The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale 1, 2. Although bats are regarded as the ...most likely natural hosts for SARS-CoV-2 3, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.
•Metagenomic analysis identified a novel coronavirus, RmYN02, from R. malayanus•RmYN02 was the closest relative of SARS-CoV-2 in most of the virus genome•Two loop deletions in RBD may reduce the binding of RmYN02 with ACE2•RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein
Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.
Abstract
Background
Overweight is a known risk factor for various chronic diseases and poses a significant threat to middle-aged and elderly adults. Previous studies have reported a strong ...association between overweight and air pollution. However, the spatial relationship between the two remains unclear due to the confounding effects of spatial heterogeneity.
Methods
We gathered height and weight data from the 2015 China Health and Retirement Long-term Survey (CHARLS), comprising 16,171 middle-aged and elderly individuals. We also collected regional air pollution data. We then analyzed the spatial pattern of overweight prevalence using Moran's I and Getis-Ord Gi* statistics. To quantify the explanatory power of distinct air pollutants for spatial differences in overweight prevalence across Southern and Northern China, as well as across different age groups, we utilized Geodetector's q-statistic.
Results
The average prevalence of overweight among middle-aged and elderly individuals in each city was 67.27% and 57.39%, respectively. In general, the q-statistic in southern China was higher than that in northern China. In the north, the prevalence was significantly higher at 54.86% compared to the prevalence of 38.75% in the south. SO
2
exhibited a relatively higher q-statistic in middle-aged individuals in both the north and south, while for the elderly in the south, NO
2
was the most crucial factor (q = 0.24,
p
< 0.01). Moreover, fine particulate matter (PM
2.5
and PM
10
) also demonstrated an important effect on overweight. Furthermore, we found that the pairwise interaction between various risk factors improved the explanatory power of the prevalence of overweight, with different effects for different age groups and regions. In northern China, the strongest interaction was found between NO
2
and SO
2
(q = 0.55) for middle-aged individuals and PM
2.5
and SO
2
(q = 0.27) for the elderly. Conversely, in southern China, middle-aged individuals demonstrated the strongest interaction between SO
2
and PM
10
(q = 0.60), while the elderly showed the highest interaction between NO
2
and O
3
(q = 0.42).
Conclusion
Significant spatial heterogeneity was observed in the effects of air pollution on overweight. Specifically, air pollution in southern China was found to have a greater impact on overweight than that in northern China. And, the impact of air pollution on middle-aged individuals was more pronounced than on the elderly, with distinct pollutants demonstrating significant variation in their impact. Moreover, we found that SO
2
had a greater impact on overweight prevalence among middle-aged individuals, while NO
2
had a greater impact on the elderly. Additionally, we identified significant statistically interactions between O
3
and other pollutants.
To mitigate environmental damage from mineral aggregate extraction, bio-based materials have garnered research interest as potential replacements for natural mineral aggregates. This work utilized ...waste wood as filler to prepare lightweight foam concrete with thermal insulation, low-temperature and corrosion resistance properties. The feasibility of using wood aggregate-based foam concrete (WFC) was explored in terms of dry density, softening coefficient, compressive strength, thermal conductivity, chloride ion permeability, freezing resistance, and sulfate attack resistance. Results showed that simultaneous addition of waste wood aggregate (WA) and foam effectively reduced WFC bulk weight and thermal conductivity while enhancing water resistance. However, the porous morphology of WA and foam caused the reduction of mechanical properties. In terms of durability, the addition of WA can increase the energy absorption capacity when WFC is subjected to expansion stress, reduce the damage to the structure, and have an inhibiting effect on the cracking of WFC caused by sulfate attack and freeze-thaw cycles. Nevertheless, WA's high water absorption loosened the matrix in WFC's interfacial transition zone (ITZ), increasing harmful pores and negatively affecting durability. In addition, in order to predict the mechanical properties of WFC and the resistance to sulfate attack, this study established a function model for the relationship between the compressive strength (Maintenance specimens of the same age and Specimen of sulfate attack) and the WA dosage. In conclusion, The use of waste wood for the preparation of WFC is more advantageous and sustainable than conventional foam concrete for the insulation of precast walls and coastal structures.
Display omitted
The CO
emissions from the cement industry and the production of waste wood chips are increasing with the rapid growth of the construction industry. In order to develop a green environmental ...protection building material with low thermal conductivity and up to standard mechanical properties, in this study, pine waste wood chips were mixed into cement-based materials as fine aggregate, and three different kinds of cementitious binders were used, including sulfur aluminate cement (SAC), ordinary Portland cement (OPC), and granulated blast furnace slag (GBFS), to prepare a recycled light cementitious composite material. The mechanical, thermal conductivity, shrinkage, water absorption, and pore structure of a wood chip light cementitious composite material were studied by changing the Ch/B (the mass ratio of wood chip to binder). The results showed that the strength, dry density, and thermal conductivity of the specimens decreased significantly with the increase in the Ch/B, while the shrinkage, water absorption, and pore size increased with the increase in the Ch/B. By comparing three different kinds of cementitious binders, the dry density of the material prepared with OPC was 942 kg/m
, the compressive strength of the material prepared with SAC was 13.5 MPa, and the thermal conductivity of the material prepared with slag was the lowest at 0.15 W/m/K. From the perspective of low-cost and low-carbon emissions, it was determined that the best way to prepare a light cementitious composite with waste wood chips is to use granulated blast furnace slag (GBFS) as the cementitious binder.
Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine ...methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy.
The burning or accumulation of a large number of corn cobs in the countryside not only pollutes the environment but also takes up land, and it is of great significance to use agricultural solid waste ...to prepare green ecological construction materials for liveable villages. Therefore, in this study, the agricultural solid waste-corn cob is used as coarse aggregate, the recycled sand as fine aggregate, and industrial solid waste-mineral powder is used as cementitious material to prepare a green low carbon recycled concrete (LCRC). Regarding the alkali exciter concentrations, fine aggregate type and pre-wetting degree of aggregate as key variables, the time-varying laws of mechanical property, thermal insulation property, drying shrinkage property and CO2 emission of LCRC were studied. The results show that LCRC with a higher concentration of alkali exciter has better mechanical and thermal insulation properties, but poorer shrinkage properties. The mechanical property and shrinkage property of LCRC by manufactured sand are more excellent but poor insulation property. 80% pre-wetted LCRC has better mechanical and shrinkage properties, but lower thermal insulation property. The 28 days compressive strength and flexural strength of LCRC can reach up to 11.6 and 1.6 MPa. The bending compression ratio and 90 days shrinkage of LCRC are between 0.07 and 0.18 and 625.9∼977.7 × 10−6, which are comparable to or even better than normal concrete. The thermal conductivity of LCRC ranges from 0.108 to 0.300 W/(m·K) and can be used as a preparation insulation material. Meanwhile, LCRC can reduce carbon emissions by up to 31% than ordinary cement.
Parkinson's disease is a neurodegenerative disorder, and ferroptosis plays a significant role in the pathological mechanism underlying Parkinson's disease. Rapamycin, an autophagy inducer, has been ...shown to have neuroprotective effects in Parkinson's disease. However, the link between rapamycin and ferroptosis in Parkinson's disease is not entirely clear. In this study, rapamycin was administered to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson's disease PC12 cell model. The results showed that rapamycin improved the behavioral symptoms of Parkinson's disease model mice, reduced the loss of dopamine neurons in the substantia nigra pars compacta, and reduced the expression of ferroptosis-related indicators (glutathione peroxidase 4, recombinant solute carrier family 7, member 11, glutathione, malondialdehyde, and reactive oxygen species). In the Parkinson's disease cell model, rapamycin improved cell viability and reduced ferroptosis. The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer (methyl (1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate) and an autophagy inhibitor (3-methyladenine). Inhibiting ferroptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects. Therefore, the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson's disease.
Purpose
Chlamydia psittaci
(
C. psittaci
) has caused sporadic, but recurring, fatal community-acquired pneumonia outbreaks worldwide, posing a serious threat to public health. Our understanding of ...host inflammatory responses to
C. psittaci
is limited, and many bronchitis cases of psittaci have rapidly progressed to pneumonia with deterioration.
Methods
To clarify the host inflammatory response in psittacosis, we analyzed clinical parameters, and compared transcriptomic data, concentrations of plasma cytokines/chemokines, and changes of immune cell populations in 17 laboratory-confirmed psittacosis cases, namely, 8 pneumonia and 9 bronchitis individuals, in order to assess transcriptomic profiles and pro-inflammatory responses.
Results
Psittacosis cases with pneumonia were found to have abnormal routine blood indices, liver damage, and unilateral pulmonary high-attenuation consolidation. Transcriptome sequencing revealed markedly elevated expression of several pro-inflammatory genes, especially interleukins and chemokines. A multiplex-biometric immunoassay showed that pneumonia cases had higher levels of serum cytokines (G-CSF, IL-2, IL-6, IL-10, IL-18, IP-10, MCP-3, and TNF-α) than bronchitis cases. Increases in activated neutrophils and decreases in the number of lymphocytes were also observed in pneumonia cases.
Conclusion
We identified a number of plasma biomarkers distinct to
C. psittaci
pneumonia and a variety of cytokines elevated with immunopathogenic potential likely inducing an inflammatory milieu and acceleration of the disease progression of psittaci pneumonia. This enhances our understanding of inflammatory responses and changes in vascular endothelial markers in psittacosis with heterogeneous symptoms and should prove helpful for developing both preventative and therapeutic strategies.
Introduction
Non-tuberculous mycobacteria
(NTM) is a major category of environmental bacteria in nature that can be divided into rapidly growing
mycobacteria
(RGM) and slowly growing
mycobacteria
...(SGM) based on their distinct growth rates. To explore differential molecular mechanisms between RGM and SGM is crucial to understand their survival state, environmental/host adaptation and pathogenicity. Comparative genomic analysis provides a powerful tool for deeply investigating differential molecular mechanisms between them. However, large-scale comparative genomic analysis between RGM and SGM is still uncovered.
Methods
In this study, we screened 335 high-quality, non-redundant NTM genome sequences covering 187 species from 3,478 online NTM genomes, and then performed a comprehensive comparative genomic analysis to identify differential genomic characteristics and featured genes/protein domains between RGM and SGM.
Results
Our findings reveal that RGM has a larger genome size, more genes, lower GC content, and more featured genes/protein domains in metabolism of some main substances (e.g. carbohydrates, amino acids, nucleotides, ions, and coenzymes), energy metabolism, signal transduction, replication, transcription, and translation processes, which are essential for its rapid growth requirements. On the other hand, SGM has a smaller genome size, fewer genes, higher GC content, and more featured genes/protein domains in lipid and secondary metabolite metabolisms and cellular defense mechanisms, which help enhance its genome stability and environmental adaptability. Additionally, orthogroup analysis revealed the important roles of bacterial division and bacteriophage associated genes in RGM and secretion system related genes for better environmental adaptation in SGM. Notably, PCoA analysis of the top 20 genes/protein domains showed precision classification between RGM and SGM, indicating the credibility of our screening/classification strategies.
Discussion
Overall, our findings shed light on differential underlying molecular mechanisms in survival state, adaptation and pathogenicity between RGM and SGM, show the potential for our comparative genomic pipeline to investigate differential genes/protein domains at whole genomic level across different bacterial species on a large scale, and provide an important reference and improved understanding of NTM.
PDF
