aquaculture practices.

Bcl6 drives stem-like memory macrophages differentiation to foster tumor progression.

Cancer development is a long-lasting process during which macrophages play a pivotal role. However, how macrophages maintain their cellular identity, persistence, expanding and pro-tumor property during malignant progression remains elusive. Inspired by the recent report of the activation of stem cell-like self-renewal mechanism in mature macrophages, we postulate that intra-tumoral macrophages might be trained to assume stem-like properties and memory-like activity favoring cancer development. Herein we demonstrated that tumor infiltrating macrophages rapidly converted into the CD11b+F4/80+Ly6C-Bcl6+ phenotype, and adopted stem cell-like properties involving expression of stemness-related genes, long-term persistence and self-renewing. Importantly, Bcl6+ macrophages stably maintained cell identity, gene signature, metabolic profile, and pro-tumor property even after long-term culture in tumor-free medium, which were hence termed stem cell-like memory macrophages (SMMs). Mechanistically, we showed that transcriptional factor Bcl6 co-opted the demethylase Tet2 and the deacetylase SIRT1 to confer the epigenetic imprinting and mitochondrial metabolic traits to SMMs, bolstering the stability and longevity of trained immunity in tumor-associated macrophages (TAMs). Furthermore, tumor-derived redHMGB1 was identified as the priming signal, which, through TLR4 and mTOR/AKT pathway, induced Bcl6-driven program underpinning SMMs generation. Collectively, our study uncovers a distinct macrophage population with a hybrid of stem cell and memory cell properties, and unveils a regulatory mechanism that integrates transcriptional, epigenetic and metabolic pathways to promote long-lasting pro-tumor immunity.

Performance of spleen stiffness measurement by 2D-shear wave elastography in evaluating the presence of high-risk varices: comparative analysis of idiopathic portal hypertension versus hepatitis B virus.

BACKGROUND: Noninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV). METHODS: A retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV. RESULTS: In patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters. CONCLUSION: SS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.

Nutrient sensing signaling and metabolic responses in shrimp Litopenaeus vannamei under acute ammonia stress.

Ammonia is the primary environmental factor affecting the growth and health of crustaceans. It would induce oxidative stress and metabolic disorders. Extra amount of energy was demanded to maintain the physiological functions under ammonia stress. However, limited information was available on its effects on the main nutrient metabolism, as well as the nutrient sensing signaling pathways. In the present study, shrimp Litopenaeus vannamei were exposed to acute ammonia stress and injected with amino acid solution. The results showed that acute ammonia exposure resulted in lower free amino acid levels in hemolymph, incomplete activation of the mechanistic target of rapamycin (mTOR) signaling and cascaded less protein synthesis in muscle. It induced autophagy and activated the AMP-activated protein kinase (AMPK) pathway. Meanwhile, ammonia exposure enhanced glycolysis and lipogenesis, but inhibited lipolysis. The results characterized the integrated metabolic responses and nutrient signaling to ammonia stress. It provides critical clues to understand the growth performance and physiological responses in shrimp under ammonia stress.

Multiple papillary intralymphatic angioendotheliomas in the spleen.

A 18-year-old man presented with multiple asymptomatic masses in the spleen that had been detected on ultrasonography performed during a physical screening. He had no history of tuberculosis, and was otherwise well. Abdominal MR demonstrated multiple masses with internal stellate scars, which appeared as marked hypointensity on T2WI and contrast-enhanced MR. Most lesions showed inhomogeneous enhancement. The capsular enhancement was also revealed at delay phase. The patient underwent laparoscopic splenectomy. Pathological examination indicated papillary intralymphatic angioendothelioma (PILA), with the following immunohistochemistry results: CK (-), CR (-), ERG (+), CD34 (+), CD31 (+), D2-40 (+), Ki67 (3%+). The patient was feeling well at 6 months of follow-up.

High-κ Polyimide-Based Dielectrics by Introducing a Functionalized Metal-Organic Framework.

In this work, novel metal-organic framework/polyimide (MOF/PI) composite films possessing dielectric properties were synthesized via a solution blending method. UiO-66 and UiO-66-NH2 nanoparticles were first prepared by a hydrothermal method and added into PI to obtain the composite films. Compared with pure PI, the dielectric properties of the MOF/PI composites were substantially enhanced. The amine functionalization gave UiO-66-NH2/PI composite films better dielectric properties in comparison with UiO-66/PI composite films because of improved interaction between PI and UiO-66-NH2. It showed that the dielectric constant of the PI composite film containing 20 wt% UiO-66-NH2 is 8.8 at 102 Hz, which was approximately 2.5 times that of the pure PI (3.5 at 102 Hz). The dielectric loss of the composite film was less than 0.034. Moreover, the breakdown strength of 20 wt% UiO-66-NH2/PI composite films was found to be 208 kV/mm. We describe this new perspective for the preparation of high-performance polymer-based dielectric materials and their application as electrical materials.

DITES: A Lightweight and Flexible Dual-Core Isolated Trusted Execution SoC Based on RISC-V.

A Trusted Execution Environment (TEE) is an efficient way to secure information. To obtain higher efficiency, the building of a dual-core system-on-chip (SoC) with TEE security capabilities is the hottest topic. However, TEE SoCs currently commonly use complex processor cores such as Rocket, resulting in high resource usage. More importantly, the cryptographic unit lacks flexibility and ignores secure communication in dual cores. To address the above problems, we propose DITES, a dual-core TEE SoC based on a Reduced Instruction Set Computer-V (RISC-V). At first, we designed a fully isolated multi-level bus architecture based on a lightweight RISC-V processor with an integrated crypto core supporting Secure Hashing Algorithm-1 (SHA1), Advanced Encryption Standard (AES), and Rivest-Shamir-Adleman (RSA), among which RSA can be configured to five key lengths. Then, we designed a secure boot based on Chain-of-Trust (CoT). Furthermore, we propose a hierarchical access policy to improve the security of inter-core communication. Finally, DITES is deployed on a Kintex 7 Field-Programmable-Gate-Array (FPGA) with a power consumption of 0.297 W, synthesized using TSMC 90 nm. From the results, the acceleration ratios of SHA1 and RSA1024 decryption/encryption can reach 75 and 1331/1493, respectively. Compared to exiting TEE SoCs, DITES has lower resource consumption, higher flexibility, and better security.

Slc38a9 Deficiency Induces Apoptosis and Metabolic Dysregulation and Leads to Premature Death in Zebrafish.

Eukaryotic cells control nutritional homeostasis and determine cell metabolic fate through a series of nutrient transporters and metabolic regulation pathways. Lysosomal localized amino acid transporter member 9 of the solute carrier family 38 (SLC38A9) regulates essential amino acids' efflux from lysosomes in an arginine-regulated fashion. To better understand the physiological role of SLC38A9, we first described the spatiotemporal expression pattern of the slc38a9 gene in zebrafish. A quarter of slc38a9-/- mutant embryos developed pericardial edema and died prematurely, while the remaining mutants were viable and grew normally. By profiling the transcriptome of the abnormally developed embryos using RNA-seq, we identified increased apoptosis, dysregulated amino acid metabolism, and glycolysis/gluconeogenesis disorders that occurred in slc38a9-/- mutant fish. slc38a9 deficiency increased whole-body free amino acid and lactate levels but reduced glucose and pyruvate levels. The change of glycolysis-related metabolites in viable slc38a9-/- mutant fish was ameliorated. Moreover, loss of slc38a9 resulted in a significant reduction in hypoxia-inducible gene expression and hypoxia-inducible factor 1-alpha (Hif1α) protein levels. These results improved our understanding of the physiological functions of SLC38A9 and revealed its indispensable role in embryonic development, metabolic regulation, and stress adaption.

Dietary lysine level affects digestive enzyme, amino acid transport and hepatic intermediary metabolism in turbot (Scophthalmus maximus).

Lysine is one of the most important essential amino acids in fish, especially in the feed formulated with high levels of plant ingredients. Lysine restriction always led to growth inhibition and poor feed utilization. However, little information was available on its effects on digestion, absorption, and metabolism response in fish. In the present study, three experimental diets were formulated with three lysine levels, 1.69% (LL group), 3.32% (ML group), and 4.90% (HL group). A 10-week feeding trial was carried out to explore the effects of dietary lysine levels on the digestive enzymes, amino acid transporters, and hepatic intermediary metabolism in turbot (Scophthalmus maximus). As the results showed, the activities of lipase and trypsin in ML group were higher than in other groups. Lysine restriction inhibited the expression levels of peptides and amino acid transporters such as PpeT1, y+LAT2, b0,+AT, and rBAT but significantly induced the expression of CAT1. Meanwhile, lysine deficiency elevated the content of T-CHO and LDL-C in plasma, while a higher HDL-C/LDL-C ratio was observed in ML group. For hepatic intermediary metabolism, the increase of lysine level induced the mRNA expression of G6Pase1 and FBPase, but no differences were observed in the expression of the key regulators in glycolysis pathway, such as GK and PK. Furthermore, an appropriate increase in the level of lysine promoted the genes involved in lipolysis, including PPARα, ACOX1, CPT1A, and LPL. However, no differences were observed in the expression of PPARγ, FAS, SREBP1, and LXR, which were important genes related to lipid synthesis. These results provide clues on the metabolic responses on dietary lysine in teleost.

Fine-Tuning of Postprandial Responses via Feeding Frequency and Leucine Supplementation Affects Dietary Performance in Turbot (Scophthalmus maximus L.).

BACKGROUND: Feeding-induced cell signaling and metabolic responses affect utilization of dietary nutrients but are rarely taken advantage of to improve animal nutrition. OBJECTIVES: We hypothesized that by modulating postprandial kinetics and signaling, improved dietary utilization and growth performance could be achieved in animals. METHODS: Juvenile turbot (Scophthalmus maximus L.) with an initial mean ± SD weight of 10.1 ± 0.01 g were used. Two feeding frequencies (FFs), either 1 or 3 meals/d at a fixed 2.4% daily body weight ration, and 2 diets that were or were not supplemented with 1% crystalline leucine (Leu), were used in the 10-wk feeding trial. At the end of the trial, a 1-d force-feeding experiment was conducted using the aforementioned FF and experimental diets. Samples were collected for the analysis of postprandial kinetics of aminoacidemia, mechanistic target of rapamycin (mTOR) signaling activities, protein deposition, as well as the mRNA expression levels of key metabolic checkpoints at consecutive time points after feeding. RESULTS: Increased FF and leucine supplementation significantly enhanced fish growth by 7.68% ± 0.53% (means ±SD) and 7.89% ± 1.25%, respectively, and protein retention by 4.01% ± 0.59% and 4.44% ± 1.63%, respectively, in feeding trial experiments. The durations of postprandial aminoacidemia and mTOR activation were extended by increased FF, whereas leucine supplementation enhanced mTOR signaling without influencing the postprandial free amino acids kinetics. Increased FF and leucine supplementation enhanced muscle protein deposition 21.6% ± 6.85% and 22.3% ± 1.52%, respectively, in a 24-h postfeeding period. CONCLUSIONS: We provided comprehensive characterization of the postprandial kinetics of nutrient sensing and metabolic responses under different feeding regimens and leucine supplementation in turbot. Fine-tuning of postprandial kinetics could provide a new direction for better dietary utilization and animal performances in aquaculture.

Study of the micromorphology and health risks of arsenic in copper smelting slag tailings for safe resource utilization.

Slag tailings are produced by "cooling-grinding-ball milling-flotation" and other processes of slag, while slag is produced by the flash smelting of the original ore. The utilization and environmental hazards of arsenic in slag tailings have become a focus of attention. This study on slag tailings reveals the presence of arsenic in copper smelting tailings from the mineralogy and leaching perspectives, and the noncarcinogenic and carcinogenic risks of arsenic to the human body were assessed by using the USEPA health risk model. The surface particles of the slag tailings were unevenly dispersed, and the mineral crystals were relatively complete. A small amount of secondary minerals had grown on the mineral surface. Most of the fine particles adhered to the surface of the main mineral to form inclusions. The mineral composition of the slag tailings was dominated by maghemite (Fe3O4) and fayalite (Fe2SiO4), and the arsenic-bearing minerals were unevenly distributed, where As (Ⅴ) fine particles were embedded in maghemite, amorphous phase and fayalite. There was a large amount of residual arsenic in the slag tailing particles, and the leaching content of arsenic in the toxicity leaching procedure was always lower than the limit of 5 mg/L. The health risk to the exposed population was evaluated by the USEPA health risk model. Since the exposed population in the industrial land is mainly adults, it is determined that the tailings will not cause harm to children's health. In this evaluation, the exposure duration (length of service of the workers) of 30 years, exposure frequency of 314 d/y and body weight of 60 kg (average weight of the workers) were taken as the parameters of three exposure pathways: hand-oral ingestion, respiratory system inhalation and skin contact. Therefore, longer activity time of the workers in the tailing workshop corresponds to a higher HI (hazard index). Although the arsenic in the slag tailings had a certain degree of bioavailability, it was not sufficient to adversely affect human health.

An exploratory study of two-dimensional shear-wave elastography in the diagnosis of acute compartment syndrome.

BACKGROUND: Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound elastography technique that uses shear waves to quantitatively measure tissue stiffness and it has recently been developed as a safe, real-time, and noninvasive imaging technique. The purpose of this study was to investigate the value of 2D-SWE in the diagnosis and treatment of acute compartment syndrome (ACS). METHODS: 2D-SWE was used to measure the elasticity values of the main muscles in the superficial compartments of the calf in 212 healthy volunteers, and the difference in the muscle elasticity values between different gender and age groups were analyzed. Nine patients with clinical suspicion of ACS were included in this study and 2D-SWE was used to measure the elasticity values of the muscles on the affected and unaffected sides, and a comparative analysis was performed. RESULTS: The mean elasticity values of the tibialis anterior (TA), peroneus longus (PL), and gastrocnemius medialis (GA) muscles in the relaxed state of the 212 healthy volunteers were 25.4 ± 3.2 kPa, 15.7 ± 1.5 kPa, and 12.1 ± 2.1 kPa, respectively. No statistically significant differences was observed in the elasticity values of the same muscle under the state of relaxation in different gender and age groups (p > 0.05). A statistically significant difference in the elasticity values of the muscle between the affected and unaffected sides in the fasciotomy group (p < 0.05, n = 5) was observed. In contrast, no difference in the elasticity values of the muscle between the affected and unaffected sides in the conservative group (p > 0.05, n = 4) was observed. There was a statistically significant difference in the elasticity values of the muscle on the affected side in the two treatment groups (p < 0.05). CONCLUSIONS: When the ACS occurs, the muscle elasticity of the affected limb increases significantly. 2D-SWE is expected to be a new noninvasive technique for the assessment of ACS and may provide a potential basis for clinical diagnosis and treatment.

HNF1B inhibits cell proliferation via repression of SMAD6 expression in prostate cancer.

Prostate cancer is the most common malignancy in men in developed countries. In previous study, we identified HNF1B (Hepatocyte Nuclear Factor 1ß) as a downstream effector of Enhancer of zeste homolog 2 (EZH2). HNF1B suppresses EZH2-mediated migration of two prostate cancer cell lines via represses the EMT process by inhibiting SLUG expression. Besides, HNF1B expression inhibits cell proliferation through unknown mechanisms. Here, we demonstrated that HNF1B inhibited the proliferation rate of prostate cancer cells. Overexpression of HNF1B in prostate cancer cells led to the arrest of G1 cell cycle and decreased Cyclin D1 expression. In addition, we re-explored data from ChIP-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq), and demonstrated that HNF1B repressed Cyclin D1 via direct suppression of SMAD6 expression. We also identified CDKN2A as a HNF1B-interacting protein that would contribute to HNF1B-mediated repression of SMAD6 expression. In summary, we provide the novel mechanisms and evidence in support HNF1B as a tumour suppressor gene for prostate cancer.