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AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Cellulose enzymatic saccharification is a key link in converting lignocellulose to fuel ethanol via a sugar platform. In this paper, the maximum information coefficient (MIC) algorithm is proposed to detect linear correlations and nonlinear correlations between bioinformatics variables from the application of bioinformatics. Meanwhile, to address the problems of excessive grid division and low statistical efficacy of MIC algorithm, BackMIC, an optimization algorithm using quiz control number of segments, is proposed to terminate the network search using the chi-square test. Then, cellulase hydrolysis and adsorption experiments were designed and performed, and the experimental data were analyzed based on the BackMIC algorithm. The optimum activity temperature of different cellulases was around 50°C, while the hydrolysis rate of cellulases of different treated raw materials increased and then decreased with the increase of temperature, and basically, the maximum was achieved in the temperature range of 50~55°C. In the pH test, the optimum temperature of cellulase hydrolysis was concentrated at 4.4~4.5. In the cellulase adsorption experiments, the enzymatic activity of steam-popped wheatgrass was adsorbed in the following order: FPA> C1> CMCase> β-Case. The study of cellulase hydrolysis based on bioinformatics reveals the synergistic relationship between cellulase hydrolysis and adsorbed properties, which provides a theoretical basis for reducing the ineffective adsorption of cellulose and the development of enzymatic strengthening technology. The theoretical basis for reducing the ineffective adsorption of cellulose and the development of enzymatic enhancement technology can help reduce the cost of lignocellulose enzymatic digestion.

Abstract Metal‐porphyrins or metal‐phthalocyanines‐based organic frameworks (POFs), an emerging family of metal‐N‐C materials, have attracted widespread interest for application in electrocatalysis due to their unique metal‐N4 coordination structure, high conjugated π‐electron system, tunable components, and chemical stability. The key challenges of POFs as high‐performance electrocatalysts are the need for rational design for porphyrins/phthalocyanines building blocks and an in‐depth understanding of structure–activity relationships. Herein, the synthesis methods, the catalytic activity modulation principles, and the electrocatalytic behaviors of 2D/3D POFs are summarized. Notably, detailed pathways are given for modulating the intrinsic activity of the M‐N4 site by the microenvironments, including central metal ions, substituent groups, and heteroatom dopants. Meanwhile, the topology tuning and hybrid system, which affect the conjugation network or conductivity of POFs, are also considered. Furthermore, the representative electrocatalytic applications of structured POFs in efficient and environmental‐friendly energy conversion areas, such as carbon dioxide reduction reaction, oxygen reduction reaction, and water splitting are briefly discussed. Overall, this comprehensive review focusing on the frontier will provide multidisciplinary and multi‐perspective guidance for the subsequent experimental and theoretical progress of POFs and reveal their key challenges and application prospects in future electrocatalytic energy conversion systems.

Genetic alteration can render tumor cells resistant to immune cell-mediated killing. Here based on a genome-wide CRISPR screening, the authors show that expression of CHMP2A confers tumor cell resistance to NK cell-mediated cytotoxicity, mechanistically involving CHMP2A-dependent regulation of extracellular vesicle secretion.

Clinical RelevanceA vergence formula may provide a simple and reliable calculation of the refractive status of aphakic eyes.BackgroundMeasuring the refractive error of pediatric eyes with aphakia is difficult. This study investigated the accuracy and applicability of a vergence formula for estimating the refractive status of such eyes.MethodsA retrospective review of the medical records, created between January 2016 and December 2018, of pediatric patients with aphakia was conducted. A vergence formula, based on axial length, was used to calculate the refractive status of the aphakic eyes. The refractive values determined using retinoscopy, an automatic refractometer, and the vergence formula were compared.ResultsA total of 72 eyes (47 patients) were analyzed. The spherical equivalents of the refractive errors (mean ± standard deviation) of the eyes were determined using retinoscopy (13.01 ± 3.27 D), automatic refractometry (12.90 ± 3.23 D), and the vergence formula (12.70 ± 3.4 D). The correlation coefficient between retinoscopy values determined using retinoscopy and the vergence formula, automatic refractometry and the vergence formula, and retinoscopy and automatic refractometry were 0.968, 0.987, and 0.979, respectively. The Bland-Altman consistency analysis revealed that the mean differences in the spherical equivalent values between retinoscopy and automatic refractometry, retinoscopy and the vergence formula, and automatic refractometry and the vergence formula were 0.11 D, 0.31 D, and 0.21 D, respectively, with 95% limits of agreement of−1.20 to 1.41 D,−1.37 to 2.00 D, and−0.90 to 1.31 D, respectively.ConclusionThe vergence formula was effective for evaluating the refractive status of aphakic eyes in pediatric patients.

Thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED) or Graves’ orbitopathy (GO), is a complex autoimmune condition causing visual impairment, disfigurement, and harm to patients’ physical and mental health. The pathogenesis of TAO has not been fully elucidated, and the mainstream view is that coantigens shared by the thyroid and orbit trigger remodeling of extraocular muscles and orbital connective tissues through an inflammatory response. In recent years, cytokines and the immune responses they mediate have been crucial in disease progression, and currently, common evidence has shown that drugs targeting cytokines, such as tocilizumab, infliximab, and adalimumab, may be novel targets for therapy. In this review, we summarize the research development of different cytokines in TAO pathogenesis in the hope of discovering new therapeutic targets.

Abstract. Adoptive immunotherapy using immune effector cells has revolutionized cancer treatments with approval of two autologous chimeric antigen receptor (CAR) T cell therapies by the US FDA. Clinical trials using natural killer (NK) cell-based adoptive immunotherapy have been shown to be safe and effective for treatment of multiple malignancies, especially acute myelogenous leukemia. However, most of these trails use primary NK cells isolated from peripheral or cord blood which can have donor-dependent variability and can be challenging to genetic engineer to improve antitumor functions, limiting the widespread use of this promising new therapy. NK cells can now be routinely produced from human pluripotent stem cells, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). These pluripotent stem cells are homogenous, easy to genetically modify on a clonal level and can be used as unlimited source of NK cells, making them ideal population to develop standardized, off-the-shelf adoptive NK cell therapy products. In this review, we discuss recent advances of obtaining and expanding hESC and iPSC-derived NK cells and novel genetic engineering strategies that are being applied to improve their antitumor functions.

Natural killer (NK) cells derived or isolated from different sources have been gaining in importance for cancer therapies. In this study, we evaluate and compare key characteristics between NK cells derived or isolated from umbilical cord blood, umbilical cord blood hematopoietic stem/progenitor cells, peripheral blood, and induced pluripotent stem cells (iPSCs). Specifically, we find CD56+ NK cells isolated and expanded directly from umbilical cord blood (UCB56) and NK cells derived from CD34+ hematopoietic stem/progenitors in umbilical cord blood (UCB34) differ in their expression of markers associated with differentiation including CD16, CD2, and killer Ig-like receptors (KIRs). UCB56-NK cells also displayed a more potent cytotoxicity compared to UCB34-NK cells. NK cells derived from iPSCs (iPSC-NK cells) were found to have variable KIR expression, with certain iPSC-NK cell populations expressing high levels of KIRs and others not expressing KIRs. Notably, KIR expression on UCB56 and iPSC-NK cells had limited effect on cytotoxic activity when stimulated by tumor target cells that express high levels of cognate HLA class I, suggesting that in vitro differentiation and expansion may override the KIR-HLA class I mediated inhibition when used across HLA barriers. Together our results give a better understanding of the cell surface receptor, transcriptional, and functional differences between NK cells present in umbilical cord blood and hematopoietic progenitor-derived NK cells which may prove important in selecting the most active NK cell populations for treatment of cancer or other therapies.

To ease the imbalance between the supply and demand for iron ore in the ferrous industry of China, a low-temperature reduction process via an ore-coal composite method was developed to recover iron from low-grade iron-ore resources (about 30%). In addition, industrial tests on this new reduction process were performed using a rotary kiln (φ1.5 m×15 m). However, rings were formed in the rotary kiln after some days of operation, and these rings affected normal operation. Ring formation during rotary kiln reduction has become a restraining factor for development of coal direct reduction processes using rotary kilns. Previous studies have mainly focused on the reduction process of high-grade ore (> 60%) for direct-reduced iron production. The manner in which highgrade ore reduction differs from low-grade ore reduction is unclear. So, the characteristics of the ring samples need to be studied primarily. Then, the characteristics that affect the formation mechanisms of the rings need to be investigated. Accordingly, relative operation may be developed and ring formation may be prevented. In this paper, ring samples formed in a rotary kiln during a low-grade iron-ore reduction process were studied. The characteristics and formation mechanisms of the ring samples were investigated in detail. The characteristics for ring samples collected from different positions in the rotary kiln were analyzed from the aspects of macro morphological, physical, and chemical compositions, softening and melting properties, and microstructural properties. Thermodynamic phase diagrams, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, X-ray diffraction, and chemical phase analyses were applied to reveal the ring formation mechanism during the rotary kiln reduction process. Results show that rings mainly comprise pellets and molten wrappage surroundings. The amount of molten wrappages and the proportions of MFe and CaO increase in the ring samples that are next to the kiln wall. The results also show that the ring samples exhibit lower softening and melting temperatures at this location. The main reason of ring formation is found to be the low melting phases including fayalite formed by FeO and SiO2 in pelletizing powder and hedenbergite compounded by CaO (brought about by coal ash). Moreover, the existence of low melting point phases promotes the diffusion and migration of newly formed iron grains between metallized pellets, which exacerbates ring formation.

Along with the rapid development of economy and urbanization, noise and air pollution are becoming major occupational health hazards in the process of industrial production. In this study, we collected data from 7293 industrial workers in China. The association between occupational exposure of noise and dust and blood pressure was investigated. Controlling for demographic variables, including sex, age, and length of service, a stepwise regression model with backward elimination was constructed. The results showed that both noise and dust decreased the level of systolic blood pressure (p

Three cyst-forming Sarcocystis species have been identified in horsemeat; however, there exists considerable confusion concerning their relationships. Here, 74% (34/46) of the examined tissue samples from horses contained sarcocysts based on examination by light microscopy (LM), and the organism was identified as Sarcocystis bertrami based on cyst structure. The S. bertrami cysts were microscopic (up to 6750 μm in length) and exhibited a striated wall with 2.0–5.1 μm villar protrusions (vps) under LM. Transmission electron microscopy (TEM) observations showed that the vps were tightly packed, similar to “type 11c”. Four genetic markers (18S, 28S, ITS1 and the mitochondrial cox1 gene) of S. bertrami were sequenced and analyzed. The 28S and ITS1 sequences are the first records for Sarcocystis in horses. The newly obtained sequences of the 18S and cox1 genes both shared the highest similarities with those of S. bertrami and S. fayeri obtained from horses. Phylogenetic analysis based on the 18S, 28S and cox1 sequences revealed that S. bertrami and S. fayeri formed an independent clade within a group comprising Sarcocystis spp. from ruminants and pigs. Therefore, S. bertrami and S. fayeri are considered to represent the same species of Sarcocystis in horses, and S. fayeri is a junior synonym of Sarcocystis bertrami.

Cannabinoid receptor 2 (CB2R) is a therapeutic target in inflammatory diseases; its activation by agonists provides important clinical information, but there are currently no methods to quantify CB2R activation in humans. Chinese hamster ovary (CHO)-K1 cells and mouse and human whole blood cells were used for experiments. CB2R was activated in cells by treatment with the agonist CP55,940. Cells were also pretreated with proprietary Compound A and B (experimental agonists). We developed our method based on the finding that CB2R ligand binding and activation stimulates acute-phase extracellular signal-regulated kinase (ERK) phosphorylation in human and rodent immune cells, after which CB2R becomes unresponsive to stimulation by a second CB2R agonist CP55940 for a certain time period. We detected ERK phosphorylation as a measure of target engagement in mouse and human whole blood cells by flow cytometry. In cells overexpressing human or mouse CB2R, pretreatment with Compound A dose-dependently inhibited ERK phosphorylation for 2 h, prolonging the time window for measuring ERK phosphorylation. Our method enables measurement of CB2R activation by its agonists in human blood cells based on detection of ERK phosphorylation, which is useful for therapeutic drug monitoring and other clinical applications.

Antioxidant vitamins supplements have been suggested as a strategy to decrease the risk of age-related cataract development. However, the results from observational studies and interventional trials of associations between antioxidant vitamins A, C, and E and cataract development have been inconsistent. We aim to evaluate the effectiveness of multivitamin/mineral supplements for decreasing the risk of age-related cataracts by conducting a systematic review and meta-analysis. In September 2013, we searched multiple databases to identify relevant studies including both cohort studies and randomized controlled trials (RCTs). A random-effects model was used to calculate the pooled relative risks (RR) with a 95% confidence interval (CI). Twelve prospective cohort studies and two RCTs were included. Pooled results from the cohort studies indicated that multivitamin/mineral supplements have a significant beneficial effect in decreasing the risk of nuclear cataracts (RR: 0.73; 95% CI: 0.64–0.82), cortical cataracts (RR: 0.81; 95% CI: 0.68–0.94), and any cataracts (RR: 0.66; 95% CI: 0.39–0.93). In addition, there were no decreases in the risk of posterior capsular cataracts (RR: 0.96; 95% CI: 0.72–1.20) or cataract surgery (RR: 1.00; 95% CI: 0.92–1.08). The two RCTs demonstrated that multivitamin/mineral supplements could decrease the risk of nuclear cataracts. There is sufficient evidence to support the role of dietary multivitamin/mineral supplements for the decreasing the risk of age-related cataracts.

The TALE (Three Amino acid Loop Extension) family consisting of Meis, Pbx and Pknox proteins is a group of transcriptional co-factors with atypical homeodomains that play pivotal roles in limb development. Compared to the in-depth investigations of Meis and Pbx protein functions, the role of Pknox2 in limb development remains unclear. Here, we showed that Pknox2 was mainly expressed in the zeugopod domain of the murine limb at E10.5 and E11.5. Misexpression of Pknox2 in the limb bud mesenchyme of transgenic mice led to deformities in the zeugopod and forelimb stylopod deltoid crest, but left the autopod and other stylopod skeletons largely intact. These malformations in zeugopod skeletons were recapitulated in mice overexpressing Pknox2 in osteochondroprogenitor cells. Molecular and cellular analyses indicated that the misexpression of Pknox2 in limb bud mesenchyme perturbed the Hox10-11 gene expression profiles, decreased Col2 expression and Bmp/Smad signaling activity in the limb. These results indicated that Pknox2 misexpression affected mesenchymal condensation and early chondrogenic differentiation in the zeugopod skeletons of transgenic embryos, suggesting Pknox2 as a potential regulator of zeugopod and deltoid crest formation.

This control-matched comparative study evaluated changes in contrast sensitivity after Zyoptix tissue-saving (TS) LASIK and Planoscan standard LASIK (Technolas 217z, Bausch & Lomb) for myopia 6 months postoperatively. 102 TS LASIK-treated eyes were matched with 102 standard LASIK-treated eyes (divided into low, moderate, and high groups). There were no significant differences in refraction outcomes between the groups postoperatively. In high group, a significant reduction in contrast sensitivity after TS LASIK was found at high spatial frequencies (P