Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

BtpB inhibits innate inflammatory responses in goat alveolar macrophages through the TLR/NF-κB pathway and NLRP3 inflammasome during Brucella infection.

Brucella species are infectious facultative intracellular pathogens. They have evolved multiple strategies to thwart immune responses and replicate in macrophages for chronic persistence in the host. As a Brucella effector, BtpB is transferred into target cells through the type IV secretion system. BtpB, a Toll/interleukin-1 receptor domain-containing protein, blocks host innate immune responses by interfering with Toll-like receptor signaling. However, the intracellular targets and their activated downstream pathways remain unclear. In this study, we constructed a strain of Brucella suis S2 with a deletion in the gene for BtpB, ΔbtpB, and the complemented strain, C-ΔbtpB with a restored copy of the btpB gene. The bacterial growth curves and stress resistance results showed that BtpB did not affect B. suis S2 growth. Infection of alveolar macrophages with WT and ΔbtpB strains showed that BtpB inhibited TLR2 and TLR4 expression and attenuated NLRP3 inflammasome activation. BtpB also attenuated secretion of the Brucella-induced proinflammatory cytokines, IL-1ß, IL-6, and TNF-α, in alveolar macrophages while up-regulating IL-10 expression. In general, the results confirmed that BtpB specifically inhibits TLR2/TLR4 and disrupts NLRP3 signaling pathways to inhibit host immune responses in early Brucella infections.

Sideband peak count-index technique for monitoring multiple cracks in plate structures using ordinary state-based peri-ultrasound theory.

This work presents a peri-ultrasound theory based on ordinary state-based peridynamics for modeling elastic waves propagating in three-dimensional (3-D) plate structures and interacting with multiple cracks. A recently developed nonlinear ultrasonic technique called sideband peak count-index (or SPC-I) is adopted for monitoring one or more cracks with thickness values equal to 0 mm (crack-free), 1, 2, and 4 mm. Three separate scenarios-one crack, two cracks, and four cracks in 3-D plate structures-are investigated. These cracks can be classified as thin and thick cracks depending on the horizon size, which is mentioned in peri-ultrasound theory. Computed results for all three cases show larger SPC-I values for thin cracks than for thick cracks and the case of no cracks. This observation is in line with the previously reported results in the literature and proves that the state-based peri-ultrasound theory can capture the expected nonlinear response of elastic waves interacting with multiple cracks without changing the cracks' surface locations artificially, and this is always needed in most of the other numerical methods. The proposed state-based peri-ultrasound theory is more flexible and reliable for solving 3-D problems, and the out-of-plane wave field can be obtained for engineering analysis.

Phosphorylated PAMAM dendrimers: an analog of dentin non-collagenous proteins, enhancing the osteo/odontogenic differentiation of dental pulp stem cells.

OBJECTIVES: Polyamidoamine (PAMAM) dendrimers have well-defined structures, with monodispersity and easily modified surface groups, and they have broad applications in biomedicine. In this study, phosphorylated PAMAM (P-PAMAM) dendrimers were synthesized based on the idea of mimicking the phosphorylated proteins of dentin non-collagenous proteins (DNCP). Then, proliferation and osteo/odontogenic differentiation effects of P-PAMAM on dental pulp stem cells (DPSCs) were investigated and were compared with DNCP. MATERIALS AND METHODS: P-PAMAM was synthesized via the Mannich-type reaction. DNCP were extracted directly from human dentin with ethylenediaminetetraacetic acid (EDTA) solution. Then, the conditioned medium of P-PAMAM and DNCP were prepared respectively and applied to DPSCs. Proliferation of P-PAMAM was investigated with CCK-8, flow cytometry, and EdU test. Osteo/odontogenic differentiation of P-PAMAM was analyzed using alkaline phosphatase activity and staining, RT-PCR, western blot, alizarin red staining, and immunofluorescence staining. RESULTS: Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed that PAMAM were successfully phosphorylated. Western blot verified that the extracted DNCP contained dentin-related proteins DSPP, OPN, and BMP2. In cell proliferation, there was no apparent difference between P-PAMAM, DNCP, and Control groups (P > 0.05). P-PAMAM and DNCP upregulated related genes and proteins expression (DSPP/DSPP, COL-1/COL-1, ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN) and matrix mineralization. Still, the potential was lower than that of DNCP (P < 0.05). CONCLUSIONS: P-PAMAM dendrimers, as a biomimetic analog of DNCP, promote osteo/odontogenic differentiation of DPSCs without influencing their proliferation at a low concentration. CLINICAL RELEVANCE: This preliminary study about P-PAMAM dendrimers is expected to provide a more convenient bioactive macromolecular material for the regeneration of the pulp-dentin complex.

A Crack Size Quantification Method Using High-Resolution Lamb Waves.

Traditional tone burst excitation cannot attain a high output resolution, due to the time duration. The received signal is much longer than that of excitation during the propagation, which can increase the difficulty of signal processing, and reduce the resolution. Therefore, it is of significant interest to develop a general methodology for crack quantification through the optimal design of the excitation waveform and signal-processing methods. This paper presents a new crack size quantification method based on high-resolution Lamb waves. The linear chirp (L-Chirp) signal and Golay complementary code (GCC) signal are used as Lamb wave excitation signals. After dispersion removal, these excitation waveforms, based on pulse compression, can effectively improve the inspection resolution in plate-like structures. A series of simulations of both healthy plates and plates with different crack sizes are performed by Abaqus CAE, using different excitation waveforms. The first wave package of the S0 mode after pulse compression is chosen to extract the damage features. A multivariate regression model is proposed to correlate the damage features to the crack size. The effectiveness of the proposed crack size quantification method is verified by a comparison with tone burst excitation, and the accuracy of the crack size quantification method is verified by validation experiments.

Analysis of second mesiobuccal root canal instrumentation in maxillary first molars with three nickel-titanium rotary instruments: a micro-computed tomographic study.

The aim of this study was to evaluate the shaping characteristics of Protaper Universal (PTU; Dentsply Tulsa Dental Specialties, Johnson City, TN), Hero Shaper (HS; MicroMega, Besacon, France) and Hyflex CM (HCM; Coltene-Whaledent, Allstetten, Switzerland) nickel-titanium systems with various apical sizes and tapers in second mesiobuccal (MB2) canal instrumentation using micro-computed tomographic imaging. A total of 27 maxillary first molars with independent patent MB2 canals were selected and randomly assigned to three groups according to the 3-dimensional morphologic aspects obtained from preoperative micro-computed tomographic scans. Canals were first negotiated with a size 8 K-file and finally prepared to F1, F2, and F3 with PTU and to sizes 20.04 taper, 25.04 taper, and 30.04 taper with HS and HCM. Postoperative scans were performed after each instrumentation with the same parameters used in the initial scan. The canal volume, canal transportation, untouched canal surface and wall thickness were measured and calculated using Mimics 10.01 software (Image Works, Materialise, Belgium). Statistical analysis was performed using one-way analysis of variance post hoc LSD tests. PTU removed more dentin than HS and HCM in all sections when instrumented to the same apical size (P < 0.05). HS and HCM presented a lower mean value of canal transportation than PTU in all measured sizes and sections. PTU presented a lower mean value of distal wall thickness than HS and HCM at the level of 1 and 2 mm below the furcation region in all measured sizes. In conclusion, for MB2 canal instrumentation, HS and HCM of 0.04 taper are safer than PTU.

Liraglutide ameliorates obesity-related nonalcoholic fatty liver disease by regulating Sestrin2-mediated Nrf2/HO-1 pathway.

Liraglutide, a glucagon-like peptide 1 (GLP-1) analogue, could reverse NAFLD-induced liver damage by improving metabolic profiles, but the exact molecular mechanism has not been elucidated. Sestrin2 is a novel antioxidant protein, essential for regulating metabolic homeostasis. However, whether sestrin2-mediated redox balance participated in the protective effects of liraglutide against NAFLD is still elusive. The aim of the study was to determine whether liraglutide could ameliorate NAFLD by increasing Sestrin2-mediated signaling in obese mice. Following a normal diet or high fat diet (HFD) for 8 weeks, male C57BL/6 mice were treated with or without liraglutide for 4 weeks. Function and histopathology of liver were conducted to evaluate liver injury. Sestrin2-related AMPK and Nrf2/HO-1 pathway were examined. Antioxidative and inflammatory genes and were determined. HFD mice displayed significantly increased body weight, fat mass, lipids levels and impaired glucose homeostasis with reduced glucose tolerance and insulin sensitivity. Metabolic profiles, hepatic injury, and hepatic lipid accumulation from HFD mice were improved by liraglutide treatment. Liraglutide enhanced Sestrin2, phosphorylated AMPK, Nrf2, and HO-1 protein levels. Additionally, Liraglutide treatment increased mRNA levels of Sestrin2, Nrf2, HO-1 and down-stream genes catalase, GCLM and NQO1, but reduced malondialdehyde and TNF-α levels. Our findings indicated that liraglutide ameliorated obesity-related NAFLD through upregulating Sestrin2-mediated Nrf2/HO-1 pathway.

Bioinformatic and biochemical findings disclosed anti-hepatic steatosis mechanism of calycosin.

As revealed in previous reports, calycosin is a functional flavonoid characterized with identified pharmacological activities. Most of evidences are used to demonstrate the anti-cancer benefits of calycosin, however, the existing study of anti-fatty liver medicated by calycosin is limitedly reported. Recently, an emerging avenue based on network pharmacology may contribute to excavate the biological targets and molecular mechanisms of calycosin for anti-fatty liver. In confirmatory experiments, the human and animal studies were subjected to verify some of bioinformatic results. Accordingly, bioinformatic data based on network pharmacology suggested that discoverable biotargets of calycosin for anti-fatty liver were aldehyde dehydrogenase (ALDH2), Niemann pick C1 (NPC1), high mobility group protein 1 (HMGB1), bilirubin UDP glucuronosyltransferase 1 (UGT1A1), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), hydroxytryptamine receptor 2 (HTR2), migration inhibitory factor (MIF), cytochrome P450, family 19A1 (CYP19A1). Furthermore, all significant biological characteristics and mechanisms of to treat fatty liver were revealed in several. In human findings, the blood tests showed changed glucose and lipid contents, elevated insulin resistance and inflammatory stress. And fatty liver sections from patients resulted in negative expressions of ALDH2, NPC1, and positive HMGB1 expression. In a study in vivo, calycosin-treated high fat diet (HFD)-fed mice exhibited reduced liver weights, decreased fasting serum glucose and insulin, liver functional transaminases, blood lipids, metabolic enzymes, and inflammatory cytokines. And the data in gene tests displayed up-regulations of ALDH2, NPC1 mRNAs, and down-regulation of HMGB1 mRNA in calycosin-treated liver samples. Together, the current bioinformatic data demonstrate biological targets, functions and mechanisms of calycosin for anti-fatty liver. Interestingly, these bioinformatic findings can be partially verified with clinical and animal samples.

Activation of α7-nAChRs protects SH-SY5Y cells from 1-methyl-4-phenylpyridinium-induced apoptotic cell death via ERK/p53 signaling pathway.

Epidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7-nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7-nAChRs; the mechanisms underlying how α7-nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7-nAChR agonist PNU-282987, we first confirmed that their addition to SH-SY5Y cells challenged with 1-methyl-4-phenylpyridinium (MPP+ ) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU-282987 showed the neuroprotective antiapoptotic effects via activating the α7-nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7-nAChRs in SH-SY5Y cells and found that suppressing α7-nAChR expression diminished the antiapoptotic effects of nicotine and PNU-282987, not the toxic effects of MPP+ . Moreover, α7-nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU-282987 on the phosphorylated extracellular signal-regulated kinase (ERK), not c-Jun amino-terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7-nAChRs and suggest that α7-nAChR agonists may be validated as novel treatments for PD.

VceC Mediated IRE1 Pathway and Inhibited CHOP-induced Apoptosis to Support Brucella Replication in Goat Trophoblast Cells.

The effectors of the type IV secretion system (T4SS) of bacteria play important roles in mediating bacterial intracellular proliferation and manipulating host-related pathway responses to bacterial infection. Brucella Spp. inhibit the apoptosis of host cells to benefit their own intracellular proliferation. However, the underlying mechanisms between T4SS effectors and Brucella-inhibited apoptosis in goat trophoblast cells remain unclear. Here, based on Brucella suis vaccine strain 2, the VceC was deleted by allelic exchange. We show that ΔVceC was able to infect and proliferate to high titers in goat trophoblast cells (GTCs) and increase C/EBP-homologous protein (CHOP)-mediated apoptosis. GRP78 expression decreased upon ΔVceC infection. In addition, we discovered that the inositolrequiring enzyme 1 (IRE1) pathway was inhibited in this process. Changing endoplasmic reticulum (ER) stress affected Brucella intracellular replication in GTCs. The replication of ΔVceC was more sensitive under the different ERstress conditions in the GTC line after treatment with ER stress inhibitors 4 phenyl butyric acid (4-PBA) or ER stress activator Tm. Together, our findings show that VceC has a protective effect on the intracellular persistence of Brucella infection, and inhibits ER stress-induced apoptosis in the CHOP pathway. The present work provides new insights for understanding the mechanism of VceC in the establishment of chronic Brucella infection.

SGK2 promotes hepatocellular carcinoma progression and mediates GSK-3ß/ß-catenin signaling in HCC cells.

The phosphoinositide 3-kinase pathway is one of the most commonly altered pathways in human cancers. The serum/glucocorticoid-regulated kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2, and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. Few studies have investigated the role of SGK2 in hepatocellular carcinoma. Here, we report that SGK2 expression levels were upregulated in hepatocellular carcinoma tissues and human hepatoma cell lines compared to the adjacent normal liver tissues and a normal hepatocyte line, respectively. We found that downregulated SGK2 inhibits cell migration and invasive potential of hepatocellular carcinoma cell lines (SMMC-7721 and Huh-7).We also found that downregulated SGK2 suppressed the expression level of unphosphorylated (activated) glycogen synthase kinase 3 beta. In addition, SGK2 downregulation decreased the dephosphorylation (activation) of ß-catenin by preventing its proteasomal degradation in the hepatocellular carcinoma cell lines. These findings suggest that SGK2 promotes hepatocellular carcinoma progression and mediates glycogen synthase kinase 3 beta/ß-catenin signaling in hepatocellular carcinoma cells.

Preoperative prediction of conversion from laparoscopic rectal resection to open surgery: a clinical study of conversion scoring of laparoscopic rectal resection to open surgery.

OBJECTIVE: The objectives of this paper were to establish a model for the conversion of laparoscopic rectal resection to open surgery and to predict possible conversion before surgery. METHODS: The clinical data of 602 cases of laparoscopic rectal resection were retrospectively assessed. Risk factors associated with conversion of laparoscopic rectal resection to open rectal surgery were identified by logistic regression analysis. Also, a scoring system was created to calculate a score for the conversion of laparoscopic rectal resection to predict possible conversion for patients who underwent laparoscopic rectal resection before surgery. RESULTS: A total of 90 patients required conversion (total conversion rate = 14.95%). The established model included six variables: male gender, surgical experience (≤25 cases), history of abdominal surgery, body mass index ≥ 28, tumor diameter ≥ 6 cm, and tumor invasion or metastasis, for which 6, 4, 5, 10, 15, and 21 points were assigned, respectively. A patient with a total score >14.5 points was considered to have a high probability of conversion, whereas a patient with a total score <14.5 points was considered at a low risk. CONCLUSION: Preoperative determination of conversion score may predict possible conversion of laparoscopic rectal resection and thus reduce unnecessary open rectal surgery.

Dentin matrix proteins (DMPs) enhance differentiation of BMMSCs via ERK and P38 MAPK pathways.

Dentin, the predominant mineralized tissue of the tooth, comprises an extracellular matrix of collagen and a heterogeneous mixture of non-collagenous components, many of which have cellular signaling properties. These properties may be important in signaling stem cell involvement in tissue regeneration following injury and the present study investigates their morphogenic effects on differentiation of Bone Marrow Stromal Stem Cells (BMMSCs) in vitro. Non-collagenous dentin matrix proteins (DMPs) were isolated from healthy human teeth and their effects on BMMSCs behavior examined during in vitro culture. In vitro, DMPs enhanced alkaline phosphatase activity and mineralization in BMMSCs cultures as well as increasing the expression of dentinogenic and osteogenic differentiation markers (including runt-related transcription factor 2, osterix, bone sialoprotein, dentin sialophosphoprotein and osteocalcin) at both transcript and protein levels, with 10 µg/mL DMPs being the optimal stimulatory concentration. Expression of phosphor-ERK/phosphor-P38 in BMMSCs was up-regulated by DMPs and, in the presence of the ERK1/2- and p38-specific inhibitors, the differentiation of BMMSCs was inhibited. These data indicate that DMPs promote the dentinogenic/osteogenic differentiation of BMMSCs via the ERK/p38 MAPK pathways.

Monitoring damage growth and topographical changes in plate structures using sideband peak count-index and topological acoustic sensing techniques.

Some topographies in plate structures can hide cracks and make it difficult to monitor damage growth. This is because topographical features convert homogeneous structures to heterogeneous one and complicate the wave propagation through such structures. At certain points destructive interference between incident, reflected and transmitted elastic waves can make those points insensitive to the damage growth when adopting acoustics based structural health monitoring (SHM) techniques. A newly developed nonlinear ultrasonic (NLU) technique called sideband peak count - index (or SPC-I) has shown its effectiveness and superiority compared to other techniques for nondestructive testing (NDT) and SHM applications and is adopted in this work for monitoring damage growth in plate structures with topographical features. The performance of SPC-I technique in heterogeneous specimens having different topographies is investigated using nonlocal peridynamics based peri-ultrasound modeling. Three types of topographies - "X" topography, "Y" topography and "XY" topography are investigated. It is observed that "X" and "XY" topographies can help to hide the crack growth, thus making cracks undetectable when the SPC-I based monitoring technique is adopted. In addition to the SPC-I technique, we also investigate the effectiveness of an emerging sensing technique based on topological acoustic sensing. This method monitors the changes in the geometric phase; a measure of the changes in the acoustic wave's spatial behavior. The computed results show that changes in the geometric phase can be exploited to monitor the damage growth in plate structures for all three topographies considered here. The significant changes in geometric phase can be related to the crack growth even when these cracks remain hidden for some topographies during the SPC-I based single point inspection. Sensitivities of both the SPC-I and the topological acoustic sensing techniques are also investigated for sensing the topographical changes in the plate structures.

Numerical modeling with experimental verification investigating the effect of various nonlinearities on the sideband peak count-index technique.

A newly developed nonlinear ultrasonic (NLU) technique called sideband band peak count-index (or SPC-I) measures the degree of nonlinearity in materials by counting the sideband peaks above a moving threshold line - larger the SPC-I values, higher is the material nonlinearity. In various published papers, the SPC-I technique has shown its effectiveness in structural health monitoring (SHM) applications. However, the effects of different types of nonlinear phenomenon on the sideband peak generation is yet to be investigated in depth. This work addresses this knowledge gap and investigates the effects of different types of nonlinearity on the SPC-I technique. Three types of nonlinearity (material nonlinearity, structural nonlinearity and contact nonlinearity) are investigated separately through numerical modeling. In this investigation the material nonlinearity and the contact nonlinearity are modeled by finite element method (FEM) using the commercial Abaqus/CAE software. The structural nonlinearity arising from stationary cracks is modeled using nonlocal peridynamics based peri-ultrasound modeling technique. Numerical modeling shows that the sideband peak values do not increase proportional to the input signal strength thus indicating nonlinear response, and different types of nonlinearities affect the SPC-I measurements differently. For the experimental verification a composite plate with impact-induced damage is considered for investigating the material nonlinearity and structural nonlinearity while a linear elastic aluminum plate is used to examine the contact nonlinearity between the transducers and the plate. The trends observed in the experimental observations matched with the numerical model predictions.

Brucella Manipulates Host Cell Ferroptosis to Facilitate Its Intracellular Replication and Egress in RAW264.7 Macrophages.

Brucella virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for Brucella to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type Brucella infection triggers host cell ferroptosis and what role it plays in Brucella infection. We assessed the effects of Brucella infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of Brucella infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of Brucella. The results demonstrated that Brucella M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased Brucella intracellular survival and suppressing host cell ferroptosis increased Brucella intracellular replication and egress. Collectively, Brucella may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how Brucella completes its intracellular life cycle.

Brucella rough RB51 infection activates P53-Slc7a11-Gpx4/GSH pathway to induce ferroptosis to attenuate the intracellular survival on macrophages.

B. abortus is a facultative intracellular bacterium that replicates within macrophages. Intracellular survival is one of the important indexes to evaluate the virulence of Brucella. Ferroptosis is a type of programmed cell death induced by the accumulation of free iron, reactive oxygen species (ROS), and toxic lipid peroxides, play roles on cancers, cardiovascular diseases, and inflammatory diseases. In this study, we found that Brucella rough strain RB51 induced ferroptosis on macrophages with reduced levels of host glutathione and glutathione peroxidase 4 (Gpx4), together with increased ferrous iron, lipid peroxidation, and ROS. The inhibitor ferrostatin-1 significantly reduced the ferroptosis of RB51-infected macrophages, confirming that ferroptosis occurred during infection with Brucella RB51. Furthermore, we found that RB51 infection induced ferroptosis is regulated by P53-Slc7a11-Gpx4/GSH signal pathway. Inhibiting P53 decreased the levels of ROS and lipid peroxidation, while the levels of Slc7a11, Gpx4 and GSH were rescued. More importantly, inhibiting ferroptosis by different ferroptosis inhibitors increased the intracellular survival of Brucella RB51, indicating ferroptosis functions on the attenuation of Brucella intracellular survival. Collectively, our observations demonstrate that Brucella RB51 infection induces ferroptosis on macrophages, which is regulated by P53-Slc7a11-Gpx4/GSH signal pathway and functions on the attenuation of intracellular survival of Brucella.

Paraspinal muscle parameters' predictive value for new vertebral compression fractures post-vertebral augmentation: Nomogram development and validation.

Objective: Prior research underscores the significance of paraspinal muscles in maintaining spinal stability. This study aims to investigate the predictive value of paraspinal muscle parameters for the occurrence of new vertebral compression fractures (NVCF) following percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCF). Methods: Retrospectively collected data from October 2019 to February 2021 (internal validation, n = 235) and March 2021 to November 2021 (external validation, n = 105) for patients with OVCF treated with PVP/PKP at our institution. They were randomly divided into training (188 cases) and validation groups (47 cases) at an 8:2 ratio. Lasso regression and multivariable logistic regression identified independent risk factors in the training set, and a Nomogram model was developed. Accuracy was assessed using receiver operating characteristic curves (ROC), calibration was evaluated with calibration curves and the Hosmer-Lemeshow test, and clinical utility was analyzed using decision curve analysis (DCA) and clinical impact curve (CIC). Results: Surgical approach, spinal computed tomography (CT) values, and multifidus skeletal muscle index (SMI) are independent predictors of postoperative NVCF in OVCF patients. A Nomogram model, based on the identified predictors, was developed and uploaded online. Internal validation results showed area under the curve (AUC) values of 0.801, 0.664, and 0.832 for the training set, validation set, and external validation, respectively. Hosmer-Lemeshow goodness-of-fit tests (χ2 = 7.311-14.474, p = 0.070-0.504) and calibration curves indicated good consistency between observed and predicted values. DCA and CIC demonstrated clinical net benefit within risk thresholds of 0.06-0.84, 0.12-0.23, and 0.01-0.27. At specificity 1.00-0.80, the partial AUC (0.106) exceeded that at sensitivity 1.00-0.80 (0.062). Conclusion: Compared to the spinal CT value, the multifidus SMI has certain potential in predicting the occurrence of NVCF. Additionally, the Nomogram model of this study has a greater negative predictive value.

Numerical prediction of glass molding process for 3D curved screen.

With the rapid development of consumer electronics industry, the demand for 3D curved screen in industry is also growing. At present, 3D curved screen is mass produced through glass molding process. However, due to the complex rheological properties of glass melt and the intricate deformation mechanism of glass molding process, the final geometry of the screen is difficult to predict. In this paper, the glass molding process for 3D curved screen is analyzed by finite element transient analysis. The trend of screen shape change is obtained and the final geometry of the screen is predicted. The results show that geometric fillet and rheological parameters have great influence on the flow of glass melt in glass molding process. This study is helpful for the selection of parameters of glass molding process and the design of 3D curved screen.

Improved Optimization of a Coextrusion Die with a Complex Geometry Using the Coupling Inverse Design Method.

The main challenge in a polymer coextrusion process is to have a good die design prior to the process, which can minimize the geometric errors that are caused by extrusion swell and interface motion. For this purpose, a coupling method of optimization and inverse design for a coextrusion die was studied for a medical striped catheter. In the study, the main material was thermoplastic polyurethane (TPU), and the auxiliary material was TPU filled with 30 wt% barium sulfate. An overall optimization design method was used to optimize the geometry of the extrusion die channel for the striped catheter, which had a complex geometry. In the global optimization process, the local inverse design method was used to design the inlet of the auxiliary material. The non-linear programming by quadratic Lagrangian (NLPQL) algorithm was used to obtain the optimal geometric solution of the coextrusion die runner. The experimental verification results showed that the coupling method for coextrusion die design improved the design efficiency of the coextrusion die remarkably. The value of the objective function, which was used to measure the geometric error of the product, was reduced by 72.3% compared with the initial die design.