Publications by authors named "Shuang Guo"

194 Publications

Insertional activation of and by HIV-1 proviruses in T cell lymphomas.

Sci Adv 2021 Oct 13;7(42):eabi8795. Epub 2021 Oct 13.

HIV Dynamics and Replication Program, CCR, National Cancer Institute, Frederick, MD, USA.

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http://dx.doi.org/10.1126/sciadv.abi8795DOI Listing
October 2021

Metabolites of gut microbiome are associated with glucose metabolism in non-diabetic obese adults: a Chinese monozygotic twin study.

Diabetol Metab Syndr 2021 Oct 9;13(1):106. Epub 2021 Oct 9.

Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.

Background: Evidence suggests gut microbiome is associated with diabetes. However, it's unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association.

Methods: Nine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites.

Results: The participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm vs. 150.8 ± 29.5 cm, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle.

Conclusions: Gut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.
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http://dx.doi.org/10.1186/s13098-021-00724-6DOI Listing
October 2021

Lipin modulates lipid metabolism during reproduction in the cabbage beetle.

Insect Biochem Mol Biol 2021 Oct 6;139:103668. Epub 2021 Oct 6.

Hubei Key Laboratory of Insect Resources Utilization and Sustainable Pest Management, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, PR China. Electronic address:

Lipids are a critical source of stored energy in insects, and their metabolism is essential for growth, development, and reproduction. Adequate provisioning of lipids and yolk proteins in the oocytes is essential to ensure reproductive output. Therefore, it is particularly important to understand the molecular mechanisms linking lipid metabolism and reproduction. Lipin proteins are emerging as pivotal modulators of lipid metabolism. They exert a dual function as phosphatidate phosphatase enzymes involved in lipid synthesis and as transcriptional coactivators of genes related to lipid metabolism. However, the functional relationship between lipid metabolism and reproduction remains unclear. In this study, the role of lipin protein in the reproduction of female cabbage beetle Colaphellus bowringi was examined. It was found that Lipin was broadly expressed in the tissues of adult females, with relatively high transcript levels in the head, midgut, fat body, malpighian tubules, and epidermis. RNA interference experiments were conducted using double-stranded RNA against Lipin in C. bowringi females. Lipin silencing blocked ovarian development and strongly suppressed transcription of vitellogenin and vitellogenin receptor genes. In addition, the reduction in Lipin expression led to a rapid increase in lipid storage in the fat body and also promoted the expression of genes related to lipid synthesis and stress tolerance. Overall, these results suggest that a Lipin-mediated lipolytic system is essential for maintaining lipid homeostasis during reproduction in C. bowringi. The findings of this study provide a foundation for future studies on the relationship between lipid metabolism and reproduction in invertebrates.
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http://dx.doi.org/10.1016/j.ibmb.2021.103668DOI Listing
October 2021

The elderly harbor greater proportions of advanced histology in subcentimeter adenomas: implications for screening colonoscopy approaches.

Eur J Gastroenterol Hepatol 2021 Sep 28. Epub 2021 Sep 28.

Department of Gastroenterology Department of Pathology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Screening and surveillance for colorectal cancer can reduce both the incidence of this disease and mortality rates attributed to it. Normally, surveillance intervals should be based on baseline colonoscopy findings, and clinicians focus on advanced polyps and perform patient risk stratification to devise surveillance schedules. The aim of the study was to determine differences in advanced colorectal polyp characteristics and consequent risk stratifications in patients of different age groups.

Material And Methods: We retrospectively reviewed 14 312 patients during a 5-year period; a total of 13 842 polyps were stratified by their sizes, locations, and histologies. Participants were categorized into three age groups, the <45 years group, the 45-59 years group and the >59 years group, and each group was further stratified as normal, low risk, and high risk.

Results: The <45 years group included 2431 subjects, the 45-59 years group 6258 subjects, and the >59 years group 5623 subjects. The frequency of adenoma and advanced polyps in the proximal colon slightly increased with age. Only 1.0% in the <45 years and 1.3% in the 45-59 years groups of subcentimeter polyps were identified as advanced polyps, less than that in the >59 years group (2.1%). Most patients, especially the elderly, considered as high risk had multiple subcentimeter adenomas.

Conclusion: The processing strategy proposed for subcentimeter polyps in the elderly still needs to be further explored in the future. Clinicians should recognize the importance of performing a detailed scan of the entire colon.
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http://dx.doi.org/10.1097/MEG.0000000000002284DOI Listing
September 2021

Comprehensive characterization genetic regulation and chromatin landscape of enhancer-associated long non-coding RNAs and their implication in human cancer.

Brief Bioinform 2021 Sep 28. Epub 2021 Sep 28.

College of Bioinformatics Science and Technology, Harbin Medical University, China.

Long non-coding RNAs (lncRNAs) that emanate from enhancer regions (defined as enhancer-associated lncRNAs, or elncRNAs) are emerging as critical regulators in disease progression. However, their biological characteristics and clinical relevance have not been fully portrayed. Here, based on the traditional expression quantitative loci (eQTL) and our optimized residual eQTL method, we comprehensively described the genetic effect on elncRNA expression in more than 300 lymphoblastoid cell lines. Meanwhile, a chromatin atlas of elncRNAs relative to the genetic regulation state was depicted. By applying the maximum likelihood estimate method, we successfully identified causal elncRNAs for protein-coding gene expression reprogramming and showed their associated single nucleotide polymorphisms (SNPs) favor binding of transcription factors. Further epigenome analysis revealed two immune-associated elncRNAs AL662844.4 and LINC01215 possess high levels of H3K27ac and H3K4me1 in human cancer. Besides, pan-cancer analysis of 3D genome, transcriptome, and regulatome data showed they potentially regulate tumor-immune cell interaction through affecting MHC class I genes and CD47, respectively. Moreover, our study showed there exist associations between elncRNA and patient survival. Finally, we made a user-friendly web interface available for exploring the regulatory relationship of SNP-elncRNA-protein-coding gene triplets (http://bio-bigdata.hrbmu.edu.cn/elncVarReg). Our study provides critical mechanistic insights for elncRNA function and illustrates their implications in human cancer.
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http://dx.doi.org/10.1093/bib/bbab401DOI Listing
September 2021

A Novel Recombinant Virus-Like Particles Displaying B and T Cell Epitopes of Japanese Encephalitis Virus Offers Protective Immunity in Mice and Guinea Pigs.

Vaccines (Basel) 2021 Sep 2;9(9). Epub 2021 Sep 2.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

Virus-like particles (VLPs) are non-replicative vectors for the delivery of heterologous epitopes and are considered one of the most potent inducers of cellular and humoral immune responses in mice and guinea pigs. In the present study, VLP-JEVe was constructed by the insertion of six Japanese encephalitis virus (JEV) envelope protein epitopes into different surface loop regions of PPV VP2 by the substitution of specific amino acid sequences without altering the assembly of the virus; subsequently, the protective efficacy of this VLP-JEVe was evaluated against JEV challenge in mice and guinea pigs. Mice immunized with the VLP-JEVe antigen developed high titers of neutralizing antibodies and 100% protection against lethal JEV challenge. The neutralizing and hemagglutination inhibition (HI) antibody responses were also induced in guinea pigs vaccinated with VLP-JEVe. In addition, immunization with VLP-JEVe in mice induced effective neutralizing antibodies and protective immunity against PPV (porcine parvovirus) challenge in guinea pigs. These studies suggest that VLP-JEVe produced as described here could be a potential candidate for vaccine development.
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http://dx.doi.org/10.3390/vaccines9090980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473392PMC
September 2021

Juvenile hormone biosynthetic genes are critical for regulating reproductive diapause in the cabbage beetle.

Insect Biochem Mol Biol 2021 Sep 24;139:103654. Epub 2021 Sep 24.

Hubei Key Laboratory of Resources Utilization and Sustainable Pest Management, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address:

In insects, the juvenile hormone (JH) biosynthetic pathway regulates the in vivo JH titer. Thus, its downregulation potentially contributes to the lowering of JH titers typically observed in insects undergoing reproductive diapause, a developmental arrest at the adult stage. However, no systematic evidence has yet been presented to demonstrate the physiological and genetic roles of JH biosynthetic genes in reproductive diapause. In this work, we performed RNA interference (RNAi)-based reverse genetic analyses by targeting JH biosynthetic genes, followed by analysis of the reproductive diapause traits in Colaphellus bowringi, an economically important cabbage beetle. We identified a total of 22 genes encoding homologues of enzymes involved in the mevalonate pathway and the JH branch of JH biosynthesis in C. bowringi. Among these, 18 genes showed significant downregulation of their expression in the long day-induced diapausing females, compared to the short day-induced reproductive females. RNAi knockdown of almost any one of the 18 genes in reproductive females reduced the expression of the JH-responsive gene, Krüppel homolog1 (Kr-h1), indicating a lowered circulating JH. Most importantly, depleting transcripts of 3-hydroxy-3-methylglutaryl-CoA reductase 2 (HMGR2), farnesyl-pyrophosphate synthase 1 (FPPS1) and juvenile hormone acid methyltransferase 1 (JHAMT1) induced diapause-associated traits, including immature and inactive ovaries, large accumulations of lipids and adult burrowing behavior. Meanwhile, genes related to ovarian development, lipid accumulation and stress response showed expression patterns like those of diapausing females. RNAi-mediated diapause phenotypes could be reversed to reproductive phenotypes by application of methoprene, a JH receptor agonist. These results suggest that photoperiodic reproductive diapause in C. bowringi is triggered by transcriptional suppression of JH biosynthetic genes, with HMGR2, FPPS1 and JHAMT1 playing a critical role in this process. This work provides sufficient evidence to reveal the physiological roles of JH biosynthetic genes in reproductive diapause.
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http://dx.doi.org/10.1016/j.ibmb.2021.103654DOI Listing
September 2021

DNA methylation dynamics of long noncoding RNA during human fetal development.

Epigenomics 2021 Sep 24;13(17):1347-1358. Epub 2021 Sep 24.

College of Bioinformatics Science & Technology, Harbin Medical University, Harbin, 150081, China.

To determine whether the promoters of long noncoding RNAs (lncRNAs) undergo dynamic changes in DNA methylation during fetal development. ANOVA and the tissue specificity index were used to identify and validate tissue-specific methylation sites. Age-associated DNA methylation signatures were identified by applying the elastic net method. The lncRNA methylome landscape was characterized in four types of fetal tissue and at three gestational time points, and specific characteristics relative to the tissue of origin and developmental age were identified. Higher levels of lncRNA methylation might be involved in tissue differentiation. LncRNAs harboring age-associated methylation signatures may participate in the fetal developmental process. This study provides novel insights into the role of lncRNA methylomes in fetal tissue specification and development.
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http://dx.doi.org/10.2217/epi-2021-0159DOI Listing
September 2021

Trapping analytes into dynamic hot spots using Tyramine-medicated crosslinking chemistry for designing versatile sensor.

J Colloid Interface Sci 2021 Sep 8;607(Pt 1):782-790. Epub 2021 Sep 8.

Department of Chemistry, Institute for Molecular Science and Fusion Technology, Kangwon National University Chuncheon 24341, Republic of Korea; Kangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address:

Hypothesis: Due to the intrinsic nature of the surface-enhanced Raman scattering (SERS), the detection of molecules with weak binding affinities toward metal substrates is critical for development of a universal SERS sensing platform. We hypothesized the physical trapping of small pesticide molecules for active hot spot generation using tyramine-mediated crosslinking chemistry and silver nanoparticles (Ag NPs) enhances SERS detection sensitivity.

Experiments: Tyramine-mediated crosslinking chemistry for sensor application was validated by ultraviolet-visible absorption spectroscopy, scanning electron microscopy, dynamic light scattering, and Raman spectroscopy. SERS sensing platform using tyramine-mediated crosslinking reaction was systematically studied for detection of 1,4-dyethylnylbenzene as a model analyte. This sensor system was applied to detect two other pesticides, thiabendazole and 1,2,3,5-tetrachlorobenzene, which have different binding affinities toward metal surfaces.

Findings: The SERS signal of 1,4-dyethylnylbenzene obtained using this sensor system was 3.6 times stronger than that obtained using the Ag colloidal due to the nanogap of approximately 1.3 nm within the generated hot spots. This sensor system based on tyramine-mediated crosslinked Ag NPs was evaluated as a promising tool to achieve a solution based sensitive detection of various pesticide molecules that cannot be adsorbed on the surfaces of typical SERS substrates such as metal nanoparticles.
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http://dx.doi.org/10.1016/j.jcis.2021.09.037DOI Listing
September 2021

Mucoadhesive versus mucopenetrating nanoparticles for oral delivery of insulin.

Acta Biomater 2021 Sep 4. Epub 2021 Sep 4.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address:

Mucoadhesive and mucopenetrating nanoparticles are commonly designed to improve mucosal drug delivery efficiency. Herein, in order to better understand the contribution of mucoadhesion and mucopenetration in oral delivery of biomacromolecules, insulin-loaded poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) with different coating layers, chitosan (CS) or alginate (Alg), were designed and their different absorption enhancing mechanisms were explored. It was demonstrated that both the mucoadhesive (Ins/PBCA/CS) and the mucopenetrating (Ins/PBCA/CS/Alg) nanoparticles showed good stability and similar release profiles in the gastrointestinal fluid, the mucoadhesive nanoparticles presented an enrichment in mucus (70%, 10 min) while most of the mucopenetrating nanoparticles penetrated through the mucus (80%, 10 min). Uptake mechanism studies revealed clathrin- and caveolae-mediated endocytosis were mainly involved in the intestinal transport of mucoadhesive nanoparticles while caveolae-mediated endocytosis and macropinocytosis contributed to the absorption of mucopenetrating nanoparticles, and especially, M cells favored the absorption of mucoadhesive nanoparticles. In vivo studies revealed that the mucopenetrating nanoparticles had a fast onset of action while the mucoadhesive nanoparticles presented a sustained hypoglycemic effect in diabetic rats, and overall no significant difference in pharmacological availability was found between the mucopenetrating (8.80%) and mucoadhesive nanoparticles (8.44%). To sum up, due to the varied absorption mechanism in intestine, the mucoadhesive nanoparticles designed herein had a comparable effect in enhancing oral insulin absorption compared with the mucopenetrating nanoparticles. STATEMENT OF SIGNIFICANCE: In order to improve oral delivery efficiency of insulin, insulin-loaded nanoparticles with opposite properties namely mucoadhesion and mucopenetration have been widely developed to either prolong their residence at the absorption site or improve their penetration across mucus. However, their individual contribution in oral insulin absorption is still unclear. In this paper, insulin-loaded poly (n-butylcyanoacrylate) nanoparticles with both properties were designed via different surface coating and their absorption enhancing mechanisms were explored. It was demonstrated that the mucoadhesive and mucopenetrating nanoparticles showed varied retention and mucus-penetration ability in mucus, with different absorption mechanism in intestine, but no statistical difference in pharmacological availability was found between them. Overall, the present work provides us a guidance for the design of oral nano-delivery system.
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http://dx.doi.org/10.1016/j.actbio.2021.08.046DOI Listing
September 2021

Fingerprints and changes analysis of volatile compounds in fresh-cut yam during yellowing process by using HS-GC-IMS.

Food Chem 2021 Aug 25;369:130939. Epub 2021 Aug 25.

Beijing Vegetable Research Center, Beijing Academy of Agriculture and Forestry Sciences, Beijing Key Laboratory of Agricultural Products of Fruits and Vegetables Preservation and Processing, Key Laboratory of Vegetable Postharvest Processing, Ministry of Agriculture and Rural Affairs, Beijing 100097, China. Electronic address:

The purpose of this study was to investigate the dynamic change in volatile components during the yellowing process. The volatile components were analyzed by headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) and the critical enzyme activities were determined by commercial kits. The results revealed that 29 signal peaks for 20 compounds were identified, which were quantified in all samples: 1 furan, 1 ester, 15 aldehydes, 3 ketones, and 9 alcohols. The contents of most of these compounds increased first and then decreased at 36 h, which were basically consistent with the enzyme activities of LOX, HPL, ADH and AAT. Subsequently, principal component analysis (PCA) results clearly showed that the fresh-cut yams for different yellowing processes were well distinguished by the volatile compounds. These results showed that the potential of HS-GC-IMS-based approaches to evaluate the volatile compound profiles of fresh-cut yam at different stages in the yellowing period.
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http://dx.doi.org/10.1016/j.foodchem.2021.130939DOI Listing
August 2021

Phosphocreatine attenuates doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and activating TAK1 to promote myocardial survival in vivo and in vitro.

Toxicology 2021 08 3;460:152881. Epub 2021 Aug 3.

Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Hubei University of Science and Technology, Xianning, 437100, China; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, China, 430062. Electronic address:

Myocardial apoptosis and necroptosis are the major etiological factor during doxorubicin (DOX) induced cardiotoxicity, and one of the important reasons that limit the drug's clinical application. Up to date, its mechanism has not been fully elucidated. The protective role of phosphocreatine (PCr) in heart surgery and medical cardiology has been observed in numerous clinical trials. This study aimed to evaluate cardioprotective actions of PCr against DOX-induced cardiotoxicity and investigate the underlying mechanism involving in transforming growth factor β-activated kinase 1 (TAK1) mediated myocardial survive signaling pathway. Male Sprague-Dawleyrats were intraperitoneally (ip) injected with normal saline (NS) or DOX (2 mg/kg) alone or DOX with PCr (200 mg/kg) used as animal model. The data showed that DOX significantly impaired cardiac function and structure, induced oxidative stress, myocardial apoptosis and necroptosis, and dramatically down-regulated the expression level of TAK1, while the intervention of PCr obviously attenuated cardiac dysfunction, oxidative stress, myocardial apoptosis and necroptosis, especially alleviated the decrease of TAK1 expression. In vitro analysis, after H9c2 cells were pretreated with or without PCr (0.5 mM) or N-Acetyl-L-cysteine (NAC, 0.5 mM) or 5Z-7-oxozeaenol (5z-7-Ox, 1 μM) for 1 h, subsequently treated with DOX (1 μM) for 24 h. The results revealed that inhibition of TAK1 further deteriorated apoptotic and necroptotic cell death induced by DOX in H9c2 cells, but didn't affect oxidative stress. While the pretreatment of PCr or NAC enhanced antioxidant activity to reduce oxidative stress, significantly alleviated apoptotic and necroptotic cell death induced by DOX in H9c2 cells. Consistent with the results in vivo, PCr or NAC significantly inhibited the decrease of TAK1 expression induced by DOX. In conclusion, oxidative stress induced by DOX inhibits the expression of TAK1, and leads to myocardial apoptotic and necroptotic death, while the intervention of PCr increases antioxidant activity to alleviate oxidative stress, which in turn activates TAK1 signaling pathway to promote myocardial survival, and finally attenuate DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1016/j.tox.2021.152881DOI Listing
August 2021

Effects of highly selective sympathectomy on neurogenic bowel dysfunction in spinal cord injury rats.

Sci Rep 2021 08 5;11(1):15892. Epub 2021 Aug 5.

School of Rehabilitation Medicine, Capital Medical University, No. 10, Jiao Men Bei Lu, Fengtai District, Beijing, 100068, China.

Neurogenic bowel dysfunction, including hyperreflexic and areflexic bowel, is a common complication in patients with spinal cord injury (SCI). We hypothesized that removing part of the colonic sympathetic innervation can alleviate the hyperreflexic bowel, and investigated the effect of sympathectomy on the hyperreflexic bowel of SCI rats. The peri-arterial sympathectomy of the inferior mesenteric artery (PSIMA) was performed in T8 SCI rats. The defecation habits of rats, the water content of fresh faeces, the intestinal transmission function, the defecation pressure of the distal colon, and the down-regulation of Alpha-2 adrenergic receptors in colon secondary to PSIMA were evaluated. The incidence of typical hyperreflexic bowel was 95% in SCI rats. Compared to SCI control rats, PSIMA increased the faecal water content of SCI rats by 5-13% (P < 0.05), the emptying rate of the faeces in colon within 24 h by 14-40% (P < 0.05), and the defecation pressure of colon by 10-11 mmHg (P < 0.05). These effects lasted for at least 12 weeks after PSIMA. Immunofluorescence label showed the secondary down-regulation of Alpha-2 adrenergic receptors after PSIMA occurred mainly in rats' distal colon. PSIMA mainly removes the sympathetic innervation of the distal colon, and can relieve the hyperreflexic bowel in rats with SCI. The possible mechanism is to reduce the inhibitory effect of sympathetic activity, and enhance the regulatory effect of parasympathetic activity on the colon. This procedure could potentially be used for hyperreflexic bowel in patients with SCI.
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http://dx.doi.org/10.1038/s41598-021-95158-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342507PMC
August 2021

Modulating Mechanism of the LSPR and SERS in Ag/ITO Film: Carrier Density Effect.

J Phys Chem Lett 2021 Aug 5;12(31):7612-7618. Epub 2021 Aug 5.

Department of Chemistry, Institute for Molecular Science and Fusion Technology, Kangwon National University, Chuncheon 24341, Korea.

Herein, we fabricated a uniform and dispersible Ag/indium tin oxide (ITO) cosputtered film on a two-dimensional ordered polystyrene template and observed distinct localized surface plasmon resonance (LSPR) properties that can be tuned by changing the doping level. The increase in the optical band gap is due to the variation in the metallic Ag content, which can effectively change the accumulation of free electrons in the conduction band, in addition to the near-IR absorbance. Surface-enhanced Raman scattering (SERS) was used to monitor the variations in the band gap and transfer of electrons, which causes variations in the SERS intensity. The presented research provides new insights into the relationships between the carrier density and maximum absorption wavelength, band gap distribution, and charge transfer process. This is the first study on the influence of the carrier density on the properties of Ag/ITO cosputtered films and suggests practical applications of these films.
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http://dx.doi.org/10.1021/acs.jpclett.1c01727DOI Listing
August 2021

Saxagliptin protects against diabetic nephropathy by inhibiting caspase 3/PARP-1-dependent nephrocyte apoptosis.

Exp Ther Med 2021 Sep 14;22(3):990. Epub 2021 Jul 14.

Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China.

Saxagliptin (SAX) can protect against tissue damage caused by diabetic nephropathy. However, whether this compound can restore kidney function, and its specific mechanism of action remain unclear. The present study explored the therapeutic effects and mechanisms of SAX. Male Wistar rats (8 weeks old) were randomly divided into the following groups: A control group (n=10); a group with streptozocin-induced diabetes mellitus (DM) treated with saline (n=20); and a group with streptozocin-induced DM treated with SAX (n=20). Following 20 weeks of treatment, renal function and the extent of renal damage were assessed based on histological staining using hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome staining. The experimental results indicated that Streptozocin induction of DM led to thicker basement membranes in mesangial cells and a more abundant extracellular matrix. These changes were ameliorated following treatment with SAX. The data demonstrated that renal tissue and renal cell apoptosis were ameliorated significantly following treatment with SAX. Furthermore, the expression levels of the apoptotic genes poly (ADP-ribose) polymerase-1 (PARP-1) and caspase 3 were significantly decreased following treatment with SAX. Therefore, SAX may reduce the extent of renal apoptosis and pathological outcomes in diabetic nephropathy by downregulating the expression of caspase 3 and PARP-1 in the death receptor pathway of apoptosis.
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http://dx.doi.org/10.3892/etm.2021.10422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311252PMC
September 2021

Quantification and discovery of quality control chemical markers for Ba-Bao-Dan by UPLC-MS/MS combined with chemometrics.

J Pharm Biomed Anal 2021 Sep 21;204:114273. Epub 2021 Jul 21.

College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China. Electronic address:

Ba-Bao-Dan (BBD) is a well-known Traditional Chinese medicine (TCM) prescription in China. It was first formulated in approximately 1555 AD. As one of the National Protected TCM, it is widely used to treat jaundice, viral hepatitis, cholecystitis, acute urinary tract infection, cancer, and other diseases. It is a healthcare medicine that is used to prevent many diseases in China. In other Asian countries and in European and American countries, BBD is used as a drug to protect the liver. However, a systematic quality study on BBD chemical markers has not been carried out. This study aimed to establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method for the quantitative determination of 43 compounds in BBD. Furthermore, the method was used to further find chemical markers for quality control through the combination with chemometrics. The modified chromatographic conditions were achieved on Waters Cortecs C column (2.1 × 100 mm, 1.6 μm) with a gradient elution consisting of 0.1 % formic acid in water and acetonitrile with methanol (1:1, V/V). All analytes were determined in the multiple reaction monitoring mode. The method was validated for linearity, detection limits, precision, repeatability, stability and accuracy. The method was used to analyze the 43 compounds in 11 batches of BBD samples. Hierarchical cluster analysis and principal component analysis were applied to evaluate intrinsic quality of BBD and to identify the potential chemical markers for quality control. In conclusion, the method rapidly and sensitively determined the 43 compounds, among which 10 compounds, namely, N-Gin R1, Gin Re, Gin Rg1, Gin Rb1, GCA, Gin Rd, CA, TCA, CDCA, and DCA, were considered as the potential chemical markers for BBD quality control.
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http://dx.doi.org/10.1016/j.jpba.2021.114273DOI Listing
September 2021

Prevalence and Characteristics of Rheumatoid-Associated Autoantibodies in Patients with COVID-19.

J Inflamm Res 2021 12;14:3123-3128. Epub 2021 Jul 12.

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.

Objective: Patients with rheumatic immune diseases were more likely to develop severe or critical COVID-19. We aimed to determine whether rheumatoid factor antibodies were present in COVID patients and the level and type of rheumatoid factor antibodies produced in COVID-19 patients were related to the degree of the patient's condition. The study also aimed to determine the prevalence and characteristics of rheumatoid factor antibodies in patients with COVID-19.

Methods: Sera collected from 129 patients with COVID-19 were tested for rheumatoid factor antibodies by ELISA. Five patients were tracked for several months to monitor dynamic changes of these antibodies.

Results: Rheumatoid-associated autoantibodies were detected in 20.16% of patients (26/129) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, IgM-RF was primarily present in critically ill patients, while IgA-RF was mainly present in mild patients. Five patients were able to track for several months to monitor dynamic changes of these antibodies. Rheumatoid factor antibodies peaks in the later phase of the disease and last for longer time. Anti-Jo-1 antibody was found in one of the five patients.

Conclusion: This was the case series report that rheumatoid-associated autoantibodies are present in patients with COVID-19. The clinical significance of these antibodies was not fully understood and needed further characterization. These autoantibodies are related to the severity of the patient's disease and exist for a long time in the patient's body, while their impact on the patient's health is unknown.
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http://dx.doi.org/10.2147/JIR.S312090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286246PMC
July 2021

Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR.

Viruses 2021 Jun 25;13(7). Epub 2021 Jun 25.

Department of Medicine, University of Pittsburgh, 3550 Terrace Street, Scaife Hall-818, Pittsburgh, PA 15261, USA.

Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed . The digital droplet PCR assays commonly used to quantify intact proviruses do not differentiate among specific repliclones, thus the dynamics of repliclones are not well defined. The major challenge in tracking repliclones is the relative rarity of the cells carrying specific intact proviruses. To date, detection and accurate quantification of repliclones requires in-depth integration site sequencing. Here, we describe a simplified workflow using integration site-specific qPCR (IS-qPCR) to determine the frequencies of the proviruses integrated in individual repliclones. We designed IS-qPCR to determine the frequencies of repliclones and clones of cells that carry defective proviruses in samples from three donors. Comparing the results of IS-qPCR with deep integration site sequencing data showed that the two methods yielded concordant estimates of clone frequencies ( = 0.838). IS-qPCR is a potentially valuable tool that can be applied to multiple samples and cell types over time to measure the dynamics of individual repliclones and the efficacy of treatments designed to eliminate them.
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http://dx.doi.org/10.3390/v13071235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310066PMC
June 2021

Association between serum 25-hydroxyvitamin D concentrations and obesity in one-year-old Chinese infants.

Food Sci Nutr 2021 Jun 3;9(6):3191-3199. Epub 2021 May 3.

Department of Epidemiology and Biostatics Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases School of Public Health Medical College of Soochow University Suzhou China.

Recent studies suggested that vitamin D is linked with obesity, but evidence in infants is scarce. Therefore, we aimed to make an exploration in infants. A total of 414 infants at one year old who visited Maternity and Child Health Care Hospital of Wuxi in China were recruited. Finger-stick blood sampling was conducted in all the subjects, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured. Maternal characteristics during pregnancy and infantile information were collected by questionnaires or extracting from medical records. Multivariable linear models were performed to assess the relationship between 25(OH)D and body mass index (BMI), while multivariable logistic regression models were used to examine the association between 25(OH)D and obesity. Among the 414 infants, 69 (16.67%) and 81 (19.57%) infants were defined as obesity and vitamin D deficiency [25(OH)D < 50 nmol/L], respectively. The mean () of 25(OH)D concentration was 68.05 (19.05) in infants without obesity, which was significantly higher than that of obese infants [60.36(18.49),  = .002]. Inverse linear relationships were observed between 25(OH)D level and BMI ( = -0.017,  = .004) as well as BMI -score ( = -0.010,  = .004). Furthermore, vitamin D deficiency was associated with an increased risk of obesity of infants (adjusted odds ratio = 2.74, 95% confidence interval = 1.20-6.25, with 25(OH)D ≥ 75 nmol/L as a reference). The results showed that serum 25(OH)D concentrations were significantly lower in infants with obesity, suggesting vitamin D deficiency may be an independent risk factor for obesity among one-year-old Chinese infants.
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http://dx.doi.org/10.1002/fsn3.2279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194735PMC
June 2021

Resveratrol-mediated neurorestoration after cerebral ischemic injury - Sonic Hedgehog signaling pathway.

Life Sci 2021 Sep 8;280:119715. Epub 2021 Jun 8.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Aims: Resveratrol pretreatment can decrease ischemic cerebral injury and enhance proliferation of neural stem cells via mediation of Sonic Hedgehog signaling. However, it is relatively little known about whether neurorestorative effects of resveratrol are mediated by Shh signaling in ischemic cerebral injury. The present study tests whether the Shh signaling pathway mediates resveratrol to promote neurorestoration of ischemic cerebral injury.

Materials And Methods: Rats or neurons before middle cerebral artery occlusion/reperfusion (MCAO/R) or oxygen-glucose deprivation/reoxygenation (OGD/R) injury were pretreated with resveratrol. Immunohistochemistry is used to be determined BrdU+/DCX+, BrdU+/Nestin+ and BrdU+/NG2+ cell (markers of new proliferated neural stem/progenitor and oligodendrocyte precursor cell, respectively), BrdU+/MAP2+ and BrdU+/CNPase+ cell (markers of new mature neuron and oligodendrocyte, respectively), BrdU+/TUNEL+ cell (marker of apoptosis for new proliferated cell), SY, NF200, Iba-1 and GFAP (markers of synaptogenesis, axon, microglia and astrocyte, respectively). Shh and Gli-1 mRNAs were detected by RT-PCR assay. Iba-1, GFAP, Shh and Gli-1 proteins were detected by Western blot.

Key Findings: Resveratrol pretreatment significantly reduced neurological deficit scores, promoted proliferation, differentiation, migration and survival of neural stem/progenitor and oligodendrocyte precursor cells, inhibited astrocyte and microglia activation, strengthened synaptophysin and NF200 expression, at the same time, promoted neurite outgrowth of neurons. Meanwhile, expression levels of Shh and Gli-1 proteins were significantly increased and Gli-1 translocated into the nucleus. However, cyclopamine, a Smo inhibitor, canceled the above effects of resveratrol.

Conclusions: It may be mediated, at least partly, by the Shh signaling pathway that resveratrol pretreament promote neurorestoration of ischemic cerebral injury.
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http://dx.doi.org/10.1016/j.lfs.2021.119715DOI Listing
September 2021

Four new secoiridoids from the stem barks of (Bl.) Hara.

Nat Prod Res 2021 Jun 6:1-10. Epub 2021 Jun 6.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, People's Republic of China.

Four new secoiridoids, syrretoside A (), syrretoside B (), 5, 8-syrretaglucone C(), 5, 8-syrretaglucone C (), together with eight known secoiridoids (-), were isolated from the stem barks of (Bl.) Hara. The structures of isolated compounds were established based on the physical and chemical means, NMR spectroscopy, high-resolution mass spectrometry (HR-ESI-MS), and circular dichroism spectrum (CD), as well as in comparison with the literature. The cytotoxicity of isolated compounds was investigated using CCK8 assay, which showed that these compounds had different degrees of inhibitory effect on two human tumor (MGC803, LN229) cell lines.
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http://dx.doi.org/10.1080/14786419.2021.1914031DOI Listing
June 2021

MeImmS: Predict Clinical Benefit of Anti-PD-1/PD-L1 Treatments Based on DNA Methylation in Non-small Cell Lung Cancer.

Front Genet 2021 20;12:676449. Epub 2021 May 20.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Immunotherapy has become an effective therapy for cancer treatment. However, the development of biomarkers to predict immunotherapy response still remains a challenge. We have developed the DNA Methylation Immune Score, named "MeImmS," which can predict clinical benefits of non-small cell lung cancer (NSCLC) patients based on DNA methylation of 8 CpG sites. The 8 CpG sites regulate the expression of immune-related genes and MeImmS was related to immune-associated pathways, exhausted T cell markers and immune cells. Copy-number loss in 1p36.33 may affect the response of cancer patients to immunotherapy. In addition, SAA1, CXCL10, CCR5, CCL19, CXCL11, CXCL13, and CCL5 were found to be key immune regulatory genes in immunotherapy. Together, MeImmS discovered the heterogeneous of NSCLC patients and guided the immunotherapy of cancer patients in the future.
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http://dx.doi.org/10.3389/fgene.2021.676449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173132PMC
May 2021

Charge-Transfer Induced by the Oxygen Vacancy Defects in the Ag/MoO Composite System.

Nanomaterials (Basel) 2021 May 14;11(5). Epub 2021 May 14.

Department of Chemistry, Institute for Molecular Science and Fusion Technology, Kangwon National University, Chunchon 24341, Korea.

In this paper, an Ag/MoO composite system was cosputtered by Ar plasma bombardment on a polystyrene (PS) colloidal microsphere array. The MoO formed by this method contained abundant oxygen vacancy defects, which provided a channel for charge transfer in the system and compensated for the wide band gap of MoO. Various characterization methods strongly demonstrated the existence of oxygen vacancy defects and detected the properties of oxygen vacancies. 4-Aminothiophenol (p-aminothiophenol, PATP) was used as a candidate surface-enhanced Raman scattering (SERS) probe molecule to evaluate the contribution of the oxygen vacancy defects in the Ag/MoO composite system. Interestingly, oxygen vacancy defects are a kind of charge channel, and their powerful effect is fully reflected in their SERS spectra. Increasing the number of charge channels and increasing the utilization rate of the channels caused the frequency of SERS characteristic peaks to shift. This interesting phenomenon opens up a new horizon for the study of SERS in oxygen-containing semiconductors and provides a powerful reference for the study of PATP.
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http://dx.doi.org/10.3390/nano11051292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156517PMC
May 2021

Calcium Channel Subunit α2δ-1 as a Potential Biomarker Reflecting Illness Severity and Neuroinflammation in Patients with Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Aug 25;30(8):105874. Epub 2021 May 25.

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China. Electronic address:

Background: Voltage-gated calcium channels (VGCCs) dysfunction is involved in the development of acute ischemic stroke (AIS). As a subunit of VGCC complexes, we detected the levels of α2δ-1 subunit in serum and cerebrospinal fluid (CSF) specimens from AIS patients.

Methods: The study included 105 patients with first-ever AIS, who were admitted within 48 hours after stroke onset. The serum and CSF levels of α2δ-1 were measured with ELISA and the severity of AIS patients was evaluated according to the National Institutes of Health Stroke Scale (NIHSS) score. The cerebral infarct volume was calculated through the Pullicino formula based on the cranial CT or MRI scan. C-reactive protein (CRP) and serum amyloid A (SAA) were measured using the latex-enhanced immunoturbidimetric assay.

Results: Compared to the control subjects, the serum α2δ-1 level was significantly increased in AIS patients with large infarct volume and in severe AIS cases with high NIHSS score, which correlated positively with the inflammatory markers CRP and SAA. Furthermore, the concentration of α2δ-1 in CSF was elevated with the infarct volume, which was higher in severe AIS patients.

Conclusion: Our study suggests that the increased α2δ-1 levels in serum and CSF specimens may be used as a potential marker for reflecting VGCCs dysfunction, illness severity and neuroinflammation in AIS patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105874DOI Listing
August 2021

A mutational signature for colorectal cancer prognosis prediction: Associated with immune cell infiltration.

Clin Transl Med 2021 05;11(5):e414

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1002/ctm2.414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101534PMC
May 2021

Risk of venous thromboembolism and endocrine therapy in older women with breast cancer in the United States.

Blood Coagul Fibrinolysis 2021 Sep;32(6):373-381

Division of Hematology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

Our aim was to evaluate the risk of venous thromboembolism (VTE) with tamoxifen and aromatase inhibitor in older women with breast cancer in the United States. The SEER-Medicare-linked database (2007--2013) was used for women of at least 65 years of age diagnosed with breast cancer in the United States. Logistic regression was used to examine unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CIs) for the risk of VTE. There were 178 059 women aged at least 65 years with breast cancer in the United States. Twenty-two thousand and forty-two (12.4%) women received tamoxifen, 64 384 (36.2%) women received aromatase inhibitors and 17 419 (9.8%) women received chemotherapy. Adjusted OR = 1.18 (95% CI 1.05--1.32) for VTE with tamoxifen for 3 years or less compared with tamoxifen use more than 3 years and OR = 1.07 (95% CI 1.05--1.16) for VTE with aromatase inhibitors 4 years or less compared with aromatase inhibitors use for more than 4 years. White women had OR = 1.19 (95% CI 1.05--1.35) and black women had OR = 1.07 (95% CI 0.76--1.51) for VTE with 3 years or less tamoxifen use compared with longer use. White women had OR = 1.09 (95% CI 1.00--1.18) and black women had OR = 1.07 (95% CI 0.86--1.34) for VTE with 4 years or less aromatase inhibitors use compared with longer use. Chemotherapy was associated with an increased risk of VTE (OR = 1.77, 95% CI 1.69--1.86). Chemotherapy combined with tamoxifen had OR = 1.64 (95% CI 1.45--1.86) and chemotherapy combined with aromatase inhibitors had OR = 1.71 95% CI 1.59-1.84). The study may help to identify a treatment profile for VTE risk that may facilitate VTE prevention.
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http://dx.doi.org/10.1097/MBC.0000000000001043DOI Listing
September 2021

Inhibition of PI3K/Akt/mTOR pathway by ammonium chloride induced apoptosis and autophagy in MAC-T cell.

Res Vet Sci 2021 May 29;136:622-630. Epub 2021 Jan 29.

Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou, Henan, China. Electronic address:

Ammonia is a harmful gas with a pungent odor, participates in the regulation of a variety of apoptosis and autophagy, which in turn affects the growth and differentiation of cells. To test the regulation of NH on the apoptosis and autophagy of mammary epithelial cells, we selected NHCl as NH donor in vitro model. MTT and CCK-8 assay kits were employed to detect cell activity. Real-time quantitative PCR and western blot methods were used to detect the abundance of inflammatory molecules, apoptosis markers, and autophagy genes. We selected TUNEL kit and the Annexin-FITC/PI method to detect apoptosis. TEM analysis was used to detect autophagic vesicles, and MDC stain evaluated the formation of autophagosome. The results indicated that NHCl reduced cell viability in a concentration-dependent manner and promoted cell inflammatory response, apoptosis, and autophagy. NHCl stimulation notable increased the autophagosomes number. Interestingly, we also detected that the addition of LY294002 and Rapamycin inhibited the PI3K/Akt pathway and the mTOR pathway, respectively, resulting in changes in both apoptosis and autophagy. Therefore, we draw a conclusion that NH may regulate the apoptosis and autophagic response of bovine mammary epithelial cells through the PI3K/Akt/mTOR signaling pathway. Further investigations on ammonia's function in other physiological respects, will be critical to provide theoretical help for the improvement of production performance. It will be also helpful for controlling the harmful gas ammonia concentration in the livestock house to protect the health of dairy cows.
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http://dx.doi.org/10.1016/j.rvsc.2021.01.020DOI Listing
May 2021

Krüppel homolog 1 regulates photoperiodic reproductive plasticity in the cabbage beetle Colaphellus bowringi.

Insect Biochem Mol Biol 2021 07 24;134:103582. Epub 2021 Apr 24.

Hubei Key Laboratory of Insect Resources Utilization and Sustainable Pest Management, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, PR China. Electronic address:

Many insects exhibit reproductive plasticity where the photoperiod determines whether the insect becomes reproductively active or enters diapause. Adult reproductive diapause is a strategy that allows insects to survive harsh environmental conditions. A deficiency in juvenile hormone (JH) leads to reproductive diapause. However, little is known about the molecular mechanisms by which JH signaling regulates reproductive diapause. In this study, we used the cabbage beetle Colaphellus bowringi, a serious pest, to investigate the role of Krüppel homolog 1 (Kr-h1) in controlling photoperiodic plasticity of female reproduction. We focused on Kr-h1, since it acts as a key mediator of JH signaling. We show here that JH-Methoprene-tolerant signaling upregulated the expression of Kr-h1 in reproductively active C. bowringi females when reared under short day conditions. In the long day-treated diapausing females, Kr-h1 transcripts decreased dramatically. Interfering with Kr-h1 function repressed reproductive development by blocking vitellogenesis and ovarian growth. Further, Kr-h1 depletion induced other diapause-like traits, including elevated lipid accumulation and high expression of diapause-related genes. RNA-Seq showed that Kr-h1 played both activating and repressive roles, depending on whether downstream genes were acting in reproduction- or diapause pathways, respectively. Finally, we identified the DNA replication gene mini-chromosome maintenance 4 and two triacylglycerol lipase genes as critical downstream factors of Kr-h1 that are critical for reproductive plasticity in C. bowringi. These results reveal that Kr-h1 is a key component of the regulatory pathway that coordinates reproduction and diapause in insects in response to photoperiodic input.
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http://dx.doi.org/10.1016/j.ibmb.2021.103582DOI Listing
July 2021

Aberrant cytokine expression in COVID-19 patients: Associations between cytokines and disease severity.

Cytokine 2021 07 31;143:155523. Epub 2021 Mar 31.

Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 86-027-67812888, China. Electronic address:

Cytokines play pleiotropic, antagonistic, and collaborative in viral disease. The high morbidity and mortality of coronavirus disease 2019 (COVID-19) make it a significant threat to global public health. Elucidating its pathogenesis is essential to finding effective therapy. A retrospective study was conducted on 71 patients hospitalized with COVID-19. Data on cytokines, T lymphocytes, and other clinical and laboratory characteristics were collected from patients with variable disease severity. The effects of cytokines on the overall survival (OS) and event-free survival (EFS) of patients were analyzed. The critically severe and severe patients had higher infection indexes and significant multiple organ function abnormalities than the mild patients (P < 0.05). IL-6 and IL-10 were significantly higher in the critically severe patients than in the severe and mild patients (P < 0.05). IL-6 and IL-10 were closely associated with white blood cells, neutrophils, T lymphocyte subsets, D-D dimer, blood urea nitrogen, complement C1q, procalcitonin C-reactive protein. Moreover, the IL-6 and IL-10 levels were closely correlated to dyspnea and dizziness (P < 0.05). The patients with higher IL-10 levels had shorter OS than the group with lower levels (P < 0.05). The older patients with higher levels of single IL-6 or IL-10 tended to have shorter EFS (P < 0.05), while the patients who had more elevated IL-6 and IL-10 had shorter OS (P < 0.05). The Cox proportional hazard model revealed that IL-6 was the independent factor affecting EFS. IL-6 and IL-10 play crucial roles in COVID-19 prognosis.
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http://dx.doi.org/10.1016/j.cyto.2021.155523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011640PMC
July 2021

MiR319-targeted OsTCP21 and OsGAmyb regulate tillering and grain yield in rice.

J Integr Plant Biol 2021 Jul 1;63(7):1260-1272. Epub 2021 Jun 1.

Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Agricultural Sciences, Guizhou University, Guiyang, 550025, China.

Multiple genes and microRNAs (miRNAs) improve grain yield by promoting tillering. MiR319s are known to regulate several aspects of plant development; however, whether miR319s are essential for tillering regulation remains unclear. Here, we report that miR319 is highly expressed in the basal part of rice plant at different development stages. The miR319 knockdown line Short Tandem Target Mimic 319 (STTM319) showed higher tiller bud length in seedlings under low nitrogen (N) condition and higher tiller bud number under high N condition compared with the miR319a-overexpression line. Through targets prediction, we identified OsTCP21 and OsGAmyb as downstream targets of miR319. Moreover, OsTCP21 and OsGAmyb overexpression lines and STTM319 had increased tiller bud length and biomass, whereas both were decreased in OsTCP21 and OsGAmyb knockout lines and OE319a. These data suggest that miR319 regulates rice tiller bud development and tillering through targeting OsTCP21 and OsGAmyb. Notably, the tiller number and grain yield increased in STTM319 and overexpression lines of OsTCP21 and OsGAmyb but decreased in OE319a and knockout lines of OsTCP21 and OsGAmyb. Taken together, our findings indicate that miR319s negatively affect tiller number and grain yield by targeting OsTCP21 and OsGAmyb, revealing a novel function for miR319 in rice.
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http://dx.doi.org/10.1111/jipb.13097DOI Listing
July 2021
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