An eco-friendly porous hydrogel adsorbent based on dextran/phosphate/amino for efficient removal of Be(II) from aqueous solution.

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.

Adult porcine (Sus scrofa) derived inner ear cells: Characteristics in in-vitro cultures.

There is a need for an animal model that closely parallels human cochlea gestational development. This study aims to document porcine inner ear anatomy, and in vitro porcine derived inner ear cell culture characteristics. Twenty-four temporal bone were harvested from 12 adult pigs (Sus scrofa). Six were formalin fixed and their maximal diameters were measured. The cochlea duct length was determined by the insertion length of a Nucleus 22 cochlear implant in two bones. Four formalin fixed bones were sectioned for histology. Cochlear and vestibular tissues were harvested from non-fixed bones, cultured and characterized at different passages (P). Gene and protein expression of multipotent stem/progenitor (Nestin and Sox2), inner ear hair (Myosin VIIa, Prestin) and supporting (Cytokeratin 18 and Vimentin) cell markers were determined. The porcine cochlea was a 3.5 turn spiral. There was a separate vestibular compartment. The cochlear mean maximal diameter and height was 7.99 and 3.77 mm, respectively. Sphere forming cells were identified on phase-contrast microscopy. The relative mRNA expression levels of KRT18, MYO7A and SLC26A5 were significantly positively correlated in cochlear cultures; and MYO7A and SLC26A5; SOX2 and KRT18; NES and SLC26A5 genes were positively correlated in vestibular cultures (p = .037, Spearman correlation [τ] = .900). Inner ear sensory and stem cell characteristics persist in passaged porcine inner ear cells. Further work is required to establish the usefulness of porcine inner ear cell cultures to the study of human inner ear disorders.

Soft and Rigid Integrated Durable Coating for Large-Scale Deicing.

Soft silicone has been widely used for anti-icing coating, but the ice adhesion strength is usually scaled with the iced area at a relatively large thickness. On the other hand, a thin rigid poly(vinyl chloride) (PVC) film could be independent of the iced area and was named a low-interfacial-toughness material. Thus, a soft and rigid integrated (SRI) coating was prepared by doping PVC particles into a silicone matrix here. The introduction of PVC particles not only served as phase II to accelerate the stress concentration but also favored the formation of a wrinkle structure. After further introducing plasticizers, this SRI coating not only has a very low ice adhesion strength at a low iced length but also tends to a limit value irrespective of the iced length, which further leads to excellent large-area deicing behavior. Furthermore, the SRI coating demonstrated outstanding chemical stability, mechanical robustness, and on-field repairability.

Imitation Learning: Progress, Taxonomies and Challenges.

Imitation learning (IL) aims to extract knowledge from human experts' demonstrations or artificially created agents to replicate their behaviors. It promotes interdisciplinary communication and real-world automation applications. However, the process of replicating behaviors still exhibits various problems, such as the performance is highly dependent on the demonstration quality, and most trained agents are limited to perform well in task-specific environments. In this survey, we provide an insightful review on IL. We first introduce the background knowledge from development history and preliminaries, followed by presenting different taxonomies within IL and key milestones of the field. We then detail challenges in learning strategies and present research opportunities with learning policy from suboptimal demonstration, voice instructions, and other associated optimization schemes.

Biomechanical Study of Arthroscopic All-Inside Anterior Talofibular Ligament Suture Augmentation Repair, Plus Suture Augmentation Repair and Anterior Tibiofibular Ligament's Distal Fascicle Transfer Augmentation Repair.

Objective: To explore the biomechanical efficacy of arthroscopic all-inside anterior talofibular ligament (ATFL) suture augmentation repair, plus suture augmentation repair and anterior tibiofibular ligament-distal fascicle (ATiFL-DF) transfer augmentation repair, so as to provide a basis for the accurate selection of ATFL repair in clinical practice. Methods: Twenty-four (12 pairs) fresh frozen human cadaver ankle specimens were used. Six of the ankle specimens were set as the normal group, and the other 18 ankle specimens were used to establish ATFL injury models. The ATFL was then repaired using arthroscopic all-inside ATFL suture augmentation repair (suture augmentation group), plus suture augmentation repair (plus suture augmentation group) and ATiFL-DF transfer augmentation repair (biological augmentation group), respectively. After the repaired ATFL was separated, the ankle specimens were fixed on an electronic universal testing machine with a customized fixture for the tensile test, and the ultimate failure load (N) and stiffness (N/mm) of the ankle specimens were compared. Results: The ultimate failure load of the plus suture augmentation group (229.3 ± 66.7 N) was significantly higher than that in the normal group (148.2 ± 39.4 N, p = 0.045) and the biological augmentation group (131.3 ± 38.8 N, p = 0.013). There was no statistical difference in ultimate failure load between the suture augmentation group (167.2 ± 47.2 N), the normal group and the biological augmentation group. The stiffness of the plus suture augmentation group (26.2 ± 8.2 N/mm) was significantly higher than that in the normal group (12.1 ± 3.8 N/mm, p = 0.005) and the biological augmentation group (12.7 ± 5.2 N/mm, p = 0.007). The stiffness of the suture augmentation group (23.6 ± 7.0 N/mm) was significantly higher than that in the normal group (p = 0.024) and the biological augmentation group (p = 0.033). There was no statistical difference in stiffness between the plus suture augmentation group and the suture augmentation group, and no statistical difference in stiffness between the normal group and the biological augmentation group. Conclusions: The tensile strength and rigidity of plus suture augmentation repair were significantly better than those of normal ATFL, suture augmentation repair and ATiFL-DF transfer augmentation repair. Suture augmentation repair can obtain tensile strength similar to normal ATFL and ATiFL-DF transfer augmentation repair, and suture augmentation repair can obtain rigidity significantly better than normal ATFL and ATiFL-DF transfer augmentation repair. ATiFL-DF transfer augmentation repair can obtain tensile strength and rigidity similar to normal ATFL.

YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth.

Chondrosarcoma (CHS) is the second most common bone malignant tumor and currently has limited treatment options. We have recently demonstrated that thioredoxin interacting protein (TXNIP) plays a crucial role in the oncogenesis of bone sarcoma, yet its implication in CHS is underdetermined. In the present study, we first found that knockdown of TXNIP promotes the proliferation of CHS cell largely through increasing their glycolytic metabolism, which is well-known as Warburg effect for providing energy. Consistent with our previous report that YAP is fundamental for CHS cell growth, herein we revealed that YAP functioned as an upstream molecule of TXNIP, and that YAP negatively regulated TXNIP mRNA and protein expression both in vitro and in vivo. Mechanistically, although knockdown of YAP upregulated both the nuclear and cytoplasmic TXNIP expression, we did not observe any obvious interaction between YAP and TXNIP; instead, miRNA-524-5p was demonstrated to be required for YAP-regulated TXNIP expression and thus controlling CHS cell growth. Together, our study reveals that TXNIP is a tumor suppressor in terms of CHS, and that the YAP/miRNA-524-5p/TXNIP signaling axis may provide a novel clue for CHS targeted therapy.

Clinical effects of antidiabetic drugs on psoriasis: The perspective of evidence-based medicine.

Psoriasis and diabetes shared common underlying pathophysiological mechanisms. Emerging data suggested that antidiabetic medications may improve the psoriasis severity in patients with diabetes mellitus. Several hypoglycemic agents including thiazolidinediones, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and biguanides have been reported to make a remarkable reduction in the Psoriasis Area and Severity Index score from baseline. This antipsoriatic effect could be mediated not only by the glucose-lowering action of these agents but also via inhibition of keratinocyte over proliferation, increase expression of differentiation markers, suppression the immune inflammatory pathway, and blocking the calcium channels and mitogen-activated protein kinase signaling pathways. On the other hand, there was no significant increase in adverse reactions associated with the treatment of pioglitazone or metformin. However, previous studies often had the relatively short duration of the trials, and did not have enough power to assess recurrence of psoriasis. Potential bias in the study and missing data could undermine the reliability of the results. Therefore, the appropriately randomized controlled studies with large sample sizes and long-term durations in various psoriasis patients are warranted for further support.

Systematic Review of the Effect of a Zero-Markup Policy for Essential Drugs on Healthcare Costs and Utilization in China, 2015-2021.

Objective: This systematic review aimed to discuss the effects of a zero-markup policy for essential drugs (ZPED) on healthcare costs and utilization in China in the years 2015-2021. Methods: We searched the PubMed, Embase, Scopus, and CINAHL databases for all associated studies carried out from January 1, 2015, to May 31, 2021, without any limitations regarding the language the studies were written in. To prevent selection bias, gray documents were tackled by other means. The methodological approaches were assessed by applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Newcastle-Ottawa Scale (NOS) collaboration tool. Results: Forty studies were selected at first and then 15 studies that met the inclusion criterion. Most of the studies showed a considerable decrease in total medical spending and drug spending in both outpatient and inpatient services. After the implementation of ZPED, studies showed that the medical services increased and total hospital income sustained, despite a decrease in drug revenue. Minimal or no government subsidy is required from a financial perspective. Conclusions: Although, the government could implement ZEPD with lower medical cost and drug cost to patients, and sustained income for health facilities, we have limited understanding of whether the increase in medical services was induced by the provider or was a response to unmet needs in the population. Further, studies using rigorous and advanced methods to study health policy, patient behaviors, provider behaviors, and government decisions are warranted.

Risk Factors for Contralateral Occult Carcinoma in Patients With Unilateral Papillary Thyroid Carcinoma: A Retrospective Study and Meta-Analysis.

Background: Bilateral lesions are common in papillary thyroid carcinoma (PTC). For patients with unilateral PTC, occult carcinoma that is not detected preoperatively, but pathologically after surgery, might remain in the contralateral lobe. In this situation, inadequate surgical extent could cause relapse and even lead to re-operation. Here, we explore the frequency and investigate the risk factors of contralateral occult PTC in unilateral PTC through a retrospective study conducted by our team and published articles online, respectively. Methods: We collected the patients' clinical data in our hospital, whose cancer was determined to be confined to the unilateral lobe by preoperative image examination (N = 204). These patients underwent initially total or near-total thyroidectomy and included their clinical data in the meta-analysis. We searched related literature in the PubMed, Embase, MEDLINE, Cochrane, and Web of Science databases until December 7, 2020, in order to perform a meta-analysis. The relevant articles were examined and the eligible studies were included to assess the association between clinicopathologic factors and contralateral occult PTC. Results: The meta-analysis included nine studies (involving 4347 patients). Of these, eight studies were from the databases, and one study was our retrospective data. The meta-analysis showed that the prevalence of contralateral occult PTC was 26.6% in all patients. A tumor size > 1 cm, ipsilateral multifocality, contralateral benign nodule, and central lymph node metastasis were significantly associated with contralateral occult PTC. In contrast, sex, age, ETE, capsular invasion, BRAF mutation, Hashimoto thyroiditis, and lateral lymph node metastasis were insignificantly associated with contralateral occult PTC. Conclusion: The meta-analysis identified a tumor size > 1 cm, ipsilateral multifocality, contralateral benign nodule, and CLNM as being significant risk factors for contralateral occult PTC. These findings may guide the extent of surgery in unilateral PTC patients.

Exploring Contact Angle Hysteresis Behavior of Droplets on the Surface Microstructure.

It is confirmed that surfaces with specific microstructures could exhibit good superhydrophobic properties, and there are also a lot of conclusions about droplet hysteresis behavior. However, most of the research methods are based on two-dimensional ideal model and experimental observation at the macroscale. Further research needs to be conducted about the hysteresis behavior of droplets on the microstructure surface under three-dimensional conditions. In this paper, the influence of curvature variation of the liquid surface between pillars on the contact angle hysteresis (CAH) has been investigated. The simulation results were in good agreement with the experimental measurements. Analyses were conducted on the morphology change and force of the liquid surface between pillars, and an index was proposed to describe the degree of difficulty of liquid surface movement. It was revealed that a change in the direction of the surface tension at the three-phase interface caused by curvature variation of the liquid surface between pillars played an important role in the movement of the liquid surface. The greater the surface tension component in the normal direction of the liquid surface, the more likely it was for the liquid surface to advance or recede. The local curvature of the liquid surface increased or the angles between the pillars increased, and the effect of the CAH would be weakened.

Aldehyde dehydrogenase 2 protects against sympathetic excitation-induced cardiac fibrosis.

Sympathetic stimulated-cardiac fibrosis imposes great significance on both disease progression and survival in the pathogenesis of many cardiovascular diseases. However, there are few effective therapies targeting it clinically. The cardioprotective effect of aldehyde dehydrogenase 2 (ALDH2) has been explored in many pathological conditions, whether it can exert benefit effects on chronic sympathetic stimulus-induced cardiac fibrosis remains unclear. In this study, we determined to explore the role of ALDH2 on isoproterenol (ISO)-induced cardiac fibroblasts (CF) proliferation and cardiac fibrosis. It was found that ALDH2 enzymatic activity was impaired in ISO-induced HCF proliferation and Aldh2 deficiency promoted mouse CF proliferation. Alda-1, an ALDH2 activator, exerted obvious suppressive effect on ISO-induced HCF proliferation, together with the induction of cell cycle arrest at G0/G1 phase and decreased expression of cyclin E1 and cyclin-dependent kinase 2 (CDK2). Mechanistically, the inhibitory role of Alda-1 on HCF proliferation was achieved by decreasing mitochondrial reactive oxygen species (ROS) production, which was partially reversed by rotenone, an inducer of ROS. In addition, wild-type mice treated with Alda-1 manifested with reduced fibrosis and better cardiac function after ISO pump. In summary, Alda-1 alleviates sympathetic excitation-induced cardiac fibrosis via decreasing mitochondrial ROS accumulation, highlighting ALDH2 activity as a promising drug target of cardiac fibrosis.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury.

BACKGROUND: Disturbance of mitochondrial fission and fusion (termed mitochondrial dynamics) is one of the leading causes of ischemia/reperfusion (I/R)-induced myocardial injury. Previous studies showed that mitochondrial aldehyde dehydrogenase 2 (ALDH2) conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes. However, whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown. METHODS: In the present study, we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation (H/R) as an in vitro model of myocardial I/R injury. RESULTS: Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation (OGD/R), and ALDH2 activation largely decreased the cardiomyocyte apoptosis. Additionally, we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R. Furthermore, we found that ALDH2 dominantly suppressed dynamin-related protein 1 (Drp1) phosphorylation (Ser616) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) but not interfered with the expression levels of mitochondrial shaping proteins. CONCLUSIONS: We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

Non­coding RNAs, including long non­coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), have significant regulatory effects on a number of biological processes in myocardial ischemia/reperfusion (I/R) injury, including cell differentiation, proliferation and apoptosis. In the present study, the expression levels of lncRNAs, miRNAs and mRNAs were evaluated in a mouse model of myocardial I/R injury. The potential functions of these differentially expressed genes were then analyzed via Gene Ontology and pathway analyses. Additionally, the interactions between lncRNA­miRNA­mRNA were predicted by constructing a competing endogenous RNA regulatory network. It was found that 14,366 lncRNAs, 151 miRNAs and 9,377 mRNAs were differentially expressed in mice hearts after I/R compared with the Sham group (fold change >2; P<0.05). The results indicated that these differentially expressed genes were involved in multiple molecular functions, including 'guanosine diphosphate binding', 'RNA polymerase II carboxy­terminal domain kinase activity', 'TATA­binding protein­class protein binding', 'nicotinamide adenine dinucleotide binding' and 'protein phosphatase type 2A regulator activity'. The interactions between lncRNA­miRNA­mRNA, including five lncRNAs, 38 miRNAs and 196 mRNAs, were predicted, specifically Gm12040­mmu­miR­125a­5p­decapping mRNA 1B, Rpl7l1­ps1­mmu­miR­124­3p­G protein­coupled receptor 146, Gm11407­mmu­miR­190a­5p­homeobox and leucine zipper encoding (HOMEZ), 1600029O15Rik­mmu­miR­132­3p­HOMEZ and AK155692­mmu­miR­1224­3p­activating transcription factor 6ß. Collectively, these findings provided novel insights for future research on lncRNAs, miRNAs and mRNAs in myocardial I/R injury.

Aldehyde Dehydrogenase 2 Protects Against Post-Cardiac Arrest Myocardial Dysfunction Through a Novel Mechanism of Suppressing Mitochondrial Reactive Oxygen Species Production.

Post-cardiac arrest myocardial dysfunction significantly contributes to early mortality after the return of spontaneous circulation. However, no effective therapy is available now. Aldehyde dehydrogenase 2 (ALDH2) enzyme has been shown to protect the heart from aldehyde toxicity such as 4-hydroxy-2-nonenal (4-HNE) and oxidative stress. In this study, we evaluated the effect of enhanced activity or expression of ALDH2 on post-cardiac arrest myocardial dysfunction and survival in a rat cardiac arrest model. Furthermore, we elucidated the underlying mechanisms with a focus on mitochondrial reactive oxygen species (ROS) production in a cell hypoxia/reoxygenation model. A total of 126 rats were used for the ALDH2 activation or cardiac overexpression of ALDH2 studies. Randomization was done 10 min before the respective agonist injection or in vivo gene delivery. We showed that enhanced activity or expression of ALDH2 significantly improved contractile function of the left ventricle and survival rate in rats subjected to cardiac arrest-cardiopulmonary resuscitation procedure. Moreover, ALDH2 prevented cardiac arrest-induced cardiomyocyte death from apoptosis and mitochondrial damage. Mechanistically, 4-HNE, a representative substrate of ALDH2, was dominantly increased in the hypoxia/reoxygenation-exposed cardiomyocytes. Direct addition of 4-HNE led to significantly augmented succinate accumulation and mitochondrial ROS production. Through metabolizing 4-HNE, ALDH2 significantly inhibited mitochondrial ROS production. Our findings provide compelling evidence of the cardioprotective effects of ALDH2 and therapeutic targeting this enzyme would provide an important approach for treating post-cardiac arrest myocardial dysfunction.

Meta-analysis of risk factors for CCLNM in patients with unilateral cN0 PTC.

Background: In patients with papillary thyroid cancer (PTC) with clinical negative central lymph nodes (cN0), the use of prophylactic central lymph node dissection remains controversial. Contralateral central lymph node metastasis (CCLNM) occurs in 3.88­30.63% of patients with cN0 PTC. Therefore, the present meta-analysis aimed to obtain evidence for CCLNM risk factors in unilateral cN0 PTC. Materials and methods: Relevant studies were identified in the PubMed, SCIE, and Wanfang databases up to Oct 31, 2019. The included patients had undergone lobectomy or total thyroidectomy with bilateral central lymph node dissection and were diagnosed pathologically with PTC. Revman 5.3 software was applied for statistical analysis. Results: Thirteen studies comprising 2449 patients were included. The factors associated with increased CCLNM risk in patients with cN0 disease were: age <45 years (odds ratio (OR) = 1.89, 95% CI = 1.43­2.49, P < 0.00001), male sex (OR = 1.67, 95% CI = 1.24­2.24, P = 0.0007), extrathyroidal extension (OR = 1.63; 95% CI = 1.17­2.28; P = 0.004), tumor size ≥1 cm (OR = 2.63, 95% CI 1.85­3.74, P < 0.00001), lymphovascular invasion (OR = 4.27, 95% CI = 2.47­7.37, P < 0.00001), and ipsilateral central lymph node metastasis (OR = 11.42, 95% CI = 5.25­24.86, P < 0.00001). However, no association was found for capsular invasion, multifocality, or Hashimoto thyroiditis. Conclusion: The meta-analysis identified that age <45 years, tumor ≥1 cm, male sex, lymphovascular invasion, extrathyroidal extension, and ipsilateral central lymph node metastasis are related to CCLNM in patients with unilateral CN0 PTC. These factors should influence the use of prophylactic central lymph node dissection in this group of patients.

A small-molecule activator of mitochondrial aldehyde dehydrogenase 2 reduces the severity of cerulein-induced acute pancreatitis.

Acute pancreatitis (AP) is one of the leading causes of hospital admission for gastrointestinal disorders. Although lipid peroxides are produced in AP, it is unknown if targeting lipid peroxides prevents AP. This study aimed to investigate the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for lipid peroxide degradation, in AP and the possible underlying mechanisms. Cerulein was used to induce AP in C57BL/6 J male mice and pancreatic acinar cells were used to elucidate underlying mechanisms in vitro. Pancreatic enzymes in the serum, lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and Bcl-2, Bax and cleaved caspase-3 were measured. ALDH2 activation with a small-molecule activator, Alda-1, reduced the levels of the pancreatic enzymes in the serum and the lipid peroxidation products MDA and 4-HNE. In addition, Alda-1 decreased Bax and cleaved caspase-3 expression and increased Bcl-2 expression in vivo and in vitro. In conclusion, ALDH2 activation by Alda-1 has a protective effect in cerulein-induced AP by mitigating apoptosis in pancreatic acinar cells by alleviating lipid peroxidation.

[Correlation of phosphorylated S6 protein expression in blood and brain tissue in mice and rats with kainic acid-induced seizure].

OBJECTIVE: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. METHODS: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. RESULTS: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure,and the expression levels increased to (1.49±0.45) times (P<0.05) and (2.55±0.66) times (P <0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (P<0.01), which was consistent with the expression of P-S6 in brain tissue (r=0.8474, P<0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (P<0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (r=0.9385, P<0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. CONCLUSIONS: Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.

Assessment of treatment efficacy using surface-enhanced Raman spectroscopy analysis of urine in rats with kidney transplantation or kidney disease.

BACKGROUND: Individuals who have kidney disease or kidney transplants need routine assessment of their kidney damage and function, which are largely measured based on histological examination of kidney biopsies, blood test, and urinalysis. These methods are practically difficult or inconvenient, and expensive. The objective of this study was to develop a model to estimate the kidney damage and function by surface-enhanced Raman spectroscopy (SERS). METHODS: Urine samples were collected from two previous studies: renal allograft recipient Lewis rats receiving anti-TGF-ß antibody or control antibody treatment and obese diabetic ZSF1 rats with kidney disease fed with whole grape powder-containing chow or control chow. Silver nanoparticle-based SERS spectra of urine were measured. SERS spectra were analyzed using principal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squires (PLS) analysis. RESULTS: PCA/LDA separated anti-TGF-ß antibody-treated group from control group with 90% sensitivity and 70% specificity in kidney transplants, and grape-fed group from controls with 72.7% sensitivity and 60% specificity in diabetic kidneys. The receiver operating characteristic curves showed that the integration area under the curve was 0.850 ± 0.095 (p = 0.008) in kidney transplant groups and 0.800 ± 0.097 (p = 0.02) in diabetic kidney groups. PLS predicted the biochemical parameters of kidney function using the SERS spectra, resulting in R2 = 0.8246 (p < 0.001,urine protein), R2 = 0.8438 (p < 0.001, urine creatinine), R2 = 0.9265 (p < 0.001, urea), R2 = 0.8719 (p < 0.001, serum creatinine), and R2 = 0.6014 (p < 0.001, urine protein to creatinine ratio). CONCLUSION: Urine SERS spectral analysis suggesting that it may become a convenient method for rapid assessment of renal impairment.

Aldehyde dehydrogenase 2 activation ameliorates cyclophosphamide-induced acute cardiotoxicity via detoxification of toxic aldehydes and suppression of cardiac cell death.

Cyclophosphamide (CY)-induced acute cardiotoxicity is a common side effect which is dose dependent. It is reported that up to 20% of patients received high dose of CY treatment suffered from acute cardiac dysfunction. However, the effective intervention strategies and related mechanisms are still largely unknown. We aimed to investigate the effects of aldehyde dehydrogenase 2 (ALDH2), an important endogenous cardioprotective enzyme, on CY-induced acute cardiotoxicity and the underlying mechanisms. It was found that ALDH2 knockout (KO) mice were more sensitive to CY-induced acute cardiotoxicity, presenting as higher serum levels of creatine kinase-MB isoform and lactate dehydrogenase, and significantly reduced myocardial contractility compared with C57BL/6 (WT) mice. In addition, cardiac cell death, especially necrosis, was obviously increased in ALDH2 KO mice compared with WT mice after CY treatment. Furthermore, accumulation of toxic aldehydes such as acrolein and 4-HNE and reactive oxygen species (ROS) in the myocardium were significantly elevated after CY in ALDH2 KO mice. Importantly, ALDH2 activation by Alda-1 pretreatment markedly attenuated CY-induced accumulation of toxic aldehydes, cardiac cell death and cardiac dysfunction, without affecting CY's anti-tumor efficacy. In conclusion, the cardioprotective effects of ALDH2 activation against CY-induced acute cardiotoxicity are exerted via reducing toxic aldehydes accumulation and potentially interrupting the acrolein-ROS-aldehydes vicious circles, and thus alleviates myocardial cell death, without antagonizing the anti-tumor efficacy of CY. Therefore, ALDH2 might be a promising prevention and treatment target for CY-induced acute cardiotoxicity.