Multiomics analysis of platelet-rich plasma promoting biological performance of mesenchymal stem cells.

Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells.

A Multimode Optical Sensor for Selective and Sensitive Detection of Harmful Heavy Metal Cr(VI) in Fresh Water and Sea Water.

Water pollution originating from heavy metals has shown great impacts on the ecological environment and human health due to their extremely low biodegradability. Hexavalent chromium Cr(VI), as one harmful heavy metal with strong oxidation, high biological permeability, and high carcinogenicity, is becoming an increasingly serious threat to human health. Therefore, conveniently but accurately, monitoring the Cr(VI) level in water to maintain its normal level and ensuring the stability of the ecosystem and human health become very valuable. However, most of these heavy metal sensors reported are turn-off type single-emission sensors. In this work, a ratiometric fluorescence/colorimetry/smartphone triple-mode turn-on optical sensor for Cr(VI) was developed based on a multifunctional metal-organic framework platform. The detection limits for these three mutual verification modes were only 1.28, 4.89, and 68.4 nM, respectively. Additionally, the color changes of the detection system under sunlight can also be observed directly by the naked eye. The accuracy and practicability of this multimode sensor were further proved by the detection of Cr(VI) in actual water and seawater samples, and the recovery rate ranged from 97.308 to 104.041%.

Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease.

BACKGROUND: Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. METHODS: Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1ß, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. RESULTS: There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. CONCLUSIONS: Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

Effects of sodium-glucose cotransporter 2 inhibitors on renal risk factors in patients with abnormal glucose metabolism: a meta-analysis of randomized controlled trials.

AIMS: Several trials have assessed the antihyperglycemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the effects of SGLT2Is on renal risk factors in patients with abnormal glucose metabolism. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were identified by searching the PubMed, Embase, Scopus, and Web of Science databases published before September 30, 2022. The intervention group received SGLT2Is as monotherapy or add-on treatment, and the control group received placebos, standard care, or active control. Risk of bias assessment was performed using the Cochrane risk of bias assessment tool. Meta-analysis was performed on studies with abnormal glucose metabolism populations and studies using the weighted mean differences (WMDs) as the measure of the effect size. Clinical trials providing changes in serum uric acid (SUA) were included. The mean change of SUA, glycated hemoglobin (HbA1c), body mass index (BMI), and estimated glomerular filtration rate (eGFR) were calculated. RESULTS: After a literature search and detailed evaluation, a total of 11 RCTs were included for quantitative analysis to analyze the differences between the SGLT2I group and the control group. The results showed that SGLT2I significantly reduced SUA (MD = -0.56, 95% CI = -0.66 ~ -0.46, I2 = 0%, P < 0.00001), HbA1c (MD = -0.20, 95% CI = -0.26 ~ -0.13, I2 = 0%, P < 0.00001), and BMI (MD = -1.19, 95% CI = -1.84 ~ -0.55, I2 = 0%, P = 0.0003). There was no significant difference in the reduction of eGFR observed in the SGLT2I group (MD = -1.60, 95% CI = -3.82 ~ 0.63, I2 = 13%, P = 0.16). CONCLUSIONS: These results showed that the SGLT2I group caused greater reductions in SUA, HbA1c, and BMI but had no effect on eGFR. These data suggested that SGLT2Is may have numerous potentially beneficial clinical effects in patients with abnormal glucose metabolism. However, these results need to be consolidated by further studies.

Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.

BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively. METHODS: Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days. RESULTS: PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice. CONCLUSION: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.

A Novel Swarm Intelligence Algorithm with a Parasitism-Relation-Based Structure for Mobile Robot Path Planning.

A multi-swarm-evolutionary structure based on the parasitic relationship in the biosphere is proposed in this paper and, according to the conception, the Para-PSO-ABC algorithm (ParaPA), combined with merits of the modified particle swarm optimization (MPSO) and artificial bee colony algorithm (ABC), is conducted with the multimodal routing strategy to enhance the safety and the cost issue for the mobile robot path planning problem. The evolution is divided into three stages, where the first is the independent evolutionary stage, with the same evolution strategies for each swarm. The second is the fusion stage, in which individuals are evolved hierarchically in the parasitism structure. Finally, in the interaction stage, a multi-swarm-elite strategy is used to filter the information through a predefined cross function among swarms. Meanwhile, the segment obstacle-avoiding strategy is proposed to accelerate the searching speed with two fitness functions. The best path is selected according to the performance on the safety and consumption issues. The introduced algorithm is examined with different obstacle allocations and simulated in the real routing environment compared with some typical algorithms. The results verify the productiveness of the parasitism-relation-based structure and the stage-based evolution strategy in path planning.

The diagnostic value of blood sample NGS in patients with early periprosthetic joint infection after total hip arthroplasty.

The diagnostic value of next-generation sequencing (NGS) of blood samples from patients with periprosthetic joint infection (PJI) after total hip arthroplasty (THA) was evaluated by comparing it with drainage fluid NGS and bacterial culture. The study was designed as a retrospective diagnostic test. Thirty-six infected patients were diagnosed with PJI according to the Musculoskeletal Infection Society (MSIS) criteria and 57 volunteers were included in our study. NGS and bacterial culture were chosen to detect PJI after THA. Blood samples and drainage fluid were collected for NGS, and the drainage fluid, which was collected at the same time as the NGS drainage fluid sample, was used for bacterial culture. The primary outcomes of interest were sensitivity, specificity, and accuracy. In the infection group, 31 patients showed positive results by blood sample NGS, 33 patients showed positive results by drainage fluid NGS, and 17 patients showed positive bacterial culture results. In the control group, the results of 2 blood sample NGS, 16 drainage fluid NGS, and 3 bacterial cultures were positive. The sensitivity, specificity, and accuracy of the blood sample were 0.86, 0.96, and 0.92, respectively. The sensitivity, specificity, and accuracy of the drainage fluid samples were 0.92, 0.72, and 0.80, respectively. The sensitivity, specificity, and accuracy of bacterial culture were 0.47, 0.95, and 0.79, respectively. The study demonstrated that both the sensitivity and specificity of NGS were higher than those of bacterial culture, regardless of the kind of sample. Compared with drainage fluid NGS, the sensitivity of blood sample NGS was slightly lower (0.86 vs 0.92), but blood sample NGS showed higher specificity (0.96 vs 0.72). In total, the diagnostic value of blood sample NGS was superior to that of drainage fluid NGS and bacterial culture. The majority of infected patients could be identified by blood sample NGS. Moreover, because of its high specificity, blood sample NGS can not only detect infectious bacteria but also distinguish infectious from non-infectious bacteria, which is dramatically different from using drainage fluid NGS.

Direct separation and enumeration of CTCs in viscous blood based on co-flow microchannel with tunable shear rate: a proof-of-principle study.

Circulating tumor cells (CTCs), which have extremely low density in whole blood, are an important indicator of primary tumor metastasis. Isolation and enumeration of these cells are critical for clinical applications. Separation of CTCs from massive blood cells without labeling and addition of synthetic polymers is challenging. Herein, a novel well-defined co-flow microfluidic device is presented and used to separate CTCs in viscous blood by applying both inertial and viscoelastic forces. Diluted blood without any synthetic polymer and buffer solution were used as viscoelastic fluid and Newtonian fluid, respectively, and they were co-flowed in the designed chip to form a sheath flow. The co-flow system provides the function of particle pre-focusing and creates a tunable shear rate region at the interface to adjust the migration of particles or cells from the sample solution to the buffer solution. Successful separation of CTCs from viscous blood was demonstrated and enumeration was also conducted by image recognition after separation. The statistical results indicated that a recovery rate of cancer cells greater than 87% was obtained using the developed method, which proved that the direct separation of CTCs from diluted blood can be achieved without the addition of any synthetic polymer to prepare viscoelastic fluid. This method holds great promise for the separation of cells in viscous biological fluid without either complicated channel structures or the addition of synthetic polymers.

Retrospective Study from a Single Center to Identify Risk Factors Associated with Reinfection in Patients Undergoing 2-Stage Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND This study identified risk factors associated with reinfection and created a scoring system designed for patients with periprosthetic joint infection (PJI) who have undergone prosthetic resection and spacer implantation. MATERIAL AND METHODS Patients who underwent 2-stage revision for PJI from January 2010 to December 2017 were retrospectively analyzed in this study. Patients were divided into 2 groups: infection recurrence and infection cure. Demographic and clinical information, laboratory test results, and radiological images that were potentially associated with infection were obtained and analyzed. RESULTS Seven independent risk (protective) factors for infection recurrence in patients with PJI who underwent 2-stage hip revision surgery were identified: C-reactive protein level, type of bacterial infection, age, immunosuppression, albumin/globulin ratio, glucose level, and magnetic resonance imaging findings. Finally, a weighted scoring system of 100-mark system was established and the area under the curve was 0.965 (95% confidential interval=0.947-0.983). The predictive scores for low risk (≤30%), moderate risk (31-69%), and high risk (≥70%) of infection recurrence were ≤45, 46-77, and ≥78, respectively. CONCLUSIONS For patients with PJI who had already undergone joint resection and spacer implantation, this newly established scoring system might help determine the accurate risk of infection recurrence after a definitive new prosthesis implantation. Patients with scores greater than 78 points would be considered very likely to have an infection recurrence. Therefore, the second-stage revision surgery should be changed to an additional anti-infection treatment or a debridement surgery instead of a definitive prosthesis implantation surgery.

Clinical and radiologic outcomes in patients undergoing primary total hip arthroplasty with Collum Femoris Preserving stems: a comparison between the direct anterior approach and the posterior approach.

BACKGROUND: The direct anterior approach (DAA) and posterior approach (PA) are two of the most common surgical approaches used for total hip arthroplasty (THA) worldwide. The curved anatomical collum femoris-preserving (CFP) stem was designed to preserve the bone of the femoral neck and allow physiologic load transfer along the trabecular systems, which may better restore hip biomechanics, improve triplanar stem stability and improve the long-term survival rate. We believe this study will demonstrate whether the DAA is suitable for THA with CFP stems. METHODS: The data of patients who underwent primary THA with CFP stems from January 2010 to December 2015 were retrospectively analysed. These patients were divided into two groups (group A, DAA; group B, PA). The approach was selected by the surgeon. The demographic characteristics, preoperative diagnoses, preoperative Harris hip score, preoperative range of motion, postoperative complications, and radiologic measurements (neck-shaft angle, coronal alignment, sagittal alignment, stress shielding, anteversion, neck-preserving ratio, acetabular anteversion, acetabular inclination angle, acetabular depth, anterior-posterior offset, lateral offset, difference in leg length) were recorded for all patients. RESULTS: In this study, a total of 248 patients (185 male and 63 female) were included. No significant differences were found between group A and group B in terms of general patient information and radiologic measurements. However, the rate of nerve injury in group A (7/5.5%) was significantly higher than that in group B (1/0.8%) (p = 0.037). At 1 month after surgery, we found a significant difference between the two groups in the Harris hip score (HHS) (71.03 ± 8.04 in group A, 68.39 ± 8.37 in group B, P = 0.014) and forgotten joint score (FJS-12) (50.78 ± 7.57 in group A, 47.68 ± 7.34 in group B, P = 0.001). At 1 year after surgery, the mean FJS-12 score in group A (68.78 ± 7.54) was higher than that in group B (58.84 ± 8.91) (P < 0.001). At 5 years after surgery, the mean FJS-12 score in group A (73.38 ± 7.21) was higher than that in group B (67.16 ± 9.12) (P < 0.001). Post hoc analysis of the 1-month, 1-year, and 5-year postoperative FJS-12 scores using multiple linear regression analysis revealed that an excellent HHS led to good patient satisfaction at each time point. CONCLUSION: In summary, unlike a "standard" femoral stem, whose alignment might be affected by the surgical approach, alignment of the CFP stem is independent from the surgical approach. Even though the DAA had a higher nerve injury rate, nerve injury from the DAA did not typically cause severe dysfunction of the lower extremity. Therefore, decisions regarding the surgical approach for patients undergoing THA with CFP stems can be made primarily based on the preference of the surgeon.

CNN-Based Hand Grasping Prediction and Control via Postural Synergy Basis Extraction.

The prediction of hand grasping and control of a robotic manipulator for hand activity training is of great significance to assist stroke patients to recover their biomechanical functions. However, the human hand and the figure joints have multiple degrees of freedom; therefore, it is complex to process and analyze all the collected data in hand modeling. To simplify the description of grasping activities, it is necessary to extract and decompose the principal components of hand actions. In this paper, the relationships among hand grasping actions are explored by extracting the postural synergy basis of hand motions, aiming to simplify hand grasping actions and reduce the data dimensions for robot control. A convolutional neural network (CNN)-based hand activity prediction method is proposed, which utilizes motion data to estimate hand grasping actions. The prediction results were then used to control a stimulated robotic model according to the extracted postural synergy basis. The prediction accuracy of the proposed method for the selected hand motions could reach up to 94% and the robotic model could be operated naturally based on patient's movement intention, so as to complete grasping tasks and achieve active rehabilitation.

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability.

Changes in mitochondrial membrane permeability are closely associated with mitochondria-mediated apoptosis. Antimicrobial peptides (AMPs), which have been found to enter cells to exert physiological effects, cause damage to the mitochondria. This paper reviews the molecular mechanisms of AMP-mediated apoptosis by changing the permeability of the mitochondrial membrane through three pathways: the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM), and mitochondrial permeability transition pore (MPTP). The roles of AMPs in inducing changes in membrane permeability and apoptosis are also discussed. Combined with recent research results, the possible application prospects of AMPs are proposed to provide a theoretical reference for the development of AMPs as therapeutic agents for human diseases.

Bazi Bushen capsule attenuates cognitive deficits by inhibiting microglia activation and cellular senescence.

CONTEXT: Bazi Bushen capsule (BZBS) has anti-ageing properties and is effective in enhancing memory. OBJECTIVE: To find evidence supporting the mechanisms and biomarkers by which BZBS functions. MATERIALS AND METHODS: Male C57BL/6J mice were randomly divided into five groups: normal, ageing, ß-nicotinamide mononucleotide capsule (NMN), BZBS low-dose (LD-BZ) and BZBS high-dose (HD-BZ). The last four groups were subcutaneously injected with d-galactose (d-gal, 100 mg/kg/d) to induce the ageing process. At the same time, the LD-BZ, HD-BZ and NMN groups were intragastrically injected with BZBS (1 and 2 g/kg/d) and NMN (100 mg/kg/d) for treatment, respectively. After 60 days, the changes in overall ageing status, brain neuron morphology, expression of p16INK4a, proliferating cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba1), postsynaptic density protein 95 (PSD95), CD11b, Arg1, CD206, Trem2, Ym1 and Fizz1, and the senescence-associated secretory phenotype (SASP) factors were observed. RESULTS: Compared with the mice in the ageing group, the HD-BZ mice exhibited obvious improvements in strength, endurance, motor coordination, cognitive function and neuron injury. The results showed a decrease in p16INK4a, Iba1 and the upregulation of PCNA, PSD95 among brain proteins. The brain mRNA exhibited downregulation of Iba1 (p < 0.001), CD11b (p < 0.001), and upregulation of Arg1 (p < 0.01), CD206 (p < 0.05), Trem2 (p < 0.001), Ym1 (p < 0.01), Fizz1 (p < 0.05) and PSD95 (p < 0.01), as well as improvement of SASP factors. CONCLUSIONS: BZBS improves cognitive deficits via inhibition of cellular senescence and microglia activation. This study provides experimental evidence for the wide application of BZBS in clinical practice for cognitive deficits.

Mixed responses to first-line alectinib in non-small cell lung cancer patients with rare ALK gene fusions: A case series and literature review.

Anaplastic lymphoma kinase (ALK) fusion is a well-defined biomarker for ALK tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC). Alectinib, a second-generation ALK-TKI, has been shown to have significantly longer progression-free survival (PFS) than first-generation ALK inhibitors in untreated ALK-rearranged NSCLC patients. However, its clinical efficacy on rare ALK fusions remains unclear. Herein, two advanced NSCLC patients received first-line alectinib treatment, given their positive ALK fusion status as determined by immunohistochemistry (IHC) testing results. Patients showed limited clinical response (PFS: 4 months) and primary resistance to alectinib respectively. Molecular profiling using next-generation sequencing (NGS) further revealed a striatin (STRN)-ALK fusion in the first patient accompanied by MET amplification, and a LIM domain only protein 7 (LMO7)-ALK fusion in another patient without any other known oncogenic alterations. Both patients demonstrated improved survival after they switched to second-line crizotinib (PFS: 11 months) and ensartinib (PFS: 18 months), respectively, up till the last follow-up assessment. In conclusion, the clinical efficacy of ALK-TKIs including alectinib for lung cancer with uncommon ALK gene fusions is still under evaluation. This study and literature review results showed mixed responses to alectinib in NSCLC patients who harboured rare ALK fusions. Comprehensive molecular profiling of tumour is thus strongly warranted for precise treatment strategies.

Discovery of novel iminosydnone compounds with insecticidal activities based on the binding mode of triflumezopyrim.

Triflumezopyrim (TFM) is a new mesoionic insecticide developed by DuPont. Like other neonicotinoid insecticides, it binds to the orthosteric site of the nicotinic acetylcholine receptor (nAChR), but the binding mode has not been reported. Nicotinic acetylcholine binding proteins (nAChBPs) are ideal alternative structure for nAChRs. In this study, molecular docking, molecular dynamics (MD) simulations, binding free energy calculation, and per-residue binding free energy decomposition were used to study the binding modes of TFM and other 12 mesoionic insecticides. By comparing the binding free energy and the insecticidal activity, it was found that the sub-pocket around the benzyl group of the mesoionic insecticide is the key area for maintaining its activity, which is composed of A: Val116, A: Met124, A: Ile126, B: Trp155 and B: Val156. In order to verify the druggability of the sub-pocket, a series of iminosydnone compounds were designed and synthesized based on the structure of the sub-pocket. The lethality rate of compound 1 against Mythimna separata were 100% at 500 mg/L. Our research provides a basis for designing new mesoionic insecticides based on structure.

Effect of external mismatch and internal mismatch caused by pointing error on performances of space chaos laser communication system.

In order to evaluate the effect of pointing error on space chaos laser communication system, we conduct bit error rate (BER) analysis with external mismatch and internal mismatch caused by pointing error. Based on BER formulae, numerical simulations are conducted to investigate the effect of external and internal mismatches on performance of the system under different boresight and jitter. Our results indicate that jitter will affect BER more than boresight and internal mismatch will affect the performance of system more than external mismatch. These results are significant for optimizing space chaos laser communication system design.

PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow.

Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro-inflammatory, suggesting that the establishment of endothelial polarity elicits an anti-inflammatory response. However, a causative relationship between polarity and inflammatory responses has not been firmly established. Here, we find that a cell polarity protein, PAR-3, is an essential gatekeeper of GSK3ß activity in response to laminar blood flow. We show that flow-induced spatial distribution of PAR-3/aPKCλ and aPKCλ/GSK3ß complexes controls local GSK3ß activity and thereby regulates endothelial planar polarity. The spatial information for GSK3ß activation is essential for flow-dependent polarity to the flow axis, but is not necessary for flow-induced anti-inflammatory response. Our results shed light on a novel relationship between endothelial polarity and vascular homeostasis highlighting avenues for novel therapeutic strategies.

Comparison of Bone Remodeling Between Collum Femoris-Preserving Stems and Ribbed Stems in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This study examined a cohort of patients who underwent bilateral THAs. CFP prostheses and ribbed prostheses were each used on both sides. We assessed the midterm clinical, radiological, and bone remodeling outcomes around prosthesis of these patients. MATERIAL AND METHODS From January 2009 to January 2013, 53 patients were enrolled in our study. We clinically evaluated all patients by recording Harris hip and Oxford hip scores. Some radiological indicators of the femoral prosthesis position were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean preoperative HHS of the CFP group and ribbed group were no significantly different (P=0.570). The neck-shaft angle in the ribbed group was significantly greater than in the CFP group (P<0.001). The CFP group had a greater offset (P<0.001). There was no significant difference in leg-length discrepancy (P=0.727) or Engh score between the 2 groups at the last follow-up (P=0.858). The preoperative BMD was increased at the last follow-up in Gruen zones 3 and 5 (P<0.05) and decreased in Gruen zones 1 and 7 (P<0.05) on the CFP side. BMD was increased in Gruen zone 4 (P=0.007) on the ribbed side. Pearson correlations and rate of complications were not significantly different. CONCLUSIONS Both the CFP and ribbed stem significantly improved the preoperative HHSs and OHSs. The bone remodeling of the CFP stem was more concentrated in the middle and distal regions of the prosthesis, while that of the ribbed stem was more concentrated in the proximal portion of the prosthesis.

Cervical insufficiency: a noteworthy disease with controversies.

Cervical insufficiency (CI) is a mainly disease leading to recurrent abortions and preterm birth which may present in about 1% of obstetric populations. Recurrent pregnancy losses caused by CI incur serious economic burdens on society as well as huge psychological burdens to family members. However, many patients even clinicians in some areas of the world still remain confused about this disease. At the same time, the etiology of CI is still uncertain and it is still a controversial disease in diagnosis and treatment. This article summarizes the potential risk factors associated with CI, which could be worthy of attention and helpful for future research. It also reviews the methods for diagnosis and treatment of CI to better understand this noteworthy disease, as well as presents the related consensus and controversies according to the newly updated guidelines, which has practical significance for conducting more in-depth investigations in the future.