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Abstract Background The APOE gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized. Methods To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development. Results We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups. Conclusion The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology.

Introduction: The objective of the study was to compare the effects of orthodontic microimplant anchorage (MIA) and conventional extraoral arch anchorage (EAA) on tooth structure and oral inflammatory response in patients with Class II Division I malocclusion. Methods: A total of 104 patients with Class II malocclusion were enrolled and were randomly assigned to receive MIA or EAA treatments. Clinical efficacy was assessed at 6 months after treatment by measuring molar shift, convex distance, and hinge angle difference between maxillary and mandibular incisors. X-ray was performed for tissue evaluations. The levels of cell adhesion molecule-1 (CAM-1), matrix metalloproteinase-2 (MMP-2), and proinflammatory cytokines in gingival sulcus fluid were measured using enzyme-linked immunosorbent assay to assess inflammatory responses to the implants. Results: Our study demonstrated superior efficacy of MIA compared to EAA in terms of overall efficacy, molar shift, convex distance between upper and middle incisors, as well as hinge angle difference between upper and middle incisors. MIA also showed greater efficacy in reducing tissue fix-point measurements, including saddle point–nasal root point–superior alveolar seat point (SNA), alveolar seat point–nasal root point–inferior alveolar seat point (ANB), overlying (OJ), and overbite (OB). Conclusions: MIA is a novel orthodontic treatment that showed stronger efficacy in inducing molar shift and correcting soft/hard tissue positions, whilst generating suppressed inflammatory responses. Our study could have significant implications for practice in the orthodontic treatment of Class II malocclusion.

Abstract Close correlation between vitamin D (VitD) deficiency and Parkinson’s Disease (PD) risk, VitD as an adjuvant treatment promising to improve PD progression. However, VitD excessive intake could induce hypercalcemia and renal damage. Therefore, upregulation of vitD receptor (VDR) is considered a compensatory strategy to overcome VitD insufficiency and alleviate PD symptoms. In this study, we discovered that VDR played antioxidative roles in dopaminergic neurons by decreasing reactive oxygen species (ROS) and maintaining mitochondrial membrane potential. Further, we newly identified VDR downstream events in C. elegans, including glutathione S-transferase (gst) and forkhead box transcription factor class O (daf-16) mediated oxidative stress resistance. VDR upregulation also mitigated microglial activation through inhibition of NLRP3/caspase-1-mediated inflammation and membrane permeabilization. These findings highlight the multifaceted protective effects of VDR in both neurons and microglia against the development of PD. Importantly, we discovered a novel deubiquitinase DUB3, whose N-terminal catalytic domain interacted with the C-terminal ligand-binding domain of VDR to reduce VDR ubiquitination. Identification of DUB3 as an essential player in the deubiquitinating mechanism of VDR provides valuable insights into VDR regulation and its potential as a therapeutic target for PD.

Genetic transformation has been a cornerstone in plant molecular biology research and molecular design breeding, facilitating innovative approaches for the genetic improvement of trees with long breeding cycles. Despite the profound ecological and economic significance of conifers in global forestry, the application of genetic transformation in this group has been fraught with challenges. Nevertheless, genetic transformation has achieved notable advances in certain conifer species, while these advances are confined to specific genotypes, they offer valuable insights for technological breakthroughs in other species. This review offers an in-depth examination of the progress achieved in the genetic transformation of conifers. This discussion encompasses various factors, including expression vector construction, gene-delivery methods, and regeneration systems. Additionally, the hurdles encountered in the pursuit of a universal model for conifer transformation are discussed, along with the proposal of potential strategies for future developments. This comprehensive overview seeks to stimulate further research and innovation in this crucial field of forest biotechnology.

ABSTRACT: Background: About one-third of patients with oral squamous cell carcinoma (OSCC) have a risk of occurrence and chemoresistance, making survival rates abysmal. We aim to evaluate the role of F-box/WD repeat-containing protein 7 (FBXW7) to further develop efficient treatment of chemoresistant OSCC. Methods: FBXW7 overexpression was induced in human OSCC cell lines including SCC9 and CAL27 by a lentiviral vector, Lv-FBXW7 or lv-NC (noncoding control), and overexpression efficiency was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot of FBXW7. Cell viability was measured using MTT assay. The effects of FBXW7 overexpression on cell migration and invasion was evaluated by the colony formation assay and Matrigel assay. Apoptosis of cells with lv-FBXW7 transfection was measured by qRT-PCR and western blot analyses of BAX, BAK, MCL1, and BCL2 expression. Growth rate and cisplatin sensitivity of CAL27 xenografts with or without FBXW7 overexpression was monitored. Ki-67 and PCMA levels—which are biomarkers of intratumoural apoptosis—BAX, MCL1, Beclin1, and LC3I&II—which are autophagy biomarkers—were assessed. Results: Transfection of lv-FBXW7 in SCC9 and CAL27 cells resulted in increased sensitivity to cisplatin treatment, as evidenced by slower cell proliferation, lower colony formation and invasion, higher apoptosis, and autophagy compared to those transfected with lv-NC. Mice with CAL27 xenografts overexpressing FBXW7 also demonstrated slower tumour growth and upregulation in Ki067 and PCNA. Tumours also showed higher apoptosis and autophagy activities. Conclusions: FBXW7 overexpression was herein shown to effectively sensitise OSCC cells to cisplatin treatment in vitro and in vivo.

Safflower (Carthamus tinctorius L.) is a multipurpose minor crop consumed by developed and developing nations around the world with limited research funding and genetic resources. Genomic selection (GS) is an effective modern breeding tool that can help to fast-track the genetic diversity preserved in genebank collections to facilitate rapid and efficient germplasm improvement and variety development. In the present study, we simulated four GS strategies to compare genetic gains and inbreeding during breeding cycles in a safflower recurrent selection breeding program targeting grain yield (GY) and seed oil content (OL). We observed positive genetic gains over cycles in all four GS strategies, where the first cycle delivered the largest genetic gain. Single-trait GS strategies had the greatest gain for the target trait but had very limited genetic improvement for the other trait. Simultaneous selection for GY and OL via indices indicated higher gains for both traits than crossing between the two single-trait independent culling strategies. The multi-trait GS strategy with mating relationship control (GS_GY + OL + Rel) resulted in a lower inbreeding coefficeint but a similar gain compared to that of the GS_GY + OL (without inbreeding control) strategy after a few cycles. Our findings lay the foundation for future safflower GS breeding.

Background: Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy. Objective: To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites. Design: A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University. Methods: The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected. Results: There is no significant correlation between OCTA outcomes and the patient’s age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter ( r = 0.419, p = 0.005 and r = 0.407, p = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP ( r = −0.378, p = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter ( r = 0.445, p = 0.003 and r = 0.434, p = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP ( r = −0.383, p = 0.011 and r = −0.424, p = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations. Conclusion: OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes.

Background: Glutamate stimuli and hyperactivation of its receptor are predominant determinants of ischemia-induced cytotoxic cerebral edema, which is closely associated with protein nanoparticle (PN)-induced increases in osmotic pressure. Herein, we investigated the electrochemical and mechanical mechanisms underlying the neuron swelling induced by PNs via the co-activation of N-methyl-D-aspartate receptor subunit (NMDAR) and excitatory metabotropic glutamate receptors (mGluRs). Results: We observed that co-activation of ionic glutamate receptor NMDAR and Group I metabotropic mGluRs promoted alteration of PN-induced membrane potential and increased intracellular osmosis, which was closely associated with calcium and voltage-dependent ion channels. In addition, activation of NMDAR-induced calmodulin (CaM) and mGluR downstream diacylglycerol (DAG)/protein kinase C α (PKCα) were observed to play crucial roles in cytotoxic hyperosmosis. The crosstalk between CaM and PKCα could upregulate the sensitivity and sustained opening of sulfonylurea receptor 1 (SUR1)-transient receptor potential cation channel subfamily M member 4 (TRPM4) and transmembrane protein 16 A (TMEM16A) channels, respectively, maintaining the massive Na+/Cl- influx, and the resultant neuron hyperosmosis and swelling. Intracellular PNs and Na+/Cl- influx were found to be as potential targets for cerebral edema treatment, using the neurocyte osmosis system and a cerebral ischemic rat model. Conclusions: This study highlights PNs as a key factor in “electrochemistry-tension” signal transduction controlling Na+/Cl- ion channels and increased osmotic pressure in ischemia-induced cytotoxic edema. Moreover, enhanced sensitivity in both Na+ and Cl- ion channels also has a crucial role in cerebral edema.

Objectives: To determine the levels of estrogen and estrogen metabolites in the urine of premenopausal women with obesity and their correlation with glucose and lipid metabolism. Methords: 135 premenopausal women were selected from the same area. According to the body mass index (BMI), they were divided into four different groups. High performance liquid chromatography-mass spectrometry (HPLC/MS) was adopted to detect the concentrations of estrogen and estrogen metabolites in the urine. The influencing factors of BMI were analyzed, the correlation between the urinary degrees of estrogen and estrogen metabolites and glucose and lipid metabolism levels was assessed. Results: (1) The concentrations of 17β-estradiol (E2), estrone (E1), 16α-hydroxyestrone (16α-OHE1) and 2-hydroxyestrone (2-OHE1) gradually increased with increasing BMI (p

BackgroundHypertension is the most prevalent chronic condition and a significant risk factor for cardiovascular and kidney diseases. The efficacy of health behavioral interventions in blood pressure (BP) control has been demonstrated by a large and expanding body of literature, with “adherence” playing a crucial role. WeChat is the most common social communication mobile app in China, and it has been shown to be an acceptable delivery platform for delivering health interventions. The WeChat-based health behavioral digital intervention program (WHBDIP) showed high feasibility and efficacy. However, the results regarding BP improvement between the WHBDIP and control groups were inconsistent. ObjectiveThe objective of this study is to develop a WHBDIP and assess its efficacy in controlling BP and improving adherence among patients with hypertension. MethodsA 2-arm, parallel-group, and randomized trial design was used. Patients older than 60 years and with hypertension were randomly assigned to either the control group or the experimental group, which received a 12-week intervention. The program, primarily developed based on the Behavior Change Wheel (BCW) theory, offers health education on exercise, diet, BP monitoring, and medicine adherence (MA). It also includes other behavior interventions guided by an intervention manual, incorporating behavior change techniques (BCTs). The primary outcomes encompass BP and adherence indicators, while the secondary outcomes encompass cardiovascular function indicators, body composition indicators, learning performance, satisfaction, and acceptability. The exercise and blood pressure monitoring adherence (BPMA) indicators for the WHBDIP group were assessed weekly via WeChat during the initial 3 months, while other outcome data for both groups will be collected at the baseline assessment phase, 3 months after the intervention, and 1 year after the program. ResultsThe trial will assess the efficacy of WHBDIP for patients with hypertension (N=68). The WHBDIP seeks to enhance participants' knowledge of healthy behaviors and assist patients in developing positive health behaviors to improve their health outcomes. Patient recruitment for individuals with hypertension commenced on September 5, 2022, and concluded on September 19, 2022. The 3-month intervention and phased data collection were finalized in January 2023. Data analysis will commence in August 2023, and the final 1-year health outcome results will be collected in September 2023. ConclusionsA successful WHBDIP will establish the management mode as a feasible approach for hypertension management in the community. Additionally, it will pave the way for the development of related mobile health programs. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200062643; https://tinyurl.com/mwyv67wk International Registered Report Identifier (IRRID)PRR1-10.2196/46883

Abstract Background RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. Methods The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. Results We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. Conclusion Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.

DNA methylation plays a crucial role in the development of somatic embryos (SEs) through the regulation of gene expression. To examine the impact of DNA methylation on gene expression during early SE development in Picea glauca, the demethylation reagent 5-aza-dC (5-aza-2′-deoxycytidine) was employed to modify DNA methylation regions and levels during the pre-maturation stage of somatic embryogenesis. The application of 2.0 µM 5-aza-dC did not induce toxicity to SEs in early development. Following treatment, the global DNA methylation level decreased significantly on the 7th day of pre-maturation and the 1st week of maturation. Methylated DNA immunoprecipitation (MeDIP) sequencing revealed that differentially methylated regions, as analyzed through Gene Ontology (GO), were related to plant development and reproduction and that they were hypomethylated on the 3rd day but hypermethylated on the 7th day in 5-aza-dC-treated embryogenic tissues. These findings indicate that 5-aza-dC treatment positively impacts early SE development, which was inhibited following 7 d of treatment. The expression of MSH7, JMJ14, and CalS10 was associated with DNA methylation, epigenetic regulation, and somatic embryogenesis. Further analysis of methylated regions revealed that the expression profiles of MSH7, JMJ14, and CalS10 were correlated with altered DNA methylation, suggesting DNA methylation at 5 mC may play a role in controlling the expression of these genes and regulating the early development of SEs in P. glauca. This study offers new insights into the regulation of somatic embryogenesis in conifers.

In order to identify the optimal sterilization parameters for HPEF on Pectobacterium carotovorum (P. carotovorum), and preliminarily explore its potential mechanism, the main factors affecting the sterilization effect were identified by measuring the survival rate of P. carotovorum under different treatment conditions of HPEF. Then, the effects of different electric field strengths and pulse duty cycles on the growth curve, fatty acid content of cell membrane, cell membrane permeability, and nucleic acid and protein leakage of P. carotovorum were studied, as well as the differences in sensitivity of P. carotovorum to HPEF in different growth periods. Finally, the kinetic model between electric field strength, pulse duty cycle and the survival rate of P. carotovorum was established. The results showed that the electric field intensity and pulse duty cycle were the main factors affecting the killing of P. carotovorum by HPEF. When the electric field strength was 28 kV/cm and the pulse duty cycle was 36.5%, the antibacterial effect was the strongest, with a reduction of logarithmic value at 1.60. Under the action of HPEF, the delay period of P. carotovorum was prolonged and its growth was inhibited. At the same time, the structure of cell membrane was damaged, and the permeability was increased, leading to the serious leakage of intracellular nucleic acid and protein. In addition, P. carotovorum in different growth period had different sensitivities to HPEF, and logarithmic growth period was the most sensitive. Finally, the kinetic equation was established between the log reduction value of lnS and the electric field strength and pulse duty cycle (y=−0.1067x+0.1166 and y=−0.0895x+0.3249). The equation was in accordance with the first-order kinetic model and reflected the growth relationship of P. carotovorum after HPEF treatment well, which provided data support for the selection of appropriate treatment conditions. In this study, the optimal parameters of HPEF inhibiting P. carotovorum were determined, which provided theoretical data for further realization of HPEF sterilization in the industrial application of postharvest and fresh-cutting industries.

Software tools for larger-scale intact glycopeptide quantification lag far behind, which hinders exploring the differential sitespecific glycosylation. Here, the authors report pGlycoQuant, a generic tool with a deep learning model for quantitative glycoproteomics at intact glycopeptide level.

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC.Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter.Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (p < 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (p > 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (p > 0.05).Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T‐cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.

Abstract Rating of perceived exertion (RPE) can serve as a more convenient and economical alternative to heart rate (HR) for exercise intensity control. This study aims to explore the influence of factors, such as indicators of demographic, anthropometric, body composition, cardiovascular function and basic exercise ability on the relationship between HR and RPE, and to develop the model predicting RPE from HR. 48 healthy participants were recruited to perform an incrementally 6-stage pedaling test. HR and RPE were collected during each stage. The influencing factors were identified with the forward selection method to train Gaussian Process regression (GPR), support vector machine (SVM) and linear regression models. Metrics of R2, adjusted R2 and RMSE were calculated to evaluate the performance of the models. The GPR model outperformed the SVM and linear regression models, and achieved an R2 of 0.95, adjusted R2 of 0.89 and RMSE of 0.52. Indicators of age, resting heart rate (RHR), Central arterial pressure (CAP), body fat rate (BFR) and body mass index (BMI) were identified as factors that best predicted the relationship between RPE and HR. It is possible to use GPR model to estimate RPE from HR accurately, after adjusting for age, RHR, CAP, BFR and BMI.

In plant breeding programs, multiple traits are recorded in each trial, and the traits are often correlated. Correlated traits can be incorporated into genomic selection models, especially for traits with low heritability, to improve prediction accuracy. In this study, we investigated the genetic correlation between important agronomic traits in safflower. We observed the moderate genetic correlations between grain yield (GY) and plant height (PH, 0.272–0.531), and low correlations between grain yield and days to flowering (DF, −0.157–0.201). A 4%–20% prediction accuracy improvement for grain yield was achieved when plant height was included in both training and validation sets with multivariate models. We further explored the selection responses for grain yield by selecting the top 20% of lines based on different selection indices. Selection responses for grain yield varied across sites. Simultaneous selection for grain yield and seed oil content (OL) showed positive gains across all sites with equal weights for both grain yield and oil content. Combining g×E interaction into genomic selection (GS) led to more balanced selection responses across sites. In conclusion, genomic selection is a valuable breeding tool for breeding high grain yield, oil content, and highly adaptable safflower varieties.

Abstract The prevalence of intracranial aneurysm (IA) is increasing, and the consequences of its rupture are severe. This study aimed to reveal specific, sensitive, and non‐invasive biomarkers for diagnosis and classification of ruptured and unruptured IA, to benefit the development of novel treatment strategies and therapeutics altering the course of the disease. We first assembled an extensive candidate biomarker bank of IA, comprising up to 717 proteins, based on altered proteins discovered in the current tissue and serum proteomic analysis, as well as from previous studies. Mass spectrometry assays for hundreds of biomarkers were efficiently designed using our proposed deep learning‐based method, termed DeepPRM. A total of 113 potential markers were further quantitated in serum cohort I (n = 212) & II (n = 32). Combined with a machine‐learning‐based pipeline, we built two sets of biomarker combinations (P6 & P8) to accurately distinguish IA from healthy controls (accuracy: 87.50%) or classify IA rupture patients (accuracy: 91.67%) upon evaluation in the external validation set (n = 32). This extensive circulating biomarker development study provides valuable knowledge about IA biomarkers.

Abstract Thermal interface materials (TIM) represented by submicron silver adhesive provide a promising solution for ultra‐high heat dissipation in chip integration. However, it is difficult to accurately characterize the thermal performance of submicron silver adhesive interfaces, and their high‐temperature degradation mechanism still remains unclear. Herein, the accelerated high‐temperature aging experiments of submicron silver adhesion interfaces are performed, and a non‐destructive testing method is provided to measure the degeneration of interfacial thermal resistance (ITR). After performing the two‐sided test, ITR can be extracted with an error of less than 4.6%. Based on scanning electron microscopy and X‐ray microstructural analysis, the microstructural evolution of silver adhesive interfaces is presented and its high‐temperature degradation mechanism is determined. It is observed for the first time that ITR would change with the aging time following a bathtub curve. Such a degenerative process can be evidently divided into three stages including secondary solidification, fluctuation, and failure. In addition, a physical model is developed to interpret the degradation mechanism of ITR at high temperatures. The change in the trend of submicron silver body and TIM–solid contact thermal resistance at different stages is presented. This work helps promote submicron silver's application as high‐performance TIM.

Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast developmental status and is essential for the photoautotrophic lifestyle of plants. Previous studies have established that tetrapyrrole biosynthesis (TPB) and plastid gene expression (PGE) play essential roles in plastid retrograde signaling during early chloroplast biogenesis; however, their functional relationship remains unknown. In this study, we generated a series of rice TPB-related gun (genome uncoupled) mutants and systematically analyzed their effects on nuclear and plastid gene expression under normal conditions or when subjected to treatments with norflurazon (NF; a noncompetitive inhibitor of carotenoid biosynthesis) and/or lincomycin (Lin; a specific inhibitor of plastid translation). We show that under NF treatment, expression of plastid-encoded polymerase (PEP)-transcribed genes is significantly reduced in the wild type but is derepressed in the TPB-related gun mutants. We further demonstrate that the derepressed expression of PEP-transcribed genes may be caused by increased expression of the PEP core subunit and nuclear-encoded sigma factors and by elevated copy numbers of plastid genome per haploid genome. In addition, we show that expression of photosynthesis-associated nuclear genes (PhANGs) and PEP-transcribed genes is correlated in the rice TPB-related gun mutants, with or without NF or Lin treatment. A similar correlation between PhANGs and PGE is also observed in the Arabidopsis gun4 and gun5 mutants. Moreover, we show that increased expression of PEP-transcribed plastid genes is necessary for the gun phenotype in NF-treated TPB-related gun mutants. Further, we provide evidence that these TPB-related GUN genes act upstream of GUN1 in the regulation of retrograde signaling. Taken together, our results suggest that the TPB-related GUN genes control retrograde plastid signaling by regulating the PGE-dependent retrograde signaling pathway.

Cancer cell invasion and metastasis are closely related to intracellular tension. The cell-polarity protein, Par3, is a mechanical transmitter that affects cytoskeletal forces and determines breast cancer aggressiveness. Increased Par3 tension caused by aPKC inactivation is involved in filopodia and lamellipodia formation. Blocking the connection between Par3 and aPKC increases breast cancer aggressiveness both in vitro and in vivo. Meanwhile, aPKC-induced Par3 cytoplasmic translocation results in JAM-A phase separation and microfilament depolymerization, which is associated with increased intracellular protein nanoparticle-induced osmotic pressure. This study demonstrated the effects of aPKC on Par3 tension and osmotic pressure in breast cancer metastasis, and introduced Par3-associated mechanical mechanisms as potential targets for breast cancer treatment.

Summary: Acute myeloid leukemia (AML) is one of the most common and fatal forms of hematopoietic malignancies. Here, we describe a mouse MLL-AF9_AML model to investigate AML. We have optimized the protocols for retrovirus infection, bone marrow transplantation (BMT), and leukemia monitoring to create a stable mouse model. In particular, we have used two rounds of BMT to enhance stability and efficiency. This model can be used to conduct drug administration and/or other interventions easily.For complete details on the use and execution of this protocol, please refer to Zhao et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Small- and medium-sized enterprises (SEMs) are the important part of economic society whose innovation activities are of great significance for building innovative country. In order to investigate how technological innovation (TI) and business model design (BMD) affect the business performance of SMEs, samples of 268 SMEs in the artificial intelligence industry and hierarchical regression models are used in the analysis. The results indicate that TI, BMD, and the matching of them have different effects on the innovation of SMEs of different sizes. These findings are helpful for enriching the theory of the fit between TI and BMD and providing theoretical guidance for the innovation activities in SEMs.

Abstract Background Zinc transporters have been found to be associated with the pathogenesis of numerous human diseases including cancer. As the most lethal gynecologic malignancy, ovarian cancer is characterized by rapid progression and widespread metastases. However, the function and underlying mechanism of zinc transporters in ovarian cancer metastasis remain unclear. Methods The relationship between zinc transporter gene expressions and clinical outcomes of ovarian cancer was assessed with the online database Kaplan-Meier plotter ( http://kmplot.com/analysis/ ). Immunohistochemistry was performed to investigate the prognostic importance of ZIP13. The expression of ZIP13 in ovarian cancer cell lines was depleted to explore its effect on proliferation, adhesion, migration, and invasion both in vitro and in vivo assays. RNA-Seq, quantitative RT-PCR, and western blot analysis were performed to explore ZIP13-regulated downstream target genes. Results The expressions of several zinc transporters were highly associated the clinical outcomes of ovarian cancer patients. Among them, high ZIP13 expression was an independent prognostic factor for poor survival in patients with ovarian cancer. ZIP13 knockout suppressed the malignant phenotypes of ovarian cancer cells both in vitro and in vivo. Further investigation revealed that ZIP13 regulated intracellular zinc distribution and then affected the expressions of genes involved in extracellular matrix organization and cytokine-mediated signaling pathway. This led to the activation of Src/FAK pathway with increased expressions of pro-metastatic genes but decreased expressions of tumor suppressor genes. Conclusions ZIP13 is shown to be a novel driver of metastatic progression by modulating the Src/FAK signaling pathway, which may serve as a promising biomarker for prognostic evaluation and targeted therapy in ovarian cancer.

Field pea is the most commonly grown temperate pulse crop, with close to 15 million tons produced globally in 2020. Varieties improved through breeding are important to ensure ongoing improvements in yield and disease resistance. Genomic selection (GS) is a modern breeding approach that could substantially improve the rate of genetic gain for grain yield, and its deployment depends on the prediction accuracy (PA) that can be achieved. In our study, four yield trials representing breeding lines' advancement stages of the breeding program (S0, S1, S2, and S3) were assessed with grain yield, aerial high-throughput phenotyping (normalized difference vegetation index, NDVI), and bacterial blight disease scores (BBSC). Low-to-moderate broad-sense heritability (0.31–0.71) and narrow-sense heritability (0.13–0.71) were observed, as the estimated additive and non-additive genetic components for the three traits varied with the different models fitted. The genetic correlations among the three traits were high, particularly in the S0–S2 stages. NDVI and BBSC were combined to investigate the PA for grain yield by univariate and multivariate GS models, and multivariate models showed higher PA than univariate models in both cross-validation and forward prediction methods. A 6–50% improvement in PA was achieved when multivariate models were deployed. The highest PA was indicated in the forward prediction scenario when the training population consisted of early generation breeding stages with the multivariate models. Both NDVI and BBSC are commonly used traits that could be measured in the early growth stage; however, our study suggested that NDVI is a more useful trait to predict grain yield with high accuracy in the field pea breeding program, especially in diseased trials, through its incorporation into multivariate models.

Infection is closely related to atherosclerosis, which is a major pathological basis for cardiovascular diseases. Vascular smooth muscle cell (VSMC) migration is an important trigger in development of atherosclerosis that is associated with Chlamydia pneumoniae (C. pneumoniae) infection. However, the mechanism of VSMC migration remains unclear, and whether antioxidant could be a therapeutic target for C. pneumoniae infection-induced atherosclerosis also remains unknown. The results showed that C. pneumoniae infection mainly impaired mitochondrial function and increased the level of mitochondrial reactive oxygen species (mtROS). The expressions of protein JunB, Fra-1 and Matrix metalloproteinase 2 (MMP) evidently increased after C. pneumoniae infection, and the interaction between JunB and Fra-1 was also enhanced. After scavenging mtROS by antioxidant Mito-TEMPO, the increasing expressions of JunB, Fra-1, MMP2 and the capacity of VSMC migration induced by C. pneumoniae infection were all inhibited. In comparison with infected ApoE-/- mice, the level of ROS in atherosclerotic lesion in ApoE-/-TLR2-/- mice with C. pneumoniae infection decreased. Knocking out TLR2 suppressed the expressions of JunB, Fra-1 and MMP2 in VSMCs and the formation of atherosclerotic lesion after C. pneumoniae infection. Furthermore, after using small interfering RNA to inhibit the expression of TLR2, the level of mtROS and the expressions of JunB, Fra-1 and MMP2 apparently decreased. Taken together, C. pneumoniae infection may promote VSMC migration and atherosclerosis development by increasing the level of mtROS through TLR2 to activate the JunB-Fra-1/MMP2 signaling pathway. The data provide the first evidence that antioxidant could reduce C. pneumoniae infection-induced VSMC migration and atherosclerosis.

Zinc is an essential element and serves as a structural or catalytic component in many proteins. Two families of transporters are involved in maintaining cellular zinc homeostasis: the ZIP (SLC39A) family that facilitates zinc influx into the cytoplasm, and the ZnT (SLC30A) family that facilitates zinc efflux from the cytoplasm. Zinc dyshomeostasis caused by the dysfunction of zinc transporters can contribute to the initiation or progression of various cancers, including prostate cancer, breast cancer, and pancreatic cancer. In addition, intracellular zinc fluctuations lead to the disturbance of certain signaling pathways involved in the malignant properties of cancer cells. This review briefly summarizes our current understanding of zinc dyshomeostasis in cancer, and discusses the potential roles of zinc or zinc transporters in cancer therapy.

Drug-carrying nanoparticles have obtained great attention for disease treatments due to the fact that they can improve drug solubility, provide drug protection and prolong release duration, thus enhancing drug bioavailability and increasing therapeutic efficacy. Although nanoparticles containing drugs can be administered via different routes such as oral, intravenous and ocular, transdermal delivery of nanoparticles mediated by microneedles has attracted considerable interest due to the capability of circumventing enzymatic degradation caused by gastrointestinal track, and increasing patient compliance by reducing pain associated with hypodermic injection. In this review, we first introduce four types of nanoparticles that were used for drug delivery, and then summarize strategies that have been employed to facilitate delivery of drug-loaded nanoparticles via microneedles. Finally, we give a conclusion and provide our perspectives on the potential clinical translation of microneedle-facilitated nanoparticles delivery.

Zinc homeostasis has been known to play a role in myocardial ischemia/reperfusion (I/R) injury, but the precise molecular mechanisms regulating the expression of ZIP transporters during reperfusion are still unclear. The aim of this study was to determine whether ER Stress/CaMKII/STAT3 pathway plays a role in the regulation of cellular zinc homeostasis. Zinc deficiency increased mRNA and protein expressions of the ER stress relevant markers Chop and Bip, and STAT3 phosphorylation in H9c2 or HL-1 cells, an effect that was abolished by ZnCl2. ER calcium concentration [(Ca2+)ER] was decreased and cytosolic calcium concentration [(Ca2+)I] was increased at the condition of normoxia or ischemia/reperfusion, indicating that zinc deficiency triggers ER stress and Ca2+ leak. Further studies showed that upregulation of STAT3 phosphorylation was reversed by Ca2+ chelator, indicating that intracellular Ca2+ is important for zinc deficiency-induced STAT3 activation. In support, zinc deficiency enhanced ryanodine receptors (RyR), a channel in the ER that mediate Ca2+ release, and Ca2+-calmodulin-dependent protein kinase (CaMKII) phosphorylation, implying that zinc deficiency provoked Ca2+ leak from ER via RyR and p-CaMKII is involved in STAT3 activation. Moreover, inhibition of STAT3 activation blocked zinc deficiency induced ZIP9 expression, and resulted in increased Zn2+ loss in cardiomyocytes, further confirming that STAT3 activation during reperfusion promotes the expression of ZIP9 zinc transporter to correct the imbalance in zinc homeostasis. In addition, suppressed STAT3 activation aggravated reperfusion injury. These data suggest that the ER Stress/CaMKII/STAT3 axis may be an endogenous protective mechanism, which increases the resistance of the heart to I/R.

Wheat yield is not only affected by three components of yield, but also affected by plant height (PH). Identification and utilization of the quantitative trait loci (QTL) controlling these four traits is vitally important for breeding high-yielding wheat varieties. In this work, we conducted a QTL analysis using the recombinant inbred lines (RILs) derived from a cross between two winter wheat varieties of China, “Nongda981” (ND981) and “Nongda3097” (ND3097), exhibiting significant differences in spike number per unit area (SN), grain number per spike (GNS), thousand grain weight (TGW), and PH. A total of 11 environmentally stable QTL for these four traits were detected. Among them, four major and stable QTLs (QSn.cau-4B-1.1, QGns.cau-4B-1, QTgw.cau-4B-1.1, and QPh.cau-4B-1.2) explaining the highest phenotypic variance for SN, GNS, TGW, and PH, respectively, were mapped on the same genomic region of chromosome 4B and were considered a QTL cluster. The QTL cluster spanned a genetic distance of about 12.3 cM, corresponding to a physical distance of about 8.7 Mb. Then, the residual heterozygous line (RHL) was used for fine mapping of the QTL cluster. Finally, QSn.cau-4B-1.1, QGns.cau-4B-1, and QPh.cau-4B-1.2 were colocated to the physical interval of about 1.4 Mb containing 31 annotated high confidence genes. QTgw.cau-4B-1.1 was divided into two linked QTL with opposite effects. The elite NILs of the QTL cluster increased SN and PH by 55.71–74.82% and 14.73–23.54%, respectively, and increased GNS and TGW by 29.72–37.26% and 5.81–11.24% in two environments. Collectively, the QTL cluster for SN, GNS, TGW, and PH provides a theoretical basis for improving wheat yield, and the fine-mapping result will be beneficial for marker-assisted selection and candidate genes cloning.

Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous and frequently fatal malignancy. The ten-eleven translocation (TET)-mediated DNA demethylation is known to be critically associated with AML pathogenesis. Through chemical compound screening, we find that the opioid receptor agonist, loperamide hydrochloride (OPA1), significantly suppresses AML cell viability. The potential therapeutic effects of opioid receptor agonists, especially OPA1, are verified in AML cells in vitro and mouse and human AML models in vivo. OPA1-induced activation of OPRM1 signaling enhances the transcription of TET2 and thus activates both catalytic-dependent and -independent functions of TET2. Notably, AMLs with TET2 mutations or chemotherapy resistance are sensitive to OPA1 as well. Our results reveal the OPRM1-TET2 regulatory axis in AML and suggest that opioid agonists, particularly OPA1, a US Food and Drug Administration (FDA)-approved antidiarrheal drug, have therapeutic potential in AML, especially in TET2-mutated and chemotherapy-resistant AMLs, which have a poor prognosis.

Sodium dodecyl sulfate-sedimentation volume is an important index to evaluate the gluten strength of common wheat and is closely related to baking quality. In this study, a total of 15 quantitative trait locus (QTL) for sodium dodecyl sulfate (SDS)-sedimentation volume (SSV) were identified by using a high-density genetic map including 2,474 single-nucleotide polymorphism (SNP) markers, which was constructed with a doubled haploid (DH) population derived from the cross between Non-gda3753 (ND3753) and Liangxing99 (LX99). Importantly, four environmentally stable QTLs were detected on chromosomes 1A, 2D, and 5D, respectively. Among them, the one with the largest effect was identified on chromosome 1A (designated as QSsv.cau-1A.1) explaining up to 39.67% of the phenotypic variance. Subsequently, QSsv.cau-1A.1 was dissected into two QTLs named as QSsv.cau-1A.1.1 and QSsv.cau-1A.1.2 by saturating the genetic linkage map of the chromosome 1A. Interestedly, favorable alleles of these two loci were from different parents. Due to the favorable allele of QSsv.cau-1A.1.1 was from the high-value parents ND3753 and revealed higher genetic effect, which explained 25.07% of the phenotypic variation, mapping of this locus was conducted by using BC3F1 and BC3F2 populations. By comparing the CS reference sequence, the physical interval of QSsv.cau-1A.1.1 was delimited into 14.9 Mb, with 89 putative high-confidence annotated genes. SSVs of different recombinants between QSsv.cau-1A.1.1 and QSsv.cau-1A.1 detected from DH and BC3F2 populations showed that these two loci had an obvious additive effect, of which the combination of two favorable loci had the high SSV, whereas recombinants with unfavorable loci had the lowest. These results provide further insight into the genetic basis of SSV and QSsv.cau-1A.1.1 will be an ideal target for positional cloning and wheat breeding programs.

BackgroundThere is growing evidence to demonstrate that the epigenetic regulation of immune characteristics, especially for N6-methyladenosine (m6A) RNA methylation. However, how m6A methylation is involved in lupus nephritis (LN) is still unclear. This study aimed to determine the role of m6A RNA methylation and their association with the immune microenvironment in LN.MethodsIn total, 87 glomeruli (73 LN, 14 living healthy donors), 110 tubulointerstitium (95 LN, 15 living healthy donors), and 21 kidney whole tissue samples (14 LN, 7 controls) were included in our research to evaluate the expression levels of m6A regulators. CIBERSORT was used to assess the abundance of infiltrating immunocytes. The m6A regulator gene signature for LN was identified using LASSO-logistic regression and verified with external data. Consensus clustering algorithms were used for the unsupervised cluster analysis of m6A modification patterns in LN. Single-sample gene-set enrichment analysis and gene set variation analysis algorithms were employed to assess the activity of immune responses and other functional pathways. Weighted gene co-expression network analysis and protein-protein interaction networks were used to identify m6A methylation markers. Lastly, the Nephroseq V5 tool was used to analyze the correlation between m6A markers and renal function.ResultsWe found that the expression of m6A regulators was more significantly different in the glomeruli in LN compared with tubulointerstitium and whole kidney tissue. We established an m6A regulator signature, comprised of METTL3, WTAP, YTHDC2, YTHDF1, FMR1, and FTO, that can easily distinguish LN and healthy individuals. Two distinct m6A modification patterns based on 18 m6A regulators were determined, with significant differences in m6A regulator expression, immune microenvironment, biological functional pathways, and clinical characteristics. Activated NK cells, most immune responses, and HLA genes had strong correlations with m6A regulators. Seven m6A markers were identified and demonstrated a meaningful correlation with GFR, indicating that they are potential prognostic biomarkers.ConclusionThis study emphasized that m6A RNA methylation and the immune microenvironment are closely linked in LN. A better understanding of m6A modification patterns provide a basis for the development of novel therapeutic options for LN.

Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism.Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules.Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy.Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.

Hypertension is a widespread chronic disease. Risk prediction of hypertension is an intervention that contributes to the early prevention and management of hypertension. The implementation of such intervention requires an effective and easy-to-implement hypertension risk prediction model. This study evaluated and compared the performance of four machine learning algorithms on predicting the risk of hypertension based on easy-to-collect risk factors. A dataset of 29,700 samples collected through a physical examination was used for model training and testing. Firstly, we identified easy-to-collect risk factors of hypertension, through univariate logistic regression analysis. Then, based on the selected features, 10-fold cross-validation was utilized to optimize four models, random forest (RF), CatBoost, MLP neural network and logistic regression (LR), to find the best hyper-parameters on the training set. Finally, the performance of models was evaluated by AUC, accuracy, sensitivity and specificity on the test set. The experimental results showed that the RF model outperformed the other three models, and achieved an AUC of 0.92, an accuracy of 0.82, a sensitivity of 0.83 and a specificity of 0.81. In addition, Body Mass Index (BMI), age, family history and waist circumference (WC) are the four primary risk factors of hypertension. These findings reveal that it is feasible to use machine learning algorithms, especially RF, to predict hypertension risk without clinical or genetic data. The technique can provide a non-invasive and economical way for the prevention and management of hypertension in a large population.

CO/CO2 hydrogenation has attracted much attention as a pathway to achieve carbon neutrality and production of synthetic natural gas (SNG). In this work, two-dimensional NiAl layered double oxide (2D NiAl-LDO) has been successfully decorated by SiO2 nanoparticles derived from SiCl4 and used as CO/CO2 methanation catalysts. The as-obtained H-SiO2-NiAl-LDO exhibited a large specific surface area of 201 m2/g as well as high ratio of metallic Ni0 species and surface adsorption oxygen that were beneficial for low-temperature methanation of CO/CO2. The conversion of CO methanation was 99% at 400 °C, and that of CO2 was 90% at 350 °C. At 250 °C, the CO methanation reached 85% whereas that of CO2 reached 23% at 200 °C. We believe that this provides a simple method to improve the methanation performance of CO and CO2 and a strategy for the modification of other similar catalysts.

Dysregulation of ketone metabolism has been reported in various types of cancer. In order to find out its role in acute myeloid leukemia (AML) pathogenesis, we first analyzed the expression levels of 10 key genes involved in ketone metabolism in AML blasts and CD34+ hematopoietic stem cells (HSCs) from healthy donors. We found that the expression level of BDH1 was significantly lower in AML than in normal HSCs. The downregulation of BDH1 gene expression in AML cell lines as compared with normal HSCs was further confirmed with real-time RT-PCR. Analysis of TCGA and other database revealed that the downregulation of BDH1 was associated with worse prognosis in AML patients. In addition, we showed that overexpression of BDH1 inhibited the viability and proliferation of AML cells. In contrast, BDH1 knock-down promoted AML cell growth. Collectively, our results suggest the previously unappreciated anti-tumor role of BDH1 in AML, and low BDH1 expression predicts poor survival.

Abstract We conducted a cross-sectional survey including 23869 participants and aimed to measure the prevalences of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a Chinese rural population. CKD and DKD status was defined according to the combination of estimated glomerular filtration rate (eGFR) and presence of albuminuria Participant completed a questionnaire involving life-style and relevant medical history, and the blood and urinary specimen were taken. The age- and gender- adjusted prevalences of CKD and DKD were calculated and risk factors associated with the presence of CKD and DKD were analyzed by logistic regression. The overall prevalence of CKD was 16.4% (15.9–16.8%) and of DKD was 2.9% (2.7–3.1%). In participants with diabetes, the overall prevalence of CKD was 35.5% (95% CI = 33.7–37.3%). Factors independently associated with renal damage were age, gender, education, personal income, alcohol consumption, overweight, obesity, diabetes, hypertension and dyslipidemia. Our study shows current prevalences of CKD and DKD in Chinese rural residents. Further researches could identify potential factors explaining the observed differences and implement the interventions to relieve the high burden of CKD and DKD in rural population.

At present, the research focus has been aimed at the pursuit of the design and synthesis of catalysts for effective photocatalytic degradation of organic pollutants in wastewater, and further exploration of novel materials of the photodegradation catalyst. In this paper, the Sol-gel route after thermal treatment was used to produce NiFe2O4 carbon aerogel (NiFe2O4-CA) nanocomposites with cotton linter cellulose as the precursor of aerogel, by co-precipitating iron and nickel salts onto its substrate. The structure and composition of these materials were characterized by X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), Raman spectra, high-resolution scanning electron microscopy (HR-SEM), high-resolution scanning electron microscope mapping (SEM-mapping), X-ray photoelectron spectroscopy (XPS) and Brunauer–Emmett–Teller (BET)’s surface area. The magnetic properties of the material were analyzed by a vibrating-sample magnetometer (VSM). Moreover, diffuse reflectance spectra (DRS), electrochemical impedance spectroscopy (EIS) and photo-luminescence spectroscopy (PL) characterized the photoelectric properties of this cellulose-aerogels-based NiFe2O4-CA. Methylene blue (MB) acted as the simulated pollutant, and the photocatalytic activity of NiFe2O4-CA nanocomposites under visible light was evaluated by adjusting H2O2 content and the pH value. The results showed that the optical absorption range of nickel ferrite was broadened by doping cellulose-aerogels-based carbon, which exerted more positive effects on photocatalytic reactions. This is because the doping of this aerogel carbon promoted a more uniform distribution of NiFe2O4 particles. Given the Methylene blue (MB) degradation reaction conformed to the first-order kinetic equation, the NiFe2O4-CA nanocomposites conducted excellent catalytic activity by maintaining almost 99% of the removal of MB (60 mg/L) within 180 min and upheld excellent stability over four consecutive cycles. This study indicated that NiFe2O4-CA nanocomposites reserved the potential as a future effective treatment of dye wastewater.

Abstract Safflower, a minor oilseed crop, is gaining increased attention for food and industrial uses. Safflower genebank collections are an important genetic resource for crop enhancement and future breeding programs. In this study, we investigated the population structure of a safflower collection sourced from the Australian Grain Genebank and assessed the potential of genomic prediction (GP) to evaluate grain yield and related traits using single and multi‐site models. Prediction accuracies (PA) of genomic best linear unbiased prediction (GBLUP) from single site models ranged from 0.21 to 0.86 for all traits examined and were consistent with estimated genomic heritability (h2), which varied from low to moderate across traits. We generally observed a low level of genome × environment interactions (g × E). Multi‐site g × E GBLUP models only improved PA for accessions with at least some phenotypes in the training set. We observed that relaxing quality filtering parameters for genotype‐by‐sequencing (GBS), such as missing genotype call rate, did not affect PA but upwardly biased h2 estimation. Our results indicate that GP is feasible in safflower evaluation and is potentially a cost‐effective tool to facilitate fast introgression of desired safflower trait variation from genebank germplasm into breeding lines.

We define the group measure matrix of the alternative scheme and the ideal scheme based on the relevant factor sequence and the system characteristic behavior sequence. Furthermore, the information distances of decision makers and decision criteria are defined, respectively. According to the information distance, we obtain each scheme’s grey matrix incidence degree for the scheme ranking. Finally, we use an example to verify the rationality of the model and compare it with other classic methods, such as TOPSIS, VIKOR, MULTI-MOORA. Compared with previous grey incidence analysis model, the proposed model can make full use of information of the decision-maker dimension and the criteria dimension. The proposed model can avoid high-dimensional information loss. The results show that the proposed method has superiority in measuring decision-maker information and decision-making standard information.

Awe is an intense emotional response to perceptually vast stimuli that dramatically transcend one’s ordinary reference frame and provoke a need to adjust the current mental structures. Dispositional awe reflects individual differences in the tendency to experience awe. The current study aims to examine the effect of dispositional awe on subjective well-being, with a focus on confirming the mediating role of meaning in life and materialism. A sample of 563 Chinese adults completed measures of dispositional awe, meaning in life, materialism, and subjective well-being. Correlation analysis revealed that dispositional awe, meaning in life, and materialism were all significantly correlated with subjective well-being. Structural equation modeling showed significant paths from dispositional awe to subjective well-being through both meaning in life and materialism. Bootstrap analysis also indicated that meaning in life and materialism mediated the relationship between dispositional awe and subjective well-being. These findings not only corroborate the critical role of dispositional awe in promoting subjective well-being, but also shed some light on why people high in dispositional awe are happier than those low in dispositional awe. Limitations and directions for future research were also discussed.

The present study attempts to explore the effect of awe on environmentalism and the mediating role of social dominance orientation in generating this effect. In Study 1, a series of questionnaires were used to investigate the correlation among trait awe, social dominance orientation, and ecological behavior. Results demonstrated that, while trait awe was positively correlated with ecological behavior, it was partially mediated by social dominance orientation. In follow-up studies, two priming experiments were conducted to test the causal relationship and the psychological mechanisms between awe and environmentalism. Results revealed that inductions of awe (relative to various control states) decreased participants’ social dominance orientation, which in turn partially enhanced their willingness to make personal sacrifices for the environment (Study 2), and intentions to engage in pro-environmental behavior (Study 3). This study not only corroborates the critical role of awe in promoting environmentalism, but also highlights the importance of social dominance orientation in explaining why awe increases environmentalism. Implications and future directions were also discussed.

Abstract In this paper we consider the existence of nonoscillatory solutions of higher-order neutral differential equations with distributed coefficients and delays. We use the B a n a c h $Banach$ contraction principle to obtain new sufficient condition for the existence of nonoscillatory solutions.

Using absolute intensity methods (metabolic equivalent of energy (METs), etc.) to determine exercise intensity in exercise prescriptions is straightforward and convenient. Using relative intensity methods (heart rate reserve (%HRR), maximal heart rate (%HRmax), etc.) is more recommended because it is more personalized. Taking target heart rate (THR) given by the relative method as an example, compared with just presenting the THR value, intuitively providing the setting parameters for achieving the THR with specific sport equipment is more user-friendly. The objective of this study was to find a method which combines the advantages (convenient and personalized) of the absolute and relative methods and relatively avoids their disadvantages, helping individuals to meet the target intensity by simply setting equipment parameters. For this purpose, we recruited 32 males and 29 females to undergo incremental cardiopulmonary exercise testing with cycling equipment. The linear regression model of heart rate and exercise wattage (the setting parameter of the equipment) was constructed for each one (R2 = 0.933, p < 0.001), and the slopes of the graph of these models were obtained. Next, we used an iterative algorithm to obtain a multiple regression model (adjusted R2 = 0.8336, p < 0.001) of selected static body data and the slopes of participants. The regression model can accurately predict the slope of the general population through their static body data. Moreover, other populations can guarantee comparable accuracy by using questionnaire data for calibration. Then, the predicted slope can be utilized to calculate the equipment’s settings for achieving a personalized THR through our equation. All of these steps can be assigned to the intelligent system.

Barley stripe mosaic virus (BSMV) is an established and extensively used virus-induced gene silencing (VIGS) vector for gene function analysis in monocots. However, the phenotypes generated by targeted gene silencing may be affected or masked by symptoms of BSMV infection. To better understand the potential effects of BSMV-VIGS in hulless barley (Hordeum vulgare var. nudum), the accumulation pattern of BSMV and its impacts on vegetative growth and water status were investigated. The results indicated that the vegetative growth of infected plants was significantly and continuously impacted by BSMV from 10 to 40 days post inoculation (dpi). When the accumulation of BSMV was extremely high (7 to 11 dpi), infected plants displayed twisted leaf tips with an increased water lose rate (WLR) and decreased water content (WC). Virus accumulation declined and stabilized after 25 dpi, at this stage, the WLR and WC were unaffected in the infected plants. The efficiency of VIGS was tested by the silencing of Phytoene desaturase (PDS). RT-qPCR indicated that BSMV-VIGS can be sustained with good efficiency for up to 40 dpi under an altered condition with lower temperature (22 ±1°C) and higher relative humidity (70 ±10%). It was concluded that 25 to 40 dpi was the appropriate time zone for drought-related gene analysis by BSMV-VIGS under such condition.

Although it has been shown that exceptional good deeds exert influences on people's prosocial behavior and intention, we have known little about how common moral actions in our daily life. The present study aimed to examine how upward moral comparison influenced prosocial behavioral intention as well as to explore the mediating role of guilt and the moderating role of moral identity in the focal relationship. An experimental study was conducted with 162 Chinese undergraduates (103 women, 59 men) randomly assigned to an upward moral comparison condition, an upward competence comparison condition or a control condition. Results indicated that participants in the upward moral comparison condition experienced higher levels of guilt and exhibited stronger motivation to act prosocially, relative to participants in the other two conditions. That is to say, upward moral comparison induces guilty experience, and then increases people's prosocial behavioral intention. Moreover, we have found that moral identity internalization moderates the upward moral comparison-guilt relationship, and the indirect effect of upward moral comparison on prosocial behavioral intention via guilt. The implications of these findings were discussed.

We consider the existence of nonoscillatory solutions of higher-order neutral differential equations with distributed coefficients. We use the Banach contraction principle to obtain new sufficient condition for the existence of nonoscillatory solutions.