A multiscale accuracy assessment of moisture content predictions using time-lapse electrical resistivity tomography in mine tailings.

Accurate and large-scale assessment of volumetric water content (VWC) plays a critical role in mining waste monitoring to mitigate potential geotechnical and environmental risks. In recent years, time-lapse electrical resistivity tomography (TL-ERT) has emerged as a promising monitoring approach that can be used in combination with traditional invasive and point-measurements techniques to estimate VWC in mine tailings. Moreover, the bulk electrical conductivity (EC) imaged using TL-ERT can be converted into VWC in the field using petrophysical relationships calibrated in the laboratory. This study is the first to assess the scale effect on the accuracy of ERT-predicted VWC in tailings. Simultaneous and co-located monitoring of bulk EC and VWC are carried out in tailings at five different scales, in the laboratory and in the field. The hydrogeophysical datasets are used to calibrate a petrophysical model used to predict VWC from TL-ERT data. Overall, the accuracy of ERT-predicted VWC is [Formula: see text], and the petrophysical models determined at sample-scale in the laboratory remain valid at larger scales. Notably, the impact of temperature and pore water EC evolution plays a major role in VWC predictions at the field scale (tenfold reduction of accuracy) and, therefore, must be properly taken into account during the TL-ERT data processing using complementary hydrogeological sensors. Based on these results, we suggest that future studies using TL-ERT to predict VWC in mine tailings could use sample-scale laboratory apparatus similar to the electrical resistivity Tempe cell presented here to calibrate petrophysical models and carefully upscale them to field applications.

Causal Effects of Plasma Haptoglobin Levels on Alzheimer's Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND: A connection between plasma levels of haptoglobin (Hp) and Alzheimer's disease (AD) has been shown in several observational studies. It is debatable, nonetheless, how the two are related causally. OBJECTIVE: To establish the causal relationship between Hp and AD using a two-sample Mendelian randomization (MR) study. METHODS: From the extensive genome-wide association studies and FinnGen dataset, summaries and statistics pertaining to AD were gathered. We investigated the possibility of a causal link between Hp and AD using a two-sample MR study. Inverse variance weighting was used as the primary analytical technique, and it was supported by the joint application of complementary analyses and fixed effects meta-analysis to combine results from various sources. RESULTS: Genetically determined Hp was causally associated with AD [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.02 to 1.09; p = 8.96×10-4]; Inverse variance-weighted estimates coming from different data sources were combined in a meta-analysis with consistent findings (OR, 1.03; 95% CI, 1.01 to 1.05; p = 2.00×10-3). The outcomes of the inverse MR analysis showed that AD had no appreciable causal impact on Hp. CONCLUSION: The present MR analysis shows that higher plasma Hp leads to an increased risk of AD. Strategies for plasma Hp testing may open up new doors for the early diagnosis and prevention of AD.

mTOR-dependent TFEB activation and TFEB overexpression enhance autophagy-lysosome pathway and ameliorate Alzheimer's disease-like pathology in diabetic encephalopathy.

BACKGROUND: Diabetic encephalopathy (DE) is a complication of type 2 diabetes mellitus (T2DM) that features Alzheimer's disease (AD)-like pathology, which can be degraded by the autophagy-lysosome pathway (ALP). Since transcription factor EB (TFEB) is a master regulator of ALP, TFEB-mediated ALP activation might have a therapeutic effect on DE, but this has yet to be investigated. METHODS: We established T2DM mouse models and cultured HT22 cells under high-glucose (HG) conditions to confirm the role of ALP in DE. To further investigate this, both mice and HT22 cells were treated with 3-methyladenine (3-MA). We also analyzed the content of TFEB in the nucleus and cytoplasm to evaluate its role in ALP. To confirm the effect of TFEB activation at the post-translational level in DE, we used rapamycin to inhibit the mechanistic target of rapamycin (mTOR). We transduced both mice and cells with TFEB vector to evaluate the therapeutic effect of TFEB overexpression on DE. Conversely, we conducted TFEB knockdown to verify its role in DE in another direction. RESULTS: We found that T2DM mice experienced compromised cognitive function, while HG-cultured HT22 cells exhibited increased cell apoptosis. Additionally, both T2DM mice and HG-cultured HT22 cells showed impaired ALP and heavier AD-like pathology. This pathology worsened after treatment with 3-MA. We also observed decreased TFEB nuclear translocation in both T2DM mice and HG-cultured HT22 cells. However, inhibiting mTOR with rapamycin or overexpressing TFEB increased TFEB nuclear translocation, enhancing the clearance of ALP-targeted AD-like pathology. This contributed to protection against neuronal apoptosis and alleviation of cognitive impairment. Conversely, TFEB knockdown lessened ALP-targeted AD-like pathology clearance and had a negative impact on DE. CONCLUSION: Our findings suggest that impaired ALP is responsible for the aggravation of AD-like pathology in T2DM. We propose that mTOR-dependent TFEB activation and TFEB overexpression are promising therapeutic strategies for DE, as they enhance the clearance of ALP-targeted AD-like pathology and alleviate neuronal apoptosis. Our study provides insight into the underlying mechanisms of DE and offers potential avenues for the development of new treatments for this debilitating complication of T2DM. Video abstract.

A Review on Applications of Time-Lapse Electrical Resistivity Tomography Over the Last 30 Years : Perspectives for Mining Waste Monitoring.

Mining operations generate large amounts of wastes which are usually stored into large-scale storage facilities which pose major environmental concerns and must be properly monitored to manage the risk of catastrophic failures and also to control the generation of contaminated mine drainage. In this context, non-invasive monitoring techniques such as time-lapse electrical resistivity tomography (TL-ERT) are promising since they provide large-scale subsurface information that complements surface observations (walkover, aerial photogrammetry or remote sensing) and traditional monitoring tools, which often sample a tiny proportion of the mining waste storage facilities. The purposes of this review are as follows: (i) to understand the current state of research on TL-ERT for various applications; (ii) to create a reference library for future research on TL-ERT and geoelectrical monitoring mining waste; and (iii) to identify promising areas of development and future research needs on this issue according to our experience. This review describes the theoretical basis of geoelectrical monitoring and provides an overview of TL-ERT applications and developments over the last 30 years from a database of over 650 case studies, not limited to mining operations (e.g., landslide, permafrost). In particular, the review focuses on the applications of ERT for mining waste characterization and monitoring and a database of 150 case studies is used to identify promising applications for long-term autonomous geoelectrical monitoring of the geotechnical and geochemical stability of mining wastes. Potential challenges that could emerge from a broader adoption of TL-ERT monitoring for mining wastes are discussed. The review also considers recent advances in instrumentation, data acquisition, processing and interpretation for long-term monitoring and draws future research perspectives and promising avenues which could help improve the design and accuracy of future geoelectric monitoring programs in mining wastes.

Autophagy and Diabetic Encephalopathy: Mechanistic Insights and Potential Therapeutic Implications.

Diabetic Encephalopathy (DE) is one of the complications of diabetes mellitus (DM) in the central nervous system. Up to now, the mechanisms of DE are not fully discussed by the field. Autophagy is an intracellular degradation pathway crucial to maintain cellular homeostasis by clearing damaged organelles, pathogens, and unwanted protein aggregates. Increasing evidence has demonstrated that autophagy might play an essential role in DE progress. In this review, we summarize the current evidence on autophagy dysfunction under the condition of DE, and provide novel insights of possibly biological mechanisms linking autophagy impairment to DE, as well as discuss autophagy-targeted therapies as potential treatments for DE.

Plasma Aß as a biomarker for predicting Aß-PET status in Alzheimer's disease：a systematic review with meta-analysis.

OBJECTIVE: Amyloid-ß positron emission tomography (Aß-PET) scan has been proposed to detect amyloid-ß (Aß) deposition in the brain. However, this approach is costly and not ideal for the early diagnosis of Alzheimer's disease. Blood-based Aß measurement offers a scalable alternative to the costly or invasive biomarkers. The aim of this study was to statistically validate whether plasma Aß could predict Aß-PET status via meta-analysis. METHODS: We systematically searched for eligible studies from PubMed, Embase and Cochrane Library, which reported plasma Aß levels of amyloid-ß positron emission tomography-positive (PET (+)) and amyloid-ß positron emission tomography-negative (PET (-)) subjects. We generated pooled estimates using random effects meta-analyses. For any study that has significant heterogeneity, metaregression and subgroup analysis were further conducted. Publication bias was appraised by funnel plots and Egger's test. RESULTS: 16 studies with 3047 participants were included in the meta-analysis. Among all the enrolled studies, 10 studies reported plasma Aß40 values, while 9 studies reported plasma Aß42 values and 13 studies reported Aß42/Aß40 ratio. The pooled standardised mean difference (SMD) was 0.76 (95% CI -0.61 to 2.14, p=0.28) in the plasma Aß40 values group. Plasma Aß42 values group has a pooled SMD of -0.60 (95% CI -0.80 to -0.41, p<0.0001). In the plasma Aß42/Aß40 ratio group, the pooled SMD was -1.44 (95% CI -2.17 to -0.72, p<0.0001). CONCLUSION: Plasma Aß40 values might not distinguish between PET (+) and PET (-) people. However, plasma Aß42 values and plasma Aß42/Aß40 ratio could be served as independent biomarkers for predicting Aß-PET status.

Validation data of parallel 3D surface-borehole electromagnetic forward modeling.

Forward modeling of geophysical electromagnetic fields over large three-dimensional volumes is a heavy computational task that demands effective accelerating strategies. As a solution to this computational challenge, a hybrid parallel computing algorithm with multiple meshes has been previously proposed for 3D forward modeling of time-domain electromagnetic (TEM) fields by Liu et al. (2019). MPI and OpenMP were used for parallel computing and multiple meshes for optimizing the design of the geological model and frequencies used in forward modeling. The data presented in this paper offers complementary information on the calculation of the different components, such as the model discretization with regular or multiple meshes, the parallel computing with even or uneven modes, and an example of 3D TEM forward modeling through the proposed algorithm.

6-Bromoindirubin-3'-oxime (6BIO) prevents myocardium from aging by inducing autophagy.

6-Bromoindirubin-3'-oxime (6BIO) is a novel small molecule that exerts positive effects on several age-related alterations. However, the anti-aging effects of 6BIO on the aging heart remain unknown. Herein, we aim to investigate the effects of 6BIO on the myocardium and its underlying mechanism in vivo and vitro. Following 6BIO treatment, an increased p53 contents, a reduced p16 and ß-gal levels, and attenuation of cardiac fibrosis were observed, suggesting 6BIO retarded aging of cardiomyocytes. As observed, 6BIO reduced p62 contents, elevated the levels of Beclin-1 and the ratio of LC3II/I, indicating the induction of autophagy, while the reduction of the accumulation of ROS indicated 6BIO alleviated oxidative stress. In addition, 6BIO treatment inhibited both GSK3ß signaling and mTOR signaling. 6BIO might be a promising agent for preventing myocardium from aging.

Design and Evaluation of Bilayer Pump Tablet of Flurbiprofen Solid Dispersion for Zero-Order Controlled Delivery.

In this study, a bilayer osmotic pump tablet of flurbiprofen (FP) solid dispersions (SDs) was developed to increase the solubility of the poorly soluble drug and controlled drug release at a constant rate. Based on the investigation of thermodynamic properties the drug, the carrier, and the calculation of the solubility parameters, the FP-SD was prepared by hot-melt extrusion technique with the povidone (PVP) VA64 carrier. Then, central composite design-response surface methodology was used to evaluate the influence of factors on the responses. Consequently, PVP VA64 was selected as the carrier for preparing FP-SD. The results of differential scanning calorimetry and X-ray confirmed that FP in FP-SD was in an amorphous state. FTIR indicated that the intermolecular hydrogen bond probably formed between FP and PVP VA64 in FP-SD. Correlation of release profiles to zero-order kinetics was significant (R2 = 0.9939). The mathematical models had good predictability because the deviation was less than 1% between the predicted value and measured value. These results demonstrated that FP-SD osmotic pump tablets successfully increased the solubility of FP and controlled the release of FP at a constant rate.

Aqueous Polymer Dispersion Coating Used for Osmotic Pump Tablets: Membrane Property Investigation and IVIVC Evaluation.

The objective of this study was to investigate the fundamental properties of propranolol hydrochloride osmotic pump tablets coated by aqueous polymer dispersion, simultaneously exploring the in vitro and in vivo correlation of the tablet. The physicochemical properties and parameters of aqueous polymer dispersion membranes (SEM, water uptake, and water vapor transmission coefficient) were investigated. In addition, the release behavior and the in vitro release and in vivo absorption profiles of the tablets coated by aqueous polymer dispersion were investigated by comparing with propranolol hydrochloride osmotic pump tablets coated by an organic solvent. Results showed that the similarity factor (f 2) between cellulose acetate-coated tablet and Eudragit-coated tablet was 78.1, and f 2 between cellulose acetate-coated tablet and Kollicoat-coated tablet was 77.6. The linear IVIVC of Eudragit-coated and Kollicoat-coated osmotic pump tablets was determined, which confirmed excellent correlation between the absorption in vivo and the drug release in vitro. Consequently, the membrane coated by aqueous polymer dispersion or organic solvent has similar in vitro release rates of controlled release. Also, compared with organic solvent coating, aqueous polymer dispersion has numerous advantages, such as reduced toxicity and no environmental damage. Therefore, the aqueous polymer dispersion technology has enormous potential as a replacement of organic solvent coating.

In vitro and In vivo Studies on a Novel Bioadhesive Colloidal System: Cationic Liposomes of Ibuprofen.

The objective of this study was to develop an ocular drug delivery system built on the cationic liposomes, a novel bioadhesive colloidal system, which could enhance the precorneal residence time, ocular permeation, and bioavailability of ibuprofen. The optimal formulation of cationic liposomes prepared by ethanol injection method was ultimately confirmed by an orthogonal L9 (33) test design. In addition, γ-scintigraphic technology and the microdialysis technique were utilized in the assessment of in vivo precorneal retention capability and ocular bioavailability individually. In the end, we acquired the optimal formulation of ibuprofen cationic liposomes (Ibu-CL) by orthogonal test design, and the particle size and entrapment efficiency (EE%) were 121.0 ± 3.5 nm and 72.9 ± 3.4%, respectively. In comparison to ibuprofen eye drops (Ibu-ED), Ibu-CL could significantly prolong the T max to 100 min and the AUC to 1.53-folds, which indicated that the Ibu-CL could improve the precorneal retention time and bioavailability of ibuprofen. Consequently, these outcomes designated that the ibuprofen cationic liposomes we researched probably are a promising application in ocular drug delivery system.

Release Mechanism Between Ion Osmotic Pressure and Drug Release in Ionic-Driven Osmotic Pump Tablets (I).

The objective of this study was to develop an authentic ionic-driven osmotic pump system and investigate the release mechanism, simultaneously exploring the in vitro and in vivo correlation of the ionic-driven osmotic pump tablet. A comparison of the ionic-driven and conventional theophylline osmotic pump, the influence of pH and the amount of sodium chloride on drug release, the relationship between the ionic osmotic pressure and the drug release, and the pharmacokinetics experiment in beagle dogs were investigated. Consequently, the similarity factor (f 2 ) between the novel and conventional theophylline osmotic pump tablet was 60.18, which indicated a similar drug-release behavior. Also, the release profile fitted a zero-order kinetic model. The relative bioavailability of the ionic-driven osmotic pump to the conventional osmotic pump calculated from the AUC (0-∞) was 93.6% and the coefficient (R = 0.9945) confirmed that the ionic-driven osmotic pump exhibited excellent IVIVC. The driving power of the ionic-driven osmotic pump was produced only by ions, which was strongly dependent on the ion strength, and a novel formula for the ionic-driven osmotic pump was derived which indicated that the drug-release rate was proportional to the ionic osmotic pressure and the sodium chloride concentration. Significantly, the formula can predict the drug-release rate and release characteristics of theophylline ionic-driven osmotic pumps, guiding future modification of the ionic osmotic pump.

Evaluation of the nitrogen content during the new-shoot-growing stage in apple leaves using two-dimensional correlation spectroscopy.

The new-shoot-growing stage is an important period of apple tree nutrition distribution. The objective of this study is to provide technical support for apple tree nutrition diagnosis by constructing quantitative evaluation models between the apple leaf nitrogen content during the new-shoot-growing stage and characteristic spectral parameters. The correlation coefficients between the original spectral data and the nitrogen content were calculated. Then, the sensitive bands of the nitrogen content were selected using the theory of two-dimensional (2D) correlation spectroscopy. Finally, partial least squares regression (PLSR) and support vector machine (SVM) evaluation models were established using 2 parameters: Rx (maximum spectral reflectivity in the waveband) and Sx (total spectral reflectivity in the waveband). The results showed that the sensitive bands in the 2D correlation synchronous and asynchronous spectrograms were 537-560 nm and 708-719 nm. The PLSR model can be used to estimate the nitrogen content. Compared with PLSR, SVM provided better modeling and testing results, with a larger coefficient of determination (R2) and a smaller root-mean-square error (RMSE). The SVM model based on Sx was a good backup method. The calibration R2 of the model was 0.821, its RMSE was 0.710 g·kg-1, the validation R2 was 0.768, and its RMSE was 1.019 g·kg-1. The SVM model based on 2D correlation spectroscopy can be used to quantitatively estimate the nitrogen content in apple leaves.

A time-adjustable pulsatile release system for ketoprofen: In vitro and in vivo investigation in a pharmacokinetic study and an IVIVC evaluation.

A time-adjustable pulsatile release system (TAPS) containing ketoprofen (KF) as an active pharmaceutical agent was developed having been designed for bedtime dosing and releasing drug in the early morning to control the symptoms of rheumatoid arthritis (RA). The formulation involved a tablet core (KF) and a control-release layer, and the coating membrane was composed of EC and Eudragit L100. A single-factor study, a central composite design and a response surface method were selected to optimize the formula and the optimum prescription was as follows: tablet core (KF 50mg, MCC 70mg, lactose 40mg, L-HPC 38mg), and film (EC 7.8g, Eudragit L100 4.2g, PEG 6000 1.8g in 95% alcohol each 200ml). The in vivo release behavior of the tablets was evaluated in Beagle dogs after a parallel oral administration of KF TAPS tablets and commercial KF capsules, when it was found that the KF TAPS tablets released the drug after a lag-time of 3.458h and the Tmax was 5.833h. The relative bioavailability was 85.01%, and the two formulations were bioequivalent in terms of Cmax and AUC0-t and the in vitro- in vivo correlations indicated that test formulation had a good in vivo-in vitro correlation (r=0.9703). These results show that the novel drug delivery system (TAPS) has the potential to be used as a KF preparation with chronophamacokinetics characteristics.

[Rapid identification for fruit drugs of rosaceae based on electrochemical oscillation reaction].

OBJECTIVE: To establish a rapid identification method for fruit drugs of Rosaceae, according to the influence of Chinese traditional medicine on the electrochemical oscillation reaction. METHODS: The experiments were carried out in H2SO4-Ce (SO4)2-CH2 (COOH)2-KBrO3 electrochemical oscillation system. The graphs and characteristic parameters which were formed by the disturbance of Rosaceous fruit drugs to the electrochemical oscillation reaction were studied. RESULTS: There were obvious distinction on the electrochemical fingerprints of five kinds of medicinal materials, and the characteristic parameters of oscillation life were significant different. CONCLUSION: The electrochemical fingerprints of five kinds of Rosaceous fruit drugs can be used to identify those medicinal materials. The method is simple, rapid, economic and reliable.

The expression of p63 is associated with the differential stage in nasopharyngeal carcinoma and EBV infection.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown. This study was aimed to investigate the association between p63 and NPC. RESULTS: p63 was expressed in 100% (202/202) of nasopharyngeal carcinoma (NPC) tissues but not in 29 nasopharynx inflammation and 17 non-cancerous nasopharyngeal epidermises on a tissue microarray by immunohistostaining. Further investigation suggested that the p63 expression was associated with the differential stage of NPC: p63 strong staining in Keratinizing squamous cell carcinoma, differentiated non-keratinizing NPC and undifferentiated non-keratinizing NPC presented the percentage of 5/8 (62.5%), 43/48 (92.5%) and 50/50 (100%), respectively. A significant difference (p = 0.001) existed between the keratinizing and non-keratinizing groups. No pathogenic mutations were detected in p63 gene in 12 primary NPC tissues and matched peripheral blood lymphocytes (PBL). Half-life measurement study revealed distinct stability of p63 protein in the different cell lines, especially between the carcinoma cell lines with EBV infection and the non-cancerous cell lines. The results of immunoprecipitation suggested a direct interaction between Epstein-Barr virus nuclear antigen 5 (EBNA-5) and p63 protein in NPC, and this binding would increase the stability of p63. CONCLUSION: Our data suggested p63 might be used as an adjunct diagnostic marker of NPC and contributed a new way to understand the contribution of the EBV in the pathogenesis of NPC.