Search

Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design.

Background Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. Methods Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. Results BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p p p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p r = 0.9813, n = 20, p Conclusion We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Background The utilization of mobile health (m-health) has rapidly expanded during the COVID-19 pandemic, and there is still a lack of relevant clinical data pertaining to chronic low-back pain (CLBP) management. This study was designed to compare the effectiveness of m-health-based exercise (via guidance plus education) versus exercise (via guidance) during CLBP management. Methods Participants (n = 40) were randomly assigned to intervention and control groups. The intervention group received m-health-based exercise (via guidance plus education), whereas the control group received m-health-based exercise (via guidance). The exercise prescription video and educational content were sent to participants by the application (app), Ding Talk. Repeated-measures analysis of variance was used to test the baseline’s intervention effects, 6-week follow-up, and 18-week follow-up. We selected function (Roland and Morris Disability Questionnaire) and pain intensity (current, mean, and most severe Numeric Rating Scale in the last 2 weeks) as the primary outcomes, changes of negative emotion (depression, anxious), and quality of life as the secondary outcomes. Results Time’s significant effect was found in pain, function, and health-related quality of life in both groups, but time did not show significant interaction effects. Participants were able to use m-based education with their anxiety and depression after treatment, but the relief only lasted until week 6. No differences were found on the aspect of mental health-related quality of life. Conclusion Preliminary findings suggest that m-health-based exercise (via guidance) may be a convenient and effective method to treat CLBP. However, additional health education didn't help more. More rigorous controlled trials are needed to improve the therapeutic effect in future studies. Trial registration Chinese Clinical Trials Registry Number ChiCTR2000041459. Registered on December 26, 2020.

Titanium alloys are one of the most important structural materials for the aerospace applications, which bring active study on microstructural and mechanical optimization of the alloys. In the present study, commercial TA2 titanium sheets with different initial textures were rolled to a strain of 4% at liquid nitrogen temperature. Microstructures of the rolled sheets were characterized using a scanning electron microscope equipped with an EBSD detector and their mechanical properties were tested through quasi-static uniaxial tension tests at room temperature. The influence of the initial texture on the microstructure and mechanical performance of the cryorolled sheet were discussed. Twinning is found to occur in the TA2 sheets after rolling even at a small strain. Initial texture is an important factor affecting both numbers and types of the twins. {11–22} contraction twinning is always the dominating type of twins for all three sheets having different initial textures. A lot of {11–22} and {11–24} twins can be found in the sheets with the initial texture of C-axes//ND, while the sheet with an initial texture of C-axes away from the ND contains few twins, with a high density of dislocations developed instead. Along with contraction twinning, many {10–12} and {11–21} twins are detected in the sheet with the initial texture of C-axes⊥ND. The cryorolled sheet having the densest twins shows the best mechanical properties, indicating a beneficial effect of a small pre-strain.

In this paper, the authors establish the (Lp(μ), Lq(μ))-type estimate for fractional commutator generated by fractional integral operators Tα with Lipschitz functions (b ∈ Lipβ (μ)), where 1

This paper presents a new method for contour measurements using a 3D scanner to determine cross-sectional residual stresses in structural components with complex configurations. The proposed method was applied to evaluate the axial residual stress distribution in a dissimilar pipe weld and the obtained results were compared with those obtained using a benchmarked contour measurement machine (CMM) equipped with a confocal laser probe for verification. It reveals a quantitative agreement between the two methods in terms of both the measured contours and the calculated residual stresses. Most importantly, this method allows a significantly reduced measurement time by ≈99 % (≈20 min, with an effective measurement speed of ≈0.2 sec/mm2), compared to the benchmarked method (≈48 hr, with an effective measurement speed of ≈28.7 sec/mm2). Based on stress uncertainty analysis, this method guarantees a longer range of stable fits due to fewer noisy data points than the benchmarked method.

Sediment is an endogenous pollution source, which often leads water systems to eutrophication due to the release of nutrients, especially phosphorus (P). Calcium nitrate (CN) was dosed to the water systems under different modes to control P release from the sediments in this study. A 63-day static laboratory test was conducted to explore the effects of intermittent dosing and one-time dosing modes of CN on P locking in the sediment and the concentrations of nitrogen (N) and P in waters. Results showed that 89% total phosphorus (TP) in the overlying water and 91% TP in the interstitial water of sediment were reduced in the intermittent dosing reactor, which were 4% and 13% higher than those in the one-time dosing reactor, respectively. Thus, the concentration of TP in the overlying water of the dosing reactors was both below 0.1 mg/L during the whole experiment. Meanwhile, the mean values of oxidation–reduction potential (ORP) in the sediment increased to − 110.7 ± 42.02 mV when CN was added intermittently, which were significantly higher than those of the one-time dosing reactor (− 158.3 ± 44.61 mV) and control reactor (− 320.7 ± 0.05 mV). Compared with one-time dosing mode, the intermittent dosing not only reduced the maximum concentrations of NO2−-N from 9.21 to 1.79 mg/L and NO3−-N from 92.42 to 27.58 mg/L but also shorten their retention time in the overlying water, which might depress the toxic threats to aquatic animals in water environments. Therefore, the intermittent dosing of CN could not only improve the P locking effect but also minimize the risks to aquatic animals in water environments under the premise of reasonable dosage selected. In a word, this research provided an effective operation mode for locking P with CN in the heavily polluted water bodies, which is also advantageous to avoid toxic threats to aquatic animals in water environment.

Background Low handgrip strength (HGS) is independently associated with a higher exacerbation risk in stable chronic obstructive pulmonary disease (COPD); however, the relationship between HGS while being admitted for COPD exacerbation and further exacerbation risk after discharge remains unclear. Methods We enrolled patients admitted for COPD exacerbation between January 2018 and June 2019. HGS tests were done within 3 days after admission. The primary endpoint was exacerbations within 12 months after the index admission, which needed emergency room visits or hospital admission. We analyzed the relationships among demographics, HGS, pulmonary function parameters, and acute exacerbation events. Results Among 43 enrolled patients, 31 (72.1%) participants (HGSw) had HGS weakness (22.1 ± 4.1 kg). The other 12 (27.9%) participants (non-HGSw) had the strength of handgrips 33.7 ± 3.1 kg. HGSw group showed a significantly higher rate of emergency room visits within 6, 9, and 12 months after the index admission than non-HGSw group (0.81 ± 1.30 vs. 0.08 ± 0.29, p = 0.045; 1.26 ± 1.59 vs. 0.17 ± 0.38, P = 0.019; 1.48 ± 1.86 vs. 0.25 ± 0.62, P = 0.027, respectively). There was a trend to have higher admission rate within 9 and 12 months in HGSw group, which did not achieve statistical significance (0.77 ± 1.38 vs. 0.08 ± 0.29, P = 0.064; 0.94 ± 1.56 vs. 0.08 ± 0.29, P = 0.062, respectively). Conclusions HGS weakness measured upon admission for COPD exacerbation was associated with a higher risk of exacerbation in the next year. Trial registration ClinicalTrials.gov Identifier: NCT04885933.

Stress corrosion cracking behavior of a copper pipe and its mechanism were investigated in a heating water supply system using both metallurgical and mechanical analyses. The X-ray diffraction and energy dispersive spectroscopy measurements showed that uniform cupric oxide and cuprous oxide were formed during service on the inside surface of the pipe, while malachite and cupric oxide were the main corrosion products on the outer surface of the pipe. Many corrosion pits were observed around the cracking areas on the outer surface by optical microscopy. Finite element modeling highlighted a region with large hoop stresses mainly brought about by the bolt load, where it became susceptible to stress corrosion cracking (SCC). The morphology of the fracture surface revealed an intergranular mode towards the outer surface but a mixed inter- and trans-granular mode near the inner surface. Based on the obtained results, a phenomenological 4-stage fracture process is proposed to describe the failure process of the copper pipe, in which the SCC initiated from the corrosion pits on the outer surface, propagated along the axial direction and penetrated towards the inner surface until final fracture.

Background In eukaryotic organisms, it has been well acknowledged that 3′ untranslated regions (3′ UTRs) of mRNA are actively involved in post-transcriptional regulations of gene expression. Although both shortening and lengthening of 3′ UTRs of specific candidate genes were explicitly documented to have functional consequences, landscape of 3′ UTR lengths in relation to evolutionary dynamics and biological meanings remains to be elucidated when large-scale data become available. Objectives The primary objective of this study was to revealed different inter- and intra-species patterns on length distribution of 3′ UTRs in comparison with 5′ UTRs and coding regions. Methods In the present study, we investigated 3′ UTR lengths in a highly curated set of 57,135 mRNA sequences among four well-studied and taxonomically diverse metazoan species (fruit fly, zebrafish, mouse and human). Results The average length ratio of 3′–5′ UTRs considerably increased from fruit fly (twofold) to human (fivefold). Moreover, genes can be characterized by the obviously different patterns of evolutionary change on 3′ UTR lengths. By utilizing the Gene Ontology annotations, genes with differential lengths of 3′ UTRs were suggested to have the divergent functional implications. In human, we further revealed that ubiquitously transcribed genes had higher median lengths of 3′ UTRs than the genes of tissue-restricted expressions. Conclusion We conducted a comprehensive analysis and provided an overview regarding 3′ UTRs biology of mRNAs in animals, whereas the mechanistic explanations of 3′ UTRs length variation in correlation to regulation of gene expression still remain to be further studied. Electronic supplementary material The online version of this article (10.1007/s13258-019-00808-8) contains supplementary material, which is available to authorized users.

Early studies of T cell structural biology using X-ray crystallography, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) focused on a picture of the αβT cell receptor (αβTCR) component domains and their cognate ligands (peptides bound to MHC molecules, i.e. pMHCs) as static interaction partners. Moving forward requires integrating this corpus of data with dynamic technologies such as NMR, molecular dynamics (MD) simulations and real-time single molecule (SM) studies exemplified by optical tweezers (OT). NMR bridges relevant timescales and provides the potential for an all-atom dynamic description of αβTCR components prior to and during interactions with binding partners. SM techniques have opened up vistas in understanding the non-equilibrium nature of T cell signaling through the introduction of force-mediated binding measurements into the paradigm for T cell function. In this regard, bioforces consequent to T-lineage cell motility are now perceived as placing piconewton (pN)-level loads on single receptor-pMHC bonds to impact structural change and αβT-lineage biology, including peptide discrimination, cellular activation, and developmental progression. We discuss herein essential NMR technologies in illuminating the role of ligand binding in the preT cell receptor (preTCR), the αβTCR developmental precursor, and convergence of NMR, SM and MD data in advancing our comprehension of T cell development. More broadly we review the central hypothesis that the αβTCR is a mechanosensor, fostered by breakthrough NMR-based structural insights. Collectively, elucidating dynamic aspects through the integrative use of NMR, SM, and MD shall advance fundamental appreciation of the mechanism of T cell signaling as well as inform translational efforts in αβTCR and chimeric T cell (CAR-T) immunotherapies and T cell vaccinology.

The endogenous release of nutrients from sediments contributes to the eutrophication of landscape water to a certain degree, which depends on the characteristics of sediments. The study explored the characteristics of nitrogen (N) and phosphorus (P) released from two different sediments, which were deposited from reclaimed water (SRW) or surface water (SSW) respectively in Xi’an moat. This paper aimed to compare the effects of nutrient release from SRW and SSW on the water quality. Results showed that the maximum increase rates reached 1.21 mg TN/(L·day) and 0.11 mg TP/(L·day), respectively, in the overlying water of SRW, which were 1.6 and 2.8 times those of SSW. The released amounts of SRW were 0.192 mg TN/g and 0.038 mg TP/g, which were 4.1 and 12.7 times those of SSW. Meanwhile, the densities of benthic algae in SRW and SSW were 5.605 × 109 and 2.846 × 108 cells/L, respectively. Moreover, the species number and individual sizes of benthic algae in SRW were also larger than those in SSW, which played an important role in the nitrogen circulation. Unexpectedly, oxidation reduction potential (ORP) level of SRW was lower than that of SSW, although SRW has a higher dissolved oxygen level. Therefore, the N and P concentrations in the overlying water of SRW were considerably higher than those of SSW, which was mainly attributed to the higher nutrient contents and lower ORP in SRW.

Morphine has been used in the treatment of pain for centuries. It is commonly used by oncology in terminal cancer cases and by surgery perioperatively for oncology surgery. Its extra-analgesic effects on cancer have been described extensively but conflicting results abound. It has been shown to have varying effects on tumour progression, cell proliferation, tumour invasion, angiogenesis, immune function, and metastatic potential. In vivo studies on the effects of morphine and the mu-opioid receptor on tumours are discussed below. Mechanisms involved are also discussed, drawn from a combination of both in vivo and in vitro methods. At present, no consensus can be drawn from data collected, and further studies are necessary to elicit the safest method and agent for analgesia in oncology patients.

The voltage was recorded to investigate the influence of the static magnetic field on droplet evolution during the magnetically controlled electroslag remelting (MC-ESR) process. MC-ESR experiments were carried out under different remelting current, and transverse static magnetic fields (TSMF) of 85 mT, 130 mT and 160 mT were superimposed. Statistical work was performed to obtain the quantitative data of the droplets. The ASPEX Explorer was utilized to investigate the inclusions evolution of GCr15 ingots. The number of the droplets was 31 in 20 s during the traditional ESR process and reached 50 and 51 under the MC-ESR process with the TSMF of 85 mT and 130 mT, respectively. When compared the traditional ESR process with the MC-ESR process, the inclusions amount reduced 67%.

A transient three-dimensional coupled numerical model has been established to clarify the influence of the external transverse static magnetic field (TSMF) on droplet evolution behaviors during the electroslag remelting (ESR) process with an alternating current (50 Hz). The development of the electromagnetic field code and the calculation procedure showed that the periodic inverse Lorentz force (50 Hz) could be fully coupled with the volume of fluid model in each iteration when an external TSMF of 0.05 T is superimposed. The droplet evolution behaviors with and without the external TSMF were demonstrated and analyzed. The numerical results showed that the huge periodic inverse Lorentz force could smash the droplet neck into numerous smaller droplets during the ESR process with the external TSMF; simultaneously, the interfacial area and falling time could be increased, indicating that the purification efficiency could be expected to improve.

An external direct current (DC) was introduced to counteract the thermoelectric magnetic effect during the directional solidification of Sn-10 wt pct Bi alloy under a 0.5 T transverse static magnetic field. The results show that the single-side Bi segregation induced by the thermoelectric magnetic effect gradually becomes weakened, disappeared, and then reversed with the increasing current density of the external DC. Therefore, a new method for counteracting the thermoelectric magnetic effect during materials processing under the magnetic field was proposed. In order to verify this method, the absolute thermoelectric power of Sn-10 wt pct Bi alloy and the internal thermoelectric current under the experimental conditions were measured and calculated, respectively. A 2D numerical simulation was established to simulate the evolution of the solid–liquid interface morphology, flow field, and composition segregation with the increasing current density of the external DC during directional solidification under a transverse static magnetic field. The present study not only facilitates the understanding of the effects of the forced flows on the directionally solidified microstructures and composition segregation, but also provides a new way for eliminating segregation and obtaining the higher-quality solidification structure by using the electromagnetic compounding technique.

The electromagnetic vibration (EMV) generated by the action of the AC current and the magnetic field was applied in the crystallizer during the semi-continuous casting of the Al-15 wt pct Sn alloy. The influences of the electromagnetic vibration frequency (EMVF) on the metallographic structure, inverse segregation, and tensile properties were studied. The results indicated that the equiaxed grain ratios of the slabs were increased by decreasing the EMVFs from 500 to 5 Hz. The inverse segregation around the sides of the slab was improved at a low EMVF. The results of the 3D numerical simulation showed that the forced flows led to the refinement of grains and the improvement of the inverse segregation. The slabs with equiaxed grains which were produced with the low EMVFs showed the poor tensile properties comparing to the slabs with columnar grains obtained with the EMVFs of 50, 200, and 500 Hz and without the EMV. This phenomenon was mainly due to the distribution of the brittle Sn-rich phases: the reticular Sn-rich phases appeared around the boundary of the equiaxed grains, while the worm-like Sn-rich phases appeared between the column dendrites intermittently in the slabs with columnar grains.

In previous work, we presented experimental and theoretical evidence that podophyllum derivatives substituted by chlorine atom in the 3-posititon of 2-aminopyridine exhibited significantly elevated potency. In this study, a series of podophyllum derivatives substituted in the 3-position of 2-aminopyridine, including methyl and fluorine groups, were synthesized. Their chemical structures were confirmed by the spectral (1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, electrospray ionization mass spectrometry) and elemental analyses. These derivatives were tested for their respective cytotoxicities in HeLa, BGC-823, A549, Huh7, and MCF-7 cells by MTT assay and the pharmacological results showed that most of them displayed potent cytotoxicities against at least one of the tested cancer cell lines. Structure–activity relationship study suggested that the introduction of the fluorine atom into the 3-posititon of 2-aminopyridine had enhanced the cytotoxicity against numerous tumor cells compared to the chlorine atom, while the methyl group did not. Furthermore, other biological experiments were consistent with the beneficial effect of fluorine atom substituent in the 3-position of 2-aminopyridine, which then inhibited the microtubule polymerization and activity of topoisomerase II when 2-amino-3-fluoropyridine substituted in podophyllotoxin and 4′-O-demethylepipodophyllotoxin, and that they work by effecting the target proteins which induce P53-dependent apoptosis.

Background Hepatitis B virus (HBV) infection is a major public health problem in China. Over a decade has passed since the last National Hepatitis Seroepidemiological Survey was conducted in 2006. The lack of updated data on hepatitis B in China makes assessing the current prevalence and burden of the disease inadequate. In response to the above situation, a systematic review and meta-analysis was conducted to provide a better understanding of hepatitis B epidemiology in the general population of China. Methods A systematic search was conducted in international databases (Medline through PubMed, EMBASE, Cochrane, Web of Science) and national databases (CBM, CNKI, WanFang Data) to retrieve primary studies published between January 1, 2013 and December 31, 2017. The pooled prevalence of HBV infection and 95% confidence intervals were calculated. Quality assessment, heterogeneity testing and publication bias assessment were also performed. Results Of the 27 studies included in the meta-analysis, the pooled estimated prevalence of HBV infection in the general population of China from 2013 to 2017 was 6.89% (95% CI:5.84–7.95%), which could be extrapolated to an estimated population of 84 million living with HBsAg in 2018. The prevalence of HBV infection in males was higher than that in females (5.88% vs 5.05%), and rural areas had a higher prevalence than urban areas (5.86% vs 3.29%). The highest prevalence of HBV infection was reported in Western provinces (8.92, 95% CI: 7.19–10.64%). In adults older than 20 years, the prevalence of HBV infection was approximately 7%, which was higher than that in children. Conclusion The prevalence of HBV infection in the general population of China was classified as higher intermediate prevalence (5–7.99%), of which more than 90% of the HBV infection population included adults older than 20 years. The blocking of mother-to-infant hepatitis B transmission and plans involving timely birth dose of hepatitis B vaccine within 24 h should be implemented. Additionally, improving the quality of life and survival rate of the infected population through antiviral therapy and high-risk adult vaccination will be the priority of our future work. Moreover, various control measures should be implemented in different provinces across China.

A transparent physical model was set up to investigate the influence of the remelting current frequencies on droplet evolution during the magnetic-field-controlled electroslag remelting process. Physical simulation experiments were done under the remelting current of 8 A with frequencies ranging from 10 to 500 Hz, and a transverse static magnetic field (TSMF) of 0.7 T was superimposed simultaneously. The high-speed camera was used to record the evolution behavior of the droplet. Representative processes of formation and detachment of the droplets were observed under different conditions. The results showed that there was little influence of the current frequencies on the evolution behavior of the droplet without the external magnetic field. Nevertheless, if a TSMF was introduced, the liquid droplet’s neck would be smashed into a lot of smaller droplets when the remelting current frequencies were lower than 100 Hz, while the smashing effect disappeared when the frequencies were higher than 100 Hz. The mechanism of the smashing effect was discussed. Statistical work was done to obtain the quantitative data to give a clear result revealing the influence of the remelting current frequencies on droplet evolution. The decrease in the diameter of the liquid droplets would remarkably increase the interface area and shorten the migrating distance of the inclusions in the droplets, which meant that a higher purifying efficiency could be expected.

Evidence is presented that waters containing high concentrations of chlorophyll are transported by internal waves to the fore-reef slope of Dongsha Atoll in the northern South China Sea. High vertical resolution mooring measurements of temperature, pressure, and chlorophyll fluorescence revealed that the internal soliton cores could transport chlorophyll vertically downward and increase concentrations by an order of magnitude near the seafloor, compared to background levels. The reef areas that are potentially nourished by the pulses of phytoplankton are dominated by alcyonacean soft corals, while other reef areas that are less or not at all affected by internal waves are dominated by scleractinian hard corals. This suggests that the delivery of phytoplankton by internal solitons provides a plentiful food source that benefits the growth of soft corals.

Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. The trial was registered with EudraCT (year = 2008, registration number = 005570–12 ) and ISRCTN (year = 2008, registration number = 77,829,558 ).

Netrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution. Axon guidance assays confirm that the DCC/FAK complex is essential for netrin-1-induced chemoattraction. We propose that netrin-1/DCC engagement creates a small cluster of P3/FAT for FAK recruitment close to the cell membrane, which exerts a concerted effect with PIP2 for FAK signaling. We also compare P3/FAT binding with paxillin/FAT binding and discuss their distinct recognition specificity on a common FAT domain for axon attraction versus integrin signaling, respectively.

Internal oceanic waves are subsurface gravity waves that can be enormous and travel thousands of kilometres before breaking but they are difficult to study; here observations of such waves in the South China Sea reveal their formation mechanism, extreme turbulence, relationship to the Kuroshio Current and energy budget. Internal waves are the underwater version of more familiar surface waves. They can be enormous and travel thousands of kilometres before breaking. The South China Sea is known to be home to the largest internal waves in the world's oceans, but their size, generation mechanisms and role in the regional energy budget are unknown. Matthew Alford and colleagues now present the results from the IWISE observational campaign and reveal that internal waves more than 200 metres high break in the South China Sea and create turbulence that is orders of magnitude larger than in the open ocean, and that wave formation is influenced by the Kuroshio current. These results now allow for a complete energy budget of the South China Sea, and for a more accurate incorporation of internal waves into climate models. Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they affect a panoply of ocean processes, such as the supply of nutrients for photosynthesis1, sediment and pollutant transport2 and acoustic transmission3; they also pose hazards for man-made structures in the ocean4. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking5, making it challenging to observe them and to include them in numerical climate models, which are sensitive to their effects6,7. For over a decade, studies8,9,10,11 have targeted the South China Sea, where the oceans’ most powerful known internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their mechanism of generation, variability and energy budget, however, owing to the lack of in situ data from the Luzon Strait, where extreme flow conditions make measurements difficult. Here we use new observations and numerical models to (1) show that the waves begin as sinusoidal disturbances rather than arising from sharp hydraulic phenomena, (2) reveal the existence of >200-metre-high breaking internal waves in the region of generation that give rise to turbulence levels >10,000 times that in the open ocean, (3) determine that the Kuroshio western boundary current noticeably refracts the internal wave field emanating from the Luzon Strait, and (4) demonstrate a factor-of-two agreement between modelled and observed energy fluxes, which allows us to produce an observationally supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions.

Human neonates are highly susceptible to a wide range of infections, which has been attributed to deficiencies in their innate and adaptive immunity. In contrast to the well-documented immaturity in neonatal adaptive immunity, deficiencies in their innate immunity are less defined. This study examined the inflammatory response of neonatal monocytes to bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) stimulation and discriminated the underlying Toll-like receptor (TLR)-mediated signal transduction pathways.Cord blood from 30 healthy newborns of full-term elective cesarean sections and peripheral blood from 25 healthy adult volunteers were collected. Ex vivo production of inflammatory cytokines was assessed by cytometric bead array, and expression of CD14, TLR4, TLR2, phosphorylated NF-κB p65 and p38 on monocytes were detected by FACScan analysis.Neonatal whole blood showed significantly decreased ex vivo TNF-α and IL-1β production in response to stimulation with the TLR4 agonist LPS, but not the TLR2 agonist PGN, when compared with adult whole blood. Consistent with the diminished inflammatory cytokine response to LPS stimulation, neonatal monocytes exhibited substantially impaired TLR-mediated signal transduction pathways characterized by down-regulated expression of CD14 and TLR4, and suppressed phosphorylation of NF-κB p65 at Ser536 and p38 following LPS stimulation. In addition, neonates had a significantly lower percentage of TLR4(+)/CD14(+) monocytes than adults.These results indicate that in contrast to the adult, human neonates display deficiencies in innate immunity-associated inflammatory cytokine responses due to their defective TLR signaling pathways, which may render them more susceptible to microbial infection.

Coatings containing Fe-Si particles were electrodeposited on 3.0wt% Si steel sheets under magnetic fields. The effects of magnetic flux density (MFD), electrode arrangement and current density on the surface morphology, the silicon content in the coatings and the cathode current efficiency were investigated. When a magnetic field was applied parallel to the current and when the MFD was less than 0.5 T, numerous needle-like structures appeared on the coating surface. With increasing MFD, the needle-like structures weakened and were transformed into dome-shaped structures. Meanwhile, compared to results obtained in the absence of a magnetic field, the silicon content in the coatings significantly increased as the MFD was increased for all of the samples obtained using a vertical electrode system. However, in the case of an aclinic electrode system, the silicon content decreased. Furthermore, the cathode current efficiency was considerably diminished when a magnetic field was applied. A possible mechanism for these phenomena was discussed.

Growing body of laboratory evidence supports the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC) prevention. Epidemiologic studies investigating the relationship between n-3 PUFAs intake and risk of CRC, however, have been inconsistent. We aimed to clarify the relation by conducting a meta-analysis of prospective studies.Eligible studies were identified by searching PubMed database and by carefully reviewing bibliographies of retrieved publications. Summary relative risks (RRs) with their 95 % confidence intervals (CIs) were computed with a random-effects model. Subgroup, meta-regression, and dose-response analyses were performed to explore potential sources of heterogeneity.A total of 14 prospective studies involving 8,775 cancer cases were included in the final analysis. Overall, total n-3 or marine PUFAs intake was not associated with risk of CRC (RR 0.99 and 1.00). However, there was a trend toward reduced risk of proximal colon cancer (total n-3 PUFAs: RR 0.83, 95 % CI 0.66-1.05; marine PUFAs: RR 0.81, 95 % CI 0.59-1.10) and a significant increased risk of distal colon cancer (total n-3 PUFAs: RR 1.26, 95 % CI 1.06-1.50; marine PUFAs: RR 1.38, 95 % CI 1.11-1.71). Furthermore, marine PUFAs intake accessed longer before diagnosis was associated 21 % reduced risk of CRC (RR 0.79, 95 % CI 0.63-1.00).Overall, this meta-analysis finds no relation between n-3 PUFAs intake and risk of CRC. The observed subsite heterogeneity within colon cancer and the possible effect modification by latency time merit further studies.

The effect of smelting processes on mechanical properties and microstructure of reduced activation ferritic steels was studied. Creep properties and impact toughness of reduced activation ferritic steels were obviously improved by vacuum induction melting followed by consumable electrode remelting process in comparison with the conventional vacuum induction melting process. The difference of impact toughness and creep properties between both steels mainly depended on the aspect ratio and mean size of precipitates. Decreasing the aspect ratio of carbides makes development of a shear band more difficult, which could increase impact energy and creep resistance.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI. In the present study we examined the impact of B7H3 on pulmonary inflammatory response, polymorphonuclear neutrophil (PMN) influx and lung tissue damage in a murine model of lipopolysaccharide (LPS)-induced direct ALI. Treatment with B7H3 protected mice against LPS-induced ALI, with significantly attenuated pulmonary PMN infiltration, decreased lung myeloperoxidase (MPO) activity, reduced bronchoalveolar lavage fluid (BALF) protein content and ameliorated lung pathological changes. In addition, B7H3 significantly diminished LPS-stimulated PMN chemoattractant CXCL2 production by inhibiting NF-κB p65 phosphorylation and substantially attenuated LPS-induced PMN chemotaxis and transendothelial migration by down-regulating CXCR2 and Mac-1 expression. These results demonstrate that B7H3 substantially ameliorates LPS-induced ALI and this protection afforded by B7H3 is predominantly associated with its inhibitory effect on pulmonary PMN migration and infiltration.

In the present study, sufu, the cheese-like, traditional fermented soybean food from China, was prepared by solid-state fungal fermentation and ripened in dressing mixtures with different NaCl content. The angiotensin I-converting enzyme (ACE) inhibitory activity and γ-aminobutyric acid (GABA) content were determined during sufu manufacturing. The influence of NaCl on ACE inhibitory activity and GABA content was also investigated. The ACE inhibitory activity and GABA content of sufu were significantly affected by processing and NaCl content. During fermentation, the ACE inhibitory activity percentage increased from 11.55 to 37.61 %, whereas the GABA content increased from 32.64 to 133.13 mg/100 g dry matter. The salting process caused a decrease in both. Generally, the ACE inhibitory activity and GABA content increased during ripening. The ACE inhibitory activity at the same ripening interval was inhibited by NaCl. After ripening for 8 weeks, the sufu samples with 5 % NaCl had the highest ACE inhibitory activity, with an IC50 of 0.79 mg/mL, whereas the samples with 8 % NaCl had the highest GABA content at 193.5 mg/100 g dry matter. A significant correlation was found between ACE inhibitory activity and peptide content. These results indicated that sufu could be useful in alleviating hypertension because it contained ACE inhibitors and GABA as antihypertensive substances. Low NaCl content could increase the antihypertensive activity.

Influenza A virus nucleoprotein (NP) forms homo-oligomers and multiple copies of NP wrap around genomic RNA, along with a trimeric polymerase making up ribonucleoprotein (RNP) complex. Sequence comparison of more than 2500 influenza A NP showed that this protein contains 30.1 % of polymorphic residues. NP is composed of a head and a body domain and a tail loop/ linker region. The head domain is more conserved than the body domain, as revealed from the structure-based sequence alignment. NP oligomerization is mediated by the insertion of the non-polymorphic and structurally conserved tail loop of one NP molecule to a groove of another NP. The different form of NP oligomers is due to the flexibility of the polymorphic linkers that join the tail loop to the rest of the protein. The RNA binding property of NP is known to involve the protruding element and the flexible basic loop between the head and body domains, both having high degree of primary sequence conservation. To bind RNA, NP may first capture the RNA by the flexible basic loop and then the RNA is clamped by the protruding element.

Gene-radiotherapy, a combination of gene therapy and radiotherapy, is a new paradigm for cancer treatment, with the potential to simultaneously improve local and systemic breast cancer control. The aim of this study was to evaluate antitumor effect of interferon (IFN)-gamma-endostatin-based gene-radiotherapy in a murine metastatic breast tumor model, and to elucidate possible mechanisms involved.Murine mammary adenocarcinoma 4T1 cells transfected with pEgr-IFN-gamma and pEgr-endostatin plasmids were irradiated (2-20 Gy). IFN-gamma and endostatin levels in the culture supernatants were measured. In vivo female BALB/c mice were inoculated with 1 x 10(5) 4T1 cells by mammary fat pad injection and divided into control, empty vector, gene therapy (pEgr-IFN-gamma and pEgr-endostatin), radiotherapy, and combined gene-radiotherapy groups. Tumor growth, tumor/body weight ratio, lung metastases, and survival of the tumor-bearing mice were observed. Splenic cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell activity and intratumor microvessel density were also assessed.Irradiation significantly enhanced IFN-gamma and endostatin secretion from the transfected 4T1 cells. In vivo mice that received combined gene-radiotherapy showed maximal attenuation in tumor growth rate and lung metastases with increased survival compared with mice that received gene therapy or radiotherapy alone. This was associated with significantly enhanced CTL and NK cell activity and reduced intratumor microvessel density.These results demonstrate that IFN-gamma-endostatin-based gene-radiotherapy provide a potent antitumor effect in a murine metastatic breast tumor model, which may relate to IFN-gamma-stimulated CTL and NK cell activation, and endostatin-induced antiangiogenic activity. Thus, gene-radiotherapy may represent a useful addition to neoadjuvant management of locally advanced breast cancer.

We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase/Akt (PI3K/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm3. Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p

Studies show a sharp difference in math achievement between students in the U.S. and students in several East Asian countries, amongst them Taiwan. It is suggested that the patterns of math instruction applied by teachers may have contributed to these differences. This study intends to investigate the patterns of math instruction applied by the Taiwanese teachers and to delve into the cultural roots of these patterns. Data source includes videotaping of instruction by three middle school math teachers and a questionnaire survey of 297 eighth-graders. It was found that the Taiwanese math instruction pattern may be summarized as a cultural activity of “practice makes perfect, on the blackboard”. The underlying cultural beliefs are further explored, including the incremental view of human intelligence, self-improvement through diligent effort, and the teacher's role as an authority figure.

The most critical step in maize domestication (Zea mays ssp. mays) was the liberation of the kernel from the hardened, protective casing that envelops the kernel in the maize progenitor, teosinte1. This evolutionary step exposed the kernel on the surface of the ear such that it could be readily utilized as a food source by humans. Here, we show that this key event in maize domestication is controlled by a single gene (teosinte glume architecture; tga1) belonging to the SBP-domain family2 of transcriptional regulators. The factor controlling the phenotypic difference between maize and teosinte maps to a 1 kilobase region within which maize and teosinte show only six fixed differences in their DNA sequences. One of these differences encodes a non-conservative amino acid substitution and may affect protein function, while the other five differences potentially affect gene regulation. Molecular evolution analyses show that this region was the target of selection during maize domestication. Our results demonstrate that modest genetic changes in single genes can induce dramatic changes in phenotype during domestication and evolution.

Osteoblasts and endothelial cells are intimately located within the skeleton, and their interaction is an integral component of bone repair, a complex process which continues for weeks under conditions of low oxygen tension. This study investigated the paracrine factors that couple angiogenesis and osteogenesis and demonstrates that hypoxia is an integral mediator of this complex phenomenon. Hypoxia stimulates vascular endothelial growth factor (VEGF) and not basic fibroblast growth factor (bFGF) release from primary human osteoblasts and is directly angiogenic, enhancing human microvascular endothelial cell proliferation and vessel tube formation in vitro. Hypoxic endothelial cells release potent osteogenic mitogens, endothelin-1 (Et-1) and insulin-like growth factor-1 (IGF-1). The conditioned medium of hypoxic osteoblasts significantly enhance blood vessel formation (indirect angiogenesis), far in excess of hypoxia alone, via a primarily VEGF-dependent mechanism. Et-1 and IGF-1 from hypoxic endothelial cells cause osteoblasts to proliferate and differentiate and further enhance their angiogenic potential. In summary, this study describes a reciprocal regulatory and autoregulatory process that couples the mutually dependent processes of angiogenesis and osteogenesis and demonstrates that the hypoxia characteristic of healing bone is an integral mediator of this complex phenomenon.

Basement membranes are fundamental to tissue organization and physiology in all metazoans. The interaction between laminin and nidogen is crucial to the assembly of basement membranes. The structure of the interacting domains reveals a six-bladed Tyr-Trp-Thr-Asp (YWTD) beta-propeller domain in nidogen bound to laminin epidermal-growth-factor-like (LE) modules III3-5 in laminin (LE3-5). Laminin LE module 4 binds to an amphitheatre-shaped surface on the pseudo-6-fold axis of the beta-propeller, and LE module 3 binds over its rim. A Phe residue that shutters the water-filled central aperture of the beta-propeller, the rigidity of the amphitheatre, and high shape complementarity enable the construction of an evolutionarily conserved binding surface for LE4 of unprecedentedly high affinity for its small size. Hypermorphic mutations in the Wnt co-receptor LRP5 (refs 6-9) suggest that a similar YWTD beta-propeller interface is used to bind ligands that function in developmental pathways. A related interface, but shifted off-centre from the pseudo-6-fold axis and lacking the shutter over the central aperture, is used in the low-density lipoprotein receptor for an intramolecular interaction that is regulated by pH in receptor recycling.

Suspension-derived protoplasts of Agropyron elongatum irradiated by ultra-violet light (UV) were fused with the suspension-derived protoplasts of Triticum astivum using PEG. Fertile intergeneric somatic hybrid plants were produced and various hybrid lines have been selected and propagated in successive generations. Their hybrid nature was confirmed by analysis of profiles of isozymes, RAPDs, and 5S rDNA spacer sequences, and via GISH analysis. By the procedure described, the phenotype and chromosome number of wheat could be maintained besides transfer of a few chromosomes and chromosomal fragments from the donor A. elongatum. The results above indicated that highly asymmetric fertile hybrid plants and hybrid progenies of wheat were produced via somatic hybridization.

The inside-out signaling of integrins regulates the ligand-binding affinity of the cell surface receptors in response to changes in the environment for cell survival. The specific binding to the cytoplasmic tail of integrin's β subunit by the intracellular protein talin is the key step of inside-out signaling. A "pull-push" mechanism has been proposed to explain how the PIP2-enriched membrane disrupts the dual auto-inhibition of the N-terminal talin-FERM domain by the C-terminal talin-rod domain such that activated talin-FERM can reach the β-tail for integrin activation.

Background Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. Methods Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias. Results Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3−CD19+ cell subset (p p +, CD3+CD4+ and CD3−CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p −CD19+ cell subset (p p Conclusions The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3−CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes.

A single chromosome was microdissected from the metaphase chromosomes of soybean by using a glass needle. After two rounds of Sau3A linker-adaptor-mediated PCR, smear DNA fragments ranged from 0.3–2.5 kb were obtained. Southern hybridization showed that the PCR products from the dissected chromosome were homologous with the soybean genomic DNA. In situ hybridization of the chromosome PCR products to the mitotic metaphase spreads showed that the PCR products were hybridized to the soybean, but the chromosomal signals were not restricted to the microdissected chromosome. The second-round PCR products from the microdissected chromosome were cloned into plasmid vector to generate a chromosome-specific microclone library, which included approximately 200,000 recombinant clones. 178 randomly selected clones were estimated to range in size from 0.3∼1.8 kb, with an average size of 830 bp, of which approximately 44% were high/medium copy clones, while 56% were low/unique copy clones.

Background: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo. Methods: In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25 μg/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, BD IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity. Results: Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25 ± 4% vs. 100 ± 28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403 ± 28% vs. 100 ± 26% for controls), at a Taurolidine concentration of 25 μg/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3 ± 1 nodules in Group B animals vs. 649 ± 101 nodules in Group A animals). Conclusions: Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.

We have grown PrBa2Cu3O7−x (PBCO) thin films on (100) SrTiO3 substrates using pulsed laser deposition (PLD). X-ray diffraction (XRD) studies indicate that the orientation of PBCO films varied with increasing deposition temperature: b axis oriented films can be grown at 680°C, and a axis oriented films at the temperature between 692°C and 705°C. Atomic force microscopy (AFM) reveals that a good flatness of the films was obtained with surface mean roughness of less than 24 A, indicating that it is suitable for use as template layers in a axis oriented epitaxial YBa2Cu3O7−y/PBCO and YBCO/tetragonal–YBCO/PBCO multilayer structures.

Recognition by integrin proteins on the cell surface regulates the adhesive interactions between cells and their surroundings1,2. The structure of the 'I' domain that is found in some but not all integrins, has been determined3,4. However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1 (refs 5–7), are recognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobulin superfamily (IgSF), but they are recognized by an I domain-containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD 11 a/CD 18). Here we present the crystal structure of the extracellular region of ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is surrounded by a relatively flat recognition surface and lies in a β-strand, whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in protruding loops. This finding suggests that there are differences in the architecture of recognition sites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked glycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens.

Background Surgical intervention-related trauma contributes largely to the development of postoperative immunosuppression, with reduced resistance to secondary bacterial infection. This study compared the impact of laparotomy versus laparoscopy on macrophage-associated bactericidal ability and examined whether laparotomy renders the host more susceptible to microbial infection. Results BALB/c mice were randomized into control, laparotomy, and laparoscopy groups. Laparotomy, but not laparoscopy, significantly downregulated CR3 expression on macrophages, diminished macrophage-induced uptake and phagocytosis of E. coli and S. aureus, and impaired macrophage-mediated intracellular bacterial killing. Consistent with this, mice that underwent laparotomy displayed substantially higher bacterial counts in the blood and visceral organs as well as a significantly enhanced mortality rate following bacterial infection, whereas mice subjected to laparoscopy did not show any defects in their bacterial clearance. Conclusion Laparotomy has an adverse effect on host innate immunity against microbial infection by impairing macrophage-mediated phagocytosis and killing of the invaded bacteria. By contrast, laparoscopy appears to preserve macrophage-associated bactericidal ability, thus alleviating the development of postoperative immunosuppression.

The thermal curves and the enthalpy changes of the interaction between some oral sustained release preparations (Contac, Fenbid and Benza sustained release capsules) and physiological saline have been measured at 298.15 K with a MS-80 standard Calvet microcalorimeter. The curves that recorded the changes of heat effect with time have clearly shown the sustained release action and process of the above preparations. A method for examining the sustained release action of sustained release preparations can be developed from the above experiments. The principle of application and the experimental procedure of this method have been expounded, and some results of the above experiments have also been discussed.