Huajuxiaoji Formula Alleviates Phenyl Sulfate-Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis.

Background: One of the most common microvascular complications of diabetes is diabetic kidney disease (DKD). The Huajuxiaoji formula (HJXJ) has shown clinical efficacy for DKD; however, its regulatory mechanisms against DKD remain elusive. We investigated NLRP3 inflammasome and the mechanisms of HJXJ by which HJXJ alleviates DKD. Methods: Phenyl sulfate (PS) was used to establish DKD models. HJXJ was administered to mice through intragastric or made into a pharmaceutical serum for the cell cultures. Biological indicator levels in mouse blood and urine were analyzed, and kidney tissues were used for HE, Masson, and PAS staining. ELISA and western blotting were used to detect inflammatory cytokines and protein levels, respectively. Reactive oxygen species (ROS) production and pyroptosis were evaluated using flow cytometry. Lentiviral vector-mediated overexpression of NLRP3 was performed to determine whether NLRP3 participates in the antipyroptotic effect of HJXJ. Results: HJXJ significantly reduced the severity of the injury and, in a dose-dependent manner, decreased the levels of biological markers including creatinine, blood urea nitrogen, urine protein, and endotoxin, as well as inflammatory cytokines such as interleukin (IL)-1ß, IL-18, tumor necrosis factor-α, and IL-6 in DKD mice. Treatment with HJXJ reversed the downregulation of podocin, nephrin, ZO-1, and occludin and upregulated ROS, NLRP3, Caspase-1 P20, and GSDMD-N induced by PS. Moreover, the upregulation of NLRP3 expression increased the number of cells positive for pyroptosis. HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression. Conclusions: Generally, HJXJ has the potential to reduce DKD injury and exerts anti-DKD effects by inhibiting the NLRP3-mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.

Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex.

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh3)3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.

Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?

Background: Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT. Methods: A total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements. Results: 74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (-0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification. Conclusions: We found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.

Tetramethylpyrazine: A review on its mechanisms and functions.

Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.

Evaluation of the efficacy of ipsilateral fibular transfer for reconstruction of large tibial defects in children: a retrospective study.

BACKGROUND: Reconstruction of large tibial defects is often a major challenge in limb salvage. This study aimed to evaluate initial follow-up results of ipsilateral fibula transfer for the treatment of large tibial defects in children. METHODS: A retrospective study was performed between September 2014 and April 2021. Ten children were identified as having large tibial defects. The children underwent ipsilateral fibula transfer. We then evaluated initial healing, tibial length discrepancy, ankle varus/valgus, fibular position, refracture, infection, and function. RESULTS: Five boys and five girls, with an average age of 7.2 years, were evaluated. The transferred fibula was united in the patients. The mean follow-up period after fibular transposition was 43 months. The patients achieved primary bone union; the mean time to union was 8.4 months (range, 4-18 months). Complications included refracture (30%), infection (40%), tibia malunion (30%), ankle varus (30%), sensory loss of toes (10%), and ankle valgus (10%). No other major complications were observed. All 10 patients were able to perform activities of daily living and return to their normal activities. CONCLUSION: Ipsilateral fibula transfer is a salvage surgery for the treatment of large tibial defects in children with congenital pseudoarthrosis of the tibia, traumatic nonunion of the tibia, and/or tibial defect after chronic osteomyelitis. However, long-term results still need to be followed up.

Prognostic Value of Pretreatment Glasgow Prognostic Score/Modified Glasgow Prognostic Score in Ovarian Cancer: A Systematic Review and Meta-Analysis.

To explore prognostic value of pretreatment Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) in ovarian cancer patients.The PubMed, EMBASE (via OVID), and Web of Science databases were comprehensively searched for eligible studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to evaluate the association of pretreatment GPS/mGPS with overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients. STATA 12.0 version software was applied for statistical analysis.A total of eight retrospective studies involving 2260 were included into this systematic review and meta-analysis. The pooled results indicated that patients with elevated pretreatment GPS or mGPS had poorer OS (HR = 1.62, 95% CI: 1.38-1.91, P＜.001) and PFS (HR = 1.40, 95% CI: 1.02-1.93, P = .039) than patients with pretreatment GPS or mGPS 0. Subgroup analysis based on the type of score (GPS or mGPS) and tumor stage for OS were also performed and the results were consistent with above findings.Pretreatment GPS/mGPS might serve as promising prognostic indexes for ovarian cancer patients. More prospective studies with high-quality are needed to verify our findings.

Prototheca spp. induce an inflammatory response via mtROS-mediated activation of NF-κB and NLRP3 inflammasome pathways in bovine mammary epithelial cell cultures.

Emergence of bovine mastitis caused by Prototheca algae is the impetus to better understand these infections. Both P. bovis and P. ciferrii belong to Prototheca algae, but they differ in their pathogenicity to induce inflammatory responses. The objective was to characterize and compare pathogenesis of inflammatory responses in bMECs induced by P. bovis versus P. ciferrii. Mitochondrial ultrastructure, activity and mtROS in bMECs were assessed with transmission electron microscopy and laser scanning confocal microscopy. Cytokines, including TNF-α, IL-1ß and IL-18, were measured by ELISA and real-time PCR, whereas expressions of various proteins in the NF-κB and NLRP3 inflammasome pathways were detected with immunofluorescence or Western blot. Infection with P. bovis or P. ciferrii damaged mitochondria, including dissolution and vacuolation of cristae, and decreased mitochondrial activity, with P. bovis being more pathogenic and causing greater destruction. There were increases in NADPH production and mtROS accumulation in infected bMECs, with P. bovis causing greater increases and also inducing higher cytokine concentrations. Expressions of NF-κB-p65, p-NF-κB-p65, IκBα and p-IκBα proteins in the NF-κB pathway, as well as NLRP3, Pro Caspase1, Caspase1 p20, ASC, Pro IL-1ß, and IL-1ß proteins in the NLRP3 inflammasome pathway, were significantly higher in P. bovis-infected bMECs. However, mito-TEMPO significantly inhibited production of cytokines and decreased expression of proteins in NF-κB and NLRP3 inflammasome pathways in bMECs infected with either P. bovis or P. ciferrii. In conclusion, P. bovis or P. ciferrii infections induced inflammatory responses in bMECs, with increased mtROS in damaged mitochondria and activated NF-κB and NLRP3 inflammasome pathways, with P. bovis causing a more severe reaction.

Mycoplasma bovis subverts autophagy to promote intracellular replication in bovine mammary epithelial cells cultured in vitro.

Mycoplasma species are the smallest prokaryotes capable of self-replication. To investigate Mycoplasma induced autophagy in mammalian cells, Mycoplasma bovis (M. bovis) and bovine mammary epithelial cells (bMEC) were used in an in vitro infection model. Initially, intracellular M. bovis was enclosed within a membrane-like structure in bMEC, as viewed with transmission electron microscopy. In infected bMEC, increased LC3II was verified by Western blotting, RT-PCR and laser confocal microscopy, confirming autophagy at 1, 3 and 6 h post-infection (hpi), with a peak at 6 hpi. However, the M. bovis-induced autophagy flux was subsequently blocked. P62 degradation in infected bMEC was inhibited at 3, 6, 12 and 24 hpi, based on Western blotting and RT-PCR. Beclin1 expression decreased at 12 and 24 hpi. Furthermore, autophagosome maturation was subverted by M. bovis. Autophagosome acidification was inhibited by M. bovis infection, based on detection of mCherry-GFP-LC3 labeled autophagosomes; the decreases in protein levels of Lamp-2a indicate that the lysosomes were impaired by infection. In contrast, activation of autophagy (with rapamycin or HBSS) overcame the M. bovis-induced blockade in phagosome maturation by increasing delivery of M. bovis to the lysosome, with a concurrent decrease in intracellular M. bovis replication. In conclusion, although M. bovis infection induced autophagy in bMEC, the autophagy flux was subsequently impaired by inhibiting autophagosome maturation. Therefore, we conclude that M. bovis subverted autophagy to promote its intracellular replication in bMEC. These findings are the impetus for future studies to further characterize interactions between M. bovis and mammalian host cells.

Atomic perspective revealing for combustion evolution of nitromethane/nano-aluminum hydride composite.

Adding aluminum hydride (AlH3) into energetic materials (EMs) can improve their combustion and energy performance effectively. However, the potential mechanism of AlH3 on EMs is still unclear. Based on the ReaxFF-lg method, the thermal decomposition of nitromethane/nano-aluminum hydride (NM/nano-AlH3) composites were studied. The addition of AlH3 reduces the energy barrier and increases the energy release during the decomposition of NM, accelerates the decomposition of NM. The main way of AlH3 oxidation involves the capture of O atoms from NM. The results show that AlH3 content and passivated layer affect the oxidation and hydrogen release of AlH3. The explosion of small particle size AlH3 leads to rapid oxidation and hydrogen release. The oxidation of large particle size AlH3 is dominated by the inward and outward diffusion of O and Al atoms. The products of NM/nano-AlH3 composites are H2O, CO2, N2 gases, and Al clusters. This work is expected to guide the application of AlH3 in EMs.

Enantioselective synthesis of 3-aryl-phthalides through a nickel-catalyzed stereoconvergent cross-coupling reaction.

A nickel-catalyzed asymmetric Suzuki-Miyaura cross-coupling of racemic 3-bromo-phthalides and arylboronic acids was realized for the synthesis of diverse chiral 3-aryl-phthalides in moderate to excellent reaction yields. The reaction proceeded in a stereoconvergent manner and high enantioselectivities were observed for most examined examples. A number of functional groups like aldehyde, ester and bromide were well tolerated. Heteroaromatic boronic acids were also competent coupling partners in this reaction.

Encapsulating aluminum nanoparticles into carbon nanotubes for combustion: a molecular dynamics study.

Metal nanoparticles are easily deactivated by migration-aggregation in combustion. Encapsulated nanoparticles are one of the tools for coping with the stability challenges of metal nanoparticles. The self-assembly details of aluminum nanoparticles (ANPs) encapsulated into carbon nanotubes (CNTs) were demonstrated by molecular dynamics simulations. The simulation results show that ANPs can completely self-roll into CNTs to form a stable core-shell structure by inertial force and van der Waals force. Inside the tubes, ANPs move toward the cap at a velocity of 2.27 Å ps-1. However, it increases to 3.17 Å ps-1 when near the cap of CNTs. The initiation of the ANPs' oxidation and degradation can be effectively checked by coating CNTs. The diffusion of the Al atoms in the encapsulated ANPs occurred earlier than their oxidation in combustion, verified by using ReaxFF molecular dynamics simulations. The morphological evolutions of the nanostructures in the initial combustion of the encapsulated ANPs are predicted. The interplay between the encapsulated ANPs' responses and external stimuli is classified into core-shell separation, shell damage, and core-shell burst, which provides insights into the oxidation mechanism of encapsulated nanoparticles.

Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The clinical significance of signet ring cells (SRCs) in surgical esophageal and esophagogastric junction adenocarcinoma (EEGJA) remains unclear now. AIM: To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies. METHODS: The PubMed, Web of Science, and EMBASE electronic databases were searched for the relevant literature up to March 28, 2021. The relative risk (RR) with 95% confidence interval (CI) was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients, and the hazard ratio (HR) with 95%CI was calculated to explore the impact of SRC on the prognosis. All statistical analyses were conducted with STATA 12.0 software. RESULTS: A total of ten articles were included, involving 30322 EEGJA patients. The pooled results indicated that the presence of SRCs was significantly associated with tumor location (RR: 0.76, 95%CI: 0.61-0.96, P = 0.022; I 2 = 49.4%, P = 0.160) and tumor-node-metastasis stage (RR: 1.30, 95%CI: 1.02-1.65, P = 0.031; I 2 = 73.1%, P = 0.002). Meanwhile, the presence of SRCs in surgical EEGJA patients predicted a poor overall survival (HR: 1.36, 95%CI: 1.12-1.65, P = 0.002; I 2 = 85.7%, P < 0.001) and disease-specific survival (HR: 1.86, 95%CI: 1.55-2.25, P < 0.001; I 2 = 63.1%, P = 0.043). CONCLUSION: The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients. However, more high-quality studies are still needed to verify the above findings.

Reactive molecular dynamics simulation of thermal decomposition for nitromethane/nano-aluminum composites.

The thermal decomposition of pure nitromethane (NM) and NM/nano-aluminum (Al) composites was simulated by reactive molecular dynamics with ReaxFF-lg corrected force field parameters. The initial decomposition pathway of NM molecules in pure NM is C-N bond rupture. However, NM is decomposed early by the initial pathway of N-O bond rupture when it mixes with nano-Al because of the strong attraction of Al to O. The decomposition process of NM/nano-Al can be divided into three stages: adsorption, slow decomposition, and rapid decomposition. The addition of nano-Al particles decreases the energy barrier in decomposition, increases the released energy, and reduces the decomposition temperature of NM. Adding 3% Al to the explosive can make the detonation pressure 3.083% higher than that of pure system. Compared with pure NM, the energy barrier of 16% Al composite is 25.63 kcal/mol lower and the energy released is 22.99 kcal/mol more. There is an optimal amount of Al contents being added to the NM composite by which the largest total numbers of gaseous products (N2, H2O, and CO2) are released. The effect of Al additives on CO2 production is the most obvious. The maximum detonation pressure can be achieved by adding an appropriate amount of nano-Al, which is similar to the experimental results. Graphical abstract.

Mycoplasma bovis-generated reactive oxygen species and induced apoptosis in bovine mammary epithelial cell cultures.

Mycoplasma bovis is an important cause of bovine mastitis in China and worldwide. We hypothesized that M. bovis damages bovine mammary epithelial cells (bMEC), with the degree of damage varying among field isolates. Our objective was to evaluate 2 novel sequence type (ST) field strains of M. bovis (ST172 and ST173) for their ability to induce oxidative stress, cytotoxicity, pathomorphological changes, and apoptosis in bMEC, as a model for pathogenesis of M. bovis-induced bovine mastitis. Cytotoxicity (as indicated by release of lactate dehydrogenase, LDH) from bMEC depended on multiplicity of infection (MOI), with a high MOI (1:1,000) being required to induce cytotoxicity. Morphological changes in bMEC, including shrinkage, loss of cell integrity, and heavy staining (hematoxylin and eosin) of cytoplasm were apparent 24 h after infection with ST172 or ST173 M. bovis, with more severe changes being induced by the latter strain. Adhesion and invasion assays both had curvilinear patterns, peaking 12 h after infection with MOI of 1:1,000. Both production of reactive oxygen species (ROS) and proportion of apoptotic cells increased with time after infection. Increased Bax/Bcl-2 ratios and activation of caspase-3 implied involvement of mitochondria-dependent pathways of apoptosis. Furthermore, intracellular ROS generation, apoptosis, and cleaved caspase-3 were mitigated by N-acetyl-l-cysteine, a ROS scavenger. Both interleukin (IL)-1ß and IL-6 were significantly upregulated by ST172 and ST173 M. bovis, with little change in expression of tumor necrosis factor-α. One ST173 M. bovis isolate had the greatest cytotoxicity of all of our field isolates, with the highest LDH release, adhesion, invasion, ROS production, and apoptosis. In conclusion, our hypothesis was supported: M. bovis damaged bMEC by generating ROS and initiating a mitochondria-dependent pathway of apoptosis, with the degree of damage varying among field isolates. This study provided new knowledge regarding pathogenesis of M. bovis-induced bovine mastitis.

Thermal Decomposition Mechanism of 1,3,5,7-Tetranitro-1,3,5,7-tetrazocane Accelerated by Nano-Aluminum Hydride (AlH3): ReaxFF-Lg Molecular Dynamics Simulation.

ReaxFF-low-gradient reactive force field with CHONAl parameters is used to simulate thermal decomposition of 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) and AlH3 composite. Perfect AlH3 and surface-passivated AlH3 particles were constructed to mix with HMX. The simulation results indicate HMX is adsorbed on the surface of particles to form O-Al and N-Al bonds. The decomposition of HMX and AlH3 composite is an exothermic reaction without energy barrier, but the decomposition of pure HMX needs to overcome the energy barrier of 133.57 kcal/mol. Active nano-AlH3 causes HMX to decompose rapidly at low temperature, and the primary decomposition pathway is the rupture of N-O and C-N bonds. Adiabatic simulation shows that the energy release and temperature increase of HMX/AlH3 is much larger than those of the HMX system. Surface-passivated AlH3 particles only affect the initial decomposition rate of HMX. In HMX and AlH3 composites, the strong attraction of Al in AlH3 to O and the activation of the intermediate reaction by H2 cause HMX to decompose rapidly. The final decomposition products of pure HMX are H2O, N2, and CO2, and those of HMX/AlH3 are H2O, N2, and Al-containing clusters dominated by C-Al. The final gas production shows that the specific impulse of HMX/AlH3 is larger than that of HMX.

Selenomethionine Suppressed TLR4/NF-κB Pathway by Activating Selenoprotein S to Alleviate ESBL Escherichia coli-Induced Inflammation in Bovine Mammary Epithelial Cells and Macrophages.

Inflammation is the hallmark of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli-induced bovine mastitis. Organic selenium can activate pivotal proteins in immune responses and regulate the immune system. The present study aimed to investigate whether selenomethionine (SeMet) attenuates ESBL E. coli-induced inflammation in bovine mammary epithelial cells (bMECs) and macrophages. Cells were treated with 0, 5/10, 10/20, 20/40, or 40/60 µM SeMet for 12 h and/or inoculated with ESBL-E. coli [multiplicity of infection (MOI) = 5] for 4/6 h, respectively. We assessed inflammatory responses, including selenoprotein S (SeS), Toll-like receptor 4 (TLR4), Ikappa-B (IκB), phospho-NF-κB p65 (Ser536), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) activities. Treatment with 40/60 µM SeMet promoted cell viability and inhibited LDH activities in both bMECs and macrophages. Inoculation with ESBL-E. coli reduced cell viability, which was attenuated by SeMet treatment in bMECs and macrophages. SeMet increased ESBL E. coli-induced downregulation of SeS and decreased LDH activities, TLR4, IκB, phospho-NF-κB p65 (Ser536), IL-1ß, and TNF-α protein expressions in bMECs and macrophages. In addition, knockdown of SeS promoted protein expression of TLR4-mediated nuclear factor-kappa (NF-κB) pathway and BAY 11-708 inhibited TNF-α and IL-1ß protein levels in bMECs and macrophages after ESBL-E. coli treatment. Moreover, ESBL-E. coli inoculation increased monocyte chemoattractant protein 1 (MCP-1), C-C motif ligand 3 (CCL-3), and CCL-5 mRNA expressions in bMECs. In conclusion, ESBL-E. coli induced expression of MCP-1, CCL-3, and CCL-5 in bMECs and then recruited and activated macrophages, whereas SeMet attenuated ESBL E. coli-induced inflammation through activated SeS-mediated TLR4/NF-κB signaling pathway in bMECs and macrophages.

Prototheca zopfii genotype II induces mitochondrial apoptosis in models of bovine mastitis.

Prototheca zopfii is an alga increasingly isolated from bovine mastitis. Of the two genotypes of P. zopfii (genotype I and II (GT-I and -II)), P. zopfii GT-II is the genotype associated with acute mastitis and decreased milk production, although its pathogenesis is not well known. The objective was to determine inflammatory and apoptotic roles of P. zopfii GT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii GT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. This P. zopfii GT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects by P. zopfii GT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α, IL-1ß and Cxcl-1) and also apoptosis of epithelial cells. Thus, we concluded P. zopfii GT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.

Molecular Modeling on Morphology of 3,4-Bis(3-nitrofurazan-4-yl)furoxan Crystals in Dichloroethane or Benzene Mixture Solvents.

According to the experiments, DNTF crystallizes in benzene/methylbenzene (1:1), benzene/methylbenzene/ethanol (2:3:5), and sym-dichloroethane solvents into two similar crystal shapes, namely strip and tetrahedral. There is a possibility that solvent changes the crystal morphology. In order to explain this phenomenon, the DNTF growth interface model was constructed according to the actual solution environment. The interaction energy between the solvent phase and the DNTF crystal face was studied by means of molecular dynamics simulation. The crystal morphology of DNTF was predicted using the classical modified attachment energy model (MAE) in benzene, methylbenzene, benzene/methylbenzene (1:1), benzene/methylbenzene/ethanol (2:3:5), and sym-dichloroethane. The results show that the DNTF growths are mainly dominated by the (011), (001), (101), (110), (111), and (11[Formula: see text]) faces in vacuum. However, only a few faces will remain in the solvents, of which the (011) and (101) faces are exposed in benzene, methylbenzene, and benzene/methylbenzene (1:1), and only the (111) faces constitute the crystal shape of the DNTF in benzene/methylbenzene/ethanol (2:3:5) and sym-dichloroethane. The predicted results successfully explained the observed phenomena in the experiment. The simulation results can provide some guidance for the crystallization process of DNTF.

Molecular dynamics simulation on the reaction of nano-aluminum with water: size and passivation effects.

The reaction of aluminum and water is widely used in the field of propulsion and hydrogen production, but its reaction characteristics at the nanometer scale have not been fully studied. In this paper, the effect of particle size and surface passivation of aluminum particle on the reaction mechanism was studied by using reactive molecular dynamics (RMD) simulation. The reduction of aluminum particle size can accelerate the reaction rate in the medium term (20-80 ps) due to the increase of activity, but it also produces an agglomeration effect as the temperature increases. The presence of surface passivation reduces the proportion of active aluminum and the yield of hydrogen decreases by 30% and 33%, respectively, as the particle size decreases from 2.5 nm to 1.6 nm. The addition of AlH3 can overcome these drawbacks when some aluminum powders are replaced by AlH3. The hydrogen yield is increased by the reaction 2AlH3 + 3H2O → Al2O3 + 6H2. In the reaction of surface passivated Al (1.6 nm in diameter) and H2O, when the proportion of AlH3 reaches 25%, the energy release and hydrogen yield increase from 59.47 kJ mol-1 and 0.0042 mol g-1 to 142.56 kJ mol-1 and 0.0076 mol g-1, respectively. This performance even approximates the reaction of pure aluminum with water: 180.67 kJ mol-1 and 0.0087 mol g-1. In addition, the surface passivation affects the reaction mechanism. Before the passivation layer melts, the reaction 4Al + Al2O3 → 3Al2O occurs inside the nanoparticles.