GSDMB involvement in the pathogenesis of abdominal aortic aneurysm through regulation of macrophage non-canonical pyroptosis.

Abdominal aortic aneurysm (AAA) is a dangerous condition affecting the aorta. Macrophage pyroptosis, phenotypic transformation, and apoptosis of aortic smooth muscle cells (ASMCs) are pivotal mechanisms in AAA pathogenesis. This study explores how Gasdermin B (GSDMB) regulates macrophage non-canonical pyroptosis and its impact on the phenotypic transformation and apoptosis of ASMCs, thereby unveiling the role of GSDMB in AAA pathogenesis. Immunofluorescence analysis was used to assess the expression levels and localization of GSDMB, cysteinyl aspartate-specific protease-4 (Caspase-4), and N-terminal of cleaved GSDMD (N-GSDMD) in AAA tissues. A cell model that mimics macrophage non-canonical pyroptosis was established by treating THP-1 cells with lipopolysaccharide (LPS). THP-1 cells with reduced or increased GSDMB were generated using small interfering RNA (siRNA) or plasmids. Co-culture experiments involving THP-1 cells and HASMCs were conducted to explore the impact of GSDMB on HASMCs. The mitochondrial reactive oxygen species (mtROS) scavenger Mito-TEMPO lowered mtROS levels in THP-1 cells. Our findings revealed that GSDMB was significantly upregulated in AAA macrophages, which was accompanied by robust non-canonical pyroptosis. THP-1 cells showed non-canonical pyroptosis in response to LPS, which was accompanied by an increase in GSDMB. Further research demonstrated that altering GSDMB, either by knockdown or overexpression, can affect macrophage non-canonical pyroptosis as well as the phenotypic transformation and apoptosis of HASMCs. LPS-induced non-canonical pyroptosis in THP-1 cells was associated with an increase in mtROS, whereas Mito-TEMPO effectively decreased non-canonical pyroptosis and the expression of GSDMB. These findings suggest that GSDMB plays a role in AAA macrophage non-canonical pyroptosis, which influences the phenotypic transformation and apoptosis of HASMCs. The mtROS-Dynamin-Related Protein 1 (Drp1) axis is likely to regulate the GSDMB-mediated non-canonical pyroptosis.

Potential mechanisms of aortic medial degeneration promoted by co-exposure to microplastics and lead.

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.

Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

S-adenosylmethionine attenuates angiotensin II-induced aortic dissection formation by inhibiting vascular smooth muscle cell phenotypic switch and autophagy.

It is well known that aortic dissection (AD) is a very aggressive class of vascular diseases. S-adenosylmethionine (SAM) is an autophagy inhibitor with anti-inflammatory and anti-oxidative stress effects; however, the role of SAM in AD is unknown. In this study, we constructed an animal model of AD using subcutaneous minipump continuous infusion of AngII-induced ApoE-/-mice and a cytopathic model using AngII-induced primary vascular smooth muscle cells (VSMCs) to investigate the possible role of SAM in AD. The results showed that mice in the AngII + SAM group had significantly lower AD incidence, significantly prolonged survival, and reduced vascular elastic fiber disruption compared with mice in the AngII group. In addition, SAM significantly inhibited autophagy in vivo and in vitro. Meanwhile, SAM also inhibited the cellular phenotypic switch, mainly by up regulating the expression levels of contractile marker proteins [α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)] and down regulating the expression levels of synthetic marker proteins [osteoblast protein (OPN), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9)]. Molecularly, SAM inhibited AD formation mainly by activating the PI3K/AKT/mTOR signaling pathway. Using a PI3K inhibitor (LY294002) significantly reversed the protective effect of SAM in AngII-induced mice and VSMCs.Our study demonstrates the protective effect of SAM on mice under AngII-induced AD for the first time. SAM prevented AD formation mainly by inhibiting cellular phenotypic switch and autophagy, and activation of the PI3K/AKT/mTOR signaling pathway is a possible molecular mechanism. Thus, SAM may be a novel strategy for the treatment of AD.

Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

Background: Large defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. Materials and methods: We extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. Results: SR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. Conclusions: In summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. The translational potential of this article: This study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.

A Voice Disease Detection Method Based on MFCCs and Shallow CNN.

The incidence rate of voice diseases is increasing year by year. The use of software for remote diagnosis is a technical development trend and has important practical value. Among voice diseases, common diseases that cause hoarseness include spasmodic dysphonia, vocal cord paralysis, vocal nodule, and vocal cord polyp. This paper presents a voice disease detection method that can be applied in a wide range of clinical. We cooperated with Xiangya Hospital of Central South University to collect voice samples from 352 different patients. The Mel Frequency Cepstrum Coefficient (MFCC) parameters are extracted as input features to describe the voice in the form of data. An innovative model combining MFCC parameters and single convolution layer CNN is proposed for fast calculation and classification. The highest accuracy we achieved was 92%, it is fully ahead of the original research results and internationally advanced. And we use advanced voice function assessment databases (AVFAD) to evaluate the generalization ability of the method we proposed, which achieved an accuracy rate of 98%. Experiments on clinical and standard datasets show that for the pathological detection of voice diseases, our method has greatly improved in accuracy and computational efficiency.

Near-noiseless and small-footprint phase sensitive optical parametric amplifier using AlGaAs-on-insulator waveguides.

Phase sensitive amplifiers (PSAs) based on optical parametric amplification feature near noiseless amplification, which is of considerable benefit for improving the performance of optical communication systems. Currently, the majority of research on PSAs is carried out on the basis of highly nonlinear fibers or periodically poled lithium niobite waveguides, with the impediments of being susceptible to environmental interference and requiring complex temperature control systems to maintain quasi-phase matching conditions, respectively. Here, a near-noiseless and small-footprint PSA based on dispersion-engineered AlGaAs-on-insulator (AlGaAsOI) waveguides is proposed and demonstrated theoretically. The phase-dependent gain and the phase-to-phase transfer function of the PSA are calculated to analyze its characteristics. Furthermore, we investigate in detail the effects of linear loss, nonlinear coefficient, and pump power on the PSA gain and noise figure (NF) in AlGaAsOI waveguides. The results show that a PSA based on an AlGaAsOI waveguide is feasible with a maximum phase sensitive gain of 33 dB, achieving an NF of less than 1 dB over a gain bandwidth of 245 nm with a gain of >15d B, which completely covers the S + C + L band. This investigation is worthwhile for noiseless PSAs on photonic integrated chips, which are promising for low-noise optical amplification, multifunctional photonic integrated chips, quantum communication, and spectroscopy, and as a reference for low-noise PSAs depending on the third-order nonlinearity, χ (3), of the waveguide material.

Chitosan nanoparticles encapsulated with BEZ235 prevent acute rejection in mouse heart transplantation.

Acute rejection may manifest following heart transplantation, despite the implementation of relatively well-established immunosuppression protocols. The significance of the mTOR signaling pathway in rejection is widely acknowledged. BEZ235, a second-generation mTOR inhibitor with dual inhibitory effects on PI3K and mTOR, holds promise for clinical applications. This study developed a nanodelivery system, BEZ235@NP, to facilitate the intracellular delivery of BEZ235, which enhances efficacy and reduces adverse effects by improving the poor solubility of BEZ235. In the complete MHCII-mismatched model, BEZ235@NP significantly prolonged cardiac allografts survival compared to free BEZ235, which was attributed to more effective suppression of effector T cell activation and promotion of greater expansion of Tregs. These nanoparticles demonstrated excellent biosafety and exhibited no short-term biotoxicity upon investigation. To elucidate the mechanism, primary T cells were isolated from the spleen and it was observed that BEZ235@NP treatment resulted in the arrest of these cells in the G0/G1 phase. As indicated by Western blot analysis, BEZ235@NP substantially reduced mTOR phosphorylation. This, in turn, suppressed downstream pathways and ultimately exerted an anti-proliferative and anti-activating effect on cells. Furthermore, it was observed that inhibition of the mTOR pathway stimulated T-cell autophagy. In conclusion, the strategy of intracellular delivery of BEZ235 presents promising applications for the treatment of acute rejection.

Gamma Nail Combined with One Cannulated Compression Screw Fixation for Treating Pauwels Type III Femoral Neck Fractures in Young and Middle-Aged Adults: Clinical Follow-Up and Biomechanical Studies.

OBJECTIVE: Recently, some clinical studies have reported the use of an intramedullary nailing system for treating unstable femoral neck fractures or femoral neck fractures combined with femoral shaft fractures in young adults, and the results have indicated certain advantages. However, no study has investigated the mechanical properties of this method. We aimed to evaluate the mechanical stability and clinical efficacy of the Gamma nail combined with one cannulated compression screw (CCS) fixation for treating Pauwels type III femoral neck fracture in young and middle-aged adults. METHODS: This study consists of two parts: a clinical retrospective study and randomized controlled biomechanical test. Twelve adult cadaver femora were used to test and compare the biomechanical properties among three fixation methods: three parallel CCS (group A), Gamma nail (group B), and Gamma nail combined with one cannulated compression screw (group C). The single continuous compression test, cyclic load test, and ultimate vertical load test were used to evaluate the biomechanical performance of the three fixation methods. We also conducted a retrospective study of 31 patients with Pauwels type III femoral neck fractures, including 16 patients with fractures fixed with three parallel CCS (CCS group) and 15 patients with fractures fixed with Gamma nail combined with one CCS (Gamma nail + CCS group). The patients were followed up for at least 3 years, and all were evaluated for surgical time (from skin incision to closure), surgical blood loss, hospital stay, and the Harris hip score. RESULTS: In mechanical experiments, we have found that the mechanical advantages of Gamma nail fixation are not as good as those of conventional CCS fixation. However, the mechanical properties of Gamma nail fixation combined with one cannulated screw perpendicular to the fracture line are much better than those of Gamma nail fixation and CCS fixation. No significant difference was found in the incidence of femoral head necrosis and nonunion between the CCS and Gamma nail + CCS groups. Moreover, there was no statistically significant difference in the Harris hip scores between the two groups. One patient in the CCS group showed significant withdrawal of cannulated screws at 5 months after surgery, whereas in the Gamma nail + CCS group, all patients, including those with femoral neck necrosis, showed no loss of stability of the fixation. CONCLUSION: Among the two fixation methods evaluated in this study, Gamma nail combined with one CCS fixation showed better biomechanical properties and may reduce complications associated with unstable fixation devices.

The sulfoximine insecticide sulfoxaflor exposure reduces the survival status and disrupts the intestinal metabolism of the honeybee Apis mellifera.

Honeybees (Apis mellifera) are indispensable pollinators in agricultural production, biodiversity conservation, and nutrients provision. The abundance and diversity of honeybees have been rapidly diminishing, possibly related to the extensive use of insecticides in ecosystems. Sulfoxaflor is a novel sulfoximine insecticide that, like neonicotinoids, acts as a competitive modulator of nicotinic acetylcholine receptors (nAChR) in insects. However, few studies have addressed the negative effects of sulfoxaflor on honeybees at environmentally relevant concentrations. In the present study, adult workers were fed a 50% (w/v) of sugar solution containing different concentrations (0, 0.05, 0.5 and 2.0 mg/L) of sulfoxaflor for two weeks consecutively. The survival rates, food intake, and body weight of the honeybees significantly decreased after continuous exposure at higher doses (0.5 and 2.0 mg/L) of sulfoxaflor when compared with the control. The change in the metabolites in the honeybee gut was determined using high-throughput non-targeted metabolomics on day 14 after sulfoxaflor treatment. The results revealed that 24 and 105 metabolites changed after exposure to 0.5 and 2.0 mg/L sulfoxaflor, respectively, compared with that of the control groups. A total of 12 changed compounds including pregenolone and glutathione were detected as potential biomarkers, which were eventually found to be enriched in pathways of the steroid hormone biosynthesis (p = 0.0001) and glutathione metabolism (p = 0.021). These findings provide a new perspective on the physiological influence of sulfoxaflor stress in honeybees.

Association between dietary inflammation and erectile dysfunction among US adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2001-2004.

Background: Although chronic low-grade inflammation has been linked to the development of erectile dysfunction (ED), the association between pro-inflammatory diets and ED is unclear. The dietary inflammation index (DII) is a novel method to quantify the inflammatory potential of a diet. Objective: Our objective was to investigate the association between the DII and ED among US males. Design: This cross-sectional study included 3,693 males 20-85 year of age from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. Multivariable-adjusted logistic regression models were used to assess the association between the DII and ED. All analyses accounted for the complex sampling design. Results: The mean ± SE of the DII was 0.8 ± 0.1 and 0.4 ± 0.1 among participants with and without ED, respectively. After adjusting for age, race/ethnicity, education, smoking status, physical activity, drinking status, hypertension, diabetes, cardiovascular disease, hypercholesterolemia, BMI, and eGFR, the DII score was associated with ED (odds ratio 1.12; 95% CI: 1.04-1.19). Moreover, this association was also stable in our subgroup analysis or sensitivity analyses. Conclusion: Dietary inflammatory potential, as estimated by the DII score, is positively associated with ED among US males.

Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis.

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women. Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis. Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16-7.03; I 2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I 2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12-4.35; I 2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70-6.35; I 2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51-6.93; I 2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50-0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22-0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27-1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15-1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17-1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38-1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, -18.92 to -12.66; I 2 = 28.4%), -0.23 (95% CI, -0.35 to -0.10; I 2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women. Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.

Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer.

CD8+ T cells are central mediators of immune responses against infections and cancer. Here we identified Dapl1 as a crucial regulator of CD8+ T cell responses to cancer and infections. Dapl1 deficiency promotes the expansion of tumour-infiltrating effector memory-like CD8+ T cells and prevents their functional exhaustion, coupled with increased antitumour immunity and improved efficacy of adoptive T cell therapy. Dapl1 controls activation of NFATc2, a transcription factor required for the effector function of CD8+ T cells. Although NFATc2 mediates induction of the immune checkpoint receptor Tim3, competent NFATc2 activation prevents functional exhaustion of CD8+ T cells. Interestingly, exhausted CD8+ T cells display attenuated NFATc2 activation due to Tim3-mediated feedback inhibition; Dapl1 deletion rescues NFATc2 activation and thereby prevents dysfunction of exhausted CD8+ T cells in chronic infection and cancer. These findings establish Dapl1 as a crucial regulator of CD8+ T cell immunity and a potential target for cancer immunotherapy.

Association Between Psoriasis and Nonalcoholic Fatty Liver Disease Among Outpatient US Adults.

Importance: Recent studies have shown an association between psoriasis and nonalcoholic fatty liver disease (NAFLD) in US inpatients, but the association is still unclear in the outpatient US population. Objective: To assess whether psoriasis is associated with NAFLD in outpatient US adults. Design, Setting, and Participants: This population-based cross-sectional study used data on US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014 cycles. Data were analyzed from June to September 2021. Exposures: Self-reported psoriasis. Main Outcomes and Measures: The main outcome was NAFLD, defined as a US fatty liver index score greater than 30. Sampling weights were calculated according to NHANES guidelines. Results: Among 5672 adults included in this study (mean age, 38.9 years [95% CI, 38.4-39.3 years]; 2999 [51.1%] female), 148 (3.0%) had psoriasis and 5524 (97.0%) did not have psoriasis. A total of 1558 participants (26.8%) were classified as having NAFLD. Compared with participants without psoriasis, those with psoriasis had a higher prevalence of NAFLD (32.7% [52] vs 26.6% [1506]). In a multivariable logistic regression model adjusted for age, sex, race and ethnicity, educational level, family income, marital status, NHANES cycles, diabetes, metabolic syndrome, and smoking and alcohol drinking status, psoriasis was associated with NAFLD (odds ratio [OR], 1.67; 95% CI, 1.03-2.70). In subgroup analyses, psoriasis was associated with NAFLD among men (OR, 2.16; 95% CI, 1.10-4.24), among those aged 20 to 39 years (OR, 2.48; 95% CI, 1.09-5.67), and among those without diabetes (1.70; 95% CI, 1.05-2.76). An association between psoriasis and NAFLD was found in sensitivity analyses that excluded potential hepatotoxic medication use (OR, 1.72; 95% CI, 1.01-2.95) or non-Hispanic Black participants (OR, 1.76; 95% CI, 1.07-2.87), redefined NAFLD based on the hepatic steatosis index score (OR, 1.59; 95% CI, 1.01-2.50), and used inverse probability of treatment weighting (OR, 1.43; 95% CI, 1.09-1.86). Conclusions and Relevance: In this cross-sectional study, psoriasis was associated with NAFLD in the outpatient US adult population in adjusted models. This association may be important to consider in the context of clinicians prescribing potentially hepatotoxic medication for psoriasis management.

Minimally Invasive Percutaneous TightRope® System Fixation for an Unstable Posterior Pelvic Ring: Clinical Follow-up and Biomechanical Studies.

OBJECTIVE: To evaluate the mechanical stability and clinical efficacy of minimally invasive percutaneous TightRope® systems applied via gun-shaped reduction forceps for unstable posterior pelvic ring fractures. MATERIALS AND METHODS: This study consists of two parts: a clinical retrospective study and a randomized controlled biomechanical test. For the clinical study, a retrospective analysis of posterior pelvic ring fractures was performed between June 2015 and May 2020. Eighteen patients underwent surgery using two TightRope® systems to fix a broken posterior pelvic ring because of unstable AO type C1 and C2 pelvic ring fractures. The patients were followed up for at least 2 years, and all patients were evaluated using the Majeed scoring system and vertical displacement. In the biomechanical tests, six embalmed adult pelvic specimens were used. The fractures were subjected to TightRope®, IS screw, and TBP fixation in a randomized block design. The specimens were placed in a biomechanical testing machine in a standing neutral posture. A cyclic vertical load of up to 500 N was applied, and the displacement of the specimens was recorded by the testing machine. The ultimate load in each group of specimens was recorded. The displacement and ultimate load were compared and analyzed by statistical methods. RESULTS: At a mean follow-up of 38.89 ± 8.72 months, the functional Majeed score was excellent in 14 patients and good in four patients. The final radiological examinations showed that the outcome was excellent in 14 patients and good in four patients. In these patients, no serious clinical complications were found. Weight-bearing was delayed in four patients. In biomechanical tests, the displacement of the specimens fixed with TightRope® was significantly lower than that of the specimens fixed with TBP (P < 0.05) when the load ranged from 300 to 500 N. The displacement in the IS screw group was significantly lower than that in either the TBP or TightRope® group (P < 0.05) when the load ranged from 0 to 500 N. The ultimate load in the IS screw group (1798 ± 83.53 N) was significantly greater than that in the TBP group (1352 ± 74.41 N) (t = 9.78, P < 0.0001) and the TightRope® group (1347 ± 54.28 N) (t = 11.11, P < 0.0001). However, no significant difference was observed between the TightRope® and TBP groups (t = 0.13, P = 0.90). CONCLUSION: Percutaneous posterior TightRope® system shows strong stability in mechanical experiments and shows good results in clinical follow-up while this system has certain advantages in lower surgical requirements and lower risk of related nerve and vascular structural damage.

Effects of Membrane Structure on Oil-Water Separation by Smoothed Particle Hydrodynamics.

Membrane has been considered an effective tool for oil-water separation. By using the smoothed particle hydrodynamics (SPH) method, the effects of membrane structure on fluid separation were studied thoroughly in this paper. The oil-water two-phase fluid was generated as particles, while the membrane was built with solid particles, which was able to select the fluid particles. In general, the developed SPH method in this paper can evaluate separation performance with different membrane shapes, pore size distributions, membrane thickness and fluid properties. We suggest to the industry a potential approach to promote separation based on our simulation results, including adding the external force in the selected direction and demulsification for the bulk phase liquid particles. The triangular membrane performs well with the conditions for various parameters, as a result of its insensitivity to inhibiting factors. The effectiveness and robustness of the proposed SPH scheme was validated by a number of numerical experiments, and we assessed the optimized membrane structure and operation manners in order to improve separation efficiency and long-term safety.

Changes of Migration, Immunoregulation and Osteogenic Differentiation of Mesenchymal Stem Cells in Different Stages of Inflammation.

Bone infection has always been the focus of orthopedic research. Mesenchymal stem cells (MSCs) are the natural progenitors of osteoblasts, and the process of osteogenesis is triggered in response to different signals from the extracellular matrix. MSCs exert important functions including secretion and immune regulation and also play a key role in bone regeneration. The biological behavior of MSCs in acute and chronic inflammation, especially the transformation between acute inflammation and chronic inflammation, has aroused great interest among researchers. This paper reviews the recent literature and summarizes the behavior and biological characteristics of MSCs in acute and chronic inflammation to stimulate further research on MSCs and treatment of bone diseases.

Features of capsule endoscopy in COVID-19 patients with a six-month follow-up: A prospective observational study.

Recently, the coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several studies indicate that the digestive system can also be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, patients with digestive symptoms should have a capsule endoscopy (CE). COVID-19 patients with gastrointestinal (GI) symptoms who underwent CE were recruited from March 2020 to April 2020. We collected patients' data and performed a prospective follow-up study for 6 months. All 11 COVID-19 cases with GI symptoms who underwent CE presented gastritis. Eight cases (72.7%) had intestinal mucosa inflammation. Among them, two cases showed intestinal ulcers or erosions. Moreover, two cases displayed colonic mucositis. One case was lost during follow-up. At 3-6 months after hospital discharge, five patients underwent CE again, presenting gastrointestinal lesions. Five of the 10 cases had GI symptoms, such as abdominal pain, diarrhea, constipation, and others. Among these five cases, the GI symptoms of three patients disappeared at the last follow-up and two patients still presented diarrhea symptoms. Overall, we observed damaged digestive tract mucosa that could be caused by SARS-CoV-2. Moreover, after discharge, some patients still presented intestinal lesions and GI symptoms.

Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups.

Cellular associations in the bone microenvironment are involved in modulating the balance between bone remodeling and resorption, which is necessary for maintaining a normal bone morphology. Macrophages and osteoclasts are both vital components of the bone marrow. Macrophages can interact with osteoclasts and regulate bone metabolism by secreting a variety of cytokines, which make a significant contribution to the associations. Although, recent studies have fully explored either macrophages or osteoclasts, indicating the significance of these two types of cells. However, it is of high importance to report the latest discoveries on the relationships between these two myeloid-derived cells in the field of osteoimmunology. Therefore, this paper reviews this topic from three novel aspects of the origin, polarization, and subgroups based on the previous work, to provide a reference for future research and treatment of bone-related diseases.

DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis.

B-cell-activating factor (BAFF) mediates B-cell survival and, when deregulated, contributes to autoimmune diseases and B-cell malignancies. The mechanism connecting BAFF receptor (BAFFR) signal to downstream pathways and pathophysiological functions is not well understood. Here we identified DYRK1a as a kinase that responds to BAFF stimulation and mediates BAFF-induced B-cell survival. B-cell-specific DYRK1a deficiency causes peripheral B-cell reduction and ameliorates autoimmunity in a mouse model of lupus. An unbiased screen identified DYRK1a as a protein that interacts with TRAF3, a ubiquitin ligase component mediating degradation of the noncanonical nuclear factor (NF)-κB-inducing kinase (NIK). DYRK1a phosphorylates TRAF3 at serine-29 to interfere with its function in mediating NIK degradation, thereby facilitating BAFF-induced NIK accumulation and noncanonical NF-κB activation. Interestingly, B-cell acute lymphoblastic leukemia (B-ALL) cells express high levels of BAFFR and respond to BAFF for noncanonical NF-κB activation and survival in a DYRK1a-dependent manner. Furthermore, DYRK1a promotes a mouse model of B-ALL through activation of the noncanonical NF-κB pathway. These results establish DYRK1a as a critical BAFFR signaling mediator and provide novel insight into B-ALL pathogenesis.