Identification of potential pathogenic genes related to osteoporosis and osteoarthritis.

BACKGROUND: Osteoarthritis (OA) and osteoporosis (OS) are the most common orthopedic diseases. OBJECTIVE: To identify important genes as biomarkers for the pathogenesis of OA and OS. METHODS: Microarray data for OA and OS were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the OA and healthy control groups and between the OS and healthy control groups were identified using the Limma software package. Overlapping hub DEGs were selected using MCC, MNC, DEGREE, and EPC. Weighted gene co-expression network analysis (WGCNA) was used to mine OA- and OS-related modules. Shared hub DEGs were identified, human microRNA disease database was used to screen microRNAs associated with OA and OS, and an miRNA-target gene network was constructed. Finally, the expression of shared hub DEGs was evaluated. RESULTS: A total of 104 overlapping DEGs were identified in both the OA and OS groups, which were mainly related to inflammatory biological processes, such as the Akt and TNF signaling pathways Forty-six hub DEGs were identified using MCC, MNC, DEGREE, and EPC modules using different algorithms. Seven modules with 392 genes that highly correlated with disease were identified in the WGCNA. Furthermore, 10 shared hub DEGs were identified between the OA and OS groups, including OGN, FAP, COL6A3, THBS4, IGFBP2, LRRC15, DDR2, RND3, EFNB2, and CD48. A network consisting of 8 shared hub DEGs and 55 miRNAs was constructed. Furthermore, CD48 was significantly upregulated in the OA and OS groups, whereas EFNB2, DR2, COL6A3, and RND3 were significantly downregulated in OA and OS. Other hub DEGs were significantly upregulated in OA and downregulated in OS. CONCLUSIONS: The ten genes may be promising biomarkers for modulating the development of both OA and OS.

Compensatory upregulation of MT2A alleviates neurogenic intermittent claudication through inhibiting activated p38 MAPK-mediated neuronal apoptosis.

Neurogenic intermittent claudication (NIC), a classic symptom of lumbar spinal stenosis (LSS), is associated with neuronal apoptosis. To explore the novel therapeutic target of NIC treatment, we constructed the rat model of NIC by cauda equina compression (CEC) method and collected dorsal root ganglion (DRG) tissues, a region responsible for sensory and motor function, for mRNA sequencing. Bioinformatic analysis of mRNA sequencing indicated that upregulated metallothionein 2A (MT2A), an apoptosis-regulating gene belonging to the metallothionein family, might participate in NIC progression. Activated p38 MAPK mediated motor dysfunction following LSS and it was also found in DRG tissues of rats with NIC. Therefore, we supposed that MT2A might affect NIC progression by regulating p38 MAPK pathway. Then the rat model of NIC was used to explore the exact role of MT2A. Rats at day 7 post-CEC exhibited poorer motor function and had two-fold MT2A expression in DRG tissues compared with rats with sham operation. Co-localization analysis showed that MT2A was highly expressed in neurons, but not in microglia or astrocytes. Subsequently, neurons isolated from DRG tissues of rats were exposed to hypoxia condition (3% O2, 92% N2, 5% CO2) to induce cell damage. Gain of MT2A function in neurons was performed by lentivirus-mediated overexpression. MT2A overexpression inhibited apoptosis by inactivating p38 MAPK in hypoxia-exposed neurons. Our findings indicated that high MT2A expression was related to NIC progression, and MT2A overexpression protected against NIC through inhibiting activated p38 MAPK-mediated neuronal apoptosis in DRG tissues.

Near-Space Wide-Area and High-Resolution Imaging System Design and Implementation.

The near-space atmosphere is thin, and the atmospheric refraction and scattering on optical observation is very small, making it very suitable for wide-area and high-resolution surveillance using high-altitude balloon platforms. This paper adopts a 9344 × 7000 CMOS sensor to obtain high-resolution images, generating large-field-of-view imaging through the swing scanning of the photoelectric sphere and image stitching. In addition, a zoom lens is designed to achieve flexible applications for different scenarios, such as large-field-of-view and high-resolution imaging. The optical design results show that the camera system has good imaging quality within the focal length range of 320 mm-106.7 mm, and the relative distortion values at different focal lengths are less than 2%. The flight results indicate that the system can achieve seamless image stitching at a resolution of 0.2 m@20 km and the imaging field of view angle exceeds 33°. This system will perform other near-space flight experiments to verify its ultra-wide (field of view exceeding 100°) high-resolution imaging application.

The Efficacy and Safety of Bionic Tiger Bone Powder for the Treatment of Knee Osteoarthritis in Early Stage: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

Objective: This study evaluated the efficacy and safety of bionic tiger bone powder (Jintiange) in comparison to placebo in treating knee osteoarthritis osteoporosis. Methods: A total of 248 patients were randomly allocated to a Jintiange group or a placebo group, undergoing 48 weeks of double-blind treatment. The Lequesne index, clinical symptoms, safety index (adverse events), and Patient's Global Impression of Change score were recorded at pre-determined time intervals. All P values ≤ .05 were deemed statistically significant. Results: Both groups showed a decreasing trend in the Lequesne index, with the Jintiange group's reduction significantly larger from the 12th week (P ≤ .01). Similarly, the effective rate of Lequesne score in the Jintiange group was significantly higher (P < .001). After 48 weeks, clinical symptom score differences between the Jintiange group (2.46 ± 1.74) and the placebo group (1.51 ± 1.73) were statistically significant (P < .05), as were differences in the Patient's Global Impression of Change score (P < .05). Adverse drug reactions were minimal with no significant difference between the groups (P > .05). Conclusion: Jintiange demonstrated superior efficacy over placebo in treating knee osteoporosis, with comparable safety profiles. Findings warrant further comprehensive real-world studies.

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility. METHODS: A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software. RESULTS: In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis. CONCLUSION: The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.

Smurf1 Facilitates Oxidative Stress and Fibrosis of Ligamentum Flavum by Promoting Nrf2 Ubiquitination and Degradation.

Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.

Association Between the Cervical Extensor Musculature and the Demographic Features, Symptoms, and Sagittal Balance in Patients with Multilevel Cervical Spondylotic Myelopathy.

OBJECTIVE: To obtain the quantitative measurements of the muscle morphology of cervical extensors in patients with multilevel cervical spondylotic myelopathy, and determine whether the morphological parameter of each muscle correlates with the patients' demographic features, symptoms, and cervical sagittal balance. METHODS: We retrospectively evaluated 100 hospitalized patients scheduled to undergo surgery for multilevel cervical spondylotic myelopathy. Demographic data, including age, sex, and body mass index, were recorded, and symptoms were evaluated using the visual analog scale (VAS), neck disability index (NDI), and modified Japanese Orthopedic Association scale scores. The cross-sectional area (CSA) of the multifidus, semispinalis capitis, semispinalis cervicis, splenius capitis and splenius cervicis were measured on magnetic resonance imaging. The CSA of the total extensor muscles, deep extensor muscles (DEM, consisting of multifidus and semispinalis capitis), and superficial extensor muscles (consisting of semispinalis cervicis, splenius capitis and splenius cervicis) were calculated. The adjusted CSA (aCSA) was calculated as the CSA of the muscle/CSA of the corresponding vertebral body. The fat infiltration ratio (FIR) of the posterior extensor muscles was assessed using a pseudocoloring technique. Sagittal parameters, including cervical lordosis (CL), C2-7 cervical sagittal vertical axis (SVA), T1-slope, mismatch between T1-slope and CL (T1S-CL), and range of motion, were measured. The measured parameters were compared between the males and the females, between the patients with higher muscle aCSA and the patients with lower muscle aCSA, and between the patients with and without sagittal balance. A Pearson correlation analysis was conducted to determine the correlations between the paraspinal muscle measurements, and the clinical and radiographic parameters. RESULTS: There were 67 males and 33 females in this study, and the mean age was 59.22 ± 9.54 years. Compared with females, male patients showed higher CSA and aCSA of extensor muscles. Patients with lower muscle aCSA were significantly older and had worse NDI scores, with significantly greater C2-7 SVA and T1S-CL. Patients with sagittal imbalance showed significantly lower aCSA of total extensor muscles and DEM, as well as a significantly higher FIR. Age was significantly correlated with the aCSA of each measured muscle and the FIR. The aCSA of the DEM was correlated with the NDI score, the visual analog scale score, the SVA, the T1-slope, and the T1S-CL. CONCLUSIONS: In patients with multilevel CSM, age and sex were demographic factors that were highly correlated with muscle morphology changes. Extensor muscles, especially DEM, play important roles in maintaining cervical sagittal balance and are associated with the severity of neck symptoms.

Micromotion-based balanced drilling technology to increase near cortical strain.

OBJECTIVE: A micromotion-based balanced drilling system was designed based on a locking plate (LP) and far cortical locking (FCL) concept to maintain the balance of micromotions of the cortex on both sides of a fracture region. The system was tested by axial compression test. METHODS: The fracture gap was set to 2 cm, and locking screws with a diameter of 5 mm and a locking plate were used to fix it. The diameters of the two sections of the stepping drill were 3.5 mm and 5.0 mm, respectively. One of the matching drilling sleeves was a standard sleeve (eccentricity, 0 mm) and the other was an eccentric sleeve (proximal eccentricity, 1 mm). A model of the fixed locking plate (AO/ASIF 33-A3) for distal femoral fractures with a gap of 2 cm was established based on data from 42 artificial femurs (SAWBONE). According to the shape of the screw holes on the cortex, the fixed fracture models were divided into a control group (standard screw hole group X126, six cases) and an experimental group (elliptical screw hole group N, 36 cases). The experimental group was further divided into six subgroups with six cases in each (N126, N136, N1256, N1356, N12356, N123456), based on the number and distribution of the screws on the proximal fracture segment. The control, N126, and N136 groups were subjected to an axial load of 500 N, and the other groups were subjected to an axial load of 1000 N. The displacements of the kinetic head, far cortex, and near cortex were measured. The integral structural stiffness of the model and the near cortical strain were calculated. The data of each group were analyzed by using a paired t-test. RESULTS: When the far cortical strains were 2%, 5%, and 10%, the near cortical strains in group N126 were 0.96%, 2.35%, and 4.62%, respectively, significantly higher than those in the control group (X126) (p < 0.05). For a different distribution of the screws, when the far cortical strains were 2%, 5%, and 10%, the near cortical strains in group N126 were significantly higher than those in group N136 (p < 0.05). However, there was no significant difference between the near cortical strains in the two groups with four screws (p > 0.05). For different numbers of screws, the near cortical strains in the three-screw groups were significantly higher than those in the four-screw groups (p < 0.05), and there was no significant difference in near cortical strains among the four-, five-, and six-screw groups (p > 0.05). CONCLUSION: The proposed drill and matching sleeves enabled a conventional locking compression plate to be transformed into an internal fixation system to improve the balanced motion of the near and far cortices. Thus, strain on a fracture site could be controlled by adjusting the diameter of the drill and the eccentricity of the sleeve.

Proteomic and Metabolomic Evaluation of Insect- and Herbicide-Resistant Maize Seeds.

Label-free quantitative proteomic (LFQ) and widely targeted metabolomic analyses were applied in the safety evaluation of three genetically modified (GM) maize varieties, BBL, BFL-1, and BFL-2, in addition to their corresponding non-GM parent maize. A total of 76, 40, and 25 differentially expressed proteins (DEPs) were screened out in BBL, BFL-1, and BFL-2, respectively, and their abundance compared was with that in their non-GM parents. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most of the DEPs participate in biosynthesis of secondary metabolites, biosynthesis of amino acids, and metabolic pathways. Metabolomic analyses revealed 145, 178, and 88 differentially accumulated metabolites (DAMs) in the BBL/ZH58, BFL-1/ZH58, and BFL-2/ZH58×CH72 comparisons, respectively. KEGG pathway enrichment analysis showed that most of the DAMs are involved in biosynthesis of amino acids, and in arginine and proline metabolism. Three co-DEPs and 11 co-DAMs were identified in the seeds of these GM maize lines. The proteomic profiling of seeds showed that the GM maize varieties were not dramatically different from their non-GM control. Similarly, the metabolomic profiling of seeds showed no dramatic changes in the GM/non-GM maize varieties compared with the GM/GM and non-GM/non-GM maize varieties. The genetic background of the transgenic maize was found to have some influence on its proteomic and metabolomic profiles.

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We measured the morphological index, nutritional composition and the expression analysis of key genes during grain development of Paeonia suffruticosa cv. 'Fengdan' grown at altitudes of 100, 650 and 1010 m in Luo-yang. The aim of this study was to examine differences in grain yield traits and the transformation of soluble sugar, starch, soluble protein and fatty acid contents, as well as the related enzyme activity and differential expression of key genes in oil metabolism. The results showed that grain yield traits increased with altitudes and that the growth period of grain at the higher altitudes was longer than that at low and mid altitudes. The soluble sugar and starch in mature grains increased with altitudes, while soluble protein and crude fat did not change. During grain development, the activities of sucrose synthase (SS) and sucrose phosphate synthase (SPS) first decreased and then increased, with the lowest occurred at 90 d after flowering. The activities of pyruvate dehydrogenase (PDH), glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminease (GOT) increased rapidly during 50-90 d after flowering and peaked at 90 d. The relative expression of acetyl-CoA carboxylase (ACCase) and stearoyl-ACP desaturase (SAD) peaked at 50 d after flowering, and ω-6 fatty acid desaturase 2 (FAD2) peaked at 90 d, in oil tree peony grain at different altitudes. There was a negative correlation of soluble sugar and starch with the accumulation of soluble protein and crude fat. SPS activity was positively correlated with the contents of soluble sugar and starch, and negatively correlated with the contents of soluble protein and crude fat during grain development. Activities of GPT and GOT were negatively associated with the content of soluble sugar and the content of starch, and had a highly significant positive correlation with the contents of soluble protein and crude fat. Activity of PDH was positively correlated with the content of soluble proteins and activities of GPT and GOT, and negatively correlated with the contents of soluble sugar and starch. It suggested that nutrient accumulation in the process of grain development of tree peony was transformed from sugar to crude fat and protein, and that metabolic enzymes, such as SPS, PDH, GPT and GOT, played an important role in this process. Palmitate acid, stearic acid and linoleic acid were negatively correlated with the relative increment of α-linolenic acid, indicating that fatty acid desaturation process in the grain development of tree peony was towards the direction of α-linolenic acid synthesis. The relative expression of ACCase, SAD, and FAD2 was positively correlated with the relative increment of α-linolenic acid accumulation, which played an important role in α-linolenic acid synthesis. The oil quality of tree peony grain was relatively stable at different altitudes, but grain production increased with altitude. Planting oil tree peony at mid to high altitudes could be an important strategy for the efficient use of marginal land in Luoyang.

Improved Active Disturbance Rejection Double Closed-Loop Control of a Rotary-Type VCM in a Moving Mirror Control System.

Aiming to address the problem of moving mirror speed fluctuations in moving mirror control systems, an improved active disturbance rejection double closed-loop controller (IADR-DCLC) is proposed and verified by simulation to realize the high-performance control of a moving mirror control system. First, the mathematical model of a rotary-type voice coil motor (RT VCM) is established, and the relationship between the angular velocity of the RT VCM and the optical path scanning velocity is analyzed. Second, in order to suppress the model uncertainty and external disturbance of the system, an improved active disturbance rejection controller (IADRC) is proposed. Compared with a conventional ADRC, the tracking differentiator of the proposed IADRC is replaced with desired signal optimization (DSO), and the actual speed is introduced to the extended state observer (ESO). The IADRC is used in the position-speed double closed-loop control model. Finally, the simulation results show that the IADR-DCLC has not only a good tracking effect but also a good anti-interference ability and can meet the requirements of the moving mirror control system for the uniformity of optical-path scanning speed and accurate control of the position of the moving mirror.

Near-Earth space balloon-based multi-band airglow imager optic design.

As a common tracer in the atmosphere, airglow can be used as an important means to study the interaction between the lower atmosphere, near space, and ionosphere. In the near-Earth space, the high-altitude balloon can realize long time flight, which makes the airglow detection realize both high range resolution and time resolution. In this paper, a balloon-based multi-band airglow imager is designed, which can observe OI (557.7 nm), Na (589.3 nm), OI (630.0 nm), and OH (720-910 nm) with annular field of view (30° inner ring and 80° outer ring), and its resolution is 500 m at 250 km. The multi-band airglow imager designed in this paper is equipped in the payload cabin and raised to above 30 km for flat flying for more than 6 h. The experimental results show that the imager worked normally, and airglow images were photographed and stored; the optical system can stand the harsh environment in the near space. The multi-band airglow imager designed in this paper will take part in other near-space exploration tasks in the future and obtain corresponding results.

The Heterogeneity of Infiltrating Macrophages in Metastatic Osteosarcoma and Its Correlation with Immunotherapy.

BACKGROUND: Metastatic osteosarcoma is a common and fatal bone tumor. Several studies have found that tumor-infiltrating immune cells play pivotal roles in the progression of metastatic osteosarcoma. However, the heterogeneity of infiltrating immune cells across metastatic and primary osteosarcoma remains unclear. METHODS: Immune infiltration analysis was carried out via the "ESTIMATE" and "xCell" algorithms in primary and metastatic osteosarcoma. Then, we evaluated the prognostic value of infiltrating immune cells in 85 osteosarcomas through the Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve. Infiltrations of macrophage M1 and M2 were evaluated in metastatic osteosarcoma, as well as their correlation with immune checkpoints. Macrophage-related prognostic genes were identified through Weighted Gene Coexpression Network Analysis (WGCNA), Lasso analysis, and Random Forest algorithm. Finally, a macrophage-related risk model had been constructed and validated. RESULTS: Macrophages, especially the macrophage M1, sparingly infiltrated in metastatic compared with the primary osteosarcoma and predicted the worse overall survival (OS) and disease-free survival (DFS). Macrophage M1 was positively correlated with immune checkpoints PDCD1, CD274 (PD-L1), PDCD1LG2, CTLA4, and TIGIT. In addition, four macrophage-related prognostic genes (IL10, VAV1, CD14, and CCL2) had been identified, and the macrophage-related risk model had been validated to be reliable for evaluating prognosis in osteosarcoma. Simultaneously, the risk score showed a strong correlation with several immune checkpoints. CONCLUSION: Macrophages potentially contribute to the regulation of osteosarcoma metastasis. It can be used as a candidate marker for metastatic osteosarcoma' prognosis and immune checkpoints blockades (ICBs) therapy. We constructed a macrophage-related risk model through machine-learning, which might help us evaluate patients' prognosis and response to ICBs therapy.

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota.

Lumbar disc herniation (LDH) is a common cause for low back pain. In this study, we aimed to explore the effects of a specific Lactobacillus paracasei (L. paracasei), L. paracasei S16, on the symptoms of LDH using a mouse model of LDH. The results showed that L. paracasei S16 treatment improved the behavior, increased the cell proliferation, and decreased the apoptosis in LDH mice. Moreover, L. paracasei S16 treatment alleviated the aberrant inflammation response in the LDH mice, which is characterized by the decreased anti-inflammatory cytokines, increased pro-inflammatory cytokines, and decreased percentage of Th1 and Th2 cells and Th17/Treg ratio. 16S rRNA sequencing results showed that the LDH mice treated with L. paracasei S16 have higher relative abundance of Lachnospiraceae and Ruminococcaceae and lower abundance of Lactobacillaceae than mice in the LDH group. Additionally, the serum metabolites involved in the linoleic acid metabolism, alanine. aspartate, and glutamate, glycerophospholipid, and TCA cycle were significantly decreased and the metabolite involved in purine metabolism was significantly increased after the L. paracasei S16 treatment in the LDH mice. These results showed that administration of L. paracasei S16 can improve inflammation response, alter gut microbiota, and modulate serum metabolomics in a mouse model of LDH.

The Predictive Value of Monocytes in Immune Microenvironment and Prognosis of Glioma Patients Based on Machine Learning.

Gliomas are primary malignant brain tumors. Monocytes have been proved to actively participate in tumor growth. Weighted gene co-expression network analysis was used to identify meaningful monocyte-related genes for clustering. Neural network and SVM were applied for validating clustering results. Somatic mutation and copy number variation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of risk scores. Monocytes were associated with glioma patients' survival and exhibited high predictive value. The prognostic value of risk score in glioma was validated by the abundant expression of immune checkpoint and metabolic profile. Additionally, high risk score was positively associated with the expression of immunogenic and antigen presenting factors, which indicated high immune infiltration. A prognostic model based on risk score demonstrated high accuracy rate of receiver operating characteristic curves. Compared with previous studies, our research dissected functional roles of monocytes from large-scale analysis. Findings of our analyses strongly support an immune modulatory and prognostic role of monocytes in glioma progression. Notably, monocyte could be an effective predictor for therapy responses of glioma patients.

Pu-miR172d regulates stomatal density and water-use efficiency via targeting PuGTL1 in poplar.

miRNAs play essential regulatory roles in many aspects of plant development and in responses to abiotic and biotic stresses. Here, we characterize Pu-miR172d, which acts as a negative regulator of stomatal density by directly repressing the expression of PuGTL1 in Populus ussuriensis. Quantitative real-time PCR and GUS reporter analyses showed that Pu-miR172d was strongly expressed in the guard cells of young leaves. Overexpression of Pu-miR172d significantly decreased stomatal density, resulting in increases in water use efficiency (WUE) and drought tolerance by reducing net photosynthetic rate, stomatal conductance, and transpiration. Molecular analysis showed that PuGTL1 was a major target of Pu-miR172d cleavage. Moreover, PuGTL1-SRDX plants, in which PuGTL1 is suppressed, phenocopied Pu-miR172d-overexpression lines with reduced stomatal density and enhanced WUE. The expression of PuSDD1, a negative regulator of stomatal development, was significantly increased in young leaves of both Pu-miR172d-overexpression and PuGTL1-SRDX plants. RNA-seq analysis of mature leaves indicated that overexpression of Pu-miR172d decreased the expression of many genes related to photosynthesis. Our findings show that the Pu-miR172d/PuGTL1/PuSDD1 module plays an important role in stomatal differentiation, and hence it is a potential target for engineering improved drought tolerance in poplar.

Ubiquitin-specific protease 49 attenuates IL-1ß-induced rat primary chondrocyte apoptosis by facilitating Axin deubiquitination and subsequent Wnt/ß-catenin signaling cascade inhibition.

Osteoarthritis (OA) is an age-related chronic joint degenerative disease. Interleukin 1 beta (IL-1ß) is considered a marker for the progression of OA. In this study, we found that Ubiquitin-Specific Peptidase 49 (USP49) was significantly less expressed in OA patients compared with healthy individuals. Treating primary rat chondrocytes with different concentrations of IL-1ß resulted in decreased Usp49 expression, while Usp49 overexpression could attenuate IL-1ß-induced chondrocyte apoptosis by promoting Axin deubiquitination. The deubiquitination of Axin led to the accumulation of the protein, which in turn resulted in ß-catenin degradation and Wnt/ß-catenin signaling cascade inhibition. Interestingly, we also found that [6]-gingerol, an anti-OA drug, could upregulate the protein level of Usp49 and suppress the Wnt/ß-catenin signaling cascade in primary rat chondrocytes. Taken together, our study not only demonstrates that Usp49 can negatively regulate the progression of OA by inhibiting the Wnt/ß-catenin signaling cascade, but also elucidates the underlying molecular mechanisms.

PuHox52-mediated hierarchical multilayered gene regulatory network promotes adventitious root formation in Populus ussuriensis.

Adventitious root (AR) formation is critically important in vegetative propagation through cuttings in some plants, especially woody species. However, the underlying molecular mechanisms remain elusive. Here, we report the identification of a poplar homeobox gene, PuHox52, which was induced rapidly (within 15 min) at the basal ends of stems upon cutting and played a key regulatory role in adventitious rooting. We demonstrated that overexpression of PuHox52 significantly increased the number of ARs while suppression of PuHox52 had the opposite effect. A multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PuHox52 was reverse-engineered and demonstrated to govern AR formation. PuHox52 regulated AR formation through upregulation of nine hub regulators, including a jasmonate signaling pathway gene, PuMYC2, and an auxin signaling pathway gene, PuAGL12. We also identified coherent type 4 feed-forward loops within this ML-hGRN; PuHox52 repressed PuHDA9, which encodes a histone deacetylase, and led to an increase in acetylation and presumably expression of three hub regulators, PuWRKY51, PuLBD21 and PuIAA7. Our results indicate that the ML-hGRN mediated by PuHox52 governs AR formation at the basal ends of stem cuttings from poplar trees.

High-Altitude Balloon-Based Sensor System Design and Implementation.

As a kind of large-scale unmanned aerial vehicle, a high-altitude balloon can carry a large load up to tens of kilometers in the near space for a long time, which brings a new way for the stratosphere atmospheric detection. In order to provide a suitable working environment for the near-space detection load, it is necessary to design a sensor system based on a high-altitude balloon, which is used to provide environmental temperature, height position, and attitude information, current working, and video surveillance. The high-altitude balloon-based sensor system designed in this paper had participated in the near-space flight experiment, whose total flight time was 30 h and 53 min, and the horizontal flight time was 28 h and 58 min crossing the day and night. The high-altitude balloon-based sensor system had withstood the severe environment of the near-space during the day and night, providing accurate temperature measurement, real-time altitude position and attitude data acquisition, reliable current monitoring, and comprehensive video surveillance. In the next three years, the high-altitude balloon-based sensor system developed in this paper will continue to participate in the experiment and provide support for more detection loads.