Analysis of eplerenone in the FDA adverse event reporting system (FAERS) database: a focus on overall patient population and gender-specific subgroups.

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug's label. Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years. Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication's package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc. Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug.

A study on the configuration of factors influencing overweight and obesity in adolescents based on fuzzy set qualitative comparative analysis.

OBJECTIVE: Overweight and obesity among adolescents are grave public health issues around the world. Although the conditions that contribute to obesity have been extensively researched, little is known about how multiple conditions interact to cause overweight and obesity. The current study intends to investigate the histomorphic configuration pathways of several conditions of adolescent overweight and obesity by gender. METHOD: The data came from a social survey conducted in June 2021 in Changchun, Jilin Province, China. The sample collected was 14-year-old adolescents, including 167 boys and 137 girls. The school physicians examined the participants' weight and height, and questionnaires were used to collect risk indicators from adolescents, such as sleep duration, electronic screens times, consumption of sugary drinks and fried foods, and physical activity. Simultaneously, a Fuzzy Qualitative Comparative Analysis will be performed to investigate the combinations of diverse conditions. RESULT: We found that there is no determining necessary condition that, once present, directly determines that an individual is in a state of overweight and obesity. Simultaneously, this study revealed nine alternative configurational paths of overweight and obesity in teenagers of different genders, with a concordance of 0.805 for six male groupings and 0.916 for three female groupings. The outcomes of overweight obesity in adolescents under different genders are similar but not identical. CONCLUSION: This study examined the interactions of a number of conditions from the individual, behavioral, learning and living environment that led to the same overweight obese outcome among adolescents of different genders. Our research will be useful to policymakers in that interventions should take into account the combined effects of a number of different aspects rather than focusing on a single factor that causes overweight and obesity.

In Situ Polymerization of a Self-Healing Polyacrylamide-Based Eutectogel as an Electrolyte for Zinc-Ion Batteries.

Gel electrolytes have attracted extensive attention in flexible batteries. However, the traditional hydrogel electrolyte is not enough to solve the fundamental problems of zinc anodes, such as dendrite growth, side reactions, and freezing failure at temperatures below zero, which seriously restricts the development of zinc-ion batteries. As a flexible energy storage device, the zinc-ion battery inevitably undergoes multiple stretches, bends, folds, or twists in daily use. Here, a self-healing and stretchable eutectogel, designated as deep eutectic solvent-acrylamide eutectic gel (DA-ETG), was developed as a solid-state electrolyte for zinc-ion batteries. This gel was prepared by immobilizing a high-concentration ZnCl2 deep eutectic solvent (DES) into a polyacrylamide matrix through in situ polymerization under ultraviolet light. The eutectogel electrolyte showed exceptional mechanical properties with a maximum fracture strength of 0.6 MPa and a high ionic conductivity of 6.4 × 10-4 S cm-1. The in situ polymerization of the DA-ETG electrolyte in the assembly of a full solid-state zinc-ion battery increased the electrode-electrolyte interface area contact, reduced the ion transport distance between the electrode and electrolyte, minimized the internal resistance, and enhanced the battery's long-term cycling stability. Using the DA-ETG electrolyte, a remarkably high capacity of 580 mAh g-1 at 0.1 A g-1 was achieved by the zinc-ion battery, and a considerable capacity of 234 mAh g-1 was maintained even at 5 A g-1, showing exceptional rate performance. After 2000 cycles at 2 A g-1, the cell with the eutectogel retained a capacity of 85% with a cycling efficiency close to 98%, which demonstrated excellent cycling stability. The self-healing function enabled the prepared soft battery to be reused multiple times, with full contact between the electrode and electrolyte interface, and without device failures.

The effect of Ca2+-calcineurin signaling pathway on the antifungal activity of Pd-D-V against Botrytis cinerea.

Gray mold, caused by Botrytis cinerea is an intractable fungal disease that causes extensive damage to agricultural products. In the search for novel antifungal active ingredients, we discovered a linear pyranocoumarin Pd-D-V was effective against B. cinerea in both in vitro and in vivo assays. Furthermore, this study investigated the effects of Ca2+ and the Ca2+-calcineurin signaling pathway on its antifungal activity against B. cinerea. The results indicated that Pd-D-V reduced the concentration of Ca2+ in the mycelia of B. cinerea; CaCl2, the Ca2+ channel blocker verapamil, or the calcineurin inhibitor cyclosporin A could affect the sensitivity of Pd-D-V against B. cinerea; the expression of genes (Bccch1, Bcmid1, BccnA, Bccnb1, Bcpmc1, and Bcpmr1) of the Ca2+-calcineurin signaling pathway decreased after Pd-D-V treatment. In summary, Pd-D-V is compound for developing fungicides against B. cinerea. Pd-D-V can reduce intracellular Ca2+ concentration and disturb Ca2+ homeostasis. The Ca2+-calcineurin signaling pathway is important in the antifungal activity of Pd-D-V against B. cinerea.

Genome-wide association mapping of quantitative trait loci for chalkiness-related traits in rice (Oryza sativa L.).

Grain chalkiness directly affects the commercial value of rice. Genes related to chalkiness reported thus far have been discovered in mutants, but it has not been identified whether these genes can be used to improve rice quality by breeding. Therefore, discovering more quantitative trait loci (QTLs) or genes related to chalkiness in the rice germplasm is necessary. This study entails a genome-wide association study on the degree of endosperm chalkiness (DEC) and percentage of grains with chalkiness (PGWC) by combining 1.2 million single-nucleotide polymorphisms (SNPs) with the phenotypic data of 173 rice accessions. Thirteen QTLs for DEC and nine for PGWC were identified, of which four were detected simultaneously for both DEC and PGWC; further, qDEC11/qPGWC11 was identified as the major QTL. By combining linkage disequilibrium analysis and SNP information, LOC_Os11g10170 was identified as the candidate gene for DEC. There were significant differences among the haplotypes of LOC_Os11g10170, and the Hap 1 of LOC_Os11g10170 was observed to reduce the DEC by 6.19%. The qRT-PCR results showed that the gene expression levels in accessions with high DEC values were significantly higher than those in accessions with low DEC values during days 21-42 after flowering, with a maximum at 28 days. These results provide molecular markers and germplasm resources for genetic improvement of the chalkiness-related traits in rice.

Leucine rich α2 glycoprotein 1 derived from malignant pleural mesothelioma cells facilitates macrophage M2 phenotypes.

Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue samples of MPM patients. Whether MPM cells affect formation of M2 macrophages is poorly understood. In this study, we focused on identification of MPM-cells-derived soluble factors with M2-promoting effects. Methods: Media of malignant pleural mesothelioma cells were collected and soluble factors affecting macrophages were analyzed by mass spectrometry. TGF-ß receptor inhibitor SB431542 was used as the entry point to explore the downstream mechanism of action by qRT-PCR, WB and immunofluorescence. Results: The serum-free culture media collected from the human MPM cells Meso1 and Meso2 significantly enhanced expression of the M2 signature molecules including IL-10, TGF-ß and CD206 in the human macrophages THP-1, while the culture medium of the human MPM cells H2452 did not show such M2-promoting effects. Analysis of proteins by mass spectrometry and ELISA suggested that Leucine rich α2 glycoprotein 1(LRG1) was a potential candidate. LRG1 time- and dose-dependently increased expression of the M2 signature molecules, confirming its M2-promoting effects. Furthermore, LRG1's M2-promoting effects were reduced by the TGF-ß receptor inhibitor SB431542, and LRG1 increased phosphorylation of Smad2, indicating that M2-promoting effects of LRG1 were via the TGF-ß receptor/Smad2 signaling pathway. Conclusions: Our results provide a potential M2-promoting new member, LRG1, which contributes to the immune escape of MPM via the TGF-ß receptor/Smad2 signaling pathway.

Accurate and highly sensitive detection of Alzheimer's disease-related extracellular vesicles via förster resonance energy transfer.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world and poses a huge challenge to global healthcare. Early and accurate detection of amyloid-ß (1-42) (Aß42), a key biomarker of AD, is crucial for effective diagnosis and intervention of AD. Specific or overexpressed proteins on extracellular vesicles (EVs) describe a close correlation with the occurrence and development of diseases. EVs are a very promising non-invasive biomarker for the diagnosis of AD and other diseases. As a sensitive, simple and rapid analytical method, fluorescence resonance energy transfer (FRET) has been widely applied in the detection of EVs. Herein, we developed a dual labelling strategy for simultaneously detecting EV membrane proteins of Aß42 and CD63 based on FRET pair consisting of Au nanoclusters (AuNCs) and polydopamine nanospheres (PDANSs). The constructed nanoprobe, termed EVMPFAP assay, could specifically measure the Aß42 and CD63 on EVs with excellent sensitivity, high specificity and satisfactory accuracy. The limit of detection of EVMPFAP assay was 1.4 × 103 particles mL-1 and the linear range was from 104 to 108 particles mL-1. EVMPFAP assay was successfully used to analyze plasma EVs to distinguish AD and healthy mice. We expect that EVMPFAP assay can be routinely applied for early diagnosis and development-monitoring of AD, thus facilitating the fight against AD.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

Vernalization promotes bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Sugar beet (Beta vulgaris L.), a biennial sugar crop, contributes about 16% of the world's sugar production. The transition from vegetative growth, during which sugar accumulated in beet, to reproductive growth, during which sugar exhausted in beet, is determined by vernalization and photoperiod. GIGANTEA (GI) is a key photoperiodic flowering gene that is induced by vernalization in sugar beet. To identify the upstream regulatory factors of BvGI, candidate transcription factors (TF) that were co-expressed with BvGI and could bind to the BvGI promoter were screened based on weighted gene co-expression network analysis (WGCNA) and TF binding site prediction. Subsequently, their transcriptional regulatory role on the BvGI was validated through subcellular localization, dual-luciferase assays and yeast transformation tests. A total of 7,586 differentially expressed genes were identified after vernalization and divided into 18 co-expression modules by WGCNA, of which one (MEcyan) and two (MEdarkorange2 and MEmidnightblue) modules were positively and negatively correlated with the expression of BvGI, respectively. TF binding site predictions using PlantTFDB enabled the screening of BvLHY, BvTCP4 and BvCRF4 as candidate TFs that negatively regulated the expression of BvGI by affecting its transcription. Subcellular localization showed that BvLHY, BvTCP4 and BvCRF4 were localized to the nucleus. The results of dual-luciferase assays and yeast transformation tests showed that the relative luciferase activity and expression of HIS3 was reduced in the BvLHY, BvTCP4 and BvCRF4 transformants, which suggested that the three TFs inhibited the BvGI promoter. In addition, real-time quantitative reverse transcription PCR showed that BvLHY and BvTCP4 exhibited rhythmic expression characteristics similar to that of BvGI, while BvCRF4 did not. Our results revealed that vernalization crosstalked with the photoperiod pathway to initiate bolting in sugar beet by inhibiting the transcriptional repressors of BvGI.

Focuses, Developments, and Publication Trends in Facial Bone Aging and Related Fields: A Systematic Bibliometric Analysis (1990-2023).

There is a current lack of bibliometric analysis in facial bone aging and relevant fields. By providing clear and intuitive references, predictions, and guidance for future research, this study aims to fill the gap in the current field, summarize the related research, and guide the researchers' future work. Literature data were retrieved from the Web of Science Core Collection database. Results Analysis and Citation Report of Web of Science, and CiteSpace software were used to optimize the visualization results, including publication characteristics, disciplines, journals, literature, countries/regions, institutions, authors, research focuses, etc. A total of 277 publications were included after manual screening, and the overall trend of annual publications and citations was increasing. On the basis of the analysis, the characteristics of facial bone aging, aging of facial soft tissue, and facial rejuvenation have been the focuses of research in this field. As stem cell research advances and researchers, deepen their comprehension of facial bone aging, basic scientific research on facial bones has witnessed a growing trend.

Global Research Trends and Focuses on Pierre Robin Sequence From 1992 to 2023: A Bibliometric Analysis of the Past 3 Decades.

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual's growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.

Identifying the Quantitative Trait Locus and Candidate Genes of Traits Related to Milling Quality in Rice via a Genome-Wide Association Study.

Milling quality directly affects production efficiency in rice, which is closely related to the brown rice recovery (BRR), the milled rice recovery (MRR) and the head milled rice recovery (HMRR). The present study investigated these three traits in 173 germplasms in two environments, finding abundant phenotypic variation. Three QTLs for BRR, two for MRR, and three for HMRR were identified in a genome-wide association study, five of these were identified in previously reported QTLs and three were newly identified. By combining the linkage disequilibrium (LD) analyses, the candidate gene LOC_Os05g08350 was identified. It had two haplotypes with significant differences and Hap 2 increased the BRR by 4.40%. The results of the qRT-PCR showed that the expression of LOC_Os05g08350 in small-BRR accessions was significantly higher than that in large-BRR accessions at Stages 4-5 of young panicle development, reaching the maximum value at Stage 5. The increase in thickness of the spikelet hulls of the accession carrying LOC_Os05g08350TT occurred due to an increase in the cell width and the cell numbers in cross-sections of spikelet hulls. These results help to further clarify the molecular genetic mechanism of milling-quality-related traits and provide genetic germplasm materials for high-quality breeding in rice.

Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults especially for females: a cross-sectional study.

BACKGROUND: Oral frailty is reported to increase the risk of new onset of mild cognitive impairment. Whereas, the association of oral frailty with cognition among older adults in both physical frail and non-physical frail status has not been sufficiently explored, and whether there are sex differences in the association is unclear. This study investigated the association of oral frailty and physical frailty with global cognitive function and executive function among older adults, as well as the sex differences in such association. METHODS: This cross-sectional study included 307 participants aged ≥ 60 years old from communities between June 2023 and August 2023, in Nanjing, China. Global cognitive function and executive function were assessed by using the Montreal Cognitive Assessment (MoCA) and Trail Making Tests A (TMT-A), respectively. Oral frailty was identified by the combination of natural tooth, Oral Frailty Index-8 (OFI-8), and oral diadochokinesis. Physical frailty was measured by using Fried phenotype model which contained 5 criteria: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Multiple linear regression analyses for overall participants and stratified by sex and presence or absence of physical frailty were performed, respectively, to examine the association between oral frailty and cognitive functions. RESULTS: The median age of participants was 70 years old. The study included 158 (51.5%) females, 53 (17.3%) individuals with physical frailty, and 65 (21.2%) participants with oral frailty. After adjustment, the association between oral frailty and global cognitive function was observed in the physical frailty group (B = -2.67, 95% Confidence Interval [CI]: -5.27 to -0.07, p = 0.045) and the females with physical frailty (B = -4, 95% CI: -7.41 to -0.58, p = 0.024). Oral frailty was associated with executive function in overall participants (B = 0.12, 95% CI: 0.01 to 0.22, p = 0.037), physical frailty group (B = 23.68, 95% CI: 1.37 to 45.99, p = 0.038). In the adjusted models, oral frailty was significantly associated with executive function in all females (B = 0.21, 95% CI: 0.05 to 0.36, p = 0.009), in females without physical frailty (B = 0.19, 95% CI: 0.02 to 0.36, p = 0.027), and in females with physical frailty (B = 48.69, 95% CI: 7.17 to 90.21, p = 0.024). CONCLUSIONS: Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults, particularly among females. It is ponderable to consider sex differences and facilitate the management of physical frailty when it comes to promoting cognitive health based on the perspective of oral health among older adults.

Genome assembly of Melilotus officinalis provides a new reference genome for functional genomics.

BACKGROUND: Sweet yellow clover (Melilotus officinalis) is a diploid plant (2n = 16) that is native to Europe. It is an excellent legume forage. It can both fix nitrogen and serve as a medicine. A genome assembly of Melilotus officinalis that was collected from Best corporation in Beijing is available based on Nanopore sequencing. The genome of Melilotus officinalis was sequenced, assembled, and annotated. RESULTS: The latest PacBio third generation HiFi assembly and sequencing strategies were used to produce a Melilotus officinalis genome assembly size of 1,066 Mbp, contig N50 = 5 Mbp, scaffold N50 = 130 Mbp, and complete benchmarking universal single-copy orthologs (BUSCOs) = 96.4%. This annotation produced 47,873 high-confidence gene models, which will substantially aid in our research on molecular breeding. A collinear analysis showed that Melilotus officinalis and Medicago truncatula shared conserved synteny. The expansion and contraction of gene families showed that Melilotus officinalis expanded by 565 gene families and shrank by 56 gene families. The contacted gene families were associated with response to stimulus, nucleotide binding, and small molecule binding. Thus, it is related to a family of genes associated with peptidase activity, which could lead to better stress tolerance in plants. CONCLUSIONS: In this study, the latest PacBio technology was used to assemble and sequence the genome of the Melilotus officinalis and annotate its protein-coding genes. These results will expand the genomic resources available for Melilotus officinalis and should assist in subsequent research on sweet yellow clover plants.

Light-Activated Nanodiamond-Based Drug Delivery Systems for Spatiotemporal Release of Antisense Oligonucleotides.

Nanodiamonds (NDs) are considered promising delivery platforms, but inaccurate and uncontrolled release of drugs at target sites is the biggest challenge of NDs in precision medicine. This study presents the development of phototriggerable ND-based drug delivery systems, utilizing ortho-nitrobenzyl (o-NB) molecules as photocleavable linkers between drugs and nanocarriers. UV irradiation specifically cleaved o-NB molecules and then was followed by releasing antisense oligonucleotides from ND-based carriers in both buffer and cellular environments. This ND system carried cell nonpermeable therapeutic agents for bypassing lysosomal trapping and degradation. The presence of fluorescent nitrogen-vacancy centers also allowed NDs to serve as biological probes for tracing in cells. We successfully demonstrated phototriggered release of antisense oligonucleotides from ND-based nanocarriers, reactivating their antisense functions. This highlights the potential of NDs, photocleavable linkers, and light stimuli to create advanced drug delivery systems for controlled drug release in disease therapy, opening possibilities for targeted and personalized treatments.

Changes in corneal biomechanics in patients with glaucoma: a systematic review and meta-analysis.

INTRODUCTION: Corneal biomechanics has been implicated in a variety of ocular diseases. The purpose of this study was to evaluate the relationship between the glaucoma and corneal biomechanical properties, and exploring the value of corneal biomechanics in the diagnosis and follow-up of glaucoma diseases. METHODS: We searched studies in PubMed, EMBASE, Web of Science and clinicaltrials.gov., as of October 8, 2022. Only English studies were included, without publication time limit. We also searched the reference lists of published reviews. This meta-analysis was conducted with random-effects models, we used mean difference(MD) to evaluate the outcome, and the heterogeneity was assessed with the I2 statistic. Subgroup analyses were performed under the appearance of high heterogeneity. We used 11 items to describe the characteristics of included studies, publication bias was performed through the Egger's test. The quality assessment were evaluated by Newcastle-Ottawa Scale(NOS) items. RESULTS: A total of 27 eligible studies were identified for data synthesis and assessment. The result of meta-analysis showed that in the comparison of included indicators, the corneal biomechanics values of glaucoma patients were statistically lower than those of normal subjects in a similar age range. The covered indicators included central corneal thickness(CCT) (MD = -8.34, 95% CI: [-11.74, -4.94]; P < 0.001), corneal hysteresis(CH)(MD = -1.54, 95% CI: [-1.88, -1.20]; P < 0.001), corneal resistance factor(CRF)( MD = -0.82, 95% CI: [-1.21, -0.44]; P < 0.001), and intraocular pressure(IOP)( corneal-compensated intraocular pressure (IOPcc): MD = 2.45, 95% CI: [1.51, 3.38]; P < 0.001); Goldmann-correlated intraocular pressure (IOPg): MD = 1.30, 95% CI: [0.41, 2.20]; P = 0.004), they all showed statistical difference. While the value of axial length(AL) did not show statistically different(MD = 0.13, 95% CI: [-0.24, 0.50]; P = 0.48). CONCLUSION: Corneal biomechanics are associated with glaucoma. The findings can be useful for the design of glaucoma screening, treatment and prognosis.

Hierarchical self-recognition and response in CSC and non-CSC micro-niches for cancer therapy.

Cancer stem cells (CSCs) characterized by self-renewal, invasiveness, tumorigenicity and resistance to treatment are regarded as the thorniest issues in refractory tumors. We develop a targeted and hierarchical controlled release nano-therapeutic platform (SEED-NPs) that self-identifies and responds to CSC and non-CSC micro-niches of tumors. In non-CSC micro-niche, reactive oxygen species (ROS) trigger the burst release of the chemotherapeutic drug and photosensitizer to kill tumor cells and reduce tumor volume by combining chemotherapy and photodynamic therapy (PDT). In CSC micro-niche, the preferentially released differentiation drug induces CSC differentiation and transforms CSCs into chemotherapy-sensitive cells. SEED-NPs exhibit an extraordinary capacity for downregulating the stemness of CD44+/CD24- SP (side population) cell population both in vitro and in vivo, and reveal a 4-fold increase of tumor-targeted accumulation. Also, PDT-generated ROS promote the formation of tunneling nanotubes and facilitate the divergent network transport of drugs in deep tumors. Moreover, ROS in turn promotes CSC differentiation and drug release. This positive-feedback-loop strategy enhances the elimination of refractory CSCs. As a result, SEED-NPs achieve excellent therapeutic effects in both 4T1 SP tumor-bearing mice and regular 4T1 tumor-bearing mice without obvious toxicities and eradicate half of mice tumors. SEED-NPs integrate differentiation, chemotherapy and PDT, which proved feasible and valuable, indicating that active targeting and hierarchical release are necessary to enhance antitumor efficacy. These findings provide promising prospects for overcoming barriers in the treatment of CSCs.

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides.

Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.