Hydraulic property variations with depth in a loess mudstone landslide.

In areas where loess is distributed, landslides represent a significant geohazard with severe implications. Among these events, loess-mudstone landslides are particularly prevalent, posing substantial risks to the safety and property of local residents, and moisture plays a pivotal role as a key factor in causing these disasters. In this study, the hydraulic properties of the soils along the longitudinal section of an ongoing loess-mudstone landslide are investigated through the variation of soil water characteristic curves, which are subsequently fitted by utilizing van Genuchten model. Moreover, a comprehensive experimental investigation was conducted on the loess, mudstone, and loess-mudstone mixtures to facilitate analysis, including X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) observation, particle size distribution (PSD) analysis, along with fundamental geotechnical tests for parameter determination. It is found that mudstone and loess have distinct SWCC distribution. The SWCC of loess at various depths exhibits a similar distribution pattern due to the occurrence of landslide. The SWCC distribution of loess-mudstone mixture displays a transitional trend between the SWCC of mudstone and that of loess, and the water retention capacity increases as the mudstone content increases. The experimental findings have demonstrated notable agreement between each other and exhibited a satisfactory level of concurrence with the observed phenomena in geological surveys.

Evaluation of pharmacist-led medication reconciliation at county hospitals in China: A multicentre, open-label, assessor-blinded, nonrandomised controlled study.

Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China. Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge. Patients in the intervention group received a pharmacist-led medication reconciliation intervention and those in the control group received standard care. We assessed the incidence of medication discrepancies at discharge, patients' medication adherence, and health care utilisation within 30 days after discharge. Results: There were 429 patients in the intervention group (mean age = 72.5 years, standard deviation (SD) = 7.0) and 526 patients in the control group (mean age = 73.6 years, SD = 7.1). Of the 1632 medication discrepancies identified at discharge, fewer occurred in the intervention group (1.9 per patient on average) than the control group (2.6 per patient on average).The intervention significantly reduced the incidence of medication discrepancy by 9.6% (95% confidence interval (CI) = -15.6, -3.6, P = 0.002) and improved patients' medication adherence, with an absolute decrease in the mean adherence score of 2.5 (95% CI = -2.8, -2.2, P < 0.001). There was no significant difference in readmission rates between the intervention and control groups. Conclusions: Pharmacist-led medication reconciliation at discharge from Chinese county-level hospitals reduced medication discrepancies and improved patients' adherence among patients aged 60 years or above, though no impact on readmission after discharge was observed. Registration: ChiCTR2100045668.

Hippocampal-derived extracellular vesicle synergistically deliver active adenosine hippocampus targeting to promote cognitive recovery after stroke.

Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.

Preparation of injectable porcine skin-derived collagen and its application in delaying skin aging by promoting the adhesion and chemotaxis of skin fibroblasts.

Collagen, as the main component of human skin, plays a vital role in maintaining dermal integrity. Its loss will lead to dermis destruction and collapse, resulting in skin aging. At present, injection of exogenous collagen is an important means to delay skin aging. In this study, high-purity collagen was extracted from porcine skin. Our research revealed that it can effectively promote the adhesion and chemotaxis of HSF cells. It can also reduce the expression of ß-galactosidase, decrease ROS levels, and increase the expression of the collagen precursors, p53 and p16 in HSF cells during senescence. After local injection into the aging skin of rats, it was found that the number of cells and type I collagen fibers in the dermis increased significantly, and the arrangement of these fibers became more uniform and orderly. Moreover, the important thing is that it is biocompatible. To sum up, the porcine skin collagen we extracted is an anti-aging biomaterial with application potential.

Iminyl radical-triggered relay annulation for the construction of bridged aza-tetracycles bearing four contiguous stereogenic centers.

Bridged tetracyclic nitrogen scaffolds are found in numerous biologically active molecules and medicinally relevant structures. Traditional methods usually require tedious reaction steps, and/or the use of structurally specific starting materials. We report an unprecedented, iminyl radical-triggered relay annulation from oxime-derived peresters and azadienes, which shows good substrate scope and functional group compatibility, and can deliver various bridged aza-tetracyclic compounds with complex molecular topology and four contiguous stereogenic centers (dr > 19 : 1) in a single operation. This transformation represents the first example of trifunctionalization of iminyl radicals through simultaneous formation of one C-N and two C-C bonds. DFT calculation studies were conducted to obtain an in-depth insight into the reaction pathways, which revealed that the reactions involved an interesting 1,6-hydrogen atom transfer process.

The relationship between body mass index and clinical efficacy of knee arthroplasty in patients with knee osteoarthritis.

Background: Increase body mass index (BMI) is often accompanied by metabolic diseases such as diabetes, which will increase the uncertainty of total knee arthroplasty (TKA) efficacy and the risk of postoperative complications. The present study was to study the relationship between increase BMI and clinical efficacy of knee arthroplasty in patients with knee osteoarthritis. Methods: A total of 97 patients (36 males and 61 females) with knee osteoarthritis (KOA) who underwent TKA surgery were selected. According to the preoperative body mass index (BMI), the patients were divided into a normal group (n=42), overweight group (n=35), and obese group (n=20). All patients received TKA after admission. Seven days after surgery, the American Knee Society (AKS) and the Hospital for Special Surgery (HSS) scales were used to evaluate the recovery of knee function. The recovery was poor if the scores of AKS and HSS were less than 70. Results: Seven days after TKA, the scores of AKS and HSS in different BMI groups were significantly different, and decreased with the increase of BMI (P<0.05). Age, increased BMI, diabetes, preoperative range of motion (ROM), intraoperative blood loss, postoperative C-reactive protein (CRP), postoperative posterior slope angle (PSA), postoperative infection, and postoperative deep vein thrombosis (DVT) of lower extremities were related to AKS score <70 (P<0.05). Diabetes, preoperative ROM, intraoperative blood loss, postoperative CRP, postoperative PSA, and postoperative infection were related to HSS score <70 (P<0.05). Increased BMI, diabetes, postoperative CRP, postoperative infection, and postoperative DVT were independent risk factors for AKS score <70 (HR =3.458, 1.152, 2.960, 1.023, 3.589, P<0.05). Increased BMI, diabetes, postoperative CRP, and postoperative infection were independent risk factors for HSS score <70 (HR =6.891, 1.263, 1.967, 1.235, P<1.235). The area under the curve (AUC) (95% CI) of BMI in diagnosing AKS <70 was 0.740 (0.641-0.839). The AUC (95% CI) of BMI in diagnosing HSS <70 was 0.809 (0.723-0.894). Conclusions: The increase of BMI is an independent risk factor for the poor recovery of knee function after TKA in patients with KOA.

Fabrication of Resveratrol-Loaded Scaffolds and Their Application for Delaying Cell Senescence In Vitro.

In this research, resveratrol (RSV)-loaded scaffolds have been prepared to control the release of resveratrol and used to delay hepatic stellate cell (HSC) senescence in vitro. The functional carboxyl group-COOH is first introduced to the surface of poly(ε-caprolactone/d,l-lactide) (P(CL-DLLA)) under the coadministration of ultra-violet (UV) treatment and photo initiator and then resveratrol are conjugated onto the surface of the modified scaffolds through esterification. The characterization of the structure of RSV-AA-P(CL-DLLA) shows that resveratrol has been successfully conjugated onto the modified surface. Cell growth exhibits a higher level of cell viability and much more obvious agglomeration on the surface of the synthetic RSV-AA-P(CL-DLLA). Meanwhile the activity of senescence-associated ß-galactosidase (SA-ß-gal) and reactive oxygen species (ROS) is downgulated for cells on RSV-AA-P(CL-DLLA), which suggests that cell senescence is delayed on RSV-AA-P(CL-DLLA). And then it is attested that cells have a lower level of p53 but SIRT1 expression is upregulated on RSV-AA-P(CL-DLLA), which might be related to resveratrol release from RSV-AA-P(CL-DLLA). It also suggested cell senescence on RSV-AA-P(CL-DLLA) has been regulated by p53 and the SIRT1 signaling pathway. In all, the present study shows that RSV-AA-P(CL-DLLA) can be successfully prepared to promote cell growth and delay cell senescence and could be used for cell-based therapy in tissue engineering.

LncRNA ROR/miR-145-5p axis modulates the osteoblasts proliferation and apoptosis in osteoporosis.

Osteoporosis (OP) is a systemic bone metabolic disease. Promotion of osteoblast proliferation and inhibition of cell apoptosis may be helpful for the prevention and clinical treatment of OP. In the current study, we focused on the expression changes and clinical values of lncRNA ROR and miR-145-5p in OP clinical serum samples, and investigated the interactive modulation effect of ROR/miR-145-5p on osteoblast function. Serum samples were obtained from 82 OP patients and 79 healthy individuals. MC3T3-E1 was applied for the cell experiments. Levels of lncRNA ROR and miR-145-5p were detected using qRT-PCR. Transient transfection was performed to regulate gene levels in cells, and cell proliferation and apoptosis were detected. A reciprocal correlation between lncRNA ROR and miR-145-5p was explored. LncRNA ROR was downregulated, and miR-145-5p was overexpressed in OP patients. The combined diagnosis of ROR and miR-145-5p showed good diagnostic value for OP. ROR knockdown promoted the MC3T3-E1 cell apoptosis and inhibited cell proliferation. Luciferase reporting assay verified the target relationship between ROR and miR-145-5p. MiR-145-5p downregulation reversed ROR silence mediated effect on MC3T3-E1 cell proliferation and apoptosis. LncRNA ROR is downregulated and miR-145-5p is highly expressed in OP patients. ROR knockdown may inhibit osteoblast proliferation via targeting miR-145-5p. It may provide a theoretical basis and experimental basis for ROR to be a potential target for the treatment of OP.

Cloning and Functional Characterization of Putative Escherichia coli ABC Multidrug Efflux Transporter YddA.

A putative multidrug efflux gene, yddA, was cloned from the Escherichia coli K-12 strain. A drugsensitive strain of E. coli missing the main multidrug efflux pump AcrB was constructed as a host and the yddA gene was knocked out in wild-type (WT) and drug-sensitive E. coliΔacrB to study the yddA function. Sensitivity to different substrates of WT E.coli, E. coliΔyddA, E. coliΔacrB and E. coliΔacrBΔyddA strains was compared with minimal inhibitory concentration (MIC) assays and fluorescence tests. MIC assay and fluorescence test results showed that YddA protein was a multidrug efflux pump that exported multiple substrates. Three inhibitors, ortho-vanadate, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and reserpine, were used in fluorescence tests. Ortho-vanadate and reserpine significantly inhibited the efflux and increased accumulation of ethidium bromide and norfloxacin, while CCCP had no significant effect on YddA-regulated efflux. The results indicated that YddA relies on energy released from ATP hydrolysis to transfer the substrates and YddA is an ABC-type multidrug exporter. Functional study of unknown ATP-binding cassette (ABC) superfamily transporters in the model organism E. coli is conducive to discovering new multidrug resistance-reversal targets and providing references for studying other ABC proteins of unknown function.

Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.

Unconjugated bilirubin, the end product of heme catabolism and antioxidant, induced brain damage in human neonates is a well-recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we investigated whether bilirubin-induced glial activation was involved in bilirubin neurotoxicity by exposing co-cultured rat glial cells and cerebellar granule neurons (CGN) to bilirubin. We found that bilirubin could markedly induce the expression of TNF-α and iNOS in glial cells, and even at low concentrations, the co-culture of glial cells with neurons significantly enhances neurotoxicity of bilirubin. Pretreatment of the co-cultured cells with minocycline protected CGN from glia-mediated bilirubin neurotoxicity and inhibited overexpression of TNF-α and iNOS in glia. Furthermore, we found that high doses of bilirubin were able to induce glial injury, and minocycline attenuated bilirubin-induced glial cell death. Our data suggest that glial cells play an important role in brain damage caused by bilirubin, and minocycline blocks bilirubin-induced encephalopathy possibly by directly and indirectly inhibiting neuronal death pathways.

Intraoperative Hepatic Blood Inflow Can Predict Early Acute Kidney Injury following DCD Liver Transplantation: A Retrospective Observational Study.

PURPOSE: Acute kidney injury (AKI) is a major and severe complication following donation-after-circulatory-death (DCD) liver transplantation (LT) and is associated with increased postoperative morbidity and mortality. However, the risk factors and the prognosis factors of AKI still need to be further explored, and the relativity of intraoperative hepatic blood inflow (HBI) and AKI following LT has not been discussed yet. The purpose of this study was to investigate the correlation between HBI and AKI and to construct a prediction model of early acute kidney injury (EAKI) following DCD LT with the combination of HBI and other clinical parameters. METHODS: Clinical data of 132 patients who underwent DCD liver transplantation at the first hospital of China Medical University from April 2005 to March 2017 were analyzed. Data of 105 patients (the first ten years of patients) were used to develop the prediction model. Then we assessed the clinical usefulness of the prediction models in the validation cohort (27 patients). EAKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria based on serum creatinine increase during 7-day of postoperative follow-up. RESULTS: After Least Absolute Shrinkage and Selection Operator (LASSO) regression and simplification, a simplified prediction model consisting of the Child-Turcotte-Pugh (CTP) score (p=0.033), anhepatic phase (p=0.014), packed red blood cell (pRBC) transfusion (p=0.027), and the HBI indexed by height (HBI/h) (p=0.002) was established. The C-indexes of the model in the development and validation cohort were 0.823 [95% CI, 0.738-0.908] and 0.921 [95% CI, 0.816-1.000], respectively. CONCLUSIONS: In this study, we demonstrated the utility of HBI/h as a predictor for EAKI following DCD LT, as well as the clinical usefulness of the prediction model through the combination of the CTP score, anhepatic phase, pRBC transfusion and HBI/h.

Oxaloacetate and adipose stromal cells-conditional medium synergistically protected potassium/serum deprivation-induced neuronal apoptosis.

Adipose stromal cells conditioned media (ASC-CM) protect neurons in a variety of neuronal death models including potassium/serum deprivation-induced neuronal apoptosis. In this study, we found that ASC-CM contained glutamate oxaloacetate transaminase and its substrate, oxaloacetate (OAA) directly protected cerebellar granule neurons (CGN) from apoptosis induced by serum and potassium deprivation. Additionally, OAA inhibited serum and potassium deprivation-induced caspase 3 activation. ASC-CM and OAA in combination had a synergistic neuroprotective effect. Clearly, different from ASC-CM-induced neuroprotection, OAA-induced neuroprotection was Akt- independent but JNK-dependent. These data establish a mechanistic basis supporting that the application of ASC-CM for neuroprotective treatments could be significantly enhanced by addition of OAA.

Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity.

Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders.

Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis.

Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating symptomatic SOD1(G93A) mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1(G93A) mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1(G93A) mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1(G93A) mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1(G93A) mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS.

Huaier aqueous extract induces apoptosis of human fibrosarcoma HT1080 cells through the mitochondrial pathway.

In recent years, aqueous extract of Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine, has been frequently used in China for complementary cancer therapy. However, the mechanisms underlying its anticancer effects have yet to be elucidated. The present study aimed to evaluate the ability of Huaier extract to inhibit proliferation, promote apoptosis and suppress mobility in the fibrosarcoma HT1080 cell line in vitro. The cells were treated with gradient doses of Huaier extract at concentrations of 0, 4, 8 or 16 mg/ml for 24, 48 or 72 h. The cell viability and motility were measured in vitro using MTT, invasive, migration and scratch assays. The distribution of the cell cycle and the extent of cellular apoptosis were analyzed by flow cytometry. The apoptotic pathways were detected using a mitochondrial membrane potential transition assay and western blotting. The results revealed that the cellular viability decreased significantly with increasing concentrations of Huaier extract. In addition, cell invasiveness and migration were also suppressed significantly. It was demonstrated that Huaier extract induced G2 cell-cycle arrest and cellular apoptosis in a time- and dose-dependent manner. The decreased mitochondrial membrane potential, the downregulation of B-cell lymphoma 2 and pro-caspase-3, and upregulation of Bcl-2-associated X protein, cleaved caspase-9 and caspase-3 suggested that Huaier extract induced the apoptosis of HT1080 cells through the mitochondrial pathway. The results of the present study indicate that Huaier extract is a potential complementary agent for the treatment of fibrosarcoma.

Serum fatty acid profiles and potential biomarkers of ankylosing spondylitis determined by gas chromatography-mass spectrometry and multivariate statistical analysis.

Ankylosing spondylitis (AS) is a common chronic inflammatory rheumatic disease. Early and accurate detection is essential for effective disease treatment. Recently, research has focused on genomics and proteomics. However, the associated metabolic variations, especially fatty acid profiles, have been poorly discussed. In this study, the gas chromatography-mass spectrometry (GC-MS) approach and multivariate statistical analysis were used to investigate the metabolic profiles of serum free fatty acids (FFAs) and esterified fatty acids (EFAs) in AS patients. The results showed that significant differences in most of the FFA (C12:0, C16:0, C16:1, C18:3, C20:4, C20:5, C22:5 and C22:6) and EFA (C12:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:4 and C22:6) concentrations were found between the AS patients and healthy controls (p < 0.05). Principal component analysis and partial least squares discriminant analysis were performed to classify the AS patients and controls. Additionally, FFAs C20:4, C12:0, C18:3 and EFAs C22:6, C12:0 were confirmed as potential biomarkers to identify AS patients and healthy controls. The present study highlights that differences in the serum FFA and EFA profiles of AS patients reflect the metabolic disorder. Moreover, FFA and EFA biomarkers appear to have clinical applications for the screening and diagnosis of AS.

Quantitative assessment of the association between CYP17 rs743572 polymorphism and prostate cancer risk.

Published data on the association between CYP17 rs743572 polymorphism and risk of PC showed inconclusive results. The aim of this study was to further estimate the pooled effect size of rs743572 polymorphism and PC progression via large-scale meta-analysis. We searched the case-control studies of rs743572 polymorphism and PC risk in PubMed, Embase, and Web of Science databases up to February 2014. Odds ratios (ORs) along with 95 % confidence intervals (CIs) were pooled by means of both fixed effects model and random effects model. A total of 38 publications consisting of 42 studies with 15,735 cases and 17,825 controls were included in this meta-analysis. Overall, no significant association was found between rs743572 polymorphism and PC risk. Stratified analyses by control source and sample size did not provide significant results. However, there was a borderline association in African population under A2A2 versus A1A2 + A1A1 genetic model (OR = 1.39, 95 % CI: 1.01-1.92, P = 0.975, I (2) = 0.0 %). Results from the current meta-analysis suggested that CYP17 rs743572 polymorphism might modify the risk of PC in the subjects of African decent.

Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function.

Mouse strain differences in immobility and in sensitivity to antidepressants have been observed in the forced swimming test (FST) and the tail suspension test (TST). However, the neurotransmitter systems and neural substrates that contribute to these differences remain unknown. To investigate the role of the hippocampal serotonin transporter (5-HTT), we measured baseline immobility and the immobility responses to fluoxetine (FLX) in the FST and the TST in male CD-1, C57BL/6, DBA and BALB/c mice. We observed strain differences in baseline immobility time, with CD-1 mice showing the longest and DBA mice showing the shortest. In contrast, DBA and BALB/c mice showed the highest sensitivity to FLX, whereas CD-1 and C57BL/6 mice showed the lowest sensitivity. Also we found strain differences in both the total 5-HTT protein level and the membrane-bound 5-HTT level (estimated by V max) as follows: DBA>BALB/c>CD-1=C57BL/6. The uptake efficiency of the membrane-bound 5-HTT (estimated by 1/K m) was highest in DBA and BALB/c mice and lowest in CD-1 and C57BL/6 mice. A correlation analysis of subregions within the hippocampus revealed that immobility time was negatively correlated with V max and positively correlated with K m in the hippocampus. Therefore a higher uptake capacity of the membrane-bound 5-HTT in the hippocampus was associated with lower baseline immobility and greater sensitivity to FLX. These results suggest that alterations in hippocampal 5-HTT activity may contribute to mouse strain differences in the FST and the TST.