Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.

PURPOSE: Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases. PATIENTS AND METHODS: Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis. RESULTS: Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-ß, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1ß, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations. CONCLUSION: This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Long-term outcomes of endovascular therapy for right subclavian artery occlusive lesions: A multi-center experience.

OBJECTIVE: To review our multi-institutional experience with endovascular therapy for right subclavian artery occlusive disease and to evaluate the long-term outcomes. METHODS: We retrospectively evaluated all patients with right subclavian artery stenosis and occlusive disease who underwent endovascular therapy between March 2014 and September 2022 at two institutions. Patient baseline demographics, lesion characteristics, treatment strategies, and in-hospital and follow-up outcomes were prospectively collected and retrospectively analyzed. RESULTS: Between March 2014 and September 2022, 73 patients underwent endovascular treatment at the two institutions. The dominant cause of lesions in this cohort was atherosclerosis. Three different types of lesions were summarized, and the corresponding endovascular strategies were performed. 66 patients (90.4%) underwent successful endovascular treatment, and 62 patients (84.9%) underwent balloon-expandable stent deployment. The mean perioperative in-hospital stay was 4.0 days (range, 3-6 days). Two patients died due to myocardial infarction, and one died of cerebral hemorrhage resulting from a traffic accident within 30 days of the intervention. The median follow-up time was 31.6 months (range, 12-96 months). No complications, including death, stroke, stent fractures, or migration, were noted in any patient during the follow-up period. The overall complication rate was 7/73 (9.6%), and 5/7 (6.9%) of the complications required reintervention. CONCLUSIONS: Endovascular treatment of right subclavian artery lesions is safe, effective, and technically achievable. The reasonable use of balloon-expandable stents can achieve satisfactory outcomes with accurate orientation and promising patency.

Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach.

Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.

Isolation and Purification of Protamine from the Cultured Takifugu flavidus and Its Physicochemical Properties.

Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable insulin and as a heparin antagonist, combatting fatigue, etc. Thus, it has been widely used in medicinal applications and food products. Cultured Takifugu flavidus is a type of pufferfish with a delicious taste that is popular in China, and its production is increasing significantly. Therefore, protamine was extracted via acid extraction from the sperm of Takifugu flavidus and further isolated and purified via sephadex gel chromatography, ion exchange chromatography, and desalination chromatography. Furthermore, the physicochemical properties of protamine were investigated. The results showed that the sperm of the cultured T. flavidus were non-toxic, and the extracted and purified protamine had high contents of arginine (36.90%) and lysine (27.02%), respectively. The secondary structure of protamine was mainly ß-folded and irregularly curled. Additionally, protamine exhibited high thermal stability with a denaturation temperature of 176 °C. This study would provide a theoretical basis for the structural analysis, bioactivity, and resource development of pufferfish protamine and help to promote the development of the pufferfish industry.

Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation.

BACKGROUND: The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO). RESULTS: The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3. CONCLUSION: We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

PEG-modified halloysite as a hydrophilic interaction and cation exchange mixed-mode sorbent for solid-phase extraction of biogenic amines in fish samples.

A novel type of PEG-modified halloysite was prepared and used as a hydrophilic interaction and cation exchange mixed-mode sorbent for solid-phase extraction of biogenic amines in fish samples. The eluates were analyzed by high-performance liquid chromatography-ultraviolet detection after the derivatization with benzoyl chloride. The developed sorbent was characterized by scanning electron microscopy, infrared spectroscopy, X-ray diffraction, zeta potential analyzer, and thermo-gravimetric analysis. After the optimization of various parameters influencing the extraction efficiency, the PEG-modified halloysite-based SPE method was evaluated. The adsorption capacities of putrescine, spermine, phenethylamine, and histamine were as high as 9.3, 8.5, 5.7, and 5.6 mg g-1, respectively. Satisfactory reproducibility of sorbent preparation was obtained with within-batch and batch-to-batch relative standard deviations (RSDs) lower than 3.9% and 8.6%, respectively. The biogenic amine spiking recoveries in fish samples ranged from 84.3 to 105.5% with good RSDs lower than 7.8%. Intra-day and inter-day precision, expressed as RSDs, were better than 8.8%. The limits of detection of histamine, putrescine, phenethylamine, and spermine were 9.4, 1.9, 0.5, and 0.9 µg L-1, respectively. This work provides a new hydrophilic interaction and cation exchange mixed-mode sorbent and is successfully applied to the extraction of trace biogenic amines from fish samples.

Long-term outcomes of thoracic endovascular aortic repair for chronic Stanford type B aortic dissection.

OBJECTIVES: The aim of this study was to report the long-term outcomes of proximal thoracic endovascular aortic repair (TEVAR) for chronic Stanford type B aortic dissection (cTBAD). METHODS: We retrospectively analyzed the clinical data of 48 cases of patients with cTBAD who underwent proximal TEVAR in Zhongshan Hospital Fudan University from January 2010 to September 2013. The preoperative and postoperative imaging examinations, overall survival rate, aortic-related survival rate, and freedom from reintervention rate data were collected to evaluate aortic remodeling and clinical outcomes. The enrolled patients received follow-up at 1, 3, 6, and 12 months following treatment and annually thereafter. RESULTS: A total of 48 patients (mean age, 58.3 ± 10.6 years; men:women, 40:8) were included, of which 38 cases (79.2%) were uncomplicated dissection and 10 cases (20.8%) were complicated. The mean follow-up time was 48.7 ± 40 months (1-120 months). The mean time interval from the initial procedure to reintervention was 50.6 ± 32.7 months (11-98 months). The following changes were observed at preoperative versus last follow-up timepoints. Descending aortic level: true lumen, 19.2 ± 7.01 mm vs. 36.9 ± 9.53 mm (p < 0.001); false lumen, 30.47 ± 15.89 mm vs. 19.16 ± 15.33 mm (p < 0.001); maximum diameter, 49.67 ± 13.96 mm vs. 56.66 ± 14.95 mm (p = 0.018). Diaphragm level: true lumen, 16.24 ± 5.41 mm vs. 24.41 ± 8.04 mm (p < 0.001); false lumen, 12.37 ± 11.49 mm vs. 14.92 ± 12.25 mm (p = 0.196); and maximum diameter, 34 ± 7.81 mm vs. 38.04 ± 7.7 mm (p < 0.001). The freedom from reintervention rate was 81% in 5 years and 50.6% in 10 years. The overall 10-years survival rate was 83% (6 of 48), and the aortic-related survival rate was 92.3% (3 of 48). CONCLUSIONS: TEVAR is a safe and effective proximal repair intervention for cTBAD that can reliably induce the positive remodeling of the descending aorta.

Cultivar-specific response of rhizosphere bacterial community to uptake of cadmium and mineral elements in rice (Oryza sativa L.).

Toxic metal-contaminated farmland from Cadmium (Cd) can enhance the accumulation of Cd and impair the absorption of mineral elements in brown rice. Although several studies have been conducted on Cd exposure on rice, little has been reported on the relationship between Cd and mineral elements in brown rice and the regulatory mechanism of rhizosphere microorganisms during element uptake. Thus, a field study was undertaken to screen japonica rice cultivars with low Cd and high mineral elements levels, analyze the quantitative relationship between Cd and seven mineral elements, and investigate the cultivar-specific response of rice rhizosphere bacterial communities to differences in Cd and mineral uptake in japonica rice. Results showed that Huaidao-9 and Xudao-7 had low Cd absorption and high amounts of mineral nutrient elements (Fe, Zn, Mg, and Ca, LCHM group), whereas Zhongdao-1 and Xinkedao-31 showed opposite accumulation characteristics (HCLM group). Stepwise regression analysis showed that zinc, iron, and potassium are the key minerals that affect Cd accumulation in japonica rice and zinc was the most important factor, accounting for 68.99 %. The accumulation of Cd and mineral elements is potentially associated with rhizosphere soil bacteria. Taxa enriched in the LCHM rhizosphere (phyla Acidobacteriota and MBNT15) indicated the high nutrient characteristics of the soil and reduced activity of Cd in soil. The HCLM rhizosphere was highly colonized by metal-activating bacteria (Actinobacteria), lignin-degrading bacteria (Actinobacteria and Chlorofexi), and bacteria scavenging nutrients and trace elements (Anaerolinea and Ketobacter). Moreover, the differences in the uptake of Cd and mineral elements affected predicted functions of microbial communities, including sulfur oxidation and sulfur derivative formation, human or plant pathogen, and functions related to the iron oxidation and nitrate reduction. The results indicate a potential association of Cd and mineral elements uptake and accumulation with rhizosphere bacteria in rice, thus providing theoretical basis and a new perspective on the maintenance of rice security and high quality simultaneously.

Optimization and multi-uncertainty analysis of best management practices at the watershed scale: A reliability-level based bayesian network approach.

Best management practices (BMPs) have been widely adopted to mitigate diffuse source pollutants, and the simulated processes of its pollutant reduction effectiveness suffer from manifold uncertainties, such as watershed model parameters and climate change. We presented a novel Bayesian modeling framework for BMPs planning, integrating process-based watershed modeling and Bayesian optimization algorithm to reveal the impact of multiple uncertainties. The proposed framework was applied to a BMPs planning case study in the Erhai watershed, the seventh-largest freshwater lake in China. Firstly, priority management areas (PMAs) were identified for BMPs siting using a simulation-optimization approach. Bayesian networks were subsequently embedded to reveal the multiple uncertainty sources in the optimal planning and the reliability level (RL) is introduced to represent the probability to meet the water quality target with BMPs implementation. The results suggest that ENS of discharge and nutrients concentration simulation by LSPC are both greater than 0.5, which displays satisfactory performance. The identified PMAs account for 0.8% of the total watershed areas while contribute to more than 15% of nutrient loadings reduction. The analysis of multiple uncertainty sources reveals that precipitation is the most influential source of uncertainties in BMP effectiveness. The construction of hedgerows plays an important role in the nutrient reduction. With the improvement of the reliability levels, the cost increases sharply, indicating that the implementation of BMPs has a marginal utility. The study addressed the urgent need for effective and efficient BMPs planning by identifying PMAs and addressing multi-source uncertainties.

Resveratrol inhibits TGF-ß1-induced fibrotic effects in human pterygium fibroblasts.

BACKGROUND: Resveratrol is a polyphenolic phytoalexin which has the properties of anti-oxidant, anti-inflammatory and anti-fibrotic effects. The aim of this study was to investigate the anti-fibrotic effects of resveratrol in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHOD: Profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). The expression of profibrotic markers, including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin, were detected by western blot and quantitative real-time-PCR after treatment with various concentrations of resveratrol in HPFs to investigate the anti-fibrotic effects. Relative signaling pathways downstream of TGF-ß1 were detected by Western blot to assess the underlying mechanism. Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry to evaluate proliferation and drug-induced cytotoxicity. Cell migration and contractile phenotype were detected through wound healing assay and collagen gel contraction assay. RESULTS: The expression of α-SMA, FN and COL1 induced by TGF-ß1 were suppressed by treatment with resveratrol in dose-dependent manner. The Smad3, mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) pathways were activated by TGF-ß1, while resveratrol attenuated those pathways. Resveratrol also inhibited cellular proliferation, migration and contractile phenotype, and induced apoptosis in HPFs. CONCLUSIONS: Resveratrol inhibit TGF-ß1-induced myofibroblast activation and extra cellular matrix synthesis in HPFs, at least partly, by regulating the TGF-ß/Smad3, p38 MAPK and PI3K/AKT pathways.

TCF20 dysfunction leads to cortical neurogenesis defects and autistic-like behaviors in mice.

Recently, de novo mutations of transcription factor 20 (TCF20) were found in patients with autism by large-scale exome sequencing. However, how TCF20 modulates brain development and whether its dysfunction causes ASD remain unclear. Here, we show that TCF20 deficits impair neurogenesis in mouse. TCF20 deletion significantly reduces the number of neurons, which leads to abnormal brain functions. Furthermore, transcriptome analysis and ChIP-qPCR reveal that the DNA demethylation factor TDG is a downstream target gene of TCF20. As a nonspecific DNA demethylation factor, TDG potentially affects many genes. Combined TDG ChIP-seq and GO analysis of TCF20 RNA-Seq identifies T-cell factor 4 (TCF-4) as a common target. TDG controls the DNA methylation level in the promoter area of TCF-4, affecting TCF-4 expression and modulating neural differentiation. Overexpression of TDG or TCF-4 rescues the deficient neurogenesis of TCF20 knockdown brains. Together, our data reveal that TCF20 is essential for neurogenesis and we suggest that defects in neurogenesis caused by TCF20 loss are associated with ASD.

Engineered Pigs Carrying a Gain-of-Function NLRP3 Homozygous Mutation Can Survive to Adulthood and Accurately Recapitulate Human Systemic Spontaneous Inflammatory Responses.

The NLRP3 inflammasome is associated with a variety of human diseases, including cryopyrin-associated periodic syndrome (CAPS). CAPS is a dominantly inherited disease with NLRP3 missense mutations. Currently, most studies on the NLRP3-inflammasome have been performed with mice, but the activation patterns and the signaling pathways of the mouse NLRP3 inflammasome are not always identical with those in humans. The NLRP3 inflammasome activation in pigs is similar to that in humans. Therefore, pigs with precise NLRP3-point mutations may model human CAPS more accurately. In this study, an NLRP3 gain-of-function pig model carrying a homozygous R259W mutation was generated by combining CRISPR/Cpf1-mediated somatic cell genome editing with nuclear transfer. The newborn NLRP3 R259W homozygous piglets showed early mortality, poor growth, and spontaneous systemic inflammation symptoms, including skin lesion, joint inflammation, severe contracture, and inflammation-mediated multiorgan failure. Severe myocardial fibrosis was also observed. The tissues of inflamed skins and several organs showed significantly increased expressions of NLRP3, Caspase-1, and inflammation-associated cytokines and factors (i.e., IL-1ß, TNF-α, IL-6, and IL-17). Notably, approximately half of the homozygous piglets grew up to adulthood and even gave birth to offspring. Although the F1 heterozygous piglets showed improved survival rate and normal weight gain, 39.1% (nine out of 23) of the piglets died early and exhibited spontaneous systemic inflammation symptoms. In addition, similar to homozygotes, adult heterozygotes showed increased delayed hypersensitivity response. Thus, the NLRP3 R259W pigs are similar to human CAPS and can serve as an ideal animal model to bridge the gap between rodents and humans.

C18-modified halloysite as a novel sorbent in matrix solid-phase dispersion for the extraction of bisphenol A and diethylstilbestrol from human placenta.

In the current study, the C18-modified halloysite was fabricated via silylation reaction and subsequently used as sorbent in matrix solid-phase dispersion (MSPD) for the extraction of bisphenol A and diethylstilbestrol from human placenta, followed by high-performance liquid chromatography-tandem mass spectrometry analysis. The as-prepared sorbent was characterized by scanning electron microscopy, energy-dispersive spectrometry, Fourier transform infrared spectroscopy, X-ray diffraction, and thermo-gravimetric analysis. Varied parameters such as methanol concentration in wash solvent, pH and salt concentration in elution solvent, elution volume, and mass ratio of sample to sorbent were optimized. The adsorption capacities of bisphenol A and diethylstilbestrol on the developed C18-modified halloysite were 6.3 and 14.2 mg g-1, respectively, higher than those on the commercial C18 silica gel. Under the optimal condition, the average recoveries of bisphenol A and diethylstilbestrol by MSPD varied from 91.0 to 106.0%, and the relative standard deviations were less than 10.6% for human placenta samples. The limits of detection in the human placenta were 0.2 µg kg-1 for bisphenol A and diethylstilbestrol. The simple C18-modified halloysite-based MSPD method holds great potential for the determination of trace bisphenol A and diethylstilbestrol in the human placenta and other tissues of pregnant women with high sensitivity, accuracy, and reliability.

Single-incision plus one-port laparoscopic gastrectomy versus conventional multi-port laparoscopy-assisted gastrectomy for gastric cancer: a retrospective study.

BACKGROUND: We compared short-term perioperative outcomes after single-incision plus one-port laparoscopic gastrectomy (SILG+1) and conventional multi-port laparoscopy-assisted gastrectomy (C-LAG) for gastric cancer. METHODS: The work was conducted between August 2017 and October 2019. A total of 90 patients with early or advanced gastric cancer were retrospectively analyzed: 43 patients of which underwent SILG+1, and 47 of which underwent C-LAG, respectively. These were divided into two groups: the total gastrectomy group (SILT+1 and C-LATG) and the distal gastrectomy group (SILD + 1 and C-LADG). The demographics, tumor characteristics, postoperative outcomes, and short-term complications of all enrolled patients were summarized and statistically analyzed. RESULTS: The mean incision length in SILT+1 group was 5.40 cm shorter than that in C-LATG group (3.15 ± 0.43 vs. 8.55 ± 2.72, P < 0.001). This comparison between the SILD + 1 and the C-LADG group produced comparable results. The SILT+1 group underwent a 56.32 min longer operation than the C-LATG group (273.03 ± 66.80 vs. 216.71 ± 82.61, P = 0.0205). SILG+1 group had better postoperative visual analog scale (VAS) and cosmetic score than those of the C-LATG group (P < 0.05). There were no significant differences in preoperative demographics or 30-day postoperative complication rates between the SILG+1 and C-LAG groups. Tumor-related index, including mass size, histological type, number of retrieved lymph nodes, pathological tumor-node-metastasis (TNM) stage, and proximal and distal edges were all equivalent between the SILG+1 and the C-LAG group. CONCLUSIONS: This retrospective study demonstrates the safety and feasibility of SILG+1 with D1+ or D2 lymphadenectomy for the treatment of early and advanced gastric cancers, compared with C-LAG.

A high-resolution nutrient emission inventory for hotspot identification in the Yangtze River Basin.

A high-resolution nutrient emission inventory can provide reliable and accurate identification of priority control areas, which is crucial for efficient decisions on water quality restoration. However, the inventories widely used in large-scale modeling are usually based on provincial inputs, which induce the challenges of lacking localized parameters and missing localized characteristic when provincial scale inputs are converted to finer scales with the down-scale methods. Based on elaborate investigations and statistical data at the county scale with multi-scale data conversion, the China Emission Inventory of Nutrients (CEIN) was developed with a spatial resolution of a 0.1° grid and sub-basin scales. The Yangtze River Basin was used as a case study to illustrate the potential applications of CEIN. The emissions of total nitrogen (TN) and total phosphorus (TP) of Yangtze River Basin is 0.43 Mt and 0.04 Mt for point sources, 11.09 Mt and 4.64 Mt for diffuse sources in 2017. The hotspot analysis for 2606 sub-basins indicated that cropland is the key source of nutrient emissions, accounting for 58.88% and 79.15% of TN and TP, respectively. Industrial sewage and freshwater aquaculture accounted for 27.39% (TN) and 21.98% (TP) of the point sources, which is substantial due to their direct discharge into surface waters. The current results also reveal that, in contrast to CEIN, the previously used common emission factors based on GDP per capita produced considerable overestimations of 2.37 and 2.65 times the actual TN and TP emissions, respectively. Additional advantages of the CEIN have been demonstrated in identifying priority control areas more accurately with reduced bias and quantifying the effects of policies at much smaller scales. For example, the CEIN helps to distinguish hotspots, which was neglected when identifying sources at the level-III sub-basin scale, and indicates that the management of fractional areas (TN: 16.97%; TP: 13.44%) provides the highest nutrient emissions control (TN: 44.34%; TP: 48.65%) for the entire basin. The evaluation of China's toilet revolution policy demonstrates that achieving equitable access to safe sanitation has resulted in a reduction of 7240 t of TN and 833 t of TP, which is extremely critical for rural water quality and health.

Hydrophilic-interaction-based magnetically assisted matrix solid-phase dispersion extraction of carbadox and olaquindox in feeds.

BACKGROUND: Carbadox and olaquindox have been banned from feeds since 1998 by the EU because of their mutagenic, photoallergic, and carcinogenic effects. Unfortunately, owing to their outstanding effect, they are frequently abused or misused in animal husbandry. There is an urgent need to develop a sensitive and reliable method for monitoring these drugs in animal feeds. RESULTS: This work reported a new method of hydrophilic-interaction-based magnetically assisted matrix solid-phase dispersion (MMSPD) extraction coupled with reversed-phase liquid chromatography-mass spectrometry for simultaneous determination of carbadox and olaquindox in animal feeds. 3-Trimethoxysilylpropyl methacrylate (γ-MAPS)-modified attapulgite (ATP) was crosslinked with γ-MAPS-modified iron(II,III) oxide (Fe3 O4 ), 1-vinyl-3-(butyl-4-sulfonate) imidazolium (VBSIm), acrylamide (AM), and N,N'-methylene-bis(acrylamide) (MBA) to synthesize ATP@Fe3 O4 @poly(VBSIm-AM-MBA) particles. The resultant particles were characterized by scanning electron microscopy, energy dispersive spectrometer, transmission electron microscopy, vibrating sample magnetometer, and Fourier transform infrared spectroscopy. Crosslinking of ATP into the magnetic particles has significantly increased the adsorption capacity of the particles. Under optimum conditions, the limits of detection (S/N = 3) were 0.3 µg kg-1 and 0.9 µg kg-1 for carbadox and olaquindox respectively. The intra-day and inter-day recoveries of the spiked targets in feed samples were in the range 83.5-98.3% with relative standard deviations of 1.0-8.3%. CONCLUSION: With a simplified procedure and a low amount of sample, the proposed hydrophilic-interaction-based MMSPD method is not only useful for the determination of carbadox and olaquindox in feeds but also holds great promise for the analysis of other polar targets in solid or semisolid matrices. © 2021 Society of Chemical Industry.

A Confidential QR Code Approach with Higher Information Privacy.

In present times, barcode decoders on mobile phones can extract the data content of QR codes. However, this convenience raises concerns about security issues when using QR codes to transmit confidential information, such as e-tickets, coupons, and other private data. Moreover, current secret hiding techniques are unsuitable for QR code applications since QR codes are module-oriented, which is different from the pixel-oriented hiding manner. In this article, we propose an algorithm to conceal confidential information by changing the modules of the QR Code. This new scheme designs the triple module groups based on the concept of the error correction capability. Additionally, this manner can conceal two secret bits by changing only one module, and the amount of hidden confidential information can be twice the original amount. As a result, the ordinary data content (such as URL) can be extracted correctly from the generated QR code by any barcode decoders, which does not affect the readability of scanning. Furthermore, only authorized users with the secret key can further extract the concealed confidential information. This designed scheme can provide secure and reliable applications for the QR system.

SPARC knockdown attenuated TGF-ß1-induced fibrotic effects through Smad2/3 pathways in human pterygium fibroblasts.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), a matricellular glycoprotein, has been found to regulate processes involved in fibrotic diseases. The aim of this study was to investigate the anti-fibrotic effects of SPARC in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHODS: The expression of SPARC in HPFs was knocked down by RNA interference-based approach. Subsequently, we examined the expression of profibrotic markers induced by transforming growth factor-ß1 (TGF-ß1), including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin (FN). The changes in signaling pathways and matrix metalloproteinases (MMPs) were also detected by western blotting. The cellular migration ability, proliferation ability, apoptosis, and contractile phenotype were detected using the wound healing assay, Cell Counting Kit-8 assay, flow cytometry, and collagen gel contraction assay, respectively. The interaction between SPARC and TGF-ß RII was detected by Co-IP RESULTS: Silencing of SPARC inhibited the basal and TGF-ß1-induced expression of COL1, α-SMA, and FN in HPFs, and suppressed the expression of p-Smad2, p-Smad3, Smad4 and MMP2, MMP9. The downregulation of SPARC also attenuated the cell migration and contractile phenotype of HPFs. SPARC could bind to TGF-ßRII under TGF-ß1 treatment. However, knockdown of SPARC did not affect the proliferation and apoptosis of HPFs. CONCLUSION: SPARC knockdown attenuated the fibrotic effect induced by TGF-ß1 at least in part by inactivating the Smad2/3 pathways in HPFs. Therefore, SPARC may be a promising therapeutic target for the treatment of pterygium.

Gasdermin D Drives the Nonexosomal Secretion of Galectin-3, an Insulin Signal Antagonist.

The inflammasomes play critical roles in numerous pathological conditions largely through IL-1ß and/or IL-18. However, additional effectors have been implied from multiple studies. In this study, through two independent mass spectrometry-based secretome screening approaches, we identified galectin-3 as an effector protein of the NLRP3 inflammasome. Although the activation of AIM2 or NLRC4 inflammasome also led to galectin-3 secretion, only the NLRP3 inflammasome controlled the serum galectin-3 level under physiological condition. Mechanistically, active gasdermin D drove the nonexosomal secretion of galectin-3 through the plasma membrane pores. In vivo, high-fat diet-fed Nlrp3-/- mice exhibited decreased circulating galectin-3 compared with wild-type animals. Of note, the improved insulin sensitivity in such Nlrp3-/- mice was aggravated by infusion of recombinant galectin-3. Moreover, galectin-3 was essential for insulin resistance induction in mice harboring the hyperactive Nlrp3A350V allele. Thus, the inflammasome-galectin-3 axis has been demonstrated as a promising target to intervene inflammasome and/or galectin-3 related diseases.

Novel synthesized attapulgite nanoparticles-based hydrophobic monolithic column for in-tube solid-phase microextraction of thiosildenafil, pseudovardenafil, and norneosildenafil in functional foods.

In this study, a novel method which involved in-tube solid-phase microextraction (SPME) using an attapulgite (ATP) nanoparticles-based hydrophobic monolithic column was successfully developed. It was coupled with high-performance liquid chromatography-ultraviolet detection for the determination of three phosphodiesterase-5 (PDE-5) inhibitors, including thiosildenafil, pseudovardenafil, and norneosildenafil, in functional foods. The monolithic column was prepared by one-step polymerization, using 3-trimethoxysilylpropyl methacrylate-modified ATP nanoparticles and 1-butyl-3-vinylimidazolium bromide (VBIMBr) as the functional monomers, and ethylene glycol dimethacrylate (EDMA) as the cross-linker. The obtained poly(ATP-VBIMBr-EDMA) monolith was characterized by scanning electron microscopy equipped with energy-dispersive analysis of X-ray, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. The adsorption capacity, up to 2.00 µg/cm calculated by the Langmuir isotherm model, was about six times that of the poly(VBIMBr-EDMA) monolith. Crucial factors affecting the extraction efficiency, including sample solvent, elution solvent, flow rates of sampling loading and elution, sample loading volume, and elution volume, were investigated in details. Under the optimal in-tube SPME conditions, the proposed method showed good reproducibility with run-to-run, column-to-column, and batch-to-batch relative standard deviations less than 7.2%, and low limits of detection of 0.5-0.9 ng/mL in real samples. Thiosildenafil was detected in four types of functional foods with the contents of 1.30-4.78 µg/g. This newly proposed in-tube SPME method based on poly(ATP-VBIMBr-EDMA) monolith may provide a simple, efficient, and promising alternative to daily monitoring of PDE-5 inhibitors in functional foods.