Publications by authors named "Jiajia Li"

327 Publications

Effects of root restriction on phytohormone levels in different growth stages and grapevine organs.

Sci Rep 2022 Jan 25;12(1):1323. Epub 2022 Jan 25.

Department of Plant Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Phytohormones play important roles in germination, blossom, senescence, abscission of plants by a series of signal transduction and molecular regulation. The purpose of this research was to investigate the influence of root restriction (RR) cultivation on plant endogenous hormone variation tendency at different growth stages in diverse organs or tissues. 'Muscat Hamburg' (Vitis 'Muscat of Alexandria' × Vitis 'Trollinger') grapevine was used as test material. High Performance Liquid Chromatography (HPLC) was used to quantify hormone levels, qRT-PCR was used to quantify the expression of genes related to hormone biosynthesis pathway, and determined parameters of growth and photosynthetic, aiming to investigate the influence of root restriction on the formation and metabolism of phytohormones, as well as the degree of correlation between phytohormones and plant growth and photosynthetic intensity under root restriction. By measuring the photosynthetic rate of leaves at the stages of core-hardening, veraison and maturity, it was found that root restriction could reduce most photosynthetic parameters. The results also revealed that RR treatment increased abscisic acid (ABA), salicylic acid (SA), zeatin riboside (ZR), N6-(delta 2-isopentenyl)-adenine nucleoside (iPR) concentrations, while reduced auxin (IAA), 3-indolepropionic acid (IPA), 3-indolebutyric acid (IBA), gibberellin A (GA), zeatin (ZT), N6-(delta 2-Isopentenyl)-adenine (iP), kinetin (KT), jasmonic acid (JA) and methyl jasmonate (MeJA) concentrations in most organs and at most developmental stages. RT-qPCR was carried out to further explore the effect of root restriction on genes expression of ABA, SA and IAA biosynthesis pathways at molecular level. Meanwhile, through correlation analysis, we found that different phytohormones contributed differently to physiological indicators, there existed strong correlation of ABA, KT, MeJA, iPR, SA, JA with leaf photosynthesis, GA, IBA, ZR, IAA, ZT with fruit quality. In addition, we also found that the shoot growth related parameters were closely correlated with JA, IPA and iP. To sum up, our results suggested that RR treatment could significantly increase soluble solid content, regulate the growth and photosynthesis of grapevine, by affecting the biosynthesis of phytohormones. It could further prove that root restriction was a feasible technique to ameliorate the phenomenon of low quality in grape berry in southern China.
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http://dx.doi.org/10.1038/s41598-021-04617-6DOI Listing
January 2022

Clinical Symptoms and Outcomes of Severe Pneumonia Caused by in Southwest China.

Front Cell Infect Microbiol 2021 6;11:727594. Epub 2022 Jan 6.

Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Here, we aimed to retrospectively analyze the clinical characteristics of 27 patients with severe pneumonia caused by between January 2019 and April 2021 in southwest China. To this end, we collected data on the exposure history, clinical symptoms, laboratory examination, imaging characteristics, evolution, etiology, treatment, and outcomes to suggest a better diagnosis and prevention system. Our results showed that a metagenomic next-generation sequencing test could provide early diagnosis. All patients were sensitive to quinolones and tetracyclines, and the recovery rate was relatively high. Overall, all patients were in critical condition with moderate to severe acute respiratory distress syndrome and shock. In conclusion, early diagnosis of pneumonia caused by depends on effective molecular testing, and most patients recover after treatment.
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http://dx.doi.org/10.3389/fcimb.2021.727594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770948PMC
January 2022

The major component of cinnamon oil as a natural substitute against Fusarium solani on Astragalus membranaceus.

J Appl Microbiol 2022 Jan 22. Epub 2022 Jan 22.

School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou, 730070, China.

Aims: Root rot caused by Fusarium solani is an important disease seriously affecting the yield and quality of Astragalus membranaceus. Therefore, this study was performed to elucidate the antifungal activities and mechanisms of cinnamaldehyde treatment against F. solani and its control effect for A. membranaceus root rot.

Methods And Results: Cinnamaldehyde significantly inhibited mycelial growth and spore germination of F. solani in dose-dependent, and the median effective concentration was 178.68 μl l . Furthermore, scanning electron microscopy (SEM), propidium iodide (PI) staining, cell leakage experiments and ergosterol quantitation illuminated that cinnamaldehyde could alter the mycelial morphology, damage the plasma membrane and hinder the biosynthesis of ergosterol. Besides, cinnamaldehyde induced the generation of reactive oxygen species (ROS) by synergistically upregulating the genes encoded subunits for NADPH oxidase. The disease suppression efficacy of 600 μl l cinnamaldehyde against A. membranaceus root rot was 92.98 ± 6.08% (P < 0.05) under greenhouse conditions.

Conclusions: This study proved that cinnamaldehyde could markedly inhibit the growth of F. solani in vitro and effectively suppress the occurrence of A. membranaceus root rot, perhaps by inducing oxidative damage, which results in the distortion of F. solani, and the destruction of cell membrane integrity and permeability.

Significance And Impact Of The Study: This study first explores the antifungal mechanisms of cinnamaldehyde against F. solani in vivo and vitro, thereby providing a promising candidate for disease bio-control.
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http://dx.doi.org/10.1111/jam.15458DOI Listing
January 2022

Measuring the urban land use efficiency of three urban agglomerations in China under carbon emissions.

Environ Sci Pollut Res Int 2022 Jan 22. Epub 2022 Jan 22.

School of Economics and Management, Tongji University, Shanghai, 200092, China.

On the basis of DMSP/OLS and NPP-VIIRS night light images, this study realized carbon emission estimations based on the municipal level from 1999 to 2017, compensating for the characteristics of incomplete statistical data and different statistical calibers. On this basis, the epsilon-based measure (EBM) super-efficiency model and the global Malmquist-Luenberger (GML) index are used to measure the urban land use efficiency (ULUE) and urban land total factor productivity (ULTFP) of the three urban agglomerations under the carbon emission constraints from 1999 to 2017. The following conclusions are drawn through research. (1) The correlation coefficient between the total value of night light pixels and energy consumption carbon emissions was relatively high in the three major urban agglomerations during 1999-2017, and they all passed the significance test of 1%. (2) The ULUE of the three major urban agglomerations generally shows a downward trend and then an upward trend, and spatial heterogeneity is obvious. The spatial distribution of the average level of ULUE is Pearl River Delta Urban Agglomeration (PRDUA) > Yangtze River Delta Urban agglomeration (YRDUA) > Beijing-Tianjin-Hebei Urban agglomeration (BTHUA). (3) The ULTFP of the three major urban agglomerations are all showing an increasing trend, but the geometric mean of URTFP in the PRDUA, BTHUA, and YRDUA decreases successively. Technological progress is the main driving force to promote the progress of ULTFP in each urban agglomeration. (4) The kernel density estimation shows a significant gap in ULUE between the three major urban agglomerations in China, and a phenomenon of polarization or multipolarization is observed. The main reason is the hysteresis of technology diffusion.
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http://dx.doi.org/10.1007/s11356-021-18124-8DOI Listing
January 2022

Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China.

Nutrients 2022 Jan 11;14(2). Epub 2022 Jan 11.

Department of Andrology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.

Background: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion.

Methods: A population-based case-control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women's and their husbands' education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR).

Results: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23-3.23). The ROR was 2.06 (95% CI: 1.04-4.10), indicating a significant positive multiplicative interaction.

Conclusions: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.
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http://dx.doi.org/10.3390/nu14020291DOI Listing
January 2022

Hydroxylation decoration patterns of flavonoids in horticultural crops: chemistry, bioactivity and biosynthesis.

Hortic Res 2022 Jan 20. Epub 2022 Jan 20.

Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou 310058, China.

Flavonoids are the most widespread polyphenolic compounds and are important dietary constituents present in horticultural crops such as fruits, vegetables, and tea. Natural flavonoids are responsible for important quality traits, such as food colors and beneficial dietary antioxidants and numerous investigations have shown that intake of flavonoids can reduce the incidence of various non-communicable diseases (NCDs). Analysis of the thousands of flavonoids reported so far has shown that different hydroxylation modifications affect their chemical properties and nutritional values. These diverse flavonoids can be classified based on different hydroxylation patterns in the B, C, A rings and multiple structure-activity analyses have shown that hydroxylation decoration at specific positions markedly enhances their bioactivities. This review focuses on current knowledge concerning hydroxylation of flavonoids catalyzed by several different types of hydroxylase enzymes. Flavonoid 3'-hydroxylase (F3'H) and flavonoid 3'5'-hydroxylase (F3'5'H) are important enzymes for the hydroxylation of the B ring of flavonoids. Flavanone 3-hydroxylase (F3H) is key for the hydroxylation of the C ring, while flavone 6-hydroxylase (F6H) and flavone 8-hydroxylase (F8H) are key enzymes for hydroxylation of the A ring. These key hydroxylases in the flavonoid biosynthesis pathway are promising targets for the future bioengineering of plants and mass production of flavonoids with designated hydroxylation patterns of high nutritional importance. In addition, hydroxylation in key places on the ring may help render flavonoids ready for degradation, the catabolic turnover of which may open the door for new lines of inquiry.
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http://dx.doi.org/10.1093/hr/uhab068DOI Listing
January 2022

Mechanistic studies on the anomalous transport behaviors of water molecules in nanochannels of multilayer graphynes.

Phys Chem Chem Phys 2022 Jan 26;24(4):2534-2542. Epub 2022 Jan 26.

Institute of Advanced Materials (IAM), State-Province Joint Engineering Laboratory of Zeolite Membrane Materials, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, People's Republic of China.

An in-depth understanding of directed transport behaviors of water molecules through nanoporous materials is essential for the design and development of next-generation filtration devices. In this work, we perform molecular dynamics (MD) simulations to explore transport properties of water molecules through nanochannels of multilayer graphyne with different pore sizes. Our simulation results reveal that the orientations of confined water molecules would periodically reverse between two opposite directions as they diffuse along the nanochannels, and such a transport mechanism shows similarities with water transport in aquaporin channels. Further, we observe that, for each orientation reversal, there is an obvious difference in the HB breaking frequency among the three graphyne systems, with an order of graphyne-4 > graphyne-5 > graphyne-3. Besides, the average HB number is found to display a periodic fluctuation with a pulse-like pattern along the diffusion direction, wherein the graphyne-4 system has the maximum fluctuation, while the graphyne-3 system has the minimum one. Such anomalous HB breaking frequency and average HB number fluctuation results finally lead to a nonmonotonic relationship between water diffusion rate and graphyne pore size, and the diffusion order follows graphyne-4 > graphyne-5 > graphyne-3. Herein, we provide a new insight into the transport mechanisms of water molecules through nanoporous materials and our findings open up opportunities for the design and development of high-performance graphyne-based membranes used for water purification and desalination.
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http://dx.doi.org/10.1039/d1cp04378aDOI Listing
January 2022

Core-shell structured magnetic covalent-organic frameworks for rapid extraction and preconcentration of okadaic acid in seawater and shellfish followed with LC-MS/MS quantification.

Food Chem 2022 Apr 6;374:131778. Epub 2021 Dec 6.

Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai 201203, China; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, China. Electronic address:

Core-shell structured magnetic covalent-organic frameworks ([email protected]) were facilely synthesized based on one-step functionalization at room temperature and applied for magnetic solid-phase extraction of okadaic acid from seawater and shellfish prior to LC-MS/MS detection. Parameters, including adsorbent amount, extraction time, desorption solution, and desorption time which could affect the extraction efficiency, were respectively investigated. The developed methods demonstrated good linearity (R > 0.99), acceptable accuracy and good precision (<15%), and low limit of detection (0.5 pg·mL for seawater and 0.04 µg·kg for shellfish). The amount of the material used (1 mg for seawater and 5 mg for shellfish) and the time required (4 min for seawater and 15 min for shellfish) for extracting analyte from 5 mL of seawater and 2 g of shellfish are both greatly shortened compared with the previous reports. In addition, we successfully applied this method to real sample analysis.
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http://dx.doi.org/10.1016/j.foodchem.2021.131778DOI Listing
April 2022

Full-Length Transcriptome of Red Swamp Crayfish Hepatopancreas Reveals Candidate Genes in Hif-1 and Antioxidant Pathways in Response to Hypoxia-Reoxygenation.

Mar Biotechnol (NY) 2022 Jan 8. Epub 2022 Jan 8.

Freshwater Fisheries Research Institute of Jiangsu Province, 79 Chating East Street, Nanjing, 210017, China.

Red swamp crayfish is particularly prone to exposure to hypoxia-reoxygenation stress on account of the respiration and rhythmic, light-dependent photosynthetic activity of the algae and aquatic grass. Up to now, the regulation mechanisms of the adverse effects of hypoxia-reoxygenation for this species were still unknown, especially the roles of the antioxidant enzymes in reducing oxidative damage during reoxygenation. To screen for vital genes or pathways upon hypoxic-reoxygenation stress, hepatopancreas gene expression profiles were investigated by using a strategy combining second and third generation sequencing. Five groups of samples, including hypoxia for 1 and 6 h with DO of 1.0 mg/L, reoxygenation for 1 and 12 h with DO of 6.8 mg/L, and the samples under normoxia condition, were used for transcriptome sequencing. Twenty Illumina cDNA libraries were prepared to screen for the differentially expressed genes (DEGs) among the 5 groups of samples. Based on the assembled reference full-length transcriptome, 389 and 533 significantly DEGs were identified in the groups under severe hypoxia treatment for 1 and 6 h, respectively. The top three enriched pathways for these DEGs were "protein processing in endoplasmic reticulum," "MAPK signaling pathway," and "endocytosis." Among these DEGs, hypoxia-inducible factor 1α (Hif-1α) and some Hif-1 downstream genes, such as Ugt-1, Egfr, Igfbp-1, Pk, and Hsp70, were significant differentially expressed when exposed to hypoxia stress. A series of antioxidant enzymes, including two types of superoxide dismutase (Cu/ZnSOD and MnSOD), catalase (CAT), and glutathione peroxidase (GPx), were identified to be differentially expressed during hypoxia-reoxygenation treatment, implying their distinct modulation roles on reoxygenation-induced oxidative stress. The full-length transcriptome and the critical genes characterized should contribute to the revelation of intrinsic molecular mechanism being associated with hypoxia/reoxygenation regulation and provide useful foundation for future genetic breeding of the red swamp crayfish.
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http://dx.doi.org/10.1007/s10126-021-10086-9DOI Listing
January 2022

Engineering for an HPV 9-valent vaccine candidate using genomic constitutive over-expression and low lipopolysaccharide levels in Escherichia coli cells.

Microb Cell Fact 2021 Dec 20;20(1):227. Epub 2021 Dec 20.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.

Background: The various advantages associated with the growth properties of Escherichia coli have justified their use in the production of genetically engineered vaccines. However, endotoxin contamination, plasmid vector instability, and the requirement for antibiotic supplementation are frequent bottlenecks in the successful production of recombinant proteins that are safe for industrial-scaled applications. To overcome these drawbacks, we focused on interrupting the expression of several key genes involved in the synthesis of lipopolysaccharide (LPS), an endotoxin frequently responsible for toxicity in recombinant proteins, to eliminate endotoxin contamination and produce better recombinant proteins with E. coli.

Results: Of 8 potential target genes associated with LPS synthesis, we successfully constructed 7 LPS biosynthesis-defective recombinant strains to reduce the production of LPS. The endotoxin residue in the protein products from these modified E. coli strains were about two orders of magnitude lower than that produced by the wild-type strain. Further, we found that 6 loci-lpxM, lpxP, lpxL, eptA, gutQ and kdsD-were suitable for chromosomal integrated expression of HPV L1 protein. We found that a single copy of the expression cassette conferred stable expression during long-term antibiotic-free cultivation as compared with the more variable protein production from plasmid-based expression. In large-scale fermentation, we found that recombinant strains bearing 3 to 5 copies of the expression cassette had 1.5- to 2-fold higher overall expression along with lower endotoxin levels as compared with the parental ER2566 strain. Finally, we engineered and constructed 9 recombinant E. coli strains for the later production of an HPV 9-valent capsid protein with desirable purity, VLP morphology, and antigenicity.

Conclusions: Reengineering the LPS synthesis loci in the E. coli ER2566 strain through chromosomal integration of expression cassettes has potential uses for the production of a 9-valent HPV vaccine candidate, with markedly reduced residual endotoxin levels. Our results offer a new strategy for recombinant E. coli strain construction, engineering, and the development of suitable recombinant protein drugs.
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http://dx.doi.org/10.1186/s12934-021-01719-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686089PMC
December 2021

Electrical Impedance Tomography Predicts Weaning Success in Adult Patients With Delayed Upper Abdominal Surgery: A Single-Center Retrospective Study.

Front Med (Lausanne) 2021 2;8:748493. Epub 2021 Dec 2.

Department of Intensive Care Unit, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

To evaluate the predictive value of electrical impedance tomography (EIT) in patients with delayed ventilator withdrawal after upper abdominal surgery. We retrospectively analyzed data of patients who were ventilated >24 h after upper abdominal surgery between January 2018 and August 2019. The patients were divided into successful (group S) and failed (group F) weaning groups. EIT recordings were obtained at 0, 5, 15, and 30 min of spontaneous breathing trials (SBTs) with SBT at 0 min set as baseline. We assessed the change in delta end-expiratory lung impedance and tidal volume ratio (ΔEELI/VT) from baseline, the change in compliance change percentage variation (|Δ(CW-CL)|) from baseline, the standard deviation of regional ventilation delay index (RVDSD), and global inhomogeneity (GI) using generalized estimation equation analyses. Receiver operating characteristic curve analyses were performed to evaluate the predictive value of parameters indicating weaning success. Among the 32 included patients, ventilation weaning was successful in 23 patients but failed in nine. Generalized estimation equation analysis showed that compared with group F, the ΔEELI/VT was lower, and the GI, RVDSD, and (|Δ(CW-CL)|) were higher in group S. For predicting withdrawal failure, the areas under the curve of the ΔEELI/VT, (|Δ(CW-CL)|), and the RVDSD were 0.819, 0.918, and 0.918, and 0.816, 0.884, and 0.918 at 15 and 30 min during the SBTs, respectively. The electrical impedance tomography may predict the success rate of ventilator weaning in patients with delayed ventilator withdrawal after upper abdominal surgery.
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http://dx.doi.org/10.3389/fmed.2021.748493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674867PMC
December 2021

Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients.

Front Microbiol 2021 3;12:723818. Epub 2021 Dec 3.

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1-3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1-3 or 4-6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with "cytokine storms" and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fmicb.2021.723818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678452PMC
December 2021

Genome-Wide Identification and Expression Analysis of the Plant U-Box Protein Gene Family in .

Front Genet 2021 30;12:710113. Epub 2021 Nov 30.

Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, China.

The gene encodes a ubiquitin ligase that contains a U-box domain. The plant U-box (PUB) protein plays an important role in the plant stress response; however, very few studies have investigated the role of these proteins in Moso bamboo (). Thus, more research on PUB proteins is necessary to understand the mechanisms of stress tolerance in . In this study, we identified 121 members of the PUB family in (), using bioinformatics based on the V2 genome build. The genes of showed an uneven distribution among the chromosomes. Phylogenetic analysis of the genes between and suggested that these genes can be classified into eight subgroups (Groups I-VIII) based on their structural and phylogenetic features. All genes and the structure of their encoded proteins were identified in . We further investigated the expression pattern of genes in different tissues, including the leaves, panicles, rhizomes, roots, and shoots. The qRT-PCR results showed that expression of three genes, , and , was upregulated at low temperatures compared to that at 25°C. The expression levels of two , and , were upregulated under drought stress. These results suggest that the genes play an important role in resistance to low temperatures and drought in . This research provides new insight into the function, diversity, and characterization of genes in and provides a basis for understanding their biological roles and molecular mechanisms.
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http://dx.doi.org/10.3389/fgene.2021.710113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669748PMC
November 2021

Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells.

Bioengineered 2021 12;12(2):12583-12596

Department of Hepatobiliary Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.

The long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been implicated in the progression of abdominal aortic aneurysms (AAA). However, the detailed mechanism requires further analysis. Our study was aimed at interrogating the mechanism of PVT1 in an HO-induced AAA model . The expression of lncRNA PVT1, microRNA miR-3127-5p, and NCK-associated protein 1-like (NCKAP1L) was examined in AAA tissues and HO-treated vascular smooth muscle cells (VSMCs). Cell proliferation was assayed using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridine (BrdU) assays. Meanwhile, 5-Ethynyl-2'-deoxyuridine (EdU) staining was performed to assess cell apoptosis and caspase-3 activity. IL-1β and caspase-1 expression was also assessed using Western blotting to determine inflammasome activation in HO-treated VSMCs. Luciferase reporter assays addressed the possible interaction between miR-3127-5p and PVT1 or NCKAP1L, which was predicted by starBase analysis. PVT1 and NCKAP1L expression was elevated in AAA tissues and induced the AAA model , whereas miR-3127-5p showed the opposite trend. Functionally, PVT1 silencing promoted cell proliferation and reduced the apoptotic rate and inflammasome activation in HO-treated VSMCs. Mechanical investigation demonstrated that PVT1 acted as a sponge of miR-3127-5p to modulate NCKAP1L expression, resulting in suppression of VSMC proliferation, induction of apoptosis, and activation of inflammation. In conclusion, PVT1 participates in AAA progression through the miR-3127-5p/NCKAP1L axis and may be a promising biosignature and therapeutic target for AAA.
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http://dx.doi.org/10.1080/21655979.2021.2010384DOI Listing
December 2021

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy.

Cell Biosci 2021 Dec 11;11(1):203. Epub 2021 Dec 11.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear.

Results: Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells. The differentially expressed genes (DEGs) between control and IgAN were predominantly enriched in NK cell-mediated cytotoxicity and cell killing pathways. Interestingly, we discovered that the number and cytotoxicity of NK cells are significantly reduced in IgAN patients, where both the number and marker genes of NK cells were negatively associated with the clinical parameters, including the levels of urine protein creatinine ratio (UPCR), serum galactose-deficient IgA1 and IgA. A distinctive B cell subset, which had suppressed NFκB signaling was predominantly in IgAN and positively associated with disease progression. Moreover, the DEGs of B cells were enriched in different viral infection pathways. Classical monocytes also significantly changed in IgAN and a monocyte subset expressing interferon-induced genes was positively associated with the clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications in IgAN.

Conclusions: We dissected the immune landscape of IgAN at the single-cell resolution, which provides new insights in developing novel biomarkers and immunotherapy against glomerulonephritis.
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http://dx.doi.org/10.1186/s13578-021-00706-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665497PMC
December 2021

Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine.

EPMA J 2021 Dec 3:1-27. Epub 2021 Dec 3.

Predictive, Preventive and Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany.

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies-all exerted system's enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a "sick eye in a sick body" makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles.
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http://dx.doi.org/10.1007/s13167-021-00265-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639411PMC
December 2021

Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice.

Bioengineered 2021 12;12(2):9803-9815

Department of Rheumatology and Immunology, Zhoushan Hospital of Zhejiang Province, Zhoushan, Zhejiang, China.

Gout can affect the quality of life of patients due to monosodium urate monohydrate (MSU) crystals. Numerous studies have proposed that long noncoding RNAs (lncRNAs) regulate gout. We aimed to reveal the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in acute gouty arthritis (GA). A GA mouse model was established by injection of MSU into footpads. The levels of SNHG8, miR-542-3p and adaptor-related protein complex 3 subunit delta 1 (AP3D1) in footpads were detected via polymerase chain reaction analysis. Hematoxylin-eosin staining revealed the paw swelling in mice. Enzyme-linked immunosorbent assay and western blot analysis were applied to determine the concentrations of proinflammatory cytokines. SNHG8 expression was identified to be upregulated after MSU treatment. Ablation of SNHG8 decreased the MSU-induced enhancement of paw swelling and foot thickness. In addition, SNHG8 depletion decreased the protein levels of proinflammatory factors in GA mice. Mechanically, SNHG8 was verified to be a sponge of miR-542-3p, and miR-542-3p targeted AP3D1 3' untranslated region. SNHG8 competitively bound with miR-542-3p to upregulate AP3D1 expression. Finally, results of rescue assays illustrated that AP3D1 upregulation offset the SNHG8-mediated inhibition on paw swelling and protein levels of proinflammatory factors in GA mice. In conclusion, SNHG8 accelerates acute GA development by upregulating AP3D1 in an miR-542-3p-dependent way in mice, providing an effective therapeutic approach to treat acute GA.
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http://dx.doi.org/10.1080/21655979.2021.1995579DOI Listing
December 2021

Hydrogen: Potential Applications in Solid Organ Transplantation.

Oxid Med Cell Longev 2021 24;2021:6659310. Epub 2021 Nov 24.

Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Ischemia reperfusion injury (IRI) in organ transplantation has always been an important hotspot in organ protection. Hydrogen, as an antioxidant, has been shown to have anti-inflammatory, antioxidant, and antiapoptotic effects. In this paper, the protective effect of hydrogen against IRI in organ transplantation has been reviewed to provide clues for future clinical studies.
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http://dx.doi.org/10.1155/2021/6659310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635874PMC
November 2021

Response of Annual Herbaceous Plant Leaching and Decomposition to Periodic Submergence in Mega-Reservoirs: Changes in Litter Nutrients and Soil Properties for Restoration.

Biology (Basel) 2021 Nov 5;10(11). Epub 2021 Nov 5.

Key Laboratory of Eco-Environments in the Three Gorges Reservoir Region (Ministry of Education), Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, College of Life Sciences, Southwest University, Chongqing 400715, China.

Litter decomposition is an important soil nutrient source that promotes vegetation in deteriorated riparian zones worldwide. The periodic submergence and sediment burial effects on two prominent annual herbaceous plants ( and ) are little known in mega-reservoir settings. Our study focuses on the mass and carbon loss and nutrient release from and litter and changes in soil properties, which are important for riparian zone rehabilitation in the Three Gorges Dam Reservoir, China. This study adopted the litter bag method to explore the nutrient change characteristics and changes in soil properties at different sediment burial depths under flooding scenarios. Three burial depths (0 cm, 5 cm, and 10 cm) were used for these two plants, and the experiment lasted for 180 days. The results revealed that the litter decay rate was high at first in the incubation experiment, and the nutrient loss rate followed the pattern of K > P > N > C. The relationship between % C remaining and % mass remaining was nearly 1:1, and the total amount of P exhibited a leaching-enrichment-release state in the decomposition process. Nutrients were changed significantly in the soil and overlying water at the first decomposition stage. Still, the total soil nutrient change was insignificant at the end, except for the 10 cm burial of . Moreover, oxidation-reduction potential was the main factor in the litter decomposition process at different burial depths. This study indicated that sediment deposition reduced litter mass loss, slowed down the release of N and P, and retained more C, but promoted the release of K. Conclusively, in litter decomposition under waterlogging, the total soil nutrient content changed little. However, litter does more to the soil than that. Therefore, it is necessary to study the residual soil litter's continuous output after the water level declines for restoration purposes.
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http://dx.doi.org/10.3390/biology10111141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614921PMC
November 2021

Adjustable dual temperature-sensitive hydrogel based on a self-assembly cross-linking strategy with highly stretchable and healable properties.

Mater Horiz 2021 Apr 4;8(4):1189-1198. Epub 2021 Mar 4.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, China.

Developing smart temperature-sensitive hydrogels with a wide response range and highly stretchable and healable properties for simulation of the temperature perception function of human skin remains a great challenge. Here, a novel PNIPAm/PNAGA double-network hydrogel was developed by a self-assembly cross-linking strategy to achieve this goal. Benefiting from the double-network structure and a large number of multiple hydrogen bond interactions between the PNIPAm and PNAGA, the PNIPAm/PNAGA hydrogel realizes wide and adjustable dual temperature response behaviors of 0-32.5 °C (LCST) and 32.5-65 °C (UCST) and exhibits extraordinary mechanical properties with a maximum tensile strength of 51.48 kPa, elongation at break over 1400%, compressive stress over 1 MPa, and Young's modulus approximately 5.51 kPa, and excellent healable properties of nearly 100% temperature-sensitive repair rate. To the best of our knowledge, this is the highest mechanical strength of the reported PNIPNm-based dual temperature-sensitive hydrogels and simultaneously achieved the healable performance of dual temperature-sensitive hydrogels for the first time. The PNIPAm/PNAGA hydrogel displayed superior capability for simulation of the human skin to monitor various ambient temperatures, such as human skin temperature, hot and cold water, a refrigerator, room temperature and oven temperature, indicating promising applications in the fields of electronic skin, wearable device, bionics, etc.
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http://dx.doi.org/10.1039/d0mh01762kDOI Listing
April 2021

Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages.

Nat Commun 2021 11 18;12(1):6699. Epub 2021 Nov 18.

Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA.

Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis.
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http://dx.doi.org/10.1038/s41467-021-27034-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602704PMC
November 2021

Rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes.

Nat Commun 2021 11 16;12(1):6627. Epub 2021 Nov 16.

State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.

The Alder-ene type reaction between alkenes and alkynes provides an efficient and atom-economic method for the construction of C-C bond, which has been widely employed in the synthesis of natural products and other functional molecules. The intramolecular enantioselective Alder-ene cycloisomerization reactions of 1,n-enynes have been extensively investigated. However, the intermolecular asymmetric version has not been reported, and remains a challenging task. Herein, we describe a rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes. A variety of chiral (E)-vinylsilane tethered cyclopentenes bearing one quaternary carbon and one tertiary carbon stereocenters are achieved in high yields and enantioselectivities. The reaction undergoes carbonyl-directed migratory insertion, β-H elimination and desymmetrization of prochiral cyclopentenes processes.
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http://dx.doi.org/10.1038/s41467-021-26955-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595345PMC
November 2021

Machine learning-based automated fungal cell counting under a complicated background with ilastik and ImageJ.

Eng Life Sci 2021 Nov 22;21(11):769-777. Epub 2021 Aug 22.

Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology College of Life Sciences Beijing Normal University Beijing P. R. China.

Measuring the concentration and viability of fungal cells is an important and fundamental procedure in scientific research and industrial fermentation. In consideration of the drawbacks of manual cell counting, large quantities of fungal cells require methods that provide easy, objective and reproducible high-throughput calculations, especially for samples in complicated backgrounds. To answer this challenge, we explored and developed an easy-to-use fungal cell counting pipeline that combined the machine learning-based ilastik tool with the freeware ImageJ, as well as a conventional photomicroscope. Briefly, learning from labels provided by the user, ilastik performs segmentation and classification automatically in batch processing mode and thus discriminates fungal cells from complex backgrounds. The files processed through ilastik can be recognized by ImageJ, which can compute the numeric results with the macro 'Fungal Cell Counter'. Taking the yeast and the filamentous fungus as examples, we observed that the customizable software algorithm reduced inter-operator errors significantly and achieved accurate and objective results, while manual counting with a haemocytometer exhibited some errors between repeats and required more time. In summary, a convenient, rapid, reproducible and extremely low-cost method to count yeast cells and fungal spores is described here, which can be applied to multiple kinds of eucaryotic microorganisms in genetics, cell biology and industrial fermentation.
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http://dx.doi.org/10.1002/elsc.202100055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576076PMC
November 2021

Relationship Between Sclerostin (SOST) Expression and Genetic Loci rs851056, rs1230399 Polymorphisms and Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes in Xinjiang.

Diabetes Metab Syndr Obes 2021 4;14:4443-4450. Epub 2021 Nov 4.

Endocrinology and Metabolism Department, Second People's Hospital of Nanyang, Nanyang, Henan Province, People's Republic of China.

Background: The Wnt signaling pathway plays a valuable role in bone metabolism. SOST is a major inhibitor of the Wnt signaling pathway. The expression of SOST and genetic polymorphism might be associated with bone mineral density in postmenopausal women with type 2 diabetes mellitus (T2DM).

Objective: This study aims to explore whether SOST protein expression and genetic locus rs851056, rs1230399 polymorphism is associated with bone mineral density in postmenopausal women with T2DM in Xinjiang.

Methods: A total of 136 Xinjiang postmenopausal women were divided into four groups: A (-/-), B (±), C (-/+), and D (+/+) by assessing their OGTT and bone mass. Genetic polymorphisms were determined using the mass ARRAY mass spectrometer.

Results: 1) Genotypes and allele frequencies at rs851056 were statistically significant differences in groups B and D patients compared to group A, respectively. 2) Individuals carrying the GG genotype had lower HDL, Ca, and ALP as compared to those carrying the GC/CC genotypes in group C. In contrast, individuals carrying the GG genotype had higher BMD (L1-4) as compared to those carrying the GC/CC genotypes in group D. 3) SOST protein expression levels were higher in groups C and D than in group A. 4). BMD (L1-4) was negatively correlated with SOST protein. 5) Multiple linear regression analysis for BMD-dependent variables showed that the decrease of BMI and TG were risk factors for BMD (L1-4), besides, the decrease of BMI, ALP, and extended years of menopause were all risk factors for BMD (femoral neck).

Conclusion: SOST protein expression and genetic locus rs851056, rs1230399 polymorphism are associated with bone mineral density in postmenopausal women with type 2 diabetes mellitus in Xinjiang.
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http://dx.doi.org/10.2147/DMSO.S305831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575445PMC
November 2021

Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.

Med Res Rev 2021 Nov 3. Epub 2021 Nov 3.

Department of Biomedical Sciences, Faculty of Health Sciences, Macau, China.

Glycogen synthase kinase-3 (GSK3) is a highly evolutionarily conserved serine/threonine protein kinase first identified as an enzyme that regulates glycogen synthase (GS) in response to insulin stimulation, which involves GSK3 regulation of glucose metabolism and energy homeostasis. Both isoforms of GSK3, GSK3α, and GSK3β, have been implicated in many biological and pathophysiological processes. The various functions of GSK3 are indicated by its widespread distribution in multiple cell types and tissues. The studies of GSK3 activity using animal models and the observed effects of GSK3-specific inhibitors provide more insights into the roles of GSK3 in regulating energy metabolism and homeostasis. The cross-talk between GSK3 and some important energy regulators and sensors and the regulation of GSK3 in mitochondrial activity and component function further highlight the molecular mechanisms in which GSK3 is involved to regulate the metabolic activity, beyond its classical regulatory effect on GS. In this review, we summarize the specific roles of GSK3 in energy metabolism regulation in tissues that are tightly associated with energy metabolism and the functions of GSK3 in the development of metabolic disorders. We also address the impacts of GSK3 on the regulation of mitochondrial function, activity and associated metabolic regulation. The application of GSK3 inhibitors in clinical tests will be highlighted too. Interactions between GSK3 and important energy regulators and GSK3-mediated responses to different stresses that are related to metabolism are described to provide a brief overview of previously less-appreciated biological functions of GSK3 in energy metabolism and associated diseases through its regulation of GS and other functions.
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http://dx.doi.org/10.1002/med.21867DOI Listing
November 2021

Spatial variation and association between maternal chemical fertilizer exposure and preterm birth in a rural area in Northern China.

Environ Sci Pollut Res Int 2021 Oct 30. Epub 2021 Oct 30.

Institute of Population Research/China Center on Population Health and development, Peking University, Beijing, 100871, China.

Whether maternal macro-environmental chemical fertilizer exposure has an association with the risk of preterm birth remains unclear. This study aimed to investigate the association between maternal exposure to chemical fertilizer during pregnancy and the risk of preterm birth. A total of 13,861 births, including 402 preterm birth from 313 villages in Pingding County, Shanxi Province, China, were analyzed to explore spatial variations of preterm birth risks at the village level. Spatial variations of preterm birth were visualized and tested with Disease Mapping, Moran's I and G* Statistic. The spatial zero-inflated negative binomial model was used to evaluate the incidence rate ratio (IRR) of preterm birth in different chemical fertilizer consumption levels at the village level. A population-based case-control study was conducted including 153 preterm births cases and 204 controls at the household level. The two-level logistic regression model was performed to estimate the association between risks of preterm birth and maternal exposure to chemical fertilizer after adjusting confounding factors. The findings indicated a remarkably clustering effect in relative risks of preterm birth and identified a high-risk clustering region of preterm birth from the south-central to the southwest and a low-risk clustering region in the northern Pingding county. The results of the spatial zero-inflated negative binomial model showed that the risk of preterm birth in the villages with chemical fertilizer consumption≥100 tons was 2.82 (95% CI: 1.50-5.57) times higher than those with <50 tons. Maternal exposure to chemical fertilizer ≥100 tons at village level was associated with an increased risk of preterm birth (aOR 2.14, 95%CI: 1.18-3.96), compared with exposure <50 tons after adjusting for confounding variables. The findings suggests that chemical fertilizers deserve more attention as a potential risk factor of preterm birth.
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http://dx.doi.org/10.1007/s11356-021-17124-yDOI Listing
October 2021

Association between livelihood capital and catastrophic health expenditure among patients with critical illness: a cross-sectional study in rural Shandong, China.

BMJ Open 2021 10 29;11(10):e051234. Epub 2021 Oct 29.

Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

Objective: The objective of this study is to examine the association between livelihood capital and catastrophic health expenditure (CHE).

Design: Between July and August 2019, a cross-sectional study was conducted in critically ill patients.

Setting: Shandong, China.

Participants: 1041 households with critically ill patients from 77 villages.

Primary And Secondary Outcome Measures: We defined expenditure as being catastrophic if a household's out-of-pocket payments were greater than or equal to 40% of their capacity to pay. Using the sustainable livelihoods framework, this study explored the associations between CHE and the various forms of livelihood capital-inclusive of human capital, natural capital, physical capital, financial capital and social capital. χ tests, t-tests, Wilcoxon tests and binary logistic regression analysis were performed to examine these associations.

Results: The incidence of CHE among households with critically ill patients was 76.37% in this study. Better livelihood capital was significantly associated with lower incidence of CHE. After controlling for confounding factors, households with healthier patients (OR 0.47, 95% CI 0.23 to 0.96), more real estate ownership (OR 0.35, 95% CI 0.19 to 0.67) and better economic status (OR 0.33, 95% CI 0.18 to 0.62) were associated with a reduction in the occurrence of CHE.

Conclusions: Livelihood capital was significantly associated with CHE in rural families with critically ill patients. This association suggests that, in addition to providing health insurance to the critically ill, more attention should be paid to their ability to create and preserve livelihood capital.
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http://dx.doi.org/10.1136/bmjopen-2021-051234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559106PMC
October 2021

Time Course of Severe Fever With Thrombocytopenia Syndrome Virus and Antibodies in Patients by Long-Term Follow-Up Study, China.

Front Microbiol 2021 12;12:744037. Epub 2021 Oct 12.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The objective was to describe the changes of severe fever with thrombocytopenia syndrome virus (SFTSV) and antibody in the disease course and explore the relationship between antibody titers and patients' prognosis. The levels of SFTSV, virus-specific immunoglobulin M (IgM), immunoglobulin G (IgG) titers, and cytokines in 37 patients with severe fever with thrombocytopenia syndrome (SFTS) were measured dynamically by real-time PCR and ELISA during the disease course; IgG titers were followed up in 53 cases. The correlation analysis of antibody titers with individual serum cytokines was calculated using the Spearman test. The average time of SFTSV duration in individual serum was 22.45 ± 7.6 days from onset. We found SFTSV turned negative within the 10th day from the onset in two patients. SFTSV-specific IgM seroconversion occurred as early as within 3 days from the onset, increased gradually within the first 2 months, decreased gradually 3 months later, and disappeared after 6 months in all the patients. The average time of SFTSV-specific IgG antibody seroconversion was at 17 days from onset in the patients; the time was later in severe cases than in mild cases (23 ± 1.4 vs. 14.3 ± 1.0 days, < 0.0001). IgG titers were maintained at the peak levels during the periods from 6 months to 1 year and decreased from the second year gradually. Severe cases had higher IgG levels than mild cases and also had a slower decreasing trend. During follow-up, only one lost IgG antibody 7 years later; no chronic infection and sequela were found among the 53 patients. None of the patients had SFTSV reinfection even if they were bitten by ticks again. The correlation analysis showed a positive relationship between inflammatory factors and IgG antibody levels. IgM antibody has important value in early diagnosis of SFTS. A moderate inflammatory response is beneficial for production and duration of IgG antibodies.
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http://dx.doi.org/10.3389/fmicb.2021.744037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546325PMC
October 2021

Quantitative Acetylomics Revealed Acetylation-Mediated Molecular Pathway Network Changes in Human Nonfunctional Pituitary Neuroendocrine Tumors.

Front Endocrinol (Lausanne) 2021 12;12:753606. Epub 2021 Oct 12.

Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China.

Acetylation at lysine residue in a protein mediates multiple cellular biological processes, including tumorigenesis. This study aimed to investigate the acetylated protein profile alterations and acetylation-mediated molecular pathway changes in human nonfunctional pituitary neuroendocrine tumors (NF-PitNETs). The anti-acetyl antibody-based label-free quantitative proteomics was used to analyze the acetylomes between NF-PitNETs (n = 4) and control pituitaries (n = 4). A total of 296 acetylated proteins with 517 acetylation sites was identified, and the majority of which were significantly down-acetylated in NF-PitNETs (p<0.05 or only be quantified in NF-PitNETs/controls). These acetylated proteins widely functioned in cellular biological processes and signaling pathways, including metabolism, translation, cell adhesion, and oxidative stress. The randomly selected acetylated phosphoglycerate kinase 1 (PGK1), which is involved in glycolysis and amino acid biosynthesis, was further confirmed with immunoprecipitation and western blot in NF-PitNETs and control pituitaries. Among these acetylated proteins, 15 lysine residues within 14 proteins were down-acetylated and simultaneously up-ubiquitinated in NF-PitNETs to demonstrate a direct competition relationship between acetylation and ubiquitination. Moreover, the potential effect of protein acetylation alterations on NF-PitNETs invasiveness was investigated. Overlapping analysis between acetylomics data in NF-PitNETs and transcriptomics data in invasive NF-PitNETs identified 26 overlapped molecules. These overlapped molecules were mainly involved in metabolism-associated pathways, which means that acetylation-mediated metabolic reprogramming might be the molecular mechanism to affect NF-PitNET invasiveness. This study provided the first acetylomic profiling and acetylation-mediated molecular pathways in human NF-PitNETs, and offered new clues to elucidate the biological functions of protein acetylation in NF-PitNETs and discover novel biomarkers for early diagnosis and targeted therapy of NF-PitNETs.
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http://dx.doi.org/10.3389/fendo.2021.753606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546192PMC
October 2021

A Dual-Control Strategy by Phosphate Ions and Local Microviscosity for Tracking Adenosine Triphosphate Metabolism in Mitochondria and Cellular Activity Dynamically.

ACS Sens 2021 11 28;6(11):4225-4233. Epub 2021 Oct 28.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Shandong Key Laboratory of Biochemical Analysis, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.

Adenosine triphosphate (ATP) acts as the main energy source for growth and development in organisms, and the disorder reflects the mitochondrial damage to a large extent. Therefore, an efficient tool for the evaluation of the ATP metabolic level is important to track mitochondrial health, providing an additional perspective for an in-depth long-term study on living activities. Herein, a twisted intramolecular charge transfer (TICT) framework is utilized to build up a sensitive receptor, Mito-VP, with a negligible background to target mitochondrial ATP metabolism by monitoring the phosphate ion (Pi) level upon ATP hydrolysis under the overall consideration of the structural and functional features of mitochondria. The responsive fluorescence could be lighted on under the dual control of Pi and local microviscosity, and the two steps of ATP hydrolysis could be captured through fluorescence. In addition to the well-behaved mitochondrial targeting, the energy metabolism at cellular and organism levels has been clarified mitosis and zebrafish development, respectively.
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http://dx.doi.org/10.1021/acssensors.1c01850DOI Listing
November 2021
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