Association Between Serum Zinc and Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis: NHANES 2011-2016.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Introducing Bacillus natto and Propionibacterium shermanii into soymilk fermentation: A promising strategy for quality improvement and bioactive peptide production during in vitro digestion.

Herein, the texture properties, polyphenol contents, and in vitro protein digestion characteristics of soymilk single- or co-fermented by non-typical milk fermenter Bacillus natto (B. natto), Propionibacterium freudenreichii subsp. shermanii (P. shermanii), and traditional milk fermenter were evaluated. Co-fermenting procedure containing B. natto or P. shermanii could raise the amounts of gallic acid, caffeic acid, and GABA when compared to the unfermented soymilk. Co-fermented soymilk has higher in vitro protein digestibility and nutritional protein quality. Through peptidomic analysis, the co-work of P. shermanii and Lactobacillus plantarum (L. plantarum) may release the highest relative percentage of bioactive peptides, while the intervention of B. natto and Streptococcus thermophilus (S. thermophilus) resulted in more differentiated peptides. The multi-functional bioactive peptides were mainly released from glycine-rich protein, ß-conglycinin alpha subunit 1, and ACB domain-containing protein. These findings indicated the potential usage of B. natto/S. thermophilus or P. shermanii/L. plantarum in bio-enhanced soymilk fermentation.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China.

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Controlling Interfacial Amidation Reaction Rate to Regulate Crystal Growth toward High-Performance FAPbBr3-Based Inverted Light-Emitting Diodes.

Controlling interfacial reactions is critical for zinc oxide (ZnO)-based inverted perovskite light-emitting diodes (PeLEDs), boosting the external quantum efficiency (EQE) of the near-infrared device to above 20%. However, violent interfacial reactions between the bromine-based perovskites and ZnO-based films severely limit the performance of inverted green PeLEDs, whose efficiency and stability lag far behind those of their near-infrared counterparts. Here, a controllable interfacial amidation between the bromine-based perovskites and magnesium-doped ZnO (ZnMgO) film utilizing caprylyl sulfobetaine (SFB) is realized. The SFB molecules strongly interact with formamidinium bromide, decelerating the amidation reaction between formamidinium and carboxylate groups on the ZnMgO film, thus regulating the crystallization of FAPbBr3. Combined with the passivation of benzylamine, a FAPbBr3 bulk film directly deposited on a ZnMgO substrate with single-crystal characteristics is obtained, exhibiting a high photoluminescence quantum yield of above 80%. The resultant PeLEDs demonstrate a peak EQE of exceeding 20% at a high luminance of 120,000 cd m-2 and a half lifetime of 26 min at 11,000 cd m-2, representing the state-of-the-art inverted green electroluminescence. This work resolves the crucial issues of violent interfacial reactions and provides a strategy toward inverted green PeLEDs with outstanding performance.

p-n heterogeneous Sb2S3/SnO2 quantum dot anchored reduced graphene oxide nanosheets for high-performance lithium-ion batteries.

Antimony sulfide (Sb2S3) has a high theoretical specific capacity due to its two reaction mechanisms of conversion and alloying during the Li+-(de)intercalation process, thus becoming a promising lithium-ion battery (LIB) anode material. However, its poor inherent conductivity and large volume expansion during repeated Li+-(de)intercalation processes greatly hinder the in-depth development of Sb2S3 based LIB anode materials. Herein, an Sb2S3/SnO2@rGO composite was prepared by using an interface engineering technique involving metal-containing ionic liquid precursors, in which Sb2S3/SnO2 quantum dots (QDs) as p-n heterojunctions are uniformly anchored on the surface of reduced graphene oxide (rGO). The p-n heterogeneous interface between Sb2S3 and SnO2 QDs induces an internal electric field, promoting the electronic/ion transport during electrochemical reactions, and the QD-sized Sb2S3/SnO2 heterostructure with a larger surface area provides more active sites for Li+-(de)intercalation reactions. In addition, the rGO matrix acts as a buffer to prevent the aggregation of active Sb2S3 and SnO2 QDs, alleviate the volume expansion, and enhance the conductivity of the composite during repeated cycles. These advantages endow the designed Sb2S3/SnO2@rGO electrode with excellent reaction kinetics and good long cycling stability. As an anode material of LIBs, it can still provide a reversible specific capacity of 474 mA h g-1 after 2000 cycles at a high current density of 3.0 A g-1, which is superior to those of most of the previously reported Sb2S3-based carbon materials. The p-n heterostructure construction strategy of nano-metal sulfide/metal oxides in this work can provide inspiration for the design and synthesis of other advanced energy storage materials.

Gestational diabetes mellitus induces congenital anomalies of the kidney and urinary tract in mice by altering RET/MAPK/ERK pathway.

Gestational diabetes mellitus (GDM) presents a substantial population health concern. Previous studies have revealed that GDM can ultimately influence nephron endowment. In this study, we established a GDM mouse model to investigate the embryological alterations and molecular mechanisms underlying the development of congenital anomalies of the kidney and urinary tract (CAKUT) affected by GDM. Our study highlights that GDM could contribute to the manifestation of CAKUT, with prevalent phenotypes characterized by isolated hydronephrosis and duplex kidney complicated with hydronephrosis in mice. Ectopic ureteric buds (UBs) and extended length of common nephric ducts (CNDs) were noted in the metanephric development stage. The expression of Ret and downstream p-ERK activity were enhanced in UBs, which indicated the alteration of RET/MAPK/ERK pathway may be one of the mechanisms contributing to the increased occurrence of CAKUT associated with GDM.

Optimized design of quaternary amino-functionalized chitosan fibers for ultra-high diclofenac adsorption from wastewater.

The extraction of non-steroidal anti-inflammatory drugs (NSAIDs) from water bodies is imperative due to the potential harm to humans and the ecosystem caused by NSAID-contaminated water. Quaternary amino-functionalized epichlorohydrin cross-linked chitosan fibers (QECFs), an economical and eco-friendly adsorbent, were successfully prepared using a simple and gentle method for efficient diclofenac (DCF) adsorption. Additionally, the optimized factors for the preparation of QECFs included epichlorohydrin concentration, pH, temperature, and (3-chloro-2-hydroxypropyl) trimethylammonium chloride (CHTAC) concentration. QECFs demonstrated excellent adsorption performance for DCF across a broad pH range of 7-12. The calculated maximum adsorption capacity and the amount of adsorbed DCF per adsorption site were determined to be 987.5 ± 20.1 mg/g and 1.2 ± 0.2, respectively, according to the D-R and Hill isotherm models, at pH 7 within 180 min. This performance surpassed that of previously reported adsorbents. The regeneration of QECFs could be achieved using a 0.5 mol/L NaOH solution within 90 min, with QECFs retaining their original fiber form and experiencing only a 9.18% reduction in adsorption capacity after 5 cycles. The Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy were used to study the characterization of QECFs, the preparation mechanism of QECFs, and the adsorption mechanism of DCF by QECFs. Quaternary ammonium groups (R4N+) were well developed in QECFs through the reaction between amino/hydroxyl groups on chitosan and CHTAC, and approximately 0.98 CHTAC molecule with 0.98 R4N+ group were immobilized on each chitosan monomer. Additionally, these R4N+ on QECFs played a crucial role in the removal of DCF.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Harnessing Nanochaperone-Mediated Autophagy for Selective Clearance of Pathogenic Tau Protein in Alzheimer's Disease.

Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid-ß (Aß) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy is demonstrated in neurodegeneration including AD, and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau-specific autophagy based on customized nanochaperone is developed for AD treatment. In this strategy, the nanochaperone can selectively bind to pathogenic tau and maintain tau homeostasis, thereby ensuring microtubule stability which is important for autophagy pathway. Meanwhile, the bound pathogenic tau can be sequestered in autophagosomes by in situ autophagy activation of nanochaperone. Consequently, autophagosomes wrapping with pathogenic tau are able to be trafficked along the stabilized microtubule to achieve successful fusion with lysosomes, resulting in the enhancement of autophagic flux and pathologic tau clearance. After treatment with this nanochaperone-mediated autophagy strategy, the tau burden, neuron damages, and cognitive deficits of AD mice are significantly alleviated in the brain. Therefore, this work represents a promising candidate for AD-targeted therapy and provides new insights into future design of anti-neurodegeneration drugs.

Streamlined synthesis of superstructure Ni-benzimidazole MOFs: Glucose electrochemical analysis.

The design and synthesis of efficient electrochemical sensors are crucial transformation technologies in electrochemistry. We successfully synthesize a three-dimensional Ni-metal-organic framework (MOF) nanostructured material with a superior architecture using benzimidazole and nickel nitrate as precursors at room temperature which is being applied in glucose electrochemical sensors. The reaction mechanism of M-6 during glucose detection is thoroughly studied using various characterization techniques, such as in situ Raman spectroscopy, in situ ultraviolet-visible spectrophotometry, synchrotron radiography, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The research findings demonstrate that the M-6 material exhibits high sensitivity for glucose detection, with a sensitivity of 2199.88 mA M-1 cm-2. This study provides an important reference for designing more efficient electrochemical reaction systems and optimizing material performance. Furthermore, the superstructural design offers new ideas and possibilities for the development and application of similar materials.

The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis.

Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

vizAPA: visualizing dynamics of alternative polyadenylation from bulk and single-cell data.

MOTIVATION: Alternative polyadenylation (APA) is a widespread post-transcriptional regulatory mechanism across all eukaryotes. With the accumulation of genome-wide APA sites, especially those with single-cell resolution, it is imperative to develop easy-to-use visualization tools to guide APA analysis. RESULTS: We developed an R package called vizAPA for visualizing APA dynamics from bulk and single-cell data. vizAPA implements unified data structures for APA data and genome annotations. vizAPA also enables identification of genes with differential APA usage across biological samples and/or cell types. vizAPA provides four unique modules for extensively visualizing APA dynamics across biological samples and at the single-cell level. vizAPA could serve as a plugin in many routine APA analysis pipelines to augment studies for APA dynamics. AVAILABILITY AND IMPLEMENTATION: https://github.com/BMILAB/vizAPA.

Transcriptome sequencing and expression analysis in peanut reveal the potential mechanism response to Ralstonia solanacearum infection.

BACKGROUND: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. RESULTS: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. CONCLUSIONS: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.

Novel fungal alternative proteins from Penicillium limosum for enhancing structural and functional properties of plant-based meat analogues.

Fungal proteins are excellent novel protein resources due to their high nutritional value and biological activity. In this study, a non-toxic strain of Penicillium limosum with a high biomass yield, protein, and essential amino acid contents, was isolated from wheat Qu (solid-state fermentation starter culture). Pea protein isolate (PPI) and P. limosum mycelial protein powder were extruded to prepare high-moisture meat analogues (HMMA), and their structural and functional properties were evaluated. Compared with 100% PPI, the addition of 5% mycoprotein enhanced the viscosity, gelling properties, chewiness, fibrous degree and in vitro protein digestibility (68.65%) of HMMA. Protein aggregates formed during high temperature extrusion, which increased the oil absorption capacity of HMMA (5% MY substitution). Conversely, their water absorption capacity indices were reduced by 5%. These findings provide a theoretical basis for the functional application of novel fungal alternative proteins.

Identifying causal associations between women's reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis.

BACKGROUND: A significant association between women's reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. METHODS: From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. RESULTS: The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512-0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407-0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR. CONCLUSIONS: Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.

Regional analysis of posterior corneal elevation after laser refractive surgeries for correction of myopia of different degrees.

PURPOSE: To evaluate regional changes in the posterior corneal elevation after three laser refractive surgeries for correction of myopia of different degrees. SETTINGS AND DESIGN: Retrospective, comparative, and non-randomized study. METHODS: Two hundred patients (200 eyes) who underwent laser epithelial keratoplasty (LASEK), femtosecond-assisted laser in-situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) were included in this study. According to preoperative spherical equivalent (SE), each surgical group was divided into two refractive subgroups: low-to-moderate myopia (LM group) and high myopia (H group). The posterior corneal elevation from Pentacam Scheimpflug tomography was analyzed preoperatively and at 1 month, 3 months, 6 months, and 12 months postoperatively. Three subregions of the posterior cornea were divided in this study as the central, paracentral, and peripheral regions. STATISTICAL ANALYSIS USED: Generalized Estimating Equations (GEE). RESULTS: For all three surgical groups, similar changing trends were seen in the two refractive subgroups. H group presented a larger changing magnitude than the LM group in FS-LASIK over time ( P < 0.05), whereas no significant difference was noted in the two refractive subgroups of LASEK or SMILE ( P > 0.05). At 12 months postoperatively, the central posterior corneal elevation returned to the preoperative level in LASEK ( P > 0.05) but shifted forward significantly in FS-LASIK and SMILE ( P < 0.05). CONCLUSION: Different posterior corneal regions respond differently to corneal refractive surgeries. LASEK, FS-LASIK, and SMILE demonstrate different trends in the regional changes in posterior corneal elevation. The corneal shape seems more stable in LASEK than in FS-LASIK and SMILE.

Co-catalpol alleviates fluoxetine-induced main toxicity: Involvement of ATF3/FSP1 signaling-mediated inhibition of ferroptosis.

BACKGROUND: Fluoxetine is often used as a well-known first-line antidepressant. However, it is accompanied with hepatogenic injury as its main organ toxicity, thereby limiting its application despite its superior efficacy. Fluoxetine is commonly traditionally used combined with some Chinese antidepressant prescriptions containing Rehmannia glutinosa (Dihuang) for depression therapy and hepatoprotection. Our previous experiments showed that co-Dihuang can alleviate fluoxetine-induced liver injury while efficiencies, and catalpol may be the key ingredient to characterize the toxicity-reducing and synergistic effects. However, whether co-catalpol can alleviate fluoxetine-induced liver injury and its toxicity-reducing mechanism remain unclear. PURPOSE: On the basis of the first recognition of the dose and duration at which pre-fluoxetine caused hepatic injury, co-catalpol's alleviation of fluoxetine-induced hepatic injury and its pathway was comprehensively elucidated. METHOD AND RESULTS: The hepatoprotection of co-catalpol was evaluated by serum biochemical indexes sensitive to hepatic injury and multiple staining techniques for hepatic pathologic analysis. Subsequently, the pathway by which catalpol alleviated fluoxetine-induced hepatic injury was predicted by network pharmacology to be predominantly the inhibition of ferroptosis. These were validated and confirmed in subsequent experiments with key technologies and diagnostic reagents related to ferroptosis. Further molecular docking showed that activating transcription factor 3 (ATF3) and ferroptosis suppressor protein 1 (FSP1) were the the most prospective molecules for catalpol and fluoxetine among many ferroptosis-related molecules. The critical role of ATF3/FSP1 signaling was further observed by surface plasmon resonance, diagnostic reagents, transmission electron microscopy, Western blot, real-time PCR, immunofluorescence, and immunohistochemistry. Results showed that fluoxetine directly bound to ATF3 and FSP1; agonisting ATF3 or blocking FSP1 abolished the alleviation of catalpol on fluoxetine-induced liver injury, and both exacerbated ferroptosis. Moreover, co-catalpol significantly enhanced the antidepressant efficacy of fluoxetine against depressive behaviours in mice. CONCLUSION: The hepatic impairment properties of fluoxetine were largely dependent on ATF3/FSP1 target-mediated ferroptosis. Co-catalpol alleviated fluoxetine-induced hepatic injury while enhancing its antidepressant efficacy, and that ATF3/FSP1 signaling-mediated inhibition of ferroptosis was involved in its co-administration detoxification mechanism. This study was the first to reveal the hepatotoxicity characteristics, targets, and mechanisms of fluoxetine; provide a detoxification and efficiency regimen by co-catalpol; and elucidate the detoxification mechanism.

Identification of two major QTLs for pod shell thickness in peanut (Arachis hypogaea L.) using BSA-seq analysis.

BACKGROUND: Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST. RESULTS: An F2 segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST. On the basis of a bulked segregant analysis sequencing (BSA-seq), four QTLs were preliminarily mapped to chromosomes 3, 8, 13, and 18. Using the genome resequencing data of YY18 and WH8, 22 kompetitive allele-specific PCR (KASP) markers were designed for the genotyping of the F2 population. Two major QTLs (qPSTA08 and qPSTA18) were identified and finely mapped, with qPSTA08 detected on chromosome 8 (0.69-Mb physical genomic region) and qPSTA18 detected on chromosome 18 (0.15-Mb physical genomic region). Moreover, qPSTA08 and qPSTA18 explained 31.1-32.3% and 16.7-16.8% of the phenotypic variation, respectively. Fifteen genes were detected in the two candidate regions, including three genes with nonsynonymous mutations in the exon region. Two molecular markers (Tif2_A08_31713024 and Tif2_A18_7198124) that were developed for the two major QTL regions effectively distinguished between thick-shelled and thin-shelled materials. Subsequently, the two markers were validated in four F2:3 lines selected. CONCLUSIONS: The QTLs identified and molecular markers developed in this study may lay the foundation for breeding cultivars with a shell thickness suitable for mechanized peanut shelling.