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Summary: Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr−/−) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.

Abstract Background The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. Methods A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. Results Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. Conclusions Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

With the rapid development of artificial intelligence (AI) technology, especially the application of deep learning (DL), the detection and quantitative evaluation of typical imaging markers of small cerebral vascular disease (CSVD) has been accelerated and the accuracy has been improved. In recent years, it has attracted much attention in the field of medical imaging. This paper intends to summarize the research progress and problems of deep learning in the imaging markers of CSVD such as cerebral microbleeds (CMBs), white matter hyperintensities (WMH), enlarged perivascular space (EPVS), lacunes, recent small subcortical infarcts (RSSI) and cerebral atrophy, so as to provide support for the precise treatment of CSVD.

Engineering Cu to achieve high catalytic selectivity towards carbon monoxide at high current density is challenging. Here, the authors report an Cu-Sb single-atom alloy catalyst that catalyzes CO2 reduction at a current density of 500 mA cm−2 with CO FE of ca. 91%.

Separation of actinides from lanthanides is very important for the safe management of nuclear waste, however still challenging due to the chemical complexity of the f-elements. Here, authors report an efficient strategy with graphene oxide membranes for ion sieving of high valent actinyl ions and spherical lanthanide ions.

(1) Background: The three sloe bugs, Dolycoris baccarum, Dolycoris indicus, and Dolycoris penicillatus, are found in the Chinese mainland and are morphologically similar. The species boundaries and phylogenetic relationships of the three species remain uncertain; (2) Methods: In this study, we generated multiple mitochondrial genomes (mitogenomes) for each of the three species and conducted comparative mitogenomic analysis, species delimitation, and phylogenetic analysis based on these data; (3) Results: Mitogenomes of the three Dolycoris species are conserved in nucleotide composition, gene arrangement, and codon usage. All protein-coding genes (PCGs) were found to be under purifying selection, and the ND4 evolved at the fastest rate. Most species delimitation analyses based on the COI gene and the concatenated 13 PCGs retrieved three operational taxonomic units (OTUs), which corresponded well with the three Dolycoris species identified based on morphological characters. A clear-cut barcode gap was discovered between the interspecific and intraspecific genetic distances of the three Dolycoris species. Phylogenetic analyses strongly supported the monophyly of Dolycoris, with interspecific relationship inferred as (D. indicus + (D. baccarum + D. penicillatus)); (4) Conclusions: Our study provides the first insight into the species boundaries and phylogenetic relationships of the three Dolycoris species distributed across the Chinese mainland.

To counter the harmful impacts of agricultural chemicals on the environment and human health, there is an increasing demand for safe, eco-friendly, and potent plant-based biopesticides. In this study, we aimed to investigate the antimicrobial effects of ginger essential oil and selected volatile compounds (linalool, eugenol, citral, and cinnamaldehyde [CA]) against Fusarium oxysporum FOX-1. Minimum inhibitory concentrations (MICs) were determined using the mycelium growth inhibition method. The compound CA exhibited the most potent antifungal effect against F. oxysporum FOX-1 and was selected for further investigation. After treatment with CA at 1/2 MIC or MIC, the spore germination of F. oxysporum FOX-1 was significantly inhibited at 12 h. Furthermore, microscopic observation revealed that CA treatment resulted in the morphological degradation of F. oxysporum FOX-1. CA destroyed the cell membrane integrity of F. oxysporum FOX-1, increasing the relative conductivity and the leakage of intracellular protein, nucleic acids, and malondialdehyde, affecting the integrity and metabolism of the cell membrane. The effects were positively related to CA concentration. Additionally, in vivo experiments with rhizome sections showed that CA significantly reduced the pathogenicity of F. oxysporum FOX-1. Overall, these findings provide evidence for the potential of using ginger essential oil components as fungicides, offering a basis for future research to develop robust and eco-friendly plant-derived fungicides that serve as a sustainable means to reduce fungus-driven agricultural losses.

Abstract Background Activating transcription factor 3 (ATF3) is a nuclear protein that is widely expressed in a variety of cells. It is a stress‐inducible transcription gene and a member of the activating transcription factor/cAMP responsive element‐binding protein (ATF/CREB) family. Methods The comprehensive literature review was conducted by searching PubMed and Google Scholar. Search terms used were “ATF3”, “ATF3 and (ALI or ARDS)”, “ATF3 and COPD”, “ATF3 and PF”, and “ATF3 and Posttranslational modifications”. Results Recent studies have shown that ATF3 plays a critical role in many inflammatory pulmonary diseases, including acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF). ATF3 participates in many signaling pathways and complex pathophysiological processes, such as inflammation, immunity, endoplasmic reticulum stress, and cell proliferation. However, the role of ATF3 in current studies is controversial, and there are reports showing that ATF3 plays different roles in different pulmonary diseases. Conclusions In this review, we first summarized the structure, function, and mechanism of ATF3 in various inflammatory pulmonary diseases. The impact of ATF3 on disease pathogenesis and the clinical implications was particularly focused on, with an overall aim to identify new targets for treating inflammatory pulmonary diseases.

Low-dimensional materials have attracted increasing attention due to their guiding significance for material preparation and potential wide-ranging applications. Through the controllable synthesis and suitably designed fusion of low-dimensional materials into ordered complex superstructures, it has become an effective way to explore new properties of materials and construct structures meeting new application needs. Based on low-dimensional materials such as metal oxides, copolymers, metal-organic complexes, and organic crystals, great efforts have been devoted to the design and construction of complex superstructures with regular repeatability. A series of unique cases including multi-block, core/multi-shell, hyperbranched and network structures have been reported, which has promoted the development of the field of material preparation. Herein, we summarize representative progress of low-dimensional complex superstructures in a reasonable structure classification manner. Ultimately, the existing challenges are discussed, and an outlook is given for future study of precise construction of superstructures as well as exploitation of potential applications.

Abstract The efficient CO2 electroreduction into high‐value products largely relies on the CO2 adsorption/activation or electron‐transfer of electrocatalysts, thus site‐specific functionalization methods that enable boosted related interactions of electrocatalysts are much desired. Here, an oriented coordination strategy is reported to introduce N‐rich auxiliary (i.e., hexamethylenetetramine, HMTA) into metalloporphyrin metal organic frameworks (MOFs) to synthesize a series of site‐specific functionalized electrocatalysts (HMTA@MOF‐545‐M, M = Fe, Co, and Ni) and they are successfully applied in light‐assisted CO2 electroreduction. Noteworthy, thus‐obtained HMTA@MOF‐545‐Co presents approximately two times enhanced CO2 adsorption‐enthalpy and electrochemical active surface‐area with largely decreased impedance‐value after modification, resulting in almost twice higher CO2 electroreduction performance than its unmodified counterpart. Besides, its CO2 electroreduction performance can be further improved under light‐illumination and displays superior FECO (≈100%), high CO generation rate (≈5.11 mol m−2 h−1 at −1.1 V) and energy efficiency (≈70% at −0.7 V). Theoretical calculations verify that the oriented coordination of HMTA can increase the charge density of active sites, almost doubly enhance the CO2 adsorption energy, and largely reduce the energy barrier of rate determining step for the boosted performance improvement. This work might promote the development of modifiable porous crystalline electrocatalysts in high‐efficiency CO2 electroreduction.

Aphids heavily rely on their olfactory system for foraging behavior. Odorant-degrading enzymes (ODEs) are essential in preserving the olfactory acuity of aphids by removing redundant odorants in the antennae. Certain enzymes within this group stand out as being enriched and/or biased expressed in the antennae, such as carboxylesterases (CXEs), cytochrome P450 (CYPs), glutathione S-transferases (GSTs), and UDP-glycosyltransferases (UGTs). Here, we performed a comparative transcriptome analysis of antennae and body tissue to isolate the antennal ODE genes of turnip aphid Lipaphis erysimi. A dataset of one CXE, seven CYPs, two GSTs, and five UGTs enriched in the antennae was identified and subjected to sequence analysis. Furthermore, qRT-PCR analyses showed that 13 ODE genes (LeCXE6, LeCYP4c1, LeCYP6a2, LeCYP6a13, LeCYP6a14.2, LeCYP6k1, LeCYP18a1, LeGST1, LeUGT1-7, LeUGT2B7, LeUGT2B13, LeUGT2C1.1, and LeUGT2C1.2) were specifically or significantly elevated in antennal tissues. Among these antennae-enriched ODEs, LeCYP4c1, LeCYP6a2, LeCYP6a13, LeCYP6a14.2, LeCYP18a1, LeUGT2B7, and LeUGT2B13 were found to exhibit significantly higher expression levels in alate aphids compared to apterous and nymph aphids, suggesting their putative role in detecting new host plant location. The results presented in this study highlight the identification and expression of ODE genes in L. erysimi, paving the path to investigate their functional role in odorant degradation during the olfactory processes.

Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.

Abstract Background Chronic kidney disease (CKD) is an important global public health issue. In China, CKD affects a large number of patients and causes a huge economic burden. This study provided a new way to predict the number of patients with CKD and estimate its economic burden in China based on the autoregressive integrated moving average (ARIMA) model. Methods Data of the number of patients with CKD in China from 2000 to 2019 were obtained from the Global Burden of Disease. The ARIMA model was used to fit and predict the number of patients with CKD. The direct and indirect economic burden of CKD were estimated by the bottom-up approach and the human capital approach respectively. Results The results of coefficient of determination (0.99), mean absolute percentage error (0.26%), mean absolute error (343,193.8) and root mean squared error (628,230.3) showed that the ARIMA (1,1,1) model fitted well. Akaike information criterion (543.13) and Bayesian information criterion (546.69) indicated the ARIMA (1,1,1) model was reliable when analyzing our data. The result of relative error of prediction (0.23%) also suggested that the model predicted well. The number of patients with CKD in 2020 to 2025 was predicted to be about 153 million, 155 million, 157 million, 160 million, 163 million and 165 million respectively, accounting for more than 10% of the Chinese population. The total economic burden of CKD from 2019 to 2025 was estimated to be $179 billion, $182 billion, $185 billion, $188 billion, $191 billion, $194 billion and $198 billion respectively. Conclusion The number of patients with CKD and the economic burden of CKD will continue to rise in China. The number of patients with CKD in China would increase by 2.6 million (1.6%) per year on average from 2020 to 2025. Meanwhile, the total economic burden of CKD in China would increase by an average of $3.1 billion per year. The ARIMA model is applicable to predict the number of patients with CKD. This study provides a new perspective for more comprehensive understanding of the future risk of CKD.

Metrnl is a new cytokine with homologous orignination from neurotrophic factor Meteorin. Meanwhile, as a secreting protein, its gene and products show low tissue specificity and is widely expressed in different tissues of host. Similar to neurotrophic factor, adipocytokines, inflammatory factor and muscle factor, the protein plays a role in neural development, immune inflammatory response and metabolism and so on.

Abstract Background The fat‐to‐muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex‐specific associations between total and regional FMR and incident dementia. Methods A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all‐cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis. Results During a median 8.65 years of follow‐up, we documented 2 225 incident all‐cause dementia cases, including 836 AD and 468 VD cases. There was an L‐shaped association between whole body FMR and all‐cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non‐linear

Abstract Objective To explore the mortality of patients with fragile hip fractures and assess the death‐associated risk factors. Methods A total of 690 patients with osteoporotic hip fractures (age, 50–103 years) that were treated from January 2010 to December 2015 were enrolled and followed‐up in this study and the clinical data were retrospectively collected. Three months, 1 year, and the total mortality were measured. Mortality‐related risk factors were assessed including age, gender, surgery, the duration from injury to operation, pulmonary infection, and the number and type of complications. The mortality of each group was compared by chi‐square test or corrected chi‐square test for univariate analysis, and the factors with statistically significant mortality difference confirmed by univariate analysis were analyzed by binary logistic multivariate analysis. Results The 3‐month mortality was 7.69%, the 1‐year mortality was 15.60%, and the total mortality of the follow‐up time was 24.06%. The 1‐year and total mortality during the follow‐up of the patients were higher in the >75‐year‐old group than those in the ≤75‐year‐old group (p = 0.000, respectively); were higher in the male patients than that in the female patients (p = 0.042; p = 0.017, respectively); were significantly lower in the operation group than that in the non‐operation group (p = 0.000, respectively); were significantly lower in the patients that underwent the operation in ≤5 days than the patients that underwent the operation within >5 days (p = 0.008; p = 0.000, respectively); were significantly lower in patients with >2 kinds of combined medical diseases than those with ≥2 kinds of chronic diseases (p = 0.000, respectively); were significantly lower in patients receiving anti‐osteoporosis treatment than in patients not receiving anti‐osteoporosis treatment (p = 0.000, p = 0.002, respectively). Binary logistic regression analysis showed that the independent risk factors affecting mortality included advanced age >75‐years‐old (OR = 5.653, p = 0.000), male (OR = 1.998, p = 0.001), non‐surgical treatment (OR = 9.909, p = 0.000), the number of combined medical diseases ≥2 (OR = 1.522, p = 0.042), and non‐anti‐osteoporosis treatment (OR = 1.796, p = 0.002). Conclusion Age, whether or not surgical treatment was performed, the number of medical diseases, and whether or not anti‐osteoporosis treatment was performed were independent risk factors for 3‐month and 1‐year mortality in patients with fragile hip fractures.