Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration.

BackgroundOne potential mechanism for early superficial cartilage wear in normal joints is alteration of the lubricant content and quality of synovial fluid. The purpose of this study was to determine if the concentration and quality of the lubricant, hyaluronan, in synovial fluid: (1) was similar in left and right knees; (2) exhibited similar age-associated trends, whether collected postmortem or antemortem; and (3) varied with age and grade of joint degeneration.MethodsHuman synovial fluid of donors (23-91 years) without osteoarthritis was analyzed for the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, 0.5-1 MDa, and 0.03-0.5 MDa. Similarity of data between left and right knees was assessed by reduced major axis regression, paired t-test, and Bland-Altman analysis. The effect of antemortem versus postmortem collection on biochemical properties was assessed for age-matched samples by unpaired t-test. The relationships between age, joint grade, and each biochemical component were assessed by regression analysis.ResultsJoint grade and the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, and 0.5-1 MDa in human synovial fluid showed good agreement between left and right knees and were similar between age-matched patient and cadaver knee joints. There was an age-associated decrease in overall joint grade (-15 %/decade) and concentrations of hyaluronan (-10.5 %/decade), and hyaluronan in the molecular weight ranges of 2.5-7 MDa (-9.4 %/decade), 1-2.5 MDa (-11.3 %/decade), 0.5-1 MDa (-12.5 %/decade), and 0.03-0.5 MDa (-13.0 %/decade). Hyaluronan concentration and quality was more strongly associated with age than with joint grade.ConclusionsThe age-related increase in cartilage wear in non-osteoarthritic joints may be related to the altered hyaluronan content and quality of synovial fluid

Geochronology, geochemistry, and tectonic significance of the Shirenshan gneiss in the southern margin of the North China Block

The Shirenshan Block is a complex geological body located in the southern margin of the North China Block (NCB). From south to north, it can be divided into the Taihua Group migmatite, and the Shirenshan gneiss and magmatic rocks. The petrographic features, tectonic setting, provenance, and geological age of the Shirenshan gneiss using comprehensive field investigations, microstructural analysis, zircon U-Pb radioactive dating, and geochemical analyses were investigated for this study. The petrology, geochemistry, and geochronology of the Shirenshan gneiss suggests that it is mainly a felsic rock and its protolith was a high-K calc-alkaline series A-type granite. The protolith is high in SiO2, Al2O3, K2O, Na2O, and low in CaO and MgO. Overall, the Sr-Nd isotope composition of the samples showed no significant difference, indicating that the Taihua Group migmatite and the Shirenshan gneiss have the same source material. The Shirenshan block may be partially melted from the Taihua group and formed during activity of the Luo-Luan Fault. By the method of zircon dating analysis, the protolith age of the Shirenshan block was determined as 1559±16Ma (Early Proterozoic). Then, the crystallization age of the syntectonic migmatite is 439.2±7.6Ma, which was formed by subduction of the Taihua Group. During the early Cretaceous (119.5±1.3Ma), the Shirenshan gneiss may have experienced regional migmatization and formed the zircon rims age of the Yanshanian period. Litho-geochemical features of the Shirenshan block are similar to A1-type granites indicating that they are post-orogenic. Therefore, the metamorphic deformation of the Shirenshan gneiss reflects the tectonics in the southern margin of the NCB.</p

Construction of a High-Density Genetic Map and Identification of Leaf Trait-Related QTLs in Chinese Bayberry (Myrica rubra)

Chinese bayberry (Myrica rubra) is an economically important fruit tree that is grown in southern China. Owing to its over 10-year seedling period, the crossbreeding of bayberry is challenging. The characteristics of plant leaves are among the primary factors that control plant architecture and potential yields, making the analysis of leaf trait-related genetic factors crucial to the hybrid breeding of any plant. In the present study, molecular markers associated with leaf traits were identified via a whole-genome re-sequencing approach, and a genetic map was thereby constructed. In total, this effort yielded 902.11 Gb of raw data that led to the identification of 2,242,353 single nucleotide polymorphisms (SNPs) in 140 F1 individuals and parents (Myrica rubra cv. Biqizhong × Myrica rubra cv. 2012LXRM). The final genetic map ultimately incorporated 31,431 SNPs in eight linkage groups, spanning 1,351.85 cM. This map was then used to assemble and update previous scaffold genomic data at the chromosomal level. The genome size of M. rubra was thereby established to be 275.37 Mb, with 94.98% of sequences being assembled into eight pseudo-chromosomes. Additionally, 18 quantitative trait loci (QTLs) associated with nine leaf and growth-related traits were identified. Two QTL clusters were detected (the LG3 and LG5 clusters). Functional annotations further suggested two chlorophyll content-related candidate genes being identified in the LG5 cluster. Overall, this is the first study on the QTL mapping and identification of loci responsible for the regulation of leaf traits in M. rubra, offering an invaluable scientific for future marker-assisted selection breeding and candidate gene analyses

3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor

Several studies have reported that amyloid fibrils in human semen formed from a naturally occurring peptide fragment of prostatic acidic phosphatase (PAP248-286), known as semen-derived enhancer of viral infection (SEVI), could dramatically enhance human immunodeficiency virus type 1 (HIV-1) infection. Accordingly, SEVI might serve as a novel target for new antiviral drugs or microbicide candidates for the prevention of sexually transmitted HIV. Theoretically, a special anti-PAP or anti-SEVI antibody could reduce the enhancement of viral infection by blocking the binding of HIV and SEVI fibrils. Here, 3-hydroxyphthalic anhydride modified anti-PAP248-286 antibody, named HP-API, exhibited broad-spectrum and highly effective anti-HIV-1 activities on different subtypes and tropism. By using time-of-addition, cell–cell fusion and a single-cycle HIV-1 infection assays, we demonstrated that HP-API is an HIV-1 entry/fusion inhibitor. Mechanism studies suggest that HP-API inhibited HIV-1 entry/fusion by targeting both HIV-1 gp120 envelop and CD4 receptor on the host cell specifically. It is noteworthy that HP-API abrogated the formation of SEVI fibrils and partially interfered with SEVI-mediated enhancement of HIV-1 infection. Based on these findings, HP-API could be considered a bifunctional HIV-1 entry/fusion inhibitor with high potential

A Rare Genetic Defect of MBL2 Increased the Risk for Progression of IgA Nephropathy

The aim of this study was to investigate the association between lectin pathway-related genetic variations and progression in IgA nephropathy. Biopsy-proven IgAN patients with eGFR ≥15 ml/min/1.73 m2 at baseline and a minimum follow-up of 12-months were enrolled. A total of 1,007 patients and 121 healthy controls were enrolled from two Chinese renal centers. The discovery cohort consisted of 606 patients, and the validation cohort consisted of 401 patients. First, promoters, all exons and their boundary regions of MBL2 and FCN2 were sequenced in 50 patients, and then 37 variations were identified. Of these variations, 7 expression-associated variations were selected and genotyped in the whole discovery cohort. We found that rs1800450 in MBL2 and rs7851696 in FCN2 were associated with an increased risk for ESRD as well as serum MBL or L-ficolin levels. However, only rs1800450 was successively validated for its association with ESRD (HR, 15.91; 3.27–77.34; P = 0.001) in the fully adjusted model in the validation cohort. In addition, 2.7% of patients, and 2.5% of healthy controls carried rs1800450-AA. IgAN patients with rs1800450-AA lacked expression of MBL in both serum and renal tissue and had more severe tubulointerstitial damage. Furthermore, a combined effect of rs1800450-AA with a previously reported clinical risk score was observed in which patients with both a high clinical risk score (≥1%) and rs1800450-AA had a strikingly increased 10-years ESRD risk by 37.1-fold (7.17 to 192.13-fold). In summary, IgAN patients carrying MBL2 rs1800450-AA have a high risk for renal function deterioration, probably due to inactivation of the complement MBL pathway

Morphological, Transcriptome, and Hormone Analysis of Dwarfism in Tetraploids of <i>Populus alba</i> × <i>P. glandulosa</i>

Breeding for dwarfism is an important approach to improve lodging resistance. Here, we performed comparative analysis of the phenotype, transcriptome, and hormone contents between diploids and tetraploids of poplar 84K (Populus alba × P. glandulosa). Compared with diploids, the indole-3-acetic acid (IAA) and gibberellin (GA3) contents were increased, whereas the jasmonic acid (JA) and abscisic acid (ABA) contents were decreased in tetraploids. RNA-sequencing revealed that differentially expressed genes (DEGs) in leaves of tetraploids were mainly involved in plant hormone pathways. Most DEGs associated with IAA and GA promotion of plant growth and development were downregulated, whereas most DEGs associated with ABA and JA promotion of plant senescence were upregulated. Weighted gene co-expression network analysis indicated that certain transcription factors may be involved in the regulation of genes involved in plant hormone pathways. Thus, the altered expression of some genes in the plant hormone pathways may lead to a reduction in IAA and GA contents, as well as an elevation in ABA and JA contents, resulting in the dwarfing of tetraploids. The results show that polyploidization is a complex biological process affected by multiple plant hormone signals, and it provides a foundation for further exploration of the mechanism of tetraploids dwarfing in forest trees

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

Abstract Background Semen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro. Results Here, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248–286) and disrupting PAP248–286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen. Conclusions Incorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV

A Study of the Vibration Characteristics of Flexible Mechanical Arms for Pipe String Transportation in Oilfields

During the drilling and repairing of wells, the pipe string transfer equipment has a high work frequency. The movement accuracy, response speed, and controllability of the equipment have significant impacts on the stability. In this paper, we propose an analysis method of mechanical arms to lift pipe strings using a rigid–flexible coupling model. With the mechanical arm as a flexible body and the mechanical hand as a rigid body, a numerical calculation model of the rigid-flexible coupling of the system was established based on the Lagrangian equation. ADAMS and Ansys software were applied to numerical simulations of this system to investigate the lifting characteristics, the influence of the operation parameters and structure parameters, and the contact collision analysis of the mechanical arm. The conditions of rigid–flexible modeling for the multi-body system and the main factors affecting the vibration characteristics of the flexible arm are described. We conclude that the arm should be modeled as a rigid body if the structure parameter [w/l] (elastic deformation/length) is between 1/650 and 1/1000, the system can be modeled as a rigid–flexible coupling if [w/l] is between 1/400 and 1/650, and the arm should be modeled as a flexible body and the influence and compensation of the control method should be considered if [w/l] is between 1/250 and 1/400

Pore Structure Alteration of Shale with Exposure to Different Fluids: The Longmaxi Formation Shale in the Sichuan Basin, China

The interaction between shale and various fluids is crucial as it modifies pore structures, which govern the effective development of shale gas and the geological storage of carbon dioxide in shale formations. In this study, samples from the Longmaxi Formation shale in Sichuan Basin of China were exposed to different fluids, including 6 MPa CO2, 12 MPa CO2, 6 MPa CO2+brine, and 12 MPa CO2+brine, at 45 °C for 100 days. Various methods, including X-ray diffraction (XRD), X-ray fluorescence (XRF), field-emission scanning electron microscopy (FESEM), and the low-pressure gas adsorption (N2) test, were adopted to evaluate chemical and structural changes during the exposure process. After being treated with supercritical CO2+brine and subcritical CO2+brine, the shale underwent significant changes in its major element composition. The content of Ca, Al, and K in shale saturated with supercritical CO2+brine decreased from 13.00% to 10.34%, from 3.65% to 3.36%, and from 1.56% to 1.37%, respectively. Meanwhile, the content of Si and Na in the same shale increased slightly after saturation. The amount of quartz and dolomite increased, while the levels of clay and calcite slightly decreased. The surface of the shale sample became rougher and small bumps and cracks appeared after saturation with different fluids, as shown by the FESEM analysis results. Furthermore, the changes in both the total pore volume and pore size followed a similar pattern to the alterations in the specific surface areas. The highest level of variation occurred with the shale that was saturated with 12 MPa of CO2, indicating that gas pressure and CO2 phase state have a significant influence on the shale’s pore structure. In addition, the distribution of pore sizes showed a bias towards larger sizes across all diameters; this suggests that the reaction resulted in a decrease in the number of micropores. This also highlights that the impact of varying fluid saturation was primarily focused on micropores and macropores. The results of this study provided experimental evidence to further test the mechanisms and permeability of geological storage of CO2 in organic-rich self-sourced shale