Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia.

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

Scaling of the strange-metal scattering in unconventional superconductors.

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

The association of immune-related genes and the potential role of IL10 with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a severe immune-related disease that is characterized by biliary obstruction and cholestasis. The etiology of BA is unclear, our aim was to explore the relationship between biliary tract inflammation and immune-related genes. METHODS: We selected 14 SNPs in 13 immune-related genes and investigated their associations with BA by using a large case‒control cohort with a total of 503 cases and 1473 controls from southern China. RESULTS: SNP rs1518111 in interleukin10 (IL10) was identified as associated with BA (P = 5.79E-03; OR: 0.80; 95% CI: 0.68-0.94). The epistatic effects of the following pairwise interactions among these SNPs were associated with BA: signal transducer and activator of transcription 4 (STAT4) and chemokine (C-X-C motif) ligand 3 (CXCL3); STAT4 and damage-regulated autophagy modulator1 (DRAM1); CXCL3 and RAD51 paralog B (RAD51B); and interferon gamma (IFNG) and interleukin26 (IL26). Furthermore, we explored the potential role of IL-10 in the pathogenesis of the neonatal mouse model of BA. IL-10 effectively prevented biliary epithelial cell injury and biliary obstruction in murine BA as well as inhibit the activation of BA-related immune cells. CONCLUSIONS: In conclusion, this study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. IMPACT: This study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. This study could infer that IL-10 may play a protective role in BA mouse model. We found that four SNPs (rs7574865, rs352038, rs4622329, and rs4902562) have genetic interactions.

Conversion of senescent cartilage into a pro-chondrogenic microenvironment with antibody-functionalized copper sulfate nanoparticles for efficient osteoarthritis therapy.

The development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic •OH from H2O2 via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.

Equivalent magnitude-dependent discomfort under vertical vibration up to 100 Hz.

The effect of vibration magnitude on frequency-dependence of discomfort of human body is always overlooked with respect to the comfort equivalence contours, particularly for high-magnitude vibration in wideband frequency. In this study, the magnitude effect of vertical vibration on discomfort of human body is investigated experimentally. Nineteen male subjects are involved in the jury test of vibration discomfort in the vertical direction with 2-5 m/s2 in magnitude up to 100 Hz. It is shown that the growth rate of discomfort may exceed 1 due to the high-magnitude vibration employed. In this condition that the rate varies around 1, the Stevens' power law is not capable to properly represent the relationship between the subjective discomfort and the vibration magnitude. It means the equivalent comfort contours are not only dependent on the frequency range but also related to the vibration magnitude. Frequency weightings of vibration discomfort are influenced by the excitation magnitude. Practitioner summary: The occupant comfort to vertical whole-body vibration is affected by vibration magnitude. This study provides the effect of vibration magnitude on frequency-dependence of discomfort to whole-body vibration. It is suggested to propose variable frequency weightings for vibration discomfort evaluation under different magnitudes to achieve better comfort design.

Torque response of seated human body to sinusoidal lateral and roll dual-axis vibration.

The biodynamic response of 14 subjects to sinusoidal dual-axis vibration in lateral and roll directions is studied. The root mean square of human response is detected by measuring the torque at the seat pan. The effects of phase difference, magnitude, and frequency on the biodynamic responses are investigated. The consistency between human responses to dual-axis and single-axis is studied. With increasing phase difference, human response is found to reach the maximum when the vibrations are anti-phase and then decrease to the minimum when they are in-phase. Besides, the dominance of the lateral excitation is confirmed in the dual-axis vibration. Finally, the principle of equivalence between lateral-roll dual-axis vibration and roll single-axis vibration is established. With the equivalence method, the biodynamic characteristics of the human body to multi-axis vibration are expected to be measured and represented with a much simpler test and dynamic model.Practitioner summary: Proposed equivalence uses one index to evaluate the compound discomfort caused by the roll and lateral vibration. Overestimation of discomfort due by summing the effects of them calculated separately can be avoided. After the equivalence, evaluation of discomfort and modelling of the human body can be carried out only in roll direction.

CD177+ cells produce neutrophil extracellular traps that promote biliary atresia.

BACKGROUND & AIMS: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA. METHODS: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1+ (Ly6C/Ly6G+) cells in the liver. Gene expression profiles of CD177+ cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177-/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177+ cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA. RESULTS: Increased levels of Gr-1+ cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177-/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177+ cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177+ cell numbers and reactive oxygen species levels, indicating a potential beneficial effect. CONCLUSIONS: Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation. CLINICAL TRIAL REGISTRATION: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505). LAY SUMMARY: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect.

Loose Pre-Cross-Linking Mediating Cellulose Self-Assembly for 3D Printing Strong and Tough Biomimetic Scaffolds.

The lack of an effective printable ink preparation method and the usual mechanically weak performance obstruct the functional 3D printing hydrogel exploitation and application. Herein, we propose a gentle pre-cross-linking strategy to enable a loosely cross-linked cellulose network for simultaneously achieving favorable printability and a strong hydrogel network via mediating the cellulose self-assembly. A small amount of epichlorohydrin is applied to (i) slightly pre-cross-link the cellulose chains for forming the percolating network to regulate the rheological properties and (ii) form the loosely cross-linked points to mediate the cellulose chains' self-assembly for achieving superior mechanical properties. The fabrication of the complex 3D structures verifies the design flexibility. The printed cellulose hydrogels exhibit a biomimetic nanofibrous topology, remarkable tensile and compressive strength (5.22 and 11.80 MPa), as well as toughness (1.81 and 2.16 MJ/m3). As a demonstration, a bilayer scaffold (mimicking the osteochondral structure) consisting of a top pristine cellulose and a bottom cellulose/bioactive glass hydrogel is printed and exhibits superior osteochondral defect repair performance, showing a potential in tissue engineering. We anticipate that our loose pre-cross-linking 3D printing ink preparation concept can inspire the development of other polymeric inks and strong 3D printing functional hydrogels, eventually spreading the applications in diverse fields.

Conducting molybdenum sulfide/graphene oxide/polyvinyl alcohol nanocomposite hydrogel for repairing spinal cord injury.

A sort of composite hydrogel with good biocompatibility, suppleness, high conductivity, and anti-inflammatory activity based on polyvinyl alcohol (PVA) and molybdenum sulfide/graphene oxide (MoS2/GO) nanomaterial has been developed for spinal cord injury (SCI) restoration. The developed (MoS2/GO/PVA) hydrogel exhibits excellent mechanical properties, outstanding electronic conductivity, and inflammation attenuation activity. It can promote neural stem cells into neurons differentiation as well as inhibit the astrocytes development in vitro. In addition, the composite hydrogel shows a high anti-inflammatory effect. After implantation of the composite hydrogel in mice, it could activate the endogenous regeneration of the spinal cord and inhibit the activation of glial cells in the injured area, thus resulting in the recovery of locomotor function. Overall, our work provides a new sort of hydrogels for SCI reparation, which shows great promise for improving the dilemma in SCI therapy.

Identification and fine mapping of qGR6.2, a novel locus controlling rice seed germination under salt stress.

BACKGROUND: Rice growth is frequently affected by salinity. When exposed to high salinity, rice seed germination and seedling establishment are significantly inhibited. With the promotion of direct-seeding in Asia, improving rice seed germination under salt stress is crucial for breeding. RESULTS: In this study, an indica landrace Wujiaozhan (WJZ) was identified with high germinability under salt stress. A BC1F2 population derived from the crossing WJZ/Nip (japonica, Nipponbare)//Nip, was used to quantitative trait loci (QTL) mapping for the seed germination rate (GR) and germination index (GI) under H2O and 300 mM NaCl conditions. A total of 13 QTLs were identified, i.e. ten QTLs under H2O conditions and nine QTLs under salt conditions. Six QTLs, qGR6.1, qGR8.1, qGR8.2, qGR10.1, qGR10.2 and qGI10.1 were simultaneously identified under two conditions. Under salt conditions, three QTLs, qGR6.2, qGR10.1 and qGR10.2 for GR were identified at different time points during seed germination, which shared the same chromosomal region with qGI6.2, qGI10.1 and qGI10.2 for GI respectively. The qGR6.2 accounted for more than 20% of phenotypic variation under salt stress, as the major effective QTL. Furthermore, qGR6.2 was verified via the BC2F2 population and narrowed to a 65.9-kb region with eleven candidate genes predicted. Based on the microarray database, five candidate genes were found with high transcript abundances at the seed germination stage, of which LOC_Os06g10650 and LOC_Os06g10710 were differentially expressed after seed imbibition. RT-qPCR results showed the expression of LOC_Os06g10650 was significantly up-regulated in two parents with higher levels in WJZ than Nip during seed germination under salt conditions. Taken together, it suggests that LOC_Os06g10650, encoding tyrosine phosphatase family protein, might be the causal candidate gene for qGR6.2. CONCLUSIONS: In this study, we identified 13 QTLs from a landrace WJZ that confer seed germination traits under H2O and salt conditions. A major salt-tolerance-specific QTL qGR6.2 was fine mapped to a 65.9-kb region. Our results provide information on the genetic basis of improving rice seed germination under salt stress by marker-assisted selection (MAS).

Down-regulation of STAT3 enhanced chemokine expression and neutrophil recruitment in biliary atresia.

Biliary atresia (BA) is an immune-related disorder and signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule in inflammation. The present study was designed to clarify the function of STAT3 in BA. STAT3 expression was examined in patients and a mouse BA model in which STAT3 levels were further altered with a specific inhibitor or activator. Neutrophil accumulation and the levels of the neutrophil chemoattractants (C-X-C motif) ligand 1 (CXCL1) and IL-8 were determined. The effects of STAT3 inhibition on IL-8 expression were examined in human biliary epithelial cell (BEC) cultures. Functional changes in liver STAT3+ neutrophils in the mouse model were analysed with 10× single cell RNA-seq methods. Results showed STAT3 and p-STAT3 expression was reduced in BA liver tissue compared with control samples. Administration of a STAT3 inhibitor increased jaundice and mortality and reduced body weight in BA mice. In contrast, the STAT3 activator ameliorated BA symptoms. Extensive neutrophil accumulation together with CXCL1 up-regulation, both of which were suppressed by an anti-CXCL1 antibody, were observed in the STAT3 inhibitor-treated group. Recombinant IL-8 administration increased disease severity in BA mice, and the STAT3 activator had the reverse effect. Inhibiting STAT3 increased apoptosis of human BECs together with up-regulated IL-8 expression. RNA-seq analysis revealed reduced the numbers of STAT3 expressing neutrophil in BA which was accompanied by marked enhanced interferon-related antiviral activities. In conclusion, STAT3 reduction, enhanced IL-8 and CXCL1 expression and promoted the accumulation of interferon-responsive neutrophils resulting in BEC damage in BA.

Biodegradable mesoporous manganese carbonate nanocomposites for LED light-driven cancer therapy via enhancing photodynamic therapy and attenuating survivin expression.

Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2 and CO2 under H2O2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.

Ionic Liquid Gating Induced Protonation of Electron-Doped Cuprate Superconductors.

Ion injection controlled by electric field has attracted growing attention due to its tunability over bulk-like materials. Here, we achieve protonation of an electron-doped high-temperature superconductor, La2-xCexCuO4, by gating in the electrochemical regime of the ionic liquid. Such a process induces a superconductor-insulator transition together with the crossing of the Fermi surface reconstruction point. Applying negative voltages not only can reverse the protonation process but also recovers superconductivity in samples deteriorated by moisture in the ambient. Our work extends the application of electric-field-induced protonation into high-temperature cuprate superconductors.

The effect of single CNTs/GNPs and complexes on promoting the interfacial catalytic activity of lipase in conventional emulsions.

BACKGROUND: The interfacial activation mechanism of lipase enables it to exhibit high catalytic activity in water-in-oil (W/O) microemulsions. However, W/O microemulsions have obvious defects such as a small water pool and a large demand for surfactants. The present study investigated the substitutability of conventional oil-in-water (O/W) and W/O emulsions as lipase catalytic systems. Carbon nanotubes (CNTs)/gold nanoparticles (GNPs) or CNT-GNP electrostatically bonded complexes were added into the conventional emulsion system. RESULTS: The simulated biphasic system and fluorescence study showed different and even contradictory results for the interfacial behavior of CNTs and CNT-GNP complexes due to the variation of the dispersibility of CNTs in cetyltrimethylammonium bromide (CTAB). Results also showed that conventional O/W emulsions were more suitable for lipase catalysis than conventional W/O emulsions. When CNTs or CNTCATB -GNP complexes were added in a conventional O/W emulsion system, the catalytic activity of lipase was significantly promoted (up to 4.8-fold using CNTs and 3.5-fold using CNTCATB -GNP complexes compared with free lipase). CONCLUSIONS: The possible reason for this promotion may be due to the increase in the interface area. The current study was not only the latest exploration of lipase activity promotion via nanomaterials, but also explored a new lipase catalytic system and provides further insight into improving the catalytic performance of lipase in conventional emulsions. © 2020 Society of Chemical Industry.

The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus-Induced Biliary Atresia.

Activation of innate immunity together with cholangiocyte damage occurs in biliary atresia (BA). However, detailed information on the inflammatory cells involved is lacking. This study investigates both the pathophysiology of CD11b+Gr-1+ cells in a mouse model of BA and their presence in BA patients. CD11b+Gr-1+ cells were targeted by an anti-Ly6G antibody in murine BA induced by inoculation with rhesus rotavirus. Expression of the Ly6G homolog CD177+ was examined in biopsies from BA patients. The symptoms of BA were ameliorated, and survival was prolonged in those mice receiving 5 to 10 µg of antibody per mouse every 3 days for four times compared with the mice treated with virus alone. However, the mice later developed chronic BA with persistent low body weight and jaundice. Hepatic inflammatory cells were reduced compared with acute BA. Blockade of extrahepatic bile ducts occurred, whereas intrahepatic ductules were partially preserved, and a progressive increase in liver fibrosis was observed. High levels of CD11b+Gr-1+ cells were present in these mice. The administration of an anti-Ly6G antibody again in those chronic BA mice reduced jaundice and restored body weight. In BA patients CD177+ cells were highly expressed in the liver. Our data suggest that the chronic mouse BA model shares key characteristics with clinical BA and indicates the importance of CD11b+Gr-1+ cells in the initiation and progression of BA.

Actively Targeted Deep Tissue Imaging and Photothermal-Chemo Therapy of Breast Cancer by Antibody-Functionalized Drug-Loaded X-Ray-Responsive Bismuth Sulfide@Mesoporous Silica Core-Shell Nanoparticles.

A theranostic platform combining synergistic therapy and real-time imaging attracts enormous attention but still faces great challenges, such as tedious modifications and lack of efficient accumulation in tumor. Here, a novel type of theranostic agent, bismuth sulfide@mesoporous silica (Bi2S3@ mPS) core-shell nanoparticles (NPs), for targeted image-guided therapy of human epidermal growth factor receptor-2 (HER-2) positive breast cancer is developed. To generate such NPs, polyvinylpyrrolidone decorated rod-like Bi2S3 NPs are chemically encapsulated with a mesoporous silica (mPS) layer and loaded with an anticancer drug, doxorubicin. The resultant NPs are then chemically conjugated with trastuzumab (Tam, a monoclonal antibody targeting HER-2 overexpressed breast cancer cells) to form Tam-Bi2S3@mPS NPs. By in vitro and in vivo studies, it is demonstrated that the Tam-Bi2S3@mPS bear multiple desired features for cancer theranostics, including good biocompatibility and drug loading ability as well as precise and active tumor targeting and accumulation (with a bismuth content in tumor being ≈16 times that of nontargeted group). They can simultaneously serve both as an excellent contrast enhancement probe (due to the presence of strong X-ray-attenuating bismuth element) for computed tomography deep tissue tumor imaging and as a therapeutic agent to destruct tumors and prevent metastasis by synergistic photothermalchemo therapy.

Zero-Dimensional Carbon Dots Enhance Bone Regeneration, Osteosarcoma Ablation, and Clinical Bacterial Eradication.

Zero-dimensional carbon dots (CD) and their effects on osteogenesis have been rarely studied in bone repair scaffolds. Here, we fabricate a novel CD doped chitosan/nanohydroxyapatite (CS/nHA/CD) scaffold with full potential to promote bone regeneration by a facile freeze-drying method. The CS/nHA/CD scaffolds enhanced cell adhesion and osteoinductivity in rat bone mesenchymal stem cells by up-regulating genes involved in focal adhesion and osteogenesis in vitro, which significantly improved the formation of vascularized new bone tissue at 4 weeks compared to pure CS/nHA scaffolds in vivo. Inspired by the excellent photothermal effect of CD, the scaffolds were applied in tumor photothermal therapy (PTT) under near-infrared (NIR) irradiation (808 nm, 1 W/cm2). The scaffolds significantly inhibited osteosarcoma cell proliferation in vitro and effectively suppressed tumor growth in vivo. Moreover, the CS/nHA/CD scaffolds possessed distinct antibacterial properties toward clinically collected S. aureus and E. coli, and their antibacterial activity was further enhanced under NIR irradiation. This work demonstrates that zero-dimensional CD can enhance the osteogenesis-inducing property of bone repair scaffolds and that CD doped scaffolds have potential for use in PTT for tumors and infections.

Silver nanoparticle treatment ameliorates biliary atresia syndrome in rhesus rotavirus inoculated mice.

Biliary atresia (BA) is a neonatal biliary system disease closely associated with viral infection and bile duct inflammation. Silver nanoparticles (AgNps) have previously revealed antiviral and anti-inflammatory properties. In this study, we have investigated the effects of AgNps in the treatment of the Rhesus rotavirus inoculation induced BA in mice. The morphology, liver histopathology, clinical biochemistry examination, and inflammatory cells were analyzed in BA mice. Results indicated that AgNps could significantly increase the survival rate of BA mice, and reduce jaundice and weight lost and the liver enzymes and bilirubin metabolism clinical parameters were close to the normal levels. Diminished numbers of NK cells were observed by flow cytometry analysis and immunohistochemical staining. Furthermore, the viral load was reduced and transcripts for TGF-ß mRNA were augmented after AgNps treatment. Collectively, our results suggest that AgNps treatment has beneficial effects on the BA mouse model partially through upregulation of TGF-ß.

Kinematic characteristics of anterior cruciate ligament deficient knees with concomitant meniscus deficiency during ascending stairs.

It is commonly believed that a torn ACL or a damaged meniscus may be associated with altered knee joint movements. The purpose of this study was to measure the tibiofemoral kinematics of ACL deficiency with concomitant meniscus deficiency. Unilateral knees of 28 ACL deficient participants were studied while ascending stairs. Among these patients, 6 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), 8 had combined ACL and lateral meniscus injuries (group III) and 6 had combined ACL and medial-lateral meniscus injuries (group IV). Both knees were then scanned during a stair climb activity using single fluoroscopic image system. Knee kinematics were measured at 0°, 5°, 10°, 15°, 30° and 60° of flexion during ascending stairs. At 0°, 15° and 30° flexion of the knee, the tibia rotated externally by 13.9 ± 6.1°,13.8 ± 9.5° and 15.9 ± 9.8° in Group I. Group II and III exhibited decreased external rotation from 60° to full extension. Statistical differences were found in 0°, 15°and 30° of flexion for the 2 groups compared with Group I. In general, the tibia showed anterior translation with respect to the femur during ascending stairs. It was further determined that Group III had larger anterior translation compared with Group IV at 0° and 5° of flexion (-6.9 ± 1.7 mm vs. 6.2 ± 11.3 mm, P = 0.041; -9.0 ± 1.8 mm vs. 8.1 ± 13.4 mm, P = 0.044). During ascending stairs the ACL deficient knee with different deficiencies in the meniscus will show significantly different kinematics compared with that of uninjured contralateral knee. Considering the varying effect of meniscus injuries on knee joint kinematics, future studies should concentrate on specific treatment of patients with combined ACL and meniscus injuries to protect the joint from abnormal kinematics and subsequent postoperative degeneration.

DNL1, encodes cellulose synthase-like D4, is a major QTL for plant height and leaf width in rice (Oryza sativa L.).

To better understand the genetic of rice agronomic traits, we selected two different rice germplasms in phenotypes, Xian80 and Suyunuo, to construct genetic population for QTL analysis. A total of 25 QTLs for six traits were found in a 175 F2 population. Major QTLs, qPH12,qLW12.2, qLL12 and qGW12.1, explaining 50.00%, 57.08%, 15.41% and 22.51% phenotypic variation for plant height, leaf width, leaf length and grain width, respectively, were located on the same interval of chromosome 12 flanking SSR markers RM519 and RM1103. In consideration of the great effects on plant height and leaf width, the locus was named DNL1 (Dwarf and Narrowed Leaf 1). Using a segregating population derived from F2 heterozygous individuals, a total of 1363 dwarfism and narrowed-leaf individuals was selected for screening recombinants. By high-resolution linkage analysis in 141 recombination events, DNL1 was narrowed to a 62.39kb region of InDel markers ID12M28 and HF43. The results of ORF analysis in target region and nucleotide sequence alignment indicated that DNL1 encodes cellulose synthase-like D4 protein, and a single nucleotide substitution (C2488T) in dnl1 result in decrease in plant height and leaf width. Bioinformatical analysis demonstrated that a conserved role for OsCSLD4 in the regulation of plant growth and development. Expression analysis for OsCSLDs showed OsCSLD4 highly expressed in roots, while other CSLD members had comparatively lower expression levels. However, no clear evidence about CSLD4/DNL1 expression was associated with its function.