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Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation., Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments., Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland., Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Che, Zhang, Xiong, Shu, Jiang, Li, Guo, Qiao, Li, Li, Chang, Zhang, Zhang, Qiu, Xi, Li, Chen, Ye and Zhang.)

A recombinant inbred line (RIL) population derived from wheat landrace Qingxinmai and breeding line 041133 exhibited segregation in resistance to powdery mildew and stripe rust in five and three field tests, respectively. A 16K genotyping by target sequencing (GBTS) single-nucleotide polymorphism (SNP) array-based genetic linkage map was used to dissect the quantitative trait loci (QTLs) for disease resistance. Four and seven QTLs were identified for adult-plant resistance (APR) against powdery mildew and stripe rust. QPm.caas-1B and QPm.caas-5A on chromosomes 1B and 5A were responsible for the APR against powdery mildew in line 041133. QYr.caas-1B , QYr.caas-3B , QYr.caas-4B , QYr.caas-6B.1 , QYr.caas-6B.2 , and QYr.caas-7B detected on the five B-genome chromosomes of line 041133 conferred its APR to stripe rust. QPm.caas-1B and QYr.caas.1B were co-localized with the pleiotropic locus Lr46/Yr29/Sr58/Pm39/Ltn2 . A Kompetitive Allele Specific Polymorphic (KASP) marker KASP_1B_668028290 was developed to trace QPm/Yr.caas.1B . Four lines pyramiding six major disease resistance loci, PmQ , Yr041133 , QPm/Yr.caas-1B , QPm.caas-2B.1 , QYr.caas-3B , and QPm.caas-6B , were developed. They displayed effective resistance against both powdery mildew and stripe rust at the seedling and adult-plant stages., Competing Interests: Author HLL was employed by Jiushenghe Seed Industry Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Hu, Lin, Qiu, Qu, Du, Hou, Ma, Wu, Liu, Zhou and Li.)

Introduction: Codonopsis pilosula is widely sought-after in China as a substitute for the more expensive ginseng. Continuous cropping of C. pilosula supports a vibrant health-supplement industry but requires significant inputs of fertilizers which increase production costs and degrade the environment., Methods: Here, three environmentally-friendly natural fertilizers, including biochar, bacterial fertilizer, and vermicompost, were used at different concentrations (undiluted, diluted 10 times, diluted 50 times) to determine their efficacy in seed germination and growth physiology of C. pilosula in continuous cropping., Results: The results showed that biochar, bacterial fertilizer, and vermicompost with different concentrations of leachate could all increase the germination rate, germination potential and germination index of C. pilosula seeds treated with inter-root soil leachate of continuous C. pilosula ; increase the activity of antioxidant enzymes (superoxide dismutase and peroxidase) in C. pilosula seedlings under the stress of inter-root soil leachate of continuous C. pilosula , reduce the over-accumulation of malondialdehyde (MDA) content, and increase the resistance of C. pilosula seedlings. After transplanting, superoxide dismutase (SOD) activity increased by an average of 16.1%. Peroxidase (POD) levels showed an average increase of 16.4%. Additionally, there was a significant reduction in the MDA content, with an average decrease of 50%, and the content of osmotic-regulating substances (free proline content and soluble protein content) exhibited a significant increase., Discussion: In conclusion, biochar, bacterial manure, and vermicompost have the potential to overcome the challenges of extensive fertilizer use in continuous cropping of C. pilosula ., Competing Interests: Author MD was employed by the company Guangdong Yifang Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Qiu, Jiang, Du and Li.)

Background: In the process of modernization, along with economic development, intensified social competition, and increasing mental health problems such as anxiety and depression, the issue of subjective well-being has received widespread attention. The level of subjective well-being of college students also affects whether society can achieve sustainable development. In philosophy, political science, economics, sociology and other disciplines, labor is regarded as an important factor affecting subjective well-being. Labor education is an educational activity carried out by Chinese universities in recent years. This further inspires the author to think, for the college students, will the labor education received on campus have an impact on the subjective well-being? What characteristics will its impact mechanism present? What are the characteristics of the influence on subjective well-being?., Methods: This research adopts a cross-sectional design, specifically employing a random sampling approach. In this study, the questionnaire was distributed to the college's students of 14 universities in China through the Internet. A total of 2100 questionnaires were collected., Results: This paper mainly used questionnaires to collect data, and on this basis, examined the relationship between labor education participation, self-efficacy, healthy lifestyle and subjective well-being of college students. The results showed that: (1) Labor education participation positively affected college students' subjective well-being. (2) Self-efficacy partially mediated the relationship between labor education participation and college students' subjective well-being. (3) Healthy lifestyle partially mediated the relationship between labor education participation and college students' subjective well-being. (4) Self-efficacy and healthy lifestyle played a chain mediating role between labor education participation and college students' subjective well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qiu, Ni and Yang.)

Brown planthopper ( Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6 -transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zha, Qiu, Guo, Liu, Li, Wu, Li, Chen, Hu, Shi, Zhou, Zhang, Du and You.)

Red and blue light-emitting diodes (LEDs) affect the quality of sweet potato leaves and their nutritional profile. Vines cultivated under blue LEDs had higher soluble protein contents, total phenolic compounds, flavonoids, and total antioxidant activity. Conversely, chlorophyll, soluble sugar, protein, and vitamin C contents were higher in leaves grown under red LEDs. Red and blue light increased the accumulation of 77 and 18 metabolites, respectively. Alpha-linoleic and linolenic acid metabolism were the most significantly enriched pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 615 genes were differentially expressed between sweet potato leaves exposed to red and blue LEDs. Among these, 510 differentially expressed genes were upregulated in leaves grown under blue light compared with those grown under red light, while the remaining 105 genes were expressed at higher levels in the latter than in the former. Among the KEGG enrichment pathways, blue light significantly induced anthocyanin and carotenoid biosynthesis structural genes. This study provides a scientific reference basis for using light to alter metabolites to improve the quality of edible sweet potato leaves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tadda, Li, Ding, Li, Wang, Huang, Fan, Chen, He, Ahiakpa, Karikari, Chen and Qiu.)

With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant-soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiu, Xu, Zhang, Zhou, Wang, Zhang, Yu, Lu, Sun, Zhou, Peijnenburg and Qian.)

It has been shown that multidrug and toxic compound extrusion/detoxification (MATE/DTX) family transporters are involved in the regulation of plant development and stress response. Here, we characterized the mini body1 ( mib1 ) mutants in mungbean, which gave rise to increased branches, pentafoliate compound leaves, and shortened pods. Map-based cloning revealed that MIB1 encoded a MATE/DTX family protein in mungbean. qRT-PCR analysis showed that MIB1 was expressed in all tissues of mungbean, with the highest expression level in the young inflorescence. Complementation assays in Escherichia coli revealed that MIB1 potentially acted as a MATE/DTX transporter in mungbean. It was found that overexpression of the MIB1 gene partially rescued the shortened pod phenotype of the Arabidopsis dtx54 mutant. Transcriptomic analysis of the shoot buds and young pods revealed that the expression levels of several genes involved in the phytohormone pathway and developmental regulators were altered in the mib1 mutants. Our results suggested that MIB1 plays a key role in the control of plant architecture establishment in mungbean., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jia, Sun, Ji, Zhang, Qiu, Cai, Xia, Yuan, Chen and Shen.)

Bracts are the metamorphic non-flower organ in angiosperm plants. The variation of the color and shape of bracts was found to be neo-functionalized (i.e., similar to petals), garnering research interest as a pollinator attractor. Bougainvillea is known for its specialized, large, and colorful bracts, which contrast with its tiny colorless flowers. As a plant whose bracts vary greatly in terms of coloration, the molecular mechanisms for Bougainvillea bract coloration and polychroism are largely unknown. The lack of genomic information for Bougainvillea largely hinders studies into the evolution and genetic basis of bract color variation. In this study, a pan-transcriptome of bracts obtained from 18 Bougainvillea glabra accessions was employed to investigate the global population-level germplasm kinship and the gene regulation network for bract color variation. Our results showed that the bracts of B. glabra accessions have largely differentiated International Commission on Illumination (CIE) L-a-b values. Moreover, germplasm kinship detected using principal component analysis, phylogeny, and admixture analysis showed three optimal subgroups, two of them distinctly clustered, which were not directly correlated with bract color variation at the population level. Differentially expressed genes (DEGs) between accessions of high vs. low L-a-b values revealed several considerable upregulated genes related to bract color L-a-b variation. A weighted gene co-expression network was constructed, and eight co-expressed regulation modules were identified that were highly correlated with variation in bract CIE L-a-b color values. Several candidate DEGs and co-expressed hub genes (e.g., GERD , SGR , ABCA3 , GST , CYP76AD1 , CYP76C , and JAZ ) that were tightly associated with bract color variation were eventually determined responsible for L-a-b colorations, which might be the core regulation factors contributing to the B. glabra bract color variation. This study provides valuable insights into the research on germplasm kinship, population-level pan-transcriptome expression profiles, and the molecular basis of color variation of key innovative bracts in horticultural Bougainvillea ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Ji, Ju, Lin, Li, Lv, Lin, Guo, Qiu, Yan and Ma.)

Broad diversity of flowers in Fabaceae provides a good system to investigate development and evolution of floral symmetry in higher plants. Many studies have demonstrated a conserved mechanism controlling development of zygomorphic flower during last decades. However, the molecular basis of how asymmetric flower established is largely unknown. In this study, we characterized mutants named keeled wings ( kw ) in mungbean ( Vigna radiata L.), which is a legume species with asymmetric flowers. Compared to those in the wild type plants, the lateral petals were ventralized in the kw mutants. Map-based cloning showed that KW was VrCYC3 gene in mungbean, the ortholog of Lotus japonicus CYC3 ( LjCYC3 ) and Pisum sativum CYC3 ( PsCYC3 ). In addition, another two CYC -like genes named VrCYC1 and VrCYC2 were identified from mungbean genome. The three CYC -like genes displayed distinct expression patterns in dorsal, lateral and ventral petals. It was found that VrCYC3 was located in nucleus. Further analysis showed that VrCYC3 had transcription activity and could interact with VrCYC1 and VrCYC2 in yeast cell. Moreover, the deletion of two amino acid residues in the R domain of VrCYC3 protein could decrease its interaction with VrCYC1 and VrCYC2 proteins. Our results suggest that LjCYC3/VrCYC3 orthologs play conserved roles determining the lateral petal shape and identity of zygomorphic flower as well as asymmetric flower in Papilionoideae., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Sun, Jia, Qiu, Peng and Zhuang.)

Orchidaceae, with more than 25,000 species, is one of the largest flowering plant families that can successfully colonize wide ecological niches, such as land, trees, or rocks, and its members are divided into epiphytic, terrestrial, and saprophytic types according to their life forms. Cellulose synthase ( CesA ) and cellulose synthase-like ( Csl ) genes are key regulators in the synthesis of plant cell wall polysaccharides, which play an important role in the adaptation of orchids to resist abiotic stresses, such as drought and cold. In this study, nine whole-genome sequenced orchid species with three types of life forms were selected; the CesA/Csl gene family was identified; the evolutionary roles and expression patterns of CesA/Csl genes adapted to different life forms and abiotic stresses were investigated. The CesA/Csl genes of nine orchid species were divided into eight subfamilies: CesA and CslA/B/C/D/E/G/H, among which the CslD subfamily had the highest number of genes, followed by CesA, whereas CslB subfamily had the least number of genes. Expansion of the CesA/Csl gene family in orchids mainly occurred in the CslD and CslF subfamilies. Conserved domain analysis revealed that eight subfamilies were conserved with variations in orchids. In total, 17 pairs of CesA/Csl homologous genes underwent positive selection, of which 86%, 14%, and none belonged to the epiphytic, terrestrial, and saprophytic orchids, respectively. The inter-species collinearity analysis showed that the CslD genes expanded in epiphytic orchids. Compared with terrestrial and saprophytic orchids, epiphytic orchids experienced greater strength of positive selection, with expansion events mostly related to the CslD subfamily, which might have resulted in strong adaptability to stress in epiphytes. Experiments on stem expression changes under abiotic stress showed that the CslA might be a key subfamily in response to drought stress for orchids with different life forms, whereas the CslD might be a key subfamily in epiphytic and saprophytic orchids to adapt to freezing stress. This study provides the basic knowledge for the further systematic study of the adaptive evolution of the CesA/Csl superfamily in angiosperms with different life forms, and research on orchid-specific functional genes related to life-history trait evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Lin, Deng, Lin, Lv, Hu, Liu, Fatima, He, Qiu and Ma.)

Objectives: To evaluate a new deep neural network (DNN)-based computer-aided diagnosis (CAD) method, namely, a prostate cancer localization network and an integrated multi-modal classification network, to automatically localize prostate cancer on multi-parametric magnetic resonance imaging (mp-MRI) and classify prostate cancer and non-cancerous tissues. Materials and methods: The PROSTAREx database consists of a "training set" (330 suspected lesions from 204 cases) and a "test set" (208 suspected lesions from 104 cases). Sequences include T2-weighted, diffusion-weighted, Ktrans, and apparent diffusion coefficient (ADC) images. For the task of abnormal localization, inspired by V-net, we designed a prostate cancer localization network with mp-MRI data as input to achieve automatic localization of prostate cancer. Combining the concepts of multi-modal learning and ensemble learning, the integrated multi-modal classification network is based on the combination of mp-MRI data as input to distinguish prostate cancer from non-cancerous tissues through a series of operations such as convolution and pooling. The performance of each network in predicting prostate cancer was examined using the receiver operating curve (ROC), and the area under the ROC curve (AUC), sensitivity (TPR), specificity (TNR), accuracy, and Dice similarity coefficient (DSC) were calculated. Results: The prostate cancer localization network exhibited excellent performance in localizing prostate cancer, with an average error of only 1.64 mm compared to the labeled results, an error of about 6%. On the test dataset, the network had a sensitivity of 0.92, specificity of 0.90, PPV of 0.91, NPV of 0.93, and DSC of 0.84. Compared with multi-modal classification networks, the performance of single-modal classification networks is slightly inadequate. The integrated multi-modal classification network performed best in classifying prostate cancer and non-cancerous tissues with a TPR of 0.95, TNR of 0.82, F1-Score of 0.8920, AUC of 0.912, and accuracy of 0.885, which fully confirmed the feasibility of the ensemble learning approach. Conclusion: The proposed DNN-based prostate cancer localization network and integrated multi-modal classification network yielded high performance in experiments, demonstrating that the prostate cancer localization network and integrated multi-modal classification network can be used for computer-aided diagnosis (CAD) of prostate cancer localization and classification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yi, Ou, Hu, Qiu, Quan, Othmane, Wang and Wu.)

While hippocampal atrophy and its regional susceptibility to Alzheimer's disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: n = 40) and healthy older adults with negative (HO-: n = 47) and positive (HO+ : n = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-β, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Shahid, Lin, Hone-Blanchet, Smith, Risk, Bisht, Loring, Goldstein, Levey, Lah and Qiu.)

Objective: To determine the different clinical features of patients with vertigo attacks alone and of those with weakness accompanying vertigo attacks before the vertebrobasilar ischemic stroke., Methods: In this 4-year retrospective study, we manually screened the medical records of 209 patients, hospitalized with vertigo attack as the main complaint who were finally diagnosed with acute vertebrobasilar ischemic stroke. Patients were divided into two groups according to their symptoms: patients who only experienced vertigo attacks prior to the vertebrobasilar stroke (VO group) and patients who had both vertigo and weakness attacks (VW group) prior to the stroke. Clinical parameters, such as infarction site and volume, relative risk factors, ABCD 2 score, and medical intervention, were compared between the two groups., Results: The prevalence of hypertension was higher in the Vertigo attacks only (VO) group (42.2 vs. 29.0%, p < 0.05). The total cerebral infarction volume in the VO group was larger than the Vertigo and weakness attacks (VW) group (4.44 vs. 2.12 cm 3 , p < 0.05). Additionally, the cerebellum was more likely to be affected in the VO group. In contrast, patients in the VW group had higher carotid stenosis (14.2 vs. 27.2%, p < 0.05) and ABCD 2 score (2.1 ± 1.2 vs. 3.6 ± 1.5, p = 0.02). The percentage of patients with medullary infarctions also increased in the VW group. Vertigo attack events occurred more frequently in the VW group (median 2.4 vs. 4.3, p < 0.04). We also found that the patients in the VW group were more likely to seek medical intervention after vertigo., Conclusions: Clinical parameters, such as infarction location, relative risk factors, and ABCD 2 score, differed between patients with vertigo symptoms with or without weakness attacks. These findings highlight the different clinical features of patients with vertigo attack only and those with weakness attacks accompanying vertigo prior to vertebrobasilar ischemic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Zhang, Zhang, Duan, Huang and Qiu.)

The citrus orchards in southern China are widely threatened by low soil pH and Huanglongbing (HLB) prevalence. Notably, the lime application has been used to optimize soil pH, which is propitious to maintain root health and enhance HLB tolerance of citrus; however, little is known about the interactive effects of soil acidity on the soil properties and root-associated (rhizoplane and endosphere) microbial community of HLB-infected citrus orchard. In this study, the differences in microbial community structures and functions between the acidified and amended soils in the Gannan citrus orchard were investigated, which may represent the response of the host-associated microbiome in diseased roots and rhizoplane to dynamic soil acidity. Our findings demonstrated that the severity of soil acidification and aluminum toxicity was mitigated after soil improvement, accompanied by the increase in root activity and the decrease of HLB pathogen concentration in citrus roots. Additionally, the Illumina sequencing-based community analysis showed that the application of soil amendment enriched functional categories involved in host-microbe interactions and nitrogen and sulfur metabolisms in the HLB-infected citrus rhizoplane; and it also strongly altered root endophytic microbial community diversity and structure, which represented by the enrichment of beneficial microorganisms in diseased roots. These changes in rhizoplane-enriched functional properties and microbial composition may subsequently benefit the plant's health and tolerance to HLB disease. Overall, this study advances our understanding of the important role of root-associated microbiota changes and ecological factors, such as soil acidity, in delaying and alleviating HLB disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Hu, Qiu, Francis, Wang and Wang.)

Background: Comparisons between high intensity interval training (HIIT) and continuous training (CT) regarding improvements of adolescents' cardiac function are scarce and the preferred intensity for cardiac improvement with restricted myocardial damage remains unknown. This study conducted a 4-weeks training in male adolescent rats under moderate (MI) or high intensity (HI) HIIT and CT programs, aiming to discover and compare exercise-induced myocardial adaptations towards these two training methods. Methods: 39 male adolescent Sprague-Dawley rats (aged 4 weeks) were randomly assigned to high intensity HIIT (HI-HIIT, n = 8), moderate intensity HIIT (MI-HIIT, n = 8), high intensity CT (HI-CT, n = 8), moderate intensity CT (MI-CT, n = 8) and sedentary control (SC, n = 7) groups. Rats in training groups were trained for 4 weeks and echocardiography was performed at baseline and after the final training. Serum creatine kinase myocardial band (CK-MB), cardiac troponin T (cTn-T) and untargeted metabolomics analysis were measured from blood samples collected 24 h after the final training. Results: HIIT groups had greater cardiac output improvement than CT groups while no significant difference was found between the HI-HIIT and the MI-HIIT groups. HI-CT group showed higher serum CK-MB and cTn-T levels compared to MI-HIIT, MI-CT and control groups. Untargeted metabolomics analysis identified eleven HI-HIIT-related metabolites, five MI-HIIT-related metabolites and two HICT-related metabolites. The majority of the identified metabolites were phospholipid-related. Phosphatidylglyceride 18 level was significantly different between the HI-CT and MI-CT groups, and was negatively associated with cTn-T in CT groups. Conclusion: HIIT and CT improve cardiac function of adolescent rats while the HIIT demonstrates better improvement and less myocardial damage. High and moderate training intensities in HIIT exert similar cardiac benefits. HI-CT induced myocardial damage might be associated with serum phospholipids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Liu, Lv, Mi, Qiu, He and Zhao.)

Wheat genotypes resistant to powdery mildew ( Blumeria graminis f. sp. tritici , Bgt ) provide a sustainable means for disease control. We developed a pair of near-isogenic lines H962R and H962S with contrasting reactions to powdery mildew from a residue heterozygous line. H962R was resistant to 127 out of the 136 Bgt isolates collected from the major wheat-producing regions of China and showed a similar virulence/avirulence pattern as Fuzhuang 30, Xiaobaidong, and Hongquanmang carrying resistance allele of Pm5e , but H962S was resistant to none of them. A dominant gene was responsible for the powdery mildew resistance of H962R as revealed by the genetic analysis using segregating populations derived from a cross between H962R and H962S. Molecular marker analysis detected a resistance locus, designated PmH962 , on a genetic interval of the chromosome arm 7BL where Pm5e resides. This locus was co-segregated with the functional marker of Pm5e . The PCR-based sequence alignment of Pm5e demonstrated that H962R had an identical sequence as Fuzhuang 30 (haplotype HapGA), and H962S possessed the same sequence as the powdery mildew susceptible cultivar Kenong 199. The genomic compositions of lines H962R and H962S were highly comparable as evidenced by only a small percentage of SNP variations detected by the 16K Genotyping by Target Sequencing (GBTS) SNP array and the 90K Illumina iSelect Wheat SNP array. The two lines performed similarly in the yield-related and plant growth traits investigated, except for greater kernel weight in H962R than in H962S. This indicates that Pm5e has no deleterious effect and can be served as an excellent disease resistance gene in wheat breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiu, Huang, Guo, Hu, Li, Zhang, Liu, Yang, Zhou, Yang, Zhang, Liu and Li.)

Background: Hypertension (HTN) is a global public health concern. However, the association between life events (LEs) and HTN is complex. Thus, we conducted a prospective cohort study to explore this complex association., Methods: A total of 8,077 government employees without HTN were recruited through cluster sampling between 2018 and 2019 in Hunan Province, China. At baseline, information regarding sociodemographic characteristics, LEs, and behavioral factors was collected. After the 1-year follow-up, the participants were revisited to obtain the HTN diagnosis. Crude and adjusted Poisson regression models were constructed to calculate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Cubic regression spline models were used to visualize the trends between LEs and HTN IRRs. Interactive and subgroup analyses were also performed., Results: The 1-year HTN incidence rate among government employees in Hunan province was 4.30% (95% CI: 3.86-4.74%). LEs were associated with a higher HTN risk (IRR, 1.02; 95% CI, 1.00-1.04). When calculating positive and negative LEs scores separately, only the latter was a risk factor for HTN incidence (IRR, 1.04; 95% CI, 1.03-1.06); conversely, positive LEs reduced the risk (IRR, 0.90; 95% CI, 0.85-0.96). Compared with patients in the lowest quartile of LEs score, those in quartiles two (IRR, 1.28; 95% CI, 0.96-1.71), three (IRR, 1.43; 95% CI, 1.04-1.96), and four (IRR, 1.73; 95% CI, 1.26-2.37) were at progressively higher risk. In restricted spline curves, a non-linear association was noted between LEs and HTN risk. Regarding the subcategories of LEs, work-related LEs, personal LEs, and all subcategories of negative LEs were associated with an increased risk of HTN. However, among positive LEs, only the family-related cases were associated with a lower risk of HTN., Conclusion: LEs had a non-linear association with an increased risk of HTN. Negative LEs were risk factors for HTN incidence, whereas positive LEs reduced the risk of HTN. Thus, the importance of LEs should be highlighted in the development of HTN prevention strategies and initiatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ouyang, He, Cheng, Qiu, Li, Bangura, Duan, Luo and Xiao.)

The plant cuticle, as a lipid membrane covering aerial plant surfaces, functions primarily against uncontrolled water loss. Herein, the cuticle chemical composition and the transpiration of wampee fruit ( Clausena lansium (Lour.) Skeels) at the green, turning, and yellow stages in cultivars of "Jixin" and "Tianhuangpi" were comprehensively studied. The coverage of wax and cutin monomers per unit of fruit surface area at the green stage was lower in "Jixin" than in "Tianhuangpi" and increased gradually during development. Cutin monomers accumulated ranging from 22.5 μg cm -2 (green) to 52.5 μg cm -2 (turning) in "Jixin" and from 36.5 μg cm -2 (green) to 81.7 μg cm -2 (yellow) in "Tianhuangpi." The total composition of waxes ranged between 6.0 μg cm -2 (green) and 11.1 μg cm -2 (turning) in "Jixin," while they increased from 7.4 μg cm -2 (green) to 16.7 μg cm -2 (yellow) in "Tianhuangpi." Cutin monomers were dominated by ω-, mid-dihydroxy fatty acids (over 40%), followed by multiple monomers of α,ω-dicarboxylic acids with or without added groups, α-monocarboxylic acids with or without ω- or mid-chain hydroxy or mid-epoxy groups, primary alcohols, and phenolics. The very-long-chain (VLC) aliphatic pattern of cuticular waxes was prominently composed of n -alkanes (ranging from 21.4% to 39.3% of total wax content), fatty acids, primary alcohols, and aldehydes. The cyclic waxes were dominated by triterpenoids (between 23.9 and 51.2%), sterols, and phenolics. Water loss in wampee fruit exhibited linear changes over time, indicating an overall monofunctional barrier to transpiration. Permeance for water in wampee fruit was higher at the green stage than at the yellow stage in both "Jixin" and "Tianhuangpi," which showed a negative correlation with the changes of VLC n -alkanes. The results showed the cuticular chemicals, including cutin monomers and waxes, in wampee fruit and further indicated the potential contributions of the cuticular chemical composition to the physiological functions in fruits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Qiu and Lu.)

The purpose of this study was to assess spatially remote effects of hemodynamic impairment on functional network topology contralateral to unilateral anterior circulation steno-occlusive disease (SOD) using resting-state blood oxygen level-dependent (BOLD) imaging, and to investigate the relationships between network connectivity and cerebrovascular reactivity (CVR), a measure of hemodynamic stress. Twenty patients with unilateral, chronic anterior circulation SOD and 20 age-matched healthy controls underwent resting-state BOLD imaging. Five-minute standardized baseline BOLD acquisition was followed by acetazolamide infusion to measure CVR. The BOLD baseline was used to analyze network connectivity contralateral to the diseased hemispheres of SOD patients. Compared to healthy controls, reduced network degree ( z -score = -1.158 ± 1.217, P < 0.001, false discovery rate (FDR) corrected), local efficiency ( z -score = -1.213 ± 1.120, P < 0.001, FDR corrected), global efficiency ( z -score = -1.346 ± 1.119, P < 0.001, FDR corrected), and enhanced modularity ( z -score = 1.000 ± 1.205, P = 0.002, FDR corrected) were observed in the contralateral, normal hemispheres of SOD patients. Network degree ( P = 0.089, FDR corrected; P = 0.027, uncorrected) and nodal efficiency ( P = 0.089, FDR corrected; P = 0.045, uncorrected) showed a trend toward a positive association with CVR. The results indicate remote abnormalities in functional connectivity contralateral to the diseased hemispheres in patients with unilateral SOD, despite the absence of macrovascular disease or demonstrable hemodynamic impairment. The clinical impact of remote functional disruptions requires dedicated investigation but may portend far reaching consequence for even putatively unilateral cerebrovascular disease., Competing Interests: SD — UNRELATED: Unpaid scientific consultation and collaboration with Ischemaview; Past travel support from Ischemaview as an individual; Scientific consulting with Regeneron as an individual; Domestic and international patent filed by institution for inventor's disclosure in the development of device to measure brain electrical properties; Grant funding paid to institution from undisclosed donor for study on the development of remote stroke detection devices. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Nahab, Allen, Hu, Dehkharghani and Qiu.)

Arsenate [As(V)] is a toxic metalloid and has been observed at high concentrations in groundwater globally. In this study, a bioelectrochemical system (BES) was used to efficiently remove As(V) from groundwater, and the mechanisms involved were systematically investigated. Our results showed that As(V) can be efficiently removed in the BES cathode chamber. When a constant cell current of 30 mA ( I cell , volume current density = 66.7 A/m 3 ) was applied, 90 ± 3% of total As was removed at neutral pH (7.20-7.50). However, when I cell was absent, the total As in the effluent, mainly As(V), had increased approximately 2-3 times of the As(V) in influent. In the abiotic control reactor, under the same condition, no significant total As or As(V) removal was observed. These results suggest that As(V) removal was mainly ascribed to microbial electrosorption of As(V) in sludge. Moreover, part of As(V) was bioelectrochemically reduced to As(III), and sulfate was also reduced to sulfides [S(-II)] in sludge. The XANES results revealed that the produced As(III) reacted with S(-II) to form As 2 S 3 , and the residual As(III) was microbially electroadsorbed in sludge. This BES-based technology requires no organic or chemical additive and has a high As(V) removal efficiency, making it an environment-friendly technique for the remediation of As-contaminated groundwater., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Huang, Jiang, Huang, Qiu, Gustave, Tang and Li.)

Leaf-chewing insects are important pests that cause yield loss and reduce seed quality in soybeans ( Glycine max ). Breeding soybean varieties that are resistant to leaf-chewing insects can minimize the need for insecticide use and reduce yield loss. The marker gene for QTL-M, Glyma.07g110300 (LOC100775351) that encodes a UDP-glycosyltransferase (UGT) is the major determinant of resistance against leaf-chewing insects in soybean; it exhibits a loss of function in insect-resistant soybean germplasms. In this study, Agrobacterium -mediated transformation introduced the CRISPR/Cas9 expression vector into the soybean cultivar Tianlong No. 1 to generate Glyma.07g110300- gene mutants. We obtained two novel types of mutations, a 33-bp deletion and a single-bp insertion in the GmUGT coding region, which resulted in an enhanced resistance to Helicoverpa armigera and Spodoptera litura . Additionally, overexpressing GmUGT produced soybean varieties that were more sensitive to H . armigera and S. litura . Both mutant and overexpressing lines exhibited no obvious phenotypic changes. The difference in metabolites and gene expression suggested that GmUGT is involved in imparting resistance to leaf-chewing insects by altering the flavonoid content and expression patterns of genes related to flavonoid biosynthesis and defense. Furthermore, ectopic expression of the GmUGT gene in the ugt72b1 mutant of Arabidopsis substantially rescued the phenotype of H. armigera resistance in the atugt72b1 mutant. Our study presents a strategy for increasing resistance against leaf-chewing insects in soybean through CRISPR/Cas9-mediated targeted mutagenesis of the UGT genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Guo, Chen, Shen, Yang, Fang, Ouyang, Mai, Chen, Chen, Hao, Yuan, Zhang, Huang, Shan, Yang, Qiu, Zhou, Cao, Li and Jiao.)

The plant cuticle covers almost all the outermost surface of aerial plant organs, which play a primary function in limiting water loss and responding to the environmental interactions. Banana fruit is susceptible to thermal changes with chilling injury below 13°C and green ripening over 25°C. Herein, the changes of surface morphology, chemical compositions of cuticle, and the relative expression of cuticle biosynthesis genes in banana fruit under low-temperature storage were investigated. Banana fruit exhibited chilling injury rapidly with browned peel appearance stored at 4°C for 6 days. The surface altered apparently from the clear plateau with micro-crystals to smooth appearance. As compared to normal ones, the overall coverage of the main cuticle pattern of waxes and cutin monomers increased about 22% and 35%, respectively, in browned banana stored under low temperature at 6 days. Fatty acids (C 16 -C 18 ) and ω-OH, mid-chain-epoxy fatty acids (C 18 ) dominated cutin monomers. The monomers of fatty acids, the low abundant ω, mid-chain-diOH fatty acids, and 2-hydroxy fatty acids increased remarkably under low temperature. The cuticular waxes were dominated by fatty acids (> C 19 ), n -alkanes, and triterpenoids; and the fatty acids and aldehydes were shifted to increase accompanied by the chilling injury. Furthermore, RNA-seq highlighted 111 cuticle-related genes involved in fatty acid elongation, biosynthesis of very-long-chain (VLC) aliphatics, triterpenoids, and cutin monomers, and lipid-transfer proteins were significantly differentially regulated by low temperature in banana. Results obtained indicate that the cuticle covering on the fruit surface was also involved to respond to the chilling injury of banana fruit after harvest. These findings provide useful insights to link the cuticle on the basis of morphology, chemical composition changes, and their biosynthesis regulations in response to the thermal stress of fruit during storage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Wang, Qiu, Zhang and Bi.)

Objective: To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open temporal lobe resection. Methods: Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH: n = 40) or open resection procedures ( n = 40) using both reliable change index (RCI) scores and a 1-SD change metric. Results: Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 [5.0%], p = 0.0064, Fisher's exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 [47.4%]) compared to laser ablation (2/19 [10.5%], p = 0.0293, Fisher's exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 [80.0%]), although it rarely occurred in such patients after SLAH (2/14, 14.3%) ( p = 0.0027, Fisher's exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection. Interpretation: These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions., Competing Interests: Medtronic, Inc., contributed research funding to Emory University, and develops products related to the research described in the paper. However, Medtronic, Inc., was not involved in the study design, data collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. RG and JW serve as consultants to Medtronic, Inc., and receive compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University and Washington University in Saint Louis in accordance with their respective conflict of interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Drane, Willie, Pedersen, Qiu, Voets, Millis, Soares, Saindane, Hu, Kim, Hewitt, Hakimian, Grabowski, Ojemann, Loring, Meador, Faught, Miller and Gross.)

Plant morphogenesis involves multiple biochemical and physical processes inside the cell wall. With the continuous progress in biomechanics field, extensive studies have elucidated that mechanical forces may be the most direct physical signals that control the morphology of cells and organs. The extensibility of the cell wall is the main restrictive parameter of cell expansion. The control of cell wall mechanical properties largely determines plant cell morphogenesis. Here, we summarize how cell wall modifying proteins modulate the mechanical properties of cell walls and consequently influence plant morphogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qiu, Xu, Wang, Zhou and Hong.)

Legume nodule development and senescence directly affect nitrogen fixation efficiency and involve a programmed series of molecular events. These molecular events are carried out synchronously by legumes and rhizobia. The characteristics and molecular mechanisms of nitrogen fixation at soybean important developmental stages play critical roles in soybean cultivation and fertilizer application. Although the gene expression of soybean were analyzed in nodules at five important soybean developmental stages, information on the expression of rhizobial genes in these nodule samples is limited. In the present study, we investigated the expression of Bradyrhizobium diazoefficiens 113-2 genes in the nodule samples from five developmental stages of soybean (Branching stage, flowering stage, fruiting stage, pod stage and harvest stage). Similar gene expression patterns of B. diazoefficiens 113-2 were existed during optimal symbiotic functioning, while different expression patterns were found among early nodule development, nitrogen fixation progress and nodule senescence. Besides, we identified 164 important different expression genes (DEGs) associated with nodule development and senescence. These DEGs included those encoding nod, nif, fix proteins and T3SS secretion system-related proteins, as well as proteins involved in nitrogen metabolism, ABC transporters and two-component system pathways. Gene Ontology, KEGG pathway and homology analysis of the identified DEGs revealed that most of these DEGs are uncharacterized genes associated with nodule development and senescence, and they are not core genes among the rhizobia genomes. Our results provide new clues for the understanding of the genetic determinants of soil rhizobia in nodule development and senescence, and supply theoretical basis for the creation of high efficiency soybean cultivation technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Zhou, Feng, Zhang, Huang, Shan, Chen, Guo, Yang, Yang, Qiu, Chen and Zhou.)

Background: High suicide rate in the elderly is an important global public health problem but has not received the attention it deserves. This study aimed to examine time trends of suicide mortality for people aged 70 years and over by sex, age, and location from 1990 to 2017, and to provide predictions up to 2030. Methods: Using data from the Global Burden of Disease study 2017, we presented elderly suicide mortality changes and compared the patterns for the elderly with that for all ages. We estimated associations between socio-demographic index (SDI) and suicide mortality rates using a restricted cubic spline smoother, and predicted suicide mortality rates up to 2030. Results: In 2017, 118,813 people aged 70 years and over died from suicide, indicating a mortality rate of 27.5 per 100,000, with the highest rates in Eastern Sub-Saharan Africa, Western Sub-Saharan Africa, and Central Sub-Saharan Africa, and for countries and territories, the highest were in South Korea, Zimbabwe, Lesotho, Mozambique, and Senegal. Between 1990 and 2017, suicide mortality rate for the elderly aged 70 years and over decreased globally (percentage change -29.1%), and the largest decreases occurred in East Asia, Southern Latin America, and Western Europe. Nationally, the largest decrease was found in Chile, followed by Czech Republic, Hungary, Turkey, and Philippines. For most countries, the elderly mortality rate was higher than the age-standardized rate, with the largest percentage differences in China and countries in Sub-Saharan Africa. The elderly suicide mortality rate decreased as SDI increased, except for a slight rebound at mid to high SDI. According to projections, 10 out of 195 countries were expected to meet the SDGs indicator of a third reduction by 2030. Conclusions: Variability in suicide mortality rates for the elderly aged 70 years and over by sex, age, region, country, and SDI can guide preventive policies, but causes of the variability need further study. Comprehensive strategies should be adopted to reduce suicide rates and close the gap to the 2030 SDGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Ouyang, Qiu, Li, Li and Xiao.)

Cystatin E/M (CST6), a representative cysteine protease inhibitor, plays both tumor-promoting and tumor-suppressing functions and is pursued as an epigenetically therapeutic target in special cancer types. However, a comprehensive and systematic analysis for CST6 in pan-cancer level is still lacking. In the present study, we explored the expression pattern of CST6 in multiple cancer types across ∼10,000 samples from TCGA (The Cancer Genome Atlas) and ∼8,000 samples from MMDs (Merged Microarray-acquired Datasets). We found that the dynamic expression alteration of CST6 was consistent with dual function in different types of cancer. In addition, we observed that the expression of CST6 was globally regulated by the DNA methylation in its promoter region. CST6 expression was positively correlated with the epithelial cell infiltration involved in epithelial-to-mesenchymal transition (EMT) and proliferation. The relationship between CST6 and tumor microenvironment was also explored. In particular, we found that CST6 serves a protective function in the process of melanoma metastasis. Finally, the clinical association analysis further revealed the dual function of CST6 in cancer, and a combination of the epithelial cell infiltration and CST6 expression could predict the prognosis for SKCM patients. In summary, this first CST6 pan-cancer study improves the understanding of the dual functional effects on CST6 in different types of human cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Ding, Cao, Yu, Wang, Qiu, Xu, Bi, Mu and Li.)

Objective: This study aimed to explore the relationships and the underlying mechanisms between work stress and mental health problems, and potential mediation effects through job dissatisfaction in a working population. Methods: A large population-based study among workers in China was conducted. The self-reported scales of assessing job dissatisfaction and work stress were included in the questionnaire. Generalized Anxiety Disorder-2 and Patient Health Questionnaire-2 were used for assessment of mental health. Univariate logistic regression was conducted to test the associations between work stress and mental health. Path analysis was conducted to test the proposed mediation model. Results: Of the 6,190 included employees, 27.72% reported that they perceived work stress, 14.84% of them reported that they were not satisfied with their work, 5.01% of the employees reported depressive symptoms, and 3.75% of the employees reported anxiety symptoms. The results of univariate logistic regression showed that employees who perceived work stress were more likely to report anxiety symptoms (adjusted odds ratio (AOR) = 2.78; 95% CI: 2.03-3.79) or depressive symptoms (AOR = 1.61; 95% CI: 1.22-2.12). The path analysis showed that work stress was positively associated with job dissatisfaction. Job dissatisfaction mediated the relationship between work stress and mental health problems among Chinese working adults. Conclusion: This study suggests the importance of psychosocial work environment for mental health among Chinese working adults. Work dissatisfaction is a stressor that may induce negative consequences on the mental health among Chinese workers. Interventions to help workers with stress management may be beneficial for their mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qiu, Li, Li, He, Ouyang, Luo and Xiao.)

Pathological neovascularization in choroid, a leading cause of blindness, is a characteristic of many fundus diseases, such as diabetic retinopathy and age-related macular degeneration. The present study aimed to elucidate the key signaling pathways in choroidal neovascularization (CNV) by analyzing the mRNA profiles of choroid and retina in tree shrews with CNV. We induced choroidal angiogenesis by laser photocoagulation in 15 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Hierarchical cluster analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, hematoxylin and eosin (HE) staining, CD31 immunohistochemistry (IHC), and reverse transcription quantitative PCR (RT-qPCR) were performed. After laser photocoagulation, we obtained a total of 350 differentially expressed genes (DEGs) in the choroid, including 59 genes in Module-FASN ("ME-FASN") module and 28 genes in Module-RPL ("ME-RPL") module. A total of 69 DEGs in retina, including 20 genes in Module-SLC ("ME-SLC") module. Bioinformatics analysis demonstrated that DEGs in choroid were mainly involved in membrane transport; DEGs in "ME-RPL" were prominent in pathways associated with IgA production, antigen presentation, and cell adhesion molecules (CAMs) signaling. DEGs in "ME-FASN" were involved in fatty acid metabolism and PPAR signaling pathway, while DEGs in "ME-SLC" were involved in GABAergic synapse, neuroactive life receptor interaction, cholinergic synapse, and retrograde endocannabinoid signaling pathway. PPI network analysis demonstrated that the ribosomal protein family genes ( RPL31, RPL7, RPL26L1, and RPL19 ) are key factors of "ME-RPL," acyl-CoA superfamily genes ( ACACA, ACAT1, ACAA2, and ACACB ) and FASN are key factors of "ME-FASN" and superfamily of solid carrier genes ( SLC17A6, SLC32A1, SLC12A5, and SLC6A1 ) and complement genes ( C4A, C3, and C2 ) are key factors of "ME-SLC." In conclusion, the present study discovered the important signal transductions (fatty acid metabolic pathway and CAMs signaling) and genes (ribosomal protein family and the complement system) in tree shrew CNV. We consider that our findings hold implications in unraveling molecular mechanisms that underlie occurrence and development of CNV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jia, Qiu, Lu, Wang, Li, Han, Tong, Sun, Wu and Dai.)

Huanglongbing (HLB) is the most destructive citrus disease worldwide. This is associated with the phloem-limited bacterium Candidatus Liberibacter, and the typical symptom is leaf blotchy mottle. To better understand the biological processes involved in the establishment of HLB disease symptoms, the comparative proteomic analysis was performed to reveal the global protein accumulation profiles in leaf petiole, where there are massive HLB pathogens of Ca. L. asiaticus-infected Newhall sweet orange ( Citrus sinensis ) plants at the asymptomatic and symptomatic stages compared to their healthy counterpart. Photosynthesis, especially the pathway involved in the photosystem I and II light reactions, was shown to be suppressed throughout the whole Ca. L. asiaticus infection cycle. Also, starch biosynthesis was induced after the symptom-free prodromal period. Many defense-associated proteins were more extensively regulated in the petiole with the symptoms than the ones from healthy plants. The change of salicylic and jasmonic acid levels in different disease stages had a positive correlation with the abundance of phytohormone biosynthesis-related proteins. Moreover, the protein-protein interaction network analysis indicated that an F-type ATPase and an alpha-1,4 glucan phosphorylase were the core nodes in the interactions of differentially accumulated proteins. Our study indicated that the infected citrus plants probably activated the non-unified and lagging enhancement of defense responses against Ca. L. asiaticus at the expense of photosynthesis and contribute to find out the key Ca. L. asiaticus-responsive genes for tolerance and resistance breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Zhang, Qiu, Francis and Wang.)

Delayed repair is a serious public health concern for diabetic populations. Intercellular adhesion molecule 1 (ICAM-1) and Lymphocyte function-associated antigen 1 (LFA-1) play important roles in orchestrating the repair process. However, little is known about their effects on endothelial cell (EC) proliferation and neutrophil activity in subjects with hyperglycemia (HG). We cultured ECs and performed a scratch-closure assay to determine the relationship between ICAM-1 and EC proliferation. Specific internally labeled bacteria were used to clarify the effects of ICAM-1 and LFA-1 on neutrophil phagocytosis. Transwell assay and fluorescence-activated cell sorting analysis evaluated the roles of ICAM-1 and LFA-1 in neutrophil recruitment. ICAM-1 + / + and ICAM-1 - / - mice were used to confirm the findings in vivo . The results demonstrated that HG decreased the expression of ICAM-1, which lead to the low proliferation of ECs. HG also attenuated neutrophil recruitment and phagocytosis by reducing the expression of ICAM-1 and LFA-1, which were strongly associated with the delayed repair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Qiu, Zhang, Zhan, Yang, Xiong, Hu, Ji and Huang.)

Background: Recurrent attacks of vertigo account for 2.6 million emergency department visits per year in the USA, of which more than 4% are attributable to ischemic infarction. However, few studies have investigated the frequency of attacks of vertigo before an ischemic stroke. Methods: We conducted this retrospective analysis and manually screened the medical records of 231 patients who experienced recurrent attacks of vertigo prior to an ischemic stroke. Patients were divided into four different groups based on the frequency of vertigo attacks as well as the region of ischemic infarction. Those with ≤2 attacks of vertigo preceding the ischemic stroke were defined as the low-frequency group. Those with ≥3 attacks were defined as the high-frequency group. Clinical parameters, including vascular risk factors, average National Institutes of Health Stroke Scale (NIHSS) score, and infarction volume, were compared between the groups. Results: On analysis, we found that patients with posterior infarction in the high-frequency group exhibited a higher prevalence of vertebral artery stenosis. However, the incidence of diabetes mellitus (DM) was higher in the low-frequency group. In addition, patients with posterior infarction in the low-frequency group were more active in seeking medical intervention after an attack of vertigo. Notably, the brain stem, especially the lateral medullary region, had a higher probability of being involved in posterior infarction in the high-frequency group. However, the cerebellum was more commonly involved in posterior infarction in the low-frequency group. Conclusions: Our findings indicate that the clinical parameters, including arterial stenosis, DM, and magnetic resonance imaging (MRI) findings, differed between the low- and high-frequency groups. We also found that patients in the low-frequency group were more willing to seek medical intervention after the attacks of vertigo. These findings could be valuable for clinicians to focus on specific examination of the patients according to the frequency of vertigo attacks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Qiu, Zhang, Deng, Xia, Duan, Wang and Zhang.)

In this study, a series of bacteria capable of degrading starch and cellulose were isolated from the aging flue-cured tobacco leaves. Remarkably, there was a thermophilic bacterium, Bacillus subtilis ZIM3, that can simultaneously degrade both starch and cellulose at a wide range of temperature and pH values. Genome sequencing, comparative genomics analyses, and enzymatic activity assays showed that the ZIM3 strain expressed a variety of highly active plant biomass-degrading enzymes, such as the amylase AmyE1 and cellulase CelE1. The in vitro and PhoA-fusion assays indicated that these enzymes degrading complex plant biomass into fermentable sugars were secreted into ambient environment to function. Besides, the amylase and cellulase activities were further increased by three- to five-folds by using overexpression. Furthermore, a fermentation strategy was developed and the biodegradation efficiency of the starch and cellulose in the tobacco leaves were improved by 30-48%. These results reveal that B. subtilis ZIM3 and the recombinant strain exhibited high amylase and cellulase activities for efficient biodegradation of starch and cellulose in tobacco and could potentially be applied for industrial tobacco fermentation., (Copyright © 2020 Dai, Dong, Xiong, Liu, Hossain, Liu, Gao, Li, Wang and Qiu.)

Blood Oxygen Level Dependent (BOLD) functional MRI is a complex neurovascular signal whose magnitude depends on baseline physiological factors such as cerebral blood flow (CBF). Because baseline CBF varies across the brain and is altered with aging, the interpretation of stand-alone aging-related BOLD changes can be misleading. The primary objective of this study was to develop a methodology that combines task fMRI and arterial spin labeling (ASL) techniques to sensitize task-induced BOLD activity by covarying out the baseline physiology (i.e., CBF) in an aging model. We recruited 11 younger and 13 older healthy participants who underwent ASL and an overt language fMRI task (semantic category member generation). We measured in-scanner language performance to investigate the effect of BOLD sensitization on BOLD-behavior relationships. The results demonstrate that our correction approach is effective at enhancing the specificity and sensitivity of the BOLD signal in both groups. In addition, the correction strengthens the statistical association between task BOLD activity and behavioral performance. Although CBF has inherent age dependence, our results show that retaining the age factor within CBF aides in greater sensitization of task fMRI signals. From a cognitive standpoint, compared to young adults, the older participants showed a delayed domain-general language-related task activity possibly due to compromised vessel compliance. Further, assessment of functional evolution of corrected BOLD activity revealed biphasic BOLD dynamics in both groups where BOLD deactivation may reflect greater semantic demand or increased premium on domain general executive functioning in response to task difficulty. Although it was promising to note that the predictability of behavior using the proposed methodology outperforms other methodologies (i.e., no correction and normalization by division), and provides moderate stability and adequate power, further work with a larger cohort and other task designs is necessary to improve the stability of predicting associated behavior. In summary, we recommend correction of task fMRI signals by covarying out baseline CBF especially when comparing groups with different neurovascular properties. Given that ASL and BOLD fMRI are well established and widely employed techniques, our proposed multi-modal methodology can be readily implemented into data processing pipelines to obtain more accurate BOLD activation maps., (Copyright © 2020 Krishnamurthy, Krishnamurthy, Drucker, Kundu, Ji, Hortman, Roberts, Mammino, Tran, Gopinath, McGregor, Rodriguez, Qiu, Crosson and Nocera.)

Airway vagal nerves play a predominant role in the neural control of the airway, and augmented airway vagal activity is known to play important roles in the pathogenesis of some chronic inflammatory airway diseases. Several lines of evidence indicate that dysfunctional central orexinergic system is closely related to the severity of airway diseases, however, whether orexins affect airway vagal activity is unknown. This study investigates whether and how orexin-A regulates the activity of medullary airway vagal preganglionic neurons (AVPNs). The expression of orexin receptor type 1 (OX 1 R) and type 2 (OX 2 R) was examined using immunofluorescent staining. The effects of orexin-A on functionally identified inspiratory-activated AVPNs (IA-AVPNs), which are critical in the control of airway smooth muscle, were examined using patch-clamp in medullary slices of neonatal rats. Airway vagal response to injection of orexin-A into the magna cisterna was examined using plethysmography in juvenile rats. The results show that retrogradely labeled AVPNs were immunoreactive to anti-OX 1 R antibody and anti-OX 2 R antibody. Orexin-A dose-dependently depolarized IA-AVPNs and increased their firing rate. In synaptically isolated IA-AVPNs, the depolarization induced by orexin-A was blocked partially by OX 1 R antagonist SB-334867 or OX 2 R antagonist TCS OX2 29 alone, and completely by co-application of both antagonists. The orexin-A-induced depolarization was also mostly blocked by Na + /Ca 2+ exchanger inhibitor KB-R7943. Orexin-A facilitated the glutamatergic, glycinergic and GABAergic inputs to IA-AVPNs, and the facilitation of each type of input was blocked partially by SB-334867 or TCS OX2 29 alone, and completely by co-application of both antagonists. Injection of orexin-A into the magna cisterna of juvenile rats significantly increased the inspiratory and expiratory resistance of the airway and consequently decreased the dynamic compliance of the lungs, all of which were prevented by atropine sulfate or bilateral vagotomy. These results demonstrate that orexin-A excites IA-AVPNs via activation of both OX 1 R and OX 2 R, and suggest that increased central synthesis/release of orexins might participate in the pathogenesis of airway diseases via over-activation of AVPNs., (Copyright © 2019 Chen, Guo, Yan, Zeng, Chen, Qiu and Wang.)

Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family members play crucial roles in plant abiotic stress response. However, the precise mechanism underlying the function of SnRKs has not been thoroughly elucidated in plants. In this research, a novel SnRK2 gene, TaSnRK2.9 was cloned and characterized from common wheat. The expression of TaSnRK2.9 was upregulated by polyethylene glycol (PEG), NaCl, H 2 O 2 , abscisic acid (ABA), methyl jasmonate (MeJA), and ethrel treatments. TaSnRK2.9 was mainly expressed in wheat young root, stamen, pistil, and lemma. Overexpressing TaSnRK2.9 in transgenic tobacco enhanced plants' tolerance to drought and salt stresses both in young seedlings and mature plants with improved survival rate, seed germination rate, and root length. Physiological analyses suggest that TaSnRK2.9 improved antioxidant system such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione (GSH) to reduce the H 2 O 2 content under drought or salt stress. Additionally, TaSnRK2.9 overexpression plants had elevated ABA content, implying that the function of TaSnRK2.9 may be ABA-dependent. Moreover, TaSnRK2.9 increased the expression of some ROS-related, ABA-related, and stress-response genes under osmotic or salt treatment. TaSnRK2.9 could interact with NtABF2 in yeast two-hybrid assay, and increased the expression of NtABF2 under mannitol or NaCl treatment in transgenic tobacco plants. In conclusion, overexpression of TaSnRK2.9 in tobacco conferred plants tolerance to drought and salt stresses through enhanced ROS scavenging ability, ABA-dependent signal transduction, and specific SnRK-ABF interaction.

Myasthenia gravis (MG) is an autoimmune-mediated disorder, the etiology of which involves both environmental factors and genetics. While the exact factors responsible for predisposition to MG remain elusive, it is hypothesized that gut microbiota play a critical role in the pathogenesis of MG. This study investigated whether gut microbiota are altered in MG patients by comparing the fecal microbiota profiles of MG patients to those of age- and sex-matched healthy controls. Phylotype profiles of gut microbial populations were generated using hypervariable tag sequencing of the V4 region of the 16S ribosomal RNA gene. Fecal short-chain fatty acids (SCFAs) were assessed by gas chromatographic analyses. The results demonstrated that, compared to the healthy cohort, the gut microbiota of the MG group was changed in terms of the relative abundances of bacterial taxa, with sharply reduced microbial richness, particularly in the genus Clostridium . The fecal SCFA content was significantly lower in the MG group. Furthermore, microbial dysbiosis was closely related to the levels of inflammatory biomarkers in the sera of MG patients.

Botrytis cinerea is one of the most notorious pathogenic species that causes serious plant diseases and substantial losses in agriculture throughout the world. We identified BcXyl1 from B. cinerea that exhibited xylanase activity. Expression of the BcXyl1 gene was strongly induced in B. cinerea infecting Nicotiana benthamiana and tomato plants, and BcXyl1 deletion strains severely compromised the virulence of B. cinerea . BcXyl1 induced strong cell death in several plants, and cell death activity of BcXyl1 was independent of its xylanase activity. Purified BcXyl1 triggered typically PAMP-triggered immunity (PTI) responses and conferred resistance to B. cinerea and TMV in tobacco and tomato plants. A 26-amino acid peptide of BcXyl1 was sufficient for elicitor function. Furthermore, the BcXyl1 death-inducing signal was mediated by the plant LRR receptor-like kinases (RLKs) BAK1 and SOBIR1. Our data suggested that BcXyl1 contributed to B. cinerea virulence and induced plant defense responses.

Verticillium dahliae is a wide-host-range fungal pathogen that causes soil-borne disease in hundreds of dicotyledonous hosts. In search of V. dahliae Vd991 cell death-inducing proteins, we identified a pectate lyase (VdPEL1) that exhibited pectin hydrolytic activity, which could induce strong cell death in several plants. Purified VdPEL1 triggered defense responses and conferred resistance to Botrytis cinerea and V. dahliae in tobacco and cotton plants. Our results demonstrated that the mutant VdPEL1 rec lacking the enzymatic activity lacked functions to induce both cell death and plant resistance, implying that the enzymatic activity was necessary. In addition, VdPEL1 was strongly induced in V. dahliae infected Nicotiana benthamiana and cotton roots, and VdPEL1 deletion strains severely compromised the virulence of V. dahliae . Our data suggested that VdPEL1 contributed to V. dahliae virulence and induced plant defense responses. These findings provide a new insight for the function of pectate lyase in the host-pathogen interaction.

The airway vagal preganglionic neurons (AVPNs) providing projections to intrinsic tracheobronchial ganglia are considered to be crucial to modulation of airway resistance in physiological and pathological states. AVPNs classified into inspiratory-activated AVPNs (IA-AVPNs) and inspiratory-inhibited AVPNs (II-AVPNs) are regulated by thyrotropin-releasing hormone (TRH)-containing terminals. TRH causes a direct excitatory current and attenuates the phasic inspiratory glycinergic inputs in II-AVPNs, however, whether and how TRH influences IA-AVPNs remains unknown. In current study, TRH regulation of IA-AVPNs and its mechanisms involved were investigated. Using retrogradely fluorescent labeling method and electrophysiology techniques to identify IA-AVPNs in brainstem slices with rhythmic inspiratory hypoglossal bursts recorded by a suction electrode, the modulation of TRH was observed with patch-clamp technique. The findings demonstrate that under voltage clamp configuration, TRH (100 nM) caused a slow excitatory inward current, augmented the excitatory synaptic inputs, progressively suppressed the inhibitory synaptic inputs and elicited a distinctive electrical oscillatory pattern (OP). Such a current and an OP was independent of presynaptic inputs. Carbenoxolone (100 μM), a widely used gap junction inhibitor, fully suppressed the OP with persistence of TRH-induced excitatory slow inward current and augment of the excitatory synaptic inputs. Both tetrodotoxin (1 μM) and riluzole (20 μM) functioned to block the majority of the slow excitatory inward current and prevent the OP, respectively. Under current clamp recording, TRH caused a slowly developing depolarization and continuously progressive oscillatory firing pattern sensitive to TTX. TRH increased the firing frequency in response to injection of a square-wave current. The results suggest that TRH excited IA-AVPNs via the following multiple mechanisms: (1) TRH enhances the excitatory and depresses the inhibitory inputs; (2) TRH induces an excitatory postsynaptic slow inward current; (3) TRH evokes a distinctive OP mediated by gap junction.

PevD1 is a fungal protein secreted by Verticillium dahliae . Our previous researches showed that this protein could induce hypersensitive responses-like necrosis and systemic acquired resistance (SAR) in cotton and tobacco. To understand immune activation mechanisms whereby PevD1 elicits defense response, the yeast two-hybrid (Y2H) assay was performed to explore interacting protein of PevD1 in Arabidopsis thaliana , and a partner AtNRP (At5g42050) was identified. Here, AtNRP homolog in Nicotiana benthamiana was identified and designated as Nbnrp1. The Nbnrp1 could interact with PevD1 via Y2H and bimolecular fluorescence complementation (BiFC) analyses. Moreover, truncated protein binding assays demonstrated that the C-terminal 132 amino acid (development and cell death, DCD domain) of Nbnrp1 is required for PevD1-Nbnrp1 interaction. To further investigate the roles of Nbnrp1 in PevD1-induced defense response, Nbnrp1-overexpressing and Nbnrp1-silence transgenic plants were generated. The overexpression of Nbnrp1 conferred enhancement of PevD1-induced necrosis activity and disease resistance against tobacco mosaic virus (TMV), bacterial pathogen Pseudomonas syringae pv. tabaci and fungal pathogen V. dahliae . By contrast, Nbnrp1-silence lines displayed attenuated defense response compared with the wild-type. It is the first report that an asparagine-rich protein Nbnrp1 positively regulated V. dahliae secretory protein PevD1-induced cell death response and disease resistance in N. benthamiana .

Powdery mildew resistance gene Pm4b , originating from Triticum persicum , is effective against the prevalent Blumeria graminis f. sp. tritici ( Bgt ) isolates from certain regions of wheat production in China. The lack of tightly linked molecular markers with the target gene prevents the precise identification of Pm4b during the application of molecular marker-assisted selection (MAS). The strategy that combines the RNA-Seq technique and the bulked segregant analysis (BSR-Seq) was applied in an F 2:3 mapping population (237 families) derived from a pair of isogenic lines VPM1/7 ∗ Bainong 3217 F 4 (carrying Pm4b ) and Bainong 3217 to develop more closely linked molecular markers. RNA-Seq analysis of the two phenotypically contrasting RNA bulks prepared from the representative F 2:3 families generated 20,745,939 and 25,867,480 high-quality read pairs, and 82.8 and 80.2% of them were uniquely mapped to the wheat whole genome draft assembly for the resistant and susceptible RNA bulks, respectively. Variant calling identified 283,866 raw single nucleotide polymorphisms (SNPs) and InDels between the two bulks. The SNPs that were closely associated with the powdery mildew resistance were concentrated on chromosome 2AL. Among the 84 variants that were potentially associated with the disease resistance trait, 46 variants were enriched in an about 25 Mb region at the distal end of chromosome arm 2AL. Four Pm4b -linked SNP markers were developed from these variants. Based on the sequences of Chinese Spring where these polymorphic SNPs were located, 98 SSR primer pairs were designed to develop distal markers flanking the Pm4b gene. Three SSR markers, Xics13 , Xics43 , and Xics76 , were incorporated in the new genetic linkage map, which located Pm4b in a 3.0 cM genetic interval spanning a 6.7 Mb physical genomic region. This region had a collinear relationship with Brachypodium distachyon chromosome 5, rice chromosome 4, and sorghum chromosome 6. Seven genes associated with disease resistance were predicted in this collinear genomic region, which included C2 domain protein, peroxidase activity protein, protein kinases of PKc&#95;like super family, Mlo family protein, and catalytic domain of the serine/threonine kinases (STKc&#95;IRAK like super family). The markers developed in the present study facilitate identification of Pm4b during its MAS practice.

Root nodule symbiosis (RNS) is one of the most productive and economical systems for nitrogen fixation, and previous studies have shown that several nodule-specific C2H2-zinc finger proteins (ZFPs) play important roles in symbiosis establishment and nodule function. However, C2H2-ZFPs are the most widespread ZFPs in eukaryotes, and a great variation of structure and function exist among the family members. It remains largely unclear whether or not special types of C2H2-ZF genes participate in symbiosis, especially in soybean. In the present study, we performed a genome-wide survey of soybean C2H2-ZF genes, and 321 soybean C2H2-ZF genes were identified and classified into 11 clearly distinguishable subsets (Gm-t1-SF, Gm-t2-SF, Gm-1i-Q-SF, Gm-1i-M-SF, Gm-1i-Z-SF, Gm-1i-D-SF, Gm-2i-Q-SF, Gm-2i-M-SF, Gm-2i-Mix-SF, Gm-3i-SF, and Gm-4i-SF) based on the arrangements, numbers, and types of C2H2-ZF domains. Phylogenetic and gene ontology analyses were carried out to assess the conserved sequence and GO function among these subsets, and the results showed that the classification of soybean C2H2-ZFPs was reasonable. The expression profile of soybean C2H2-ZFPs in multiple tissues showed that nearly half of soybean C2H2-ZFPs within different subsets had expressions in nodules, including a clustering branch consisting of 11 Gm-1i-Q-SF genes specifically expressed in symbiotic-relative tissues. RNA-Seq was used to identify symbiosis-related soybean C2H2-ZFPs, and the expression pattern of the soybean C2H2-ZFPs in roots and nodules at different development stages showed that soybean C2H2-ZFPs mainly played roles in nodule development or nodule function rather than nodulation signal transduction, and nearly half of these genes had high expressions and/or different expression patterns during soybean nodule development, especially for the six clustering branches of genes consisting of different subsets of C2H2-ZFPs. Furthermore, the selected symbiosis-related soybean C2H2-ZFPs might function in legume-rhizobium symbiosis through regulating or interacting with other key proteins. Taken together, our findings provided useful information for the study on classification and conservative function of C2H2-ZFPs, and offered solid evidence for investigation of rhizobium symbiosis-related C2H2-ZFPs in soybean or other legumes.

Interactions between the brain networks and subnetworks are crucial for active and resting cognitive states. Whether a subnetwork can restore the adequate function of the parent network whenever a disease state affects the parent network is unclear. Investigations suggest that the control of the anterior insula-based network (AIN) over the default-mode network (DMN) and central-executive network (CEN) is decreased in individuals with mild cognitive impairment (MCI). Here, we hypothesized that the posterior insula-based network (PIN) attempts to compensate for this decrease. To test this, we compared a group of MCI and normal cognitive individuals. A dynamical causal modeling method has been employed to investigate the dynamic network controls/modulations. We used the resting state functional MRI data, and assessed the interactions of the AIN and of the PIN, respectively, over the DMN and CEN. We found that the greater control of AIN than that of DMN (Wilcoxon rank sum: Z = 1.987; p = 0.047) and CEN ( Z = 3.076; p = 0.002) in normal group and the lower (impaired) control of AIN than that of CEN ( Z = 8.602; p = 7.816 × 10 -18 ). We further revealed that the PIN control was significantly higher than that of DMN ( Z = 6.608; p = 3.888 × 10 -11 ) and CEN ( Z = 6.429; p = 1.278 × 10 -10 ) in MCI group where the AIN was impaired, but that control was significantly lower than of DMN ( Z = 5.285; p = 1.254 × 10 -7 ) and CEN ( Z = 5.404; p = 6.513 × 10 -8 ) in normal group. Finally, the global cognitive test score assessed using Montreal cognitive assessment and the network modulations were correlated (Spearman's correlation: r = 0.47; p = 3.76 × 10 -5 and r = -0.43; p = 1.97 × 10 -4 ). These findings might suggest the flexible functional profiles of AIN and PIN in normal aging and MCI.