ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.

Organic phosphorus levels change the hyphosphere phoD-harboring bacterial community of Funneliformis mosseae.

The phoD-harboring bacterial community is responsible for organic phosphorus (P) mineralization in soil and is important for understanding the interactions between arbuscular mycorrhizal (AM) fungi and phosphate-solubilizing bacteria (PSB) at the community level for organic P turnover. However, current understanding of the phoD-harboring bacterial community associated with AM fungal hyphae responses to organic P levels remains incomplete. Here, two-compartment microcosms were used to explore the response of the phoD-harboring bacterial community in the hyphosphere to organic P levels by high-throughput sequencing. Extraradical hyphae of Funneliformis mosseae enriched the phoD-harboring bacterial community and organic P levels significantly altered the composition of the phoD-harboring bacterial community in the Funneliformis mosseae hyphosphere. The relative abundance of dominant families Pseudomonadaceae and Burkholderiaceae was significantly different among organic P treatments and were positively correlated with alkaline phosphatase activity and available P concentration in the hyphosphere. Furthermore, phytin addition significantly decreased the abundance of the phoD gene, and the latter was significantly and negatively correlated with available P concentration. These findings not only improve the understanding of how organic P influences the phoD-harboring bacterial community but also provide a new insight into AM fungus-PSB interactions at the community level to drive organic P turnover in soil.

MR imaging phenotypes and features associated with pathogenic mutation to predict recurrence or metastasis in breast cancer.

OBJECTIVES: Distant metastasis remains the main cause of death in breast cancer. Breast cancer risk is strongly influenced by pathogenic mutation.This study was designed to develop a multiple-feature model using clinicopathological and imaging characteristics adding pathogenic mutations associated signs to predict recurrence or metastasis in breast cancers in high familial risk women. METHODS: Genetic testing for breast-related gene mutations was performed in 54 patients with breast cancers. Breast MRI findings were retrospectively evaluated in 64 tumors of the 54 patients. The relationship between pathogenic mutation, clinicopathological and radiologic features was examined. The disease recurrence or metastasis were estimated. Multiple logistic regression analyses were performed to identify independent factors of pathogenic mutation and disease recurrence or metastasis. Based on significant factors from the regression models, a multivariate logistic regression was adopted to establish two models for predicting disease recurrence or metastasis in breast cancer using R software. RESULTS: Of the 64 tumors in 54 patients, 17 tumors had pathogenic mutations and 47 tumors had no pathogenic mutations. The clinicopathogenic and imaging features associated with pathogenic mutation included six signs: biologic features (p = 0.000), nuclear grade (p = 0.045), breast density (p = 0.005), MRI lesion type (p = 0.000), internal enhancement pattern (p = 0.004), and spiculated margin (p = 0.049). Necrosis within the tumors was the only feature associated with increased disease recurrence or metastasis (p = 0.006). The developed modelIincluding clinico-pathologic and imaging factors showed good discrimination in predicting disease recurrence or metastasis. Comprehensive model II, which included parts of modelIand pathogenic mutations significantly associated signs, showed significantly more sensitivity and specificity for predicting disease recurrence or metastasis compared to Model I. CONCLUSIONS: The incorporation of pathogenic mutations associated imaging and clinicopathological parameters significantly improved the sensitivity and specificity in predicting disease recurrence or metastasis. The constructed multi-feature fusion model may guide the implementation of prophylactic treatment for breast cancers at high familial risk women.

SGLT2 inhibition restrains thyroid cancer growth via G1/S phase transition arrest and apoptosis mediated by DNA damage response signaling pathways.

BACKGROUND: Although the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5-10% patients. Several studies found sodium-glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear. MATERIALS AND METHODS: The levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay. RESULTS: SGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3. CONCLUSIONS: SGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.

The perirenal fat thickness was independently associated with serum uric acid level in patients with type 2 diabetes mellitus.

BACKGROUND: Obesity is an important risk factor for hyperuricemia. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 257 patients with T2DM recruited from Beijing Luhe Hospital from September 2019 to May 2020. The basic and clinical information such as age, gender, duration of diabetes was collected through the medical records. All patients underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures and diastolic blood pressure. The venous blood and urine samples were collected to measure SUA, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and glycosylated hemoglobin. PrFT and PnFT were measured via ultrasonography. Pearson correlation test and linear regression analysis were used to analyze the association between PrFT and PnFT and SUA. RESULTS: We found that PrFT and PnFT increased according to the tertiles of SUA level (P = 0.001 and P = 0.009, respectively). In addition, the PrFT and PnFT were positively associated with SUA level (r = 0.25, P < 0.001, r = 0.23, P < 0.001, respectively). Moreover, this association was stronger in males, non-obesity patients and patients with normal renal function. In the multivariate analysis, the PrFT was independently associated with SUA level after adjusting confounding factors. CONCLUSIONS: The PrFT was independently associated with SUA level in patients with T2DM.

Bacterial community evolution along full-scale municipal wastewater treatment processes.

Sewage pollution is a major threat to public health because sewage is always accompanied by pathogens. Generally, wastewater treatment plants (WWTP) receive and treat sewage to control pathogenic risks and improve environmental health. This study investigated the changes in the bacterial community over the course of treatment by a WWTP. Illumina MiSeq high-throughput sequencing was performed to characterize the bacterial communities in the WWTP. This study found that potential pathogens in the WWTP, especially the genera Arcobacter and Acinetobacter, were greatly reduced. In addition, high chemical oxygen demand levels provided excessive growth substrates for the genera Hyphomicrobium and Rhodoplanes, the abundance of which could exceed autotrophic bacteria, increasing the ammonium removal. According to the network analysis, the bacterial assemblage was not randomly arranged in the WWTP, and various defined processes led to higher intra-phylum (such as Proteobacteria) coexistence than expected. Moreover, the metabolic functions of bacterial communities significantly improved in the WWTP compared with the influent. Together, the data in this study emphasize the need to understand the bacterial community of WWTPs better. When analyzing the risks of WWTP drainage systems to the environment and human health, these data should be considered.

Detection of novel germline mutations in six breast cancer predisposition genes by targeted next-generation sequencing.

In this study, a customized amplicon-based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next-generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease-causing mutations on four genes were identified in 20 samples. The percentages of possible disease-causing mutation carriers in the BC group (8.9%) and in the high-risk group (8.5%) were higher than that in the control group (1.8%). The BRCA1 possible disease-causing mutation group had a higher prevalence in family history and triple-negative breast cancer, while the BRCA2 possible disease-causing mutation group was younger and more likely to develop axillary lymph node metastasis (P < 0.05). Among the 146 patients, 47 with a family history of breast cancer were also sequenced with another 14 moderate-risk genes. Three additional possible disease-causing mutations were found on PALB2, CHEK2, and PMS2 genes, respectively. The results demonstrate that the six-gene targeted NGS panel may provide an approach to assess the genetic risk of breast cancer and predict the clinical prognosis of breast cancer patients.

Investigation of pharmacokinetics, tissue distribution and excretion of schisandrin B in rats by HPLC-MS/MS.

Schisandrin B has received much attention owing to its various biological activities. The present study was aimed at the formulation development of schisandrin B and investigation of the pharmacokinetic profiles, distribution and excretion of schisandrin B in Sprague-Dawley rats. In this study, micronized schisandrin B particles with particle size of 10-20 µm were chosen as the research object. Chromatographic separation was carried out on a BDS Hypersil C18 column (50 × 2.1 mm, i.d. 3.5 µm). Schisandrin B and deoxyschizandrin (internal standard) were detected without interference in the multiple reaction monitoring mode with positive electrospray ionization. The pharmacokinetic parameters were calculated by a noncompartmental method. The area under concentration-time curve and the maximum concentration showed a significant difference in gender. The calculated absolute oral bioavailability of schisandrin B was ~55.0% for female rat and 19.3% for male rat. Schisandrin B exhibited linear pharmacokinetics properties within the range of the tested oral dose (10, 20 and 40 mg/kg). After oral administration of schisandrin B, it was extensively distributed in ovary and adipose tissue. The result also showed very low urinary, biliary and fecal excretion of schisandrin B implying that schisandrin B was excreted mainly in the forms of metabolites.

IL-13 -1112 polymorphism and periodontitis susceptibility: a meta-analysis.

BACKGROUND: Several studies have examined the association between the IL-13 -1112C/T polymorphism and the risk of periodontitis. However, these studies have reached different conclusions. The aim of the current study was to investigate the link between this IL-13 -1112 polymorphism and susceptibility to periodontitis. METHODS: We utilized electronic databases, including the CNKI (China National Knowledge Infrastructure), Wanfang, PubMed, Embase, and Cochrane Library databases, to manually search for relevant research published through November 30, 2016. The Chinese and English terms used to search the literature included "periodontitis", "periodontal disease", "IL 13", "IL-13", and "interleukin-13". In accordance with our inclusion criteria, we selected studies that involved case-control trials. All of these case-control trials described their objectives, design and specific statistical methods. For all included studies, odds ratios (ORs) and 95% confidence intervals (95% CIs) were provided or could be calculated from the study data. The quality of the included literature was evaluated using the Newcastle-Ottawa scale (NOS). STATA 12.0 was used to calculate the sizes of the combined effects and conduct a sensitivity analysis of the results. RESULTS: Our meta-analysis included 4 articles representing 5 case-control studies with a total of 710 cases and 671 control subjects. The meta-analysis results indicated that the CC vs TT model, CT vs TT model and TT vs CT + CC model (CC VS TT: OR = 0.615, 95% CI = 0.395-0.957; CT vs TT: OR = 0.518, 95% CI = 0.323-0.830; and TT vs CT + CC: OR = 1.739, 95% CI = 1.130-2.676) were significant in five IL-13 -1112 gene polymorphism and periodontitis susceptibility models. Subgroup analysis indicated that the CC vs TT, CT vs TT and TT vs CT + CC models were significant in the chronic periodontitis (CP) group, whereas no significant differences were found in the five aggressive periodontitis (AgP) group models. The sensitivity analysis showed that dropping any single study did not affect the pooled analysis results. CONCLUSION: The IL-13 -1112 polymorphism may be associated with susceptibility to periodontitis. The IL-13 -1112 gene polymorphism may be associated with susceptibility to CP but not to AgP. Thus, large-scale, multi-ethnic case-control trials are still warranted.

Poison and alarm: the Asian hornet Vespa velutina uses sting venom volatiles as an alarm pheromone.

In colonial organisms, alarm pheromones can provide a key fitness advantage by enhancing colony defence and warning of danger. Learning which species use alarm pheromone and the key compounds involved therefore enhances our understanding of how this important signal has evolved. However, our knowledge of alarm pheromones is more limited in the social wasps and hornets compared with the social bees and ants. Vespa velutina is an economically important and widespread hornet predator that attacks honey bees and humans. This species is native to Asia and has now invaded Europe. Despite growing interest in V. velutina, it was unknown whether it possessed an alarm pheromone. We show that these hornets use sting venom as an alarm pheromone. Sting venom volatiles were strongly attractive to hornet workers and triggered attacks. Two major venom fractions, consisting of monoketones and diketones, also elicited attack. We used gas chromatography coupled to electroantennographic detection (GC-EAD) to isolate 13 known and 3 unknown aliphatic ketones and alcohols in venom that elicited conspicuous hornet antennal activity. Two of the unknown compounds may be an undecen-2-one and an undecene-2,10-dinone. Three major compounds (heptan-2-one, nonan-2-one and undecan-2-one) triggered attacks, but only nonan-2-one did so at biologically relevant levels (10 hornet equivalents). Nonan-2-one thus deserves particular attention. However, the key alarm releasers for V. velutina remain to be identified. Such identification will help to illuminate the evolution and function of alarm compounds in hornets.

[Preliminary clinical observation for platelet-rich fibrin in site preservation].

OBJECTIVE: To observe the clinical effect on site preservation with self platelet-rich fibrin (PRF) in posterior dental areas after extraction.
 METHODS: Thirty patients who asked to extract posterior teeth and were ready for dental implantation were enrolled. PRF was implanted immediately in alveolar fossa after extraction. Cone beam computer tomography (CBCT) images were taken after 4-6 months and the changes in height and width of alveolar bone were observed.
 RESULTS: There was no statistical difference in the height and width between the alveolar bone treated with PRF after the extraction of tooth and the bone condition before the extraction of tooth.
 CONCLUSION: The site preservative technology with PRF could maintain the mass of alveolar bone in posterior dental areas, which provide a better bone condition for later dental implantation.

Saikosaponin-D enhances radiosensitivity of hepatoma cells under hypoxic conditions by inhibiting hypoxia-inducible factor-1α.

BACKGROUND: Our previous study revealed that the combination of Saikosaponin-d ( SSd) and radiation is more effective in the treatment of liver cancer than the application of either of these monotherapeutic methods. However, the molecular mechanisms of the radiosensitizing effect of SSd on liver cancer remained ill defined. METHODS: Cells were treated with different interventions; afterward, cell viability, apoptosis, and cell survival of SMMC-7721 and HepG2 hepatoma cells were examined. Xenograft tumor models were established by subcutaneously injecting SMMC-7721 cells. The molecular mechanism was assessed by western blot. RESULTS: SSd dose-dependently increased radiosensitivity of hepatoma cells under hypoxic condition. The growth inhibitory effect of the combined treatment was correlated with cell apoptosis. Further mechanistic analysis indicated that SSd induced the upregulation of p53 and Bax as well as the downregulation of Bcl-2 by attenuating HIF-1α expression under hypoxic condition. These effects were enhanced when the HIF-1α inhibitor PX-478 was introduced. In vivo data also presented a more significant suppression of tumor xenograft growth from the combined therapy than from either of the monotherapeutic methods. CONCLUSIONS: Our study provides evidence for a radiosensitizing effect of SSd on hepatoma cells under hypoxic conditions by inhibiting HIF-1α expression. Thus, SSd can be used as a potential sensitizer in hepatoma radiotherapy. © 2014 S. Karger AG, Basel.

Effects of polyethylene microplastics stress on soil physicochemical properties mediated by earthworm Eisenia fetida.

Microplastics (MPs) are widely distributed in soil environments, but their ecological risks are not fully understood. To fill this knowledge gap, incubation experiments were conducted to explore the physiological response of Eisenia foetida (E. fetida) to polyethylene MP stress and its effects on soil physicochemical properties. E. fetida was incubated in soils amended with MPs of two particle sizes (13 µm and 130 µm) at six concentrations (0, 1, 3, 6, 10 and 20 g MPs·kg-1 soil) under laboratory conditions. The toxicity of 13 µm MPs on the growth and survival of E. fetida was greater than that of 130 µm MPs. Excessive reactive oxygen species accumulation induced by high MP concentrations decreased superoxide dismutase activity and increased malondialdehyde content. Soil pH increased significantly in the 130 µm treatments. MPs increased the contents of soil organic carbon and available potassium. However, the presence of MPs did not significantly alter available phosphorus or nitrate nitrogen content. MP contamination in soil may have adverse impacts on the growth of earthworms, induce oxidative stress in earthworms, and change soil physicochemical properties. In addition, the effects of MPs are size-dependent and dose-dependent. This study provides new evidence for the ecological risks of MP pollution in the earthworm-soil systems.

Construction of novel Ag/AgI/Bi4Ti3O12 plasmonic heterojunction: A study focusing on the performance and mechanism of photocatalytic removal of tetracycline.

As a result of the insufficient absorption of visible light, the application of Bi4Ti3O12 in the field of photocatalysis is limited. Ag/AgI was uniformly modified on the surface of the nanoflower bulb of Bi4Ti3O12 by simple precipitation method and photodeposition. The fabricated Ag/AgI/Bi4Ti3O12 obtained an ultra-high tetracycline (TC) removal rate under visible light irradiation. And the synergetic effects caused by the surface plasmon resonance (SPR) effect of Ag, the photosensitivity of AgI and the p-n heterojunction are the key to improving the photocatalytic performance of materials. Besides, four plausible photodegradation pathways of TC were proposed and its intermediates were evaluated for toxicity, showing a significant decrease in toxicity after photoreaction.

Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.

Background: The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function. Materials and methods: Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV1, FVC, and FEV1/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results. Results: The MR results confirmed four taxa were found causally associated with the risk of IPF. Order Bifidobacteriales (OR=0.773, 95% CI: 0.610-0.979, p=0.033), Family Bifidobacteriaceae (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and Genus RuminococcaceaeUCG009 (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while Genus Coprococcus2 (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in Class Deltaproteobacteria, Order Desulfovibrionales, Family Desulfovibrionaceae, Class Verrucomicrobiae, Order Verrucomicrobiales and Family Verrucomicrobiaceae being the most prominent beneficial microbiota, while those in Family Lachnospiraceae, Genus Oscillospira, and Genus Parasutterella were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV1 and FVC on the increased abundance of six taxa (Phylum Actinobacteria, Class Actinobacteria, Order Bifidobacteriales, Family Bifidobacteriaceae, Genus Bifidobacterium, and Genus Ruminiclostridium9) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF. Conclusion: The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.

Di-aldehyde tunicate cellulose nanocrystal (D-tCNC) aerogels for drug delivery: Effect of D-tCNC composition on aerogel structure and release properties.

Aerogels as drug carriers have the characteristics of a large specific surface area, high porosity and an elastic skeleton structure. Compared with traditional drug carriers, the use of aerogels as drug carriers can avoid the complexity of drug delivery and improve the efficiency of drug loading. In this work, the oxidation of tunicate cellulose nanocrystals (tCNCs) with NaIO4 was used to prepare di-aldehyde tunicate cellulose nanocrystals (D-tCNCs). Tetracycline (TC) was used as a drug model and pH-responsive drug-loaded aerogels were prepared by the Schiff base reaction between TC and the aldehyde group on D-tCNCs. The chemical structure, crystallinity, morphology, compression properties, porosity, swelling rate and drug loading properties were investigated by FT-IR, XRD, SEM and universal testing machines. The results showed that the porosity and equilibrium swelling ratio of the D-tCNC-TC aerogels were 95.87 % and 17.52 g/g, respectively. The stress of the D-tCNC-TC aerogel at 15 % compression was 0.07 MPa. Moreover, the analysis of drug-loaded aerogels indicated that the drug loading and encapsulation rates of D-tCNC-TC aerogels were 16.86 % and 78.75 %, respectively. In in vitro release experiments, the cumulative release rate of drug-loaded aerogel at pH = 1.2 and pH = 7.4 was 87.5 % and 79.3 %, respectively. These results indicated that D-tCNC-TC aerogels have good drug loading capacity and are pH-responsive in the pH range of 1.2 to 7.4. The prepared D-tCNC-TC aerogels are expected to be applied in drug delivery systems.

The efficacy of modified contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) using Sonazoid in diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.

Background: The contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) is an algorithm for the diagnosis of hepatocellular carcinoma (HCC) in high-risk populations. Previous studies have shown the algorithm to have high specificity and moderate sensitivity. Nevertheless, it is designated for utilization solely with blood pool contrast agents. Sonazoid, a contrast agent that combines blood pools and Kupffer cells properties, has recently gained approval for marketing in an increased number of countries. Enhanced sensitivity in diagnosing HCC may be achieved through the distinctive Kupffer phase (KP) exhibited by Sonazoid. Certain academics have suggested the modified CEUS LI-RADS using Sonazoid. The main criteria of mild and late (≥60 seconds) washout in CEUS LI-RADS LR-5 were replaced by KP (>10 minutes) defects as the primary criteria. The purpose of this research was to evaluate the effectiveness of the modified CEUS LI-RADS using Sonazoid in diagnosing HCC. Methods: Original studies on Sonazoid and CEUS LI-RADS were searched in the PubMed, Embase, Cochrane Library, and Web of Science databases until 13 July 2023, with no restrictions on language. We enrolled studies that applied Sonazoid for CEUS in patients at high risk of HCC and modified CEUS LI-RADS for the diagnosis of intrahepatic nodules. Meta-analyses, evaluations, case studies, correspondences, remarks, and summaries of conferences were excluded. Additionally, studies that fell outside the scope of this study and contained data on the same patients were also excluded. We evaluated the quality of research by employing the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A bivariate mixed effects model was utilized to conduct a meta-analysis, summarizing the sensitivity and specificity in the diagnosis of HCC. The investigation of potential factors contributing to study heterogeneity was conducted using meta-regression analysis. Results: Out of the 103 studies screened, 6 studies (835 lesions) were included in the final results. Modified CEUS LR-5 exhibited a sensitivity of 0.77 [95% confidence interval (CI): 0.70-0.82; I2=71.98%; P=0.00] and a specificity of 0.88 (95% CI: 0.83-0.92; I2=0.00; P=0.47) for HCC diagnosis, with heterogeneity in sensitivity. The presence of heterogeneity in the study was found to have a significant association with factors such as the study design, the number of image reviewers, the proportion of cirrhosis, the proportion of other non-HCC malignancies (OM) cases, and the type of reference standard (P≤0.05). Conclusions: The modified CEUS LI-RADS LR-5 categorization demonstrates a reasonable level of sensitivity 0.77, but an insufficient level of specificity 0.88 when diagnosing HCC. KP defects cannot be used as a primary feature in the diagnosis of HCC by CEUS LI-RADS, perhaps as an ancillary feature.

Distribution and biomagnification of Hexabromocyclododecanes (HBCDs) in edible marine fish in the Beibu Gulf, China: Implication for seafood dietary risk.

Hexabromocyclododecanes (HBCDs) are legacy additive brominated flame retardant. In present study, the distribution, biomagnification and potential human health risk associated with HBCDs were investigated in six edible marine fish species collected from three bays in the Beibu Gulf, China, between March and October 2021. The concentration of HBCDs ranged from 0.05 to 200 ng/g lipid weight (lw), with Scoliodon laticaudus and Trichiurus nanhaiensis having the highest and lowest concentration, respectively. The α-HBCD was dominant in most studied fish, expect for Scoliodon laticaudus. Dietary source was the primary factor for the diastereomeric profiles of HBCDs in fish. Only γ-HBCD demonstrated trophic magnification in the studied fish species. Finally, the estimated daily intake (EDI) was 0.18 ng/kg/day for adults, 0.17 ng/kg/day for teenager and children, and all corresponding margin of exposure (MOE) values were lager than 8 indicating relatively low human exposure risks from fish consumption.

Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. METHODS: Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. RESULTS: 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. CONCLUSIONS: Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.

Structural characterization and in vitro fermentation properties of polysaccharides from Polygonatum cyrtonema.

Polysaccharides, the major active ingredient and quality control indicator of Polygomatum cyrtonema are in need of elucidation for its in vitro fermentation characteristics. This study aimed to investigate the structural characteristics of the homogeneous Polygomatum cyrtonema polysaccharide (PCP-80 %) and its effects on human intestinal bacteria and short chain fatty acids (SCFAs) production during the in vitro fermentation. The results revealed that PCP-80 % was yielded in 10.44 % and the molecular weight was identified to be 4.1 kDa. PCP-80 % exhibited a smooth, porous, irregular sheet structure and provided good thermal stability. The analysis of Gas chromatograph-mass spectrometer (GC-MS) suggested that PCP-80 % contained six glycosidic bonds, with 2,1-linked-Fruf residues accounted for a largest proportion. Nuclear magnetic resonance (NMR) provided additional evidence that the partial structure of PCP-80 % probably consists of →1)-ß-D-Fruf-(2 â†’ as the main chain, accompanied by side chains dominated by →6)-ß-D-Fruf-(2→. Besides, PCP-80 % promoted the production of SCFAs and increased the relative abundance of beneficial bacteria such as Megamonas, Bifidobacterium and Phascolarctobacterium during in vitro colonic fermentation, which changed the composition of the intestinal microbiota. These findings indicated that Polygomatum cyrtonema polysaccharides were able to modulate the structure and composition of the intestinal bacteria flora and had potential probiotic properties.