Lysophosphatidic acid contributes to myocardial ischemia/reperfusion injury by activating TRPV1 in spinal cord.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that plays a crucial role in cardiovascular diseases. Here, we question whether LPA contributes to myocardial ischemia/reperfusion (I/R) injury by acting on transient receptor potential vanilloid 1 (TRPV1) in spinal cord. By ligating the left coronary artery to establish an in vivo I/R mouse model, we observed a 1.57-fold increase in LPA level in the cerebrospinal fluid (CSF). The I/R-elevated CSF LPA levels were reduced by HA130, an LPA synthesis inhibitor, compared to vehicle treatment (4.74 ± 0.34 vs. 6.46 ± 0.94 µg/mL, p = 0.0014). Myocardial infarct size was reduced by HA130 treatment compared to the vehicle group (26 ± 8% vs. 46 ± 8%, p = 0.0001). To block the interaction of LPA with TRPV1 at the K710 site, we generated a K710N knock-in mouse model. The TRPV1K710N mice were resistant to LPA-induced myocardial injury, showing a smaller infarct size relative to TRPV1WT mice (28 ± 4% vs. 60 ± 7%, p < 0.0001). Additionally, a sequence-specific TRPV1 peptide targeting the K710 region produced similar protective effects against LPA-induced myocardial injury. Blocking the K710 region through K710N mutation or TRPV1 peptide resulted in reduced neuropeptides release and decreased activity of cardiac sensory neurons, leading to a decrease in cardiac norepinephrine concentration and the restoration of intramyocardial pro-survival signaling, namely protein kinase B/extracellular regulated kinase/glycogen synthase kinase-3ß pathway. These findings suggest that the elevation of CSF LPA is strongly associated with myocardial I/R injury. Moreover, inhibiting the interaction of LPA with TRPV1 by blocking the K710 region uncovers a novel strategy for preventing myocardial ischemic injury.

Analysis on the physiological changes of residents before and during the COVID-19 pandemic: A cross-sectional study.

People's lifestyles have changed dramatically during the coronavirus disease 2019 (COVID-19) pandemic, yet data on physical examinations in the Chinese population before and during the pandemic are rarely reported. The study was based on the data from the physical examination center of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. We collected the data of physical examinations information between January 2017 and March 2022. The data of participants before December 31, 2019 were classified as "before COVID-19 pandemic group," while data after December 31, 2019 were classified as "during COVID-19 pandemic group." We used t-test and χ2  test to compare the differences before and during COVID-19 pandemic. A total of 72 257 individuals participated in the physical examinations, and finally retained 65 629 individuals for analysis. During the COVID-19 pandemic, body mass index (BMI), high-density lipoprotein, total cholesterol levels, as well as pulmonary nodule and thyroid nodule proportion of participants were higher than those before the pandemic, and the levels of systolic blood pressure and diastolic blood pressure of participants were lower than those before the pandemic. Ongoing assessment and surveillance are necessary to assess whether lifestyle changes caused by the COVID-19 pandemic are likely to increase chronic disease risk in the future.

Characteristics of intestinal flora in patients with cerebral infarction complicated with Type 2 diabetes mellitus. / 脑梗死合并2åž‹ç³–å°¿ç— æ‚£è€ çš„è‚ é“èŒç¾¤ç‰¹å¾(英文).

OBJECTIVES: The intestinal microbial characteristics of patients with simple cerebral infarction (CI) and CI complicated with Type 2 diabetes mellitus (CI-T2DM) are still not clear. This study aims to analyze the differences in the variable characteristics of intestinal flora between patients simply with CI and CI-T2DM. METHODS: This study retrospectively collected the patients who were admitted to the Affiliated Hospital of Putian University from September 2021 to September 2022. The patients were divided into a CI group (n=12) and a CI-T2DM group (n=12). Simultaneously, 12 healthy people were selected as a control group. Total DNA was extracted from feces specimens. Illumina Novaseq sequencing platform was used for metagenomic sequencing. The Knead Data software, Kraken2 software, and Bracken software were applied for sequencing analysis. RESULTS: At phylum level, the average ratio of Firmicutes, Bacteroidetes, and Proteobacteria in the CI-T2DM group were 33.07%, 54.80%, and 7.00%, respectively. In the CI group, the ratios of each were 14.03%, 69.62%, and 11.13%, respectively, while in the control group, the ratios were 50.99%, 37.67%, and 5.24%, respectively. There was significant differences in the distribution of Firmicutes (F=6.130, P=0.011) among the 3 groups. At the family level, compared with the CI group, the relative abundance of Eubacteriaceae (t=8.062, P<0.001) in the CI-T2DM group was significantly increased, while Corynebacteriaceae (t=4.471, P<0.001), Methanobacteriaceae (t=3.406, P=0.003), and Pseudomonadaceae (t=2.352, P=0.028) were decreased significantly. At the genus level, compared with the CI group, there was a relative abundance of Cutibacterium (t=6.242, P<0.001), Eubacterium (t=8.448, P<0.001), and Blautia (t=3.442, P=0.002) in the CI-T2DM group which was significantly increased. In terms of Methanobrevibacter (t=3.466, P=0.002), Pyramidobacter (t=2.846, P=0.009) and Pseudomonas (t=2.352, P=0.028), their distributions were decreased significantly in the CI-T2DM group. At the species level, compared with the CI group, the relative abundance of Cutibacterium acnes (t=6.242, P<0.001) in the CI-T2DM group was significantly increased, while Pseudomonas aeruginosa (t=2.352, P=0.028) was decreased significantly. Still at the genus level, linear discriminant analysis effect size (LEfSe) analysis showed that the distributions of Pseudomonas and Blautia were determined to be the most significantly different between the CI-T2DM and the CI group. At the species level, the total number of operational taxonomic units (OTUs) in the 3 groups was 1 491. There were 169, 221, and 192 kinds of OTUs unique to the CI-T2DM, CI, and control group, respectively. CONCLUSIONS: From phylum level to species level, the composition of intestinal flora in the patients with CI-T2DM is different from those in the patients simply with CI. The change in the proportion of Firmicutes, Bacteroidetes and Proteus compared with the healthy population is an important feature of intestinal flora imbalance in the patients with CI and with CI-T2DM. Attention should be paid to the differential distribution of Bacteroides monocytogenes and butyrate producing bacteria.

Inhibition of DRG-TRPV1 upregulation in myocardial ischemia contributes to exogenous cardioprotection.

Myocardium ischemia-reperfusion injury (IRI) is the major cause of postoperative cardiac dysfunction. While intrathecal morphine preconditioning (ITMP) can reduce IRI in animals, the molecular processes underlying IRI and ITMP remain elusive. Transient receptor potential vanilloid type 1 (TRPV1) is highly expressed in cardiac sensory neurons and has a crucial role in detecting myocardial ischemia. This study aimed to determine the role of up-regulated dorsal root ganglion (DRG)-TRPV1 in IRI and whether its inhibition contributes to ITMP-induced cardioprotection. Animal model of IRI was established by left coronary artery occlusion (30 min) and reperfusion (2 h) in rats. Intrathecal intubation was prepared for morphine preconditioning, TRPV1-shRNA or selective TRPV1 antagonist administration. After IRI, both protein and phosphorylation levels of TRPV1 were significantly increased, and the immunofluorescence intensity of TRPV1 was increased and colocalized with µ-opioid receptors in DRG. Intrathecal pre-administration of either TRPV1-shRNA or TRPV1 antagonist significantly reduced myocardial injury and the upregulation of TRPV1 in DRG induced by IRI. Simultaneously, ITMP significantly suppressed TRPV1 protein expression and phosphorylation in DRG, as well as the heart infarct size and arrhythmia score caused by IRI. The suppression of TRPV1 elevation and activation by ITMP were reversed by intrathecal injection of the selective µ receptor antagonist. Furthermore, IRI elevated DRG cAMP, while intrathecal administration of the selective cAMP-PKA inhibitor reduced myocardial injury. Finally, we showed that activation of opioid receptor by morphine inhibited PKA activator-induced TRPV1 channel activity at the cellular level. These findings suggest that the elevation and activation of TRPV1 in DRG during myocardial ischemia-reperfusion might be responsible for cardiac injury. ITMP exerts cardioprotection by inhibiting DRG-TRPV1 activity via modulation cAMP. Therefore, inhibition of TRPV1 upregulation in DRG might be used as a novel therapeutic mechanism for myocardium ischemia-reperfusion injury.

Splicing repression is a major function of TDP-43 in motor neurons.

Nuclear depletion of TDP-43, an essential RNA binding protein, may underlie neurodegeneration in amyotrophic lateral sclerosis (ALS). As several functions have been ascribed to this protein, the critical role(s) of TDP-43 in motor neurons that may be compromised in ALS remains unknown. We show here that TDP-43 mediated splicing repression, which serves to protect the transcriptome by preventing aberrant splicing, is central to the physiology of motor neurons. Expression in Drosophila TDP-43 knockout models of a chimeric repressor, comprised of the RNA recognition domain of TDP-43 fused to an unrelated splicing repressor, RAVER1, attenuated motor deficits and extended lifespan. Likewise, AAV9-mediated delivery of this chimeric rescue repressor to mice lacking TDP-43 in motor neurons delayed the onset, slowed the progression of motor symptoms, and markedly extended their lifespan. In treated mice lacking TDP-43 in motor neurons, aberrant splicing was significantly decreased and accompanied by amelioration of axon degeneration and motor neuron loss. This AAV9 strategy allowed long-term expression of the chimeric repressor without any adverse effects. Our findings establish that splicing repression is a major function of TDP-43 in motor neurons and strongly support the idea that loss of TDP-43-mediated splicing fidelity represents a key pathogenic mechanism underlying motor neuron loss in ALS.

Intrathecal lentivirus-mediated RNA interference targeting nerve growth factor attenuates myocardial ischaemia-reperfusion injury in rat.

BACKGROUND: Nerve growth factor (NGF) has been implicated in hyperalgesia by sensitising nociceptors. A role for NGF in modulating myocardial injury through ischaemic nociceptive signalling is plausible. We examined whether inhibition of spinal NGF attenuates myocardial ischaemia-reperfusion injury and explored the underlying mechanisms. METHODS: In adult rats, lentivirus-mediated short-hairpin RNA targeted at reducing NGF gene expression (NGF-shRNA) or a transient receptor potential vanilloid 1 (TRPV1) antagonist (capsazepine) was injected intrathecally before myocardial ischaemia-reperfusion. Infarct size (expressed as the ratio of area at risk) and risk of arrhythmias were quantified. Whole-cell clamp patch electrophysiology was used to record capsaicin currents in primary dorsal root ganglion neurones. The co-expression of substance P (SP) and calcitonin gene-related peptide (CGRP), plus activation of TRPV1, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) were also quantified. RESULTS: NGF levels increased by 2.95 (0.34)-fold in dorsal root ganglion and 2.12 (0.27)-fold in spinal cord after myocardial ischaemia-reperfusion injury. Intrathecal injection of NGF-shRNA reduced infarct area at risk from 0.58 (0.02) to 0.37 (0.02) (P<0.01) and reduced arrhythmia score from 3.67 (0.33) to 1.67 (0.33) (P<0.01). Intrathecal capsazepine was similarly cardioprotective. NGF-shRNA suppressed expression of SP/CGRP and activation of Akt/ERK and TRPV1 in spinal cord. NGF increased capsaicin current amplitude from 144 (42) to 840 (132) pA (P<0.05), which was blocked by the TRPV1 antagonist 5'-iodoresiniferatoxin. Exogenous NGF enhanced capsaicin-induced Akt/ERK and TRPV1 activation in PC12 neuroendocrine tumour cells in culture. CONCLUSIONS: Spinal NGF contributes to myocardial ischaemia-reperfusion injury by mediating nociceptive signal transmission.

Whole-Exome Sequencing Reveals Novel Genetic Variation for Dilated Cardiomyopathy in Pediatric Chinese Patients.

Dilated cardiomyopathy (DCM) is characterized by left or bilateral ventricular dilation and systolic dysfunction without rational conditions, which can lead to progressive heart failure and sudden cardiac death. Most of the pathogenic genes have been reported in adult population by locus mapping in familial cases and animal model studies. However, it still remains challenging to decipher the role of genetics in the etiology of pediatric DCM. We applied whole-exome sequencing (WES) for 30 sporadic pediatric DCM subjects and 100 non-DCM local controls. We identified the pathogenic mutations using bioinformatics tools based on genomic strategies synergistically and confirmed mutations by Sanger sequencing. We identified compound heterozygous nonsense mutations in DSP (c.3799C > T, p.R1267X; c.4444G > T, p.E1482X). In sporadic cases, the two heterozygous mutations in XIRP2 were identified. Then we performed an exome-wide association study with 30 case and 100 control subjects. Interestingly, we could not identify TTN truncating variants in all cases. Collectively, we observed a significant risk signal between carriers of TTN deleterious missense variants and DCM risk (odds ratio 4.0, 95% confidence interval 1.1-22.2, p = 3.12 × 10-2). Our observations expanded the spectrum of mutations and were valuable in the pre- and postnatal screening and genetic diagnosis for DCM.

Posterior corneal stability after small incision lenticule extraction with different optical zones.

BACKGROUND: To assess the changes in the posterior corneal surface following small incision lenticule extraction (SMILE) with different optical zones. METHODS: In this retrospective study, 106 eyes of 106 patients who underwent SMILE were recruited 3 years after the procedure. Eyes were divided into two groups according to the size of the surgical optical zone: group A (52 eyes, ≤6.2 mm) and group B (54 eyes, ≥6.5 mm). Posterior central elevation (PCE) and 12 other points at 45°, 135°, 225° and 315° with distances of 1 mm, 2 mm and 3 mm from the centre were recorded from Pentacam. RESULTS: No iatrogenic keratectasia was identified, and eyes in the two groups showed comparable visual results. The overall trend in posterior corneal elevation changes was consistent for both groups. PCE decreased significantly from 1.33 ± 2.32 to 0.75 ± 2.41 in group A (P = 0.024) and from 0.87 ± 2.61 to 0.06 ± 2.74 in group B (P = 0.003). All points in the central 2 mm region in both groups were reduced postoperatively. In the 4 mm and 6 mm corneal annulus, almost all points at 225°and 315° showed backward displacement, with the most prominent change occurring at 315° in the 6 mm annulus (P < 0.001), indicating no forward protrusion in the inferior area. CONCLUSIONS: No forward protrusion in the posterior corneal surface was observed 3 years after SMILE with different optical zones. Comprehensive preoperative measurements are essential for ensuring corneal stability and avoiding iatrogenic keratectasia.

[The Study of PI3K-â ¢ Like Functional Polypeptide on Leukemia Cell K562 during the Process of Programmed Cell Death].

OBJECTIVE: To study the molecular mechanism of PI3K-Ⅲ like functional domain inducing programmed cell death of leukemia cell line K562. METHODS: The purified PI3K-Ⅲ like functional domain protein was obtained by Pichia pastoris expression system. MTT assay and colony-forming assay were used to detect the effects of PI3K-Ⅲ like functional domain protein on K562 cell proliferation. The effects of PI3K-Ⅲ like functional domain protein on apoptosis and cell cycle of on K562 cells were detected by flow cytometry. The ultrastructural changes were detected by transmission electron microscopy. The expression of caspase-3 was detected by ELISA. The protein expressions of ATG4B, Beclin-1, Bcl-2 and LC3-II were evaluated by Western blot. RESULTS: PI3K-Ⅲ like functional domain protein could inhibit the proliferation and clony formation of K562 cells, which was significantly higher than the control group (P<0.05). In the experimental group, apoptosis and autophagosome were shown in K562 cells. The proportion of cells in G0/G1 phase increased significantly, while in S phase decreased significantly. Cell growth mostly stagnated in G0/G1 phase, which was significantly different from the control group (P<0.05). With the increase of concentration, the expression of caspase-3 protein increased significantly compared with the control group (r=0.966, P<0.05). The expression of ATG4B and beclin-1 appeared from increase to decrease, LC3-II increased while Bcl-2 decreased at different time points. CONCLUSION: PI3K-Ⅲ like functional polypeptide could induce programmed cell death of leukemia cell K562. Beclin-1/Bcl-2 and caspase pathway may be involved in this way, which suggesting meant autophagy and apoptosis may work together at the same time.

Case Report: Rare Iliac Vein Compression (May-Thurner) Syndrome in a Pediatric Patient.

Iliac vein compression syndrome (IVCS) or May-Thurner syndrome occurs predominantly in young to middle-aged women. Here we reported a case of IVCS in a 5-year-old boy. The child was admitted to our vasculocardiology department with left lower extremity that had been swollen for 1 month. Blood tests revealed coagulation routine and platelets in the normal ranges. Computer tomography angiography (CTA) and magnetic resonance imaging (MRI) showed the left common iliac vein had become narrow before it entered the right common iliac vein. To further clarify, we performed angiography, which clearly showed the stenosis and the blood return of the left common iliac vein. So IVCS was diagnosed. What is more, we found the aorta descended to the right of the spine, and this may be the reason for the apparent compression of the left common iliac vein. Given the young age and mild symptoms of the child, the treatment was conservative mainly including elevation of the affected limb, wearing medical elastic socks, and short-term oral aspirin for anticoagulation. Meanwhile, the boy is being followed up closely. If the swelling of the left lower extremity significantly increases, stent placement may need to be considered in the future.

Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias.

Objective: Voltage-gated sodium channel Nav1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro. Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5' end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818*)] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.

Facilitated transport of nTiO2-kaolin aggregates by bacteria and phosphate in water-saturated quartz sand.

The soil major component of clay plays an important role in governing the fate and transport of engineered nanomaterials (e.g., the most commonly used titanium dioxide nanoparticles; nTiO2) in the subsurface environments via forming nTiO2-clay aggregates. This research is designed to unravel the interplay of naturally-occurring bacteria (Escherichia coli) and phosphate on the transport and retention of nTiO2-kaolin aggregates in water-saturated porous media. Our results showed that nTiO2-nTiO2 homoaggregates and nTiO2-kaolin heteroaggregates dominated in the nTiO2-kaolin nanoaggregate suspension. Transport of nTiO2-kaolin aggregates was enhanced with the copresence of E. coli and phosphate, particularly at the low pH of 6.0. This effect is due to the greater adsorption of phosphate and thus the greater enhancement in repulsive interaction energies between aggregates and sand grains at pH 6.0 (vs. pH 9.0). The charged "soft layer" of E. coli cell surfaces changed the aggregation state and the heterogeneous distribution of nTiO2-kaolin aggregates, and subsequently stabilized the nTiO2-nTiO2 homoaggregates and nTiO2-kaolin heteroaggregates via TEM-EDX measurements and promoted the physical segregation between the aggregates (separation distance = 0.486 vs. 0.614 µm without vs. with the presence of E. coli) via 2D/3D AFM identifications, both of which caused greater mobility of nTiO2-kaolin aggregates with the presence of E. coli. Nonetheless, transport of nTiO2-kaolin aggregates was lower with the copresence of E. coli and phosphate vs. the singular presence of phosphate due to the competitive adsorption of less negatively charged E. coli (vs. phosphate) onto the aggregates. Taken altogether, our findings furnish new insights into better understanding the fate, transport, and potential risks of nTiO2 in real environmental settings (soil and sediment aquifer) where clay, bacteria, and phosphate ubiquitously cooccur.

Left Bundle Pacing for Left Bundle Branch Block and Intermittent Third-Degree Atrioventricular Block in a MYH7 Mutation-Related Hypertrophic Cardiomyopathy With Restrictive Phenotype in a Child.

Hypertrophic cardiomyopathy (HCM) is a group of myocardial diseases defined by cardiac hypertrophy which cannot be explained by secondary causes with a non-dilated left ventricle and preserved or increased ejection fraction. Sometimes it can be combined with restrictive cardiomyopathy. Here we describe a very rare case of a 12-year-old girl with non-obstructive hypertrophic cardiomyopathy accompanied by restrictive phenotype, complete left bundle branch block and intermittent third-degree atrioventricular block, who presented with recurrent syncope. Her father was also found to have hypertrophic cardiomyopathy and treated with implantable cardioverter defibrillator for ventricular tachycardia. Her younger brother is currently asymptomatic but echocardiogram showed hypertrophic cardiomyopathy. Genetic analysis identified a heterozygous missense mutation (c.2155C>T, p.R719W) of MYH7 in the proband girl, her father and her brother. The girl was treated with left bundle pacing and recovered well. The case we present further demonstrates the feasibility of left bundle pacing in children.

Case Report: Identification of Mutations in LAMP2 in Two Chinese Infants With Danon Disease.

Danon disease (DD) is a monogenic lysosomal storage disorder characterized by cardiomyopathy, skeletal myopathy, and variable degrees of intellectual disability. It is caused by a deficiency of lysosomal-associated membrane protein 2 (LAMP2). Two unrelated boys who presented with severe hypertrophic cardiomyopathy and elevated levels of liver enzymes, and were diagnosed with Danon disease at a very young age, were investigated. One boy was diagnosed at 4 months old and died soon after; his mother also died of hypertrophic cardiomyopathy shortly after his birth. Another developed hypertrophic cardiomyopathy at 3 months old but reported no significant cardiovascular symptoms during more than 5 years follow-up. Genetic screening found compound variants of LAMP2 and MYH7 in both of them. This report highlights the clinical heterogeneity in DD. The timely identification of LAMP2 mutation plays a critical role in their treatment and family counseling.

Spinal NGF induces anti-intrathecal opioid-initiated cardioprotective effect via regulation of TRPV1 expression.

Evidences from previous studies confirmed that intrathecal morphine preconditioning (ITMP) reduces the cardiac injury of ischemia-reperfusion (IR) via the central nervous system. However, the molecular mechanism is not fully understood. The breath of central nerve growth factor (NGF) during nociceptive transmission has been well documented, and little is known about the significance of NGF in myocardial injury of IR and intrathecal morphine-induced cardioprotection. To address these questions, we over-expressed or silenced NGF in the spinal cord by using intrathecal injection of lentivirus-NGF or shRNA respectively, accompanied by ITMP in the IR rat model. The levels of NGF and tropomyosin receptor kinase A (Trka) as well as transient receptor potential vanilloid 1 (TRPV1) in the T2-6 spinal cord were evaluated. The results showed that cardiac damage indicators induced by IR, including the increased infarct size, arrhythmia score and serum troponin levels were attenuated after ITMP. However, overexpression of spinal NGF significantly reversed these decreases, as well as reduced the expression and phosphorylation of TRPV1 that was elicited by ITMP. Conversely, silencing of spinal NGF enhanced ITMP-induced cardioprotective effects. Phosphorylation and expression of TRPV1 in the spinal cord were significantly decreased after regional NGF silencing. These findings suggested that the cardioprotective effects of ITMP may implement by mediating through spinal NGF expression, wherein it involves the nociceptor TRPV1. NGF may act as a potential therapeutic target in the development of new agents for the treatment of cardiac injury induced by IR.

Effect of myocardial ischemic preconditioning on ischemia-reperfusion stimulation-induced activation in rat thoracic spinal cord with functional MRI.

BACKGROUND: Myocardial ischemia and reperfusion-evoked spinal reflexes involve nociceptive signals that trigger neuronal excitation through cardiac afferents, projecting into the thoracic spinal cord. Ischemic preconditioning (IPC) involves brief episodes of sublethal ischemia and reperfusion enhances the resistance of the myocardium to subsequent ischemic insults. This study investigated the effects of IPC on ischemia-reperfusion (I/R) stimulation-induced activation in the thoracic spinal cord of rats. METHODS: A new remotely controlled I/R model was established. The infarct size was determined as a percentage of area at risk (IS/AAR) and arrhythmia scores were evaluated. Non-invasive in vivo fMRI was used for signal quantitative analysis of thoracic spinal spatiotemporal. The role of IPC on the excitability of substantia gelatinosa (SG) neurons was assessed by spinal patch clamp recording technique. The altered expressions of c-Fos, SP, and CGRP in T4 segment were detected by immunohistochemical staining. RESULTS: The novel I/R model was induced successfully and reliably utilized, and IPC treatment markedly reduced the myocardial infarct size. fMRI analysis revealed that IPC reduced the increased BOLD signals induced by prolonged ischemia-reperfusion. Patch clamp recording showed that IPC treatment reversed the enhanced excitability of SG neurons during I/R treatment. The results of immunofluorescent staining indicated that IPC mitigated the I/R-induced dramatic increase of c-Fos, and reduced the release of SP and CGRP in dorsal horns of spinal cord. CONCLUSIONS: These results suggested that IPC suppressed neuronal activation induced by I/R stimuli in rat thoracic spinal cord using spinal cord fMRI and patch clamp recording techniques.

Synergetic effect of hydrochar on the transport of anatase titanium dioxide nanoparticles in the presence of phosphate in saturated quartz sand.

The rapid development of nanomaterials has led to the unavoidable leakage and release of nanoparticles (NPs) into soil and the underlying groundwater. It is possible for chars and phosphate introduced into soil to improve crop soil properties by improving contact with NPs. In this study, the influences of hydrochar and/or phosphate on the anatase nTiO2 transport behaviors were investigated under different conditions. The breakthrough curves (BTCs) and retention profiles were obtained by the saturated sand column experiments. The additional analysis of zeta potentials, sedimentation kinetics, Raman mapping, and the two-site kinetic attachment model (TSKAM) was conducted to explore the possible underlying mechanisms. The simultaneous presence of phosphate and hydrochar acted in a synergetic fashion to enhance the transport of nTiO2 in a sand medium compared to the facilitated effect of single phosphate or hydrochar. The higher levels of hydrochar induce the more nTiO2 in the high IC solution passing through the saturated sand columns in the co-presence of phosphate. It was attributed to the competitive adsorption of hydrochar with nTiO2 to the sand site and the phosphate adsorption on nTiO2 occurred simultaneously through the sand columns. The fitting results of BTCs using TSKAM showed that the value of k2 for nTiO2 (the irreversible attachment coefficient at site 2) was smaller than that of k1d/k1 (the first-order reversible detachment and attachment coefficient at site 1, respectively), suggesting irreversible retention of anatase nTiO2 at site 1. The value of k1d/k1 could be better used to explain the retention of nTiO2 with combined phosphate and hydrochar. This study provides insight into the implications of phosphate and/or hydrochar for nTiO2 transport in crop soil environments. Graphical abstract ᅟ.

Effects of Escherichia coli and phosphate on the transport of titanium dioxide nanoparticles in heterogeneous porous media.

Transport behaviors of titanium dioxide nanoparticles (nTiO2) were examined in the individual- and co-presence Escherichia (E.) coli and phosphate in heterogeneous sand (uncoated and iron oxyhydroxide-coated sand) columns. The results showed that for the individual presence of phosphate, the degree of nTiO2 deposition was less in uncoated than in iron oxide-coated sands. In contrast, an opposite trend that greater deposition of nTiO2 in uncoated than in coated sands occurred in the individual presence of E. coli. These observations are due to the phosphate adsorption changing the charge of NPs and iron oxyhydroxide-coated sand, or the preferential adhesion of bacterial to coated sand. In the copresence of E. coli and phosphate, interestingly, the phosphate level plays an important role in influencing nTiO2 transport. At a high phosphate concentration (>1.0 mM), the deposition of nTiO2 with the individual presence of E. coli was stronger than nTiO2 in the copresence of both E. coli and phosphate, regardless of sand type. The potential mechanism was that phosphate adsorption led to the formation of more negatively charged NPs-bacteria complexes that have higher mobility in sand columns. At a low phosphate level (≤0.1 mM), a similar observation occurred in uncoated sand. Nevertheless, the deposition of nTiO2 with copresence of E. coli and phosphate was greater than nTiO2 with E. coli in oxyhydroxide-coated sand. It was attributed to the formation of large NPs-bacteria-phosphate clusters (less mobile) and the preferential adhesion of E. coli cells to iron oxyhydroxide coating simultaneously. Taken together, our findings provide crucial knowledge for better understanding the fate, transport, and potential risks of engineered nanoparticles in complicated environmental settings where bacteria and phosphate are ubiquitous.

Age-Related Changes in Corneal Spherical Aberration.

PURPOSE: To analyze the age-related changes in corneal spherical aberration (CSA) and higher order aberrations (HOAs) and to develop a novel model to estimate the change in CSA with age. METHODS: This was a cross-sectional study of the right eyes of 3,769 patients. Anterior corneal spherical aberration (ASA), posterior corneal spherical aberration (PSA), total corneal spherical aberration (TSA), and the root mean square of corneal HOAs were measured using a Scheimpflug tomographer. Smoothed fitting curves were plotted as a function of age and the average change in spherical aberration was calculated for different ages. RESULTS: The mean magnitude of ASA, PSA, TSA, and HOAs (6 and 4 mm) were 0.270 ± 0.111, -0.144 ± 0.031, 0.228 ± 0.120, 0.453 ± 0.194, and 0.141 ± 0.075 µm, respectively. All parameters showed a statistically significant non-linear change with age. The age after which the aberrations increased at a faster rate, namely the turning points of age, were 39 years for ASA, PSA, TSA, and 6-mm HOAs (95% confidence interval [CI]: 35 to 42, 36 to 41, 36 to 42, and 35 to 56 years, respectively) and 46 years for 4-mm HOAs (95% CI: 36 to 56 years). There were significant increases in increment rates after the turning points. The average change of TSA was -0.013 µm/10 years from 18 to 39 years and 0.057 µm/10 years after 39 years. There were statistically significant correlations between ASA and TSA (r = 0.976, P < .001) and PSA and TSA (r = 0.192, P < .001), but not between ASA and PSA (r = -0.003, P = .835). CONCLUSIONS: CSA and HOAs increased non-linearly with age and became more positive after 39 and 46 years of age, respectively. Based on the increment rates and turning points of age, a novel model is provided to help calculate the value required to compensate for the increasing CSA associated with the aging cornea. [J Refract Surg. 2018;34(11):760-767.].

Facilitated transport of titanium dioxide nanoparticles via hydrochars in the presence of ammonium in saturated sands: Effects of pH, ionic strength, and ionic composition.

The widespread use of nanoparticles (NPs) has led to their inevitable introduction into environmental systems. How the existence of hydrochars in crop soils will affect the mobility of nanoparticle titanium dioxide (nTiO2), especially in the presence of ammonium (NH4+), remains unknown. Research is needed to study the effects of hydrochars on the transport and retention of nTiO2 and to uncover the mechanisms of these effects on nTiO2 transport. Column experiments with nTiO2 and hydrochars were performed in various electrolyte (NaCl, NH4Cl, and CaCl2) solutions under a controlled pH (6.0 and 8.0). Additionally, the size distributions and scanning electron microscope (SEM) and transmission electron microscope (TEM) images of the NPs were observed. The experimental results suggested that the mobility of the hydrochars was much better than that of nTiO2. Thus, the mobility of nTiO2 was improved upon their attachment to the hydrochars. The facilitated transport of nTiO2 in the presence of hydrochars was stronger at pH8.0 than at pH6.0, and facilitated transport was nearly independent of the electrolyte cation at pH8.0. However, at pH6.0, the facilitated transport in various electrolytes had the following order: NaCl>NH4Cl>CaCl2. The conversion from a completely reversible to a partially irreversible deposition of nTiO2 in sand was induced by the partially irreversible retention of hydrochars, and this phenomenon was more pronounced in the presence of NH4+ than in the presence of Na+. In particular, the irreversible deposition of nTiO2-hydrochars was enhanced as the cation concentration increased. The increased irreversible retention of nTiO2 was related to the greater k2 value (irreversible attachment coefficients) on site 2 for hydrochars based on two-site kinetic retention modeling. Thus, there is a potential risk of contaminating crops, soil, and underground water when nTiO2 exists in a hydrochar-amended environment, especially when associated with NH4-N fertilizer.