The association between SARS‐CoV‐2 infection with increased risk for new‐onset neurodegenerative diseases remains unclear. Therefore, this meta‐analysis aims to elucidate whether new‐onset ...neurodegenerative diseases are long‐term sequelae of SARS‐CoV‐2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched for articles published up to January 10, 2023. A systematic review and meta‐analysis were performed to calculate the pooled effect size, expressed as hazard ratios (HR) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 33 146 809 individuals (2 688 417 post‐COVID‐19 cases and 30 458 392 controls) were included in the present meta‐analysis. The pooled analyses compared with control groups showed a significant association between SARS‐CoV‐2 infection and increased risk for new‐onset Alzheimer's disease (HR = 1.50, 95% CI 1.22–1.85, I2 = 97%), dementia (HR = 1.66, 95% CI 1.42–1.94, I2 = 91%), and Parkinson's disease (HR = 1.44, 95% CI 1.06–1.95, I2 = 86%) among COVID‐19 survivors. SARS‐CoV‐2 infection may be associated with a higher risk for new‐onset neurodegenerative diseases in recovered COVID‐19 patients. Future studies are warranted to determine the biological mechanisms underlying the neurodegenerative consequences of COVID‐19 as long‐term sequelae of SARS‐CoV‐2 infection.
Different substances are combined to compensate for each other's drawbacks and create an appropriate biomaterial. A novel Polyvinyl alcohol (PVA)/chitosan (CS) porous hydrogel was designed and ...applied to the treatment of osteochondral defects.
Hydrogels of various PVA/CS ratios were tested for physiochemical and mechanical properties in addition to cytotoxicity and biocompatibility. The hydrogels with the best PVA/CS ratio were used in the animal study. Osteochondral defects were created at the articular cartilage of 18 rabbits. They were assigned to different groups randomly (n = 6 per group): the osteochondral defect only group (control group), the osteochondral defect treated with hydrogel group (HG group), and the osteochondral defect treated with hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) group (HG-BMSCs group). The cartilage was collected for macro-observation and histological evaluation at 12 weeks after surgery.
The Hydrogel with PVA/CS ratio of 6:4 exhibited the best mechanical properties; it also showed stable physical and chemical properties with porosity and over 90% water content. Furthermore, it demonstrated no cytotoxicity and was able to promote cell proliferation. The HG-BMSCs group achieved the best cartilage healing.
The novel PVA/CS porous composite hydrogel could be a good candidate for a tissue engineering material in cartilage repair.
Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates ...which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Na
1.8 channels. We show that knockout of PGE2 receptor 4 in sensory nerves significantly reduces spinal hypersensitivity. Inhibition of osteoclast formation by knockout Rankl in the osteocytes significantly inhibits LSI-induced porosity of endplates, sensory innervation, and spinal hypersensitivity. Knockout of Netrin-1 in osteoclasts abrogates sensory innervation into porous endplates and spinal hypersensitivity. These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain.
Tea Camellia sinensis (L) O. Kuntze, Theaceae is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, ...survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis'), GO terms (e.g., 'response to karrikin') and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology.
Osteoarthritis (OA) is a prevalent degenerative disease accompanied by the activation of innate and adaptive immune systems-associated inflammatory responses. Due to the local inflammation, the ...expression of various cytokines was altered in affected joints, including CC motif chemokine ligands (CCLs) and their receptors (CCRs). As essential members of chemokines, CCLs and CCRs played an important role in the pathogenesis and treatment of OA. The bindings between CCLs and CCRs on the chondrocyte membrane promoted chondrocyte apoptosis and the release of multiple matrix-degrading enzymes, which resulted in cartilage degradation. In addition, CCLs and CCRs had chemoattractant functions to attract various immune cells to osteoarthritic joints, further leading to the aggravation of local inflammation. Furthermore, in the nerve endings of joints, CCLs and CCRs, along with several cellular factors, contributed to pain hypersensitivity by releasing neurotransmitters in the spinal cord. Given this family's diverse and complex functions, targeting the functional network of CCLs and CCRs is a promising strategy for the prognosis and treatment of OA in the future.
Sleep stage estimation is crucial to the evaluation of sleep quality and is a proven biometric in diagnosing cardiovascular diseases. In this paper, we design a continuous wave (CW) Doppler radar to ...accurately measure sleep-related signals, including respiration, heartbeat, and body movement. Body movement index, respiration per minute (RPM), variance of RPM, amplitude difference accumulation (ADA) of respiration, rapid eye movement parameter, sample entropy, heartbeat per minute (HPM), variance of HPM, ADA of heartbeat, deep parameter, and time feature have been extracted and fed into different machine learning classifiers. A total of 11 all night polysomnography recordings from 13 healthy examinees were used to validate the proposed CW Doppler radar system and the ability to detect sleep stage information from it. Comparative studies and statistical results have shown that the subspace K-nearest neighbor algorithm outperforms the other classifiers with the highest accuracy of up to 86.6%. With the Relief F algorithm, features have been ranked, and the selected feature subsets have been preliminary tested to identify the optimal feature subset. Meanwhile, comparative analysis of our classification performance under different sleep stage patterns with prior works has been carried out to show the significant improvements over state-of-the-art solutions. These results suggest that the proposed scheme is suitable for long-term sleep monitoring.
Gradient nanostructure was introduced to enhance the strength and ductility via deformation incompatibility accommodated by geometrical necessary dislocations for most metallic materials recently. ...However, few intensive researches were carried out to investigate the effect of gradient structure on the deformation twin evolution and resulting performance improvements. In the present paper, we produced gradient-structured AZ31 Mg alloy with fine-grain layers, parallel twin laminates and a coarse-grain core from two upmost surfaces to the center of plate. Surprisingly, this architected Mg alloy exhibited simultaneous enhancement of strength and ductility. Subsequent microstructural observations demonstrated that abundant twin-twin interactions resulting from higher strength and multi-axial stress state could make great contributions to the increase of work-hardening capability. This was further proved by the measurement of full-field strain evolution during the plastic deformation. Such a design strategy may provide a new path for producing advanced structure materials in which the deformation twinning works as one of the dominant plasticity mechanisms.
Alzheimer's disease (AD) is the most common neurodegenerative disease, and numerous recent findings suggest that several pathologic signs, including loss of muscle strength and mass, are also ...detected in these patients. In the present study, we evaluated muscle cross-sectional area (CSA), myonuclear number, satellite cell (SC) content, and myosin heavy chain (MyHC) types in an animal model of AD and examined the possible role of resistance training in controlling skeletal muscle size in this disease. Fifty-eight male rats were randomly divided into four groups: healthy-control (H-C), healthy-exercise (H-Ex), Alzheimer-control (A-C), and Alzheimer-exercise (A-Ex). AD was induced by the single injection of 1-42 amyloid into the CA1 region of the hippocampus (1 μl/site). The rats in H-Ex and A-Ex groups performed a 5-week resistance training period (17 sessions). The results indicated that AD induces significant skeletal muscle atrophy and reduces the myonuclear number and SC content in gastrocnemius muscle in both whole muscle cross-sections and isolated myofibers. Interestingly, we did not find any significant differences in the different MyHC distributions of AD animals compared with controls, while resistance training significantly increased the CSA of MyHC IIb fibers in both AD and healthy animals. Altogether, these observations suggest that the skeletal muscle of AD animals are more prone to atrophy and loss of myonuclear number and satellite cell content, while resistance training successfully restores these impairments.
Lysine crotonylation, as a novel evolutionarily conserved type of post-translational modifications, is ubiquitous and essential in cell biology. However, its functions in tea plants are largely ...unknown, and the full functions of lysine crotonylated proteins of tea plants in nitrogen absorption and assimilation remains unclear. Our study attempts to describe the global profiling of nonhistone lysine crotonylation in tea leaves and to explore how ammonium (NH
) triggers the response mechanism of lysine crotonylome in tea plants.
Here, we performed the global analysis of crotonylome in tea leaves under NH
deficiency/resupply using high-resolution LC-MS/MS coupled with highly sensitive immune-antibody. A total of 2288 lysine crotonylation sites on 971 proteins were identified, of which contained in 15 types of crotonylated motifs. Most of crotonylated proteins were located in chloroplast (37%) and cytoplasm (33%). Compared with NH
deficiency, 120 and 151 crotonylated proteins were significantly changed at 3 h and 3 days of NH
resupply, respectively. Bioinformatics analysis showed that differentially expressed crotonylated proteins participated in diverse biological processes such as photosynthesis (PsbO, PsbP, PsbQ, Pbs27, PsaN, PsaF, FNR and ATPase), carbon fixation (rbcs, rbcl, TK, ALDO, PGK and PRK) and amino acid metabolism (SGAT, GGAT2, SHMT4 and GDC), suggesting that lysine crotonylation played important roles in these processes. Moreover, the protein-protein interaction analysis revealed that the interactions of identified crotonylated proteins diversely involved in photosynthesis, carbon fixation and amino acid metabolism. Interestingly, a large number of enzymes were crotonylated, such as Rubisco, TK, SGAT and GGAT, and their activities and crotonylation levels changed significantly by sensing ammonium, indicating a potential function of crotonylation in the regulation of enzyme activities.
The results indicated that the crotonylated proteins had a profound influence on metabolic process of tea leaves in response to NH
deficiency/resupply, which mainly involved in diverse aspects of primary metabolic processes by sensing NH
, especially in photosynthesis, carbon fixation and amino acid metabolism. The data might serve as important resources for exploring the roles of lysine crotonylation in N metabolism of tea plants. Data were available via ProteomeXchange with identifier PXD011610.
Platelets are traditionally considered to be essential components of primary hemostasis. Recent investigations have revealed that platelets can be activated in patients with sepsis and are implicated ...in the development of sepsis and sepsis-induced-acute kidney injury (SAKI). In the present study, ticagrelor was used to induce a mouse model of SAKI by cecal ligation and puncture. It was found that ticagrelor could inhibit platelet activity, decrease the levels of interleukin-1β and serum creatinine, reduce infiltration of neutrophils in renal tissue, and attenuate cell apoptosis in the kidney. The results suggested that ticagrelor could protect renal function by inhibiting inflammation, recruitment of neutrophils into the kidney, and cell apoptosis in renal tissue. Thus, the findings might provide new strategies for preventing SAKI.
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