[Preliminary results of biportal endoscopic lumbar interbody fusion, decompression and pedicle screw insertion assisted with endoscopic technique for lumbar spinal stenosis combined with spondylolisthesis or instability].

Objectives: To evaluate the preliminary clinical outcomes of biportal endoscopic lumbar interbody fusion (BE-LIF), decompression and pedicle screw insertion assisted with endoscopic technique for lumbar spinal stenosis combined with spondylolisthesis or instability. Methods: The data of 9 patients with single-level lumbar spinal stenosis who underwent BE-LIF, decompression and pedicle screw insertion assisted with biportal endoscopy in Xinjiang Production and Construction Corps Hospital from March 1st 2022 to April 30th 2022 were analyzed retrospectively. The visual analogue scales (VAS) for pain in back and legs, and the Oswestry disability index (ODI) of all the patients were collected before operation, on the third day after operation and at the last follow-up. Moreover, the operation time, intra-operation blood loss, radiation shots for pedicle screw insertion, post-operation drainage and ambulation time were recorded. The screw position was checked with CT after the operation. Results: All the patients were female with a mean age of (70.3±8.4) years (ranged 56-84 years); the patients were followed-up for 12-16 weeks. All 9 patients had good clinical results. The VAS scores for back pain on the third day after operation and at the last follow-up were both significantly lower than that preoperatively[(2.9±0.6), (1.8±0.4) vs (6.4±1.1) points, both P<0.05]. The VAS scores for leg pain on the third day after operation and at the last follow-up were both significantly lower than that preoperatively[(1.9±0.3), (1.4±0.5) vs (7.3±1.6) points, P<0.05]. The ODI scores at last follow-up was significantly lower than that before the operation ((24.0%±6.5% vs 55.7%±12.8%, P<0.05). The intra-operative blood loss was (177±103) ml, the drainage amounts post-operation was (122±56) ml, the operation time was (207.8±32.7)min, the ambulation time was (2.3±0.5) days. The total radiation shots for pedicle screw insertion were 20-42 times, the average radiation shots per screw was (6.9±1.5) times. No severe complications or adverse events occurred. No nerve root injury or dural tear occurred in the operation, and no revision surgery needed. Conclusions: The pedicle screw insertion assisted with biportal endoscopic technique can decrease the radiation exposure with good feasibility and safety during the BE-LIF. The BE-LIF combined with the pedicle screw insertion assisted with biportal endoscopy is an effective and safe surgery for lumbar spinal stenosis with good early results.

[Progression and clinical application in unilateral biportal endoscopic].

With the advantages of less operative injury and quicker postoperative recovery time, percutaneous endoscopic spine surgery system is currently one of the most widely used minimal invasive spine surgery techniques in China. However, this technique usually requires surgeon to operate in a single cannula, which brings much inconvenience such as limited vision, small range of motion and low efficiency. Meanwhile, the increasingly popular technique of unilateral biportal endoscopic (UBE) surgery possesses the advantages of better operation visual field, more flexible in operation, shorter learning curve period, handier surgical instruments for spine surgeon, and minimize radiation dosage caused by intraoperative fluoroscopy when comparing with single cannula endoscopic technique, since UBE requires an additional portal for surgical instruments while the anther portal is placed for arthroscope and pressure pump irrigation system. This technique has been applied to the treatment of degenerative diseases of cervical and lumbar spine, facet cyst, spinal epidural lipomatosis and abscess, and has achieved satisfactory clinical results.

High-velocity projectile impact induced 9R phase in ultrafine-grained aluminium.

Aluminium typically deforms via full dislocations due to its high stacking fault energy. Twinning in aluminium, although difficult, may occur at low temperature and high strain rate. However, the 9R phase rarely occurs in aluminium simply because of its giant stacking fault energy. Here, by using a laser-induced projectile impact testing technique, we discover a deformation-induced 9R phase with tens of nm in width in ultrafine-grained aluminium with an average grain size of 140 nm, as confirmed by extensive post-impact microscopy analyses. The stability of the 9R phase is related to the existence of sessile Frank loops. Molecular dynamics simulations reveal the formation mechanisms of the 9R phase in aluminium. This study sheds lights on a deformation mechanism in metals with high stacking fault energies.

Measurement of Heavy Ion Irradiation Induced In-Plane Strain in Patterned Face-Centered-Cubic Metal Films: An in Situ Study.

Nanocrystalline Ag, Cu, and Ni thin films and their coarse grained counterparts are patterned using focused ion beam and then irradiated by Kr ions within an electron microscope at room temperature. Irradiation induced in-plane strain of the films is measured by tracking the location of nanosized holes. The magnitude of the strain in all specimens is linearly dose-dependent and the strain rates of nanocrystalline metals are significantly greater as compared to that of the coarse grained metals. Real-time microscopic observation suggests that substantial grain boundary migration and grain rotation are responsible for the significant in-plane strain.

What determines the interfacial configuration of Nb/Al2O3 and Nb/MgO interface.

Nb films are deposited on single crystal Al2O3 (110) and MgO(111) substrates by e-beam evaporation technique. Structure of Nb films and orientation relationships (ORs) of Nb/Al2O3 and Nb/MgO interface are studied and compared by the combination of experiments and simulations. The experiments show that the Nb films obtain strong (110) texture, and the Nb film on Al2O3(110) substrate shows a higher crystalline quality than that on MgO(111) substrate. First principle calculations show that both the lattice mismatch and the strength of interface bonding play major roles in determining the crystalline perfection of Nb films and ORs between Nb films and single crystal ceramic substrates. The fundamental mechanisms for forming the interfacial configuration in terms of the lattice mismatch and the strength of interface bonding are discussed.

Extraordinary light absorptance in graphene superlattices.

Extraordinary absorption decrease in graphene superlattices in the visible range is presented. Due to competition between loss and resonant reflection at resonance, the absorption displays non-monotonic behavior. As the period number increases above a certain critical value, absorption decreases with the increase in the period number. This is in contrast to ordinary absorption for a non-resonant condition, which monotonically increases with the period number. Moreover, this extraordinary property can also be controlled by applying a gate voltage to graphene sheets. The results provide not only a new understanding of graphene physics but also an application in nanophotonics and optoelectronics.

Damage-tolerant nanotwinned metals with nanovoids under radiation environments.

Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from high density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials.

In situ study of defect migration kinetics and self-healing of twin boundaries in heavy ion irradiated nanotwinned metals.

High energy particles introduce severe radiation damage in metallic materials, such as Ag. Here we report on the study on twin boundary (TB) affected zone in irradiated nanotwinned Ag wherein time accumulative defect density and defect diffusivity are substantially different from those in twin interior. In situ studies also reveal surprising resilience and self-healing of TBs in response to radiation. This study provides further support for the design of radiation-tolerant nanotwinned metallic materials.

Removal of stacking-fault tetrahedra by twin boundaries in nanotwinned metals.

Stacking-fault tetrahedra are detrimental defects in neutron- or proton-irradiated structural metals with face-centered cubic structures. Their removal is very challenging and typically requires annealing at very high temperatures, incorporation of interstitials or interaction with mobile dislocations. Here we present an alternative solution to remove stacking-fault tetrahedra discovered during room temperature, in situ Kr ion irradiation of epitaxial nanotwinned Ag with an average twin spacing of ~8 nm. A large number of stacking-fault tetrahedra were removed during their interactions with abundant coherent twin boundaries. Consequently the density of stacking-fault tetrahedra in irradiated nanotwinned Ag was much lower than that in its bulk counterpart. Two fundamental interaction mechanisms were identified, and compared with predictions by molecular dynamics simulations. In situ studies also revealed a new phenomenon: radiation-induced frequent migration of coherent and incoherent twin boundaries. Potential migration mechanisms are discussed.

Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.

AIMS/HYPOTHESIS: Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations. METHODS: We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotype-based promoter activity assays and the gel electrophoretic mobility shift assay. RESULTS: The -420G and the -537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (-537A and -420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the -420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects. CONCLUSIONS/INTERPRETATION: Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.

Role of the CC chemokine receptor 9/TECK interaction in apoptosis.

Chemokine receptors are members of the G protein coupled receptor (GPCR) supergene family whose expression is highly restricted to hematopoietic cells. Although the primary role of chemokine and chemokine receptor interaction is believed to be regulation of chemotaxis of leukocytes, subsequent information clearly suggests that multiple immune regulatory functions are attributed to chemokine receptor signaling. We recently showed that activation of the CC chemokine 9 receptor (CCR9), a thymus-specific chemokine receptor, led to potent cFLIP(L)-independent resistance to cycloheximide-induced apoptosis and modest resistance to Fas-mediated apoptosis possibly via activation of multiple signaling components involving Akt and glycogen synthase kinase 3beta. The fact that these two apoptotic signals involve activation of similar arrays of death execution machinery such as caspase-8, caspase-9, or caspase-3, suggests that chemokine receptor signaling may provide a wide range of antiapoptotic activities to hematopoietic cells under certain biological conditions. GPCR is a large family of cell surface receptors, many of which are critically involved in hormonal and behavioral control. Recent observations also suggest that GPCR signaling plays a pivotal role in immune cell activation. Heterotrimeric G protein is an integral part of GPCR signaling. Thus, dissection of signaling components involved in the CCR9-mediated antiapoptosis could be a framework for cell survival mechanisms and may provide options for therapeutic interventions for neurdegenerative diseases or T cell malfunctioning.

Blocking of c-FLIP(L)--independent cycloheximide-induced apoptosis or Fas-mediated apoptosis by the CC chemokine receptor 9/TECK interaction.

Chemokines play a pivotal role in regulating leukocyte migration as well as other biological functions. CC chemokine receptor 9 (CCR9) is a specific receptor for thymus-expressed CC chemokine (TECK). It is shown here that engagement of CCR9 with TECK leads to phosphorylation of Akt (protein kinase B), mitogen-activated protein kinases (MAPKs), glycogen synthase kinase--3 beta (GSK-3 beta), and a forkhead transcription factor, FKHR, in a human T-cell line, MOLT4, that naturally expresses CCR9. By means of chemical inhibitors, it is shown that phosphoinositide-3 kinase (PI-3 kinase), but not MAPK, is required for CCR9-mediated chemotaxis. Akt, GSK-3 beta, FKHR, and MAPK have been previously implicated in cell survival signals in response to an array of death stimuli. When MOLT4 cells, which expressed Fas as well as CXCR4, were stimulated with cycloheximide (CHX), an agonistic anti-Fas antibody, or a combination of these, the cells rapidly underwent apoptosis. However, costimulation of MOLT4 cells with TECK or stromal derived factor--1 significantly blocked CHX-mediated apoptosis, whereas stimulation only with TECK partially blocked Fas-mediated apoptosis. Concomitant with this blocking, cleavage of poly (adenosine 5'-diphosphate--ribose) polymerase and activation of caspase 3 were significantly attenuated, but the expression level of FLICE inhibitory protein c-FLIP(L), which had been shown to be regulated by CHX, was unchanged. This demonstrates that activation of CCR9 leads to phosphorylation of GSK-3 beta and FKHR and provides a cell survival signal to the receptor expressing cells against CHX. It also suggests the existence of a novel pathway leading to CHX-induced apoptosis independently of c-FLIP(L). (Blood. 2001;98:925-933)

The seventh transmembrane domain of cc chemokine receptor 5 is critical for MIP-1beta binding and receptor activation: role of MET 287.

CC chemokine receptor 5 (CCR5) is a high-affinity receptor for macrophage inflammatory protein (MIP)-1beta and functions as the major coreceptor for entry of macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1). To evaluate the role of transmembrane domains (TM) in the receptor function of CCR5, the seventh transmembrane domain (TM7) was examined in a series of chimeric receptor constructs including CCR5TM (CCR5 backbone/CCR5 TM7 replaced with CCR1 TM7) and mutants of CCR5TM. The CCR5TM chimera exhibited a dramatic reduction in receptor activation, as well as little or no MIP-1beta binding. Further mutational analysis revealed that Met 287 in TM7 of CCR5 is a critical molecular determinant for both MIP-1beta binding and receptor activation. Interestingly, all of the chimeric/mutated receptors were biologically active in an HIV-1 coreceptor fusion assay, demonstrating that chemokine binding is independent of HIV-1 coreceptor activity.

SIMPL is a tumor necrosis factor-specific regulator of nuclear factor-kappaB activity.

The IL-1 receptor-associated kinase (IRAK/mPLK) is linked to the regulation of nuclear factor-kappaB (NF-kappaB)-dependent gene expression. Here we describe a novel binding partner of IRAK/mPLK that we term SIMPL (signaling molecule that associates with the mouse pelle-like kinase). Overexpression of SIMPL leads to the activation of NF-kappaB-dependent promoters, and inactivation of SIMPL inhibits IRAK/mPLK as well as tumor necrosis factor receptor type I-induced NF-kappaB activity. Dominant inhibitory alleles of IkappaB kinase (IKKalpha or IKKbeta) block the activation of NF-kappaB by IRAK/mPLK and SIMPL. Furthermore, SIMPL binds IRAK/mPLK and the IKKs in vitro and in vivo. In the presence of antisense mRNA to SIMPL, the physical association between IRAK/mPLK and IKKbeta but not IRAK/mPLK and IKKalpha is greatly diminished. Moreover, dominant-negative SIMPL blocks IKKalpha- or IKKbeta-induced NF-kappaB activity. These results lead us to propose a model in which SIMPL functions to regulate NF-kappaB activity by linking IRAK/mPLK to IKKbeta/alpha-containing complexes.

Thymus size and its relationship to perinatal events.

A retrospective study was conducted to assess radiographically the thymus size in well and sick neonates and to search for a possible relationship to perinatal events. Thymus size was expressed as cardiothymic:thoracic ratio (CT/T) by measuring the width of the cardiothymic shadow at the level of carina and dividing it by the width of the thorax at the costophrenic angles. The CT/T was measured on chest radiographs obtained on day 1 in well term neonates consecutively born in our nursery and sick neonates with meconium staining of the amniotic fluid, meconium aspiration syndrome or respiratory distress syndrome (RDS). Neonates with congenital anomalies, congenital heart disease or intrauterine growth retardation were excluded. There were no significant relationships between CT/T and sex, birth route, birthweight or gestational age in well and sick term neonates. The CT/T were comparable among well and sick term neonates and were significantly greater in the preterm neonates with RDS than in the preterm neonates without RDS. The CT/T was correlated to the birth route only in the preterm neonates. We conclude that thymus involution in the perinatal period is a complex process and the response is different between term and preterm neonates.

A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis.

TR6 (decoy receptor 3 (DcR3)) is a new member of the tumor necrosis factor receptor (TNFR) family. TR6 mRNA is expressed in lung tissues and colon adenocarcinoma, SW480. In addition, the expression of TR6 mRNA was shown in the endothelial cell line and induced by phorbol 12-myristate 13-acetate/ionomycin in Jurkat T leukemia cells. The open reading frame of TR6 encodes 300 amino acids with a 29-residue signal sequence but no transmembrane region. Using histidine-tagged recombinant TR6, we screened soluble forms of TNF-ligand proteins with immunoprecipitation. Here, we demonstrate that TR6 specifically binds two cellular ligands, LIGHT (herpes virus entry mediator (HVEM)-L) and Fas ligand (FasL/CD95L). These bindings were confirmed with HEK 293 EBNA cells transfected with LIGHT cDNA by flow cytometry. TR6 inhibited LIGHT-induced cytotoxicity in HT29 cells. It has been shown that LIGHT triggers apoptosis of various tumor cells including HT29 cells that express both lymphotoxin beta receptor (LTbetaR) and HVEM/TR2 receptors. Our data suggest that TR6 inhibits the interactions of LIGHT with HVEM/TR2 and LTbetaR, thereby suppressing LIGHT- mediated HT29 cell death. Thus, TR6 may play a regulatory role for suppressing in FasL- and LIGHT-mediated cell death.

Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand.

Among members of the tumor necrosis factor receptor (TNFR) superfamily, 4-1BB, CD27, and glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) share a striking homology in the cytoplasmic domain. Here we report the identification of a new member, activation-inducible TNFR family member (AITR), which belongs to this subfamily, and its ligand. The receptor is expressed in lymph node and peripheral blood leukocytes, and its expression is up-regulated in human peripheral mononuclear cells mainly after stimulation with anti-CD3/CD28 monoclonal antibodies or phorbol 12-myristate 13-acetate/ionomycin. AITR associates with TRAF1 (TNF receptor-associated factor 1), TRAF2, and TRAF3, and induces nuclear factor (NF)-kappaB activation via TRAF2. The ligand for AITR (AITRL) was found to be an undescribed member of the TNF family, which is expressed in endothelial cells. Thus, AITR and AITRL seem to be important for interactions between activated T lymphocytes and endothelial cells.