Construction of recombinant pseudorabies virus expressing PCV2 Cap, PCV3 Cap, and IL-4: investigation of their biological characteristics and immunogenicity.

Background: Porcine circovirus type 2 (PCV2) is a globally prevalent and recurrent pathogen that primarily causes slow growth and immunosuppression in pigs. Porcine circovirus type 3 (PCV3), a recently discovered virus, commonly leads to reproductive disorders in pigs and has been extensively disseminated worldwide. Infection with a single PCV subtype alone does not induce severe porcine circovirus-associated diseases (PCVD), whereas concurrent co-infection with PCV2 and PCV3 exacerbates the clinical manifestations. Pseudorabies (PR), a highly contagious disease in pigs, pose a significant threat to the swine industry in China. Methods: In this study, recombinant strains named rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 was constructed by using a variant strain XJ of pseudorabies virus (PRV) as the parental strain, with the TK/gE/gI genes deleted and simultaneous expression of PCV2 Cap, PCV3 Cap, and IL-4. The two recombinant strains obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster Syrian kidney-21 (BHK-21) cells and is safe to mice. Results: rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 exhibited good safety and immunogenicity in mice, inducing high levels of antibodies, demonstrated 100% protection against the PRV challenge in mice, reduced viral loads and mitigated pathological changes in the heart, lungs, spleen, and lymph nodes during PCV2 challenge. Moreover, the recombinant viruses with the addition of IL-4 as a molecular adjuvant outperformed the non-addition group in most indicators. Conclusion: rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 hold promise as recombinant vaccines for the simultaneous prevention of PCV2, PCV3, and PRV, while IL-4, as a vaccine molecular adjuvant, effectively enhances the immune response of the vaccine.

FTY720 Suppresses Pathogenic Retinal Müller Cell Activation and Chronic Progression by Inhibiting the mTOR/NF-κB Signaling Pathway and Regulating Autophagy.

PURPOSE: FTY720 is an agonist of the Sphingosine-1-phosphate (S1P) receptor 1, 3, 4, and 5 and a functional antagonist of the S1P1 receptor; it can inhibit the activation of mTOR/NF-κB and has therapeutic potential in inflammatory disease. This study was designed to determine the role of the inflammatory process in diabetic retinopathy and investigate the effect of FTY720 on high glucose (HG)-induced rat retinal Müller cells (rMC-1 cells). METHODS: In the present study, the role of FTY720 in inhibiting inflammation and its underlying mechanism were investigated. rMC-1 cells were treated without or with HG, FTY720, CQ, or RAP. Cell viability was examined by CCK-8 assay; cell activation was assessed by western blot analysis and IF staining; and cell migration was evaluated by a scratch wound healing assay. The expression of inflammation-associated proteins and autophagy-related proteins was evaluated by transmission electron microscopy, AO staining, MDC-labeled autophagic vacuoles, western blot analysis and ELISA. RESULTS: Western blot analysis and IF staining showed that the level of the rMC-1 cell marker GFAP was decreased, while GS was increased in FTY720 groups compared to that in the HG group. The healing assay results showed that compared with HG treatment, FTY720 treatment significantly reduced cell migration. Western blot analysis, ELISA and IF staining showed that compared with HG, FTY720 reduced proinflammatory proteins by inhibiting the mechanistic target of the mTOR/NF-κB signaling pathway and regulating autophagy. CONCLUSIONS: This study suggests that in an HG-induced rMC-1 cell model, FTY720 significantly inhibited the production of inflammatory cytokines by inhibiting mTOR/NF-κB signaling and regulating autophagy. These findings were associated with a decrease in rMC-1 cell injury, suggesting that FTY720 or related compounds may be valuable modulators of HG-induced retinal injury.

Screening for thalassemia carriers among the Han population of childbearing age in Southwestern of China.

Purpose: Thalassemia is a severe hereditary blood disorder that poses a significant threat to human health and leads to mortality and disability. It is one of the most prevalent monogenic diseases worldwide. The aim of this study was to analyze the molecular epidemiological data of individuals of childbearing age from the Han ethnic group with thalassemia in Southwest China and to explore the application of next-generation sequencing (NGS) technology in screening thalassemia carriers. Methods: The participants were Han males and females of childbearing age who sought medical advice at the West China Second University Hospital, Sichuan University from June 2022 to June 2023. We detected α- and ß-thalassemia mutations using full-length capture of the thalassemia genes and NGS technology. Results: In a cohort of 1,093 participants, 130 thalassemia carriers were identified, with an overall detection rate of 11.89% (130/1,093). Among these, 0.91% (10/1,093) had mutations that could not be detected using traditional PCR techniques. The proportions of carriers with α-, ß-, and α-complexed ß-thalassemia gene mutations were 7.68% (84/1,093), 3.93% (43/1,093), and 0.27% (3/1,093), respectively. We identified a novel HBA2 c.166del variant that has not been previously reported. Conclusion: Using NGS technology, we found that the mutation-carrying rate of thalassemia genes was 11.89% in the Han population of childbearing age in Southwest China. Compared with the results of traditional PCR techniques, NGS detected an additional 0.91% (10/1,093) rare genetic variants. NGS technology should be utilized as the primary screening method for thalassemia carriers among Han nationality people of childbearing age in Southwest China.

Exploring Tunable Properties, Solvent-Modulated Dynamics, and Novel C(sp3)-H Activation Mechanisms in Electron Donor-Acceptor Complexes.

Electron donor-acceptor (EDA) complex photochemistry has emerged as a vibrant area in visible-light-mediated synthetic radical chemistry. However, theoretical insights into the reaction mechanisms remain limited. Our study investigates the influence of solvent polarity and halogen atom types on radical reaction pathways in EDA complexes. We demonstrate that solvent polarity modulates the charge transfer and spatial arrangement within EDA complexes, thereby influencing their stability and reaction kinetics. Iodide ions play a crucial role in facilitating free radical generation and stabilizing reaction intermediates. Different halogen atom types exhibit distinct effects on radical reactions. Variations in radical concentration and solvent environment further affect the pathway selectivity. Additionally, light conditions influence the free radical generation and pathway selectivity. Our findings enhance the understanding of EDA complex photochemistry and radical reactions, offering insights for organic synthesis and photochemistry applications.

Transcriptome and metabolome analysis reveals PRV XJ delgE/gI/TK protects intracranially infected mice from death by regulating the inflammation.

Pseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK-STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.

Reproductive factors and subsequent pregnancy outcomes in patients with prior pregnancy loss.

BACKGROUND: At present, individualized interventions can be given to patients with a clear etiology of pregnancy loss to improve the subsequent pregnancy outcomes, but the current reproductive status of the patient cannot be changed. The aim of this study was to investigate the association between female reproductive status and subsequence pregnancy outcome in patients with prior pregnancy loss (PL). METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to February 2022, a total of 1955 women with at least one previous PL were enrolled. Maternal reproductive status and subsequent reproductive outcomes were recorded through an electronic medical record system and follow-up. Logistic regression was used to evaluate the association between reproductive status and the risk of subsequent reproductive outcomes. RESULTS: Among all patients, the rates of subsequent infertility, early PL, late PL, and live birth were 20.82%, 24.33%, 1.69% and 50.77% respectively. In logistic regression, we found that age (OR 1.08, 95% CI 1.04-1.13) and previous cesarean delivery history (OR 2.46, 95% CI 1.27-4.76) were risk factors for subsequent infertility in patients with PL. Age (OR 1.06, 95% CI 1.03-1.10), age at first pregnancy (OR 1.06, 95% CI 1.03-1.10), BMI (OR 1.06, 95% CI 1.02-1.11), previous PL numbers (OR 1.18, 95% CI 1.04-1.57) and without pre-pregnancy intervention (OR 1.77, 95% CI 1.35-2.24) were risk factors for non-live birth. Age (OR 1.06, 95% CI 1.03-1.09), age at first pregnancy (OR 1.06, 95% CI 1.02-1.09), BMI (OR 1.07, 95% CI 1.02-1.11), previous PL numbers (OR 1.15, 95% CI 1.02-1.31) and without pre-pregnancy intervention (OR 2.16, 95% CI 1.65-2.84) were risk factors for PL. CONCLUSIONS: The reproductive status of people with PL is strongly correlated with the outcome of subsequent pregnancies. Active pre-pregnancy intervention can improve the subsequent pregnancy outcome. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

The Quality Evaluation of Highland Barley and Its Suitability for Chinese Traditional Tsampa Processing.

The physicochemical traits of highland barley prominently affect the quality of Tsampa. To find out the relevance between the physicochemical properties of raw material and the texture parameters of processed products, twenty-five physicochemical traits and ten quality parameters for seventy-six varieties of highland barley were measured and analyzed. The results showed that there was a significant difference between the physicochemical indexes for highland barleys of various colors. The dark highland barley generally has more fat, protein, total dietary fiber, phenolic, Mg, K, Ca, and Zn and less amylose, Fe, Cu, and Mo than light colored barley. Then, these highland barleys were made into Tsampa. A comprehensive quality evaluation model based on the color and texture parameters of Tsampa was established through principal component analysis. Then, cluster analysis was used to classify the tested samples into three edible quality grades predicated on the above evaluation model. At last, the regression analysis was applied to establish a Tsampa quality predictive model according to the physicochemical traits of the raw material. The results showed that amylose, protein, ß-Glucan, and a* and b* could be used to predict the comprehensive quality of Tsampa. The predicted results indicated that 11 of 14 validated samples were consistent with the actual quality, and the accuracy was above 78.57%. Our study built the approach of the appropriate processing varieties evaluation. It may provide reference for processing specific highland barley.

The construction and immunogenicity analyses of a recombinant pseudorabies virus with Senecavirus A VP3 protein co-expression.

Senecavirus A (SVA)-associated porcine idiopathic vesicular disease (PIVD) and Pseudorabies (PR) are highly contagious swine disease that pose a significant threat to the global pig industry. In the absence of an effective commercial vaccine, outbreaks caused by SVA have occurred in many parts of the world. In this study, the PRV variant strain PRV-XJ was used as the parental strain to construct a recombinant PRV strain with the TK/gE/gI proteins deletion and the VP3 protein co-expression, named rPRV-XJ-ΔTK/gE/gI-VP3. The results revealed that PRV is a suitable viral live vector for VP3 protein expressing. As a vaccine, rPRV-XJ-ΔTK/gE/gI-VP3 is safe for mice, vaccination with it did not cause any clinical symptoms of PRV. Intranasal immunization with rPRV-XJ-ΔTK/gE/gI-VP3 induced strong cellular immune response and high levels of specific antibody against VP3 and gB and neutralizing antibodies against both PRV and SVA in mice. It provided 100% protection to mice against the challenge of virulent strain PRV-XJ, and alleviated the pathological lesion of heart and liver tissue in SVA infected mice. rPRV-XJ-ΔTK/gE/gI-VP3 appears to be a promising vaccine candidate against PRV and SVA for the control of the PRV variant and SVA.

Preliminary nomogram model for predicting irreversible organ damage of patients with systemic sclerosis.

OBJECTIVE: To investigate predictive factors for irreversible organ damage in systemic sclerosis (SSc) and establish a nomogram model. METHODS: This retrospective study included patients with SSc who were treated at our hospital between March 2013 and March 2023. Irreversible organ damage included heart failure, respiratory failure, renal failure, and gangrene of the hands and feet. Cox and LASSO regression analyses were performed to determine the predictive factors. Based on the results, a nomogram model was developed. The model was evaluated using the C-indices, calibration plots, and DCA. RESULTS: A total of 361 patients with systemic sclerosis were randomly divided into the development (n = 181) and validation (n = 180) groups. Multivariate Cox regression analysis showed that age ≥65 years, weight loss, digital ulcers, mRSS ≥16, elevated creatinine, elevated myoglobin, elevated C-reactive protein, renal involvement, and cardiac involvement were independent risk factors. Based on the LASSO analysis, a nomogram model of irreversible organ damage was established. The C-indices of the development group at 24, 60, and 96 m were 96.7, 84.5, and 85.7, whereas those of the validation group at 24, 60, and 96 m were 86.6, 79.1, and 78.5, respectively. The results of the DCA showed that the nomogram can be used as a valuable tool to predict irreversible organ damage in patients with SSc. CONCLUSION: We included commonly used clinical indicators. According to the nomogram, the probability of irreversible organ damage can be calculated and high-risk patients can be identified.

Magnetic Resonance Spectroscopy Spectral Registration Using Deep Learning.

BACKGROUND: Deep learning-based methods have been successfully applied to MRI image registration. However, there is a lack of deep learning-based registration methods for magnetic resonance spectroscopy (MRS) spectral registration (SR). PURPOSE: To investigate a convolutional neural network-based SR (CNN-SR) approach for simultaneous frequency-and-phase correction (FPC) of single-voxel Meshcher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data. STUDY TYPE: Retrospective. SUBJECTS: Forty thousand simulated MEGA-PRESS datasets generated from FID Appliance (FID-A) were used and split into the following: 32,000/4000/4000 for training/validation/testing. A 101 MEGA-PRESS medial parietal lobe data retrieved from the Big GABA were used as the in vivo datasets. FIELD STRENGTH/SEQUENCE: 3T, MEGA-PRESS. ASSESSMENT: Evaluation of frequency and phase offsets mean absolute errors were performed for the simulation dataset. Evaluation of the choline interval variance was performed for the in vivo dataset. The magnitudes of the offsets introduced were -20 to 20 Hz and -90° to 90° and were uniformly distributed for the simulation dataset at different signal-to-noise ratio (SNR) levels. For the in vivo dataset, different additional magnitudes of offsets were introduced: small offsets (0-5 Hz; 0-20°), medium offsets (5-10 Hz; 20-45°), and large offsets (10-20 Hz; 45-90°). STATISTICAL TESTS: Two-tailed paired t-tests for model performances in the simulation and in vivo datasets were used and a P-value <0.05 was considered statistically significant. RESULTS: CNN-SR model was capable of correcting frequency offsets (0.014 ± 0.010 Hz at SNR 20 and 0.058 ± 0.050 Hz at SNR 2.5 with line broadening) and phase offsets (0.104 ± 0.076° at SNR 20 and 0.416 ± 0.317° at SNR 2.5 with line broadening). Using in vivo datasets, CNN-SR achieved the best performance without (0.000055 ± 0.000054) and with different magnitudes of additional frequency and phase offsets (i.e., 0.000062 ± 0.000068 at small, -0.000033 ± 0.000023 at medium, 0.000067 ± 0.000102 at large) applied. DATA CONCLUSION: The proposed CNN-SR method is an efficient and accurate approach for simultaneous FPC of single-voxel MEGA-PRESS MRS data. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Multiomics was used to clarify the mechanism by which air pollutants affect chronic obstructive pulmonary disease: A human cohort study.

Exposure to air pollutants has been associated with various adverse health outcomes, including chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanism by which air pollution impacts COPD through remains insufficiently understood. To elucidated the molecular mechanism by which air pollutant exposure contributes to alterations in the gut microbiome and metabolism in AECOPD patients, we employed metagenomics and untargeted metabolomics to analyse the gut microbial, faecal, and serum metabolites. The correlations among air pollutants, gut microbes, serum metabolites, and blood biochemical markers were assessed using generalised additive mixed models and Spearman correlation analysis. The findings revealed that for every 10 µg/m3 increase in PM2.5 concentration, the α-diversity of the gut flora decreased by 2.16% (95% CI: 1.80%-2.53%). We found seven microorganisms that were significantly associated with air pollutants, of which Enterococcus faecium, Bacteroides fragilis, Ruthenibacterium lactatiformans, and Subdoligranulum sp.4_3_54A2FAA were primarily associated with glycolysis. We identified 13 serum metabolites and 17 faecal metabolites significantly linked to air pollutants. Seven of these metabolites, which were strongly associated with air pollutants and blood biochemical indices, were found in both serum and faecal samples. Some of these metabolites, such as 2,5-furandicarboxylic acid, C-8C1P and melatonin, were closely associated with disturbances in lipid and fatty acid metabolism in AECOPD patients. These findings underscore the impact of air pollutants on overall metabolism based on influencing gut microbes and metabolites in AECOPD patients. Moreover, these altered biomarkers establish the biologic connection between air pollutant exposure and AECOPD outcomes.The identification of pertinent biomarkers provides valuable insights for the development of precision COPD prevention strategies.

Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Maternal CHD7 gonosomal mosaicism in a fetus with CHARGE syndrome.

Parental mosaicism is important in families with de novo mutations. Herein, we report a case of fetal CHARGE syndrome (CS) with a CHD7 variant inherited from maternal CHD7 gonosomal mosaicism. The variant was detected through trio-based whole-exome sequencing and Sanger sequencing. High-depth whole-exome sequencing was performed for the identification of parental mosaicism. A novel heterozygous CHD7 nonsense mutation (c.5794G>T/ p.E1932*) was detected in the tissue from the aborted fetus. The parents were wild-type, indicating that the mutation was a de novo variant. The mutation was suspected to be the cause of the fetal CS. However, high-depth whole-exome sequencing revealed maternal gonosomal mosaicism at a variant allele frequency of 3.2%-23.3%. The variant was identified in various tissues (peripheral blood, hair follicles, buccal epithelia, and pharyngeal epithelia) from the asymptomatic mother. We confirmed maternal CHD7 gonosomal mosaicism as a genetic cause of fetal CS. Our results emphasize the importance of clinical analysis in accurately determining the parents' status in detecting the CHD7 de novo variant in fetal CS, as this analysis has vital implications for evaluating the recurrence risk for genetic counseling.

Prevalence of dry eye during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: During the COVID-19 pandemic, many people devoted longer time to screen viewing due to the need for study, work, and online social activities, instead of outdoor activities, which may have led to an increase in dry eye symptoms. This study aimed to evaluate the prevalence of dry eye during the COVID-19 pandemic. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were searched from January 1, 2020 to October 20, 2022. Cross-sectional surveys on dry eye prevalence conducted after January 1, 2020 were included. Two review authors independently performed data extraction and assessed study quality. The random-effects model was used to analyze the prevalence of dry eye, and the odds ratio was used to assess the strength of the association between variables. Subgroup analysis was performed to detect heterogeneity, the leave-one-out method for sensitivity analysis, and the Egger test for publication bias. RESULTS: A total of eleven studies with 15692 individuals met the eligibility criteria. The prevalence of dry eye during the COVID-19 pandemic was 61.0% (95%CI: 51.8%-70.2%) globally and 56.7% (95%CI: 45.3%-68.1%) in Asia. The prevalence of dry eye had significant differences in sex and visual display time, with higher prevalence among females and visual display time of more than 4 hours per day. Subgroup analysis was performed based on diagnostic tools, study population, and average age. A significant difference was found in diagnostic tools, but no significant change in heterogeneity (P<0.05). The leave-one-out method showed stable results, and the Egger test identified no significant publication bias. CONCLUSION: The prevalence of dry eye during the COVID-19 pandemic is significantly higher than before, and a higher prevalence is found among females and those having a visual display time of more than 4 hours per day.

Complete mitochondrial genome of the endangered Prunus pedunculata (Prunoideae, Rosaceae) in China: characterization and phylogenetic analysis.

Introduction: Prunus pedunculata (Prunoideae: Rosaceae), a relic shrub with strong resistance and multiple application values, is endangered in China. Extensive research had been devoted to gene expression, molecular markers, plastid genome analysis, and genetic background investigations of P. pedunculata. However, the mitochondrial genome of this species has not been systematically described, owing to the complexity of the plant mitogenome. Methods: In the present research, the complete mitochondrial genome of P. pedunculata was assembled, annotated, and characterized. The genomic features, gene content and repetitive sequences were analyzed. The genomic variation and phylogenetic analysis have been extensively enumerated. Results and discussion: The P. pedunculata mitogenome is a circular molecule with a total length of 405,855 bp and a GC content of 45.63%, which are the smallest size and highest GC content among the known Prunus mitochondrial genomes. The mitogenome of P. pedunculata encodes 62 genes, including 34 unique protein-coding genes (PCGs, excluding three possible pseudogenes), three ribosomal RNA genes, and 19 transfer RNA genes. The mitogenome is rich in repetitive sequences, counting 112 simple sequence repeats, 15 tandem repeats, and 50 interspersed repetitive sequences, with a total repeat length of 11,793 bp, accounting for 2.91% of the complete genome. Leucine (Leu) was a predominant amino acid in PCGs, with a frequency of 10.67%, whereas cysteine (Cys) and tryptophan (Trp) were the least adopted. The most frequently used codon was UUU (Phe), with a relative synonymous codon usage (RSCU) value of 1.12. Selective pressure was calculated based on 20 shared PCGs in the mitogenomes of the 32 species, most of which were subjected to purifying selection (Ka/Ks < 1), whereas ccmC and ccmFn underwent positive selection. A total of 262 potential RNA editing sites in 26 PCGs were identified. Furthermore, 56 chloroplast-derived fragments were ascertained in the mitogenome, ranging from 30 to 858 bp, and were mainly located across IGS (intergenic spacer) regions or rRNA genes. These findings verify the occurrence of intracellular gene transfer events from the chloroplast to the mitochondria. Furthermore, the phylogenetic relationship of P. pedunculata was supported by the mitogenome data of 30 other taxa of the Rosaceae family. Understanding the mitochondrial genome characteristics of P. pedunculata is of great importance to promote comprehension of its genetic background and this study provides a basis for the genetic breeding of Prunus.

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. METHODS: RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. RESULTS: The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. CONCLUSION: We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

Associations between vitamin C intake and serum uric acid in US adults: Findings from National Health and Nutrition Examination Survey 2011-2016.

BACKGROUNDS: Dietary factors has been found to influence serum uric acid (SUA) levels. We further explored the associations between dietary and supplemental vitamin C intake and SUA in a large population-based study. METHODS: The cross-sectional study included 6308 participants (3146 males and 3162 females) aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 in the United States. The dietary vitamin C was log-transformed for statistical analysis. Hyperuricemia was defined as SUA concentrations >420 umol/L in males or >360 umol/L in females. The associations of dietary vitamin C and supplemental vitamin C with SUA levels and hyperuricemia risk were evaluated using weighted linear regression models and weighted multivariate logistic regression models, and a subgroup analysis stratified by gender was also conducted. RESULTS: In this large-scale database study, there was a negative association between dietary vitamin C (log transformed) and SUA levels in US adults (ß = -7.27, 95% CI: -11.58, -2.97). The inverse relationship existed among males but not females (P for interaction = 0.02). There was inverse correlation between dietary vitamin C (log transformed) and hyperuricemia risk (OR = 0.68, 95% CI: 0.57, 0.81), especially in males compared to females determined through an interaction test (P = 0.04). There were no associations between supplemental vitamin C and SUA levels (ß = 1.00 (95% CI: -4.44, 6.44) or hyperuricemia risk (OR = 0.98 (95% CI: 0.78, 1.24). High-dosage supplemental vitamin C (>300 mg) and hyperuricemia risk were not associated (OR = 1.04, 95% CI: 0.69, 1.56). CONCLUSIONS: This study demonstrated that there were negative associations between dietary vitamin C and SUA levels and hyperuricemia risk among US adults. The inverse correlations between dietary vitamin C and hyperuricemia risk were more significant in males compared to females. There were no associations between supplemental vitamin C and SUA levels or hyperuricemia risk.

Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility.

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss-of-function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility.

NIR-II photoacoustic imaging-guided synergistic cancer therapy with a tumor-targeting copper selenide-iron manganese layered double hydroxide nanocomplex.

A novel biodegradable layered double hydroxide-copper selenide nanocomplex was prepared by anchoring copper selenide on manganese iron layered double hydroxide nanosheets. This nanocomplex can specifically release CuSe, Mn2+ and Fe3+ in the tumor microenvironment, which implements NIR-II photoacoustic imaging-guided synergistic cancer therapy under 1064 nm laser irradiation.

Detecting schizophrenia with 3D structural brain MRI using deep learning.

Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.