Global risk factor analysis of myopia onset in children: A systematic review and meta-analysis.

INTRODUCTION: This work aimed to comprehensively assess the risk factors affecting myopia in children to develop more effective prevention and treatment strategies. To this end, data from database were employed to assess the relationship between the incidence of myopia and its risk factors. METHODS: We searched eight databases online in June 2022. Cohort studies were included that measured the connection between risk factors and myopia. Eligibility was not restricted by language. The Newcastle-Ottawa Scale (NOS) was used to measure the risk of bias and conducted GRADE evaluation to determine the certainty of evidence. Potential risk factors with positive or negative results were seen. Inplasy Registration: https://inplasy.com/inplasy-2022-4-0109/. RESULTS: Evidence that risk factors for myopia are mixed, comprising both positive (20) and null (17) findings. In 19 cohort studies on 3578 children, girls were more likely to develop myopia (RR: 1.28 [1.22-1.35]). Myopia can occur at any age, from early childhood to late adulthood. Children whose parents had myopia were more likely to develop myopia. Longer outdoor activities time (RR: 0.97 [0.95-0.98]) and less near-work time (RR: 1.05 [1.02-1.07]) appeared to be significantly decrease the incidence of myopia. Children with lower SE, longer AL, a lower magnitude of positive relative accommodation, worse presenting visual acuity, deeper anterior chamber, and thinner crystalline lens may be related to myopia onset. The burden of myopia in underprivileged countries is higher than in developed countries (RR: 5.28 [2.06-13.48]). The quality of evidence for the evaluated factors was moderate to low or very low. CONCLUSIONS: Genetic factors, environmental factors (such as excessive use of electronic products, and poor study habits) and lifestyle factors (such as lack of outdoor activities, poor nutrition, etc.) are the main risk factors for myopia in children. Myopia prevention strategies should be designed based on environmental factors, gender, parental myopia and eye indicators in order to explore a lifestyle that is more conducive to the eye health of children.

Carbon dots-mediated synthesis of gold nanodendrites with extended absorption into NIR-II window for in vivo photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT. RESULTS: By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI. CONCLUSIONS: We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window.

Tuning the Organ Tropism of Polymersome for Spleen-Selective Nanovaccine Delivery to Boost Cancer Immunotherapy.

The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non-specific distribution in non-targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver- and spleen-selective delivery is reported. By using a library screening approach, spleen-targeted polymersome PH9-Aln-8020 and liver-targeted polymersome PA9-ZP3-5050 are identified accordingly. Meanwhile, the second near-infrared (NIR-II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9-Aln-8020 is employed as a systemic nanocarrier to co-deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ-selective delivery and other biomedical applications.

Study on the influence mechanism of adoption of smart agriculture technology behavior.

Smart agricultural (SA) technology has become a technological support for modern agriculture. By exploring the decision-making process and psychological motivation of farmers in adopting SA technology, it is conducive to achieving the popularisation of SA technology and promoting the modernisation of agriculture. Based on microscopic research data, a Structural Equation Model (SEM) is used to analyse the influencing factors and extent of cotton farmers' adoption of SA technologies, using Deconstructive Theory of Planned Behavior (DTPB) as the analytical framework. This was combined with in-depth interviews to further reveal the motivations and influencing mechanisms of cotton farmers' adoption of SA technologies. The results show that under the behavioural belief dimension, cotton farmers value the positive effect of perceived usefulness even though the risk of the technology itself has a dampening effect on adoption intentions. Under the normative belief dimension, superior influence influenced the willingness to adopt SA technologies to a greater extent than peer influence. Under the control belief dimension, factors such as self-efficacy and information channels influence willingness to adopt technology and behaviour. In addition, behavioural attitudes, subjective norms, and perceived behavioural control all contribute to cotton farmers' willingness to adopt SA technologies, and can also influence behaviour directly or indirectly through willingness to adopt. Policy and technology satisfaction positively moderate the transition from willingness to behaviour. Therefore, preferential policies are proposed to reduce the cost of adopting SA technologies; to continuously improve the level of SA technologies; to establish SA technology test plots to provide a reference base; and to increase knowledge training on SA and expand access to information.

The plant unique ESCRT component FREE1 regulates autophagosome closure.

The energy sensor AMP-activated protein kinase (AMPK) can activate autophagy when cellular energy production becomes compromised. However, the degree to which nutrient sensing impinges on the autophagosome closure remains unknown. Here, we provide the mechanism underlying a plant unique protein FREE1, upon autophagy-induced SnRK1α1-mediated phosphorylation, functions as a linkage between ATG conjugation system and ESCRT machinery to regulate the autophagosome closure upon nutrient deprivation. Using high-resolution microscopy, 3D-electron tomography, and protease protection assay, we showed that unclosed autophagosomes accumulated in free1 mutants. Proteomic, cellular and biochemical analysis revealed the mechanistic connection between FREE1 and the ATG conjugation system/ESCRT-III complex in regulating autophagosome closure. Mass spectrometry analysis showed that the evolutionary conserved plant energy sensor SnRK1α1 phosphorylates FREE1 and recruits it to the autophagosomes to promote closure. Mutagenesis of the phosphorylation site on FREE1 caused the autophagosome closure failure. Our findings unveil how cellular energy sensing pathways regulate autophagosome closure to maintain cellular homeostasis.

MicroRNA-155-5p Aggravates Adriamycin-Induced Focal Segmental Glomerulosclerosis through Targeting Nrf2.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix and usually associated with nephrotic range proteinuria. FSGS is a huge burden to society; however, the mechanisms remain unclear and treatment is still lacking. METHODS: Adriamycin nephropathy was induced by Adriamycin injection and some mice were also injected with Anti-miR-155-5p LNA or YC-1 (a pharmacological inhibitor of HIF-1). At 6 weeks, the mice were sacrificed, and kidneys, blood and urine samples were collected for further analysis. RESULTS: We demonstrated a significant increase of miR-155-5p in kidney tissues in Adriamycin-induced FSGS mouse models. We also found Adriamycin treatment led to the activation of HIF-1, and inhibition of HIF-1 using YC-1 partly prevented the induction of miR-155-5p. Functionally, anti-miR-155-5p attenuated kidney injury and delayed the progression of renal fibrosis. Further, anti-miR-155-5p also enhanced the expression of Nrf2 following Adriamycin treatment. Further, our luciferase microRNA target reporter assay verified Nrf2 as a direct target of miR-155-5p. Our further results indicated anti-miR-155-5p could suppress kidney oxidative stress and inflammation, also supporting Nrf2 was the direct target of miR-155-5p. Finally, we also found miR-155-5p did not increase in serum but significantly increased in urine, indicating urinary miR-155-5p may be useful for FSGS diagnosis. CONCLUSION: This study identified a HIF-1/miR-155-5p/Nrf2 axis which can promote kidney oxidative stress and inflammation, finally aggravating kidney injury and accelerating the progression of renal fibrosis in FSGS. Moreover, the increase in urinary miR-155-5p may be useful for the diagnosis of FSGS.

Identification of Aly1 and Aly2 as Modulators of Cytoplasmic pH in Saccharomyces cerevisiae.

The regulation of intracellular pH in yeast (Saccharomyces cerevisiae) cells is critical for cell function and viability. In yeast, protons (H+) can be excreted from the cell by plasma membrane ATPase PMA1 and pumped into vacuoles by vacuolar H+-ATPase. Because PMA1 is critical to the survival of yeast cells, it is unknown whether other compensatory components are involved in pH homeostasis in the absence of PMA1. To elucidate how intracellular pH is regulated independently of PMA1, we employed a screening approach by exposing the yeast haploid deletion mutant library (ver 4.0) to the selective plant plasma membrane H+-ATPase inhibitor PS-1, which we previously reported. After repeated screenings and verification, we identified two proteins, Aly1 and Aly2, that play a role in the regulation of intracellular pH when PMA1 is deficient. Our research uncovers a new perspective on the regulation of intracellular pH related to PMA1 and also preliminarily reveals a role for Aly1 and Aly2 in the regulation of intracellular pH.

Mass Balance-Based Method for Quantifying the Oil Moveable Threshold and Oil Content Evaluation of Lacustrine Shale in the Paleogene Shahejie Formation, Nanpu Sag, Bohai Bay Basin.

Substantial heterogeneity in lacustrine shale brings significant challenges to oil exploration. Therefore, a clear and effective resource evaluation standard can significantly reduce the exploration risk and cost, thus further guiding the prediction in productive areas. However, due to the lack of consideration of the thermal maturity and kerogen type, the present evaluation standards may result in the misjudgment of the resource quality of shale oil reservoirs. In this study, a method based on mass balance involving a hydrocarbon generation statistical model was proposed to calculate oil movable threshold (OMT) values. The OMT values for different types of kerogens are determined from simple and easily obtained pyrolysis parameters. Based on the OMT values, a three-dimensional resource quality evaluation model is constructed and applied to the source rocks in Member (Mbr) 1 of the Shahejie Formation (Fm) Nanpu Sag, Bohai Bay Basin, eastern China. The results show that the Mbr 1 of Shahejie Fm shale is a set of high-quality source rocks with high total organic matter (TOC) and S1c (calibrated free hydrocarbons) content. Meanwhile, the hydrocarbon generation potential of the studied lacustrine shales are in the order of type I > type II1 > type II2 > type III, whereas the OMT values show a similar order. From type I to type III, the hydrocarbon expulsion threshold (HET) values for the four types of shales correspond to pyrolysis peak temperatures (T max) at 438, 426, 428, and 432 °C with the maximum OMT values being 143, 128, 127, and 122 mg HC/g TOC, respectively. The movable and favorable shale oil accumulations are mainly associated with type II1 and II2 shales. Our work provides a novel method for distinguishing the resource quality and locating a favorable exploration target for lacustrine shale, improving efficiency and reducing exploration risks.

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury.

Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.

Lipophilic Red-Emitting Carbon Dots for Detecting and Tracking Lipid Droplets in Live Cells.

Lipid droplets (LDs), a dynamic organelle, are of vital importance in regulating the storage of neutral lipids and energy homeostasis. The aberrant expression of LDs is found to be highly associated with diverse metabolic diseases. Thus, detecting and monitoring LDs are essential to study the pathological and physiological processes of LDs in living bodies. However, it remains challenging to obtain suitable imaging probes to track LDs in vivo. Fortunately, the emergence of carbon dots (CDs), which are fluorescent nanomaterials with good biocompatibility and high stability, has provided us an unprecedented choice. In this work, CDs were synthesized via a solvothermal treatment of commercial reagents, 3-dimethylaminophenol. Interestingly, the prepared CDs show an intense red emission in non-hydrogen-bonding solution and have strong LD-targeting ability without any postmodification of ligands. Moreover, due to their low phototoxicity and excellent photostability, CDs were successfully applied to track the dynamics of LDs in live cells and image LDs in different cell lines and lipid-rich tissues. Overall, this work here proposed an LD-specific red-emitting CD probe, which will be of great value for learning more about LD-associated behaviors and diseases.

Effect of modified electroconvulsive therapy on neuro metabolites and magnetic resonance spectroscopy imaging signals in patients with refractory obsessive-compulsive disorder.

OBJECTIVE: This study was aimed to investigate the effect of modified electroconvulsive therapy (MECT) on neurometabolites and magnetic resonance spectroscopy imaging (MRSI) signals in patients with refractory obsessive-compulsive disorder (OCD). METHODS: From January 2018 to January 2020, 64 patients with OCD consecutively treated in the Psychiatric Department of our hospital were randomly divided into a study group treated with MECT and a control group treated with drugs alone. The obsessive-compulsive state, anxiety and depression, MRSI signals, neuro metabolite ratio, and quality of life were all observed in both groups. RESULTS: After treatment, the scores of compulsive behaviors, obsessive thoughts, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) in the study group were lower than those of the control group. The N-acetylaspartate to creatine ratio (NAA/Cr) value was increased in the study group while it was decreased in the control group. In addition, the choline/creatine (Cho/Cr) ratio was decreased in the study group, whereas it was increased in the control group (P < 0.05). Compared to the control group, the study group's social and physiological functions, role limitations, and overall health scores were significantly higher. The amplitudes of low-frequency fluctuations were reduced considerably following MECT treatment in the right anterior cerebellar lobe, left inferior parietal lobule, right paracentral lobule, and right precentral gyrus. CONCLUSIONS: MECT can effectively relieve obsessive-compulsive symptoms, regulate neuro metabolite levels, improve quality of life, reduce anxiety and depression, and is linked to changes in right brain functional activities.

PAMP-INDUCED SECRETED PEPTIDE 3 modulates salt tolerance through RECEPTOR-LIKE KINASE 7 in plants.

High soil salinity negatively affects plant growth and development, leading to a severe decrease in crop production worldwide. Here, we report that a secreted peptide, PAMP-INDUCED SECRETED PEPTIDE 3 (PIP3), plays an essential role in plant salt tolerance through RECEPTOR-LIKE KINASE 7 (RLK7) in Arabidopsis (Arabidopsis thaliana). The gene encoding the PIP3 precursor, prePIP3, was significantly induced by salt stress. Plants overexpressing prePIP3 exhibited enhanced salt tolerance, whereas a prePIP3 knockout mutant had a salt-sensitive phenotype. PIP3 physically interacted with RLK7, a leucine-rich repeat RLK, and salt stress enhanced PIP3-RLK7 complex formation. Functional analyses revealed that PIP3-mediated salt tolerance is dependent on RLK7. Exogenous application of synthetic PIP3 peptide activated RLK7, and salt treatment significantly induced RLK7 phosphorylation in a PIP3-dependent manner. Notably, MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6 were downstream of the PIP3-RLK7 module in salt response signaling. Activation of MPK3/6 was attenuated in pip3 or rlk7 mutants under saline conditions. Therefore, MPK3/6 might amplify salt stress response signaling in plants for salt tolerance. Collectively, our work characterized a novel ligand-receptor signaling cascade that modulates plant salt tolerance in Arabidopsis. This study contributes to our understanding of how plants respond to salt stress.

Prevalence of anisometropia and associated factors in Shandong school-aged children.

Objective: To investigate anisometropia's prevalence and associated factors in school-aged children. Methods: A cross-sectional school-based study was conducted in Shandong Province, China, including children aged 4 to 17 from 9 schools. Anisometropia was defined as the differences between the two eyes in spherical equivalent (SE) or cylinder degree of 1.00 diopter (D) or more [SE or cylindrical (CYL) difference ≥ 1.00 D] after cycloplegic autorefraction. The Generalized Linear Model (GLM) was used to analyze the effects of ocular parameters [the differences between eyes in axial length (AL), habitual visual acuity (HVA), and corneal astigmatism (CA)] and lifestyle parameters (time spent indoor near work and outdoor activities) on anisometropia. Results: Total 4,198 (93.4%) of the 4,494 children were included in the statistical analysis. The mean difference in inter-eye SE was 0.42 ± 0.61 D. The prevalence of anisometropia was 13.2% (95%CI: 12.1 to 14.2%) (SE anisometropia's prevalence:10.3%; CYL anisometropia's prevalence: 4.1%), increased with older age (OR = 1.10, P = 0.002), the worse myopic eye (myopia vs. premyopia, OR = 1.87, P = 0.002), the worse hyperopic eye (hyperopia vs. premyopia, OR = 1.77, P = 0.013), larger difference in inter-eye AL (0.1-0.3 vs. ≤ 0.1, OR = 1.67, P = 0.008; >0.3 vs. ≤ 0.1, OR = 28.61, P < 0.001), HVA (>0.2 vs. ≤ 0.2, OR = 3.01, P < 0.001), CA (OR = 6.24, P < 0.001), the worse stereoacuity (>100 vs. ≤ 100, OR = 1.59, P = 0.001), longer indoor near work time per day on weekends (4-8 vs. <4, OR = 1.41, P = 0.038; ≥8 vs. <4, OR = 1.40, P = 0.131), and shorter outdoor activity time per day on weekdays (≥1 vs. <1, OR = 0.75, P = 0.046) in multivariable analysis. In the SE anisometropia group, the difference in inter-eye AL (>0.3 vs. ≤ 0.1, ß: 0.556, 95%CI: 0.050 to 1.063), HVA (>0.2 vs. ≤ 0.2, ß: 0.511, 95%CI: 0.312 to 0.710), and CA (ß: 0.488, 95%CI: 0.289 to 0.688), stereoacuity (>100 vs. ≤ 100, ß: 0.299, 95%CI: 0.110 to 0.488) had a positive impact on the difference in inter-eye SE. Conclusions: Ocular parameters and lifestyle parameters are associated with the occurrence of anisometropia in children aged 4 to 17 years, including the difference in inter-eye AL, HVA, CA, stereoacuity, indoor near work time, and outdoor activity time. Preventing myopia and early treating anisometropic amblyopia may be effective ways to reduce the prevalence of anisometropia.

Dynamic changes of phosphatidylinositol and phosphatidylinositol 4-phosphate levels modulate H+-ATPase and Na+/H+ antiporter activities to maintain ion homeostasis in Arabidopsis under salt stress.

Plant metabolites are dynamically modified and distributed in response to environmental changes. However, it is poorly understood how metabolic change functions in plant stress responses. Maintaining ion homeostasis under salt stress requires coordinated activation of two types of central regulators: plasma membrane (PM) H+-ATPase and Na+/H+ antiporter. In this study, we used a bioassay-guided isolation approach to identify endogenous small molecules that affect PM H+-ATPase and Na+/H+ antiporter activities and identified phosphatidylinositol (PI), which inhibits PM H+-ATPase activity under non-stress conditions in Arabidopsis by directly binding to the C terminus of the PM H+-ATPase AHA2. Under salt stress, the phosphatidylinositol 4-phosphate-to-phosphatidylinositol (PI4P-to-PI) ratio increased, and PI4P bound and activated the PM Na+/H+ antiporter. PI prefers binding to the inactive form of PM H+-ATPase, while PI4P tends to bind to the active form of the Na+/H+ antiporter. Consistent with this, pis1 mutants, with reduced levels of PI, displayed increased PM H+-ATPase activity and salt stress tolerance, while the pi4kß1 mutant, with reduced levels of PI4P, displayed reduced PM Na+/H+ antiporter activity and salt stress tolerance. Collectively, our results reveal that the dynamic change between PI and PI4P in response to salt stress in Arabidopsis is crucial for maintaining ion homeostasis to protect plants from unfavorable environmental conditions.

Can feeding sound attract flower fish (Ptychobarbus kaznakovi)?

The use of acoustic attractants may have the potential to guide native migratory species towards safe passage. Flower fish Ptychobarbus kaznakovi, a short-distance migratory fish whose population is in decline in the past decades, was exposed to three acoustic stimuli (feeding sound, ambient riverine noise and the pure tone 1000 Hz) to examine the phonotaxic responses using playbacks approaches in a fibreglass tank. The results showed that the flower fish showed significantly greater positive phonotaxis and swam towards the sound sources significantly faster in response to the feeding sounds than to ambient riverine noise and the pure tone during the 5-min exposure. Distribution experiments were conducted to study the preference of flower fish to the three sounds stimuli. The results showed that the experimental fish in feeding sound trials spent significant more time in areas closer to the sound sources than that in the pure tone and the ambient riverine noise trials, respectively. This study indicates that the feeding sounds may serve as potential acoustic attractants to guide flower fish to safe passage routes.

Cu2+ enhanced chemiluminescence of carbon dots-H2O2 system in alkaline solution.

Herein, Chemiluminescence (CL) behaviour of carbon dots (CDs) was investigated by using H2O2 as co-reactant in alkaline solution. The study demonstrated O2-, OH and 1O2 involved in the CL reaction processes. These reactive oxygen species reacted with CDs to produce CD•+ and CD•-, then the CD•+ reacted with CD•-to generate energy release in the form of CL emission. Importantly, we found that Cu2+ ion could greatly enhanced CL intensity (7.5 times) of CDs-H2O2 system, which was ascribed to Cu2+-catalysed H2O2 decomposition. Based on this system, the CL assay of ascorbic acid (AA) was developed. The limit of detection was as low as 0.03 µM, and the linear range was from 0.1 µM to 100 µM. The proposed method has been successfully utilized to determinate AA in beverage samples with satisfactory results.

Dual-Readout Tyrosinase Activity Assay Facilitated by a Chromo-Fluorogenic Reaction between Catechols and Naphthoresorcin.

Analyte-responsive chromo-fluorogenic reactions under accessible conditions are important for designing small-molecule spectroscopic probes. We describe a series of newly constructed motifs based on the chromo-fluorogenic reaction between catechol derivatives (typically hydroxytyrosol, dopamine, and levodopa) and naphthoresorcin (NR) in aqueous solution under ambient conditions. The weakly absorptive and fluorogenic catechols/NR was converted to products having visible absorption and bright fluorescence within several minutes. The chromo-fluorophores produced from this reaction had a maximum absorbance at 458 nm and emission at 480 nm with high fluorescence quantum yields (30-84%). Inspired by the tyrosinase-catalyzed hydroxylation of monophenols to catechols, the tyrosinase-enabled chromo-fluorogenic reaction was verified by using monophenol (typically tyrosol) as the substrate. In this regard, a dual-readout tyrosinase activity assay was developed by virtue of the in situ "turn-on" optical signals. Furthermore, a test of tyrosinase inhibition, by using a common inhibitor kojic acid, demonstrated the potential of the chromo-fluorogenic reaction for developing other tyrosinase related assays and signal transduction.

Highly Luminescent and Self-Enhanced Electrochemiluminescence of Tris(bipyridine) Ruthenium(II) Nanohybrid and Its Sensing Application for Label-Free Detection of MicroRNA.

Inspired by the coreactive activity of carbon nanodots (CDs) and branched polyethylenimine (BPEI) toward electrochemiluminescence (ECL) of Ru(bpy)32+, a highly luminescent and self-enhanced ECL nanohybrid (Ru-BCDs) was synthesized through covalently linking BPEI-coated carbon dots (BCDs) with Tris (4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)32+). The composition and morphological characterization demonstrated that the spherical Ru-BCDs particles with 12.1 ± 1.4 nm diameter were obtained. The enhanced ECL property of Ru-BCDs was proved to originate from the dual coreactive contribution of BPEI and CDs as coreactants as well as the intramolecular electron transfer process, which could shorten the electron transfer path and minimize energy loss. A carbon nitride nanosheet (CNN) was utilized to stabilize the Ru-BCDs-modified glassy carbon electrode, which greatly improved the stability of solid-state ECL. By utilizing the affinity discrepancy of the CNN to single-stranded and double-stranded nucleic acids, a label-free and signal-on ECL biosensor was constructed for the determination of microRNA-133a (miR-133a), a potential biomarker of acute myocardial infarction. The designed biosensor exhibited good performance of miR-133a detection with a detection limit of 60 fM and could be used for the detection of real human serum with satisfactory results. The self-enhanced ECL nanohybrid with distinguished ECL efficiency holds a promising prospect in biosensing and bioimaging applications.

Effect of coronary collateral circulation on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction treated with underwent primary percutaneous coronary intervention.

Investigate the effect of coronary collateral circulation (CCC) on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction (STEMI) and acute total occlusion (ATO) of a single epicardial coronary artery.Three hundred forty-six advanced-age patients (age ≥60 years) with STEMI and ATO who underwent primary percutaneous coronary intervention (PCI) were enrolled in this study. According to the Rentrop grades, the patients were assigned to the poor CCC group (Rentrop grade 0-1) and good CCC group (Rentrop grade 2-3).Multivariate logistic regression analysis revealed that poor coronary collateral circulation was an independent factor for Killip class ≥2 (odds ratio [OR]: -1.559; 95% confidence interval [CI]: 1.346-2.378; P = .013), the use of an intra-aortic balloon pump (IABP) (OR: -1.302; 95% CI: 0.092-0.805; P = .019), and myocardial blush grade (MBG) 3 (OR: 1.516; 95% CI: 2.148-9.655; P < .001). We completed a 12-month follow-up, during which 52 patients (15.0%) were lost to follow-up and 19 patients (5.5%) died. Univariate analysis (Kaplan-Meier and log-rank tests) suggested that poor CCC had a significant effect on all-cause mortality (P = .046), while multivariate analysis (Cox regression analysis) indicated that CCC had no statistically significant effect on all-cause mortality (P = .089) after the exclusion of other confounding factors. After excluding the influence of other confounding factors, this study showed that the mortality rate increased by 26.9% within 1 year for every 1-hour increment of time of onset. The mortality rate in patients with Killip class ≥2 was 8.287 times higher than that in patients with Killip class 0 to 1. The mortality rate in patients over 75 years was 8.25 times higher than that in patients aged 60 to 75 years. The mortality rate in patients with myocardial blush grade 3 (MBG 3) was 5.7% higher than that in patients with MBG 0-2.The conditions of CCC in the acute phase had no significant direct effect on all-cause mortality in patients, but those with good CCC had a higher rate of MBG 3 after primary PCI and a lower rate of Killip ≥2.

Protein arginine methyltranferase-1 induces ER stress and epithelial-mesenchymal transition in renal tubular epithelial cells and contributes to diabetic nephropathy.

BACKGROUND: In this study, we examined the association of PRMT1 with ER stress and epithelial-mesenchymal transition (EMT), two critical pathogenic mechanisms leading to DN development, in proximal tubular epithelial cells (PTECs). METHODS: The level of PRMT1 was compared between the serum from DN patients and healthy individuals by ELISA, and between renal tissues of DN mice and normal mice using RT-qPCR and immunohistochemistry. Using high-glucose-treated PTEC cell line, HK2 cells as the model system, the significance of PRMT1 in ER stress and EMT was assessed by shRNA targeting PRMT1 (sh-PRMT1) and/or by overexpressing PRMT1. Mechanistic studies focused on three major pathways controlling ER stress: protein kinase R-like ER kinase (PERK), inositol requiring-1α (IRE1α), and activating transcription factor 6 (ATF6). RESULTS: PRMT1 was up-regulated in the serum of DN patients and renal tissues of DN mice. High glucose administration induced elevation of PRMT1 expression in HK2 cells in vitro, accompanied with ER stress and EMT activation. PRMT1 knockdown attenuated high glucose-induced ER stress and apoptosis by inactivating PERK and ATF6, but not IRE1α. PRMT1 activated ATF6 by recruiting H4R3me2as to the promoter. Furthermore, PRMT1-induced ER stress was concomitant with the activation of an EMT-like state. Specifically, inhibition of ATF6, but not PERK blocked PRMT1-induced EMT in high-glucose-treatment HK2 cells. CONCLUSIONS: By activating ER stress, PRMT1 essentially regulates the apoptosis and EMT of PTECs in response to diabetic milieu. Thus, targeting PRMT1 may alleviate both tissue injury and renal fibrosis, and thus benefit the treatment of DN.