In this study, changes in plant diversity and aboveground biomass, soil chemical properties, microbial biomass and respiration, microbial composition, and microbial N-cycling potential (represented ...by the abundance of genes involved in N reaction) were studied after 3 years of urea fertilization (0, 25, 50, and 100 kg N ha
−1
year
−1
) in a semiarid grassland in China. The microbial composition and N-cycling genes were determined using metagenome sequencing. Urea fertilization significantly decreased soil bacterial diversity, possibly through its negative effect on plant diversity, whereas it increased fungal diversity, and microbial biomass and respiration through enhancing aboveground biomass production with increases in the C input into the soil. However, above the threshold N rate of 50 kg N ha
−1
year
−1
, microbial biomass and respiration decreased probably because of a strong N inhibitory effect on aboveground biomass. Further, urea fertilization increased the gene abundances of
narH
,
nrfA
,
nirB
, and
napA
, which are involved in dissimilatory nitrate reduction, and those of
nifH
and
nifD
, involved in N
2
fixation,
gdh
, involved in organic N decomposition, and
glnA
, involved in glutamine synthesis and ureC. These findings suggested that urea addition has a positive effect on N-turnover potential.
Burkholderiales
and
Rhizobiales
play an important role in soil N cycling. Changes in plant community (diversity and biomass) were responsible for the shift in microbial diversity, biomass, and respiration, whereas alterations in inorganic N levels (exchangeable NH
4
+
and NO
3
−
) potentially affected microbial N cycling. Our results show that N-mediated environmental stresses can play an important role in microbial diversity and functions, which appear to be mediated largely by plant–soil interactions.
Background
This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid ...arthritis–related interstitial lung disease (RA-ILD).
Methods
PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively.
Results
Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI: 1.35–4.68;
P
= 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI: 0.17–0.62;
P
= 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD = − 0.03; 95% CI: − 0.89–0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI: − 0.26–0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI: 2.19–3.71; P < 0.00001) and serum RF titer was significantly correlated with the risk of RA-ILD (SMD = 0.35; 95% CI: 0.23–0.46; P < 0.00001). However, for the analysis of RF dichotomous data, the funnel shape was asymmetric and the p value of egger test was less than 0.05, which indicated potential publication bias.
Conclusions
ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention.
Key Points
•
Autoantibodies ACPA and RF increase the risk of RA-ILD.
•
Regions may be related to RA-ILD.
Iguratimod (IGU) is a novel synthetic small molecule disease modified anti-rheumatic drug approved only in Japan and China up to date. IGU plays an important immunomodulatory role in the synovial ...tissue of rheumatoid arthritis by inhibiting the production of immunoglobulins and cytokines and regulating T lymphocyte subsets. IGU also regulates bone metabolism by stimulating bone formation while inhibiting osteoclast differentiation, migration, and bone resorption. In clinical trials, IGU was shown to be superior to placebo and not inferior to salazosulfapyridine. Combined therapy of IGU with other disease-modifying anti-rheumatic drugs showed significant improvements for disease activity. IGU has good efficacy and tolerance as an additional treatment for rheumatoid arthritis patients with inadequate response to methotrexate and biological disease-modifying anti-rheumatic drugs. In this review, we summarize current landscape on the mechanism of action of IGU and its clinical effectiveness and safety. It is expected that further translational studies on IGU will pave the road for wider application of IGU in the treatment of autoimmune diseases other than rheumatoid arthritis.
In order to construct global solutions to two-dimensional (2D for short) Riemann problems for nonlinear hyperbolic systems of conservation laws, it is important to study various types of wave ...interactions. This paper deals with two types of wave interactions for a 2D nonlinear wave system with a nonconvex equation of state: Rarefaction wave interaction and shock-rarefaction composite wave interaction. In order to construct solutions to these wave interactions, the authors consider two types of Goursat problems, including standard Goursat problem and discontinuous Goursat problem, for a 2D self-similar nonlinear wave system. Global classical solutions to these Goursat problems are obtained by the method of characteristics. The solutions constructed in the paper may be used as building blocks of solutions of 2D Riemann problems.
Pectobacterium spp. are necrotrophic bacterial plant pathogens of the family Pectobacteriaceae, responsible for a wide spectrum of diseases of important crops and ornamental plants including soft ...rot, blackleg, and stem wilt. P. carotovorum is a genetically heterogeneous species consisting of three valid subspecies, P. carotovorum subsp. brasiliense (Pcb), P. carotovorum subsp. carotovorum (Pcc), and P. carotovorum subsp. odoriferum (Pco).
Thirty-two P. carotovorum strains had their whole genomes sequenced, including the first complete genome of Pco and another circular genome of Pcb, as well as the high-coverage genome sequences for 30 additional strains covering Pcc, Pcb, and Pco. In combination with 52 other publicly available genome sequences, the comparative genomics study of P. carotovorum and other four closely related species P. polaris, P. parmentieri, P. atrosepticum, and Candidatus P. maceratum was conducted focusing on CRISPR-Cas defense systems and pathogenicity determinants. Our analysis identified two CRISPR-Cas types (I-F and I-E) in Pectobacterium, as well as another I-C type in Dickeya that is not found in Pectobacterium. The core pathogenicity factors (e.g., plant cell wall-degrading enzymes) were highly conserved, whereas some factors (e.g., flagellin, siderophores, polysaccharides, protein secretion systems, and regulatory factors) were varied among these species and/or subspecies. Notably, a novel type of T6SS as well as the sorbitol metabolizing srl operon was identified to be specific to Pco in Pectobacterium.
This study not only advances the available knowledge about the genetic differentiation of individual subspecies of P. carotovorum, but also delineates the general genetic features of P. carotovorum by comparison with its four closely related species, thereby substantially enriching the extent of information now available for functional genomic investigations about Pectobacterium.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prime editing (PE), as a "search-and-replace" genome editing technology, has shown the attractive potential of versatile genome editing ability, which is, in principle, currently superior to other ...well-established genome-editing technologies in the all-in-one operation scope. However, essential technological solutions of PE technology, such as the improvement of genome editing efficiency, the inhibition of potential off-targets and intended edits accounting for unexpected side-effects, and the development of effective delivery systems, are necessary to broaden its application. Since the advent of PE, many optimizations have been performed on PE systems to improve their performance, resulting in bright prospects for application in many fields. This review briefly discusses the development of PE technology, including its functional principle, noteworthy barriers restraining its application, current efforts in technical optimization, and its application directions and potential risks. This review may provide a concise and informative insight into the burgeoning field of PE, highlight the exciting prospects for this powerful tool, and provide clues for questions that may propel the field forward.
Porcine reproductive and respiratory syndrome virus 2 (PRRSV2) is a major threat to the global pig industry, particularly in China, the world’s largest pig-rearing and pork-production country. ...Continuously monitoring the epidemiological and genetic characteristics of PRRSV epidemic strains is beneficial for prevention and control of infection. Previously, we reported the epidemiological and genetic characteristics of PRRSV2 in China from 2012 to 2016. Here, the epidemiological and genetic characteristics of PRRSV2 in China from 2017 to 2018 are reported. During these two years, we collected different types of porcine samples from 2428 pig farms in 27 provinces in China. Of the 7980 samples collected, 2080 (26.07%) were positive for PRRSV2 ORF5 by RT-PCR. The positive rate of PRRSV detection between different regions of China ranged from 8.12% to 29.33%, and from 7.96% to 55.50% between different months. Phylogenetic analysis based on the ORF5 gene revealed that the PRRSV2 strains currently circulating in China belong to five clades, and most of the PRRSVs detected are highly pathogenic PRRSVs (HP-PRRSVs; clade IV) and PRRSV NADC30-like strains (clade I). Sequence analysis revealed multiple amino acid mutation types, including amino acid changes and deletions in both the GP5 and Nsp2 proteins. The presence of these mutations may have an effect on the evolution of the virus by altering the viral titer and/or affecting the antibody response against the virus.
The circulating tumor DNA (ctDNA), as a promising biomarker of liquid biopsy, has potential clinical relevance on the molecular diagnosis and monitoring of cancer. However, the trace concentration ...level of ctDNA in the peripheral blood restricts its extensive clinical application. Recently, high-throughput-based methodologies have been leveraged to improve the sensitivity and specificity of ctDNA detection, showing a promising avenue towards liquid biopsy. This review briefly summarizes the high-throughput data features concerned by current ctDNA detection strategies and the technical obstacles, potential solutions, and clinical relevance of current ctDNA profiling technologies. We also highlight future directions improving the limit of detection of ctDNA for better clinical application. This review may serve as a reference for the crosslinks between data science and ctDNA-based liquid biopsy, benefiting clinical translation in advanced cancer diagnosis.
As an infrastructure of Internet of Things, WSNs (Wireless Sensor Networks) play a more and more important role. However, WSNs are vulnerable to malware and malware can destroy their data security ...and integrity, which motivates us to explore the role of malware propagation in WSNs. First, according to the actual propagation characteristics of malware in the WSNs and the process of the density change of all node types, we propose an epidemiology-based malware propagation model in consideration of a secondary immune mechanism. Then we set up differential equations to describe the propagation model. By solving differential equations, we can obtain two kinds of equilibrium points indicating that the density of all node types tends to be stable in the WSNs. One is to achieve an equilibrium where only susceptible nodes exist in the WSNs. The other is that malware always exists in the WSNs. Moreover, we prove the local and global stability of these two equilibrium points. Eventually, we analyze the influence and effect of the secondary immunity, forgetting mechanism and containment mechanism on malware propagation in the WSNs, and validate the proposed model through simulations.
Abstract
Metabolic reprogramming in malignant cells is a hallmark of cancer that relies on augmented glycolytic metabolism to support their growth, invasion, and metastasis. However, the impact of ...global adipose metabolism on tumor growth and the drug development by targeting adipose metabolism remain largely unexplored. Here we show that a therapeutic paradigm of drugs is effective for treating various cancer types by browning adipose tissues. Mirabegron, a clinically available drug for overactive bladders, displays potent anticancer effects in various animal cancer models, including untreatable cancers such as pancreatic ductal adenocarcinoma and hepatocellular carcinoma, via the browning of adipose tissues. Genetic deletion of the uncoupling protein 1, a key thermogenic protein in adipose tissues, ablates the anticancer effect. Similarly, the removal of brown adipose tissue, which is responsible for non-shivering thermogenesis, attenuates the anticancer activity of mirabegron. These findings demonstrate that mirabegron represents a paradigm of anticancer drugs with a distinct mechanism for the effective treatment of multiple cancers.
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