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Although aboveground biodiversity has been extensively studied, the impact of nutrient enrichment on soil microbial populations remains unclear. Soil microorganisms serve as important indicators in shaping soil nutrient cycling processes and are typically sensitive to nutrient additions. For this, we employed a factorial combination design to examine the impact of nutrient additions on the composition and function of soil bacteria in a temperate steppe. Nitrogen addition promoted the growth of copiotrophic bacteria (Proteobacteria, Firmicutes, and Bacteroidota) but inhibited the growth of oligotrophic bacteria (Acidobacteria, Chloroflexi, and Verrucomicrobiota). Phosphorus addition alleviated phosphorus deficiency, resulting in a decrease in the abundance of phoD-harboring bacteria (Actinobacteria and Proteobacteria). Significant enhancement of soil bacterial alpha diversity was observed only in treatments with added phosphorus. Changes in NO3−-N, NH4+-N, available phosphorus, and dissolved organic carbon resulting from nutrient addition may have a greater impact on microbial community structure than changes in soil pH caused by nitrogen addition. Moreover, nutrient addition may indirectly impact microbial ecological function by altering nutrient availability in the soil. In conclusion, our study suggests that soil nutrient availability, particularly available phosphorus, affects soil bacterial communities and potentially regulates the biogeochemical cycles of soil ecosystems.

Thermal rectification is a phenomenon similar to electrical rectification, in which heat transfer in one direction is favored and reverse heat transfer is hindered. In this study, the finite element method with interface thermal resistance for transient problems is proposed, and then transient thermal rectification of composite structures during the heating and cooling processes is investigated. Numerical results show that, in the initial 50 s of heating phase, increasing interface thermal resistance from 0 to 0.005 m2·K/W raised the average transient thermal rectification ratio from 1.32 to 1.46 for periodic boundaries, and from 1.22 to 1.31 for constant boundaries. During cooling, the ratio initially decreases due to resistance but then stabilizes, and the average thermal rectification ratio can be increased from 1.1 to 1.3 by increasing the interface thermal resistance. By changing the frequency, the oscillation frequency and amplitude of the thermal rectification ratio can be adjusted. In addition, a bimetallic structure with bi-directional heat transfer is designed, which includes the interface thermal resistance. The transient thermal rectification ratio is significantly increased by an order of magnitude through various interface heat transfer modes, and can be further improved through parameter optimization.

A bony Bankart lesion is a condition where the labroligamentous complex is detached from the anterior glenoid rim, often accompanied by a fracture. It is a common occurrence found in up to 70% of traumatic shoulder dislocations. Arthroscopic surgery has become the mainstream approach for treating this condition. However, the commonly used techniques, such as labrum alone, transosseous, and double-row, can encounter difficulties passing sutures and may cause damage to the surrounding tissues, especially when dealing with large bony fragments. In this technical note, we describe our preferred technique for fixing bony Bankart lesions, which involves fixing the bony Bankart fragment through the bone tunnel using an all-suture anchor. The surgery is performed with the patient in the lateral decubitus position. Our technique offers a reliable and effective approach to treat bony Bankart lesions while minimizing the risks of complications associated with conventional techniques.

Abstract The prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.

Abstract Objective To evaluate the biomechanical effects of different miniplates on restorative laminoplasty. Methods Assembled restorative laminoplasty models were developed based on 3D printed L4 lamina. Based on different internal fixations, the research was divided into H-shaped miniplates (HSMs) group, two-hole miniplates (THMs) group, and L-shaped miniplates (LSMs) group. The static and dynamic compression tests were analyzed to investigate the biomechanical effects of different internal fixations in restorative laminoplasty, until the failure and fracture of miniplates, or the collapse of miniplates. The static compression tests adopted the speed control mode, and the dynamic fatigue compression tests adopted the load control mode. Results The “door close” and the collapse of lamina occurred in THMs group and LSMs group, and plate break occurred in LSMs group. However, these phenomenon was absent in HSMs group, and only plate crack around a screw and looseness of a screw tail cap were found in HSMs group. The sustainable yield load of HSMs group was greater than that of THMs group and LSMs group (P 0.05), while both were much less than that of THMs (P LSMs group > THMs group (P

Abstract The aim of this study was to explore a novel method to determine the orientation of acetabular prosthesis in total hip arthroplasty (THA) by refering to the anatomical landmarker of acetabular notches. Forty-one normal developmental hips were included in the present study. The acetabulums were reamed according to standard surgical procedures of THA on life-size 3D printing pelvis models. The inferior edge of acetabular cup were placed (1–5) mm proximal and distal to the proximal line of the anterior and posterior acetabular notches (PLAPAN) respectively to determine cup inclination. The inferior edge of acetabular cup were placed (1–5) mm pronating and supinating around the proximal point of acetabular posterior notch (PPAPN) respectively to determine cup anteversion. The pelvis plain radiographs were took and the inclination and anteversion of the acetabular cup at 22 positions were calculated. In the normal developmental hip, the mean inclination of acetabular prothesis were (35.10 ± 3.22)° and (45.90 ± 2.68)° when the inferior edge of the acetabular cup was 3 mm proximal and 1 mm distal to the PLAPAN. The optimal cup inclination could be obtained when the inferior edge of the acetabular cup was 1 mm proximal to the PLAPAN (the mean inclination was (40.71 ± 2.80)°). The mean anteversion of acetabular prothesis were (10.67 ± 4.55)° and (20.86 ± 4.44)° when the inferior edge of the acetabular cup was 1 mm pronating and 1 mm supinating around the PPAPN. The optimal cup anteversion could be obtained when the inferior edge of the acetabular cup was parallel to the PLAPAN (the mean anteversion was (18.00 ± 1.64)°). The inclination and anteversion of acetabular prosthesis could be determined by refering the anatomical landmarks of acetabular notches, which could help orthopedists to install the acetabular prosthesis quickly and safely in THA.

BackgroundThe impact of inflammatory factors on the development of Ankylosing Spondylitis (AS) is widely recognized, but the exact causal relationship remains unclear.MethodsThe bidirectional mendelian-randomization study utilized genetic data from a genome-wide association study (GWAS) of 186 AS cases and 456,162 controls of European ancestry. Inflammatory cytokines were obtained from a GWAS summary of 8,293 healthy participants. Causal associations were primarily investigated using the inverse variance-weighted method, supplemented by MR Egger, weighted median and weighted mode analyses. Heterogeneity in the results was assessed using the Cochrane Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers (MR-PRESSO) test. Sensitivity analysis was conducted through leave-one-out analysis.ResultsThe results suggest a genetically predicted potential association between beta-nerve growth factor (βNGF), Interleukin-1-beta (IL-1β), and TNF-related apoptosis inducing ligand (TRAIL) with the risk of AS (OR: 2.17, 95% CI: 1.13-4.16; OR: 0.41, 95% CI: 0.18-0.95,; OR: 1.47, 95% CI: 1.02-2.13).Additionally, Interleukin-12p70 (IL-12p70), Interleukin-17 (IL-17), Interleukin-6 (IL-6), Interleukin-4 (IL-4), Stromal-cell-derived factor 1 alpha (SDF−1α), Macrophage inflammatory protein 1β (MIP1β), Monocyte chemoattractant protein-3 (MCP-3), Platelet-derived growth factor bb (PDGFbb), Granulocyte-colony stimulating factor (GCSF), Fibroblast growth factor basic (bFGF), TNF-related apoptosis inducing ligand (TRAIL), and Interferon-gamma (IFN -γ) are suggested as consequences of AS in genetically prediction.No evidence of horizontal pleiotropy or heterogeneity between the genetic variants was found (P>0.05), and a leave-one-out test confirmed the stability and robustness of this association.ConclusionThese findings suggest that βNGF, IL-1β, and TRAIL may play a crucial role in the pathogenesis of AS. Additionally, AS may impact the expression of cytokines such as IL-12p70, IL-17, IL-6, IL-4, SDF−1α, MIP1β, MCP-3, PDGFbb,GCSF, bFGF,TRAIL,and IFN-γ. Further investigations are warranted to determine whether these biomarkers can be utilized for the prevention or treatment of AS.

Calvin-Benson-Bassham cycle (cbbL)-carrying bacteria in soil are essential to renew and circulate organic matter. However, the relation between cbbL-carrying bacteria and soil carbon dynamics under tillage managements, especially across the aggregate size remains unclear. Thus, in our study, soil organic carbon (SOC) storages, mineralization, and the cbbL-carrying bacterial community across five soil aggregate sizes were thoroughly investigated under four tillage treatments: conventional rotary tillage (CT), deep plowing (DP), subsoiling (SS), no-tillage (NT). We found macroaggregates (>2 mm) contributed most with regard to SOC stocks, whereas microaggregates (1 mm) with the highest cumulative SOC mineralization were found in subsoiling, whereas microaggregates had the lowest cumulative mineralization under no-tillage. By physically protecting, no-tillage specifically inhibited carbon dioxide (CO2) emissions in macroaggregates (>1 mm), whereas increased SOC levels and encouraged CO2 releases across microaggregates. Shifts in the co-occurrence network demonstrated that subsoiling promoted the joint symbiotic function between cbbL-carrying bacteria, the efficiency of matter and energy, and information transfer. And the keystone species, the enhanced cooperation and stochastic processes of autotrophic microorganisms under subsoiling lead to increased carbon fixation and reduced CO2 emissions in microaggregates with limited oxygen and nutrients. Overall, our work verified physical protection of large aggregates under no-tillage and improvement of microbial interaction efficiency under subsoiling. This may offer a theoretical foundation for the choice of tillage practices in fluvo-aquic soil regions.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. Xanthium mongolicum Kitag (X. mongolicum) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China.Methods: Fractions of X. mongolicum were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage in vitro. The major active compounds were identified by UPLC-MS and quantified by HPLC. The anti-RA effects of the active fraction was evaluated in complete freund’s adjuvant (CFA)-induced arthritis and collagen-induced arthritis (CIA) mouse models in vivo and LPS-stimulated macrophage in vitro.Results: Sesquiterpene lactones-enriched fraction from X. mongolicum (SL-XM) exhibited the strongest anti-RA activity among all components in vitro. Five major constituents i.e., Xanthinosin (1), Xanthatin (2), Mogolide D (3), Mogolide E (4), and Mogolide A (5) were identified as major compounds of SL-XM. SL-XM ameliorated symptoms of CFA and CIA induced arthritis mice model. Furthermore, SL-XM treatment inhibited LPS-induced M1 macrophages polarization. In addition, SL-XM inhibited the phosphorylation of NF-κB and MAPK signaling pathways in LPS-induced macrophage and CIA-challenged mice.Discussion: The main anti-RA active fraction of X. mongolicum may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization via the NF-κB and MAPK signaling pathway.

IntroductionProtists play an important role in nutrient cycling, microbiome stability and soil fertility maintenance. However, the driving force of protistan functional groups remains poorly understood in agricultural ecosystems.MethodsWe investigated the impacts of fertilization regimes on the diversity, composition and functional groups of protists and further disentangled the effects of multiple factors shaping the community composition of functional groups in a 5-year fertilization regime (CK, no fertilization; M, organic fertilization; MNPK, combined inorganic and organic fertilization; NPK, inorganic fertilization).ResultsFertilization significantly changed the community composition of protists rather than diversity. The MNPK treatment significantly increased the relative abundance of phototrophs and decreased that of the parasites and consumers. Partial least squares path modeling indicated that fertilization indirectly regulated protistan consumers via changes in the P content, which affected the composition of consumers mainly by regulating fungal community composition. Soil moisture (SM) and available phosphorus (AP) were identified as the top predictors for the composition of parasites, and the composition of phototrophs was mainly affected by SM, indicating that parasites and phototrophs were more sensitive to abiotic factors in the fertilization system.DiscussionTaken together, our findings highlight that fertilization significantly affects the composition of functional groups of protists and their biotic or abiotic regulatory processes, which have implications for the potential changes in their ecosystem functions for soil management systems.

Bone metastatic breast cancer has severely threatened the survival and life quality of patients. Due to the suboptimal efficacy of anti-metastatic chemotherapeutic drugs and the complicated bone marrow microenvironments, effective treatment of metastatic breast cancer remains challenging for traditional clinical approaches. In this work, we developed a mesoporous nanoplatform (m-CuS-PEG) with the co-loading of CuS nanodots and a chemotherapeutic drug cisplatin for the combined photothermal-chemotherapy of bone-metastasized breast cancer. The CuS nanodots were decorated onto mesoporous silica (m-SiO2) surface with dendritic mesoporous channels, into which the cisplatin was accommodated. The carboxyl-terminated poly (ethylene glycol) (PEG) was further functionalized onto the surface to obtain the functional nanoplatform m-CuS-PEG. The drug release of the loaded cisplatin exhibited pH- and thermal-dual responsive manner. The attached CuS nanodots rendered the mesoporous nanoplatform with high photothermal conversion ability. Upon irradiation with a near-infrared laser in the second near-infrared (NIR-II) window, m-CuS-PEG dispersions exhibited rapid temperature elevation and high photostability. The results revealed that m-CuS-PEG had excellent biocompatibility. The cisplatin-loaded m-CuS-PEG not only showed superior cancer cell-killing effects, but also significantly inhibit the growth of metastatic tumors. The tumor-induced bone destruction was also dramatically attenuated by the mesoporous nanoplatform-mediated combined therapy. Overall, the developed functional nanoplatform integrates photothermal therapy and efficient chemotherapeutic drug delivery to offer an alternative approach for combating breast cancer bone metastasis.

The decline in soil quality is becoming a significant process of soil degradation. Optimizing organic fertilizer incorporation practices in cropland is essential to enhancing crop productivity and soil health. However, that requires a comprehensive understanding of crop yield and soil quality reaction across an application gradient of organic fertilizer. We investigated the effect of organic fertilizer incorporation practices on crop yield, soil quality, and fauna feeding activity from fluvo-aquic soils on wheat (Triticum aestivum)-maize (Zea mays) rotation field. The six treatments included were unfertilized N control (UC), traditional chemical fertilizer application (TF, 600 N kg ha−1 year−1), and recommended chemical fertilization (RF, 400 N kg ha−1 year−1) with no organic fertilizer application rate, low-level 15.0 (RFLO), medium-level 30.0 (RFMO), and high-level 45.0 t ha−1 year−1 (RFHO) application, respectively. The research findings show that the yield with organic fertilizer incorporation treatments increased 26.4%–44.6% for wheat and 12.5%–40.8% for maize compared to RF plots. The long-term organic fertilizer incorporation rate increased organic carbon from 54.7% to 110.6% versus UC plots and 27.9%–74.0% versus chemical fertilizer (TF and RF) treatments, and the total nitrogen content of soil increased from 41.8% to 59.2%, and 24.6%–39.2%. The long-term inorganic fertilizer combined with organic fertilizer incorporation practices significantly enhanced soil sucrose (30.1%–51.9%), urease (28.4%–38.3%), and β-1,4-glucosidase (34.6%–122.4%) activity. Still, nitrite reductase, polyphenol oxidase, and catalase significantly lower 27.3%–49.9%, 8.5%–26.3% and 23.3%–34.3% than single applications of inorganic N fertilizer groups. Meanwhile, the results showed that organic fertilizer incorporation practices improved soil fauna feeding activity by 35.2%–42.5%, and the excessive application of inorganic N fertilizer reduced the activity level of soil fauna.

BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.MethodsThe target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.ResultsPLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.ConclusionPLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.

Abstract Background The objectives of this study were to investigate the anatomic morphology of patellar ridge using computed tomography-based three-dimensional (3D) computer models and to assess the center of the patellar ridge after virtual resections. Methods We selected 80 patients, 40 males (age, 33.2±6.8 years) and 40 females (age, 30.6±7.2 years), who were slightly symptomatic with soft tissue injury of the knee joint. The right or left knees were scanned by computed tomography (CT). The CT data of 160 knees was used to construct 3D computer models by image analysis software (Mimics). Variables such as the angle between the patellar ridge and patellar long axis, the distance between the center of the patellar ridge and the center of patellar cut after virtual resections were measured. We detect differences between the sides and genders with the 3D computer models by Student’s t test. Simple linear regression and correlation test was used to correlate the patellar ridge center to the center of the patellar cut. Results According to the available data, there were significant gender differences in the length and width of patellar cut after virtual resections even with strict control for the height and weight of the patients. The angle between the patellar ridge and the patellar long axis was 11.24° ± 3.62°. The angle in male patients was 10.17° ± 4.82°, and it was 12.28°± 3.78° in female patients. The morphological difference was statistically significant (P

Microplastics (MPs), as new pollutants in agroecosystems, have already attracted widespread attention from scientists. However, our understanding of MP geographic distribution and its influencing factors across spatial scales remains poor. Here, a regional-scale field investigation was conducted to assess the distribution characteristic of MPs in five major rice-growing regions of China, and we explored the roles of biological and abiotic factors, especially stoichiometry and microbial influences on MP distribution. MPs were observed in all sampling sites, averaging 6,390 ± 2,031 items⋅kg–1. Sizes less than 0.5 mm and black and transparent MPs dominated. Fiber, classified as one of the MP shapes, occurred most frequently. MP community analysis, firstly used in paddy soil, revealed more black MPs abundance in Henan (HE), more rayon, blue, and other colors MPs in Hunan (HN), more transparent MPs in Tianjing (TJ), and more PE MPs in Heilongjiang (DB). Higher MP community diversity was found in most south paddy soils of this study, due to a broader range of sources. C/N showed a positive relationship with pellet-shaped MP abundance and MPs of size between 2 and 5 mm (P < 0.05). Chao1 index of soil microbial communities was positively correlated with the MP abundance, MPs of size less than 0.5 mm, and fiber abundance. The minimum temperature was positively correlated with MP abundance (P < 0.05), implying the potential effects of the freeze-thaw process might exist. The regression analysis highlighted the important role of population quantity in determining MP abundance (R = 0.421, P = 0.02). This study confirmed the wide distribution of MPs in different soil depths of paddy lands in China and demonstrated that its distribution was influenced by population quantity and environmental variables, such as microbiology. These findings could provide a basis for the toxicological behavior of MPs and the potential risk to human health.

Abstract Total hip arthroplasty and total knee arthroplasty are extensively used for the treatment of the end-stage degenerative joint diseases. Currently, periprosthetic bone loss is still the major cause of aseptic loosening, resulting in implant failures. Previous literature introduced some widely accepted protocols for the prevention and treatment of periprosthetic bone loss, but no guideline has been proposed. Denosumab, a human monoclonal immunoglobulin G2 (IgG2) antibody, can inhibit bone resorption by binding to the receptor activator of nuclear factor kappa-B ligand (RANKL). This article reviews the present findings and evidence concerning the effect of denosumab on the periprosthetic bone loss after total hip arthroplasty and total knee arthroplasty. Overall, the current evidence suggests that denosumab is a promising agent for the treatment of periprosthetic bone loss.

The human gut microbiota has been proven to have great effects on the regulation of bone health. However, the association between gut microbiota and particle-induced osteolysis, which is the primary cause of aseptic loosening, is still unknown. In this study, we used a combination of wide-spectrum antibiotics to eliminate the majority of gut microbiota and found that reduction of gut commensal bacteria significantly alleviated the progression of osteolysis, in which anaerobe was the biggest culprit in the exacerbation of osteolysis. Furthermore, colonization of enteropathogenic Escherichia coli (EPEC), a subspecies of anaerobe, could promote the development of particle-induced osteolysis by increasing the secretion of peripheral 5-hydroxytryptamine (5-HT) from the colon. Elevated 5-HT level decreased the phosphorylation of CREB and inhibited the proliferation of osteoblasts. Collectively, these results indicated EPEC colonization suppressed the bone formation and aggravated particle-induced osteolysis in vivo. Thus, clearance of EPEC is expected to become a potential preventive approach to treat debris-induced osteolysis and aseptic loosening.

CO2 fixation by autotrophic microbes has a significant effect on the carbon cycle in temperate grasslands. Nitrogen (N) deposition in soil has been steadily increasing for decades, which has consequences for soil microorganisms. However, the impact of this deposition on the diversity and abundance of CO2-fixing soil microorganisms remains unclear in temperate grasslands. In the present study, the cbbL gene, a key gene in the Calvin–Benson–Bassham cycle that encodes the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, was used to study CO2-fixing microbes under different rates of N addition (0, 15, 30, 50, 100, and 150 kg N ha–1 yr–1) in a 9-year field experiment in a temperate grassland. The results showed that N addition led to significant reductions in cbbL gene abundance and genetic diversity and altered cbbL gene community composition. High N addition enhanced the relative abundances of Acidiferrobacterales and Rhizobiales but reduced those of Burkholderiales and Rhodobacterales. Structural equation modeling further revealed that N addition primarily reduced cbbL genetic diversity by increasing the soil NO3-N content and decreasing the soil pH. N addition indirectly reduced cbbL gene abundance, possibly by increasing the soil N/phosphorus (P) ratio and decreasing the soil pH. These findings suggest that N addition increases the soil available N and causes soil acidification, which may inhibit growth of CO2-fixing microbes to some extent.

Osteosarcoma is a malignancy with high aggressiveness and poor prognosis, which occurs mainly in children. The therapeutic strategy against osteosarcoma includes surgery combined with chemotherapy and radiotherapy. Although the treatment of osteosarcoma has been improved in recent years, there is a large proportion of patients with incurable osteosarcoma. Investigation of the mechanism of osteosarcoma progression would be of great help in discovering therapeutic targets for this disease. Long non-coding RNAs play critical roles in the pathogenesis of different types of cancer. The current study showed that long non-coding RNA NR_027471 was downregulated in osteosarcoma cells. In vitro and in vivo studies indicated that upregulation of NR_027471 impeded the viability, proliferation, and invasion of osteosarcoma, as well as induced cell cycle arrest at G1. In addition, binding of miR-8055 to NR_027471 was demonstrated, thereby influencing the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1). Knockdown of NR_027471 promoted epithelial–mesenchymal transition by inhibiting E-cadherin and increasing the expression of zinc finger E-box-binding homeobox 1 (ZEB1), Snail, and fibronectin. These results suggested that overexpression of NR_027471 upregulated TP53INP1 by sponging to miR-8055, leading to suppression of osteosarcoma cell proliferation and progression.

Purpose: Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on enhanced recovery post-TKA. Methods: A prospective randomized single-blinded trial assessed tourniquet’s effects on postoperative pain, swelling, and early outcome in TKA. One-hundred and two patients with knee osteoarthritis were randomized to full-course (FC) and second half-course (SHC) application ( n = 51/group). Tumor necrosis factor-alpha (TNF-α), C-C motif chemokine ligand 2(CCL-2), pentraxin-3 (PTX-3), prostaglandin E-2 (PGE-2), superoxide dismutase-1 (SOD-1), and myoglobin (Mb) were assessed by enzyme-linked immunosorbent assay, while the visual analog scale (VAS), range of motion (ROM), and thigh circumference growth rate were recorded. Results: Average tourniquet duration significantly differed between the SHC (37.5 ± 5.1 min) and FC (66.4 ± 7.2 min) groups ( p < 0.01); VAS and thigh circumference growth rate in the SHC group were much lower compared with the FC group, while ROM was higher within 48 h of tourniquet removal ( p < 0.01). Blood TNF-α, PTX3, CCL2, PGE2, SOD-1, and Mb were lower in the SHC group than the FC group ( p < 0.01). Additionally, intraoperative blood loss was significantly elevated in the SHC group than the FC group ( p < 0.01), with lower postoperative blood loss in the drain ( p = 0.001). Postoperative drainage volume was reduced in the SHC group compared with the FC group ( p < 0.01); five and two patients in the FC and SHC groups required blood transfusion, respectively ( p = 0.025). Hospital stay tended to be shorter in the SHC group ( p = 0.023), and no tourniquet-related complications were recorded. Conclusion: Improved therapeutic outcome was observed in the SHC group, indicating patients should routinely undergo TKA with SHC tourniquet application.

Abstract Background The aim of this study was to report our previous results of treatments for trochanteric fractures with proximal femoral locking plates (PFLP) and to analyze the underlying mechanisms and possible risk factors associated with the high failure rate of this technique. Methods From January 2010 to October 2014, 273 consecutive patients with trochanteric femoral fractures were identified, and 95 patients (with 97 fractures) ultimately met the inclusion criteria. Clinical records regarding demographic features and intraoperative data including total incision length, operation time, blood loss, and failures detected in radiographs were documented and assessed. The collected data were analyzed with SPSS 19.0 software. Results The stable group (AO/OTA 31 A1 and A2.1) had less blood loss than the unstable group (AO/OTA 31 A2.2, A2.3, and A3). The ultimate failure rate was 36% in 97 fractures. The obvious complications in this study included nonunion in 7 (7.2%) fractures, implant breakage in 4 (4.1%) fractures, varus deformity in 34 (35%) fractures, and loosening of the proximal femoral screw in 21 (21.6%) fractures. Six patients received reoperations. The total failure rate in the stable group was 17% and was 50% in the unstable group. In patients greater than 60 years old in the unstable group, the failure rate was 60.5%. Conclusions High failure rates of PFLP were observed in patients with trochanteric fracture, especially in patients who were greater than 60 years old with unstable fracture types. PFLP was not an appropriate treatment for trochanteric fractures.

Background/Aims: MicroRNAs (miRNAs) have been reported to be involved in Rheumatoid arthritis (RA) pathogenesis and prognosis. However, little is known about the disease mechanism in RA. Here, we aim to investigate the potential association between miR-338-5p and NFAT5 in RA. Methods: Aberrant expression of miR-338-5p in RA tissues and rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) compared to the normal were determined by RT-qPCR. Cell viability was determined using the CCK-8 assay, and cell apoptosis was analyzed via Annexin V-FITC/PI double staining and was detected using flow cytometry. The targeted relationship was determined by TargetScan database and dual luciferase reporter gene assay. Results: Upregulation of miR-338-5p facilitated the proliferation, migration, invasion and induced G0/G1 arrest of RAFLSs while miR-338-5p inhibitor functioned oppositely. Nuclear factor of activated T-cells 5 (NFAT5) was confirmed as a downstream target of miR-338-5p which expression was directly suppressed by miR-338-5p. Overexpression of NFAT5 attenuated the proliferation and metastasis of RAFLSs and those changes could be rescued by co-transfection of miR-338-5p. Conclusion: miR-338-5p promotes RAFLS’s viability and proliferation, migration by targeting NFAT5, suggesting a novel therapeutic strategy for RA.

Background/Aims: Diabetic fracture have poor treatment and serious complications. Therefore, how to treat diabetic fracture is receiving increasing attention. This study aimed to investigate the effects of transplanting CXCL13-stimulated bone marrow stromal cells (BMSCs) on the fracture healing in diabetic rats. Methods: In vitro, RT-PCR was employed to examine the expression of CXCL13 in BMSCs in high glucose environment. MTT assay and apoptosis assay were utilized to determine the effects of CXCL13 overexpression on the proliferation and apoptosis of BMSCs respectively. ALP staining was applied to detect the ALP activity. In vivo, CXCL13-stimulated BMSCs were transplanted into the fracture sites of diabetic rats. At the 1st week, 2nd weeks, 4th week and 6th week after the operation, bone mineral density (BMD) and callus area measurement, ELISA detection, and HE staining were performed to evaluate the fracture healing. Results: Low BMD and less area of callus in diabetic rats showed that the recovery after fracture was worse in diabetic rats than in non-diabetic rats. Meanwhile, the expression of CXCL13 in serum was lower in diabetic rats than in non-diabetic rats. Overexpression of CXCL13 promoted the proliferation of BMSCs in vitro high glucose environment. After BMSCs transfected with CXCL13 being transplanted into the fracture sites of diabetic rats, it was found that the fracture healing was enhanced and ALP expression in serum became higher. HE staining results further verified the effects of transplantation of BMSCs transfected with CXCL13 on fracture healing in diabetic rats. Conclusion: These finding indicated that CXCL13 may play a critical role in the process of fracture healing, which could provide a deeper insight into molecular targets for the fracture healing in diabetic people.

Objective: Hidden blood loss (HBL), commonly seen after total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. Recent studies demonstrated that oxidative stress might be involved in HBL. However, whether the antioxidants proanthocyanidin (PA) or hydrogen water (HW) can ameliorate HBL remains poorly understood. The aim of this study was to evaluate the effects of PA and HW on HBL. Materials and Methods: A rat HBL model was established through administration of linoleic acid with or without treatment with PA or HW. The levels of hemoglobin (Hb), red blood cell (RBC) count, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-PX) activity, malondialdehyde (MDA), and ferryl Hb were measured. Results: RBC and Hb values as well as the activity of SOD and GSHPX were reduced after administration of linoleic acid, which was ameliorated by treatment with PA or HW. In addition, the quantity of MDA was significantly decreased with the administration of PA or HW. Conclusion: PA and HW could ameliorate HBL in a rat model by reducing oxidative stress, suggesting that they might be used as a novel therapeutic approach in the prophylaxis or treatment of HBL in clinics.

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.

Grassland soil organic carbon (SOC) accounts for 15.5% of the SOC in reservoirs of terrestrial carbon (C) and is a major component of the global C cycle. Current and future reactive N deposited on grassland soils may alter biogeochemical processes and soil microbes. Microorganisms perform most of the decomposition on Earth and shift SOC accumulation. However, how variation in the identity and composition of the bacterial community influences SOC is far from clear. The objective of this study is to investigate the responses of SOC concentration to multiple rates of N addition as well as the roles of bacteria in SOC accumulation. We studied SOC storage and bacterial community composition under N addition treatments (0, 1.5, 3.0, 5.0, 10.0, 15.0, 20.0, and 30.0 g N·m-2 yr−1) in a 6-yr field experiment in a temperate grassland. We determined the soil inorganic nitrogen concentration and pH in a 0−10 cm soil layer. We used high-throughput genetic sequencing to detect bacteria. N addition led to significant increases in the concentrations of SOC. N addition reduced the soil pH but increased the NO3-N and NH4-N levels. The bacterial diversity was highest under low nitrogen addition. N addition increased the relative abundance of Proteobacteria, and Proteobacteria became the second dominant phylum under high N addition. Structural equation modeling further revealed that soil pH and bacterial community structure have an impact on SOC under N deposition. Nitrogen-regulated SOC is associated with Proteobacteria and Planctomycetes. These findings suggest that N deposition may alter the SOC content, highlighting the importance of understanding changes in the bacterial community for soil nutrients under N deposition.

Background: Osteosarcoma is the most common primary bone malignancy in children and young adults. Most failures of osteosarcoma treatment were due to resistance to chemotherapy. Development of new therapy required elucidation underlying molecular mechanism. Many miRNAs have been proved to be involved in the pathogenesis of osteosarcoma. Methods: MiR-3928 expression level was assayed by qRT-PCR. MiRNA mimics or ASO were transfected for up-regulation or down-regulation of miR-3928 expression. Cell proliferation was assayed by formazan test. Apoptosis and cell cycle were assayed by FACS. MiR-3928 targeted genes were predicated by bioinformatics algorithm (TargetScanHuman). The correlation between targeted gene and miR-3928 was analyzed by Pearson's correlation coefficient analysis. Results: MiR-3928 was down-regulated in osteosarcoma tissues. Over-expression of miR-3928 inhibited tumor growth, induced cell apoptosis, increased the percent of cells in G1 phrase and decreased the percent of cells in S phrase. Down-regulation of miR-3928 promoted cell proliferation. ERBB3, IL-6R and CDK6 may be the targeted genes of miR-3928. Conclusions: Down-expression of miR-3928 in osteosarcoma promoted tumor growth by targeting ERBB3, IL-6R and CDK6. MiR-3928 may be a potential therapy target worth further investigation.

Articular cartilage defects have been addressed by using multiple strategies. In the last two decades, promising new strategies by using assorted scaffolds and cell sources to induce tissue regeneration have emerged, such as autologous chondrocyte implantation (ACI) and mesenchymal stem cell implantation (MSCI). However, it is still controversial in the clinical strategies when to choose these treatments. Thus, we conducted a systematic review and meta-analyses to compare the efficacy and safety of different cartilage treatments. In our study, 17 studies were selected to compare different treatments for cartilage defects. The results of meta-analyses indicated that cell-based cartilage treatments showed significant better efficacy than cell-free treatments did (OR: 4.27, 95% CI: 2.19–8.34; WMD: 10.11, 95% CI: 2.69–16.53). Another result indicated that MACT had significant better efficacy than traditional ACI did (OR: 0.49, 95% CI: 0.30–0.82). Besides, the incidence of graft hypertrophy of MACT was slightly lower than that of traditional ACI (OR: 2.43, 95% CI: 1.00–5.94). Current data showed that the cell-based treatments and MACT are better options for cartilage treatments, but more well-designed comparative studies are still needed to enhance our understanding of different treatments for cartilage defects.

Wear particle-induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the synovial fibroblasts present in the periprosthetic membrane are important targets of wear debris during osteolysis. However, the interaction mechanisms between the wear debris and fibroblasts remain largely unknown. In the present study, we investigated the effect of ER (endoplasmic reticulum) stress induced by TiAl6V4 particles (TiPs) in human synovial fibroblasts and calvarial resorption animal models. The expression of ER stress markers, including IRE1-α, GRP78/Bip and CHOP, were determined by western blot in fibroblasts that had been treated with TiPs for various times and concentration. To address whether ER stress was involved in the expression of RANKL, the effects of ER stress blockers (including 4-PBA and TUDCA) on the expression of RANKL in TiPs-treated fibroblasts were examined by real-time PCR, western blot and ELISA. Osteoclastogenesis was assessed by tartrate resistant acid phosphatase (TRAP) staining. Our study demonstrated that ER stress markers were markedly upregulated in TiPs-treated fibroblasts. Blocking ER stress significantly reduced the TiPs-induced expression of RANKL both in vitro and in vivo. Moreover, the inhibition of ER stress ameliorated wear particle-induced osteolysis in animal models. Taken together, these results suggested that the expression of RANKL induced by TiPs was mediated by ER stress in fibroblasts. Therefore, down regulating the ER stress of fibroblasts represents a potential therapeutic approach for wear particle-induced periprosthetic osteolysis.