Publications by authors named "Jing Zhang"

10,817 Publications

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Blood extracellular vesicles carrying synaptic function- and brain-related proteins as potential biomarkers for Alzheimer's disease.

Alzheimers Dement 2022 Jul 2. Epub 2022 Jul 2.

Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.

Introduction: Objective and accessible markers for Alzheimer's disease (AD) and other dementias are critically needed.

Methods: We identified NMDAR2A, a protein related to synaptic function, as a novel marker of central nervous system (CNS)-derived plasma extracellular vesicles (EVs) and developed a flow cytometry-based technology for detecting such plasma EVs readily. The assay was initially tested in our local cross-sectional study to distinguish AD patients from healthy controls (HCs) or from Parkinson's disease (PD) patients, followed by a validation study using an independent cohort collected from multiple medical centers (the Alzheimer's Disease Neuroimaging Initiative). Cerebrospinal fluid AD molecular signature was used to confirm diagnoses of all AD participants.

Results: Likely CNS-derived EVs in plasma were significantly reduced in AD compared to HCs in both cohorts. Integrative models including CNS-derived EV markers and AD markers present on EVs reached area under the curve of 0.915 in discovery cohort and 0.810 in validation cohort.

Discussion: This study demonstrated that robust and rapid analysis of individual neuron-derived synaptic function-related EVs in peripheral blood may serve as a helpful marker of synaptic dysfunction in AD and dementia.
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http://dx.doi.org/10.1002/alz.12723DOI Listing
July 2022

Exploring Ganweikang Tablet as a Candidate Drug for NAFLD Through Network Pharmacology Analysis and Experimental Validation.

Front Pharmacol 2022 14;13:893336. Epub 2022 Jun 14.

Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

Nonalcoholic fatty liver disease (NAFLD) is defined as liver disease in which more than 5% of hepatocytes are steatotic with little or no alcohol consumption. NAFLD includes benign nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Importantly, NASH is an advanced progression of NAFL and is characterized by steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis. However, to date, no drugs specifically targeting NAFLD have been approved by the FDA. Therefore, a new drug or strategy for NAFLD treatment is necessary. However, the pathogenesis of NAFLD is complex and no single-target drugs have achieved the desired results. Noticeably, traditional Chinese medicine formulations are a complex system with multiple components, multiple targets, and synergistic effects between components. The Ganweikang tablet is a compound formula based on traditional Chinese medicine theory and clinical experience. In this study, network pharmacology analysis indicates Ganweikang tablet as a candidate for NAFLD treatment. Furthermore, we evaluated the therapeutic effects of Ganweikang tablet on the NAFL and NASH and tried to clarify the underlying molecular mechanisms in animal models and cell experiments. As expected, Ganweikang tablet was found to improve NAFL and NASH by modulating inflammation, apoptosis, and fatty acid oxidation by inhibiting NFκB, caspase-8, and activating PPARα, which not only indicates that Ganweikang tablet as a drug candidate but also provides a theoretical basis of Ganweikang tablet for the treatment of NAFL and NASH.
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http://dx.doi.org/10.3389/fphar.2022.893336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239345PMC
June 2022

Transcriptomic Analysis of Mature Transgenic Poplar Expressing the Transcription Factor Gene in Two Different Environments.

Front Bioeng Biotechnol 2022 14;10:929681. Epub 2022 Jun 14.

State Key Laboratory of Tree Genetics and Breeding, Research Institute of Forestry, Chinese Academy of Forestry, Beijing, China.

During the last several decades, a number of transgenic or genetically modified tree varieties with enhanced characteristics and new traits have been produced. These trees have become associated with generally unsubstantiated concerns over health and environmental safety. We conducted transcriptome sequencing of transgenic × expressing the transcription factor JERF36 gene (ABJ01) and the non-transgenic progenitor line (9#) to compare the transcriptional changes in the apical buds. We found that 0.77% and 1.31% of the total expressed genes were significant differentially expressed in ABJ01 at the Daqing and Qiqihar sites, respectively. Among them, 30%-50% of the DEGs contained cis-elements recognized by . Approximately 5% of the total number of expressed genes showed significant differential expression between Daqing and Qiqihar in both ABJ01 and 9#. 10 DEGs resulting from foreign gene introduction, 394 DEGs that resulted solely from the environmental differences, and 47 DEGs that resulted from the combination of foreign gene introduction and the environment were identified. The number of DEGs resulting from environmental factors was significantly greater than that resulting from foreign gene introduction, and the combined effect of the environmental effects with foreign gene introduction was significantly greater than resulting from the introduction of alone. GO and KEGG annotation showed that the DEGs mainly participate in the photosynthesis, oxidative phosphorylation, plant hormone signaling, ribosome, endocytosis, and plant-pathogen interaction pathways, which play important roles in the responses to biotic and abiotic stresses ins plant. To enhance its adaptability to salt-alkali stress, the transgenic poplar line may regulate the expression of genes that participate in the photosynthesis, oxidative phosphorylation, MAPK, and plant hormone signaling pathways. The crosstalk between biotic and abiotic stress responses by plant hormones may improve the ability of both transgenic and non-transgenic poplars to defend against pathogens. The results of our study provide a basis for further studies on the molecular mechanisms behind improved stress resistance and the unexpected effects of transgenic gene expression in poplars, which will be significant for improving the biosafety evaluation of transgenic trees and accelerating the breeding of new varieties of forest trees resistant to environmental stresses.
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http://dx.doi.org/10.3389/fbioe.2022.929681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237257PMC
June 2022

Enrichment of sulfur-oxidizing bacteria using S-doped NiFeO nanosheets as the anode in microbial fuel cell enhances power production and sulfur recovery.

Sci Total Environ 2022 Jun 27:156973. Epub 2022 Jun 27.

National Engineering Laboratory for VOCs Pollution Control Material & Technology, Research Center for Environmental Material and Pollution Control Technology, University of Chinese Academy of Sciences, Beijing 101408, China; Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Microbial fuel cells (MFCs) have great promise for power generation by oxidizing organic wastewater, yet the challenge to realize high efficiency in simultaneous energy production and resource recovery remains. In this study, we designed a novel MFC anode by synthesizing S-doped NiFeO nanosheet arrays on carbon cloth ([email protected]) to build a three-dimensional (3D) hierarchically porous structure, with the aim to regulate the microbial community of sulfur-cycling microbes in order to enhance power production and elemental sulfur (S) recovery. The [email protected] anode obtained a faster start-up time of 2 d and the highest power density of 4.5 W/m in acetate-fed and mixed bacteria-based MFCs. More importantly, hydrogen sulfide removal efficiency (98.3 %) (initial concentration of 50 mg/L S) could be achieved within 3 d and sulfur (S) could be produced. Microbial community analysis revealed that the [email protected] anode markedly enriched sulfur-oxidizing bacteria (SOB) and promoted enrichment of SOB and sulfate-reducing bacteria (SRB) in the bulk solution as well, leading to the enhancement of power generation and S recovery. This study shows how carefully designing and optimizing the composition and structure of the anode can lead to the enrichment of a multifunctional microbiota with excellent potential for sulfide removal and resource recovery.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156973DOI Listing
June 2022

Dihydroartemisinin alleviates deoxynivalenol induced liver apoptosis and inflammation in piglets.

Ecotoxicol Environ Saf 2022 Jun 27;241:113811. Epub 2022 Jun 27.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Deoxynivalenol (DON) is one of the mycotoxins that contaminate cereals and feed, thereby endangering human and animal health. Dihydroartemisinin (DHA), a derivative of artemisinin, has anti-inflammatory and antioxidant functions in addition to anti-malaria and anti-cancer. The purpose of this study was to investigate the effects of DHA on alleviating liver apoptosis and inflammation induced by DON in piglets. The experimental design followed a 2 (normal diet and DON-contaminated diet) × 2 (with and without supplementation of DHA) factorial arrangement. 36 weaned piglets were subjected to a 21-day experiment. Results showed that DON increased ALT activity, the levels of TNF-α, IL-1β and IL-2, and reduced the levels of total protein (TP) and albumin (ALB) in the serum. However, DHA decreased the levels of TNF-α, IL-1β and IL-2, and increased the levels of TP and ALB. Also, DON decreased glutathione (GSH) content and catalase (CAT) activity, and increased methane dicarboxylic aldehyde (MDA) content. But GSH content was increased by DHA. In addition, DHA decreased DON-induced increase in apoptosis rate of hepatocytes. Furthermore, DON activated death receptor pathway to promote apoptosis by up-regulating the protein expression of FasL and caspase-3, and the mRNA expression of FasL, TNFR1, caspase-8, Bid, Bax, CYC and caspase-3. However, DHA reduced caspase-3 protein expression, as well as the mRNA expression of FADD, Bid, Bax, CYC and caspase-3. Besides, DON also activated TNF/NF-κB pathway to induce an inflammatory response by up-regulating TNF-α protein expression, and the mRNA expression of TNFR1, RIP1, IKKβ, IκBα, IL-1β and IL-8. Nevertheless, DHA reduced the mRNA expression of RIP1, IκBα, NF-κB, IL-1β and IL-6, and the protein expression of TNF-α and NF-κB. In conclusion, DHA improved DON-induced negative effects on serum biochemical parameters and inflammatory cytokine levels, hepatic antioxidant capacity, hepatic apoptosis and inflammation.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113811DOI Listing
June 2022

Effects of periodic drought with severe exhaust exposure on particle retention capacity and physiological responses of Photinia × fraseri Dress.

Ecotoxicol Environ Saf 2022 Jun 27;241:113807. Epub 2022 Jun 27.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Lin'an 311300, China. Electronic address:

Urban plants are regarded as an effective agent to control particulate matter (PM) pollution by absorbing PM. Repeated PM and drought stress in urban areas often cause morphological and physiological damage to plants, resulting in lower ecological benefits. Nevertheless, knowledge in PM retention capability, morphology and physiology of plants under repeated stress and cross stress has been barely available. In order to investigate changes in these aspects under repeated stress, we applied periodic drought with severe exhaust exposure on Photinia × fraseri Dress (a common urban tree species with strong PM retention ability). The study was carried out in a six-period scenario, with a duration of 10 days for each period: initial value (R0), initial stress period (S1), initial recovery period (R1) second stress period (S2), second recovery period (R2) and final stress period (S3). The results are as follows: In terms of periodic factor, PM retention of tail gas stress group (P) and cross stress group (PD) in S2 decreased by 10.00 μg/cm and 12.60 μg/cm respectively compared with those during S1 (p > 0.05). During S3, the total amount of PM on leaf surface in both P and PD demonstrated a significant decrease (p < 0.05). The retention capacity of P. fraseri may be dramatically limited under multi-period stress. In this experiment, we attribute the decrease of PM retention to the morphological changes (shedding of mature leaves, smaller leaf area and thinner wax layer) and physiological responses (an increase in gas exchange) under multi-period stress. In terms of cross-stress factor, the total retained PM on leaf surface in PD was higher than that in P, especially during S3, and the interaction between drought and PM reached a significant level (p < 0.01, η = 0.808), which indicated that drought reduced the loss of dust under PM stress. Changes in morphology and gas exchange indicated that the mechanisms for the high dust retention rate on the leaf surface of PD group varied in the three stress periods. In addition, except the chlorophyll relative value, the alleviated accumulation of MDA and intense production of soluble sugar with PD showed favorable responses to disturbance compared with those in P under the repeated stress. Therefore, we infer that, under multi-period stress of drought and tail gas, P. fraseri may better maintain PM retention ability and resistance than under single stress.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113807DOI Listing
June 2022

Enhancing the bifunctional activity of CoSe nanocubes by surface decoration of CeO for advanced zinc-air batteries.

J Colloid Interface Sci 2022 Jun 23;625:839-849. Epub 2022 Jun 23.

Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China; Shenzhen Research Institute, China University of Geosciences, Shenzhen 518000, China. Electronic address:

The coupling of oxygen evolution and reduction reactions (OER and ORR) plays a key role in rechargeable Zn-air batteries (ZABs). However, both OER and ORR still suffer from sluggish kinetics, even when using the mainstream precious metal-based catalysts. Herein, oxygen vacancies-rich CeO decorated CoSe nanocubes are proposed as a novel air electrode to drive OER and ORR for ZABs. The resultant CeO coupled CoSe nanocubes ([email protected]) catalyst exhibits a significantly enhanced bifunctional activity relative to the pristine CoSe-NCs and the pristine CeO. Moreover, an assembled ZABs using this [email protected] electrode delivers a high output power density of 153 mW cm and a long-life stability over 400 cycles, superior to the benchmark Pt/C-IrO electrode. Theoretical calculations reveal that the electronic interaction and oxygen vacancies in [email protected] contribute to efficient oxygen electrocatalysis. This protocol provides a promising approach of constructing oxygen vacancies in hybrid catalysts for energy conversion and storage devices.
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http://dx.doi.org/10.1016/j.jcis.2022.06.094DOI Listing
June 2022

DJ-1/FGFR-1 Signaling Pathway Contributes to Sorafenib Resistance in Hepatocellular Carcinoma.

Oxid Med Cell Longev 2022 20;2022:2543220. Epub 2022 Jun 20.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Sorafenib is the first-line therapeutic regimen targeting against advanced or metastatic stage of hepatocellular carcinoma (HCC). However, HCC patients at these stages will eventually fail sorafenib treatment due to the drug resistance. At present, molecular mechanisms underlying sorafenib resistance are not completely understood. Our past studies have shown that DJ-1 is upregulated in HCC, while DJ-1 knockdown inhibits HCC xenograft-induced tumor growth and regeneration, implying that DJ-1 may be a potential target in for HCC treatment. However, whether DJ-1 plays a regulatory role between tumor cells and vascular endothelial cells and whether DJ-1 contributes to sorafenib resistance in HCC cells are largely unclear. To address these questions, we have performed a series of experiments in the current study, and we found that (1) DJ-1, one of the molecules secreted from HCC cells, promoted angiogenesis and migration of vascular endothelial cells (i.e., ECDHCC-1), by inducing phosphorylation of fibroblast growth factor receptor-1 (FGFR-1), phosphorylation of mTOR, phosphorylation of ERK, and phosphorylation of STAT3; (2) downregulation of FGFR1 inhibited tube formation and migration of ECDHCC-1 cells stimulated by DJ-1; (3) FGFR1 knockdown attenuated the phosphorylation of FGFR1 and impaired the activity of Akt, ERK, and STAT3 signals induced by DJ-1 in ECDHCC-1 cells; (4) knocking down FGFR1 led to the elevated expression of proapoptotic molecules but deceased level of antiapoptotic molecules in sorafenib-resistant HCC cells; and (5) Downregulation of FGFR1 suppressed tumor growth and angiogenesis of sorafenib-resistant HCC cells . Altogether, our results hinted that DJ-1 plays vital roles in tumor microenvironment in HCC development, and DJ-1/FGFR1 signaling pathway may be a therapeutic target for overcoming sorafenib resistance in treating HCC patients at the late stage.
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http://dx.doi.org/10.1155/2022/2543220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236769PMC
July 2022

Causal Effects of Circulating Cytokines on the Risk of Psoriasis Vulgaris: A Mendelian Randomization Study.

Front Genet 2022 13;13:941961. Epub 2022 Jun 13.

Anhui Prevention and Treatment Center for Occupational Disease, Anhui No. 2 Provincial People's Hospital, Hefei, China.

Psoriasis vulgaris is an inflammatory skin disease. Observational studies have shown associations between circulating cytokine levels and psoriasis vulgaris. But the causal relationship between circulating cytokine and psoriasis vulgaris remains elusive. To assess the causal effects of cytokine levels on the risk of psoriasis vulgaris and vice versa, we performed a two-sample Mendelian randomization (MR) study by using the inverse-variance weighted (IVW), weighted median, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) in genome-wide association summary statistics of 41 circulating cytokines in up to 8,293 individuals and psoriasis vulgaris in 399,883 individuals. We identified that increasing RANTES level induced an elevated risk of psoriasis vulgaris in IVW ( = 0.33, S.E. = 0.12, = 0.006). This causal effect showed consistency across the weighted median ( = 0.35, S.E. = 0.15, = 0.022) and MR-PRESSO method ( = 0.33, S.E. = 0.11, = 0.028). Our results suggest a potential causal effect of elevated RANTES concentration on the increased risk of psoriasis vulgaris.
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http://dx.doi.org/10.3389/fgene.2022.941961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234291PMC
June 2022

B10 Cells Are Associated With Clinical Prognosis During Adult Symptomatic Acute HBV Infection.

Front Immunol 2022 13;13:906650. Epub 2022 Jun 13.

The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

There are few reports about the role of B10 cells in acute hepatitis B (AHB) infection. In this study, based on 48 acute hepatitis B infected patients, we analysis the correlation of B10 cells with HBV clinical prognosis. The results showed that B10 was positively correlated with HBsAg and HBeAg and inversely correlated with anti-HBs. The level of B10 in one week before HBsAg clearance was significantly lower than 2 weeks prior to HBsAg clearance and after 1-2 weeks of HBsAg clearance. B10 cell frequency displayed no correlation with HBV DNA; however, it showed significant temporal synchronization with hepatic inflammatory markers such as ALT. B10 level also associated with hospitalization time. These results indicated that B10 is closely related to the clinical prognosis of acute HBV infection.
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http://dx.doi.org/10.3389/fimmu.2022.906650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234142PMC
July 2022

Genetic prion diseases presenting as frontotemporal dementia: clinical features and diagnostic challenge.

Alzheimers Res Ther 2022 Jun 29;14(1):90. Epub 2022 Jun 29.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.

Background: To elucidate the clinical and ancillary features of genetic prion diseases (gPrDs) presenting with frontotemporal dementia (FTD) to aid early identification.

Methods: Global data of gPrDs presenting with FTD caused by prion protein gene mutations were collected from literature review and our records. Fifty-one cases of typical FTD and 136 cases of prion diseases admitted to our institution were included as controls. Clinical and ancillary data of the different groups were compared.

Results: Forty-nine cases of gPrDs presenting with FTD were identified. Compared to FTD or prion diseases, gPrDs presenting with FTD were characterized by earlier onset age (median 45 vs. 61/60 years, P < 0.001, P < 0.001) and higher incidence of positive family history (81.6% vs. 27.5/13.2%, P < 0.001, P < 0.001). Furthermore, GPrDs presenting with FTD exhibited shorter duration (median 5 vs. 8 years) and a higher rate of parkinsonism (63.7% vs. 9.8%, P < 0.001), pyramidal signs (39.1% vs. 7.8%, P = 0.001), mutism (35.9% vs. 0%, P < 0.001), seizures (25.8% vs. 0%, P < 0.001), myoclonus (22.5% vs. 0%, P < 0.001), and hyperintensity on MRI (25.0% vs. 0, P < 0.001) compared to FTD. Compared to prion diseases, gPrDs presenting with FTD had a longer duration of symptoms (median 5 vs. 1.1 years, P < 0.001), higher rates of frontotemporal atrophy (89.7% vs. 3.3%, P < 0.001), lower rates of periodic short-wave complexes on EEG (0% vs. 30.3%, P = 0.001), and hyperintensity on MRI (25.0% vs. 83.0%, P < 0.001). The frequency of codon 129 Val allele in gPrDs presenting with FTD was significantly higher than that reported in the literature for gPrDs in the Caucasian and East Asian populations (33.3% vs. 19.2%/8.0%, P = 0.005, P < 0.001).

Conclusions: GPrDs presenting with FTD are characterized by early-onset, high incidence of positive family history, high frequency of the Val allele at codon 129, overlapping symptoms with prion disease and FTD, and ancillary features closer to FTD. PRNP mutations may be a rare cause in the FTD spectrum, and PRNP genotyping should be considered in patients with these features.
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http://dx.doi.org/10.1186/s13195-022-01033-4DOI Listing
June 2022

CHREBP suppresses gastric cancer progression via the cyclin D1-Rb-E2F1 pathway.

Cell Death Discov 2022 Jun 29;8(1):300. Epub 2022 Jun 29.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China.

Accumulating evidence has demonstrated that carbohydrate response element binding protein (CHREBP) has a crucial function in tumor pathology. In this study, we found CHREBP downregulation in gastric cancer (GC) tissues, and CHREBP was determined to be an independent diagnostic marker of GC. The downregulation of CHREBP promoted cell proliferation and inhibited apoptosis. Moreover, the level of cyclin D1 was significantly correlated with CHREBP expression in GC and paracancerous normal samples. In addition, CHREBP transcriptionally inhibited cyclin D1 expression in GC cells. Tumor suppressor activity of CHREBP could be affected by the upregulation of cyclin D1. In summary, CHREBP was found to be an independent diagnostic marker of GC and to influence GC growth and apoptosis via targeting the cyclin D1-Rb-E2F1 pathway.
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http://dx.doi.org/10.1038/s41420-022-01079-1DOI Listing
June 2022

Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases.

Iran J Immunol 2022 Jun;19(2)

Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

Background: Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD.

Objectives: To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci.

Methods: A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and patients with 394 Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method.

Results: Allele C and combinational genotype AC+CC of rs3212227 within il-23 significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within il-17ra significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within il-17f significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (il-23r-il-23-il-17ra-il-17f-sex) was identified in AITD, GD, and HT patients with GMDR analysis.

Conclusions: Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.
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http://dx.doi.org/10.22034/iji.2022.93744.2255DOI Listing
June 2022

Adaptive Semantic-Enhanced Transformer for Image Captioning.

IEEE Trans Neural Netw Learn Syst 2022 Jun 29;PP. Epub 2022 Jun 29.

In the research on image captioning, rich semantic information is very important for generating critical caption words as guiding information. However, semantic information from offline object detectors involves many semantic objects that do not appear in the caption, thereby bringing noise into the decoding process. To produce more accurate semantic guiding information and further optimize the decoding process, we propose an end-to-end adaptive semantic-enhanced transformer (AS-Transformer) model for image captioning. For semantic enhancement information extraction, we propose a constrained weaklysupervised learning (CWSL) module, which reconstructs the semantic object's probability distribution detected by the multiple instances learning (MIL) through a joint loss function. These strengthened semantic objects from the reconstructed probability distribution can better depict the semantic meaning of images. Also, for semantic enhancement decoding, we propose an adaptive gated mechanism (AGM) module to adjust the attention between visual and semantic information adaptively for the more accurate generation of caption words. Through the joint control of the CWSL module and AGM module, our proposed model constructs a complete adaptive enhancement mechanism from encoding to decoding and obtains visual context that is more suitable for captions. Experiments on the public Microsoft Common Objects in COntext (MSCOCO) and Flickr30K datasets illustrate that our proposed AS-Transformer can adaptively obtain effective semantic information and adjust the attention weights between semantic and visual information automatically, which achieves more accurate captions compared with semantic enhancement methods and outperforms state-of-the-art methods.
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http://dx.doi.org/10.1109/TNNLS.2022.3185320DOI Listing
June 2022

The effect of ovarian stimulation on aneuploidy of early aborted tissues and preimplantation blastocysts: comparison of the GnRH agonist long protocol with the GnRH antagonist protocol.

J Assist Reprod Genet 2022 Jun 29. Epub 2022 Jun 29.

Center for Reproductive Medicine, Department of Gynecology & Obsterics, Tang Du Hospital, the Air Force Military Medical University, Xi'an, Shaan xi, People's Republic of China.

Purpose: To compare aneuploidy rates in early aborted tissues or blastocysts between in vitro fertilization (IVF) cycles after the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol.

Methods: This was a retrospective cohort study from a university-affiliated fertility center. In total, 550 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the GnRH-ant or GnRH-a long protocol were analyzed to compare aneuploidy rates in early aborted tissues. To compare aneuploidy rates in blastocysts, 404 preimplantation genetic testing for aneuploidy (PGT-A) cycles with the GnRH-ant protocol or GnRH-a long protocol were also analyzed.

Results: For early miscarriage patients who conceived through IVF/ICSI, compared to the GnRH-a long protocol group, the GnRH-ant protocol group had a significantly higher rate of aneuploidy in early aborted tissues (48.51% vs. 64.19%). Regarding PGT-A cycles, the rate of blastocyst aneuploidy was significantly higher in the GnRH-ant protocol group than the GnRH-a long protocol group (39.69% vs. 52.27%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and blastocysts [OR (95% CI) 1.81 (1.21, 2.71), OR (95% CI) 1.65 (1.13, 2.42)]. Furthermore, the blastocyst aneuploidy rate in the GnRH-ant protocol group was significantly higher but only in young and normal ovarian responders [OR (95% CI) 5.07 (1.99, 12.92)].

Conclusion: Compared to the GnRH-a long protocol, the GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and blastocysts. These results should be confirmed in a multicenter, randomized controlled trial.
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http://dx.doi.org/10.1007/s10815-022-02557-2DOI Listing
June 2022

Direct Synthesis of Adipic Esters and Adiponitrile via Photoassisted Cobalt-Catalyzed Alkene Hydrodimerization.

Chemistry 2022 Jun 29. Epub 2022 Jun 29.

Wuhan University, the Institute for Advanced Studies, 299 Bayi Road, 430072, Wuhan, CHINA.

The direct hydrodimerization of acrylates and acrylonitrile offers a general streamlined access to industrially important intermediates to nylon 6,6. However, a practical catalytic method for this process has thus far underdeveloped owing to the challenges in regioselectivity and environmental compatibility of applied reagents. Here, we report a cobalt-catalyzed tail-to-tail hydrodimerization of activated alkenes driven by a visible-light photoredox catalysis at ambient temperature, which is applicable to both adipates and adiponitrile synthesis from potentially renewable feedstocks. This protocol utilizes half equivalent of hantzsch ester as a recyclable two-electron and two-proton donor with the assistance of catalytic amount of base as a proton shuttle, and has been shown to be highly regioselective and efficient for hydrodimerizing various activated alkenes to 1,4-difunctionalized butane derivatives.
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http://dx.doi.org/10.1002/chem.202201442DOI Listing
June 2022

Synergistic Crystallization and Passivation by A Single Molecular Additive for High Performance Perovskite Solar Cells.

Adv Mater 2022 Jun 29:e2204098. Epub 2022 Jun 29.

Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Key Laboratory for Advanced Energy Devices, Shaanxi Engineering Lab for Advanced Energy Technology, Institute for Adv. Energy Mater., School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China.

With its power conversion efficiency surpassed those of all other thin film solar cells only a few years after its invention, the perovskite solar cell has become a superstar. Controlling intermediate phase of crystallization is a key to obtain high-quality perovskite films. Herein, a single molecule additive, N, N-Dimethylimidodicarbonimidic diamide hydroiodide (DIAI), is incorporated into perovskite precursor to eliminate the influence of intermediate phases. By taking advantage of interaction of DIAI and DMSO, the intermediate phase FAI-PbI -DMSO complex is eliminated, and δ-FAPbI is entirely converted to desired α-FAPbI during the crystallization step, resulting in enlarged grain size and im proved crystalline quality. This is the first observation in solution method that FAPbI can be obtained without intermediate phase for high-performance perovskite solar cells. Furthermore, DIAI is effective at passivating surface defects, resulting in reduced defect density, increased carrier lifetime, and improved device efficiency and stability. The champion device achieved an efficiency of 24.13%. Furthermore, the bare device without any encapsulation maintains 94.1% of its initial efficiency after ambient exposure over 1000 hours. This work contributes a strategy of synergistic crystallization and passivation to directly form α-FAPbI from the precursor solution without the influence of intermediate impurities for high performance perovskite applications. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204098DOI Listing
June 2022

SARS-CoV-2 ORF10 antagonizes STING-dependent interferon activation and autophagy.

J Med Virol 2022 Jun 28. Epub 2022 Jun 28.

Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.

A characteristic feature of COVID-19, the disease caused by SARS-CoV-2 infection, is the dysregulated immune response with impaired type I and III interferon (IFN) expression and an overwhelming inflammatory cytokine storm. RIG-I-like receptors (RLRs) and cGAS-STING signaling pathways are responsible for sensing viral infection and inducing IFN production to combat invading viruses. Multiple proteins of SARS-CoV-2 have been reported to modulate the RLR signaling pathways to achieve immune evasion. Although SARS-CoV-2 infection also activates the cGAS-STING signaling by stimulating micronuclei formation during the process of syncytia, whether SARS-CoV-2 modulates the cGAS-STING pathway requires further investigation. Here, we screened 29 SARS-CoV-2-encoded viral proteins to explore the viral proteins that affect the cGAS-STING signaling pathway and found that SARS-CoV-2 ORF10 targets STING to antagonize IFN activation. Overexpression of ORF10 inhibits cGAS-STING-induced IRF3 phosphorylation, translocation, and subsequent IFN induction. Mechanistically, ORF10 interacts with STING, attenuates the STING-TBK1 association, and impairs STING oligomerization and aggregation and STING-mediated autophagy; ORF10 also prevents the endoplasmic reticulum (ER)-to-Golgi trafficking of STING by anchoring STING in the ER. Taken together, these findings suggest that SARS-CoV-2 ORF10 impairs the cGAS-STING signaling by blocking the translocation of STING and the interaction between STING and TBK1 to antagonize innate antiviral immunity. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27965DOI Listing
June 2022

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BMC Cancer 2022 Jun 28;22(1):710. Epub 2022 Jun 28.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, People's Republic of China.

Background: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC.

Methods: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy.

Discussion: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety.

Trial Registration: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-022-09786-9DOI Listing
June 2022

Corneal densitometry after allogeneic small-incision intrastromal lenticule implantation for hyperopia correction.

BMC Ophthalmol 2022 Jun 29;22(1):286. Epub 2022 Jun 29.

Jinan Mingshui Eye Hospital, Number 5601, Longquan Road, Zhangqiu District, 250200, Jinan, China.

Purpose: To evaluate corneal densitometry after allogeneic corneal small-incision intrastromal lenticule implantation (SILI) for hyperopia.

Methods: A retrospective study. Thirty-one hyperopic eyes of 24 patients who underwent SILI were enrolled in this study. Examinations took place preoperatively and 1 week, 1 month, 3 months, and 6 months postoperatively. Corneal densitometry (CD) from different concentric radial zones (0-2, 2-6, and 6-10 mm annulus) and layers (anterior, central, and posterior) were obtained using Scheimpflug imaging. The association between CD changes and the uncorrected distance visual acuity (UDVA), spherical equivalent (SE), central corneal thickness (CCT) and K value were examined.

Results: No serious intraoperative complications occurred during SILI. The mean total CD increased postoperatively compared to preoperatively (P < 0.01). However, no significant differences were found among the four subsequent follow-up time points (P > 0.05). At 6 months postoperatively, the CD values showed an increase of 2.71 ± 2.52, 2.23 ± 2.25, and 1.87 ± 2.46 at the 0-2, 2-6, and 6-10 mm annuli, respectively (all at P < 0.01). The anterior 120 μm displayed the highest densitometry before and after surgery (all at P < 0.01). No significant increase was found within the posterior 60 μm of the cornea (P > 0.05). No correlation was found between the CD and relevant parameters(all at P > 0.05).

Conclusions: SILI resulted in an increase in CD within the surgically altered area, however such change has no significant correlation with visual outcomes.
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http://dx.doi.org/10.1186/s12886-022-02454-3DOI Listing
June 2022

Determination of 23 related analytes in bone marrow fluid and hippocampus of C57BL/6 mice on cerebral ischemia-reperfusion injury by HPLC-FLD.

Biomed Chromatogr 2022 Jun 28:e5435. Epub 2022 Jun 28.

Chongqing Research Center for Pharmaceutical Engineering, School of Pharmacy, Chongqing Medical University, Chongqing, China.

The study of brain diseases has long been of interest to researchers worldwide, and stroke is the third leading cause of death that threatens human health. At the same time, a cerebral ischemia-reperfusion injury is closely associated with high rates of disability and mortality. The conditions of the 6-Aminoquinolyl N-hydroxysccinimidyl carbamate (AQC) method for the derivatization of amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice with cerebral ischemia/reperfusion injury were explored and optimized, such as the column temperature, concentration of derivatization reagents, and mobile phase concentration were investigated and optimized. The mobile phase consisted of 20 mM sodium acetate solution (phosphoric acid to adjust pH 5.0) and 60% acetonitrile solution at the flow rate of 1 mL•min . The 23 analytes were separated and determined in a gradient elution procedure; the correlation coefficient r was greater than 0.9990 in the range of 0.1-8.0 μg•mL . The results showed that the content of relevant analytes was significantly changed in the cerebral ischemia-reperfusion injury model, the method was suitable for the simultaneous determination of 23 amino acids in bone marrow fluid and hippocampus of C57BL/6 mice.
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http://dx.doi.org/10.1002/bmc.5435DOI Listing
June 2022

Corrigendum to "Metagenomics-based insights into the microbial community profiling and flavor development potentiality of baijiu Daqu and huangjiu wheat Qu" [Food Res. Int. 152 (2022) 110707].

Food Res Int 2022 Jul 15;157:111448. Epub 2022 Jun 15.

National Engineering Laboratory for Cereal Fermentation Technology, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, Zhejiang 31200, China; National Engineering Research Center of Huangjiu, Zhejiang Guyuelongshan Shaoxing Wine Co., Ltd., Shaoxing, Zhejiang 31200, China. Electronic address:

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http://dx.doi.org/10.1016/j.foodres.2022.111448DOI Listing
July 2022

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial.

Nat Commun 2022 Jun 27;13(1):3654. Epub 2022 Jun 27.

The Sixth Laboratory, National Vaccine and Serum Institute (NVSI), Beijing, China.

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.
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http://dx.doi.org/10.1038/s41467-022-31379-0DOI Listing
June 2022

PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction.

PLoS Pathog 2022 Jun 27;18(6):e1010667. Epub 2022 Jun 27.

State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.
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http://dx.doi.org/10.1371/journal.ppat.1010667DOI Listing
June 2022

Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma.

Front Immunol 2022 10;13:902318. Epub 2022 Jun 10.

Department of Respiratory and Critical Care Medicine, The Center for Biomedical Research, NHC Key Laboratory of Respiratory Disease, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Asthma is a multifactorial disorder characterized by the airway chronic inflammation, hyper-responsiveness (AHR), remodeling, and reversible obstruction. Although asthma is known as a heterogeneous group of diseases with various clinical manifestations, recent studies suggest that more than half of the clinical cases are ''T helper type 2 (Th2)-high'' type, whose pathogenesis is driven by Th2 responses to an inhaled allergen from the environmental exposures. The intensity and duration of inflammatory responses to inhaled allergens largely depend on the balance between effector and regulatory cells, but many questions regarding the mechanisms by which the relative magnitudes of these opposing forces are remained unanswered. Regulatory T cells (Tregs), which comprise diverse subtypes with suppressive function, have long been attracted extensive attention owing to their capability to limit the development and progression of allergic diseases. In this review we seek to update the recent advances that support an essential role for Tregs in the induction of allergen tolerance and attenuation of asthma progression once allergic airway inflammation established. We also discuss the current concepts about Treg induction and Treg-expressed mediators relevant to controlling asthma, and the therapies designed based on these novel insights against asthma in clinical settings.
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http://dx.doi.org/10.3389/fimmu.2022.902318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226301PMC
June 2022

Improving Estimation of Winter Wheat Nitrogen Status Using Random Forest by Integrating Multi-Source Data Across Different Agro-Ecological Zones.

Front Plant Sci 2022 10;13:890892. Epub 2022 Jun 10.

MARA Key Laboratory for Crop System Analysis and Decision Making, Jiangsu Key Laboratory for Information Agriculture, National Engineering and Technology Center for Information Agriculture, MOE Engineering and Research Center for Smart Agriculture, Collaborative Innovation Center for Modern Crop Production Co-sponsored by Province and Ministry, Nanjing Agricultural University, Nanjing, China.

Timely and accurate estimation of plant nitrogen (N) status is crucial to the successful implementation of precision N management. It has been a great challenge to non-destructively estimate plant N status across different agro-ecological zones (AZs). The objective of this study was to use random forest regression (RFR) models together with multi-source data to improve the estimation of winter wheat ( L.) N status across two AZs. Fifteen site-year plot and farmers' field experiments involving different N rates and 19 cultivars were conducted in two AZs from 2015 to 2020. The results indicated that RFR models integrating climatic and management factors with vegetation index (R = 0.72-0.86) outperformed the models by only using the vegetation index (R = 0.36-0.68) and performed well across AZs. The Pearson correlation coefficient-based variables selection strategy worked well to select 6-7 key variables for developing RFR models that could achieve similar performance as models using full variables. The contributions of climatic and management factors to N status estimation varied with AZs and N status indicators. In higher-latitude areas, climatic factors were more important to N status estimation, especially water-related factors. The addition of climatic factors significantly improved the performance of the RFR models for N nutrition index estimation. Climatic factors were important for the estimation of the aboveground biomass, while management variables were more important to N status estimation in lower-latitude areas. It is concluded that integrating multi-source data using RFR models can significantly improve the estimation of winter wheat N status indicators across AZs compared to models only using one vegetation index. However, more studies are needed to develop unmanned aerial vehicles and satellite remote sensing-based machine learning models incorporating multi-source data for more efficient monitoring of crop N status under more diverse soil, climatic, and management conditions across large regions.
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http://dx.doi.org/10.3389/fpls.2022.890892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226625PMC
June 2022

The Development of Predictive Nomogram of Recurrence for Patients With Endometrioma After Cystectomy Who Were Younger Than 45 Years Old and Received Postoperative Therapy.

Front Med (Lausanne) 2022 9;9:872481. Epub 2022 Jun 9.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: This study aimed to establish an effective prognostic nomogram for the postoperative recurrence of endometrioma or endometriosis-related pain for patients with endometrioma after long-term follow-up, who were younger than 45 years old and received postoperative therapy.

Methods: The predictive nomogram was based on 323 patients who underwent cystectomy for endometrioma at Perking Union Medical College Hospital from January 2009 to April 2013, and the last follow-up occurred in September 2018. We collected information on all included patients, including preoperative data, intraoperative data, and long-term follow-up data after surgery. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The survival curve was depicted based on Kaplan-Meier method and compared by log-rank method. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. In addition, calculating the area under the curve (AUC) via risk scores of patients aimed to further access the prediction ability of the model.

Results: On multivariate analysis of derivation cohort, independent factors for recurrence such as dysmenorrhea degree, sum of both cyst diameters, presence of adenomyosis, and other essential factors for recurrence such as age at surgery, presence of uterine fibroids were all selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.683 (95% CI, 0.610- 0.755). The calibration curve for probability of recurrence for 7 years and 9 years showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 7-year and 9-year were 0.680 and 0.790 respectively.

Conclusion: This research tried to develop the predictive nomogram of recurrence for patients with endometrioma after cystectomy. The C-index and calibration curve of nomogram, as well as the AUC of the nomogram was potential to predict the recurrence probability. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.
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http://dx.doi.org/10.3389/fmed.2022.872481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218256PMC
June 2022

Binding mechanism and antioxidant activity of piperine to hemoglobin.

Food Chem 2022 Jun 22;394:133558. Epub 2022 Jun 22.

School of Chemical Engineering, Sichuan University, Chengdu 610065, China.

Piperine (PIP) is the most active main component in pepper. The interaction of small molecules with biomolecules leads to structural and functional changes. In this study, the binding mechanism and antioxidant activity of PIP with hemoglobin (Hb) are presented using spectroscopic and computational methods. Results showed that the redox activity of PIP on Hb showed concentration dependence. Fluorescence and isothermal titration calorimetric experiments showed that the Hb-PIP system had a static quenching mechanism at a single binding site. The addition of PIP caused a slight perturbation to the secondary structure of Hb by structural analysis. The structural stability of the Hb-PIP binding system was demonstrated by molecular dynamics simulations, and molecular docking and thermodynamic constants confirmed that the electrostatic interaction force was dominant in the energy contribution of the system. Research results are conducive to the potential use of PIP in related meat products.
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http://dx.doi.org/10.1016/j.foodchem.2022.133558DOI Listing
June 2022

Age-related endoplasmic reticulum stress represses testosterone synthesis via attenuation of the circadian clock in Leydig cells.

Theriogenology 2022 Jun 17;189:137-149. Epub 2022 Jun 17.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China. Electronic address:

Senile animals exhibit a high risk of elevated endoplasmic reticulum (ER) stress, attenuated circadian clock, and impaired steroidogenesis in testes. However, how these three processes are intertwined in mouse Leydig cells remains unclear. In this study, a mouse model of aging and hydrogen peroxide (HO)-induced senescent TM3 Leydig cells were used to dissect the connections among ER stress, circadian oscillators, and steroidogenesis in Leydig cells. Additionally, thapsigargin (Tg, 60 nM)/tunicamycin (Tm, 60 ng/mL)-induced ER stress were established to investigate the underlying mechanisms by which ER stress regulated testosterone synthesis via circadian clock-related signaling pathways in TM3 cells and primary Leydig cells. Elevated ER stress, attenuated circadian clock, and diminished steroidogenesis were detected in the testes of aged mice (24-month-old) and HO-induced (200 μM) senescent TM3 cells in comparison with their control groups. Tg/Tm-induced ER stress reduced the transcription of the circadian clock and steroidogenic genes in TM3 cells and LH-treated (100 ng/mL) primary Leydig cells. Furthermore, 4-phenylbutyric acid (4-PBA, 1 μM), an inhibitor of ER stress, alleviated the inhibitory effect of Tg-mediated ER stress on Per2:Luc oscillations in primary Leydig cells isolated from mPer2 knock-in mice, and attenuated the repressive effect of HO-induced or Tg-mediated ER stress on the transcription of circadian clock and steroidogenic genes expression and testosterone synthesis in TM3 cells. Collectively, these data indicate that age-related ER stress represses testosterone synthesis via attenuation of the circadian clock in Leydig cells.
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http://dx.doi.org/10.1016/j.theriogenology.2022.06.010DOI Listing
June 2022

The dephosphorylation of FADD at S191 induces an excessive expansion of TCRαβ IELs in the intestinal mucosa.

Immunology 2022 Jun 26. Epub 2022 Jun 26.

The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

Intestinal intraepithelial lymphocytes (IELs) play a crucial role in host defense against pathogens in the intestinal mucosa. The development of intestinal IELs is distinct from peripheral T lymphocytes and remains elusive. Fas-associated protein with death domain (FADD) is important for T cell development in the thymus. Here we describe a novel function of FADD in the IEL development. FADD (S191A), a mouse FADD mutant at Ser191 to Ala mimicking constitutively unphosphorylated FADD, promoted a rapid expansion of TCRαβ IELs, not TCRγδ IELs. Mechanism investigation indicated that the dephosphorylation of FADD was required for cell activation mainly in TCRαβ CD8 T cells. Consistently, FADD (S191A) as dephosphorylated FADD led to a high NF-κB activation in the TCR-dependent cell expansion. In addition, The FADD (S191A)-induced abnormal IEL populations resulted in the increased incidence and severity of colitis in mice. In summary, FADD signaling is involved in the intestinal IEL development and might be a regulator for intestinal mucosal homeostasis.
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http://dx.doi.org/10.1111/imm.13533DOI Listing
June 2022
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