Publications by authors named "Xiang Yu"

714 Publications

HBI Transcription Factor-Mediated ROS Homeostasis Regulates Nitrate Signal Transduction.

Plant Cell 2021 Jun 15. Epub 2021 Jun 15.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao, 266237, China.

Nitrate is both an important nutrient and a critical signaling molecule that regulates plant metabolism, growth, and development. Although several components of the nitrate signaling pathway have been identified, the molecular mechanism of nitrate signaling remains unclear. Here, we showed that the growth-related transcription factors HOMOLOG OF BRASSINOSTEROID ENHANCED EXPRESSION2 INTERACTING WITH IBH1 (HBI1) and its three closest homologs (HBIs) positively regulate nitrate signaling in Arabidopsis thaliana. HBI1 is rapidly induced by nitrate through NLP6 and NLP7, which are master regulators of nitrate signaling. Mutations in HBIs result in the reduced effects of nitrate on plant growth and approximately 22% nitrate-responsive genes no longer to be regulated by nitrate. HBIs increase the expression levels of a set of antioxidant genes to reduce the accumulation of reactive oxygen species (ROS) in plants. Nitrate treatment induces the nuclear localization of NLP7, whereas such promoting effects of nitrate are significantly impaired in the hbi-q and cat2 cat3 mutants, which accumulate high levels of H2O2. These results demonstrate that HBI-mediated ROS homeostasis regulates nitrate signal transduction through modulating the nucleocytoplasmic shuttling of NLP7. Overall, our findings reveal that nitrate treatment reduces the accumulation of H2O2, and H2O2 inhibits nitrate signaling, thereby forming a feedback regulatory loop to regulate plant growth and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/plcell/koab165DOI Listing
June 2021

RLIM: a recursive and latent infection model for the prediction of US COVID-19 infections and turning points.

Nonlinear Dyn 2021 May 31:1-14. Epub 2021 May 31.

Mechatronics, Embedded Systems and Automation Lab, University of California, Merced, CA USA.

Initially found in Hubei, Wuhan, and identified as a novel virus of the coronavirus family by the WHO, COVID-19 has spread worldwide at exponential speed, causing millions of deaths and public fear. Currently, the USA, India, Brazil, and other parts of the world are experiencing a secondary wave of COVID-19. However, the medical, mathematical, and pharmaceutical aspects of its transmission, incubation, and recovery processes are still unclear. The classical susceptible-infected-recovered model has limitations in describing the dynamic behavior of COVID-19. Hence, it is necessary to introduce a recursive, latent model to predict the number of future COVID-19 infection cases in the USA. In this article, a dynamic recursive and latent infection model (RLIM) based on the classical SEIR model is proposed to predict the number of COVID-19 infections. Given COVID-19 infection and recovery data for a certain period, the RLIM is able to fit current values and produce an optimal set of parameters with a minimum error rate according to actual reported numbers. With these optimal parameters assigned, the RLIM model then becomes able to produce predictions of infection numbers within a certain period. To locate the turning point of COVID-19 transmission, an initial value for the secondary infection rate is given to the RLIM algorithm for calculation. RLIM will then calculate the secondary infection rates of a continuous time series with an iterative search strategy to speed up the convergence of the prediction outcomes and minimize the maximum square errors. Compared with other forecast algorithms, RLIM is able to adapt the COVID-19 infection curve faster and more accurately and, more importantly, provides a way to identify the turning point in virus transmission by searching for the equilibrium between recoveries and new infections. Simulations of four US states show that with the secondary infection rate initially set to 0.5 within the selected latent period of 14 days, RLIM is able to minimize this value at 0.07 and reach an equilibrium condition. A successful forecast is generated using New York state's COVID-19 transmission, in which a turning point is predicted to emerge on January 31, 2021.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-021-06520-1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11071-021-06520-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166369PMC
May 2021

Prediction of 10-year atherosclerotic cardiovascular disease risk among community residents in Shanghai, China - a comparative analysis of risk algorithms.

Nutr Metab Cardiovasc Dis 2021 Apr 20. Epub 2021 Apr 20.

School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, 200032, China. Electronic address:

Background And Aims: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai.

Methods And Results: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221).

Conclusion: The proportion of participants with a 10-year ASCVD high risk predicted by China-PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.04.009DOI Listing
April 2021

Wavelength-Selective Activation of Photocaged DNAzymes for Metal Ion Sensing in Live Cells.

ACS Omega 2021 May 12;6(20):13153-13160. Epub 2021 May 12.

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.

RNA-cleaving DNAzymes are widely applied as sensors for detecting metal ions in environmental samples owing to their high sensitivity and selectivity, but their use for sensing biological metal ions in live cells is challenging because constitutive sensors fail to report the spatiotemporal heterogeneity of biological processes. Photocaged DNAzymes can be activated by light for sensing purposes that need spatial and temporal resolution. Studying complex biological processes requires logic photocontrol, but unfortunately all the literature-reported photocaged DNAzymes working in live cells cannot be selectively controlled by light irradiation at different wavelengths. In this work, we developed photocaged DNAzymes responsive to UV and visible light using a general synthetic method based on phosphorothioate chemistry. Taking the Zn-dependent DNAzyme sensor as a model, we achieved wavelength-selective activation of photocaged DNAzymes in live human cells by UV and visible light, laying the groundwork for the logic activation of DNAzyme-based sensors in biological systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c00976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158819PMC
May 2021

Observation on China's Strategies to Prevent the Resurgence of the COVID-19 Epidemic.

Risk Manag Healthc Policy 2021 18;14:2011-2019. Epub 2021 May 18.

School of Media and Law, Ningbo Institute of Technology, Zhejiang University, Ningbo, Zhejiang Province, People's Republic of China.

After the first wave of the COVID-19 pandemic that began in early 2020 was brought under control, there have been some regional and small-scale cases of new infections in China. In order to prevent the resurgence of the epidemic, the Chinese government has continued the use of effective prevention and control measures in key epidemic areas. New prevention and control measures have also been developed based on the characteristics of the epidemic and the social habits of the Chinese people. The strategies applied in China include large-scale nucleic acid testing, travel health code management, and patient treatment based on a combination of Chinese and Western medicine. These measures can provide a reference point for the global public health system that is facing the pandemic. The article suggests that to prevent a pandemic, we must not only rely on vaccines and drugs, but also need to take actions and apply social measures to manage the risk of infectious diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S305413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140918PMC
May 2021

The metabolic hormone leptin promotes the function of T cells and supports vaccine responses.

Nat Commun 2021 05 24;12(1):3073. Epub 2021 May 24.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Follicular helper T (T) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human T differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs T generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of T cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23220-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144586PMC
May 2021

Estriol dissolving microneedle patches for protection against ionizing radiation-induced injury.

Eur J Pharm Sci 2021 Aug 15;163:105881. Epub 2021 May 15.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Shandong University of Traditional Chinese Medicine, Jinan 250355, China. Electronic address:

Estriol can be used to treat radiation-induced leukopenia by increasing peripheral blood leukocytes and therefore it plays an important role in radiation protection. However, only high-dose injectable suspensions are available when estriol is used to combat against ionizing radiation-induced injury. Intramuscular (i.m.) administration of estriol is very painful and inconvenient, and the lack of timely self-administered formulation greatly limits the wide application of estriol. This will facilitate quick response under emergent conditions in complementary with the available estriol formulations. Herein, we prepared estriol microneedle (MNs) patches for the convenient and efficient treatment of radiation-induced injury. A biocompatible polymer, polyvinylpyrrolidone K90, was dissolved in an estriol solution of methanol and cast into a mold to obtain conical-shaped MNs. N-vinyl pyrrolidone was poured on the base of the MNs and photocured to enhance the mechanical strength of estriol MNs (EMNs). EMNs were easily pierced 200 μm into the mouse skin. More importantly, the EMNs tips were dissolved very quickly within 5 min so that the drugs could permeate across skin. Mouse models of ionizing radiation-induced injury were established with 6.5 Gy radiation of Co γ ray. Moreover, EMNs increased peripheral blood leukocytes in irradiated mice, protected the bone marrow hematopoietic system, and improved the survival rate of the irradiated mice to 80%. EMNs are a promising transdermal drug delivery system that allows for easy, rapid administration and protects the body from damage caused by ionizing radiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2021.105881DOI Listing
August 2021

Characteristics of the Microbial Community in the Production of Chinese Rice-Flavor Baijiu and Comparisons With the Microflora of Other Flavors of Baijiu.

Front Microbiol 2021 29;12:673670. Epub 2021 Apr 29.

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.

Rice-flavor baijiu is one of the four basic flavor types of Chinese baijiu. Microbial composition plays a key role in the classification of baijiu flavor types and the formation of flavor substances. In this study, we used high-throughput sequencing technology to study the changes of microbial community in the production of rice-flavor baijiu, and compared the microbial community characteristics during production of rice-, light-, and strong-flavor baijiu. The results showed that the species diversity of bacteria was much higher than that of fungi during the brewing of rice-flavor baijiu. The bacterial diversity index first increased and then decreased, while the diversity of fungi showed an increasing trend. A variety of major microorganisms came from the environment and raw rice materials; the core bacteria were , , , , , etc., among which was dominant (62.88-99.23%). The core fungi were (7.06-83.50%) and (15.21-90.89%). Temperature and total acid content were the main physicochemical factors affecting the microbial composition. Non-metric multidimensional scaling analysis showed that during the fermentation of rice-, light-, and strong-flavor baijiu, their microbial communities formed their own distinct systems, with considerable differences among different flavor types. Compared with the other two flavor types of baijiu, in the brewing process of rice-flavor baijiu, microbial species were fewer and dominant microorganisms were prominent, which may be the main reason for the small variety of flavor substances in rice-flavor baijiu. This study provides a theoretical basis for the production of rice-flavor baijiu, and lays a foundation for studying the link between baijiu flavor formation and microorganisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.673670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116502PMC
April 2021

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of plastrum testudinis in treating senile osteoporosis.

J Ethnopharmacol 2021 Aug 11;276:114198. Epub 2021 May 11.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

Ethnopharmacological Relevance: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown.

Aim Of The Study: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation.

Materials And Methods: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings.

Results: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway.

Conclusion: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114198DOI Listing
August 2021

Microlattice Metamaterials with Simultaneous Superior Acoustic and Mechanical Energy Absorption.

Small 2021 Jun 13;17(24):e2100336. Epub 2021 May 13.

Department of Mechanical Engineering, National University of Singapore, Singapore, 117575, Singapore.

The advent of 3D printing brought about the possibilities of microlattice metamaterials as advanced materials with the potentials to surpass the functionalities of traditional materials. Sound absorbing materials which are also tough and lightweight are of particular importance as practical engineering materials. There are however a lack of attempts on the study of metamaterials multifunctional for both purposes. Herein, we present four types of face-centered cubic based plate and truss microlattices as novel metamaterials with simultaneous excellent sound and mechanical energy absorption performance. High sound absorption coefficients nearing 1 and high specific energy absorption of 50.3 J g have been measured. Sound absorption mechanisms of microlattices are proposed to be based on a "cascading resonant cells theory", an extension of the Helmholtz resonance principle that we have conceptualized herein. Characteristics of absorption coefficients are found to be essentially geometry limited by the pore and cavity morphologies. The excellent mechanical properties in turn derive from both the approximate membrane stress state of the plate architecture and the excellent ductility and strength of the base material. Overall, this work presents a new concept on the specific structural design and materials selection for architectured metamaterials with dual sound and mechanical energy absorption capabilities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202100336DOI Listing
June 2021

Plastrum testudinis extract suppresses osteoclast differentiation via the NF-κB signaling pathway and ameliorates senile osteoporosis.

J Ethnopharmacol 2021 Aug 8;276:114195. Epub 2021 May 8.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

Ethnopharmacological Relevance: Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported.

Aim Of The Study: To explore the potential of PTE as a therapeutic treatment for bone loss caused by senile osteoporosis (SOP).

Materials And Methods: We evaluated whether PTE could inhibit RANKL-induced osteoclast differentiation both in vitro and in vivo, and investigated PTE-induced phenotypes of human peripheral blood monocytes.

Results: We found that PTE inhibited osteoclast differentiation and bone resorption in vitro in a concentration-dependent manner and that PTE treatment is most effective during the early stages of osteoclastogenesis. Moreover, we found that PTE could block the NF-κB signaling pathway in vitro, leading to the down-regulation of osteoclast-specific genes including C-FOS and NFATC1. The results from our in vivo mouse study suggest that PTE treatment suppresses osteoclast formation and mitigates bone loss caused by SOP. Notably, we also found that PTE inhibited RANKL-induced osteoclast differentiation in human peripheral blood monocytes.

Conclusion: Our results suggest that PTE treatment suppresses osteoclastogenesis and ameliorates bone loss caused by SOP by selectively blocking the nuclear translocation of NF-κB/p50.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114195DOI Listing
August 2021

Integrative analysis of miRNAs and mRNAs revealed regulation of lipid metabolism in dairy cattle.

Funct Integr Genomics 2021 May 7. Epub 2021 May 7.

College of Animal Science, Jilin University, Changchun, 130062, People's Republic of China.

Lipid metabolism in bovine mammary epithelial cells has been the primary focus of the research of milk fat percentage of dairy cattle. Functional microRNAs can affect lipid metabolism by regulating the expression of candidate genes. The purpose of the study was to screen and identify differentially expressed miRNAs, candidate genes, and co-regulatory pathways related to the metabolism of milk fat. To achieve this aim, we used miRNA and transcriptome data from the mammary epithelial cells of dairy cattle with high (H, 4.85%) and low milk fat percentages (L, 3.41%) during mid-lactation. One hundred ninety differentially expressed genes and 33 differentially expressed miRNAs were significantly enriched in related regulatory networks, of which 27 candidate genes regulated by 18 differentially expressed miRNAs significantly enriched in pathways related to lipid metabolism (p < 0.05). Target relationships between PDE4D and bta-miR-148a, PEG10 and bta-miR-877, SOD3 and bta-miR-2382-5p, and ADAMTS1 and bta-miR-2425-5p were verified using luciferase reporter assays and quantitative RT-PCR. The detection of triglyceride production in BMECs showed that bta-miR-21-3p and bta-miR-148a promote triglyceride synthesis, whereas bta-miR-124a, bta-miR-877, bta-miR-2382-5p, and bta-miR-2425-5p inhibit triglyceride synthesis. The conjoint analysis could identify functional miRNAs and regulatory candidate genes involved in lipid metabolism within the co-expression networks of the dairy cattle mammary system, which contributes to the understanding of potential regulatory mechanisms of genetic element and gene signaling networks involved in milk fat metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10142-021-00786-9DOI Listing
May 2021

Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization.

Mater Sci Eng C Mater Biol Appl 2021 May 26;124:112063. Epub 2021 Mar 26.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China; Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112063DOI Listing
May 2021

Global Analysis of RNA-Dependent RNA Polymerase-Dependent Small RNAs Reveals New Substrates and Functions for These Proteins and SGS3 in Arabidopsis.

Noncoding RNA 2021 Apr 27;7(2). Epub 2021 Apr 27.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

RNA silencing pathways control eukaryotic gene expression transcriptionally or posttranscriptionally in a sequence-specific manner. In RNA silencing, the production of double-stranded RNA (dsRNA) gives rise to various classes of 20-24 nucleotide (nt) small RNAs (smRNAs). In , smRNAs are often derived from long dsRNA molecules synthesized by one of the six genomically encoded RNA-dependent RNA Polymerase (RDR) proteins. However, the full complement of the RDR-dependent smRNAs and functions that these proteins and their RNA-binding cofactors play in plant RNA silencing has not been fully uncovered. To address this gap, we performed a global genomic analysis of all six RDRs and two of their cofactors to find new substrates for RDRs and targets of the resulting RDR-derived siRNAs to uncover new functions for these proteins in plants. Based on these analyses, we identified substrates for the three RDRγ clade proteins (RDR3-5), which had not been well-characterized previously. We also identified new substrates for the other three RDRs (RDR1, RDR2, and RDR6) as well as the RDR2 cofactor RNA-directed DNA methylation 12 (RDM12) and the RDR6 cofactor suppressor of gene silencing 3 (SGS3). These findings revealed that the target substrates of SGS3 are not limited to those solely utilized by RDR6, but that this protein seems to be a more general cofactor for the RDR family of proteins. Additionally, we found that RDR6 and SGS3 are involved in the production of smRNAs that target transcripts related to abiotic stresses, including water deprivation, salt stress, and ABA response, and as expected the levels of these mRNAs are increased in and mutant plants. Correspondingly, plants that lack these proteins ( and mutants) are hypersensitive to ABA treatment, tolerant to high levels of PEG8000, and have a higher survival rate under salt treatment in comparison to wild-type plants. In total, our analyses have provided an extremely data-rich resource for uncovering new functions of RDR-dependent RNA silencing in plants, while also revealing a previously unexplored link between the RDR6/SGS3-dependent pathway and plant abiotic stress responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ncrna7020028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167712PMC
April 2021

Inhalable Jojoba Oil Dry Nanoemulsion Powders for the Treatment of Lipopolysaccharide- or HO-Induced Acute Lung Injury.

Pharmaceutics 2021 Apr 2;13(4). Epub 2021 Apr 2.

Graduates Department, Anhui Medical University, Hefei 230032, China.

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (HO). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on HO-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or HO-induced ALI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics13040486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065502PMC
April 2021

Transition-Metal-Modified Vanadoborate Clusters as Stable and Efficient Photocatalysts for CO Reduction.

Inorg Chem 2021 May 23;60(10):7364-7371. Epub 2021 Apr 23.

Key Laboratory of Polyoxometalate Science of Ministry of Education, School of Chemistry, Northeast Normal University, Changchun, Jilin 130024, P. R. China.

Photocatalytic carbon dioxide reduction (CORR) is considered to be a promising sustainable and clean approach to solve environmental issues. Polyoxometalates (POMs), with advantages in fast, reversible, and stepwise multiple-electron transfer without changing their structures, have been promising catalysts in various redox reactions. However, their performance is often restricted by poor thermal or chemical stability. In this work, two transition-metal-modified vanadoborate clusters, [Co(en)][VBO(OH)]·17HO (VB-Co) and [Ni(en)][VBO(OH)]·17HO (VB-Ni), are reported for photocatalytic CO reduction. VB-Co and VB-Ni can preserve their structures to 200 and 250 °C, respectively, and remain stable in polar organic solvents and a wide range of pH solutions. Under visible-light irradiation, CO can be converted into syngas and HCOO with VB-Co or VB-Ni as catalysts. The total amount of gaseous products and liquid products for VB-Co is up to 9.5 and 0.168 mmol g h. Comparing with VB-Co, the yield of CO for VB-Ni declines by 1.8-fold, while that of HCOO increases by 35%. The AQY of VB-Co and VB-Ni is 1.1% and 0.93%, respectively. These values are higher than most of the reported POM materials under similar conditions. The density functional theory (DFT) calculations illuminate the active site of CORR and the reduction mechanism. This work provides new insights into the design of stable, high-performance, and low-cost photocatalysts for CO reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.1c00499DOI Listing
May 2021

Molybdenum disulfide nanosheets vertically grown on self-supported titanium dioxide/nitrogen-doped carbon nanofiber film for effective hydrogen peroxide decomposition and "memory catalysis".

J Colloid Interface Sci 2021 Aug 27;596:384-395. Epub 2021 Mar 27.

Environmental Engineering and Science Program, Department of Chemical and Environmental Engineering (ChEE), University of Cincinnati, Cincinnati, OH 45221-0012, United States. Electronic address:

A self-supporting catalyst consisting of 1D/2D vertical molybdenum [email protected] dioxide/nitrogen-doped carbon nanofiber ([email protected]/NCNFs) was prepared and tested. It showed efficient hydrogen peroxide (HO) decomposition to generate hydroxyl radical (OH) and degradation of various pollutants under solar irradiation. The contribution of the increase in MoS edges for decomposing HO was 0.0698 min. That is 9.83 times the rate of the original MoS edges resulting from the vertical structure. Specially, the catalyst degraded various aromatic pollutants even in the dark by releasing electrons stored in its graphite component to realize "memory catalysis". Also, it exhibited high degradation efficiency under outdoor solar irradiation. The catalyst was easily separated from the treated water, avoiding complex separation processes. All these features suggest this catalyst has great potential in practical water and sewage treatment applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.03.140DOI Listing
August 2021

Observation on China's efficient mobilization and external dependencies in COVID-19 detection reagents, vaccines and drugs development.

Authors:
Xiang Yu Na Li

Pak J Pharm Sci 2020 Sep;33(5):2193-2198

Law at Ningbo University, 818st Fenghua Road, Ningbo Zhejiang, China.

Respiratory infectious diseases had happened in China in recent years, and the outbreak of Corona Virus Disease 2019(COVID-19) had drawn worldwide attention. In order to control such high-mortality infectious diseases, the work of the Chinese government and the medical community in detection reagents, drugs, and vaccines had been speeded up. This research extensively searched the medical data of drugs, vaccines and kits development, the company's business report and the government's policy documents and conducted case analysis. We found some national mobilization measures had been put on the agenda and some special marketing authorization measures had been adopted. Due to the limitations of biotechnology research and the pharmaceutical industry, some key technologies and drugs still had a high external dependence. In the process of development, it was necessary to attach importance to scientific, ethical, and safety construction, and to strengthen international cooperation.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2020

Anthrathiadiazole Derivatives: Synthesis, Physical Properties and Two-photon Absorption.

Chemistry 2021 Mar 29. Epub 2021 Mar 29.

Wuhan Institute of Technology, School of Chemical Engineering and Pharmacy, CHINA.

Anthrathiadiazole is a key synthon for the construction of large azaacenes, however, the attachment of different substituents onto the skeleton of anthrathiadiazole is difficult but highly desirable because it could be easy to enrich the structures of azaacenes. Here, we demonstrate that anthrathiadiazole derivatives with -Br, -CN, and -OCH 3 groups could be easily constructed through a simple [4+2] cycloaddition reaction between a, a, a', a'-tetrabromo o-xylenes derivatives and benzo[c][1,2,5]thiadiazole-4,7-dione. The structures of the as-prepared compounds with different substituents were carefully characterized. Moreover, the basic physical properties of the as-prepared anthrathiadiazole derivatives were fully investigated, where the cyano-substituted derivative (BTH-CN) has the highest stability and the methoxy-substituted derivative ( BTH-OCH 3 ) is easy to be oxidized. Moreover, the two-photon absorption (TPA) characteristics of different anthrathiadiazoles are also studied by using the femtosecond Z-scan technique. The results show that the fused anthrathiadiazole skeletons possess large TPA cross-section values δ 2 in the range of 3000-5000 GM, where the nature, position and strength of the substituted groups have strong effect on these values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202100307DOI Listing
March 2021

A Simple-to-Use Nomogram for Predicting Survival in Children with Acute Myeloid Leukemia.

Biomed Res Int 2021 11;2021:7264623. Epub 2021 Mar 11.

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Background: The research analyzed a group of patients to develop a statistical nomogram and a web-based survival rate predictor for the comprehensive estimate of the overall survival (OS) of children with acute myeloid leukemia.

Methods: Between 1999 to 2015, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to evaluate and randomly divide 440 children diagnosed with AML into the population of training ( = 309) and validation ( = 131). The analysis of Lasso Cox was used to identify separate predictive variables. We have used essential forecasting considerations to construct a nomogram and a web-based calculator focused on Cox regression analysis. Nomogram validation was tested through discrimination and calibration.

Results: Compared to the multivariate training cohort models, a nomogram integrating gender, age of diagnose, WBC at diagnosis, bone marrow leukemic blast percentage, and chromosomal abnormalities [(8; 21), inv(16)] were designed for the prediction of OS. We also developed a predictive survival nomogram and a web-based calculator. C-indexes validated internally and checked externally were 0.747 and 0.716. The calibration curves have shown that the nomogram might accurately forecast 3-year and 5-year OS.

Conclusions: A nomogram effectively predicts survival in children with AML. This prognostic model can be used in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/7264623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972835PMC
May 2021

Double-side effect of B/C ratio on BDD electrode detection for heavy metal ion in water.

Sci Total Environ 2021 Jun 28;771:145430. Epub 2021 Jan 28.

Beijing Key Laboratory of Materials Utilisation of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences (Beijing), 29 Xueyuan Road, Haidian, Beijing 100083, China. Electronic address:

BDD (Boron-doped Diamond) electrode may hold a promising application to detect heavy metal ions for actual water monitoring and early warning, but a poor understanding of influence mechanism of B/C ratio on detection performance is in the way of its fabrication and application. This work is intended to reveal the double-side effect of B/C ratio on detection performance of BDD electrode so as to facilitate its actual application. SBDD (Self-supported Boron-doped Diamond) electrode is introduced for the first time to get rid of the interference factors such as substrate. A systematic investigation is conducted for the influence of B/C ratio on microstructure and electrochemical behavior of SBDD electrodes. With the increase of B/C ratio, the grain size continuously increases, and the preferred orientation gradually changes from plane (220) to (111). The gradual increasing of impurity phase content indicates a deterioration of diamond phase quality. In addition, the electrode electrochemical behavior initially gets better then worse. SBDD electrode with a B/C ratio of 1/500 has the largest active surface area of 2.1 cm, the smallest diffusion resistance and the highest signal response. Under optimal parameter set, the SBDD electrode enjoys a sensitivity of 0.42 μA L μg cm and a detection limit of 1.12 μg L in a wide linear range of 5-120 ppb. The phase quality and grain morphology jointly contribute to the double-side effect. A suitable B-sp-C content, preferred orientation of (111) and small particle size may make the performance improvement of BDD electrode available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.145430DOI Listing
June 2021

General Method for Post-Synthetic Modification of Oligonucleotides Based on Oxidative Amination of 4-Thio-2'-deoxyuridine.

Bioconjug Chem 2021 04 17;32(4):721-728. Epub 2021 Mar 17.

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.

Functionalized oligonucleotides (ONs) are widely applied as target binding molecules for biosensing and regulators for gene expression. Numerous efforts have been focused on developing facile methods for preparing these useful ONs carrying diverse modifications. Herein, we present a general method for postsynthetic modification of ONs via oxidative amination of 4-thio-2'-deoxyuridine (4SdU). 4SdU-containing ON can be derived by both alkyl and aromatic amines. Using this approach, ONs are successfully attached with alkyne/azide, biotin and dansylamide moieties, and these as-prepared ONs possess the expected biorthogonal reactivity, streptavidin affinity and fluorescent property, respectively. Furthermore, we also directly install fluorophores to the ON nucleobase based on oxidative amination of 4SdU, and these fluorophores exhibit distinct luminescence behaviors before and after conjugation. We believe our method will be a versatile strategy for constructing various functionalized ONs used in a wide range of nucleic acid applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.1c00016DOI Listing
April 2021

Enhanced Comprehensive Learning Particle Swarm Optimization with Dimensional Independent and Adaptive Parameters.

Authors:
Xiang Yu Yu Qiao

Comput Intell Neurosci 2021 5;2021:6628564. Epub 2021 Feb 5.

School of Mathematics and Information Science, Shaanxi Normal University, Xi'an, Shaanxi 710119, China.

Comprehensive learning particle swarm optimization (CLPSO) and enhanced CLPSO (ECLPSO) are two literature metaheuristics for global optimization. ECLPSO significantly improves the exploitation and convergence performance of CLPSO by perturbation-based exploitation and adaptive learning probabilities. However, ECLPSO still cannot locate the global optimum or find a near-optimum solution for a number of problems. In this paper, we study further bettering the exploration performance of ECLPSO. We propose to assign an independent inertia weight and an independent acceleration coefficient corresponding to each dimension of the search space, as well as an independent learning probability for each particle on each dimension. Like ECLPSO, a normative interval bounded by the minimum and maximum personal best positions is determined with respect to each dimension in each generation. The dimensional independent maximum velocities, inertia weights, acceleration coefficients, and learning probabilities are proposed to be adaptively updated based on the dimensional normative intervals in order to facilitate exploration, exploitation, and convergence, particularly exploration. Our proposed metaheuristic, called adaptive CLPSO (ACLPSO), is evaluated on various benchmark functions. Experimental results demonstrate that the dimensional independent and adaptive maximum velocities, inertia weights, acceleration coefficients, and learning probabilities help to significantly mend ECLPSO's exploration performance, and ACLPSO is able to derive the global optimum or a near-optimum solution on all the benchmark functions for all the runs with parameters appropriately set.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6628564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880717PMC
February 2021

Understanding the beginning of a pandemic: China's response to the emergence of COVID-19.

Authors:
Xiang Yu Na Li

J Infect Public Health 2021 Mar 29;14(3):347-352. Epub 2020 Dec 29.

School of Law, Ningbo University, 818st, Fenghua Road, Ningbo, Zhejiang 315211, China; Research Academy of Belt & Road, Ningbo University, 818st, Fenghua Road, Ningbo, Zhejiang 315211, China. Electronic address:

China had suffered the COVID-19 outbreak from the end of 2019, SARS-CoV-2 began to spread secretly within the community and in hospitals, causing numerous citizens to be infected without knowing it. After the official confirmation of COVID-19, hospital diagnosis and treatment systems were under great pressure, and medical supplies were scarce. Then the pandemic experienced an explosive growth and quickly peaked. In order to respond to the challenge, the Chinese government quickly built hospitals, adjusted the diagnosis and treatment systems, deployed medical staff to support areas affected by the epidemic, isolated and treated infected patients as much as possible, reminded citizens to use good protection, and controlled the epidemic step-by-step. In this paper, we used official published data and medical literature about the transmission of COVID-19 as well as prevention and control guidelines issued by the Chinese government and hospitals, adopted a multi-dimensional analysis framework, divided the outbreak into three phases: (1) "blind man touching the elephant" phase, (2) "opening Pandora's box" phase, (3) "whole offensive and whole defensive tactics" phase. This was done to describe the development of and response to the pandemic. This paper suggested that when dealing with similar outbreaks in the future, we should do a better job of providing protective guidance and material reserves in advance, strengthen the emergency response capacity of medical institutions, and aim to share this information with the public medical systems of other countries which also face severe tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiph.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836925PMC
March 2021

Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway.

Front Mol Biosci 2020 28;7:602282. Epub 2021 Jan 28.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2020.602282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876332PMC
January 2021

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients.

Front Oncol 2020 28;10:621435. Epub 2021 Jan 28.

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Surgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FRCTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.

Methods: In this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FRCTC analysis. FRCTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FRCTC level and the prognosis in these patients was evaluated.

Results: Overall, preoperative FRCTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes ( = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FRCTC level was significantly different ( = 0.028). Further, patients with lower preoperative FRCTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FRCTC level (RFS: not reached vs. 33.3 months, = 0.018; OS: not reached vs. 72.0 months, = 0.13). In a multivariate COX regression analysis, FRCTC level (HR = 4.10; 95% CI, 1.23-13.64; =0.022) and pathological stage (HR = 3.16; 95% CI, 1.79-10.14; = 0.0011) were independent prognostic factors of RFS. Moreover, FRCTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FRCTC or adenocarcinoma subtype alone.

Conclusion: Our study demonstrated that the preoperative FRCTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FRCTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.621435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876466PMC
January 2021

Organic Nanoparticles with Persistent Luminescence for In Vivo Afterglow Imaging-Guided Photodynamic Therapy.

Chemistry 2021 Apr 17;27(23):6911-6916. Epub 2021 Mar 17.

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, P. R. China.

Optical imaging-guided photodynamic therapy (PDT), with precise localization and non-invasive treatment of tumors, is an emerging technique with great potential for cancer therapy. However, impaired by tissue auto-fluorescence that causes low signal-to-background ratio (SBR), most fluorescence imaging systems show poor sensitivity to tumors in vivo. In this study, we synthesized organic nanoparticles (ONPs) with persistent luminescence and good biocompatibility for afterglow imaging-guided PDT. The ONPs displayed near-infrared light emission with half-life time at minute level, which offered high SBR and good tissue penetration for in vivo afterglow tumor imaging. Taking advantage of their abundant singlet oxygen generation by NIR laser irradiation guided to the tumor sites, the ONPs also enabled imaging-guided PDT for efficient suppression of tumor growth in mice with minimal damage to major organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202100406DOI Listing
April 2021

HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis.

Dig Dis Sci 2021 Feb 8. Epub 2021 Feb 8.

Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuding East Rd, Zhifu District, Yantai, 264000, Shangdong, China.

Background: Gastric cancer (GC) is a common leading cause of cancer-related mortality of all malignancies. LncRNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) has been identified to involve in the development of GC. Therefore, we further explored the detailed molecular mechanism of HIF1A-AS2 in GC progression.

Methods: The expression of HIF1A-AS2, microRNA-429 (miR-429), and programmed cell death ligand 1 (PD-L1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8 (CCK-8) or transwell assay. The interaction between miR-429 and HIF1A-AS2 or PD-L1 was confirmed by luciferase reporter assay. Murine xenograft model was established to investigate the role of HIF1A-AS2 in vivo.

Results: HIF1A-AS2 was elevated in GC tissues and cell lines. Functional experiments showed that HIF1A-AS2 knockdown inhibited GC cell proliferation, migration, and invasion in vitro, as well as hindered tumor growth in vivo. Moreover, HIF1A-AS2 directly bound to miR-429 based on bioinformatics prediction and luciferase assay, and inhibition of miR-429 abolished the effects of HIF1A-AS2 knockdown on GC cells. Furthermore, miR-429 directly targeted PD-L1, and overexpression of miR-429 suppressed GC tumorigenesis via PD-L1. Besides that, PD-L1 also performed an oncogenic role in GC cell proliferation and metastasis. Additionally, HIF1A-AS2 could indirectly regulate PD-L1 expression via sponging miR-429.

Conclusion: HIF1A-AS2 is a dependable predictor of malignancy and prognosis in GC and functions as an oncogene to promote GC cell proliferation and metastasis by regulating miR-429/PD-L1 axis, indicating a new insight into the search for novel biomarkers and therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-020-06819-wDOI Listing
February 2021

Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis.

Sci Transl Med 2021 Feb;13(579)

Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.

Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[F]fluoro-d-glucose positron emission tomography and computerized tomography ([F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abd7618DOI Listing
February 2021

Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis.

Sci Transl Med 2021 Feb;13(579)

Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.

Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[F]fluoro-d-glucose positron emission tomography and computerized tomography ([F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abd7618DOI Listing
February 2021