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The plasticizer is crucial in the plant-based soft capsule. However, meeting the quality requirements of these capsules with a single plasticizer is challenging. To address this issue, this study first investigated the impact of a plasticizer mixture containing sorbitol and glycerol in varying mass ratios and the performance of the pullulan soft film and capsule. The multiscale analysis demonstrates that the plasticizer mixture exhibits superior effectiveness in enhancing the performance of the pullulan film/capsule compared to a single plasticizer. Furthermore, thermogravimetric analysis, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy indicate that the plasticizer mixture enhances the compatibility and thermal stability of the pullulan films without altering their chemical composition. Among the different mass ratios examined, a 15:15 ratio of sorbitol to glycerol (S/G) is identified as the most optimal, leading to superior physicochemical properties and meeting the requirements for brittleness and disintegration time set by the Chinese Pharmacopoeia. This study provides significant insights into the effect of the plasticizer mixture on the performance of pullulan soft capsules and offers a promising application formula for future use.

The scarcity of Groundwater on Earth increases the necessity to make full use of the ubiquitous atmospheric water (H2O). Photocatalytic conversion of the H2O from the air to hydrogen (H2) under visible-light irradiation by metal-free conjugated polymer photocatalysts (CMPs) would be an interesting and challenging route for fully utilizing H2O resources and converting to sustainable and green energy. However, there is no such strategy reported up to now, to the best of our knowledge. Here, for the first time, we used various CMPs for H2 production using captured moisture by ionic liquids (ILs) under visible-light irradiation. The presence of ILs in the H2O-absobed H2O/ILs mixtures could enhance photocatalytic H2 evolution rate when compared to the pure H2O. Particularly, the accelerated effect of [BMIM][BF4] was the highest (29-fold), with the highest H2 production rate of 96.5 μmol g−1 h−1 among all the IL-related systems investigated. We attributed the high efficiency of H2 photo-evolution from atmospheric H2O to the activation of H2O by ILs and the highly dispersion of photocatalysts in H2O/ILs system. This work might open a new field to convert sustainable and ubiquitous atmospheric H2O resources to clean H2 fuels.

The autoimmune polyglandular syndromes (APS) are rare immune-mediated endocrinopathies causing destruction of multiple endocrine and non-endocrine organs. Involvement of adrenal glands associated with any type of APS results in Addison’s disease. While patients with Addison’s disease often suffer from symptoms of neuroglycopenia, lethal hypotension and hypoglycemia are uncommon. Here, we report a fatal case of APS type 1 with hypotension and profound hypoglycemia in a 24-year-old man who was found unconsciousness at home and progressively evolved into pulseless electrical activity. Although his condition was initially considered to be possibly due to drug toxicity, subsequent drug screening tests failed to detect alcohol or any other substances. Emergent medical evaluation revealed severe hypotension (51/30 mm/Hg) and profound hypoglycemia (blood glucose of 20–30 mg/dl). Despite vigorous supportive care, the patient died following 3 days of respiratory dependency due to irreversible anoxic brain injury. Postmortem examination revealed severely atrophic adrenal glands with lymphocytic infiltration. Subsequent review of the patient’s medical history and correlation with autopsy findings confirmed the presence of multiple organ involvement, consistent with APS type 1. This case serves as a reminder for forensic pathologists that death from an acute adrenal (Addisonian) crisis, while uncommon, should remain a differential diagnostic consideration. Furthermore, it underscores the fact that Addison’s disease can occur as part of a constellation of autoimmune manifestations within the context of an underlying polyglandular syndrome, such as APS type 1.

Negative expression of estrogen receptor (ER) predicts response to chemotherapy in breast cancers (BCs). ER negative cancers are those with less than 1 % of nuclear staining. Tumors with 1-10 % staining are sub-classified as "low-positive" (ER-low). HER2 negative tumors with ER low staining are considered biologically and clinically equivalent to ER negative tumors. This study investigates whether ER low expression in HER2-positive (HER2+) BCs has different clinical behavior than ER negative HER2-positive tumors. We used a sample of 171 patients with HER2+ BCs to compare risk of residual cancer after neoadjuvant chemotherapy by different ER expression strength. Patients were classified into 3 groups: ER-negative (ER1 %); ER-low (ER10 %, any intensity or33 % staining, weak intensity); and ER-high (ER = 10-33 %, moderate to strong intensity or33 %, any intensity). The risk of residual cancer in patients with ER-low tumors was similar to the risk in patients with ER-negative tumors (RR = 0.76, 95 % CI: 0.30-1.93). Conversely, patients with ER-high tumors had twice the risk of residual cancer than patients with ER-negative tumors (RR = 2.20, 95 % CI: 1.46-3.31). These findings persisted after adjusting for tumor grade, clinical tumor and lymph node stage, chemotherapy regimen, and progesterone receptor status. In this cohort of patients with HER2+ BCs, ER-low tumors had a similar pathologic response to chemotherapy as ER-negative tumors suggesting similar clinical behavior. Future research should address biological explanations to these similarities between ER negative and ER low breast cancers such as HER2 enriched phenomenon.

Powassan virus (POWV) is a flavivirus of the tick-borne encephalitis serogroup that causes a rare and potentially life-threatening neuroinvasive disease. Viral transmission occurs during zoonotic spillover from mammals by the bite of an infected tick in endemic regions of North America. The number of reported POWV cases has recently increased in the United States. We report a fatal case of POWV meningoencephalomyelitis in Northern Wisconsin following a documented tick bite. Histologic examination of the brain demonstrated widespread intraparenchymal and perivascular lymphohistocytic infiltration, microglial nodule formation, and marked neuronal degeneration, most severely involving the substantia nigra, anterior horn of spinal cord and cerebellum. Although no viral inclusions were seen in routine light microscopy, electron microscopy identified multiple neurons containing cytoplasmic clusters of virus particles ∼50 nm in diameter. POWV infection was confirmed using immunohistochemical analysis and reverse transcription-polymerase chain reaction. This report demonstrates in detail regional central nervous system involvement and ultrastructural characteristics of Powassan viral particles by transmission electron microscopy, while highlighting the utility of evaluating fixed autopsy tissues in cases of unexplained meningoencephalomyelitis.

The pollution from nuclear leaks and nuclear disasters (e.g. radioactive iodine) would cause serious harm to human beings and ecosystems for many years. Cocoon silk and deep eutectic solvents (DESs) are both green substances. DESs are easily synthesized, cheap, highly biocompatible and highly biodegradable. Here, we combine the removal of organic dyes and the capture of radioactive iodine by using green DES-pretreated cocoon silk. It is the first time organic dyes have been removed from wastewater by DES-disrupted silk for the purpose of favourably removing iodine. Organic dyes-captured DES-pretreated cocoon silk could be used to capture iodine efficiently. It opens a new route to dispose of one waste from nuclear energy with organic dyes from wastewater captured by green solvents-pretreated natural silk.

Diabetic foot ulcer is a severe complication of diabetes and is prone to being a chronic non-healing wound. We previously demonstrated that endothelial progenitor cell-derived exosomes, which contain miR-221-3p, alleviate diabetic ulcers. Here, to explore the mechanisms underlying this wound healing, we investigated the potential angiogenic effects of miR-221-3p in vitro using cultured human umbilical vein endothelial cells (HUVECs) and in vivo using a streptozotocin-induced mouse model of diabetes. We found that miR-221-3p promoted HUVEC viability, migration, and capillary-like tube formation. HUVECs cultured in high glucose showed up-regulated expression of homeodomain-interacting protein kinase 2 (HIPK2), a predicted target of miR-221-3p that may decrease angiogenesis. Knockdown of HIPK2 enhanced high glucose-suppressed HUVEC viability, migration, and tube formation, counteracting the effects of high glucose. Using a dual luciferase reporter assay, we found that HIPK2 was indeed a direct target of miR-221-3p. Subcutaneous injection of miR-221-3p agomir into diabetic mice promoted wound healing and suppressed HIPK2 expression in wound margin tissue. These findings indicate that HIPK2, as a direct target of miR-221-3p, contributes to the regulatory role of miR-221-3p in diabetic wound healing and may be a novel therapeutic target for diabetic foot ulcer.

The collapse problem of transmission tower upon strong winds was well noted in past few years. This article analyses the wind-induced collapse problem of a long-span transmission tower–line system. The member buckling effect was particularly considered. In doing so, a three-dimensional finite element model of the long-span transmission tower–line system was established in ABAQUS based on a practical project. The transmission tower and line were simulated by the frame and truss elements, respectively. The nonlinear behavior of a compressive member was simulated using the Marshall model, and the nonconvergence of numerical calculation was set to be the collapse criterion. The critical wind speed, damage position, and collapse probability were obtained from a collapse analysis of the long-span transmission tower–line system under different wind attack angles. The collapse mechanism of the long-span transmission tower–line system under a wind attack angle of 45° was investigated, and an incremental dynamic analysis was performed to evaluate the collapse-resistant capacity of the transmission tower. The study reveals that the interaction between bending moment and shear deformation is critical to the collapse of transmission tower.

BiFeO3 (BFO) and Bi1−x La x Fe0.9Cr0.1O3 (x = 0.1–0.2, BLFC x=0.1–0.2) ceramics were prepared by modified solid-state reaction. The influence of La/Cr codoping on the microstructure, leakage, dielectric and magnetic properties of BFO was studied. It is found that the La/Cr codoping can induce a structural transformation from a rhombohedral (R3c) phase to a triclinic (P1) phase, suppress the formation of oxygen vacancies and modulate the spiral spin structure. With the increasing La concentration, the leakage current density can be diminished by over two orders of magnitude compared with undoped BFO, in a reasonable range for device applications. The dielectric loss follows almost the same trend as the leakage current, while the dielectric constant is raised to 400.8 at 100 kHz for x = 0.2, over eight times larger than that of undoped BFO. The substantially enhanced magnetization can be mainly attributed to the suppression of the spiral spin structure and a new ferromagnetic Fe3+–O2−–Cr3+ super-exchange interaction. More interestingly, abrupt changes are observed around x = 0.15, not only in microstructure but also in electrical and magnetic properties, which may indirectly reflect the coupling effect among them. The BLFC x=0.2 ceramic shows the highest magnetization and dielectric constant together with the lowest leakage current and dielectric loss. The results indicate that the La/Cr codoping can effectively improve the magnetic and electrical properties of BFO ceramic for potential applications in magnetoelectric devices.

Parathyroid adenomas are slow growing benign neoplasms associated with hypercalcemia, while atypical parathyroid adenomas and parathyroid carcinomas are uncommon tumors and their histologic features may overlap with parathyroid adenomas. LncRNAs participate in transcription and in epigenetic or post-transcriptional regulation of gene expression, and probably contribute to carcinogenesis. We analyzed a group of normal, hyperplastic, and neoplastic parathyroid lesions to determine the best immunohistochemical markers to characterize these lesions and to determine the role of selected lncRNAs in tumor progression. A tissue microarray consisting of 111 cases of normal parathyroid (n = 14), primary hyperplasia (n = 15), secondary hyperplasia (n = 10), tertiary hyperplasia (n = 11), adenomas (n = 50), atypical adenomas (n = 7), and carcinomas (n = 4) was used. Immunohistochemical staining with antibodies against chromogranin A, synaptophysin, parathyroid hormone, and insulinoma-associated protein 1(INSM1) was used. Expression of lncRNAs including metastasis-associated lung adenocarcinoma transcript one (MALAT1), HOX transcript antisense intergenic RNA (HOTAIR), and long intergenic non-protein coding regulator of reprograming (Linc-ROR or ROR) was also analyzed by in situ hybridization and RT-PCR. All of the parathyroid tissues were positive for parathyroid hormone, while most cases were positive for chromogranin A (98%). Synaptophysin was expressed in only 12 cases (11%) and INMS1 was negative in all cases. ROR was significantly downregulated during progression from normal, hyperplastic, and adenomatous parathyroid to parathyroid carcinomas. These results show that parathyroid hormone and chromogranin A are useful markers for parathyroid neoplasms, while synaptophysin and INSM1 are not very sensitive broad-spectrum markers for these neoplasms. LincRNA ROR may function as a tumor suppressor during parathyroid tumor progression.

The head of nuclear pressure vessel is a key component to guarantee the safety of nuclear power plant, so it is necessary to improve its mechanical properties during manufacturing. In the practical production, due to the huge size of the ingots from which the head is manufactured, coarse grains and voids are common defects existing in the material. Furthermore, cracks may appear in the forming process. It is highly demanded that the forming process must be properly designed with suitable parameters to compact the voids, to refine and homogenize the grains and to avoid cracks. Therefore, the research on the evolution of internal voids, grain size and cracks is very important to determine the forming process of huge components. SA508-3 steel is the material to manufacture the head of pressure vessel in the nuclear island. In the previous studies, we have separately built models to evaluate the evolution of internal voids, grain size and cracks during the hot forming process for SA508-3 steel. This study integrates the models for multi-scale simulation of the forging process of the head of nuclear pressure vessel in order to control the quality of the forgings. Through the software development, the models are integrated with a commercial finite element code DEFORM. Then, the extended forging and final forging processes of the head are investigated, and some appropriate deformation parameters are recommended.

Cu(Cr0.96−xMg0.04Mnx)O2−δ ceramics (0 ≤ x ≤ 15 at.%) were prepared by solid-state reaction. The influence of Mg acceptor codoping on microstructure, magnetic, and optical properties was studied. The codoping with Mg acceptors and the resulting lattice expansion are both favorable for the enhancement of hole density. Furthermore, the lower valence of Mg2+ compared with Cr3+ enables the mixed valence state of Mn ions: Mn3+ and Mn4+, and hence induces the hole-mediated double-exchange mechanism not only between Mn3+ and Cr3+ but also between Mn3+ and Mn4+. The coexistence of two ferromagnetic interactions and the high hole density are responsible for the improved saturation magnetization and Curie temperature. For photoluminescence, an unusual near-infrared emission at 1.5 eV is observed in the Mn-contained samples and can be attributed to the internal transition between the e and t2 states of the Mn3+ impurity band. The emission intensity is primarily affected by two factors: the Mn3+ concentration and the position of the Fermi level. The results show that codoping with Mg acceptors is an effective way to strengthen the hole-mediated ferromagnetic interactions in CuCrO2 delafossite.

A soft measurement method based on extended Kalman filter is proposed for the measurement of Intelligent Vehicle CG Side-slip Angle. Firstly, the nonlinear dynamic state model of intelligent vehicle is established, the state equation of Side-slip Angle is determined, and the extended Kalman soft measurement method is used for analysis. Secondly,through the establishment of a real vehicle test system, the soft measurement method of Side-slip Angle is verified under two working conditions and different vehicle speeds on the actual road. The test results show that the extended Kalman soft measurement method is reliable and accurate. The extended Kalman soft measurement method can meet the requirements of the full vehicle control system, and it has a certain value of full vehicle application research.

Curve is the accident road section, reducing the speed of vehicles in curve is an effective measure to reduce traffic accidents. How to predict the speed of vehicles in the safe curve is the basis of vehicle active control. In this paper, the vehicle dynamics model and the curve speed prediction model based on the cooperation of people and vehicles are established. Based on this model, the simulation analysis of the curve speed prediction is carried out, and the safe speed of the vehicle under different loading mass and road adhesion coefficient is obtained. (Abstract)

Nutrition education is significantly lacking from healthcare provider educational curricula despite its proven benefit for some of the most chronic and challenging diseases facing Americans today. We successfully developed and implemented an interprofessional, experiential nutrition education course for healthcare professional students that emphasizes evidence-based nutrition interventions for patient care.

Transcription factor FOXM1 plays a critical role in maintenance of stem cell pluripotency through stimulating the transcription of pluripotency-related genes in mouse pluripotent stem cells. In this study, we have found that the repression of FOXM1 expression is mediated by FOXM1 3′UTR during retinoic acid-induced differentiation of human pluripotent NT2/D1 embryonal carcinoma cells. FOXM1 3′UTR contains a microRNA response element (MRE) for miR-134, which has been shown to attenuate the expression of pluripotency-related genes post-transcriptionally during mouse embryonic stem cell differentiation. We have determined that miR-134 is induced during RA-induced differentiation of NT2/D1 cells and the overexpression of miR-134 represses the expression of FOXM1 protein but not FOXM1 mRNA. Furthermore, the expression of OCT4 is diminished by FOXM1 knockdown and the OCT4 promoter is regulated directly by FOXM1, suggesting that FOXM1 is required for maintaining the expression of OCT4 in NT2/D1 cells. Together, our results suggest that FOXM1 is essential for human pluripotent stem cells and miR-134 attenuates its expression during differentiation.

The collapse of a transmission tower under wind action is studied in this paper. A three-dimensional finite element model of the transmission tower is established based on a real project. The birth-to-death element technique is adopted in ABAQUS/Explicit. Kaimal fluctuating wind power spectrum and the harmony superposition method are used to simulate the fluctuating wind speed time history. The dynamic behavior and the collapse mechanism of the transmission tower under three different angles of attack α = 0o, 45o and 90o are carried out, respectively. The results show that the collapse of the transmission tower at 45o angle of attack occurs easily, but it is contrary at 90o angle of attack. The fracture position of the transmission tower under wind excitation is obtained, and the initial damage of the members happens simultaneously in the main and the secondary element. The results of the collapse analysis can provide reference to the design of the transmission tower and the reinforcement of this structure to prevent the collapse of the tower.

MAGNETIC IRON OXIDE NANOPARTICLES (IONPs) have been used as contrast agents of magnetic resonance imaging (MRI) for diagnostic imaging (1-3) and more recently for developing MRI-based molecular imaging probes in various biomedical applications, including cell tracking (4,5), biomarker targeted cancer imaging (6-8), and image guided drug delivery (9-11). IONPs, as a superparamagnetic agent, primarily shorten transverse relaxation times, ie, T2 and T2*, which leads to prominent signal decrease or "negative contrast" of targeted tissue on T2- and T2*-weighted images (12-14). The typical drawback of the T2- and T2*-weighted negative contrast is its poor sensitivity when used to study areas with low background signal. In addition, T2- and T2*-weighted imaging methods are also vulnerable to blooming artifacts and the partial volume errors from the effect of local magnetic inhomogeneity and high susceptibility of paramagnetic IONPs (15,16), making accurate localization and quantitative imaging of magnetic nanoparticles more difficult. It should also be mentioned that further improvement of negative contrast is limited by the threshold of the negative contrast which is the difference between the signal level of IONP affected area and signal intensity of zero (17). Therefore, conventional T2- and T2*-weighted imaging methods may not be able to take advantage of those magnetic nanoparticle probes with very high r2 relaxivity or increase of the dosage of administered IONPs because of the threshold of the negative contrast, as the maximal contrast that the negative contrast can reach is the signal intensity of zero. Therefore, a method of generating positive contrast from magnetic nanoparticles, ie, signal brightening, to improve the detection, and even quantification, of magnetic nanoparticles is desirable and has attracted increasing effort in translating magnetic nanoparticle imaging probes to broader applications (18-20). A number of approaches have been investigated to obtain positive contrast from IONPs, including ultrashort echo time (UTE) imaging (18,21,22), off-resonance saturation (ORS) techniques (23), sweep imaging with Fourier transformation (SWIFT) (24-27), phase contrast (28-30) and, most recently, adiabatic imaging (31,32). Among them, UTE imaging offers a relatively simple strategy by taking advantage of high longitudinal relaxivity r1 of IONPs while reducing the contribution of predominant T2 and T2* and spin dephase effects of IONPs that are also sources of imaging artifacts. With a very short echo time, typically below 0.1 msec, UTE imaging enables capturing signal enhancement from T1 effect with little influence of signal decay from the T2 and T2* effect, allowing for obtaining positive contrast on T1-weighted UTE images. Furthermore, the signal enhancement obtained from the UTE imaging is a function of T1 relaxation times of IONPs at different core sizes and concentrations in a certain range (18). A recent study by Girard et al (22) discussed the general strategy to optimize IONP detection sensitivity using UTE imaging. Through detailed computer simulation, imaging experiments on IONP phantoms in vitro and a proof-of-concept mouse model bearing human prostate tumors in vivo, it was shown that UTE imaging and subtraction of a longer echo signal from that of the UTE (SubUTE) were good approaches for imaging of IONP. In the present study, we report further investigation and application of UTE and SubUTE imaging for the detection and visualization of the receptor targeted IONP imaging probes in cancer xenograft mouse models using positive contrast enhancement. The main purpose was to demonstrate the capability of UTE imaging to obtain positive contrast from biomarker targeted magnetic nanoparticle probes selectively accumulated in the human pancreatic and breast cancer xenograft models in the mice in vivo.

In this paper, tuned mass dampers with optimal parameters for long span transmission tower-line system are investigated. Equations of motion for a structure-TMD system are derived, and the parameters of TMD, stiffness and damping are optimized, respectively. According to a real project, three-dimensional finite element models of both transmission tower and transmission tower-line system are created and their vibration performances are analyzed using SAP2000 software, respectively. Wind load time history is simulated based on wind theory. Using numerical simulation, vibration control with optimal tuned mass damper installed in transmission tower-line system is carried out. Time history curves and the maximum responses of system without and with tuned mass damper under wind excitation are analyzed and discussed. The results show that the optimal tuned mass damper could effectively decrease the wind-induced response of long span transmission tower-line system.

The ability to reliably detect sentinel lymph nodes for sentinel lymph node biopsy and lymphadenectomy is important in clinical management of patients with metastatic cancers. However, the traditional sentinel lymph node mapping with visible dyes is limited by the penetration depth of light and fast clearance of the dyes. On the other hand, sentinel lymph node mapping with radionucleotide technique has intrinsically low spatial resolution and does not provide anatomic details in the sentinel lymph node mapping procedure. This work reports the development of a dual modality imaging probe with magnetic resonance and near infrared imaging capabilities for sentinel lymph node mapping using magnetic iron oxide nanoparticles (10 nm core size) conjugated with a near infrared molecule with emission at 830 nm. Accumulation of magnetic iron oxide nanoparticles in sentinel lymph nodes leads to strong T2 weighted magnetic resonance imaging contrast that can be potentially used for preoperative localization of sentinel lymph nodes, while conjugated near infrared molecules provide optical imaging tracking of lymph nodes with a high signal to background ratio. The new magnetic nanoparticle based dual imaging probe exhibits a significant longer lymph node retention time. Near infrared signals from nanoparticle conjugated near infrared dyes last up to 60 min in sentinel lymph node compared to that of 25 min for the free near infrared dyes in a mouse model. Furthermore, axillary lymph nodes, in addition to sentinel lymph nodes, can be also visualized with this probe, given its slow clearance and sufficient sensitivity. Therefore, this new dual modality imaging probe with the tissue penetration and sensitive detection of sentinel lymph nodes can be applied for preoperative survey of lymph nodes with magnetic resonance imaging and allows intraoperative sentinel lymph node mapping using near infrared optical devices.

FoxA1 belongs to the fork head/winged-helix transcription factor family and participates in stimulating neuronal differentiation of pluripotent stem cells at early stages. To explore the biological roles of FoxA1 during this process, the stable expression of a GFP-FoxA1 fusion protein was established in P19 pluripotent embryonal carcinoma cells. Although they still express pluripotency-related transcription factors such as Oct4, Nanog, and Sox2, the generated P19 GFPFoxA1 cells exhibited a decreased activity of alkaline phosphatase and an increased expression of SSEA-3 compared with P19 cells. Elevated levels of nestin expression and prominin-1+ populations were observed in P19 GFPFoxA1 cells, implicating that the stable expression of FoxA1 promoted P19 cells to gain partial characteristics of neural stem cells. Furthermore, the promoter of nestin was confirmed to be bound and activated by FoxA1 directly. The expression of neuron-specific marker tubulin betaIII also existed in P19 GFPFoxA1 cells. P19 GFPFoxA1 cells showed an earlier onset of differentiation during RA-induced neuronal differentiation, evidenced by a more rapid change on the Nanog decrease and the tubulin betaIII increase. Thus, overexpression of FoxA1 alone may promote pluripotent P19 cells to become neural stem-like cells.

Brucellosis is a zoonotic disease caused by a number ofBrucellaspecies and is characterized by chronic macrophage infection. However, genes that may contribute to intracellular survival of theBrucellaspecies are not well studied. This review presents, first, genomic islands that are present or absent in variousBrucellaspecies that may help establishBrucellainfection and survival strategies. Second, the alteration in macrophage transcription byBrucellato permit its long-term survival within this hostile intracellular environment. A large number of macrophage gene transcripts are altered followingBrucellainfection indicating thatBrucellais not a silent invader of host cells. Macrophage transcript levels associated with inflammation, apoptosis, signal transduction and vesicular intracellular trafficking are altered duringBrucellainfection, and likely contribute to intracellular survival ofBrucella. Lastly, the host–pathogen interaction events associated withBrucellainfection in living mice visualized in real-time using biophotonic imaging. Mice are often used to evaluateBrucellainfections; however,Brucelladissemination and pathogenesis is poorly understood in mice. Biophotonic imaging ofBrucellainfections revealed sites of bacterial localization similar to human infections and different patterns of infection by attenuated or virulentBrucella.

Oligochitosan, which has greater than 3 but less than 10 saccharide (N-acetylglucosamine or glucosamine) residues, is obtained by either chemical or enzymatic hydrolysis of chitosan. In this work, we demonstrated that oligochitosan had an in vitro stimulatory effect on the release of tumor necrosis factor-alpha and interleukin-1 beta in macrophages. Moreover, we observed that oligochitosan could be uptaken by macrophages through confocal laser microscopy. Scatchard analysis of internalization of 2-aminoacridone-oligochitosan in macrophages indicated its internalization was mediated by a specific receptor on macrophage membrane with a Kd of 2.1 x 10(-5) M. Competition studies showed that mannose could inhibit oligochitosan internalization, while lipopolysaccharide and beta-glucan could not do it. Inhibition of mannose-BSA, fucose-BSA, and N-acetylglucosamine-BSA on oligochitosan internalization further suggests that oligochitosan internalization is mediated by a macrophage lectin receptor like with mannose specificity.

The formation of jet-like structures is widely reported in the explosive dispersal of powders surrounding high explosive charges. The jetting of powder beds initiates upon the shock wave reaches the outer edge of the charge. Opposed to the interface instability theory, a hollow sphere based bulk fragmentation model is established to account for the jetting of powders. A two-phase process, namely the nucleation and free expansion of hollow spheres, corresponds to the unloading process of the powder compact caused by the rarefaction waves which governs the fragmentation of the powders. The separation between adjacent hollow spheres dictates the size of the particle clusters, which would evolve into particle jets in later times. The predicted breakup time and the size of particle jets agree well with the experimental results. The increased moisture content in powders results in an increased number of particle jets. This moisture effect can be understood in light of the varied energy distribution due to the incompressibility of the interstitial liquids trapped inside the inter-grain pores. The portion of shock energy which is not consumed in the shock compaction of the wet powders would be dissipated through the viscous shear flows during the unloading of the wet powder compact. The excessive viscous energy requires to activate more localized shear flows, accordingly leading to an increased number of particle jets.

To establish a method for in vitro expansion of human natural CD4⁺CD25⁺ T regulatory cell (Treg) cells for clinical study and immunotherapy.Human natural CD4⁺CD25⁺ Treg were isolated from peripheral blood monocyte cells (PBMCs) by magnetic activated cell sorting (MACS) and expanded by CD3/CD28 expansion beads, IL-2 and rapamycin. The number and the viability of the freshly isolated and expanded Treg were detemined by trypan blue staining. The phenotype and the purity of the freshly isolated and expanded Treg were analyzed by FACS. Treg suppression activity was assessed by mixed lymphocyte reaction (MLR) assay.Human natural Treg were expanded up to 2 000 folds after 3 weeks in culture, and the activity was more than 97%. The expanded Treg retained Treg phenotype as shown by their freshly isolated counterparts, and the purity of CD4⁺CD25⁺FoxP3⁺ Treg was (94.22 ± 2.12)%. The expanded Treg demonstrated a similar potent suppression of both proliferating auto- and allo- CD4⁺CD25⁻ effector T cells in vitro in a cell number-dependent manner.An in vitro expansion of human natural Treg was established to obtain large numbers of human Treg with highly suppressive phenotype and function, thereby providing a solution to the availability of sufficient human natural Treg in clinical study and immunotherapy.

Granular materials subjected to blast loading caused by a central explosion exhibit a distinctive dual jetting phenomenon. A large number of fine particle jets are ejected from the outer edge of the charge upon the reflection of the shock wave from the free surface, and are soon overtaken and overlapped by a second set of much thicker particle jets from the inner edge. Our numerical studies suggest that these two distinct sets of particle jets arise from a subsequent fragmentation of the outer and inner particle layers formed during shock interaction. The instability onset of the inner particle layer, which remains intact after the spallation of the outer particle layer, corresponds to the destabilizing viscous forces prevailing over the stabilizing inertial forces. The physical mechanism responsible for the spallation of the outer particle layer is accounted for by a three-phase cavitation model consisting of nucleation, unconditioned and conditioned growth of voids. The theoretically predicted fragmentation onset and fragment size are well consistent with the experimental results. Moreover, by incorporating the moisture effect into the granular material model, results of the cavitation model indicate an increased number of jets generated by saturated particles, as observed in experiments. With minor shock energy being consumed on the saturated particle compaction thanks to the remarkably low compressibility of saturated particles, the shock wave retains the steep front during propagation and subsequently produces a sharp reflection wave leading to a considerably higher strain relaxation rate in saturated particles than that in dry particles. The pressure relaxation duration prescribes the time the activated nucleation sites are allowed to communicate with each other. Consequently nucleation sites in saturated particles have more chances to survive and fully develop than those in dry particles giving rise to smaller fragments.

The seismic control of power transmission tower-line coupled system subjected to multicomponent excitations is studied in this paper. The schematic of tuned mass damper is introduced, and equations of motion of a system with tuned mass damper under multi-component excitations are proposed. Three-dimensional finite tower-line system models are created based on practical engineering in studying the response of this system without and with control. The time domain analysis takes into account geometric nonlinearity due to finite deformation. The optimal design of the transmission tower-line system with tuned mass damper is obtained according to different mass ratio. The effects of wave travel, coherency loss, and different site conditions on the system without and with control are investigated, respectively.

Somatic mutations in isocitrate dehydrogenase (IDH)1 and 2 have been identified in a subset of gliomas, rendering these tumors with elevated levels of “oncometabolite,” D-2-hydroxyglutarate (2HG). Herein, we report that 2HG can be precisely detected by magnetic resonance (MR) in human glioma specimens and used as a reliable biomarker to identify this subset of tumors. Specifically, we developed a two-dimensional correlation spectroscopy resonance method to reveal the distinctive cross-peak pattern of 2HG in the complex metabolite nuclear MR spectra of brain tumor tissues. This study demonstrates the feasibility, specificity, and selectivity of using MR detection and quantification of 2HG for the diagnosis and classification of IDH1/2 mutation-positive brain tumors. It further opens up the possibility of developing analogous non-invasive MR-based imaging and spectroscopy studies directly in humans in the neuro-oncology clinic.

Transcription factor FoxA1 plays a critical role during embryonic development and is activated during retinoic acid (RA)-induced neural differentiation of pluripotent P19 embryonal carcinoma cells at the early stage, which is marked by decreased expression of Nanog and increased expression of neural stem cell marker Nestin. To further understand how FoxA1 mediates neural differentiation, we have overexpressed FoxA1 through an adenovirus vector in P19 cells and identified that early neurogenesis-related sonic hedgehog (Shh) gene is activated directly by FoxA1. Knockdown of FoxA1 expression during P19 cell neural differentiation results in prevention of Shh and Nestin induction. FoxA1 binds to Shh promoter at -486 to -462 bp region and activates the promoter in cotransfection assays. Furthermore, overexpression of FoxA1 alone in P19 cells stimulates expression of Nestin and results in decreased protein levels of Nanog. During RA-induced P19 cell differentiation, elevated levels of FoxA1 increase the population of neurons, evidenced by stimulated expression of neuron-specific Neurofilament-1 and Tubulin betaIII. Together, our results suggest a critical involvement of FoxA1 in stimulating neural differentiation of pluripotent stem cells at early stages.

Toll-like receptors (TLRs) play essential roles in the activation of innate immune responses against microbial infections. TLRs and downstream adaptor molecules contain a conserved cytoplasmic TIR domain. TIRAP is a TIR domain-containing adaptor protein that recruits the signaling adaptor MyD88 to a subset of TLRs. Many pathogenic microorganisms subvert TLR signaling pathways to suppress host immune responses to benefit their survival and persistence. Brucella encodes a TIR domain-containing protein (TcpB) that inhibits TLR2- and TLR4-mediated NF-κB activation. Sequence analysis indicated a moderate level of similarity between TcpB and the TLR adaptor molecule TIRAP. We found that TcpB could efficiently block TIRAP-induced NF-κB activation. Subsequent studies revealed that by analogy to TIRAP, TcpB interacts with phosphoinositides through its N-terminal domain and colocalizes with the plasma membrane and components of the cytoskeleton. Our findings suggest that TcpB targets the TIRAP-mediated pathway to subvert TLR signaling. In vivo mouse studies indicated that TcpB-deficient Brucella is defective in systemic spread at the early stages of infection.