Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen.

BACKGROUND: Gene-environment interactions contribute to metabolic disorders such as diabetes and dyslipidemia. In addition to affecting metabolic homeostasis directly, drugs and environmental chemicals can cause persistent alterations in metabolic portfolios across generations in a sex-specific manner. Here, we use inorganic arsenic (iAs) as a prototype drug and chemical to dissect such sex differences. METHODS: After weaning, C57BL/6 WT male mice were treated with 250 ppb iAs in drinking water (iAsF0) or normal water (conF0) for 6 weeks and then bred with 15-week-old, non-exposed females for 3 days in cages with only normal water (without iAs), to generate iAsF1 or conF1 mice, respectively. F0 females and all F1 mice drank normal water without iAs all the time. RESULTS: We find that exposure of male mice to 250 ppb iAs leads to glucose intolerance and insulin resistance in F1 female offspring (iAsF1-F), with almost no change in blood lipid profiles. In contrast, F1 males (iAsF1-M) show lower liver and blood triglyceride levels than non-exposed control, with improved glucose tolerance and insulin sensitivity. The liver of F1 offspring shows sex-specific transcriptomic changes, with hepatocyte-autonomous alternations of metabolic fluxes in line with the sex-specific phenotypes. The iAsF1-F mice show altered levels of circulating estrogen and follicle-stimulating hormone. Ovariectomy or liver-specific knockout of estrogen receptor α/ß made F1 females resemble F1 males in their metabolic responses to paternal iAs exposure. CONCLUSIONS: These results demonstrate that disrupted reproductive hormone secretion in alliance with hepatic estrogen signaling accounts for the sex-specific intergenerational effects of paternal iAs exposure, which shed light on the sex disparities in long-term gene-environment interactions.

M13 Bacteriophage-Assisted Recognition and Signal Spatiotemporal Separation Enabling Ultrasensitive Light Scattering Immunoassay.

The demand for the ultrasensitive and rapid quantitative analysis of trace target analytes has become increasingly urgent. However, the sensitivity of traditional immunoassay-based detection methods is limited due to the contradiction between molecular recognition and signal amplification caused by the size effect of nanoprobes. To address this dilemma, we describe versatile M13 phage-assisted immunorecognition and signal transduction spatiotemporal separation that enable ultrasensitive light-scattering immunoassay systems for the quantitative detection of low-abundance target analytes. The newly developed immunoassay strategy combines the M13 phage-assisted light scattering signal fluctuations of gold nanoparticles (AuNPs) with gold in situ growth (GISG) technology. Given the synergy of M13 phage-mediated leverage effect and GISG-amplified light scattering signal modulation, the practical detection capability of this strategy can achieve the ultrasensitive and rapid quantification of ochratoxin A and alpha-fetoprotein in real samples at the subfemtomolar level within 50 min, displaying about 4 orders of magnitude enhancement in sensitivity compared with traditional phage-based ELISA. To further improve the sensitivity of our immunoassay, the biotin-streptavidin amplification scheme is implemented to detect severe acute respiratory syndrome coronavirus 2 spike protein down to the attomolar range. Overall, this study offers a direction for ultrasensitive quantitative detection of target analytes by the synergistic combination of M13 phage-mediated leverage effect and GISG-amplified light scattering signal modulation.

The role of distractors in rapid serial visual presentation reveals the mechanism of attentional blink by EEG-based univariate and multivariate analyses.

Attentional blink pertains to the performance of participants with a severe decline in identifying the second target presented after the first target reported correctly within 200-500 ms in a rapid serial visual presentation. The current study was conducted to investigate the neural mechanism of the effect of the distractor (D1) that immediately follows first target to attentional blink by altering whether D1 was substituted with a blank with electroencephalography recording. The results showed that D1 interfered with the attentional enhancement and working memory encoding in both single-target rapid serial visual presentation task and dual-target rapid serial visual presentation task, which were mainly manifested in delayed and attenuated P3a and diminished P3b of first target. Single-trial analysis indicated that first target and second target will compete with each other for working memory encoding resources in short lag, but not in the long lag. In addition, D1 interfered with the working memory encoding of second target under short lag rather than long lag in the dual-target rapid serial visual presentation task. These results suggested that attentional blink can be attributed to the limited working memory encoding resource, whereas the amount of available resources is subject to modulation by attention. The D1 hinders the attention enhancement of first target, thereby exacerbating attentional blink.

Piezoelectric enhanced sulfur doped graphdiyne nanozymes for synergistic ferroptosis-apoptosis anticancer therapy.

Graphdiyne has excellent potential due to its enzymatic properties. Metal-free sulfur-doped Graphdiyne (S-GDY) has piezoelectric characteristics, and ultrasonic excitation of S-GDY enhances peroxidase activity. It can turn hydrogen peroxide into toxic hydroxyl radicals and induce apoptosis in 4T1 cells. More importantly, the ultrasound (US) enhanced nanozyme induced 4T1 cell ferroptosis by promoting an imbalanced redox reaction due to glutathione depletion and glutathione peroxidase 4 inactivation. S-GDY exhibited enhanced nanozyme activity in vitro and in vivo that may directly trigger apoptosis-ferroptosis for effective tumor therapy. Altogether, this study was expected to provide new insights into the design of piezoelectric catalytic nanozyme and expand their application in the catalytic therapy of tumors.

The efficacy and safety of one-stage endoscopy combined with intrarenal surgery (mini-nephrostomy tract) in the prone split-leg position for complex renal calculi.

Background: The goal of this study was to determine the safety and efficacy of endoscopic combined intrarenal surgery (ECIRS) performed in the prone split-leg position for the treatment of complex renal stones. Materials and methods: A mature ECIRS protocol was designed. Retrospective analysis was conducted of medical records between January 2020 and December 2021 of patients with complex renal stones at one center who underwent ECIRS by 2 skilled surgeons using retrograde flexible ureteroscopy and mini-percutaneous nephrolithotomy in the prone split-leg position. Results: A total of 44 patients were included in this study. Mean stone size was 26.1 ± 12.7 mm, and the number of calyces involved was 4.36 ± 2.09. Mean operative time was 71.1 ± 21.8 minutes. Postoperative decline in hemoglobin was 15.8 ± 9.8 g/L. Seventy-five percent of patients achieved stone-free status. The mean number of residual stones was 2.8 ± 2.3, and the mean residual stone size was 10.30 ± 4.76 mm. Six patients (13.6%) developed postoperative complications, including 4 with fever during the first 2 days postoperatively and 2 patients with transient postoperative pain. No patients developed severe complications. Conclusions: Endoscopic combined intrarenal surgery in the prone split-leg position can be performed safely by experienced surgeons using retrograde flexible ureteroscopy in conjunction with mini-percutaneous nephrolithotomy as a successful technique for the treatment of complex renal stones.

Efficacy and safety of Runzao Zhiyang capsule for chronic urticaria: a systematic review and meta-analysis of randomized controlled trials.

Background: Chronic urticaria (CU) is a commonly seen skin disorder featured by recurring wheals, with or without angioedema, lasting for at least 6 weeks. Runzao Zhiyang capsule (RZC) has been widely applied to treat patients with CU. This study is aimed at systematically evaluating the efficacy and safety of RZC in treating CU. Materials and Methods: Randomized controlled trials (RCTs) of RZC on treating CU from Chinese and English databases were searched. Data were collected by two independent researchers. The Cochrane Collaboration tool was adopted for evaluating the risk of bias. The meta-analysis was performed with Review Manager 5.3 software. Sensitivity analysis and publication bias assessment were conducted by Stata 14.0 software. Results: Totally 27 studies were included in the analysis, involving 2,703 patients. The pooled results showed that compared with second-generation H1-antihistamines (sgAHs) therapy alone, RZC combined with sgAHs is more effective in improving the total effective rate (RR = 1.32, 95% CI: 1.25 to 1.39, p < 0.00001), the quality of life measured by Dermatology Life Quality Index (DLQI) (MD = -2.63, 95% CI: -3.68 to -1.58, p < 0.00001) and the serum IFN-γ level (SMD = 3.10, 95% CI: 1.58 to 4.62, p < 0.0001), and reducing the recurrence rate (RR = 0.39, 95% CI: 0.27 to 0.55, p < 0.00001), the serum total IgE level (SMD = -2.44, 95% CI: -3.51 to -1.38, p < 0.00001), the serum IL-4 level (SMD = -2.96, 95% CI: -4.10 to -1.83, p < 0.00001), and the incidence of adverse events including dizziness, fatigue, dry mouth, and constipation (RR = 0.53, 95% CI: 0.33 to 0.85, p = 0.009; RR = 0.46, 95% CI: 0.26 to 0.84, p = 0.01; RR = 0.57, 95% CI: 0.34 to 0.95, p = 0.03; RR = 0.24, 95% CI: 0.07 to 0.85, p = 0.03). Conclusion: The current evidence indicates that RZC may be an efficient therapeutic regimen in patients with CU. Nevertheless, owing to the suboptimal quality of the included studies, more large-scale, well-designed RCTs are required to verify the obtained findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier: CRD42022313177.

Nanobody based immunoassay for alpha fetal protein detection using streptavidin-conjugated polymerized horseradish peroxidase for signal amplification.

The enzyme-linked immunosorbent assay (ELISA) offers several advantages, including simple operation, high throughput, and low cost, making it an ideal immunoassay method for efficient screening of disease-related biomarkers in clinical samples. However, the traditional colorimetric ELISA has relatively low sensitivity, which promotes the continuous emergence of various novel signal amplification technologies. In this work, we fused the AFP-specific nanobody (A1) with the streptavidin-binding peptide (SBP) to develop a fusion protein (A1-SBP) as biorecognition element in a colorimetric ELISA for detecting AFP. Besides, to further improve the sensitivity of the traditional colorimetric ELISA, the streptavidin-conjugated polymerized horseradish peroxidase (SA-PolyHRP) were selected as a detection probe for signal amplification. The proposed signal enhancement strategy demonstrated a limit of detection (LOD) of 0.597 ng/mL for the SA-polyHRP-based ELISA, which is 7.67-fold lower than that of the traditional SA-HRP-based ELISA without additional steps. Furthermore, the proposed SA-polyHRP-based ELISA showed a good correlation with the detection of clinical samples using the Roche E601 chemiluminescence immunoassay analyzer. Therefore, the proposed signal enhancement strategy is an attractive approach for improving the sensitivity of immunoassay without requiring additional steps.

All-fiberized linearly polarized superfluorescent fiber source with 5 kW power output.

A superfluorescent fiber source (SFS) is a special fiber source that commonly possesses high temporal stability and a wide spectral linewidth. In this work, an all-fiberized linearly polarized SFS with, to our knowledge, record output power and near-diffraction-limited beam quality is presented. Up to 5.03 kW SFS is achieved at a pump power of 6.18 kW with a corresponding conversion efficiency of ∼81.1%. At maximum output power, the signal-to-noise ratio to background spectral noise is over 50 dB, the polarization extinction ratio is ∼17d B, and the beam quality factor is M x 2=1.49, M y 2=1.44. Further comparisons confirm the power scalability of fiber amplifiers employing SFSs as seed lasers. Overall, this work could provide a good reference for potential exploration of high-power fiber laser systems.

Comparison of the carotid corrected flow time and tidal volume challenge for assessing fluid responsiveness in robot-assisted laparoscopic surgery.

We aimed to compare the ability of carotid corrected flow time assessed by ultrasound and the changes in dynamic preload indices induced by tidal volume challenge predicting fluid responsiveness in patients undergoing robot-assisted laparoscopic gynecological surgery in the modified head-down lithotomy position. This prospective single-center study included patients undergoing robot-assisted laparoscopic surgery in the modified head-down lithotomy position. Carotid Doppler parameters and hemodynamic data, including corrected flow time, pulse pressure variation, stroke volume variation, and stroke volume index at a tidal volume of 6 mL/kg predicted body weight and after increasing the tidal volume to 8 mL/kg predicted body weight (tidal volume challenge), respectively, were measured. Fluid responsiveness was defined as a stroke volume index ≥ 10% increase after volume expansion. Among the 52 patients included, 26 were classified as fluid responders and 26 as non-responders based on the stroke volume index. The area under the receiver operating characteristic curve measured to predict the fluid responsiveness to corrected flow time and changes in pulse pressure variation (ΔPPV6-8) after tidal volume challenge were 0.82 [95% confidence interval (CI) 0.71-0.94; P < 0.0001] and 0.85 (95% CI 0.74-0.96; P < 0.0001), respectively. The value for pulse pressure variation at a tidal volume of 8 mL/kg was 0.79 (95% CI 0.67-0.91; P = 0.0003). The optimal cut-off values for corrected flow time and ΔPPV6-8 were 357 ms and > 1%, respectively. Both the corrected flow time and Changes in pulse pressure variation after tidal volume challenge reliably predicted fluid responsiveness in patients undergoing robot-assisted laparoscopic gynecological surgery in the modified head-down lithotomy position. And pulse pressure variation at a tidal volume of 8 mL/kg maybe also a useful predictor.Trial registration: Chinese Clinical Trial Register (CHiCTR2200060573, Principal investigator: Hongliang Liu, Date of registration: 05/06/2022).

Identification of geothermal potential based on land surface temperature derived from remotely sensed data.

With the continuous development of thermal infrared remote sensing technology and the maturation of remote sensing inversion algorithms based on surface temperatures, identifying high-temperature anomalous areas by inverting surface temperatures has become an crucial approach to finding geothermal potential areas. The eastern region of Longyang in western Yunnan Province is renowned for geothermal resources, though the distribution area of geothermal potential remains unknown. Therefore, this study used Landsat-8 TIRS data and four surface temperature inversion algorithms, namely, mono-window algorithm, single-channel algorithm, Du split window algorithm (SWD), and Jiménez-Muñoz split window algorithm (SWJ), to explore the astern region of Longyang. The inversion results were compared with Moderate Resolution Imaging Spectroradiometer Land Surface Temperature (MODIS LST) results for analysis and cross-validation to select the optimal algorithm. A multi-view remote sensing temperature anomaly information extraction method was adopted. Moreover, the overall threshold method, the fracture structure buffer method, and the joint analysis of diurnal temporal data were combined for the reduction of the thermal anomaly area as well as for comprehensively defining the geothermal prospective area in the study area. The results demonstrated that the mono-window algorithm had the highest accuracy with a Pearson coefficient of 0.77, which is more suitable for the surface temperature inversion in Longyang area. Furthermore, three geothermal anomalies (A, B, and C) were identified in the study area, with larger thermal anomaly in A and C, but a smaller one in B. All three areas had hot spring points verified, with A and C exhibiting more significant development potential. The research results provide a reliable methodological basis for the development of geothermal resources in the region.

Correlation between High Incidence of Colorectal Neoplastic Polyps and High-risk Adenomas in Patients with Diabetes Mellitus: A Retrospective Study.

BACKGROUND: Early detection and resection of colorectal polyps by routine colonoscopy screening can be effective in reducing the risk of colorectal cancer (CRC). OBJECTIVE: This study aimed to determine the association between diabetes mellitus (DM) and different types of colorectal polyps in the Chinese population. METHODS: A retrospective analysis was performed on inpatients admitted to the Gastroenterology Department of our hospital from January to December 2019. Clinical data, and colonoscopy and pathology findings of the subjects were collected. Bivariate analysis was used to assess factors associated with colorectal polyps. Significant variables from the bivariate evaluation were included in a stepwise multivariate logistic regression analysis to recognize independent predictors of neoplastic polyps and high-risk adenomas. RESULTS: The proportion of patients with DM was significantly higher in patients with neoplastic polyps and high-risk adenomas than in patients without polyps. Age ≥ 50 years, male gender, and a first-degree relative with a history of CRC were independent risk factors for neoplastic polyps and high-risk adenomas, even in non-smokers. An independent risk factor analysis that did not include a family history of CRC showed that age, gender, and alcohol consumption were independent risk factors for neoplastic polyps and high-risk adenomas. DM was an independent risk factor for high-risk adenomas (OR=2.902, 95% CI=1.221-6.899; p=0.016) after adjusting for age, gender, alcohol consumption, and body mass index. Thus, a history of DM significantly increases the risk of high-risk adenomas. CONCLUSION: This study demonstrated that patients with DM, age ≥ 50 years, male gender, alcohol consumption, and a first-degree relative with a history of CRC should undergo regular endoscopic screening and colonic polypectomy.

Sanhuang decoction inhibits autophagy of periodontal ligament fibroblasts during orthodontic tooth movement by activating PI3K-Akt-mTOR pathway.

BACKGROUND: Orthodontic tooth movement (OTM) is a typical treatment that corrects malaligned teeth by applying mechanical forces. However, mechanical overload often leads to damage of PDL fibroblasts. Sanhuang decoction (SHD) is commonly used to inhibit inflammation and oxidative stress. However, the mechanism of SHD for OTM treatment is still unclear. Therefore, this study attempts to explore the underlying mechanism through relevant experiments. METHODS: In the present paper, we established a OTM rat model and further explored the effects of SHD on the PDL of OTM rats. The OTM model and effects of SHD were determined by micro-CT, and the PDL pathological changes, PDL width and capillaries in PDL were observed by H&E staining. Subsequently, the ROS levels in PDL was determined using flow cytometry analysis with DCFH-DA staining, MDA contents and antioxidative enzymes activities were also measured using commercial kits. Furthermore, the autophagy of PDL fibroblasts and proteins in the PI3K/Akt/mTOR pathway were detected using immunoluminescence, qPCR and western blotting assays. RESULTS: The results showed SHD treatment can alleviate the decrease of PDL cells and capillaries induced by OTM, and improve the MDA and ROS levels in PDL, as well as enhance the activities of SOD and GSH-Px. Further experiments indicated SHD decreased the autophagy levels of PDL fibroblasts via promoting the phosphorylation levels of mTOR, PI3K and Akt proteins. CONCLUSION: SHD inhibited autophagy of periodontal ligament fibroblasts during orthodontic tooth movement by inhibiting oxidative stress via activating PI3K-Akt-mTOR pathway. Our present findings suggested SHD treatment would be useful for management of the possible disorders occurs in orthodontic tooth movement therapy.

Stepwise Au decoration-assisted double signal amplified lateral flow strip for ultrasensitive detection of morphine in fingerprint sweat.

Point-of-care testing (POCT) of morphine (MOP) without invasion of privacy is of critical importance for law-enforcement departments to realize on-site rapid screening. In this study, ultrasensitive and non-invasive screening of MOP residues in the fingerprint sweat was easily realized by stepwise Au decoration-assisted double signal amplification and antibody-saving strategies on lateral flow strip (LFS). The construction of LFS was not intrinsically changed compared with traditional LFS except the labeling material on conjugation pad for enhanced signal reporting. The gold nanoparticle-seeded SiO2 was adopted as the labeling materials in place of traditional gold nanoparticles, which acted as the first-round signal amplification and ready for second-round gold deposition-assisted amplification. And the second-round amplification could be completed in just 10 s, which did not alter the intrinsic simplicity of LFS for rapid and on-site screening. With the designed signal amplification principle of LFS, target MOP in the fingerprint sweat can be effectively transferred to the LFS for analysis without invasion of privacy. As low as 0.5 pg MOP in fingerprint sweat can be visually judged with this double signal amplified LFS, the sensitivity of which has been improved at least 10-fold compared with traditional Au-labeled LFS, guaranteeing accurate screening of trace MOP in the fingerprint sweat. Of great importance, the consumption of valuable antibody can be reduced to just 1/20, which greatly reduces the cost of high-throughput screening. This stepwise Au decoration-assisted double signal amplified LFS holds great potential in the ultrasensitive screening of trace analytes in various fields and further widens the application scope of lateral flow strips.

Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?

Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.

Different Fenton treatments on diverse landfill organics: Discover the underestimated effect of derived-DOM.

Fenton is one of the most promising processes for the removal of dissolved organic matter (DOM). It has always been highly suspected that derived-DOM would be generated during Fenton reaction, but there is lack of direct evidence at the molecular level. The present study explored the molecular properties of the derived-DOM of five common Fenton technologies for degradation of nine landfill organics including leachates and concentrates based on UPLC Orbitrap MS/MS analysis. The comparative results confirmed that DOM derivation was essential for Fenton technologies, with the DOM derivation rate as high as 17.3%-70.3%. The derived-DOM are dominated by trace organic contaminants (CHON-DOM), and typical new contaminants (PPCPs, flavors, etc.). Heterogeneous Fenton had significantly lesser derived-DOM (35.1% ± 16.9%) than other Fenton technologies. Among all landfill organics, medium leachate was most likely to derive DOM (51.4% ± 13.9%), while unexpectedly old leachate had the lowest derivation rate (32.0% ± 5.3%). In the overall membrane treatment process, the secondary membrane concentrate is more susceptible to DOM derivation (43.4% ± 5.5%-49.6% ± 3.8%) than the primary membrane concentrate (40.7% ± 14.1%), and the elements and subcategories composition and molecular property indexes of the derived-DOM become more complex. On the contrary, the DOM derivatization rate of the biological treatment effluent after Fenton treatment was much lower than that of the various concentrates after Fenton treatment and the molecular property are simpler. Therefore, Fenton may replace the membrane process directly as a deep treatment process after biological treatment of landfill leachate. These information would help the selection and application of Fenton technologies.

Real-Time Nondestructive Viscosity Measurement of Soft Tissue Based on Viscoelastic Response Optical Coherence Elastography.

Viscoelasticity of the soft tissue is an important mechanical factor for disease diagnosis, biomaterials testing and fabrication. Here, we present a real-time and high-resolution viscoelastic response-optical coherence elastography (VisR-OCE) method based on acoustic radiation force (ARF) excitation and optical coherence tomography (OCT) imaging. The relationship between displacements induced by two sequential ARF loading-unloading and the relaxation time constant of the soft tissue-is established for the Kelvin-Voigt material. Through numerical simulation, the optimal experimental parameters are determined, and the influences of material parameters are evaluated. Virtual experimental results show that there is less than 4% fluctuation in the relaxation time constant values obtained when various Young's modulus and Poisson's ratios were given for simulation. The accuracy of the VisR-OCE method was validated by comparing with the tensile test. The relaxation time constant of phantoms measured by VisR-OCE differs from the tensile test result by about 3%. The proposed VisR-OCE method may provide an effective tool for quick and nondestructive viscosity testing of biological tissues.

Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.

Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.

Catalytic efficiency and thermal stability promotion of the cassava linamarase with multiple mutations for better cyanogenic glycoside degradation.

In our previous study, we found that cassava cyanogenic glycosides had an acute health risk. Therefore, to solve this problem, the improvement of specific degradation of cyanogenic glycosides of cassava linamarase during processing is the key. In this study, the catalytic activity and thermal stability of enzymes were screened before investigating the degradation efficiency of cyanogenic glycosides with a cassava linamarase mutant K263P-T53F-S366R-V335C-F339C (CASmut) -controlled technique. The CASmut was obtained with the optimum temperature of 45 °C, which was improved by 10 °C. The specific activity of CASmut was 85.1 ±â€¯4.6 U/mg, which was 2.02 times higher than that of the wild type. Molecular dynamics simulation analysis and flexible docking showed there were more hydrogen bonding interactions at the pocket, and the aliphatic glycoside of the linamarin was partially surrounded by hydrophobic residues. The optimum conditions of degradation reactions was screened with CASmut addition of 47 mg/L at 45 °C, pH 6.0. The CASmut combined with ultrasonication improved the degradation from 478.2 ±â€¯10.4 mg/kg to 86.7 ±â€¯7.4 mg/kg. Those results indicating the great potential of CASmut in applying in the cassava food or cyanogenic food. However, challenges in terms of the catalytic mechanism research is worthy of being noticed in further studies.

Association between the triglyceride-glucose index and calcified aortic stenosis in elderly patients: a cross-sectional study.

Insulin resistance (IR) is associated with a variety of cardiovascular diseases, but there are few studies on the correlation between IR and calcified aortic stenosis (CAS). In this study, the triglyceride-glucose (TyG) index, which reflects IR, was used to investigate the correlation between IR and CAS. The study included 183 elderly patients who were diagnosed with CAS by transthoracic echocardiography. The patients were matched 1:1 according to age and sex, and elderly patients who were hospitalized during the same period and underwent transthoracic echocardiography without aortic stenosis were included as the control group. The relationship between the TyG index and CAS was analyzed by a multivariable logistic regression model, curve fitting and trend test. Multivariate logistic regression analysis showed that the TyG index as a continuous variable was negatively associated with CAS (P < 0.001); trend tests and curve fitting further supported this association. Our study showed that the TyG index was negatively associated with CAS in elderly patients, which may be related to the impairment of insulin receptors and signaling pathways in IR.