Fabrication of Carboxylate-Functionalized 2D MOF Nanosheet with Caged Cavity for Efficient and Selective Extraction of Uranium from Aqueous Solution.

The efficient removal of radioactive uranium from aqueous solution is of great significance for the safe and sustainable development of nuclear power. An ultrathin 2D metal-organic framework (MOF) nanosheet with cavity structures was elaborately fabricated based on a calix[4]arene ligand. Incorporating the permanent cavity structures on MOF nanosheet can fully utilize its structural characteristics of largely exposed surface area and accessible adsorption sites in pollutant removal, achieving ultrafast adsorption kinetics, and the functionalized cavity structure would endow the MOF nanosheets with the ability to achieve preconcentration and extraction of uranium from aqueous solution, affording ultrahigh removal efficiency even in ultra-low concentrations. Thus, more than 97% uranium can be removed from the concentration range of 50-500 µg L-1 within 5 min. Moreover, the 2D nano-material exhibits ultra-high anti-interference ability, which can efficiently remove uranium from groundwater and seawater. The adsorption mechanism was investigated by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) analysis, and density functional theory (DFT) calculations, which revealed that the cavity structure plays an important role in uranium capture. This study not only realizes highly efficient uranium removal from aqueous solution but also opens the door to achieving ultrathin MOF nanosheets with cavity structures, which will greatly expand the applications of MOF nanosheets.

Functions of actin-binding proteins in cilia structure remodeling and signaling.

Cilia are microtubule-based organelles found on the surfaces of many types of cells, including cardiac fibroblasts, vascular endothelial cells, human retinal pigmented epithelial-1 (RPE-1) cells, and alveolar epithelial cells. These organelles can be classified as immotile cilia, referred to as primary cilia in mammalian cells, and motile cilia. Primary cilia are cellular sensors that detect extracellular signals; this is a critical function associated with ciliopathies, which are characterized by the typical clinical features of developmental disorders. Cilia are extensively studied organelles of the microtubule cytoskeleton. However, the ciliary actin cytoskeleton has rarely been studied. Clear evidence has shown that highly regulated actin cytoskeleton dynamics contribute to normal ciliary function. Actin-binding proteins (ABPs) play vital roles in filamentous actin (F-actin) morphology. Here, we discuss recent progress in understanding the roles of ABPs in ciliary structural remodeling and further downstream ciliary signaling with a focus on the molecular mechanisms underlying actin cytoskeleton-related ciliopathies.

Does a nurse-led interventional program improve clinical outcomes in patients with atrial fibrillation? A meta-analysis.

BACKGROUND: Being the most common type of arrhythmia, atrial fibrillation (AF) is progressively increasing with an annual rate of 5 million new cases. Recent guidelines highlight the importance of using collaborative multidisciplinary teams in order to improve outcomes during management of patients with AF. A nurse-led program including a nurse-directed education, counselling and intervention has shown to improve patients' outcomes in candidates with AF. In this analysis, we aimed to systematically compare the clinical outcomes observed in patients with AF who were assigned to a nurse-led interventional program versus a usual care group. METHODS: EMBASE, MEDLINE, Http://www. CLINICALTRIALS: gov , Web of Science; Google Scholar and Cochrane databases were the data sources. The clinical outcomes were considered as the endpoints in this study. This is a meta-analysis, and the statistical analysis was conducted by the RevMan software (version 5.4). Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data after statistical analysis. RESULTS: Six studies with a total number 2916 participants were included whereby 1434 participants were assigned to a nurse-led intervention and 1482 participants were assigned to the usual care group. Our results showed that participants with AF who were assigned to the nurse-led interventional group had a significantly lower risk of composite endpoints (RR: 0.82, 95% CI: 0.70-0.96; P = 0.01), heart failure (RR: 0.66, 95% CI: 0.47-0.92; P = 0.02), atrial fibrillation (RR: 0.77, 95% CI: 0.63-0.94; P = 0.01) and re-admission (RR: 0.78, 95% CI: 0.62-0.99; P = 0.04). However, the risks of all-cause mortality (RR: 0.86, 95% CI: 0.68-1.09; P = 0.21), cardiac death (RR: 0.67, 95% CI: 0.33-1.39; P = 0.28), myocardial infarction (RR: 0.70, 95% CI: 0.35-1.42; P = 0.33), stroke (RR: 0.75, 95% CI: 0.44-1.26; P = 0.28), all bleeding events (RR: 1.11, 95% CI: 0.81-1.53; P = 0.51) and major bleeding events (RR: 0.91, 95% CI: 0.56-1.49; P = 0.71) were not significantly different. CONCLUSIONS: The nurse-led interventional program significantly improved composite endpoints including heart failure and the recurrence of AF, resulting in a significantly lower admission rate compared to the usual care group. However, nurse-led interventional program did not affect mortality, stroke, myocardial infarction and bleeding events. Based on our current results, a nurse-led interventional programs apparently could be beneficial in patients with AF. Future larger trials would be able to confirm this hypothesis.

Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis.

INTRODUCTION: Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated. OBJECTIVES: Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3). METHODS: Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting. RESULTS: Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect. CONCLUSIONS: All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.

An improved strategy for identification and annotation of easily in-sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example.

RATIONALE: Diterpene lactones (DL) in Andrographis paniculata (AP) are known as "natural antibiotics" for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H2 O, producing high in-source fragment peaks and affecting the characterization of these components. METHODS: Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps. Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H2 O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database. RESULTS: Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C3 H4 , Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation. CONCLUSIONS: MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.

Dissecting chemical markers for controlling "Paozhi" method of traditional Chinese medicine with untargeted metabolomics: Vinegar-baked Euphorbia kansui as a case study.

The processing of Traditional Chinese Medicine requires the appropriate parameters, while the specific chemical markers are still absent to obtain the optimized processing. In this study, we used vinegar-baked Euphorbia kansui as a case to dissect the chemical markers for the baking process using untargeted metabolomics. The robust chemical markers were selected based on the three rules, correlation, significant difference, and controllability. All the differential features were categorized based on their mass defects. After the differential analysis, 310 differential compounds were screened out and could be mainly divided into six categories: diacylglycerols and triacylglycerols demonstrated increasing trends with the baking time in the discriminant model, while ingenane-type diterpenes, jatrophane-type diterpenes, fatty acid esters, and fatty acids had decreasing trends. It was unexpected to find that the diterpenes did not correlate with the baking time. Only very few compounds meet the three rules. They were validated with a high-performance liquid chromatography method. Finally, only 13-Hydroxy-9,11-octadecadienoic acid and its isomer 9-Hydroxy-10,12-octadecadienoic acid could be used further to differentiate the commercial vinegar-baked Euphorbia kansui. It would be of interest to evaluate whether these two compounds could be utilized as markers to control more processing methods in future studies.

Autosomal recessive bestrophinopathy combined with neurofibromatosis type 1 in a patient.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that may affect multiple systems of the body. Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by autosomal recessively mutations in bestrophin 1 (BEST1) gene. So far, we have not retrieved any case report of the same patient with both NF1 and BEST1 gene mutations. CASE PRESENTATION: An 8-year-old female patient with café-au-lait spots, freckling on skin presented to our ophthalmology clinic for routine ophthalmological examination. Her best corrected visual acuity (BCVA) was 20/20 in both eyes. Slit-lamp examination of both eyes revealed few yellowish-brown dome-shaped Lisch nodules over the iris surface. Fundus examination was notable for bilateral confluent yellowish subretinal deposits at macula, few yellow flecks at temporal retina, and cup-to-disc ratio of 0.2. Optical coherence tomography (OCT) revealed subretinal fluid (SRF) involving the fovea, elongated photoreceptor outer segments and mild intraretinal fluid (IRF) at bilateral macula. Fundus autofluorescence demonstrated hyperautofluorescence in the area corresponding to the subretinal deposits. Whole-exome sequencing and Sanger sequencing were used to investigate genetic mutation in the patient and her parents. A BEST1 gene heterozygous missense c.604 C > T (p.Arg202Trp) was identified in the patient and her mother. Also, the patient carries an NF1 nonsense mutation c.6637 C > T (p.Gln2213*) with the mosaic generalized phenotype. There were no visual impairments or obvious neurological, musculoskeletal, behavioral or other symptoms in this patient, so she was managed conservatively and advised to follow up regularly for a long time. CONCLUSIONS: ARB and NF1, which are caused by two different pathogenic gene mutations, have rarely coexisted in the same patient. The discovery of pathogenic gene mutations may play a crucial role in more accurate diagnostics and genetic consultations for individuals and their families.

Deciphering the potential ability of RG108 in cisplatin-induced HEI-OC1 ototoxicity: a research based on RNA-seq and molecular biology experiment.

BACKGROUND: Drug-induced hearing loss (DIHL) is very common, and seriously affects people's happiness in life. RG108 is a small molecule inhibitor. RG108 is protective against DIHL. Our purpose is to probe the incidence of RG108 on cisplatin-induced ototoxicity. MATERIALS AND METHODS: In our research, the ototoxicity of RG108 was investigated in HEI-OC1. We observed under the microscope whether RG108 had an effect on cisplatin-induced cochlear hair cells. RNA-seq experiments were further performed to explore possible gene ontology (GO) and pathways. ROS assay was applied to supervisory the effect of RG108 on oxidative harm of auditory cells. In auditory cells, RG108 was tested for its effects on apoptosis-related proteins by Western blotting (WB). RESULTS: GO analysis showed that RG108 associated with apoptosis. KEGG analysis shows RG108 may act on PI3K-AKT signaling pathway (PASP) in hearing loss. BIOCARTA analysis showed that RG108 may affect oxidative stress by activating NRF2 pathway. ROS ascerted that RG108 could rescue oxidative harm in HEI-OC1. RG108 rescued cisplatin-induced significant increase in Bax and significant decrease in BCL2. RG108 attenuates cisplatin-induced cochlear apoptosis through upregulated phosphorylated PI3K and phosphorylated AKT and down-regulated caspase3. MTT experiments showed that both PI3K and AKT inhibitors could significantly rescue the damage caused by cisplatin to HEI-OC1. RG108 significantly increases the level of NRF2/HO-1/NQO1 in cisplatin-induced cells. CONCLUSION: Overall, these results provide evidence that NRF2/PI3K-AKT axis may mediate RG108 in the treatment of DIHL, which provide a broader outlook on drug-induced deafness treatment.

Mechanical Training Enabled Reinforcement of Polyrotaxane-Containing Hydrogel.

Many strategies have been developed for constructing anisotropic hydrogels, however, it remains a challenge to fabricate hydrogels with anisotropic nanocrystalline domains from intrinsically soft networks. Here, we report a naphthotube-based polyrotaxane-containing hydrogel that can be reinforced via mechanical training. During the training process, the hydrogel can adopt reorientation of polymer chains to form anisotropic structures driven by external uniaxial force. Due to the multiple hydrogen bonding sites and movable feature of naphthotube, the sliding of naphthotube on PEG chains simultaneously inducing the zipping of adjacent polymer chains to form densely anisotropic nanocrystalline domains through hydrogen bonded networks. Thus, the trained hydrogel exhibits an enhanced tension stress of ≈110 kPa, which realize a remarkable enhancement of ≈10 times compare to initial state. This study provides a new tactic for improving the mechanical performance of soft materials.

Information Entropy-Based Strategy for the Quantitative Evaluation of Extensive Hyperspectral Images to Better Unveil Spatial Heterogeneity in Mass Spectrometry Imaging.

Hyperspectral images can be generated from mass spectrometry imaging (MSI) data for the intuitive data visualization purpose. However, hundreds of HSIs can be generated by different dimensionality reduction methods, which poses great challenges in selecting the high-quality images with the best intuitive visualization results of the MSI data. Here, we presented a novel approach that objectively evaluates the image quality of the hyperspectral images. The applicability of this method was demonstrated by analyzing the MSI data acquired from human prostate cancer biopsy samples and mouse brain tissue section, which harbored an intrinsic tissue heterogeneity. Our method was based on the information entropy and contrast measured from image information content and image definition, respectively. The heterogeneity of the MSI data from high-dimensional space was reduced to three-dimensional embeddings and thoroughly evaluated to achieve satisfactory visualization results. The application of information entropy and contrast can be used to choose the optimized visualization results rapidly and objectively from an extensive number of hyperspectral images and be adopted to evaluate and optimize different dimensionality reduction algorithms and their hyperparameter combinations. In conclusion, the information entropy-based strategy could be a bridge between chemometrician and biologists.

Introducing Zirconium Organic Gels for Efficient Radioiodine Gas Removal.

Iodine radioisotope, as one of the most important fission products of uranium, may cause severe damage to human health when it is accidentally discharged into the environment. Hence, efficient removal of radioactive iodine is one of the most critical issues for both used nuclear fuel (UNF) reprocessing and environmental remediation. In this work, three metal-organic gels (MOGs) were introduced for iodine removal. The presented zirconium-based MOGs, namely, CWNU, CWNU-NH2, and CWNU-2NH2, were prepared via moderate solvothermal reactions. These MOGs all exhibit excellent chemical stability and reusability, marked iodine sorption capability, and favorable machinability, which can even rival commercial ones. The sorption capacities are determined to be 3.36, 4.10, and 4.20 g/g, respectively. The increased amount of amino group is considered to be responsible for the elevated iodine sorption capacity and kinetics, as confirmed by combined sorption studies and XPS analysis. The presented work sheds light on the utilization of MOGs for radioiodine capture.

Schistosoma japonicum infection associated with membranous nephropathy: a case report.

BACKGROUND: Schistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man. CASE PRESENTATION: A 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy. CONCLUSIONS: Different classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Quantitative imaging of natural products in fine brain regions using desorption electrospray ionization mass spectrometry imaging (DESI-MSI): Uncaria alkaloids as a case study.

Uncaria species (Rubiaceae) are used as traditional Chinese medicines (TCMs) to treat central nervous system (CNS) diseases, and monoterpene indole alkaloids are the main bioactive constituents. Localization and quantification of CNS drugs in fine brain regions are important to provide insights into their pharmacodynamics, for which quantitative mass spectrometry imaging (MSI) has emerged as a powerful technique. A systematic study of the quantitative imaging of seven Uncaria alkaloids in rat brains using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was presented. The distribution of the alkaloids in thirteen brain regions was quantified successfully using the calibration curves generated by a modified on-tissue approach. The distribution trend of different Uncaria alkaloids in the rat brain was listed as monoterpene indole alkaloids > monoterpene oxindole alkaloids, R-configuration epimers > S-configuration epimers. Particularly, Uncaria alkaloids were detected directly in the pineal gland for the first time and their enrichment phenomenon in this region had an instructive significance in future pharmacodynamic studies.

Mass spectrometry imaging: new eyes on natural products for drug research and development.

Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed.

A simple and effective method for identification of Fraxini Cortex from different sources by multi-mode fingerprint combined with chemometrics.

Fraxini Cortex has a long history of being used as a medicinal plant in traditional Chinese medicine. However, it is challenging to differentiate and make quality evaluations for Fraxini Cortex from different origins due to their similarities in morphological features, as well as general chemical composition using traditional chemical analytical methods. In this study, a simple and effective method was developed to identify Fraxini Cortex from different origins by multi-mode fingerprint combined with chemometrics. Digital images of the high-performance thin-layer chromatography profiles were converted to grayscale intensity, and the common patterns of high-performance thin-layer chromatography fingerprints were generated with ChemPattern software. Authentication and quality assessment were analyzed by similarity analysis, hierarchical cluster analysis, principal component analysis, and multivariate analysis of variance. The ultra-high-performance liquid chromatography fingerprints were analyzed by similarity analysis, principal component analysis, and orthogonal partial least square-discriminant analysis. When combined with chemometrics, high-performance thin-layer chromatography and ultra-high-performance liquid chromatography fingerprint provided a simple and effective method to evaluate the comprehensive quality of Fraxini Cortex, and to distinguish its two original medicinal materials (Fraxinus chinensis Roxb. and Fraxinus rhynchophylla Hance.) recorded in the Chinese Pharmacopeia and its three adulterants (Fraxinus mandschurica Rupr., Fraxinus pennsylvanica Marsh., and Juglans mandshurica Maxim.). A similar workflow may be applied to establish a differentiation method for other medicinal and economic plants.

Characterization of chemical constituents in Shuanghuanglian oral dosage forms by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry.

Shuanghuanglian is a common traditional Chinese medicine prescription. It is an herbal formula composed of Lonicerae Japonicae Flos, Scutellariae Radix, and Forsythiae Fructus. A comprehensive understanding of Shuanghuanglian oral dosage forms components was obtained using a method based on ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry for the separation and characterization of Shuanghuanglian oral liquids, granules, soft capsules, and effervescent tablets. A total of 358 components were chemically defined or tentatively identified, including flavonoids, caffeic acid derivatives, lignans, coumarins, iridoids, triterpenes, and anthraquinones. The results will provide a basis for the general study of Shuanghuanglian and be meaningful for the composition identification of traditional Chinese medicine prescriptions.

Changes of retinal ganglion cell complex after vitrectomy in rhegmatogenous retinal detachment patients and its correlation with inflammatory blood biomarkers.

PURPOSE: To compare retinal ganglion cell complex (GCC) parameters between rhegmatogenous retinal detachment (RRD) eyes and normal contralateral eyes after vitrectomy and to evaluate their correlation with inflammatory blood markers. METHODS: We investigated 25 eyes that underwent vitrectomy due to RRD. Venous blood samples were collected from all participants before 08:00 a.m. on the second day of admission after a 12-hour fast for blood counts. The differences of retinal structure between RRD and contralateral eyes were compared 1 week postoperatively. RESULTS: Focal loss volume (FLV) (2.009 ± 1.286)% was significantly increased compared with the contralateral eyes (p <  0.001). Monocyte-to-high-density lipoprotein was significantly positively correlated with GCC thickness parameters, and negatively correlated with FLV and global loss volume (GLV). Postoperative best-corrected visual acuity was negatively correlated with GLV (p = 0.039, R2 = 0.172). CONCLUSION: Retinal ganglion cells (RGCs) loss might present early postoperatively in RRD eyes, and was associated with systemic inflammation. RGCs loss might affect postoperative vision.

Association between dietary fiber intake and atherosclerotic cardiovascular disease risk in adults: a cross-sectional study of 14,947 population based on the National Health and Nutrition Examination Surveys.

BACKGROUND: This study aimed to investigate the association between dietary fiber intake and long-term cardiovascular disease (CVD) risk based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 14,947 participants aged 20-79 from the NHANES database were included in this study between 2009 and 2018. The atherosclerotic cardiovascular disease (ASCVD) score was utilized to predict the 10-year risk of CVD in individuals (low, borderline, intermediate, and high risk). Weighted univariate and multinomial multivariate logistic regression analyses were used to analyze the association between dietary fiber intake and long-term CVD risk. RESULTS: Higher dietary fiber density may be associated with a reduced ASCVD risk in participants with intermediate risk [odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.61-0.94] and high risk (OR = 0.60; 95%CI, 0.45-0.81) compared with those in the group with low risk. Higher total dietary fiber intake may also reduce ASCVD risk in participants with high risk (OR = 0.84; 95%CI, 0.75-0.95). Subgroup analyses showed that higher dietary fiber density may be related to reduced ASCVD risk in intermediate-risk participants aged 20-39 (OR = 0.62; 95%CI, 0.43-0.89) and 40-59 (OR = 0.67; 95%CI, 0.49-0.94). In high-risk participants, higher dietary fiber density may reduce ASCVD risk in 20-39-year-old (OR = 0.38; 95%CI, 0.19-0.77), 40-59-year-old (OR = 0.37; 95%CI, 0.20-0.70), male (OR = 0.47; 95%CI, 0.23-0.97) and female (OR = 0.57; 95%CI, 0.38-0.86) participants. CONCLUSION: Higher dietary fiber density and total dietary fiber intake were associated with a lower long-term CVD risk, especially in the 20-39 and 40-59 age groups, where the reduction was most significant.

Explore the effect of LLY-283 on the ototoxicity of auditory cells caused by cisplatin: A bioinformatic analysis based on RNA-seq.

BACKGROUND: Cisplatin is a commonly used chemotherapeutic drug in clinics, and long-term application will lead to hearing impairment. LLY-283, an inhibitor of PRMT5, has not been reported in deafness. Our study aimed to explore the mechanism of LLY-283 in hearing impairment. MATERIALS AND METHODS: First, we performed RNA-seq (cisplatin in the experimental group and DMSO in the control group) to obtain the biological processes mainly involved in differentially expressed genes (DEGs). CCK-8 and LDH experiments were used to observe the effect of LLY-283 on cisplatin-induced auditory cell injury. ROS experiment was used to monitor the impact of LLY-283 on oxidative damage of auditory cells. Effect of LLY-283 on apoptosis of auditory cells detected by TUNEL experiment. PCR and Western blotting were used to detect the expression of genes and proteins related to auditory cell apoptosis in LLY-283 cells. Meanwhile, we explored the effect of LLY-283 on the expression of PRMT5 in cisplatin-induced hearing impaired cells at RNA and protein levels. RESULTS: Biological process analysis showed that DEGs were mainly enriched in the apoptotic process involved in morphogenesis (-Log10 P = 3.71). CCK-8 and LDH experiments confirmed that LLY-283 could save cisplatin-induced auditory cell injury. ROS experiments confirmed that LLY-283 could rescue cisplatin-induced oxidative damage to auditory cells. TUNEL experiments confirmed that LLY-283 could protect cisplatin-induced apoptosis of auditory cells. Meanwhile, LLY-283 could inhibit the expression of PRMT5 in auditory cells induced by cisplatin. CONCLUSION: LLY-283 can rescue cisplatin-induced auditory cell apoptosis injury. LLY-283 can inhibit the increase in PRMT5 expression induced by cisplatin.

Composition of Urine Collected from Non-Stone-Forming Chinese Persons during Different Short-Term Periods of the Day.

The purpose of this study in a small group of non-stone-forming Chinese persons was to measure the levels of supersaturation with calcium oxalate and calcium phosphate and pH with the aim of confirming if any of the different short-term urine samples were better for risk evaluation than a 24-h sample. Nine normal men and 1 woman collected urine during 4 periods of the day. Period 1 between 08 and 12 h, Period 2 between 12 and 18 h, Period 3 between 18 and 22 h, and Period 4 between 22 and 08 h. Each sample was analysed for calcium, oxalate, citrate, magnesium and phosphate, and estimates of supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP) were expressed in terms of AP(CaOx) and AP(CaP) index. An estimate of the solute load of CaOx was also calculated. Urine composition for 24-h urine (Period 24) was obtained mathematically from the analysed variables. Urine composition corresponding to 14-h urine portions 22-12 h (Period 14N) and 08-22 h (Period 14 D) were calculated. The lowest pH levels were recorded in Period 1 urine. The highest level of AP(CaOx) index was recorded during Period 1, and the product AP(CaOx) index × 107 × hydrogen ion concentration was significantly higher in Period 1 urine than in 24-h urine (p = 0.02). Also, the product SL(CaOx) × 107 × hydrogen ion concentration was significantly higher in Period 1 urine (p = 0.02). Low AP (CaP) index levels were recorded in Period 4, but also in all periods following dietary loads of calcium and phosphate. With the important reservation that the analytical results were obtained from non-stone-forming persons, the conclusion is that analysis of urine samples collected between 08 and 12 h might be an alternative to 24-h urine. The risk evaluation might advantageously be expressed either in terms of the product AP(CaOx) index × 107 × hydrogen ion concentration or the product SL(CaOx) × 107 × hydrogen ion concentration.