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Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance. Headings: •IbGCS gene was cloned from the sweetpotato cultivar Xu18. • The multiple abiotic stresses significantly increased the expression of IbGCS gene. • Overexpression of IbGCS significantly improved the salt and drought stress tolerance [ABSTRACT FROM AUTHOR]

Background: Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. Methods: We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. Results: The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. Conclusion: Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment. [ABSTRACT FROM AUTHOR]

A modified multipath error mitigation method using the multi-point hemispherical grid model (MHGM) is proposed, and the influence of changes in the observation environments of IGS stations on their data quality is evaluated. The multipath error models of different satellite pairs for different observation periods can be established using the integrated multi-GNSS data in the proposed method. The test under deliberate high multipath environment reveals that this method can effectively estimate the GNSS multipath error, detect and present the orientation of the interference sources around the station. The RMS of residuals and the kinematic positioning accuracy on day 237 of 2018 are improved by 68% and 61%, respectively. Compared with the empirical site model (ESM), which can also visualize the effects of the multipath, the RMS of residuals when applying the MHGM is improved by 20%. The test with IGS historical observations shows that MHGM can effectively reflect the influence of changing multipath interference around stations on carrier phase observations, with an average improvement of 25% in the RMS of carrier phase residuals in the extrapolated 9-day validations over the past 18 years. The results of a kinematic positioning experiment in 2019 generally coincide with the RMS statistic results of carrier phase residuals as well. The MHGM demonstrates distinct potential in the influence evaluation of changes for the multipath interference around the stations on their observation quality. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). Methods: A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. Results: The patients' median age was 37 years (range, 20–76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to −0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031). Conclusions: BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy. [ABSTRACT FROM AUTHOR]

X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism. [ABSTRACT FROM AUTHOR]

Raw observation processing method with prior knowledge of ionospheric delay could strengthen the ambiguity resolution (AR), but it does not make full use of the relatively longer wavelength of wide-lane (WL) observation. Furthermore, the accuracy of calculated atmospheric delays from the regional augmentation information has quite different in quality, while the atmospheric constraint used in the current methods is usually set to an empirical value. A proper constraint, which matches the accuracy of calculated atmospheric delays, can most effectively compensate the residual systematic biases caused by large inter-station distances. Therefore, the standard deviation of the residual atmospheric parameters should be fine-tuned. This paper presents an atmosphere-constrained AR method for undifferenced network RTK (URTK) rover, whose ambiguities are sequentially fixed according to their wavelengths. Furthermore, this research systematically analyzes the residual atmospheric error and finds that it mainly varies along the positional relationship between the rover and the chosen reference stations. More importantly, its ionospheric part of certain location will also be cyclically influenced every day. Therefore, the standard deviation of residual ionospheric error can be modeled by a daily repeated cosine or other functions with the help of data one day before, and applied by rovers as pseudo-observation. With the data collected at 29 stations from a continuously operating reference station network in Guangdong Province (GDCORS) in China, the efficiency of the proposed approach is confirmed by improving the success and error rates of AR for 10-20 % compared to that of the WL-L1-IF one, as well as making much better positioning accuracy. [ABSTRACT FROM AUTHOR]

Objectives: Oral colonization of Candida could lead to later development of oropharyngeal candidiasis or candidemia among the immunocompromised patients. This study aims to describe the occurrence and risk factors of oral Candida colonization in patients with malignancies. Materials and methods: From October 2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients with gastrointestinal tract tumor (group II), 79 patients with hematopoietic system malignant tumor (group III), and 101 healthy controls were consecutively recruited in a hospital in Beijing, China. The oral rinse samples were taken and Candida species were identified; the enzymes activities were tested. Results: In total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls, respectively. The oral colonization rate with Candida albicans in group III (12.7 %) was significant lower than that in group I (30.8 %), group II (33.7 %), and control group (25.7 %). The oral colonization rates with non- albicans Candida species in group I, group II, and group III were 15.4, 10.9, and 12.7 %, respectively, while only one non- albicans Candida strain was identified in control group. The non- albicans Candida species exhibited a lower virulence than C. albicans. Age was an independent risk factor for Candida colonization in patients with pulmonary cancer and digestive tract malignant tumor, 'Teeth brush <1 time/day' was an independent risk factor for Candida colonization in patients with hematopoietic system tumor. Conclusions: The differences of risk factors for oral Candida colonization in patients with different cancers require different strategies for the prevention and control of Candida infection. Clinical relevance: Old aged patients with pulmonary cancer and digestive tract malignant tumor are high-risk population for Candida colonization. Increasing frequency of teeth brush might be helpful for preventing Candida colonization. [ABSTRACT FROM AUTHOR]

Purposes: North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations. The aims of this study were to assess the clinical features of a Chinese family with NCMD and to identify the underlying genetic cause of the disease. Methods: Three patients from a Chinese family were included in this study. Detailed ophthalmological examinations were performed, including best corrected visual acuity (BCVA), slit lamp, dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence, full-field electroretinography (ERG), and electrooculography (EOG). Genomic DNA was extracted from peripheral blood samples. Whole-genome sequencing and long-read genome sequencing were applied to detect the pathogenic variants. Sanger sequencing was performed to confirm the breakpoints. Results: All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD. The BCVA ranged from 20/50 to 20/20. OCT revealed varying degrees of macular structure disorganization. The ERG responses were normal, and the Arden ration of the EOG was reduced. A novel 134.6 kb (g.99932464-100067110dup) tandem duplication on chromosome 6 (NC_000006.11) encompassing the entire CCNC and PRDM13 genes and a DNase 1 hypersensitivity site in the MCDR1 locus was identified. Conclusion: A novel large tandem duplication in MCDR1 locus was confirmed in a Chinese family with NCMD with a variety of macular phenotypes. [ABSTRACT FROM AUTHOR]

The floral transition is a critical developmental switch in plants, and has profound effects on the flower production and yield. Magnolia × soulangeana 'Changchun' is known as a woody ornamental plant, which can bloom in spring and summer, respectively. In this study, anatomical observation, physiological measurement, transcriptome, and small RNA sequencing were performed to investigate potential endogenous regulatory mechanisms underlying floral transition in 'Changchun'. Transition of the shoot apical meristem from vegetative to reproductive growth occurred between late April and early May. During this specific developmental process, a total of 161,645 unigenes were identified, of which 73,257 were significantly differentially expressed, while a number of these two categories of miRNAs were 299 and 148, respectively. Further analysis of differentially expressed genes (DEGs) revealed that gibberellin signaling could regulate floral transition in 'Changchun' in a DELLA-dependent manner. In addition, prediction and analysis of miRNA targeted genes suggested that another potential molecular regulatory module was mediated by the miR172 family and other several novel miRNAs (Ms-novel_miR139, Ms-novel_miR229, and Ms-novel_miR232), with the participation of up- or down-regulating genes, including MsSVP, MsAP2, MsTOE3, MsAP1, MsGATA6, MsE2FA, and MsMDS6. Through the integrated analysis of mRNA and miRNA, our research results will facilitate the understanding of the potential molecular mechanism underlying floral transition in 'Changchun', and also provide basic experimental data for the plant germplasm resources innovation in Magnolia. [ABSTRACT FROM AUTHOR]

α-L-Fucosidase (AFU) is a promising therapeutic target for the treatment of inflammation, cancer, cystic fibrosis, and fucosidosis. Some of the existing analytical methods for the assessment of AFU activity are lacking in sensitivity and selectivity, since most of them are based on spectrofluorimetric methods. More recently, mass spectrometry (MS) has evolved as a key technology for enzyme assays and inhibitor screening as it enables accurate monitoring of the conversion of substrate to product in enzymatic reactions. In this study, UHPLC-MS has been utilized to develop a simple, sensitive, and accurate assay for enzyme kinetics and inhibition studies of AFU3, a member of the AFU family. A reported method for analyzing saccharide involving a porous graphitic carbon column, combined with reduction by NaBH4/CH3OH, was used to improve sensitivity. The conversion of saccharide into alditol could reach nearly 100% in the NaBH4 reduction reaction. In addition, the bioanalytical quantitative screening method was validated according to US-FDA guidance, including selectivity, linearity, precision, accuracy, stability, and matrix effect. The developed method displayed a good accuracy, high sensitivity (LOD = 0.05 mg L−1), and good reproducibility (RSD < 15%). The assay accurately measured an IC50 value of 0.40 μM for the known AFU inhibitor, deoxyfuconojirimycin, which was consistent with results reported in the literature. Further validation of the assay was achieved through the determination of a high Z′-factor value of 0.89. The assay was applied to screen a marine-derived chemical library against AFU3, which revealed two marine-oriented pyrimidine alkaloids as potential AFU3 inhibitors. Graphical abstract [ABSTRACT FROM AUTHOR]

Surveillance monitoring for microbial water quality typically involves collecting single discrete grab samples for analyzing only one contaminant. While informative, current approaches suffer from poor recoveries and only provide a limited snapshot of the microbial contaminants only at the time of collection. To overcome these limitations, bivalves have been proposed as effective biosentinels of water quality particularly for their ability to efficiently concentrate and retain microbial contaminants for long periods of time. In this study, we examined the use of indigenous blue mussels ( Mytilus spp.) as biosentinels to monitor for the presence of Toxoplasma gondii and Cryptosporidium water. An efficient method to extract oocyst DNA from various mussel tissues followed by PCR-based detection of these pathogens was developed, which resulted in the detection down to 10 oocysts. This method was then used to conduct a small survey in Point Lobos and Morro Bay, California to determine prevalence T. gondii and Cryptosporidium. Results revealed that mussels from Morro Bay were contaminated with T. gondii (33 %), while mussels from Point Lobos were contaminated with T. gondii (54 %) and Cryptosporidium (26.9 %) oocysts. Phylogenetic analysis using the SSU rRNA gene identified two novel Cryptosporidium parvum-like genotypes. Overall, this study demonstrated the application of using native California Mytilus spp. as biosentinels for pathogen contamination along the central California shorelines. More importantly, T. gondii and Cryptosporidium were found at higher prevalence rates in Morro Bay and in Point Lobos, an area not previously reported to be contaminated with these pathogens. [ABSTRACT FROM AUTHOR]