The brain is particularly susceptible to oxidative damage which is a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's ...disease. The shuttling of glutathione (GSH) precursors from astrocytes to neurons has been shown to be instrumental for the neuroprotective activity. Here, we revealed that short chain fatty acids (SCFA), which have been related to AD and PD, could promote glutamate-glutamine shuttle to potentially resist oxidative damage in neurons at cellular level. Furthermore, we performed nine-month-long dietary SCFA supplementations in APPswe/PS1dE9 (APP/PS1) mice, and showed that it reshaped the homeostasis of microbiota and alleviated the cognitive impairment by reducing Aβ deposition and tau hyperphosphorylation. Single-cell RNA sequencing analysis of the hippocampus revealed SCFA can enhance astrocyte-neuron communication including glutamate-glutamine shuttle, mainly by acting on astrocyte in vivo. Collectively, our findings indicate that long-term dietary SCFA supplementations at early aging stage can regulate the neuroenergetics to alleviate AD, providing a promising direction for the development of new AD drug.
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•SCFA contribute to the glutamate-glutamine shuttle by acting on glutamine synthetase.•Long-term SCFA diet alleviates cognitive and spatial memory defeat in APP/PS1 mice.•Long-term SCFA diet reduces Aβ deposition and abnormal phosphorylation of tau.•SCFA promote astrocyte-neuron metabolic coupling to reduce oxidative damage.
Abstract
This paper comprehensively evaluated the static mechanical compressive properties, permeability, and cell adhesion effect on the inner wall of the Primitive triply periodic minimal surface ...Ti6Al4V bionic scaffolds with different axial diameter ratios through numerical simulation and experiments. The results show that when the axial diameter ratio is 1:2, the elastic modulus of the scaffold is about 1.25 and the yield strength is about 1.36. The scaffold's longitudinal and transverse mechanical properties align with human bone tissue. Its permeability is also better than that of circular pores. The scaffold with an axial diameter ratio of 1:3 has the best permeability, ranging from 1.28e−8 to 1.60e−8 m
2
, which is more conducive to the adsorption of cells on the inner wall of the scaffold. These results show that the scaffold structure with an axial diameter ratio of not 1:1 has more advantages than the ordinary uniform scaffold structure with an axial diameter ratio of 1:1. This is of great significance to the optimal design of scaffold.
The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein ...in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the ...biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3'-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.
•Simplified model was developed to estimate subsurface fluxes.•Subsurface fluxes of nutrient losses dominated in drier rice cropping areas.•Precipitation determines relative importance of subsurface ...fluxes to surface runoff.•Spatially flexible set for mitigating nutrient losses is needed for paddy fields.
Rice paddy fields pose a high risk of water pollutions for the surrounding waterbodies through surface runoff and subsurface fluxes. Compared to surface runoff, subsurface flux from rice paddy fields has received less attention and is still poorly quantified, mainly due to low-frequency measurements at field scale and limited modeling capability at regional scale. Here we proposed a simplified modeling approach to estimate the subsurface fluxes of water, nitrogen (N) and phosphorus (P) from rice paddy fields and examined their relative importance compared to surface runoff. This model was established based on the high-frequency field measurements over two rice growing seasons in central China and the extended datasets across the East Asia. Two-year site-based observations indicate the significance of subsurface fluxes of water (737–785 mm season−1), N (28.5–40.0 kg N ha−1) and P (0.7–4.3 kg P ha−1) compared to those of surface runoff (178–199 mm season−1, 4.5–12.9 kg N ha−1, 0.5–2.6 kg P ha−1). Our regional estimations in the East Asia reveal that subsurface fluxes from rice paddy fields were comparable with surface fluxes, primarily controlled by the magnitude of seasonal precipitation. Subsurface fluxes were the dominant pathway of nutrient losses in drier rice cropping areas, while surface runoff was the more important process in wetter areas. In the light of the regional differences, we suggest that a spatially flexible set of policies for mitigating nutrient losses from rice paddy fields would be beneficial for the future water-quality improvements in the surrounding waterbodies.
Abstract
Croplands are the single largest anthropogenic source of nitrous oxide (N2O) globally, yet their estimates remain difficult to verify when using Tier 1 and 3 methods of the Intergovernmental ...Panel on Climate Change (IPCC). Here, we re-evaluate global cropland-N2O emissions in 1961–2014, using N-rate-dependent emission factors (EFs) upscaled from 1206 field observations in 180 global distributed sites and high-resolution N inputs disaggregated from sub-national surveys covering 15593 administrative units. Our results confirm IPCC Tier 1 default EFs for upland crops in 1990–2014, but give a ∼15% lower EF in 1961–1989 and a ∼67% larger EF for paddy rice over the full period. Associated emissions (0.82 ± 0.34 Tg N yr–1) are probably one-quarter lower than IPCC Tier 1 global inventories but close to Tier 3 estimates. The use of survey-based gridded N-input data contributes 58% of this emission reduction, the rest being explained by the use of observation-based non-linear EFs. We conclude that upscaling N2O emissions from site-level observations to global croplands provides a new benchmark for constraining IPCC Tier 1 and 3 methods. The detailed spatial distribution of emission data is expected to inform advancement towards more realistic and effective mitigation pathways.
A new variant of concern for SARS-CoV-2, Omicron (B.1.1.529), was designated by the World Health Organization on November 26, 2021. This study analyzed the viral genome sequencing data of 108 samples ...collected from patients infected with Omicron. First, we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to. Second, the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time (median: 62 vs. 45), especially in the Spike gene. Mutations in the Spike gene confer alterations in 32 amino acid residues, more than those observed in other SARS-CoV-2 variants. Moreover, a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein, which could potentially affect the replication, infectivity, and antigenicity of SARS-CoV-2. Third, there are 53 mutations between the Omicron variant and its closest sequences available in public databases. Many of these mutations were rarely observed in public databases and had a low mutation rate. In addition, the linkage disequilibrium between these mutations was low, with a limited number of mutations concurrently observed in the same genome, suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent variants. To improve our ability to detect and track the source of new variants rapidly, it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.
, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients' ...skin and transmit to others. Despite numerous reports of
isolation in various countries, many studies have reported contradictory results.
A bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling
infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva's articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for 'drug resistance,' 'antifungal susceptibility test,' 'infection,' '
' and 'identification.' The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of
.
The bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling
Abscisic acid (ABA) is a key phytohormone involved in wound healing in fruits and vegetables, while fluridone (FLD) is its synthetic inhibitor. However, it is unknown whether ABA signaling and ...downstream transcription factors are involved in the synthesis of phenolic acids and lignin monomers in muskmelon wounds, and the underlying mechanisms. In our study, exogenous ABA promoted endogenous ABA synthesis by increasing the levels of β-carotenoid and zeaxanthin, activating 9-cis-epoxycarotenoid dioxygenase (NCED) and zeaxanthin epoxidase (ZEP), facilitated ABA signaling by increasing the expression levels of protein phosphatases type 2C (
CmPP2C
) and ABA-responsive element binding factors (
CmABF
), upregulated the expression levels of
CmMYB1
and
CmWRKY1
, and ABA induced phenylpropanoid metabolism by activating phenylalanine ammonia-lyase (PAL), 4-coenzyme A ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD), which further increased the synthesis of phenolic acids and lignin monomers in muskmelon wounds during healing. Taken together, exogenous ABA induced phenylpropanoid metabolism and increased the synthesis of phenolic acid and lignin monomer in muskmelon wounds during healing, and may be involved in endogenous ABA synthesis and signaling and related transcription factors.
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and ...generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.
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