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Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long noncoding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid–liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line–based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for patients with esophageal cancer. Overall, this study uncovers the physiologic roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR–ILF3–HIF1α axis as a potential target for cancer therapy.Significance:Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid–liquid phase separation and activation of HIF1α signaling to promote cancer progression.

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Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long noncoding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid–liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line–based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for patients with esophageal cancer. Overall, this study uncovers the physiologic roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR–ILF3–HIF1α axis as a potential target for cancer therapy. Significance: Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid–liquid phase separation and activation of HIF1α signaling to promote cancer progression.

BACKGROUND Kaposi's sarcoma (KS) is a malignancy that usually affects the skin of the lower extremities, and may involve internal organs. It originates from the vascular endothelium. It is well known that the development of KS is associated with human herpes virus 8 (i.e. HHV8) infections. Sporadic KS cases have mainly been found in Africa. Isolated splenic KS in Asia has rarely been reported. We present here a case of KS primarily involving the spleen in a human immunodeficiency virus (HIV)-negative Chinese patient. CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort, reduced food intake and weight loss. Medical examination revealed that the patient had moderate anemia, a low platelet count, slight fatty liver and a huge mass in the spleen. Spleen lymphoma was considered. An anti-HIV test was negative. The whole spleen was surgically excised. The final pathological diagnosis was nodular stage spleen KS, and the patient underwent total splenectomy. He recovered well and was discharged from hospital 12 d after surgery. Two weeks later, the patient developed liver metastasis and died within 1 mo after surgery. CONCLUSION KS is difficult to diagnose and pathological examination is necessary. KS has a poor prognosis and should be diagnosed and treated early to improve survival.

Curcumin has anticancer functions in various tumors. It has been shown to induce apoptosis through p53-dependent pathways. p73 gene is a member of the p53 family which encodes both a tumor suppressor (transactivation-competent p73 (TAp73)) and a putative oncogene (dominant-negative p73 (DNp73)); the former shares similarity with the tumor suppressor p53, and the latter behaves as dominant-negative proteins that interfere with the activity of TAp73. To understand the p73-dependent mechanisms that are engaged during curcumin-induced apoptosis, we established a p73 overexpression cell models using p53-deficient Hep3B cells (Hep3B(TAp73/DNp73)). Our results demonstrated that curcumin at concentrations of 40 and 80 μM induced DNA damage, increased TAp73/DNp73 ratio, and also led to apoptosis in the Hep3B(TAp73/DNp73) cells. The apoptotic cell death was concurrent with the loss of mitochondrial membrane potential; release of cytochrome c from mitochondria; and the cleavage of caspase 9, caspase 3, and poly(ADP-ribose) polymerase (PARP). These results demonstrated a p73-dependent mechanism for curcumin-induced apoptosis that involves the mitochondria-mediated pathway.

Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-β protein precursor (AβPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature. Subchronic treatment of adult AβPP/PS1 mice with GDF11 rescued cognitive function and ameliorated cerebrovascular function. In particular, the de novo genesis of small blood vessels and the expression of vascular-related proteins were significantly higher than in the vehicle-treated AβPP/PS1 mice, whereas the expressions of the inflammatory markers Iba-1 and GFAP significantly decreased in proportion to the lower ratio of two forms of amyloid-β (Aβ40/42). Daily intravenous treatment with GDF11-injection can rejuvenate respects of cognition and cerebrovascular changes in AD mice.

The transboundary information transmission across the air-and-sea interface is of great practical significance. No matter from the perspective of scientific research or from the view of applications, transboundary communication is a hot and challenging field. Magnetic induction communication has the unique advantages of two-way transboundary transmission, insusceptible to complex hydro-logical environment, and especially suitable for shallow water channel and other environments with harsh propagation characteristics, providing a promising solution for transboundary information transmission. However, the rapid attenuation of magnetic field component with the increase of distance and frequency limits the coverage and transmission rate of the transboundary magnetic induction communication. Therefore, enhancing magnetic field component at a distance has become a focus of magnetic induction communication research. An undersea-to-air transboundary magnetic induction communication scheme based on relay transmission is proposed in this paper, in which a virtual distributed antenna array is formed by processing and relaying the received signals performed at the relay terminals, and the distributed spatial diversity gain can be obtained which is used to enhance the underwater magnetic field component, expand the magnetic induction propagation range, and increase the transmission bandwidth and improve the receiving signal-to-noise ratio as well. Moreover, even in a dynamic marine environment, the relay transmission can be effectively realized and the communication performance can be guaranteed. In this paper, the propagation model of relay transmission based undersea-to-air transboundary magnetic induction communication is established by using the magnetic dipole model in layered conductive media. The effective communication range of direct and relay communication are defined by using their receiving thresholds, and the basic methods and steps to determine the relay location are presented. The communication coverage and available transmission bandwidth of undersea-to-air transboundary magnetic induction communication under different relay scenarios are analyzed and compared by calculating the underwater magnetic induction strength distribution. The numerical results indicate that the underwater coverage and available bandwidth of transboundary magnetic induction communication can be simultaneously doubled under the appropriate number and location of relays. The research in this paper suggests that the relay transmission scheme for magnetic induction communication is suitable for the application in dynamic environment with high propagation loss, which greatly increases the feasibility and effectiveness of the magnetic induction communication as a transboundary communication technology.

As the weak area of the residence envelope’s, window’s sound insulation is very important in the way of indoor quiet assurance. Base on the road traffic noise as sound sources, the sound insulation comparative studies is made between the insulating laminated glass and double insulated glass. The article choose two similar rooms near the Gaoerji road in Dalian assembled with the different windows, one room’s window was assembled with the insulating laminated glasses, and the other was assembled with double insulated glasses. Research shows that sound insulation effect of the wall with insulating laminated glass is better than the wall with double insulated glass 4dB.

IEEE802.15.4 defines MAC and PHY specification for low-rate wireless personal area networks (LR-WPANS), which targets wireless networking among low-rate, low-power and low-cost devices for short range telecommunication. As the wireless sensor network used in ward monitoring system need to handle large amounts of data, this paper proposes an improved backoff algorithm in slotted CSMA/CA by introducing a weighting algorithm of. According to the comparison of and , we can dynamic change the minimum contention window each time at CSMA/CA begins. By NS2 simulation, when the traffic load is large, the delay time, packet loss rate and jitter of the improved dynamic algorithm can be significantly reduced.

These online tools, led by the Google Earth virtual globe, are changing the way we interact with spatial data. This paper focused on how to develop a virtual globe-based interactive service system for risk assessment of dam-break in Barrier Lake. Unlike existing work, virtual globe technology was used as a medium for geographic visualization and analysis. Moreover, GIS spatial analysis and real-time interactive operation with the service system will also be implemented to support the simulation analysis of dab-break flood routing. The experimental results show that the scheme developed in this paper is efficient and feasible.

BACKGROUND: Type 2 innate lymphoid cells (ILC2s) were shown to be involved in Th2-type immune responses in allergic disease animal models. ILC2s enrichment was shown in nasal polyps in chronic rhinosinusitis (CRS) patients and peripheral blood from asthma animal models; the role of ILC2s9 contribution of Th2 response in CRS and asthma remains to be investigated. AIMS: We hypothesized that there would be enhanced expression of ILC2s in peripheral blood of patients with CRS and asthma, which may show correlation with clinical features. METHODS: 6 CRS patients ,5 Asthma patients 5 healthy controls were recruited in our out-patient allergy clinic , ILC2 were quantized as Lin-CRTH2+CD127+ from PBMSs of subjects by using flowcytometry. SNOT-20 , VAS score and levels of IgE were also documented.IL-5 and IL-10 were measured in serum samples from patients by ELISA RESULTS: There were higher IC2 ratio (number of IC2s / one million PBMC %) in CRS group(0.958 ± 0.6209) and Asthma group(1.1191 ± 0.2611) , ,compared to healthy control(0.4831 ±0.0564).(p CONCLUSIONS: Our results showed the IL2s ratio were correlated with clinical features of allergic airway patients, type 2 innate immune responses were higher in CRS and asthma,ILC2 maybe a good marker of airway eosinophilic inflammation and peripheral blood is useful for evaluating type 2 innate immunity in human.

Ultrasonic-assisted extraction (UAE) method was developed for continued extraction of flavonols and anthocyanins from Blueberry. Response surface methodology (RSM) was employed to optimize experimental conditions for extraction of flavonols and anthocyanins. Three major independent variables such as ultrasonic power (W), extraction time (min), liquid to solid ratio (mL/g) were studied. The optimal extraction conditions of flavonols and anthocyanins were determined as follows: ultrasonic power 512.7 W, extraction time 29.8 min, liquid to solid ratio 9.5:1 mL /g. Under a modified condition (ultrasonic power 510W, extraction time 30 min, liquid to solid ratio 10:1 mL /g), the experimental yields of flavonols and anthocyanins were 0.806mg/g and 2.903mg/g respectively, which were agreed closely with the predicted values (0.804mg/g and 2.899mg/g).

Structurally novel 5H-chromeno[2,3-b]pyridine (azaxanthene) selective glucocorticoid receptor (GR) modulators have been identified. A screening paradigm utilizing cellular assays of GR-mediated transrepression of proinflammatory transcription factors and transactivation of GR-dependent genes combined with three physiologically relevant assays of cytokine induction in human whole blood has allowed for the identification of high affinity, selective GR ligands that display a broad range of pharmacological profiles. Agonist efficacy in reporter assays can be tuned by halogenation of a pendent phenyl ring and correlates well with efficacy for cytokine inhibition in human whole blood. A hypothetical binding mode is proposed, invoking an expanded ligand binding pocket resembling that of arylpyrazole-bound GR structures. Two compounds of close structural similarity (35 and 37; BMS-776532 and BMS-791826, respectively) have been found to maintain distinct and consistent levels of partial agonist efficacy across several assays, displaying anti-inflammatory activity comparable to that of prednisolone 2 in suppressing cytokine production in whole blood and in rodent models of acute and chronic inflammation.

OBJECTIVE: To determine factors affecting liver and bile duct contrast enhancement during computed tomographic cholangiography (CTC) in living-donor transplant candidates. METHODS: Forty-four candidates underwent preoperative triphasic CT followed by intravenous infusion of 20 mL of iodipamide for CTC. Body size indices and liver volume were correlated to parenchymal and biliary enhancement. Bile duct visibility was compared to duct enhancement. RESULTS: Poorly visualized first- and second-order bile ducts demonstrated diminished enhancement (P < 0.015). Both CTC parenchymal and biliary enhancement correlated inversely with body surface area, height, and weight (P < 0.001); inverse correlation was also seen between liver volume and parenchymal enhancement (P < 0.001). A moderately positive correlation was noted between CTC biliary and parenchymal portal venous enhancement (r = 0.421; P = 0.004). CONCLUSIONS: Computed tomographic cholangiography parenchymal and biliary enhancement diminishes with increased body size and liver volume, supporting a need for adjustable contrast dosing. Portal venous parenchymal enhancement may serve as a preinfusion indicator.

Pneumatosis intestinalis is defined as the presence of gas within the wall of the gastrointestinal tract. Originally described on plain abdominal radiographs, it is an imaging sign rather than a specific diagnosis and it is associated with both benign and life-threatening clinical conditions. The most common life-threatening cause of pneumatosis intestinalis is bowel ischaemia. Computed tomography (CT) is usually requested to detect underlying disease. The presence of pneumatosis intestinalis often leads physicians to make a diagnosis of serious disease. However, an erroneous diagnosis of pneumatosis intestinalis may be made (i.e. pseudo-pneumatosis) when intraluminal beads of gas are trapped within or between faeces and adjacent mucosal folds. The purpose of this pictorial essay is to review and describe the CT imaging findings of pneumatosis and pseudo-pneumatosis intestinalis and to discuss key discriminatory imaging features.

Purpose To retrospectively evaluate CT findings of xanthogranulomatous cholecystitis (XGC) and to measure diagnostic performance for distinguishing it from gallbladder (GB) cancer. Methods and materials Our institutional review board approved this retrospective study. Three blinded radiologists, first independently and then in consensus, retrospectively evaluated postcontrast CT images of 35 patients with histopathologically proved XGC and GB cancer, all of whom subsequently had cholecystectomy. These included 18 patients with XGC (13 male, 5 female; age range, 35–84, mean 63 years) and 17 with GB cancer (6 male, 11 female; age range, 45–95, mean 69). Differences in CT findings between XGC and GB cancer and diagnostic performances for each CT finding were calculated. Sensitivity, specificity, and accuracy were calculated for each radiologist and observer performance was also determined by receiver-operating-characteristic curve analysis. Results Five CT findings showed significant differences between XGC and GB cancer. Sensitivity, specificity, and accuracy of each finding for the differentiation of XGC were 89%, 65%, 77% with diffuse GB wall thickening, 67%, 82%, 74% with a continuous mucosal line, 61%, 71%, 66% with intra-mural hypo-attenuated nodules, 72%, 77%, 74% with absence of macroscopic hepatic invasion, and 67%, 71%, 69% with absence of intra-hepatic bile duct dilatation, respectively. When at least three of these five CT findings were observed in combination, sensitivity, specificity, and accuracy were 83%, 100% and 91%, respectively. Sensitivities, specificities and Az values for the differentiation of XGC from GB cancer were 83%, 88%, 0.94 for reader 1, 78%, 88%, 0.93 for reader 2, and 78%, 82%, 0.84 for reader 3. Conclusions The combination of three of the five CT findings that are common with XGC can provide excellent accuracy for the differentiation of XGC and GB cancer.

Asthma is one of the most common chronic airway inflammatory diseases. The clinical hallmarks of asthma include elevated serum levels of immunoglobulin E (IgE), eosinophilic inflammation and airway hyper-responsiveness (AHR). Arsenic trioxide (As2O3) is considered a carcinogen; however, it has also been used to treat diseases, such as syphilis, in traditional Chinese and Western medicine. Today, As2O3 is used as one of the standard therapies for acute promyelocytic leukemia (APL). Previous studies have indicated that As2O3 can induce apoptosis in eosinophils. However, the effect of As2O3 on asthma has not been investigated. We used ovalbumin (OVA)-immunized mice as a model for asthma and treated mice with As2O3 at doses of 2.5 and 5 mg/kg. The mice were then monitored for OVA-specific IgE production, airway inflammatory cell infiltration and AHR. We found that administration of As2O3 in OVA-immunized mice abrogated airway eosinophil recruitment by downregulating eotaxin expression but did not alter serum IgE or IL-5 levels in bronchoalveolar lavage fluid (BALF). Furthermore, the development of AHR and cellular infiltration into the airway were reduced by treating mice with As2O3. In vitro data suggested that low concentrations of As2O3 could induce only a small degree of apoptosis in primary pulmonary cells but could significantly inhibit the secretion of eotaxin by these cells. These results indicate that the administration of As2O3 to OVA-immunized mice can suppress lung allergic inflammatory responses. As2O3 might therefore have therapeutic potential in treating allergic airway inflammatory diseases.

The purpose of our study was to evaluate the performance of a computer-aided program that performs automated matching of pulmonary nodules imaged in three serial screening chest MDCT studies.Forty subjects with pulmonary nodules depicted in three annual (T0, T1, T2) low-dose MDCT screening studies for lung cancer were selected from the National Lung Screening Trial database at a single institution. All CT images were reevaluated by two radiologists in consensus. One hundred forty-three nodules were identified and characterized by type (solid parenchymal, juxtavascular, juxtapleural, and ground-glass opacity) and size (or = 4 mm, 4-6 mm, 6-8 mm, and8 mm). Using an automated program, nodules at T0 were matched to nodules at T1, and the same nodules at T1 were matched to nodules at T2. Associations between nodule matching rate (i.e., number of nodules matched by the program divided by the number of nodules determined to match by radiologists) and nodule type or size were analyzed.The combined matching rate of the nodules was 92.7% (T0 vs T1, 91.6%; T1 vs T2, 93.7%). By nodule type, the matching rate was 94.6% (parenchymal), 98.4% (juxtavascular), 85.8% (juxtapleural), and 100% (ground-glass opacity), with the rate significantly lower for juxtapleural nodules (p0.01). Matching rates were not significantly influenced by nodule size (p = 0.67).The automated matching rate for pulmonary nodules in screening MDCT scans was high (92.7%) and was not affected by the nodule size but was slightly lower with nodules at juxtapleural locations.

In this report, we investigate the link between nutrient limitation, RelA-mediated (p)ppGpp production, and virulence in the phytopathogenErwinia carotovorasubsp.atroseptica. ArelAnull mutant (JWC7) was constructed by allelic exchange, and we confirmed that, unlike the wild-type progenitor, this mutant did not produce elevated levels of (p)ppGpp upon nutrient downshift. However, (p)ppGpp production could be restored in strain JWC7 during nutrient limitation by supplyingrelAintrans. During growth on exoenzyme-inducing minimal medium, therelAmutant showed a diminution in secreted pectate lyase and protease activities and a severe defect in motility. TherelAmutant was also impaired in its ability to cause rot in potato tubers. In the presence of serine hydroxamate (a competitive inhibitor of seryl tRNA synthase and a potent inducer of the stringent response in wild-typeE. carotovorasubsp.atroseptica), exoenzyme production was essentially abolished in JWC7 but could be restored in the presence of plasmid-bornerelA. The inhibition of exoenzyme production in JWC7 caused by serine hydroxamate could not be overcome by addition of the quorum-sensing signal molecule,N-3-oxohexanoyl-l-homoserine lactone. Quantitative reverse transcription-PCR analysis of selected RNA species confirmed that the effects ofrelAon secreted pectate lyase activity and motility could be attributed to a reduction in transcription of the corresponding genes. We conclude that nutrient limitation is a potent environmental cue that triggers (p)ppGpp-dependent exoenzyme production inE. carotovorasubsp.atroseptica. Furthermore, our data suggest that nutrient limitation [or rather, (p)ppGpp accumulation] is a prerequisite for effective quorum-sensing-dependent activation of exoenzyme production.

Adenylate kinase (ADK) has been explored widely, through both experimental and theoretical studies. However, still less is known about how the functional dynamics of ADK is modulated explicitly by its natural substrates. Here, we report a quantitative study of the dynamic energy landscape for ADK responding to the substrate binding by integrating both experimental investigations and theoretical modeling. We make theoretical predictions which are in remarkable agreement with the single molecule experiments on the substrate-bound complex. With our combined models of ADK in its apo form, in the presence of AMP or ATP, and in complex with both substrates, we specifically address the following key questions: (1) Are there intermediate state(s) during their catalytic cycle and if so how many? (2) How many pathways are there along the open-to-closed transitions and what are their corresponding weights? (3) How do substrates influence the pathway weights and the stability of the intermediates? (4) Which lid's motion is rate-limiting along the turnover cycle, the NMP or the LID domain? Our models predict two major parallel stepwise pathways and two on-pathway intermediates which are denoted as IN (NMP domain open while LID domain closed) and IL (LID domain open and NMP domain closed), respectively. Further investigation of temperature effects suggests that the IN pathway is dominant at room temperature, but the IL pathway is dominant at the optimal temperature. This leads us to propose that the IL pathway is more dominant by entropy and IN pathway by enthalpy. Remarkably, our results show that even with maximum concentrations of natural substrates, ADK still fluctuates between multiple functional states, reflecting an intrinsic capability of large-scale conformational fluctuations which may be essential to its biological function. The results based on the dual-ligands model provide the theoretical validation of random bisubstrate biproducts (Bi-Bi) mechanism for the enzymatic reaction of ADK. Additionally, the pathway flux analysis strongly suggests that the motion of the NMP domain is the rate-determining step for the conformational cycle (opening and closing).

Many Gram-negative bacteria employ a mechanism of cell–cell communication known as quorum sensing (QS). The role of QS is to enable the cells in a culture to coordinate their gene expression profile with changes in the population cell density. The best characterized mechanisms of QS employ N-acylated homoserine lactones (AHLs) as signalling molecules. These AHLs are made by enzymes known as Luxl homologs, and accumulate in the culture supernatant at a rate proportional to the increase in cell density. Once the AHL concentration exceeds a certain threshold value, these ligands bind to intracellular receptors known as LuxR homologs. The latter are transcriptional regulators, whose activity alters upon binding the AHL ligand, thereby eliciting a change in gene transcription. Over the last five years, it has become increasingly obvious that this is a rather simplistic view of AHL-dependent QS, and that in fact, there is considerable diversity in the way in which Luxl-R homologs operate. The aim of the current review is to describe these variations on the basic theme, and to show how functional genomics is revolutionizing our understanding of QS-controlled regulons.

A finite element analysis method was used to simulate the stamping process of the blade of a large concrete-mixer truck. The updated Lagrange method and the elasto-plastic constitutive equation were adopted to solve the large strain and displacement deformation of the blade. A modified Coulomb friction model was used to solve the sliding contact between the blade and the dies. The von Mises stress distribution in the blade, the spatial displacement variation and the spring-back of the typical node were investigated in the simulation. The von Mises stress in the blade where the spring-back occurs is lowered from 463.0 MPa to 150.0 MPa before and after the spring-back. A typical node in the blade has a 3.33 mm spring-back in Z direction. The results of the experiments agree well with the simulation. The analysis results are valuable for designing optimal tool dies.

To investigate the regulating effects of catalpol on the hypothalamic-pituitary- adrenocortical-axis (HPA) in an Alzheimer's disease (AD) rat model.Healthy male Wistar Rats were selected. The AD model was generated by orthotopic injection of beta-amyloid 25-35 (Abeta25-35) into the right lateral ventricle. The animals were divided into five study groups: Catalpol at low dose (5 mg/kg), Catalpol at high dose (10 mg/kg), model control group and sham surgery control group, n = 9 respectively. The serum concentration of hydrocortisone (HYD), adrenocorticotropin (ACTH) and corticotropin releasing hormone (CRH) determined by Enzyme-Linked Immunosorbent Assay (ELISA). Structural alterations of the hypothalamus were examined by HE stain and electron microscope. The CRH receptor 1 (CRHR1) positive neurons were detected with immunohistochemistry.Serum HYD level was significantly increased (p0.01), and both ACTH and CRH were dramatically decreased (p0.01) in the AD model group rats compared with normal control rats at day 7. Catalpol treatment was able to improve the hormone secretion disorder in AD model group rats compared with the model group (p0.01 or p0.05) in particular at 21 days. Structure damage of hypothalamus in the AD rat as evidenced less CRHR1 positive neurons, rough endoplasmic reticulum dilation and degranulation, and mitochondrial swelling under electron microscope. Catalpol treatment at both high and low doses was able to alleviate the structure damage of the hypothalamus in the AD rats.Catalpol could improve the endocrine function of the HPA and alleviate the structural damage of hypothalamus in AD rats.

Aiolos encodes a zinc finger DNA-binding protein that is highly expressed in mature B cells and is homologous to Ikaros. In the periphery of mice homozygous for an Aiolos -null mutation, B cells exhibit an activated cell surface phenotype and undergo augmented antigen receptor (BCR)-mediated in vitro proliferative responses, even at limiting amounts of stimulant. In vivo, T cell–dependent B cell responses, including the formation of germinal centers and elevated serum IgG and IgE, are detected in Aiolos-deficient mice in the absence of immunization. Auto-antibodies and development of B cell lymphomas are frequently seen among aging Aiolos mutants. In sharp contrast to conventional B cells, B cells of the peritoneum, of the marginal zone, and the recirculating bone marrow population are greatly reduced.

Mice homozygous for an Ikaros null mutation display distinct defects in the development of fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and adult B lymphocytes and their earliest progenitors are absent. Postnatally, hematopoietic stem cells give rise to thymocyte precursors that undergo aberrant differentiation into the CD4 lineage and clonal expansion. The lack of NK cells and some gamma delta T cell subsets and a large reduction in thymic dendritic APCs suggest that Ikaros is essential for establishing early branch points in the postnatal T cell pathway. The lymphoid defects detected in Ikaros null mice reveal critical molecular differences between fetal and postnatal hematopoietic progenitors that dictate their ability to give rise to T cells. These studies also establish Ikaros as a tumor suppressor gene acting during thymocyte differentiation. Phenotypic comparison of this null mutation with a severe dominant-negative Ikaros mutation identifies molecular redundancy in the postnatal hemolymphoid system.

This paper presents the nucleotide sequences of the cDNAs encoding three acidic phospholipases A2 and one basic phospholipase A2 from Deinagkistrodon acutus venom. The deduced primary structure of the basic enzyme is closest to that of the basic neurotoxic enzyme from Trimeresurus mucrosquamatus venom, while the acidic phospholipases from D. acutus have highest sequence similarity to that from Agkistrodon halys pallas. The phylogeny of this monotypic species is discussed.

In-situ analysis the chemical composition of tibial articular cartilage of female Hartley guinea pigs with Fourier transform infrared (FTIR) microspectroscopy was conducted. The infrared spectrum survey consists of three ages (1 months, 2 months and 3 months) and three cartilage layers (surface, middle and deep). The results demonstrated that with ages increasing, the peak positions of main absorbance bands in surface and middle shifted to a lower wavenumber, and in deep they shifted to a lower wavenumber first, then shifted to a higher wavenumber. Infrared spectrum character of collagen, nucleic acid and proteoglycan were compared and analyzed. The ratios of I1 657/I 1 548, I1 074/I1 548 and I1 074/I1 237 tend to decrease with ages increasing in surface and middle. However, the ratios at 2 months are less than other ages in deep. These results are consistent with the regular pattern of cartilage ingredient change in different degradation stage, while the tibial platform images created by microscopic spectral imaging technology is highly compliant with pathology description. The authors' primary result illustrated that FTIR microspectroscopy can be used for in-situ analysis of molecular constituents of different levels cartilages. The molecular information obtained from the study is important for understanding the pathogenesis of cartilage diseases.

Hematopoietic stem cells (HSC) are the source of all blood cells, which can differentiate into various hematopoietic hierarchy cells. Physiological level of reactive oxygen species (ROS) plays an important role in regulating functions of HSC as excessive ROS is harmful to HSC. Oxidative reductases and antioxidants can eliminate cellular ROS to maintain ROS homeostasis and thus avoid excessive ROS-caused damages. There are several types of oxidative reductases in cells such as catalase, manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1), thioredoxin reductase 1 (Txrnd1) and Nqo1 [NAD(P)H dehydrogenase quinone 1]. However, the functional roles of various oxidative reductases in regulating ROS level in hematopoietic cells remain unclear. This study was to investigate the expression patterns of these oxidative reductases in mouse hematopoietic cells that were sorted out via flow cytometry and to find out important oxidative reductases involving in HSC ROS regulation. The expression of various oxidative reductases was detected by semi-quantitative real-time PCR. The results showed that the expression level of catalase in T cell population was 0.14 times that in LT-HSC population (P0.05). The expression levels of MnSOD in CLP population and myeloid cells were 0.56 and 0.47 times that in LT-HSC population respectively (P0.05). The expression levels of GPX1 in ST-HSC, GMP, Myeloid cells, MEP, T lymphocytes and B lymphocytes were 1.79, 2.96, 2.07, 0.58, 0.10, 0.6 times that in LT-HSC population respectively (P0.05). The expression levels of Txrnd1 in ST-HSC, MPP, CMP, GMP, Myeloid cells, T lymphocytes and B lymphocytes were 3.36, 3.18, 4.19, 6.39, 4.27, 0.016, 0.56 time that in LT-HSC population, respectively (P0.05). The expression levels of Nqo1 in ST-HSC, MPP, CMP, GMP, CLP and B cell were 0.30, 0.17, 0.25, 0.10, 0.04, 0.01 times that in LT-HSC population, respectively (P0.05). It is concluded that the expression levels of oxidative reductases (catalase, MnSOD, GPX1, Txrnd1 and Nqo1) in hematopoietic hierarchy cells are cell-type specific. It suggests that reductases may play divergent roles in various hematopoietic cell populations. More importantly, the expression level of Nqo1 in LT-HSC population significantly increased as compared with other cell populations, thereby suggesting its unique regulatory role in HSC.

To observe the effects of Astragalus polysaccharides (APS) on the BG, insulin and C-peptide in serum, ultrastructure and Fas expression of pancreatic beta-cells in diabetes mellitus (DM) rats.Thirty DM rats induced by streptozotocin (STZ) were randomly divided into three groups: DM group, APS 200 mg/kg group, APS 400 mg/kg group, another 10 normal rats were taken as the control group. The drug was given by intraperitoneal for 6 weeks. The level of BG was determined by ONE TOUCH II machine. The levels of insulin and C-peptide in serum were measured by radioimmunoassay. The expression of Fas was observed by immunohistochemistry. Moreover, the TEM was used to observe the ultrastructure of pancreatic beta-cells.(1) DM rats showed significant increase in BG compared with control group (P0.05). APS could decrease the level of FG (P0.05). (2) DM rats showed significant decrease in insulin and C-peptide in serum compared with control group (P0.05). APS has no appearance effects on the levels of them (P0.05). (3) The expression of Fas of beta-cells was significantly increased in DM rats, which was significantly inhibited by APS treatment. (4) It showed degenerative changes of pancreatic beta-cells ultramicroscopic structure of the DM rats, while APS treatment could significantly improve the damage.APS exerts its therapeutic effects on DM, which maybe related to the significant decreasing of the Fas expression and inhibiting the apoptosis of beta-cells.

In the study, a gene encoding Tat protein N terminal 1- 21 amino acid residues-deleted mutant (Tat22-101) was amplified by PCR from a full length Tat gene of human immunodeficiency virus type 1, and the prokaryotic expression plasmid pET32a-Tat22-101 was constructed. After identification by digestion with endonucleases and sequencing, the recombinant plasmid pET32a-Tat22-101 was transformed into E. coli BL21(DE3) and expressed with IPTG induction. The mutant fusion protein with deleted Tat N terminal was purified by an affinity chromatography column Ni(2+)-NTA and subsequently identified by SDS-PAGE and Western blotting. The results showed that the molecular weight of the mutant protein was approximately 26.9kD. Furthermore, BALB/c mice were immunized with the mutant protein and the anti-sera were collected. ELISA results showed that the mutant protein preserved its immunogenicity, particularly it could improve the production of antibodies to other epitopes in addition to the N terminal epitope of Tat protein, which might provide some valuable information for the study of Tat functions as well as for development of potential novel HIV Tat vaccine.

The Ikaros gene encodes a family of early hematopoietic- and lymphocyte-restricted transcription factors. Mice homozygous for a germline mutation in the Ikaros DNA-binding domain lack not only T and B lymphocytes and natural killer cells but also their earliest defined progenitors. In contrast, the erythroid and myeloid lineages were intact in these mutant mice. We propose that Ikaros promotes differentiation of pluripotential hematopoietic stem cell(s) into the lymphocyte pathways. In the absence of a functional Ikaros gene, these stem cells are exclusively diverted into the erythroid and myeloid lineages.

Protein antigens must be taken up, processed, and displayed on the surface of antigen-presenting cells in association with major histocompatibility complex molecules before they can be recognized by T cells. Whether recognition of the haptens used to study allergic contact hypersensitivity in murine models similarly requires processing has not been determined. We analyzed whether presentation of trinitrophenol to trinitrophenol reactive T-cell hybridomas requires antigen processing by studying the effects of inhibitors of antigen processing and presentation on the ability of a syngeneic B-cell tumor (A20) to present trinitrophenol to a series of interleukin-2 producing, trinitrophenol specific, major histocompatibility complex class II-restricted T-cell hybridomas. The ability of trinitrophenol modified A20 cells to stimulate the hybridomas was completely inhibited by monoclonal, anti-trinitrophenol, or anti-Ia antibodies and was significantly reduced by paraformaldehyde fixation immediately after trinitrophenol modification. Trinitrophenol-modified A20 cultured at 37 °C for 2 h prior to fixation was significantly more effective at stimulating the hybridomas than trinitrophenol-modified A20 fixed immediately. The ability of A20 to present trinitrophenol was inhibited by chloroquine. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of trinitrophenol modified lymph node dendritic cells to stimulate the trinitrophenol specific hybridomas. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of A20 cells to present ovalbumin to ovalbumin-specific hybridomas as they had on the ability of trinitrophenol modified A20 cells to present trinitrophenol to the trinitrophenol specific hybridomas. One of seven T-cell hybridomas responded to trinitrophenol modified ovalbumin but not other trinitrophenol modified proteins. These results suggest that, at least in part, T cells in the contact hypersensitivity response to trinitrophenol recognize antigens that require processing and that trinitrophenol modified proteins can be recognized.

To observe the morphological change of prominence through CT three-dimensional reconstruction before and after manipulative treatment and in order to investigate biomechanical effect of manipulation in treating lumbar intervertebral disc herniation (LIDH).From December 2009 to May 2010, 24 patients with LIDH (32 herniated discs) with the unilateral typing,which were treated with manipulation (on alternate day one time and every time about 20 min, 3 weeks as a course of treatment). There were 10 males and 14 females, ranging in age from 25 to 54 years with an average of 36.2 years, in course of disease from 2 days to 10 years with an average of 6.9 years. Protrusible 12 discs were in L4,5 and 20 discs were in L5S1. According to typing of distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 5 cases were type I, 13 cases were type II and 6 cases were type III. After a course of treatment,the morphological changes of prominences were analyzed in the same level of CT three-dimensional reconstruction, including contour map of nerve root sheath side distance (TD), the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), the deviated angle of prominence (AN value) and the sagittal index (SI value).From the contour map of TD, 19 patients (79.2% of the total) can be identified morphological changes after the treatment; from the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 7 cases with type II turned into type I and 2 cases with type III turned into type II after treatment; AN value increased after treatment (P0.05),it showed prominence occurred morphological change toward deviated direction of intervertebral foramina; there was no significant difference in SI value between before and after treatment (P0.05).Standard manipulation can make prominence change, the prominence and nerve roots release, and mutual position improve,which can provide imaging evidence for the study in biomechanical effects.

To investigate the role of Ara-C in regulating anti-CD3/anti-Pgp mediating T-lymphocytes activities against multi-drug resistant leukemia cells.The diabody of anti-CD3/anti-Pgp was purified by E-tag affinity chromatography. K562 and K562/A02 cells were treated with Ara-C. The expressions of B7-1 and B7-2 on K562 and K562/AO2 cells were detected by FACS. The cytotoxicity of T-lymphocytes combined with anti-CD3/anU-Pgp plus Ara-C was analyzed by CytoTox 96 nonradioactive method.The expressions of B7-1 and B7-2 on K562 and K562/A02 cells treated by Ara-C was significantly higher than those untreated. The effect/target ratio was from 0.39:1 to 25:1, and the killing rate of activated T cells to anti-drug-resistant leukemia cells was from (16.44 +/- 1.20)% to (60.49 +/- 2.90)%. The killing rates were increased gradually, with both the effect/target ratio and the antibody concentration increasing (P0.05).Ara-C may be an important adjuvant for improving anti-CD3/anti-Pgp mediating T-lymphocytes activities against multi-drug resistant leukemia cells.

The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown.The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients (agedor = 60 years) with primary non-small cell lung cancer (NSCLC) were analyzed by real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). In addition, twenty young patients (aged60 years) with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls.CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis (TNM) stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types.The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.

The major idea of this article is to discuss standardization and normalization for the product standard of medical devices. Analyze the problem related to the physical performance requirements and test methods during product standard drafting process and make corresponding suggestions.

OBJECTIVES To develop a semiautomated segmentation method based on a graph-cuts technique from multidetector computed tomography images for kidney segmentation and to evaluate and compare it with the conventional manual delineation segmentation method. MATERIALS AND METHODS We have developed a semiautomated segmentation method that is based on a graph-cuts technique with enhanced features including automated seed growing. Multidetector computed tomography images were obtained from 15 consecutive patients who were being evaluated as possible living donors for kidney transplant. Two observers independently performed the segmentation of the kidney from the multidetector computed tomography images using the manual and semiautomated methods. The efficiency of the 2 methods were measured by segmentation processing times and then compared. The interobserver and method reproducibility was determined by Dice similarity coefficient (DSC), which measures how closely 2 segmented volumes overlap geometrically and the coefficient of variation of volume measurements. RESULTS The mean segmentation processing time was (manual vs semiautomated, P < 0.001) 96.8 +/- 13.6 vs 13.7 +/- 3.5 minutes for observer 1 and 44.3 +/- 4.7 vs 16.2 +/- 5.1 minutes for observer 2. The mean interobserver reproducibility was (manual vs semiautomated, P < 0.001) 93.6 +/- 1.6% vs 97.3 +/- 0.9% for DSC and 5.3 +/- 2.6% vs 2.2 +/- 1.3% for coefficient of variation, indicating higher interobserver reproducibility with the semiautomated than manual method. The agreement between the 2 segmentation methods was high (mean intermethod DSC 95.8 +/- 1.0% and 94.9 +/- 0.8%) for both observers. CONCLUSIONS The semiautomated method was significantly more efficient and reproducible than the manual delineation method for segmentation of kidney from MDCT images.

This HIPAA-compliant study was exempt from institutional review board approval because the 10 image data sets were deidentified in the Osteoarthritis Initiative database, and they were processed and analyzed without any clinical information being accessed. The purpose of this study was to prospectively evaluate the efficiency and reproducibility of the semiautomated graph-cut method (SA method) in the segmentation of knee cartilage and to compare its performance with that of the conventional manual delineation segmentation method (M method). Two radiologists independently performed segmentation with each method in two separate sessions: They performed the M method (M1 and M2 for the first and second sessions, respectively) for every third section and the SA method (SA1 and SA2 for the first and second sessions, respectively) for every section. The SA method was significantly more efficient (mean processing time, 53 minutes vs 156 minutes for SA1 vs M1 and 53 minutes vs 118 minutes for SA2 vs M2; P < .001) and reproducible (mean volume overlap, 94.3% vs 87.8% for the SA method vs the M method; P < .001) than the M method.

To establish a three-step purification method of preparative-scale antiCD20 (Fab')2 using AKTA prime.AntiCD20 (Fab')2 was extracted by hyperosmotic solution and then purified by CM sepharose FF, phenyl sepharose FF, and protein G sepharose FF.Around 8 mg anti-CD20 (Fab')2, whose purification was 96.678%, was purified. The antigen-binding activity of antiCD20 (Fab')2 was similar to that of antiCD20 (Fab')2 purified by protein G sepharose FF and S-100.The three-step purification method can obtain high-purity preparative-scale antiCD20 (Fab')2 in a simple way.

The purpose of our study was to retrospectively evaluate the effect of body weight and iodine dose on aortic and hepatic contrast enhancement in pediatric patients who underwent 64-MDCT of the abdomen and pelvis.Eighty-seven consecutive pediatric patients (50 boys and 37 girls; median age, 12.1 years; age range, 3.8-17.6 years) underwent standard abdominopelvic CT with a 64-MDCT scanner. Contrast medium (350 mg I/mL) was injected using a power injector at 2 mL/s followed by 15-20 mL of saline flush. According to our CT protocol, the volume of administered contrast medium was approximately 1.8 mL/kg of body weight, up to the maximum volume of 80 mL. CT scanning was initiated 60 seconds after the start of the contrast medium injection. CT attenuations of the aorta and liver were measured. For each patient, the injected contrast medium iodine mass per body weight index (g I/kg) (hereafter, iodine mass body index) was calculated. Linear regression analysis was performed between iodine mass body index and aortic and hepatic attenuations.A wide range of patient weights (19-82 kg; mean, 48.6 kg [95% CI, 45.3-51.9 kg]) and contrast volumes (30-80 mL; median, 80.0 mL) were observed. The median attenuations were 149.0 HU (141.0-160.0 HU) for the aorta and 113.5 HU (109.5-120.0 HU) for the liver. Moderately high correlations were observed between iodine mass body index and aortic (Spearman's rho [r(s)] = 0.60 [0.45-0.72]; p0.001) and hepatic (r(s) = 0.60 [0.42-0.70]; p0.001) attenuations. The regression formulae for aortic attenuation (58.4 + 176.3 x iodine mass body index [p0.001]) and hepatic attenuation (58.7 + 108.5 x iodine mass body index [p0.001]) indicate that 1.5 and 1.8 mL/kg (350 mg I/mL) of contrast media are required to achieve 116 and 127 HU, respectively, of contrast-enhanced attenuation in the liver.In our study, using abdominal 64-MDCT in pediatric patients, we found that approximately 1.5 mL/kg, or 0.525 g I/kg, yields 116 HU of hepatic attenuation or 50-55 HU of hepatic enhancement.

To prepare monoclonal antibody (McAb) against anti-CD3 ScFv for purifying and detecting serum anti-CD3 antibody concentration.McAb against anti-CD3 ScFv was prepared by hybridoma technique and used to prepare affinity chromatography column, which was used to purify anti-CD3 ScFv and Diabody [CD3 x Pgp] without E-tag. The binding activities of anti-CD3 ScFv, Diabody [CD3 x Pgp] without E-tag, and Diabody [CD3 x Pgp] purified by anti-CD3 affinity chromatography column or anti-E-tag affinity chromatography column against K562/A02 cell and Jurket cells were detected by fluorescence activated cell sorting (FACS) method. ELISA was used to identify the specificity of the McAb.McAb against anti-CD3 ScFv specifically detected serum anti-CD3 ScFv without reacting with sera. The anti-CD3 ScFv purified by anti-CD3 affinity chromatography column and purified by anti-E-tag affinity chromatography column had the same specific binding activity with Jurkat cells. The positive binding rates of Diabody [CD3 x Pgp] without E-tag to K562/A02 and Jurkat cells were 89.87% and 83.95%, respectively. In the competitive binding experiments with K562/A02 and Jurkat cells, the binding rates of Diabody [CD3 x Pgp] without E-tag decreased to 56.30% and 43.78%, respectively.The McAb against anti-CD3 ScFv prepared in our lab can be used to purify and detect serum anti-CD3 antibody concentration.