Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, ...30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1β, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of
in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of
, and the relative abundance of
and
in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis.
Phyllosphere and rhizosphere are unique and wide‐ranging habitats that harbor various microbial communities, which influence plant growth and health, and the productivity of the ecosystems. In this ...study, we characterized the shared microbiome of the phyllosphere and rhizosphere among three plants (Ipomoea pes‐caprae, Wedelia chinensis, and Cocos nucifera), to obtain an insight into the relationships between bacteria (including diazotrophic bacteria) and fungi, present on these host plants. Quantitative PCR showed that the abundances of the microbiome in the soil samples were significantly higher than those in the phyllosphere samples, though there was an extremely low abundance of fungi in bulk soil. High‐throughput sequencing showed that the alpha‐diversity of bacteria and fungi was higher in the rhizosphere than the phyllosphere samples associated with the same plant, while there was no obvious shift in the alpha‐diversity of diazotrophic communities between all the tested phyllosphere and soil samples. Results of the microbial composition showed that sample‐specific bacteria and fungi were found among the phyllosphere and rhizosphere of the different host plants. About 10%–27% of bacteria, including diazotrophs, and fungi overlapped between the phyllosphere and the rhizosphere of these host plants. No significant difference in microbial community structure was found among the tested rhizosphere samples, and soil properties had a higher influence on the soil microbial community structures than the host plant species.
In this study, we characterized the shared microbiome of the phyllosphere and rhizosphere among three plants on Yongxing Island, South China Sea. We found that about 10%~27% of bacteria, including diazotrophs, and fungi overlapped between the phyllosphere and rhizosphere of these host plants. No significant difference in microbial community structure was found among the rhizosphere samples, and soil properties had a higher influence on soil community structure than on the host plant species.
Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling ...in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rankl) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP-positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain.
Pain is the most prominent symptom of osteoarthritis (OA) progression. However, the relationship between pain and OA progression remains largely unknown. Here we report osteoblast secret ...prostaglandin E2 (PGE2) during aberrant subchondral bone remodeling induces pain and OA progression in mice. Specific deletion of the major PGE2 producing enzyme cyclooxygenase 2 (COX2) in osteoblasts or PGE2 receptor EP4 in peripheral nerve markedly ameliorates OA symptoms. Mechanistically, PGE2 sensitizes dorsal root ganglia (DRG) neurons by modifying the voltage-gated sodium channel Na
V
1.8, evidenced by that genetically or pharmacologically inhibiting Na
V
1.8 in DRG neurons can substantially attenuate OA. Moreover, drugs targeting aberrant subchondral bone remodeling also attenuates OA through rebalancing PGE2 production and Na
V
1.8 modification. Thus, aberrant subchondral remodeling induced Na
V
1.8 neuronal modification is an important player in OA and is a potential therapeutic target in multiple skeletal degenerative diseases.
Many people will suffer from joint pain as they age, particularly in their knees. The most common cause of this pain is osteoarthritis, a disease that affects a tissue inside joints called cartilage. In a healthy knee, cartilage acts as a shock absorber. It cushions the ends of bones and enables them to move smoothly against one another. But in osteoarthritis, cartilage gradually wears away. As a result, the bones within a joint rub against each other whenever a person moves. This makes activities such as running or climbing stairs painful.
But how does this pain arise? Previous work has implicated cells called osteoblasts. Osteoblasts are found in the area of the bone just below the cartilage. They produce new bone tissue throughout our lives, enabling our bones to regenerate and repair. Each time we move, forces acting on the knee joint activate osteoblasts. The cells respond by releasing a key molecule called PGE2, which is a factor in pain pathways. The joints of people with osteoarthritis produce too much PGE2. But exactly how this leads to increased pain sensation has been unclear.
Zhu et al. now complete this story by working out how PGE2 triggers pain. Experiments in mice reveal that PGE2 irritates the nerve fibers that carry pain signals from the knee joint to the brain. It does this by activating a channel protein called Na
v
1.8, which allows sodium ions through the membranes of those nerve fibers. Zhu et al. show that, in a mouse model of osteoarthritis, Na
v
1.8 opens too widely in response to binding of PGE2, so the nerve cells become overactive and transmit a stronger pain sensation. This means that even small movements cause intense pain signals to travel from the joints to the brain.
Building on their findings, Zhu et al. developed a drug that acts directly on bone to reduce PGE2 production, and show that this drug reduces pain in mice with osteoarthritis. At present, there are no treatments that reverse the damage that occurs during osteoarthritis, but further testing will determine whether this new drug could one day relieve joint pain in patients.
Crystalline silicon (c-Si) is the dominating photovoltaic technology today, with a global market share of about 90%. Therefore, it is crucial for further improving the performance of c-Si solar cells ...and reducing their cost. Since 2014, continuous breakthroughs have been achieved in the conversion efficiencies of c-Si solar cells, with a current record of 26.6%. The great efficiency boosts originate not only from the materials, including Si wafers, emitters, passivation layers, and other functional thin films, but also from novel device structures and an understanding of the physics of solar cells. Among these achievements, the carrier-selective passivation contacts are undoubtedly crucial. Current carrier-selective passivation contacts can be realized either by silicon-based thin films or by elemental and/or compound thin films with extreme work functions. The current research and development status, as well as the future trends of these passivation contact materials, structures, and corresponding high-efficiency c-Si solar cells will be summarized.
The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the ...expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.
During the COVID-19 pandemic, more than ever, data science has become a powerful weapon in combating an infectious disease epidemic and arguably any future infectious disease epidemic. Computer ...scientists, data scientists, physicists and mathematicians have joined public health professionals and virologists to confront the largest pandemic in the century by capitalizing on the large-scale 'big data' generated and harnessed for combating the COVID-19 pandemic. In this paper, we review the newly born data science approaches to confronting COVID-19, including the estimation of epidemiological parameters, digital contact tracing, diagnosis, policy-making, resource allocation, risk assessment, mental health surveillance, social media analytics, drug repurposing and drug development. We compare the new approaches with conventional epidemiological studies, discuss lessons we learned from the COVID-19 pandemic, and highlight opportunities and challenges of data science approaches to confronting future infectious disease epidemics. This article is part of the theme issue 'Data science approaches to infectious disease surveillance'.
The emergence of coronavirus disease 2019 (COVID-19) has infected more than 62 million people worldwide. Control responses varied across countries with different outcomes in terms of epidemic size ...and social disruption. This study presents an age-specific susceptible-exposed-infected-recovery-death model that considers the unique characteristics of COVID-19 to examine the effectiveness of various non-pharmaceutical interventions (NPIs) in New York City (NYC). Numerical experiments from our model show that the control policies implemented in NYC reduced the number of infections by 72% interquartile range (IQR) 53-95 and the number of deceased cases by 76% (IQR 58-96) by the end of 2020. Among all the NPIs, social distancing for the entire population and protection for the elderly in public facilities is the most effective control measure in reducing severe infections and deceased cases. School closure policy may not work as effectively as one might expect in terms of reducing the number of deceased cases. Our simulation results provide novel insights into the city-specific implementation of NPIs with minimal social disruption considering the locations and population characteristics.
Because of their attractive photoelectrical properties, perovskite-phase, CsPbX3 (X = I, Br, or Cl) materials have recently gained attention for their applications in resistive switching (RS) ...memories. However, phase transition of the CsPbI3 from perovskite (cubic phase) to nonperovskite (orthorhombic phase) at room temperature is problematic; it remains a challenge to apply nonperovskite CsPbI3 in RS memories. In the present work, a polymethylmethacrylate (PMMA)-assisted deposition method for nonperovskite CsPbI3 is introduced to fabricate a composite film of CsPbI3 with PMMA (PMMA@CsPbI3) with a smooth surface morphology on fluorine-doped tin oxide (FTO) substrates. Devices with a Ag/PMMA@CsPbI3/FTO architecture show nonvolatile RS characteristics with an ON/OFF ratio around 102, endurance over 500 cycles, and a retention time of 103 s. Analyses suggested that a Schottky barrier at the Ag/PMMA@CsPbI3 interface and a bias-induced migration of Ag ions within the composite films are responsible for the RS operation. This is the first record for RS devices based on nonperovskite CsPbI3, and it may bring the future research on nonperovskite CsPbI3 applied in RS memory devices some new inspiration..
Characterizing the relationship between vegetation phenology and urbanization indicators is essential to understand the impacts of human activities on urban ecosystems. In this study, we explored the ...response of vegetation phenology to urbanization in Beijing (China) during 2001-2018, using impervious surface area (ISA) and the information of urban-rural gradients (i.e., concentric rings from the urban core to surrounding rural areas) as the urbanization indicators. We found the change rates of vegetation phenology in urban areas are 1.3 and 1.1 days per year for start of season (SOS) and end of season (EOS), respectively, about three times faster than that in forest. Moreover, we found a divergent response of SOS with the increase of ISA, which differs from previous results with advanced SOS in the urban environment than surrounding rural areas. This might be attributed to the mixed land cover types and the thermal environment caused by the urban heat island in the urban environment. Similarly, a divergent pattern of phenological indicators along the urban-rural gradient shows a non-linear response of vegetation phenology to urbanization. These findings provide new insights into the complicated interactions between vegetation phenology and urban environments. High-resolution weather data are required to support process-based vegetation phenology models in the future, particularly under different global urbanization and climate change scenarios.
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•We firstly characterized the response of vegetation phenology to urbanization using quantitative indicators.•A distinct divergent response of vegetation phenology to urbanization was observed.•Suburban with a medium urbanization level has the earliest date of start of season.•Process-based phenology models are encouraged to explain this divergent pattern.
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