DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice.

As of December 2022, 2,603 cases laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we constructed two vaccine candidates of DNA and replicating Vaccinia Tian Tan (VTT) vector that carried the MERS-CoV Spike (S) protein. Compared with homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The mice immunized generated robust binding antibodies and broader neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates but also proposes a heterologous sequential immunization strategy worthy of further development.

Amino acid substitution of the membrane-proximal external region alter neutralization sensitivity in a chronic HIV-1 clade B infected patient.

The membrane-proximal external region (MPER) represents a highly conserved region of the Human Immunodeficiency Virus (HIV) envelope glycoprotein (env) targeted by several broadly neutralizing antibodies (bnAbs). In this study, we employed single genome amplification to amplify 34 full-length env sequences from the 2005 plasma sample of CBJC504, a chronic HIV-1 clade B infected individual. We identified three amino acid changes (N671S, D674N, and K677R) in the MPER. A longitudinal analysis revealed that the proportion of env sequences with MPER mutations increased from 26.5 % in 2005 to 56.0 % in 2009, and the sequences with the same mutation clustered together. Nine functional pseudoviruses were generated from the 34 env sequences to examine the effect of these mutations on neutralizing activity. Pseudoviruses carrying N674 or R677 mutations demonstrate increased sensitivity to autologous plasma and monoclonal antibodies 2F5, 4E10, and 10E8. Reverse mutations were performed in env including N674, R677, D659, and S671/N677 mutations, to validate the impact of the mutations on neutralizing sensitivity. Neutralization assays indicated that the N671S mutation increased neutralization sensitivity to 2F5 and 10E8. The amino acid R at position 677 increased viral resistance to 10E8, whereas N enhanced viral resistance to 4E10 and 10E8. It has been proposed that critical amino acids in the extra-MPER and the number of potential N-like glycosylation sites (PNGSs) in the V1 loop may have an impact on neutralizing activity. Understanding the mutations and evolution of MPER in chronically infected patients with HIV-1 is crucial for the design and development of vaccines that trigger bnAbs against MPER.

A near-zero quiescent power breeze wake-up anemometer based on a rolling-bearing triboelectric nanogenerator.

Wind sensors have always played an irreplaceable role in environmental information monitoring and are expected to operate with lower power consumption to extend service lifetime. Here, we propose a breeze wake-up anemometer (B-WA) based on a rolling-bearing triboelectric nanogenerator (RB-TENG) with extremely low static power. The B-WA consists of two RB-TENGs, a self-waking-up module (SWM), a signal processing module (SPM), and a wireless transmission unit. The two RB-TENGs are employed for system activation and wind-speed sensing. Once the ambient wind-speed exceeds 2 m/s, the wake TENG (W-TENG) and the SWM can wake up the system within 0.96 s. At the same time, the SPM starts to calculate the signal frequency from the measured TENG (M-TENG) to monitor the wind speed with a sensitivity of 9.45 Hz/(m/s). After the wind stops, the SWM can switch off the B-WA within 0.52 s to decrease the system energy loss. In quiescent on-duty mode, the operating power of the B-WA is less than 30 nW, which can greatly extend the service lifetime of the B-WA. By integrating triboelectric devices and rolling bearings, this work has realized an ultralow quiescent power and self-waked-up wireless wind-speed monitoring system, which has foreseeable applications in remote weather monitoring, IoT nodes, and so on.

Evaluation of monolithic crystal detector with dual-ended readout utilizing multiplexing method.

Objective.Monolithic crystal detectors are increasingly being applied in positron emission tomography (PET) devices owing to their excellent depth-of-interaction (DOI) resolution capabilities and high detection efficiency. In this study, we constructed and evaluated a dual-ended readout monolithic crystal detector based on a multiplexing method.Approach.We employed two 12 × 12 silicon photomultiplier (SiPM) arrays for readout, and the signals from the 12 × 12 array were merged into 12 X and 12 Y channels using channel multiplexing. In 2D reconstruction, three methods based on the centre of gravity (COG) were compared, and the concept of thresholds was introduced. Furthermore, a light convolutional neural network (CNN) was employed for testing. To enhance depth localization resolution, we proposed a method by utilizing the mutual information from both ends of the SiPMs. The source width and collimation effect were simulated using GEANT4, and the intrinsic spatial resolution was separated from the measured values.Main results.At an operational voltage of 29 V for the SiPM, an energy resolution of approximately 12.5 % was achieved. By subtracting a 0.8 % threshold from the total energy in every channel, a 2D spatial resolution of approximately 0.90 mm full width at half maximum (FWHM) can be obtained. Furthermore, a higher level of resolution, approximately 0.80 mm FWHM, was achieved using a CNN, with some alleviation of edge effects. With the proposed DOI method, a significant 1.36 mm FWHM average DOI resolution can be achieved. Additionally, it was found that polishing and black coating on the crystal surface yielded smaller edge effects compared to a rough surface with a black coating.Significance.The introduction of a threshold in COG method and a dual-ended readout scheme can lead to excellent spatial resolution for monolithic crystal detectors, which can help to develop PET systems with both high sensitivity and high spatial resolution.

Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis.

PURPOSE: Mitofusin 2 (Mfn2) is one of two mitofusins involved in regulating mitochondrial size, shape and function, including mitophagy, an important cellular mechanism to limit oxidative stress. Reduced expression of Mfn2 has been associated with impaired osteoblast differentiation and function and a reduction in the number of viable osteocytes in bone. We hypothesized that the genetic absence of Mfn2 in these cells would increase their susceptibility to aging-associated metabolic stress, leading to a progressive impairment in skeletal homeostasis over time. METHODS: Mfn2 was selectively deleted in vivo at three different stages of osteoblast lineage commitment by crossing mice in which the Mfn2 gene was floxed with transgenic mice expressing Cre under the control of the promoter for Osterix (OSX), collagen1a1, or DMP1 (Dentin Matrix Acidic Phosphoprotein 1). RESULTS: Mice in which Mfn2 was deleted using DMP1-cre demonstrated a progressive and dramatic decline in bone mineral density (BMD) beginning at 10 weeks of age (n = 5 for each sex and each genotype from age 10 to 20 weeks). By 15 weeks, there was evidence for a functional decline in muscle performance as assessed using a rotarod apparatus (n = 3; 2 males/ 1 female for each genotype), accompanied by a decline in lean body mass. A marked reduction in trabecular bone mass was evident on bone histomorphometry, and biomechanical testing at 25 weeks (k/o: 2 male/1 female, control 2 male/2 female) revealed severely impaired femur strength. Extensive regional myofiber atrophy and degeneration was observed on skeletal muscle histology. Electron microscopy showed progressive disruption of cellular architecture, with disorganized sarcomeres and a bloated mitochondrial reticulum. There was also evidence of neurodegeneration within the ventral horn and roots of the lumbar spinal cord, which was accompanied by myelin loss and myofiber atrophy. Deletion of Mfn2 using OSX-cre or Col1a1-cre did not result in a musculoskeletal phenotype. Where possible, male and female animals were analyzed separately, but small numbers of animals in each group limited statistical power. For other outcomes, where sex was not considered, small sample sizes might still limit the strength of the observation. CONCLUSION: Despite known functional overlap of Mfn1 and Mfn2 in some tissues, and their co-expression in bone, muscle and spinal cord, deletion of Mfn2 using the 8 kB DMP1 promoter uncovered an important non-redundant role for Mfn2 in maintaining the neuromuscular/bone axis.

Sequential heterologous immunization with COVID-19 vaccines induces broader neutralizing responses against SARS-CoV-2 variants in comparison with homologous boosters.

The recently prevalent variants of concerns (VOCs) of SARS-CoV-2 belong to Omicron variants which display increased transmissibility and evade from immune protection generated by vaccines and/or natural infections. Better immunization strategies should be explored to induce broader immune responses against evolving SARS-CoV-2 variants. Here, we used inactivated vaccines derived from ancestral (Wu), Delta (Del) and Omicron (Omi) strains to immunize mice with homologous booster (3 × Wu, 3 × Del and 3 × Omi) or heterologous sequential booster (Wu/Del/Omi and Omi/Wu/Del) to evaluate their responses against two pre-Omicron (Wu and Del) and four Omicron variants. Even though neutralization responses against Wu and Del variants were similar in heterologous and homologous immunization groups, heterologous immunization groups induced significantly stronger neutralizing antibody against BA.1 (4.1-11 folds higher) and BA.2 (4.7-14.2 folds higher) than those of homologous immunization groups. While homologous immunization only induced strong neutralizing responses to either pre-Omicron variants (Wu and Del) in 3 × Wu and 3 × Del groups or to Omicron variants (BA.1 and BA.2) in 3 × Omi group, heterologous immunization groups induced strong and broader neutralizing responses to both pre-Omicron (Wu, Del) and Omicron variants (BA.1 and BA.2). Homologous and heterologous immunization groups elicited similar antigen-specific T cell (IFN-γ+) and B cell responses. Compared with homologous immunization, heterologous immunization could induce stronger plasma cell responses, which have the potential to generate broader and stronger neutralizing antibodies. However, neither heterologous nor homologous immunization groups induced strong neutralizing antibody against variants with bigger genetic deviation, such as BA.4/5 or BF.7, only weak neutralizing responses were induced. Surveillance on SARS-CoV2 variants evolution and immunization strategy are needed to explore better vaccines with broader and stronger neutralizing antibodies against post pandemic COVID-19.

Moxibustion treatment for Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. METHODS: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson's Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. DISCUSSION: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

Dynamics of a delayed reaction-diffusion predator-prey model with the effect of the toxins.

In this study, we investigate a delayed reaction-diffusion predator-prey system with the effect of toxins. We first investigate whether the internal equilibrium exists. We then provide certain requirements for the presence of Turing and Hopf bifurcations by examining the corresponding characteristic equation. We also study Turing-Hopf and Hopf bifurcations brought on by delays. Finally, numerical simulations that exemplify our theoretical findings are provided. The quantitatively obtained properties are in good agreement with the findings that the theory had predicted. The effects of toxins on the system are substantial, according to theoretical and numerical calculations.

Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Identifying key genes related to inflammasome in severe COVID-19 patients based on a joint model with random forest and artificial neural network.

Background: The coronavirus disease 2019 (COVID-19) has been spreading astonishingly and caused catastrophic losses worldwide. The high mortality of severe COVID-19 patients is an serious problem that needs to be solved urgently. However, the biomarkers and fundamental pathological mechanisms of severe COVID-19 are poorly understood. The aims of this study was to explore key genes related to inflammasome in severe COVID-19 and their potential molecular mechanisms using random forest and artificial neural network modeling. Methods: Differentially expressed genes (DEGs) in severe COVID-19 were screened from GSE151764 and GSE183533 via comprehensive transcriptome Meta-analysis. Protein-protein interaction (PPI) networks and functional analyses were conducted to identify molecular mechanisms related to DEGs or DEGs associated with inflammasome (IADEGs), respectively. Five the most important IADEGs in severe COVID-19 were explored using random forest. Then, we put these five IADEGs into an artificial neural network to construct a novel diagnostic model for severe COVID-19 and verified its diagnostic efficacy in GSE205099. Results: Using combining P value < 0.05, we obtained 192 DEGs, 40 of which are IADEGs. The GO enrichment analysis results indicated that 192 DEGs were mainly involved in T cell activation, MHC protein complex and immune receptor activity. The KEGG enrichment analysis results indicated that 192 GEGs were mainly involved in Th17 cell differentiation, IL-17 signaling pathway, mTOR signaling pathway and NOD-like receptor signaling pathway. In addition, the top GO terms of 40 IADEGs were involved in T cell activation, immune response-activating signal transduction, external side of plasma membrane and phosphatase binding. The KEGG enrichment analysis results indicated that IADEGs were mainly involved in FoxO signaling pathway, Toll-like receptor, JAK-STAT signaling pathway and Apoptosis. Then, five important IADEGs (AXL, MKI67, CDKN3, BCL2 and PTGS2) for severe COVID-19 were screened by random forest analysis. By building an artificial neural network model, we found that the AUC values of 5 important IADEGs were 0.972 and 0.844 in the train group (GSE151764 and GSE183533) and test group (GSE205099), respectively. Conclusion: The five genes related to inflammasome, including AXL, MKI67, CDKN3, BCL2 and PTGS2, are important for severe COVID-19 patients, and these molecules are related to the activation of NLRP3 inflammasome. Furthermore, AXL, MKI67, CDKN3, BCL2 and PTGS2 as a marker combination could be used as potential markers to identify severe COVID-19 patients.

Insights into the regulation of energy metabolism during the seed-to-seedling transition in marine angiosperm Zostera marina L.: Integrated metabolomic and transcriptomic analysis.

Seed development is a crucial phase in the life cycle of seed-propagated plants. As the only group of angiosperms that evolved from terrestrial plants to complete their life cycle submerged in marine environments, the mechanisms underlying seed development in seagrasses are still largely unknown. In the present study, we attempted to combine transcriptomic, metabolomic, and physiological data to comprehensively analyze the molecular mechanism that regulates energy metabolism in Zostera marina seeds at the four major developmental stages. Our results demonstrated that seed metabolism was reprogrammed with significant alteration of starch and sucrose metabolism, glycolysis, the tricarboxylic acid cycle (TCA cycle), and the pentose phosphate pathway during the transition from seed formation to seedling establishment. The interconversion of starch and sugar provided energy storage substances in mature seeds and further acted as energy sources to support seed germination and seedling growth. The glycolysis pathway was active during Z. marina germination and seedling establishment, which provided pyruvate for TCA cycle by decomposing soluble sugar. Notably, the biological processes of glycolysis were severely inhibited during Z. marina seed maturation may have a positive effect on seed germination, maintaining a low level of metabolic activity during seed maturation to preserve seed viability. Increased acetyl-CoA and ATP contents were accompanied with the higher TCA cycle activity during seed germination and seedling establishment, indicating that the accumulations of precursor and intermediates metabolite that can strengthen the TCA cycle and facilitate energy supply for Z. marina seed germination and seedling growth. The large amount of oxidatively generated sugar phosphate promotes fructose 1,6-bisphosphate synthesis to feed back to glycolysis during seed germination, indicating that the pentose phosphate pathway not only provides energy for germination, but also complements the glycolytic pathway. Collectively, our findings suggest these energy metabolism pathways cooperate with each other in the process of seed transformation from maturity to seedling establishment, transforming seed from storage tissue to highly active metabolic tissue to meet the energy requirement seed development. These findings provide insights into the roles of the energy metabolism pathway in the complete developmental process of Z. marina seeds from different perspectives, which could facilitate habitat restoration of Z. marina meadows via seeds.

Altered Expression of Several Molecular Mediators of Cerebrospinal Fluid Production in Hyp Mice.

Context: X-linked hypophosphatemia (XLH) is a genetic disease, causing life-long hypophosphatemia due to overproduction of fibroblast growth factor 23 (FGF23). XLH is associated with Chiari malformations, cranial synostosis, and syringomyelia. FGF23 signals through FGFR1c and requires a coreceptor, α-Klotho, which is expressed in the renal distal convoluted tubules and the choroid plexus (ChP). In the ChP, α-Klotho participates in regulating cerebrospinal fluid (CSF) production by shuttling the sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) to the luminal membrane. The sodium/potassium/chloride cotransporter 1 (NKCC1) also makes a substantial contribution to CSF production. Objective: Since CSF production has not been studied in XLH, we sought to determine if there are changes in the expression of these molecules in the ChP of Hyp mice, the murine model of XLH, as a first step toward testing the hypothesis that altered CSF production contributes to the cranial and spinal malformations seen this disease. Methods: Semi-quantitative real-time PCR was used to analyze the level of expression of transcripts for Fgfr1c, and thee key regulators of CSF production, Klotho, Atp1a1 and Slc12a2. In situ hybridization was used to provide anatomical localization for the encoded proteins. Results: Real-time polymerase chain reaction (RT-PCR) demonstrated significant upregulation of Klotho transcripts in the fourth ventricle of Hyp mice compared to controls. Transcript levels for Fgfr1c were unchanged in Hyp mice. Atp1a1 transcripts encoding the alpha-1 subunit of Na+/K+-ATPase were significantly downregulated in the third and lateral ventricles (LV). Expression levels of the Slc12a2 transcript (which encodes NKCC1) were unchanged in Hyp mice compared to controls. In situ hybridization (ISH) confirmed the presence of all 4 transcripts in the LV ChP both of WT and Hyp mice. Conclusion: This is the first study to document a significant change in the level of expression of the molecular machinery required for CSF production in Hyp mice. Whether similar changes occur in patients with XLH, potentially contributing to the cranial and spinal cord abnormalities frequently seen in XLH, remains to be determined.

Eco-Corona Dictates Mobility of Nanoplastics in Saturated Porous Media: The Critical Role of Preferential Binding of Macromolecules.

Nanoplastics are an increasing environmental concern. In aquatic environments, nanoplastics will acquire an eco-corona by interacting with macromolecules (e.g., humic substances and extracellular polymeric substances (EPS)). Here, we show that the properties of the eco-corona and, consequently, its ability to enhance the transport of nanoplastics vary significantly with the surface functionality of nanoplastics and sources of macromolecules. The eco-corona derived from the EPS of Gram-negative Escherichia coli MG1655 enhances the transport of polystyrene (PS) nanospheres in saturated porous media to a much greater extent than the eco-corona derived from soil humic acid and fulvic acid. In comparison, the eco-corona from all three sources significantly enhance the transport of carboxylated PS (HOOC-PS). We show that the eco-corona inhibits the deposition of the two types of nanoplastics to the porous media mainly via steric repulsion. Accordingly, an eco-corona consisting of a higher mass of larger-sized macromolecules is generally more effective in enhancing transport. Notably, HOOC-PS tends to acquire macromolecules of lower hydrophobicity than PS. The more disordered and flexible structures of such macromolecules may result in greater elastic repulsion between the nanoplastics and sand grains and, consequently, greater transport enhancement. The findings of this study highlight the critical role of eco-corona formation in regulating the mobility of nanoplastics, as well as the complexity of this process.

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field.

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-ß-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-ß-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.

Atractylodes lancea volatile oils target ADAR2-miR-181a-5p signaling to mesenchymal stem cell chondrogenic differentiation.

Atractylodeslancea Rhizoma (Rhizoma atractylodis [RA]) has long been recommended for the treatment of arthritis in traditional Chinese medicine, but its mechanism of action is still unclear. RA contains a large amount of Atractylodes lancea volatile oils (Atr). In this study, we investigated whether Atr can promote mesenchymal stem cells (MSCs) chondrogenic differentiation. The Atr were extracted from RA by steam distillation method, and the effect of Atr on MSCs was detected by the CCK8 assay. The optimal concentration of Atr for MSCs cultivation was 3 µg/ml. The differentially expressed miR-181a-5p was screened by miRNA microarray assay, and its mimics and inhibitors were transfected into MSCs. It was found that the inhibitor of miR-181a-5p could upregulate cartilage-specific genes such as SOX9, COL2A1, and ACAN. Meanwhile, we also found that the expression of gene editing enzyme ADAR2 was significantly increased in the chondrogenic differentiation of MSCs induced by Atr, and the bases of precursor sequence of miR-181a-5p were changed from A to G. After ADAR2 deletion, the expression of cartilage-specific genes was significantly down-regulated and the precursor sequence bases of miR-181a-5p were not changed. Bioinformatics analysis revealed that the predicted target gene of miR-181a-5p was yingyang1 (YY1), and the targeting relationship was verified by dual-luciferase reporter assay. After deleting YY1, the expression of cartilage-specific genes was significantly down-regulated. In conclusion, our study demonstrated that Atr can promote chondrogenic differentiation of MSC through regulation of the ADAR2-miR-181a-5p signaling pathway. This may provide a new insight into the possible mechanism of traditional Chinese medicine (Atr) in treating inflammatory joint diseases.

Dietary vitamin E intake and risk of Parkinson's disease: a cross-sectional study.

Objective: Current evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years. Methods: We conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD. Results: According to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P < 0.05 for interaction). Conclusion: Among participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.

Engineered Dynamic Hydrogel Niches for the Regulation of Redox Homeostasis in Osteoporosis and Degenerative Endocrine Diseases.

Osteoporosis and degenerative endocrine diseases are some of the major causes of disability in the elderly. The feedback loop in the endocrine system works to control the release of hormones and maintain the homeostasis of metabolism, thereby regulating the function of target organs. The breakdown of this feedback loop results in various endocrine and metabolic disorders, such as osteoporosis, type II diabetes, hyperlipidemia, etc. The direct regulation of redox homeostasis is one of the most attractive strategies to redress the imbalance of the feedback loop. The biophysical regulation of redox homeostasis can be achieved through engineered dynamic hydrogel niches, with which cellular mechanics and redox homeostasis are intrinsically connected. Mechanotransduction-dependent redox signaling is initiated by cell surface protein assemblies, cadherins for cell-cell junctions, and integrins for cell-ECM interactions. In this review, we focused on the biophysical regulation of redox homeostasis via the tunable cell-ECM interactions in the engineered dynamic hydrogel niches. We elucidate processes from the rational design of the hydrogel matrix to the mechano-signaling initiation and then to the redox response of the encapsulated cells. We also gave a comprehensive summary of the current biomedical applications of this strategy in several degenerative endocrine disease models.

Comparative analysis of mitochondrial genomes reveals marine adaptation in seagrasses.

BACKGROUND: Seagrasses are higher marine flowering plants that evolved from terrestrial plants, but returned to the sea during the early evolution of monocotyledons through several separate lineages. Thus, they become a good model for studying the adaptation of plants to the marine environment. Sequencing of the mitochondrial (mt) genome of seagrasses is essential for understanding their evolutionary characteristics. RESULTS: In this study, we sequenced the mt genome of two endangered seagrasses (Zostera japonica and Phyllospadix iwatensis). These data and data on previously sequenced mt genomes from monocotyledons provide new evolutionary evidence of genome size reduction, gene loss, and adaptive evolution in seagrasses. The mt genomes of Z. japonica and P. iwatensis are circular. The sizes of the three seagrasses (including Zostera marine) that have been sequenced to date are smaller than that of other monocotyledons. Additionally, we found a large number of repeat sequences in seagrasses. The most abundant long repeat sequences were 31-40 bp repeats. Our study also found that seagrass species lost extensive ribosomal protein genes during evolution. The rps7 gene and the rpl16 gene of P. iwatensis are exceptions to this trend. The phylogenetic analysis based on the mt genome strongly supports the previous results. Furthermore, we identified five positive selection genes (atp8, nad3, nad6, ccmFn, and matR) in seagrasses that may be associated with their adaptation to the marine environment. CONCLUSIONS: In this study, we sequenced and annotated the mt genomes of Z. japonica and P. iwatensis and compared them with the genome of other monocotyledons. The results of this study will enhance our understanding of seagrass adaptation to the marine environment and can inform further investigations of the seagrass mt genome.

Cerium-Doped Iron Oxide Nanorod Arrays for Photoelectrochemical Water Splitting.

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe2O3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe2O3, which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe2O3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe2O3 nanorod arrays (FT). The Hydrogen (H2) production from PEC water splitting of Fe2O3 was highly improved by Ce doping to achieve an evolution rate of 21 µmol/cm2/h.

DESIGN, CONSTRUCTION AND TEST OF GAMMA IONIZATION CHAMBERS.

Ionization chamber is considered as the golden standard for the dosemeter. This work fabricated one graphite-walled and two polymethyl methacrylate (PMMA)-walled ionization chambers, tested respectively and compared their characteristic parameters. The performance of graphite-walled chamber was similar to that of the PMMA-walled chamber. The relative energy response of ionization chambers was lower than 4% from 50 keV to 50 MeV based on the FLUKA code simulation results. The experimental data showed that the ionization chambers performed well in linearity and repeatability. Assuming the chambers sensitive volume and HV bias was constant, the measured maximum saturation absorbed dose of ionization chambers changed with the diameter variation of chambers anode based on the comparison results of two PMMA-walled ionization chambers.