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Abstract Background Osteoarthritis (OA) is a common degenerative joint disease, and chondrocyte extracellular matrix (ECM) degradation is one vital pathological feature of OA. Long noncoding RNA (lncRNA), a new kind of gene regulator, plays an important role in pathogenesis of many diseases like OA. Recent studies have confirmed that lncRNA plasmacytoma variant translocation 1 (PVT1) expression was upregulated in OA patients; however, its effect on ECM degradation remained unknown. Methods Cartilage tissue samples were obtained from 6 OA patients admitted in Guangdong Second Traditional Chinese Medicine Hospital. Chondrocytes were isolated and cultured from the collected cartilage tissue. Plasmid construction, RNA interference, cell transfection, fluorescence in situ hybridization (FISH), and pull-down assay were carried out during the research. Results In this study, PVT1 expression was significantly increased in chondrocytes stimulated by interleukin-1β (IL-1β). In addition, inhibition of PVT1 significantly downregulated the increased expressions of ADAM metallopeptidase with thrombospondin type 1 motif-5 (ADAMTS-5) and matrix metalloproteinase-13 (MMP-13) induced by IL-1β. Further investigation revealed that PVT1 was an endogenous sponge RNA, which directly bound to miR-140 and inhibited miR-140 expression. Conclusion To sum up, this study showed that PVT1 promoted expressions of ADAMTS-5 and MMP-13 as a competing endogenous RNA (ceRNA) of miR-140 in OA, which eventually led to aggravation of ECM degradation, thus providing a new and promising strategy for the treatment of OA.

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Abstract Background A tourniquet is a device commonly used to control massive hemorrhage during knee replacement surgery. However, the question remains whether the use of tourniquets affects the permeability of the bone cement around the knee prosthesis. Moreover, the long-term effects and stability of the knee prosthesis are still debatable. The aim of this study was to examine whether the use of a tourniquet increases the thickness of the cement mantle and affects the postoperative blood loss and pain during primary total knee arthroplasty (TKA) using meta-analysis. Methods We searched the Cochrane Central Library, MEDLINE, Embase, PubMed, CNKI, and Wang Fang databases for randomized controlled trials (RCTs) on primary TKA, from inception to November 2019. All RCTs in primary TKA with and without a tourniquet were included. The meta-analysis was conducted using RevMan 5.2 software. Results A total of eight RCTs (677 knees) were analyzed. We found no significant difference in the age and sex of the patients. The results showed that the application of tourniquet affects the thickness of the bone cement around the tibial prosthesis (WMD = 0.16, 95%CI = 0.11 to 0.21, p < 0.00001). However, in our study, there was no significant difference in postoperative blood loss between the two groups was observed (WMD = 12.07, 95%CI = − 78.63 to 102.77, p = 0.79). The use of an intraoperative tourniquet can increase the intensity of postoperative pain (WMD = 1.34, 95%, CI = 0.32 to 2.36, p = 0.01). Conclusions Tourniquet application increases the thickness of the bone cement around the prosthesis and may thus increase the stability and durability of the prosthesis after TKA. The application of an intraoperative tourniquet can increase the intensity of postoperative pain.

Background: Asymmetrical foot posture and properties alterations of the gastrocnemius muscle (GM) and Achilles tendon (AT) were observed in knee osteoarthritis (KOA). We aimed to investigate the inter-limbs asymmetries in foot posture and the properties of GM and AT and explore the association between them.Methods: A total of 62 subjects with unilateral or bilateral KOA were included in this study: 30 patients with unilateral pain and 32 patients with bilateral pain were assigned to the bilateral group (BG) and unilateral group (UG), respectively. The relatively serious leg (RSL) and relatively moderate leg (RML) were judged according to the severity of symptoms assessed by using visual analogue scale (VAS) motion. Foot posture and asymmetrical foot posture scores were assessed based on Foot Posture index (FPI-6). Subsequently, all the participants received an assessment for properties of GM and AT, including tone/tension (Hz), stiffness (N/m), and elasticity. We calculated the asymmetry index of AT (Asy-AT) in both legs and the difference of muscle properties between medial and lateral gastrocnemius (D-MLG) in the ipsilateral limb.Results: Asymmetry of foot posture was categorized into three types including normal, asymmetry, and severe asymmetry. The percentage of subjects classified as normal was higher in the BG (62.5%) than in the UG (36.67%), p < 0.05. Tension of AT and tone of lateral gastrocnemius (LG) in RSL were higher than those in RML (15.71 ± 0.91 vs. 15.23 ± 1.01; 25.31 ± 2.09 vs. 23.96 ± 2.08, p < 0.01 and p < 0.01, respectively), and stiffness of AT in the RSL was higher than that in RML (676.58 ± 111.45 vs. 625.66 ± 111.19, p < 0.01). Meanwhile, a positive relationship was found between ipsilateral FPI and tone of MG and LG in the left leg (0.246 per degree, 95% CI: −0.001, 0.129; p = 0.054 and 0.293 per degree, 95% CI: −0.014, 0.157; p = 0.021, respectively) and right leg (0.363 per degree, 95% CI: 0.033, 0.146; p = 0.004 and 0.272 per degree, 95% CI: 0.007, −0.144; p = 0.032, respectively). Moreover, a positive link was observed between asymmetrical FPI scores and K/L grade (0.291 per degree, 95% CI: 0.018, 0.216; p = 0.022). Furthermore, a significantly greater Asy-AT(tension) was detected in the UG than that in the BG (UG vs. UG: 8.20 ± 5.09% vs. 5.11 ± 4.72%, p < 0.01). Additionally, an increased asymmetrical FPI score (i.e., more severe asymmetry) was significantly associated with increases in Asy-AT(tension) and Asy-AT(stiffness) (0.42 per degree, 95% CI: 0.533, 1.881; p = 0.001 and 0.369 per degree, 95% CI: 0.596, 2.82; p = 0.003, respectively).Conclusions: The stiffness and tension of AT and the tone of LG in RSL were higher than those in RML in KOA patients, and inter-limbs foot posture and tension of AT were more asymmetrical in unilateral KOA patients compared to patients with bilateral KOA. Notably, foot posture, as an important biomechanical factor, was significantly associated with properties of GM, AT, and K/L grade in KOA patients.

The effects of increasing blood flow on the pathogenic wall shear stress (pWSS) of subclavian arteries (SAs) are currently unclear. Patient-specific models of the SA were constructed based on computed tomographic images from two patients. Using the Ansys Fluent 19.0 transient laminar flow solver, the finite volume method was chosen to solve the Navier–Stokes equation governing fluid behavior. The time-averaged wall shear stress, ratio of risk area, cumulative ratio of risk area ( P ¯ ), ratio of risk time, and ratio contour of risk time were calculated to describe the temporal and spatial distributions of pWSS. Virtually all pWSS occurred during the diastolic phase. The P ¯ was 2.3 and 1.29 times higher on the left than on the right in Patients 1 (P1) and 2 (P2), respectively. Increasing the blood flow volume of the left SA by 20%, 40%, and 60% led to a 9.27%, 15.10%, and 20.99% decrease in P ¯ for P1 and a 5.74%, 11.55%, and 17.14% decrease in P ¯ for P2, respectively, compared with baseline values. In conclusion, the left SA showed greater diastolic pWSS than the right SA, and increasing the blood flow volume reduced the pWSS in the left SA.

Distributed group consensus control problems of heterogeneous multi-agent systems with time-varying topologies and communication delay are investigated in this paper. Two different types of control protocols without relative velocity information are designed. By reformulating the original problem and utilizing the property of Metzler matrix, sufficient group consensus criteria under some assumptions for the two proposed protocols are developed, respectively. Simulation examples are exploited to illustrate the results.

Objective: The benefits of Pilates for blood glucose and lipids remain unclear. The purpose of this study was to examine the effect of Pilates on their levels.Methods: Searches were conducted in five databases to identify relevant articles published until October 29, 2020. Paired reviewers independently screened the articles and extracted data from each included study. Meta-analysis was performed to assess the effects of Pilates on blood glucose and lipids. Subgroup analyses and sensitivity analyses were conducted to explore heterogeneity.Results: According to the inclusion and exclusion criteria, 15 randomized controlled trials (RCTs) comprising 587 participants were included in the study. Overall, the Pilates group (PG) had a significantly greater reduction in post-prandial blood glucose than the control group (CG) (MD = −22.25 mg/dL, 95% CI: [−28.34, 16.17] mg/dL, P < 0.00001, I2 = 0%); glycated hemoglobin (HbA1c) (MD = −0.78%, 95% CI: [−1.13, −0.42]%, P < 0.0001, I2 = 88%); total cholesterol (TC) (MD = −20.90 mg/dL, 95% CI: [−37.21, −4.60] mg/dL, P = 0.01, I2 = 84%); triglycerides (TG) (MD = −12.59 mg/dL, 95% CI: [−19.88, −5.29] mg/dL, P = 0.0007, I2 = 86%); and low density lipoprotein cholesterol (LDL-C) (MD = −12.39 mg/dL, 95% CI: [−16.82, −7.95] mg/dL, P < 0.00001, I2 = 45%) compared to CG, whereas no significant difference was detected between the two groups in fasting blood glucose (MD = −7.04 mg/dL, 95% CI: [−17.26, 3.17] mg/dL, P = 0.18, I2 = 93%), insulin (MD = −1.44 μU/mL, 95% CI: [−4.30, 1.41] μU/mL, P = 0.32, I2 = 0%); and high density lipoprotein cholesterol (HDL-C) (MD = −2.68 mg/dL, 95% CI: [−9.03, 3.67] mg/dL, P = 0.41, I2 = 89%). However, by subgroup analysis, we found that compared to the CG, PG showed no significant improvement in blood glucose and lipids levels for non-diabetics, while it presented a significantly greater decrease in post-prandial blood glucose, TC, TG, and LDL-C for diabetic patients. Notably, for diabetic patients, Pilates and medication treatments showed no significant reduction in fasting blood glucose (MD = −7.00 mg/dL, 95% CI: [−26.06, 12.06] mg/dL, P = 0.40) and HbA1c (MD = −0.23%, 95% CI: [−0.58, 0.13]%, P = 0.21, I2 = 0%) than medications treatment used alone, and Pilates combined with medications and dietary treatments presented no significant improvement in fasting blood glucose than a combination of medications and dietary treatments (MD = −10.90 mg/dL, 95% CI: [−32.35, 10.54] mg/dL, P = 0.32, I2 = 94%).Conclusions: Overall, Pilates could improve post-prandial blood glucose, fasting blood glucose, HbA1c, TG, TC, and LDL-C for diabetic patients, which could be influenced by its duration and intensity. Moreover, it had no significant effect on blood glucose and lipids for non-diabetic individuals. However, Pilates, as an adjunctive treatment to medications was not superior to medications used alone in lowering fasting blood glucose and HbA1c. Furthermore, Pilates combined with medications and dietary treatments showed no significant improvement in fasting blood glucose, whereas it had a greater reduction in post-prandial blood glucose and HbA1c for diabetic patients.Systematic Review Registration:https://osf.io/xgv6w.

Abstract Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m6A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m6A reader, increases tumor-related variants through m6A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m6A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m6A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa.

BACKGROUND: Studies show that poststroke depression (PSD) increases mortality risk at 1 year. However, whether PSD increases the risk of recurrent stroke at 1 year remains unclear. This study was to investigate whether PSD at 2 weeks following a stroke could increase risk of recurrent stroke at 1 year. METHODS AND RESULTS: This was a multi-centered prospective cohort study. A total of 2306 patients with acute stroke were enrolled in our study. PSD was diagnosed according to the criteria set by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcomes of recurrent stroke were followed up via face-to-face or phone interview. A total of 1713 patients had complete follow-up data, with 481 (28.1%) cases of PSD and 158 (9.2%) cases of cumulative recurrent stroke at 1 year. Multivariate logistic regression analysis showed a 49% increase of OR of recurrent stroke at 1 year in patients with PSD, compared to patients without PSD following a stroke (OR=1.49, 95%CI: 1.03-2.15). There was no significant correlation between anti-depressant drugs and the risk of recurrent stroke at 1 year following a stroke (OR=1.96, 95%: CI 0.95-4.04). CONCLUSIONS: Based on the DSM-IV diagnostic criteria, nearly 3 out of 10 hospitalized stroke patients in China were diagnosed with PSD at 2 weeks following a stroke. PSD is associated with a higher risk of recurrent stroke at 1 year. Our study did not find benefit of anti-depressant drugs in reducing such risk.

Wafer-scale rare-earth iron garnet (RIG) single crystal thick films were fabricated on 3-in. gadolinium gallium garnet (GGG) substrates using liquid phase epitaxy. The terahertz transmittance of the RIG crystals improved after removing the GGG substrate by polishing. The time-domain spectra at Terahertz (THz) frequencies indicate the existence of a magneto-optical effect in RIG samples. The results indicate that the RIG samples exhibit a high refractive index of ∼4.50 within the 0.1–1.0 THz frequency range, a transmittance of around 40%, and an absorption rate of only 10–50 cm−1. The Faraday rotation angles of the thick single-crystal films of the RIG samples were measured using a THz-TDS system. The RIG has a thickness of ∼330 μm. The Faraday rotation angles of RIG crystals at THz frequencies can reach up to 16° when an external magnetic field of 0.18 T is applied. The Verdet constants of the RIG sample were calculated to be ∼120°/mm/T. To improve the transmittance of the RIG sample, epoxy resin and polymethylpentene (TPX) were used as anti-reflective films. The transmittance of the RIG sample increased by ∼5% for the 80 μm thick epoxy and about 10% for the 320 μm thick TPX. Therefore, this RIG single crystal thick film can achieve a low loss, a high transmittance, and a strong magneto-optical effect in the terahertz region with the cooperation of a reflection-reducing film. It is expected to have wide applications in terahertz magnetic polarization conversion, non-reciprocal phase shifters, and isolators.

Abstract Background Brown root rot disease is one of the devastating diseases in the rubber production process. It is not easy to be detected in the early stage of the disease. Our early research revealed that the rubber tree brown root rot fungus Pyrrhoderma noxium Pn006 was effectively inhibited by Bacillus subtilis Czk1 and 25% propiconazole–tebuconazole, and that the two agents might work in synergy. Therefore, in this investigation, we used non-targeted metabolomic method to evaluate the synergistic mechanism of B. subtilis Czk1 and 25% propiconazole–tebuconazole on Pyrrhoderma noxium Pn006. Results Metabolomics analysis identified 708 unique metabolic markers, including mainly lipids and lipid-like molecules, organic acids, alcohols, ketones, alkaloids and their derivatives, nucleotides and their analogues, benzene ring compounds and amino acids and their derivatives. Further screening identified 105 key metabolic markers that could be potential biomarkers to reveal the mechanism of biocontrol bacteria and chemical fungicides combination synergy. Three key metabolic pathways were found in pathway enrichment, including linolenic acid metabolism, benzoic acid degradation, and valine, leucine and isoleucine degradation. Conclusions The mechanism might be related to the influence of the energy supply and cell functional integrity of pathogenic fungal cells. Critical relevance statement A metabolomic method was utilized to investigate the synergistic effects of B. subtilis Czk1 and 25% propiconazole–tebuconazole use on Pyrrhoderma noxium Pn006. Graphical Abstract

Background: In patients with sepsis, platelets are activated and adhere to neutrophils, forming platelet-leukocyte aggregates (PLAs) that lead to the development of MODS. ARDS is one of the main manifestations of septic MODS. We designed this study to explore the effects of different anti-plate therapy drugs on platelet activation and platelet-leukocyte aggregate (PLA) formation in the early stage of septic ARDS. Methods: Sixty adult male SD rats were randomly divided into: Control group; ARDS group, ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group. ARDS was performed via instill lipopolysaccharide (LPS) intratracheally at a dose of 5 mg/kg. Aspirin or clopidogrel were given by gavage immediately after modeling. Tirofiban were given by intraperitoneal injection immediately after modeling. Rats in every group were euthanized by rapid decapitation 6 h after modeling. Platelet activation and PLA were assessed using flow cytometry and immunofluorescence staining. Histology of lung was performed by hematoxylin and eosin staining. Results: Aspirin, clopidogrel and tirofiban decreased CRP, IL-1 and TNF-α significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban decreased platelet function and ratio of wet/dry significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban increased PaO2 significantly in septic ARDS (P < 0.05). Platelet activation and PLA in the ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group decreased significantly compared to the ARDS group (P < 0.05). At 6 h after ARDS operation, obvious histological damage was observed in the lungs. All of these histological changes were quantitatively evaluated using injury scores. Aspirin, clopidogrel and tirofiban reduced the histological damages in ARDS group (P < 0.05). Conclusions: Aspirin, clopidogrel and tirofiban alleviated the inflammatory response and pulmonary edema, reduced platelet function, and alleviated hypoxemia in early septic ARDS. Aspirin, clopidogrel and tirofiban reduced platelet activation and PLA formation in early septic ARDS. Aspirin, clopidogrel and tirofiban ultimately alleviated lung injury in early septic ARDS. [ABSTRACT FROM AUTHOR]

Wafer-scale rare-earth iron garnet (RIG) single crystal thick films were fabricated on 3-in. gadolinium gallium garnet (GGG) substrates using liquid phase epitaxy. The terahertz transmittance of the RIG crystals improved after removing the GGG substrate by polishing. The time-domain spectra at Terahertz (THz) frequencies indicate the existence of a magneto-optical effect in RIG samples. The results indicate that the RIG samples exhibit a high refractive index of ∼4.50 within the 0.1–1.0 THz frequency range, a transmittance of around 40%, and an absorption rate of only 10–50 cm−1. The Faraday rotation angles of the thick single-crystal films of the RIG samples were measured using a THz-TDS system. The RIG has a thickness of ∼330 μm. The Faraday rotation angles of RIG crystals at THz frequencies can reach up to 16° when an external magnetic field of 0.18 T is applied. The Verdet constants of the RIG sample were calculated to be ∼120°/mm/T. To improve the transmittance of the RIG sample, epoxy resin and polymethylpentene (TPX) were used as anti-reflective films. The transmittance of the RIG sample increased by ∼5% for the 80 μm thick epoxy and about 10% for the 320 μm thick TPX. Therefore, this RIG single crystal thick film can achieve a low loss, a high transmittance, and a strong magneto-optical effect in the terahertz region with the cooperation of a reflection-reducing film. It is expected to have wide applications in terahertz magnetic polarization conversion, non-reciprocal phase shifters, and isolators. [ABSTRACT FROM AUTHOR]

A wafer-scale single crystal thick film of rare-earth iron garnet (RIG) has been successfully produced on a 3-in. gadolinium gallium garnet (GGG) substrate using the liquid phase epitaxy method. The RIG crystal's thickness measures ∼550 μm. By removing the GGG substrate through polishing, we improved the terahertz (THz) transmittance of the RIG crystal. In the frequency range of 0.1–1.0 THz, the RIG material exhibits a large refractive index of around 4.50, with a transmittance of ∼60% and an absorption rate of only 10–50 cm−1. Furthermore, we investigated the THz magneto-optical effect in the RIG material through THz time-domain spectroscopy. The observed results demonstrate the presence and significance of the magneto-optical effect in the RIG crystal. To provide further insights, we measured the THz Faraday rotation angle of the 550 μm-thick RIG crystal using the THz-TDS system under an external magnetic field of 0.17 T. The measured Faraday rotation angle reached 22°, and the calculated Verdet constant for the RIG sample was ∼120°/mm/T. Considering these findings, our study highlights the unique properties of this wafer-scale single crystal thick film of RIG, including its low loss, high transmission, and strong magneto-optical effect in the THz range. These characteristics make it a promising candidate for various applications, such as THz magnetic polarization conversion, non-reciprocal phase shifters, and isolators. [ABSTRACT FROM AUTHOR]