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Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls. Several differences in the concentration of amino acids were observed in AD patients compared to both healthy controls and VD patients. However, no significant distinction was found between healthy controls and VD patients. Considering comorbidities, cystine levels were higher in AD than in VD among non-diabetic patients, but not in those with diabetes. Notably, creatine, spermidine, cystine, and tyrosine demonstrated favorable results in decision curve analyses and good discriminative performances, suggesting their potential for clinical application. These fundings give novel perspectives of serum amino acids for predicting metabolic pathways in AD and VD pathogenesis., Competing Interests: Declarations. Ethical approval: Approval was obtained from the ethics committee of the Ethics Committee of Anhui Medical University, Hefei Hospital Affiliated to Anhui Medical University and the First Affiliated Hospital of Soochow University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

An in-depth understanding of the soil nutrient status and balance relationship can help the effective recovery and management of alpine degraded meadows. In order to study the balance relationship among soil carbon, nitrogen, and phosphorus nutrients during the heavy degradation stage of meadows, field sampling and investigation, indoor analysis, and mathematical statistics were used to explore the characteristics and driving factors of changes in soil carbon, nitrogen, and phosphorus content, storage, and ecological stoichiometry during the heavy degradation stage of alpine meadows in the Sanjiangyuan region. The results showed that in the heavy degradation stage, miscellaneous grass plants occupied absolute dominance, soil C∶N∶P was approximately 32.83∶3.87∶0.67, and there was certain nitrogen limitation. The coefficients of variation of soil carbon, nitrogen, and phosphorus content were in the following order： organic carbon （1.09） > total nitrogen （0.63） > total phosphorus （0.29）. The organic carbon content and the carbon and nitrogen ratio showed a significant linear decreasing trend with the increase in the grassland degradation index （GDI）, while the total phosphorus content and organic carbon storage showed a significant non-linear change, in which the total phosphorus content showed a significant gentle U-shaped distribution, and the organic carbon storage decreased more gently at the beginning of the heavy degradation stage and then decreased sharply when the GDI was 57.9. The results of Mantel correlation analysis showed that the soil carbon to nitrogen ratio, carbon to phosphorus ratio, and nitrogen to phosphorus ratio showed significant correlation with organic carbon content and storage and total nitrogen storage. The results of structural equation modeling indicated that soil water content had direct effects as well as indirect through vegetation factors, soil carbon, nitrogen, and phosphorus ecological stoichiometry ratios, and soil water content and vegetation factors （height, cover, and biomass） were key environmental factors affecting soil ecological stoichiometry. The research results can provide scientific basis and practical guidance for the restoration of heavily degraded grassland in alpine meadows.

In a recent paper (ChemPhysChem, 2023, 24, e202200947), based on the results computed using DFT method, the perfect core-shell octahedral configuration Be@B 38 and Zn@B 38 was reported to be the global minima of the MB 38 (M=Be and Zn) clusters. However, this paper presents the lower energy structures of MB 38 (M=Be and Zn) clusters as a quasi-planar configuration, the Be atom is found to reside on the convex surface of the quasi-planar B 38 isomer, while the Zn atom tends to be attached to the top three B atoms of the quasi-planar B 38 isomer. Our results show that quasi-planar MB 38 (M=Be and Zn) at DFT method have lower energy than core-shell octahedral configuration M@B 38 (M=Be and Zn). Natural atomic charges, valence electron density, electron localization function (ELF) analyses identify the MB 38 (M=Be and Zn) to be charge transfer complexes (Be 2+ B 38 2- and Zn 1+ B 38 1- ) and suggest primarily the electrostatic interactions between doped atom and B 38 fragment. The photoelectron spectra of the corresponding anionic structures were simulated, providing theoretical basis for future structural identification., (© 2024 Wiley-VCH GmbH.)

To clarify the regulating effect of vegetation and soil factors on microbial communities in the alpine steppe under degradation on the Qinghai-Xizang Plateau, the alpine steppe in the Sanjiangyuan area of the Qinghai-Tibet Plateau was chosen. We analyzed the differences in vegetation and soil factors in different stages of degradation （non-degradation, moderate degradation, and severe degradation） and detected the variations in microbial community characteristics in the alpine steppe under different degradation stages using high-throughput sequencing technology. Eventually, redundancy analysis （RDA） and multiple regression matrixes （MRM） based on the similarity or dissimilarity matrix were used to identify key environmental factors regulating microbial （bacterial and fungal） community changes under degradation. The results showed that the degradation of the alpine steppe significantly changed the community coverage, height, biomass, and important value of graminae； significantly reduced the contents of soil organic matter, total nitrogen, total phosphorus, and silt； and increased the soil bulk density and sand content. Degradation did not change the composition of bacteria and fungi, but their composition proportions changed and also resulted in the loss of microbial richness （Chao1 index and Richness index） but did not significantly change the microbial diversity （Shannon index）. With the occurrence of degradation, the vegetation characteristics, soil physicochemical properties, and microbial diversity showed a consistent change trend. Combined with the characteristics of the network topology changes （the number of nodes and clustering coefficient significantly decreased）, it was found that degradation of the alpine steppe led to the decline of interspecies interactions, decentralization of network, and homogenization of microorganisms, but the cooperation relations among the species were maintained （positive correlation connections accounted for more than 90% in all degradation stages）. Under the alpine steppe degradation, the vegetation-soil interaction had the greatest effect on soil bacterial community, whereas soil physicochemical properties had the greatest influence on soil fungal community. Specifically, vegetation community height, biomass, and soil bulk density were the mutual factors regulating soil microorganisms, whereas the vegetation Simpson index, important value of graminae, soil total phosphorus, total potassium, and silt content were the unique factors affecting the soil bacterial community, and soil pH and total nitrogen content were the particular factors affecting the soil fungal community.

Background: Microglia-mediated neuroinflammation in Alzheimer's disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD., Methods: Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining., Results: A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD., Conclusions: The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD., (© 2024. The Author(s).)

A new kind of nonmetallic atom-doped boron cluster is described herein theoretically. When a phosphorus atom is added to the B 12 motif and loses an electron, a novel B 12 cage is obtained, composed of two B 3 rings at both ends and one B 6 ring in the middle, forming a triangular bifrustum. Interestingly, this B 12 cage is formed by three B 7 units joined together from three directions at an angle of 120°. When two P atoms are added to the B 12 motif, this novel B 12 cage is also obtained, and two P atoms are attached to the B 3 rings at both ends of the triangular bifrustum, forming a triangular bipyramid (Johnson solid). Amazingly, the global minimums of neutral, monocationic, and monoanionic P 2 B 12 +/0/- have the same cage structure with a D 3 h symmetry; this is the smallest boron cage with the same structure. The P atom has five valence electrons, according to adaptive natural density partitioning bonding analyses of cage PB 12 + and P 2 B 12 , in addition to one lone pair, the other three electrons of the P atom combine with an electron of each B atom on the B 3 ring to form three 2c-2e σ bonds and form three electron sharing bonds with B atoms through covalent interactions, stabilizing the B 12 cage. The calculated photoelectron spectra can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of P n B 12 - ( n = 1-2)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

We present a theoretical study of structural evolution, electronic properties, and photoelectron spectra of two sulfur atom-doped boron clusters S 2 B n 0/- ( n = 2-13), which reveal that the global minima of the S 2 B n 0/- ( n = 2-13) clusters show an evolution from a linear-chain structure to a planar or quasi-planar structure. Some S-doped boron clusters have the skeleton of corresponding pure boron clusters; however, the addition of two sulfur atoms modified and improved some of the pure boron cluster structures. Boron is electron-deficient and boron clusters do not form linear chains. Here, two sulfur atom doping can adjust the pure boron clusters to a linear-chain structure (S 2 B 2 0/- , S 2 B 3 0/- , and S 2 B 4 - ), a quasi-linear-chain structure (S 2 B 6 - ), single- and double-chain structures (S 2 B 6 and S 2 B 9 - ), and double-chain structures (S 2 B 5 , and S 2 B 9 ). In particular, the smallest linear-chain boron clusters S 2 B 2 0/- are shown with an S atom attached to each end of B 2 . The S 2 B 2 cluster possesses the largest highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap of 5.57 eV and the S 2 B 2 - cluster possesses the largest average binding energy E b of 5.63 eV, which shows the superior chemical stability and relative stability, respectively. Interestingly, two S-atom doping can adjust the quasi-planar pure boron clusters (B 7 - , B 10 - , and B 12 0/- ) to a perfect planar structure. AdNDP bonding analyses reveal that linear S 2 B 3 and planar SeB 11 - have π aromaticity and σ antiaromaticity; however, S 2 B 2 , planar S 2 B 6 , and planar S 2 B 7 - clusters have π antiaromaticity and σ aromaticity. Furthermore, AdNDP bonding analyses reveal that planar S 2 B 4 , S 2 B 10 , and S 2 B 12 clusters are doubly (π and σ) aromatic, whereas S 2 B 5 - , S 2 B 8 , S 2 B 9 - , and S 2 B 13 - clusters are doubly (π and σ) antiaromatic. The electron localization function (ELF) analysis shows that S 2 B n 0/- ( n = 2-13) clusters have different electron delocalization characteristics, and the spin density analysis shows that the open-shell clusters have different characteristics of electron spin distribution. The calculated photoelectron spectra indicate that S 2 B n - ( n = 2-13) have different characteristic peaks that can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of these doped boron clusters. Our work enriches the new database of geometrical structures of doped boron clusters, provides new examples of aromaticity for doped boron clusters, and is promising to offer new ideas for nanomaterials and nanodevices., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A theoretical research of structural evolution, electronic properties, and photoelectron spectra of selenium-doped boron clusters SeB n 0/- (n = 3-16) is performed using particle swarm optimization (CALYPSO) software in combination with density functional theory calculations. The lowest energy structures of SeB n 0/- (n = 3-16) clusters tend to form quasi-planar or planar structures. Some selenium-doped boron clusters keep a skeleton of the corresponding pure boron clusters; however, the addition of a Se atom modified and improved some of the pure boron cluster structures. In particular, the Se atoms of SeB 7 - , SeB 8 - , SeB 10 - , and SeB 12 - are connected to the pure quasi-planar B 7 - , B 8 - , B 10 - , and B 12 - clusters, which leads to planar SeB 7 - , SeB 8 - , SeB 10 - , and SeB 12 - , respectively. Interestingly, the lowest energy structure of SeB 9 - is a three-dimensional mushroom-shaped structure, and the SeB 9 - cluster displays the largest HOMO-LUMO gap of 5.08 eV, which shows the superior chemical stability. Adaptive natural density partitioning (AdNDP) bonding analysis reveals that SeB 8 is doubly aromatic, with 6 delocalized π electrons and 6 delocalized σ electrons, whereas SeB 9 - is doubly antiaromatic, with 4 delocalized π electrons and 12 delocalized σ electrons. Similarly, quasi-planar SeB 12 is doubly aromatic, with 6 delocalized π electrons and 14 delocalized σ electrons. The electron localization function (ELF) analysis shows that SeB n 0/- (n = 3-16) clusters have different local electron delocalization and whole electron delocalization effects. The simulated photoelectron spectra of SeB n - (n = 3-16) have different characteristic bands that can identify and confirm SeB n - (n = 3-16) combined with future experimental photoelectron spectra. Our research enriches the geometrical structures of small doped boron clusters and can offer insight for boron-based nanomaterials.

Here, the ground-state structures, electronic structures, polarizability, and spectral properties of metal-free phthalocyanine (H 2 Pc) under different external electric fields (EEFs) are investigated. The results show that EEF has an ultrastrong regulation effect on various aspects of H 2 Pc; the geometric structures, electronic properties, polarizability, and spectral properties are strongly sensitive to the EEF. In particular, an EEF of 0.025 a.u. is an important control point: an EEF of 0.025 a.u. will bend the benzene ring subunits to the positive and negative x directions of the planar molecule. Flipping the EEF from positive (0.025 a.u.) to negative (-0.025 a.u.) flips also the bending direction of benzene ring subunits. The H 2 Pc shows different dipole moments projecting an opposite direction along the x direction (-84 and 84 Debye for EEFs of -0.025 and 0.025 a.u., respectively) under negative and positive EEF, revealing a significant dipole moment transformation. Furthermore, when the EEF is removed, the molecule can be restored to the planar structure. The transformation of the H 2 Pc structure can be induced by the EEF, which has potential applications in the molecular devices such as molecular switches or molecular forceps. EEF lowers total energy and reduces highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap; especially, an EEF of 0.025 a.u. can reduce the HOMO-LUMO gap from 2.1 eV (in the absence of EEF) to 0.37 eV, and thus, it can enhance the molecular conductivity. The first hyperpolarizability of H 2 Pc is 0 in the absence of EEF; remarkably, an EEF of 0.025 a.u. can enhance the first hyperpolarizability up to 15,578 a.u. Therefore, H 2 Pc under the EEF could be introduced as a promising innovative nonlinear optical (NLO) nanomaterial such as NLO switches. The strong EEF (0.025 a.u.) causes a large number of new absorption peaks in IR and Raman spectra and causes the redshift of electronic absorption spectra. The changes of EEF can be used to regulate the structure transformation and properties of H 2 Pc, which can promote the application of H 2 Pc in nanometer fields such as molecular devices., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Genomic instability is a key cancer indicator. It results from defects in the DNA damage response (DDR) and increased replication stress. Herein, we examined how ataxia-telangiectasia mutated interactor (ATMIN), a DDR pathway involved in mismatch repair-proficient (microsatellite stability [MSS]), acts in colorectal carcinoma (CRC). Firstly, ATMIN mRNA expression was detected in CRC specimens with MSS characteristics, and the effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were gauged in MSS cell lines. To understand the molecular mechanism, co-immunoprecipitation analyses in vitro were employed. Interestingly, ATMIN expression was positively correlated with advanced stages ( P < .001), lymph node metastases ( P = .002), and deeper invasion ( P = .037) in MSS tumors; and significantly changed the cell motility in vitro. In the high-throughput analysis, ATMIN was found to act on the Wnt signaling pathway via PARP1. PAPR1 inhibition, in turn, significantly decreased invasion abilities resulting from ATMIN overexpression in cancer cell. Taken together, ATMIN, which alters the Wnt signaling pathway regulating CRC progression, plays as a crucial prognostic factor in MSS tumors., Competing Interests: None., (AJCR Copyright © 2022.)

A theoretical study of geometrical structures, electronic properties, and spectral properties of single-atom transition metal-doped boron clusters MB 24 - (M = Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) is performed using the CALYPSO approach for the global minimum search, followed by density functional theory calculations. The global minima obtained for the MB 24 - (M = Sc, Ti, V, and Cr) clusters correspond to cage structures, and the MB 24 - (M = Mn, Fe, and Co) clusters have similar distorted four-ring tubes with six boron atoms each. Interestingly, the global minima obtained for the NiB 24 - cluster tend to a quasi-planar structure. Charge population analyses and valence electron density analyses reveal that almost one electron on the transition-metal atoms transfers to the boron atoms. The electron localization function (ELF) of MB 24 - (M = Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) indicates that the local delocalization of MB 24 - (M = Sc, Ti, V, Cr, and Ni) is weaker than that of MB 24 - (M = Mn, Fe, and Co), and there is no obvious covalent bond between doped metal and B atoms. The spin density and spin population analyses reveal that open-shell MB 24 - (M = Ti, Cr, Fe, and Ni) has different spin characteristics which are expected to lead to interesting magnetic properties and potential applications in molecular devices. The polarizability of MB 24 - (M = Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) shows that MB 24 - (M = Mn, Fe, and Co) has larger first hyperpolarizability, indicating that MB 24 - (M = Mn, Fe, and Co) has a strong nonlinear optical response. Hence, MB 24 - (M = Mn, Fe, and Co) might be considered as a promising nonlinear optical boron-based nanomaterial. The calculated spectra indicate that MB 24 - (M = Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) has different and meaningful characteristic peaks that can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of these single-atom transition metal-doped boron clusters. Our work enriches the database of geometrical structures of doped boron clusters and can provide an insight into new doped boron clusters., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Constant DNA damage occurs in cells, and the cells are programmed to respond constitutively. This study explored the roles of ataxia-telangiectasia mutated interactor (ATMIN), one of the impaired pathways involving the DNA damage response (DDR) in mismatch repair-deficient [microsatellite instability (MSI)-high] colorectal carcinoma (CRC)., Methods: Expression of ATMIN messenger RNA (mRNA) was detected in CRC specimens with microsatellite instability (MSI) characteristics. The effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were evaluated in MSI-high cell lines, and liver metastasis ability was investigated in vivo. Protein-protein interactions were assessed by coimmunoprecipitation analyses in vitro., Results: Decreased ATMIN expression was positively correlated with advanced stage of disease (P < 0.05), lymph node metastases (P < 0.05), and deeper invasion (P < 0.05) in MSI-high tumors. Transient or stable ATMIN knockdown significantly increased cell motility. Moreover, in the high-throughput microarray and gene set enrichment analysis, ATMIN was shown to act on the Wnt-signaling pathway via PARP1. This cascade influences β-catenin/transcription factor 4 (TCF4) binding affinity in MSI-high tumors, and PARP1 inhibition significantly decreased the number of metastases from ATMIN knockdown cancer cells., Conclusions: The results not only indicated the critical role of ATMIN, but also shed new light on PARP1 inhibitors, providing a basis for further clinical trials of MSI-high CRC., (© 2021. Society of Surgical Oncology.)

Objectives: To study the effect of different maintenance doses of caffeine citrate on the success rate of ventilator weaning in very preterm infants (gestational age of ≤32 weeks) with respiratory distress syndrome (RDS)., Methods: A total of 162 preterm infants with RDS who were admitted to the hospital from January 2016 to December 2018 were enrolled in this prospective trial. These infants had a gestational age of ≤32 weeks and required invasive mechanical ventilation. They were randomly divided into a high-dose caffeine group and a low-dose caffeine group, with 81 infants in each group. Within 6 hours after birth, both groups were given caffeine at a dose of 20 mg/kg. After 24 hours, the high- and low-dose caffeine groups were given caffeine at a maintenance dose of 10 mg/kg and 5 mg/kg, respectively. The two groups were compared in terms of re-intubation rate within 48 hours after ventilator weaning, durations of ventilation and oxygen therapy, enteral feeding, weight gain, and the incidence rates of complications and adverse reactions during hospitalization., Results: The high-dose caffeine group had a significantly lower re-intubation rate within 48 hours after ventilator weaning than the low-dose caffeine group ( P <0.05), with frequent apnea as the main reason for failed ventilator weaning in both groups. The high-dose caffeine group had significantly shorter durations of mechanical ventilation and oxygen therapy than the low-dose caffeine group ( P <0.05). There were no significant differences between the two groups in the time to total enteral feeding, average daily weight gain, body weight at discharge, and the incidence rates of complications (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intracranial hemorrhage) and adverse reactions (tachycardia, hypertension, and feeding intolerance) ( P >0.05)., Conclusions: A high maintenance dose of caffeine can safely and effectively reduce the incidence rate of apnea after ventilator weaning and the failure rate of ventilator weaning in RDS preterm infants with a gestational age of ≤32 weeks, and therefore, it holds promise for clinical application.

A theoretical study of geometrical structures, electronic properties, and spectral properties of single-atom transition metal-doped boron clusters MB 24 (M = Sc, V, and Mn) is performed using the CALYPSO approach for the global minimum search, followed by density functional theory calculations. The global minima obtained for the VB 24 and MnB 24 clusters correspond to cage structures. Interestingly, the global minima obtained for the ScB 24 cluster tend to a three-ring tubular structure. Population analyses and valence electron density analyses reveal that partial electrons on transition-metal atoms transfer to boron atoms. The localized orbital locator of MB 24 (M = Sc, V, and Mn) indicates that the electron delocalization of ScB 24 is stronger than that of VB 24 and MnB 24 , and there is no obvious covalent bond between doped metals and B atoms. The spin density and spin population analyses reveal that MB 24 (M = Sc, V, and Mn) have different spin characteristics which are expected to lead to interesting magnetic properties and potential applications in molecular devices. The calculated spectra indicate that MB 24 (M = Sc, V, and Mn) has meaningful characteristic peaks that can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of these single-atom transition metal-doped boron clusters. Our work enriches the database of geometrical structures of doped boron clusters and can provide an insight into new doped boron clusters., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background : Metastasis is a severe problem in patients with oral squamous cell carcinoma (OSCC), which is the fifth most common cancer worldwide. Leukemia inhibitory factor (LIF) has been studied in different cancers, while the role of LIF in OSCC remains unclear. Methods : LIF expression was detected in 100 OSCC samples by immunohistochemistry. Effects of LIF on cell motility were evaluated in OSCC cell lines. High-throughput microarray analysis was also conducted. The correlation between LIF and the downstream effector was analyzed by real-time quantitative reverse transcription PCR. Results : Patients with OSCC who had lymph node metastasis or advanced cancer stages showed high LIF expression. OSCC patients with higher LIF expression, advanced stage, large tumor size, or lymph node metastasis had significantly shorter overall survival. LIF regulated cancer cell motilities through outside-in signaling. The i nhibin beta A subunit ( INHBA ) gene was identified as a crucial downstream effector of LIF-promoted OSCC progression and restored migration and invasion abilities in LIF knockdown transfectants. Conclusion : LIF enhances regional lymphatic spread, thus leading to an advanced cancer stage. Regulation of LIF downstream molecules such as INHBA inhibits the invasion or migration ability of cancer cells. Thus, LIF can be a potential target in preventing cancer metastasis and spread., Competing Interests: The authors declare that they have no competing interests.

Background/purpose: Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear., Methods: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and mitochondrial biogenesis related genes was measured by real-time polymerase chain reaction or Western blot analysis., Results: CTGF decreased OCR, ECAR, adenosine triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression in SAS cells., Conclusion: CTGF can decrease glycolysis, mitochondrial oxidative phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA protein degradation through ubiquitin proteasome pathway and in turn reduces migration and invasion of OSCC cells. Therefore, CTGF may be developed as a potential additive therapeutic drug for oral cancer in the near future., (Copyright © 2017. Published by Elsevier B.V.)

Background: The quality of the lateral compartment cartilage is important to preoperative evaluation and prognostic prediction of unicompartmental knee arthroplasty (UKA). Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables noninvasive assessment of glycosaminoglycan (GAG) content in cartilage. This study aimed to determine the GAG content of the lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA., Methods: From December 2016 to May 2017, twenty patients (20 osteoarthritic knees) conforming to the indications for Oxford medial UKA were included as the osteoarthritis (OA) group, and 20 healthy volunteers (20 knees) paired by sex, knee side, age (±3 years), and body mass index (BMI) (±3 kg/m2) were included as the control group. The GAG contents of the weight-bearing femoral cartilage (wbFC), the posterior non-weight-bearing femoral cartilage (pFC), the lateral femoral cartilage (FC), and tibial cartilage (TC) were detected using dGEMRIC. The dGEMRIC indices (T1Gd) were calculated in the middle three consecutive slices of the lateral compartment. Paired t-tests were used to compare the T1Gd in each region of interest between the OA group and control group., Results: The average age and BMI in the two groups were similar. In the OA group, T1Gd of FC and TC was 386.7 ± 50.7 ms and 429.6 ± 59.9 ms, respectively. In the control group, T1Gd of FC and TC was 397.5 ± 52.3 ms and 448.6 ± 62.5 ms, respectively. The respective T1Gd of wbFC and pFC was 380.0 ± 47.8 ms and 391.0 ± 66.3 ms in the OA group and 400.3 ± 51.5 ms and 393.6 ± 57.9 ms in the control group. Although the T1Gd of wbFC and TC tended to be lower in the OA group than the control group, there was no significant difference between groups in the T1Gd in any of the analyzed cartilage regions (P value of wbFC, pFC, FC, and TC was 0.236, 0.857, 0.465, and 0.324, respectively)., Conclusions: The GAG content of the lateral compartment cartilage in knees conforming to indications for Oxford medial UKA is similar with those of age- and BMI-matched participants without OA.

Background: Lateral compartmental osteoarthritis (LCOA), a major complication after medial mobile-bearing unicompartmental knee arthroplasty (UKA), is highly associated with the increased stress of the lateral compartment. This study aimed to analyze the effects on the stress and load distribution of the lateral compartment induced by lower limb alignment and coronal inclination of the tibial component in UKA through a finite element analysis., Methods: Eight three-dimensional models were constructed based on a validated model for analyzing the biomechanical effects of implantation parameters on the lateral compartment after medial Oxford UKA: postoperative lower limb alignment of 3° valgus, neutral and 3° varus, and the inclination of tibial components placed in 4°, 2° valgus, square, and 2° and 4° varus. The contact stress of femoral and tibial cartilage and load distribution were calculated for all models., Results: In the 3° valgus lower limb alignment model, the contact stress of femoral (3.38 MPa) and tibial (3.50 MPa) cartilage as well as load percentage (45.78%) was highest compared to any other model, and was increased by 36.75%, 47.70%, and 27.63%, respectively when compared to 3° varus. In the condition of a neutral position, the outcome was comparable for the different tibial tray inclination models. The inclination did not greatly affect the lateral compartmental stress and load distribution., Conclusions: This study suggested that slightly varus (undercorrection) lower limb alignment might be a way to prevent LCOA in medial mobile-bearing UKA. However, the inclination (4° varus to 4° valgus) of the tibial component in the coronal plane would not be a risk factor for LCOA in neutral position.

Background: The lateral pillar of the femoral head is an important site for disease development such as osteonecrosis of the femoral head. The femoral head consists of medial, central, and lateral pillars. This study aimed to determine the biomechanical effects of early osteonecrosis in pillars of the femoral head via a finite element (FE) analysis., Methods: A three-dimensional FE model of the intact hip joint was constructed from the image data of a healthy control. Further, a set of six early osteonecrosis models was developed based on the three-pillar classification. The von Mises stress and surface displacements were calculated for all models., Results: The peak values of von Mises stress in the cortical and cancellous bones of normal model were 6.41 MPa and 0.49 MPa, respectively. In models with necrotic lesions in the cortical and cancellous bones, the von Mises stress and displacement of lateral pillar showed significant variability: the stress of cortical bone decreased from 6.41 MPa to 1.51 MPa (76.0% reduction), while cancellous bone showed an increase from 0.49 MPa to 1.28 MPa (159.0% increase); surface displacements of cortical and cancellous bones increased from 52.4 μm and 52.1 μm to 67.9 μm (29.5%) and 61.9 μm (18.8%), respectively. In addition, osteonecrosis affected not only pillars but also adjacent structures in terms of the von Mises stress and surface displacement levels., Conclusions: This study suggested that the early-stage necrosis in the femoral head could increase the risk of collapse, especially in lateral pillar. On the other hand, the cortical part of lateral pillar was found to be the main biomechanical support of femoral head.

High utilization and loading of sulfur in cathodes holds the key in the realization of Li-S batteries. We here synthesized a Co 4 N mesoporous sphere, which was made up of nanosheets, via an easy and convenient method. This material presents high affinity, speedy trapping, and absorbing capacity for polysulfides and acts as a bifunctional catalysis for sulfur redox processes; therefore it is an ideal matrix for S active material. With such a mesoporous sphere used as a sulfur host in Li-S batteries, extraordinary electrochemistry performance has been achieved. With a sulfur content of 72.3 wt % in the composite, the Co 4 N@S delivered a high specific discharge capacity of 1659 mAh g -1 at 0.1 C, almost reaching its theoretic capacity. Also, the battery exhibited a large reversible capacity of about 1100 mAh g -1 at 0.5 C and 1000 mAh g -1 at 1 C after 100 cycles. At a high rate of 2 C and 5 C, after 300 cycles, the discharge capacity finally stabilized at 805 and 585 mAh g -1 . Even at a 94.88% sulfur content, the cathode can still deliver an extremely high specific discharge capacity of 1259 mAh g -1 with good cycle performance.

WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD). We first measured the WISP-1 expression levels using a transforming growth factor-β (TGF-β)-induced renal fibrosis tubular epithelial cell (TEC) model and a mouse model of obstructive nephropathy. We then evaluated the correlation between serum WISP-1 levels and fibrosis scores in biopsy-proven renal fibrosis of patients with CKD. Based on the findings from both in vivo and in vitro studies, the levels of WISP-1 and fibrotic parameters (collagen I, fibronectin and α-smooth muscle actin) were significantly increased in the fibrotic models. Consistently, patients with focal proliferative IgA nephropathy, focal segmental glomerular sclerosis and diabetic nephropathy displayed markedly elevated serum WISP-1 levels and fibrosis scores of renal biopsies compared with normal subjects and patients with minimal change disease (P<0.05). Importantly, the serum WISP-1 levels were positively correlated with fibrosis scores in the renal biopsies of these patients (r=0.475, P=0.0001). Thus, serum WISP-1 levels may be used as a potential noninvasive biomarker of renal fibrosis in patients with CKD., Competing Interests: None.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

Objectives: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear., Materials and Methods: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided., Results: ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression., Conclusions: The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To investigate the early intellectual developmental outcome of late preterm infants., Methods: A total of 106 late preterm infants with a gestational age of 34-36 +6 weeks who were admitted to the neonatal ward between January 2012 and January 2015, cured, discharged, and regularly followed up at the outpatient service for high-risk children were enrolled as the preterm group. A total of 120 healthy full-term infants during the same period were randomly selected as the term group. Neonatal behavioral neurological assessment (NBNA) was performed for late preterm infants at a corrected gestational age of 40 weeks and full-term infants at a gestational age of 40 weeks. The Gesell Developmental Scale was used for late preterm infants at a corrected age of 3, 6, and 12 months and full-term infants at an age of 3, 6, and 12 months., Results: The preterm group had an NBNA score of <37 and a significantly lower NBNA score than the term group (P<0.05). At the corrected age of 3 months, the preterm group had significantly lower scores of gross motor, fine motor, and social competence than the term group (P<0.05). At the corrected age of 6 months, the preterm group had significantly lower scores of adaptability, gross motor, and fine motor than the term group (P<0.05). At the corrected age of 12 months, the preterm group had significantly lower scores of adaptability, gross motor, and social competence than the term group (P<0.05)., Conclusions: Late preterm infants have early intellectual developmental delay. It is necessary to perform neurodevelopmental monitoring for late preterm infants.

CCN family members are involved in many physiologic and pathological functions, and be detected in many different cancer types. Immunohistochemistry (IHC) is an important diagnostic pathology tool to demonstrate protein expression in clinical and research fields. Here, we explain the preparation of sample slides, staining procedure, and the problems that might be met during the time. The differential staining of CCN proteins is shown in breast cancer, oral cancer, lung cancer, colorectal cancer, and gastric cancer.

Background: Glycolysis machinery regulates cancer cell behavior. However, the roles of these glycolysis enzymes in oral squamous cell carcinoma (OSCC) progression remain unknown., Methods: Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected using quantitative real-time polymerase chain reaction (PCR). The functions of ALDOC in migration and invasion were determined using gain and loss of function approaches. An orthotopic OSCC animal model was performed to investigate the effects of ALDOC on metastasis and tumorigenesis in vivo., Results: ALDOC expression is negatively significantly correlated with clinical outcome and cell migration in vitro and in vivo. ALDOC blocks adenosine triphosphate generation and lactate production, and mutation constructs of Arg42 and Lys146 functionally restore ALDOC-inhibited cell migration and invasion., Conclusion: ALDOC functions as an OSCC prognosis marker clinically, and suppresses migration and invasion by its catalytic domain of Arg42 and Lys146. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1075-E1085, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Postoperative knee soft tissue irritation is a common complication after retrograde nail fixation of femoral fractures. Distal locking screw prominence is one of the causes for soft tissue irritation. This study aimed to determine whether the use of the femoral condyles tangential views improve the diagnostic accuracy compared with anteroposterior (A-P) view in detecting distal locking screw penetrations during retrograde femoral nailing., Methods: The angle between the sagittal plane and lateral aspect of the condyle and the angle between the sagittal plane and medial aspect of condyle were measured on computed tomography (CT) images. After the angles were measured and recorded, cadaveric femurs were used in a simulated surgical procedure. The retrograde femoral nail was inserted into the femur and placed distal locking screws, which were left 2, 4, and 6 mm proud of the medial and lateral condyles for each femur. A-P view, lateral condyle tangential view and medial condyle tangential view were obtained. All fluoroscopic images were recorded and sent to three observers blinded to the experimental procedure to determine whether screws penetrated the condyle cortex or not., Results: According to the results of CT scan, the lateral condyle view was 20.88 ± 0.98° and the medial condyle view was 40.46 ± 3.14°. In the A-P view, we detected 0% at 2 mm penetration, 16.7% (lateral condyle screw) and 25.0% (medial condyle screw) at 4 mm, and 41.7% (lateral condyle screw) and 58.3% (medial condyle screw) at 6 mm. In the lateral tangential view, we detected 91.7% at 2 mm penetration of the lateral condyle and 100% at 4 mm and 6 mm. In the medial tangential view, we detected 66.7% at 2 mm penetration of the medial condyle and 100% at 4 mm and 6 mm. The femoral condyle tangential views provided significant improvement in detecting screw penetrations at all lengths (2, 4, and 6 mm) compared with the A-P view (P < 0.05)., Conclusions: The femoral condyles tangential views increased the accuracy of detecting screw penetrations on the medial and lateral condyles. Routine clinical use of the femoral condyles tangential views has the potential to increase accuracy in detecting distal locking screw penetration during retrograde femoral nailing.

Background: To assess the correlations and functions of complement C1r/C1s, Uegf, Bmp1 domain-containing protein-1 (CDCP1) in identifying colorectal cancer (CRC) patients who are at high risk for metastasis., Methods: Tumor specimens from 101 patients were analyzed by real-time polymerase chain reaction to detect CDCP1 expression. CDCP1 expression plasmids and shRNA were used to knock down CDCP1 expression in this study to investigate migratory and invasive abilities by Boyden chambers. The mRNA expression profiles in shCDCP1 transfectants were compared to those in control cells by conducting microarray analysis. Its downstream effectors were also invested in this study., Results: CRC patients with a high CDCP1 expression had a statistically significant lower overall survival and disease-free survival compared to those exhibiting low CDCP1 expression. In vitro, knock-down CDCP1 expression significantly decreased migratory and invasive abilities in HCT116. Aberrant expression of CDCP1 increased cancer cell migration and invasion. By using integrated genomics, we identified ROCK1 (rho-associated, coiled-coil-containing protein kinase 1 pseudogene 1) as a downstream effector in CDCP1-mediated migration and as an invasion mediator. Clinically, ROCK1 and CDCP1 mRNA expression exhibited a strong positive correlation in CRC patient samples., Conclusions: Our results implicated CDCP1 as a key regulator of CRC migration and invasion, and suggest that it is a useful prognostic factor for patients with CRC. Improved identification of a high-risk subset of early metastatic patients may guide indications of individualized treatment in clinical practice.

The aim of this study is to introduce a self-designed, minimally invasive technique for repairing an acute Achilles tendon rupture percutaneously. Comparing with the traditional open repair, the new technique provides obvious advantages of minimized operation-related lesions, fewer wound complications as well as a higher healing rate. However, a percutaneous technique without direct vision may be criticized by its insufficient anastomosis of Achilles tendon and may also lead to the lengthening of the Achilles tendon and a reduction in the strength of the gastrocnemius. To address the potential problems, we have improved our technique using a percutaneous Kirschner wire leverage process before suturing, which can effectively recover the length of the Achilles tendon and ensure the broken ends are in tight contact. With this improvement in technique, we have great confidence that it will become the treatment of choice for acute Achilles tendon ruptures., (© 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.)

Background: Anterior cervical decompression and fusion (ACDF) has long been the preferred treatment for cervical spondylotic myelopathy (CSM). However, few studies have focused on surgical results of CSM in patients with developmental canal stenosis (DCS). The purpose of this study was to investigate DCS as a comorbidity in patients with CSM and the correlation between surgical results and DCS., Methods: From January 1995 to December 2005, 122 patients treated with ACDF for CSM were enrolled in this retrospective study. Pavlov's ratio was used to evaluate cervical spinal canal size, with a value of < 0.82 at least one level indicating DCS. Patients were divided into two groups: those with DCS preoperatively (DCS group, n = 50 [41.0 %]) and those without DCS (non-DCS group, n = 72). Clinical data and radiological parameters were compared between groups., Results: There were no significant differences in preoperative and 2-year follow-up Japanese Orthopedic Association scores between groups. Both groups achieved satisfactory fusion rates (DCS, 92.0 %; non-DCS, 93.0 %). Adjacent-segment degeneration (ASD) was detected in 66.0 % of patients in the DCS group and in 43.0 % of patients in the non-DCS group (p = 0.01). However, there was no significant difference in the incidence of ASD requiring surgery between groups (p = 0.20)., Discussion: DCS is a common comorbidity in patients with CSM. The findings of this study have added knowledge on the correlation between DCS and ASD after anterior fusion surgery., Conclusions: DCS did not affect neurologic improvement postoperatively at short-term follow-up. Although DCS increased the incidence of ASD after anterior fusion, it did not predict ASD requiring surgery. Therefore, patients with DCS must receive close follow-up.

Objective: To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR)., Methods: A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups., Results: The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well., Conclusions: Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

Objective: The aim of this study was to investigate the therapeutic response and toxicity of intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (c-RT) as adjuvant therapy in patients with pelvic locoregional recurrence of cervical cancer after radical surgery., Methods: This retrospective study included 161 patients with unresectable pelvic locoregional recurrence of cervical cancer after radical surgery between March 2003 and May 2012. All patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer and received radical hysterectomy and pelvic lymphadenectomy. A total of 82 patients were treated with c-RT, whereas the remaining 79 patients underwent IMRT. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation., Results: The mean dose delivered to the planning target volume was significantly higher in the IMRT group than in the c-RT group (61.8 vs 50.3 Gy, P = 0.029). Intensity-modulated radiation therapy plans yielded better dose sparing of small bowel, bladder, and rectum than did c-RT (P < 0.05). Moreover, the IMRT patients experienced less acute and chronic toxicities (P < 0.05) and better short-term effects (complete response + partial response) than did those treated with c-RT (89.9% vs 63.4%, P = 0.03). Three- and 5-year overall survival rates were significantly higher in the IMRT group than in the c-RT group (3-year: 58.4% vs 39.1%, P = 0.012; 5-year: 35.4% vs 21.4%, P = 0.007). Furthermore, 5-year progression-free survival rates were significantly higher in the IMRT group than in the c-RT group (26.1% vs 15.1%, P = 0.031)., Conclusions: Intensity-modulated radiation therapy achieved outcomes superior to c-RT in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. The acute and chronic toxicities were acceptable, and the adjacent organs at risk were well protected.

Objective: To study the incidence and risk factors for extrauterine growth retardation (EUGR) at discharge in premature infants., Methods: A retrospective analysis was performed on 596 premature infants who were admitted to the neonatal intensive care unit between 2006 and 2010. These subjects were classified into EUGR (n=217) and non-EUGR groups (n=379) based on the body weight at discharge. The risk factors for the occurrence of EUGR were studied by multivariate logistic regression analysis., Results: Based on the body weight, length, and head circumference, the incidence of EUGR at discharge was 36.4% (217 cases), 42.0% (250 cases), and 22.8% (136 cases), respectively. Low gestational age, low birth weight, intrauterine growth retardation (IUGR), delayed enteral feeding and complications of the respiratory system were identified as risk factors for EUGR (OR=6.508, 14.522, 5.101, 1.366, and 1.501, respectively)., Conclusions: The incidence of EUGR might be greatly decreased by strengthening the perinatal care, reducing the incidence of premature delivery and IUGR, undertaking early enteral feeding, and actively preventing postnatal complications.

Objectives: MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown., Materials and Methods: We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo., Results: The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression., Conclusion: MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Quartz in the veins at the Shenxigou section of Wenchuan earthquake fault zone was investigated by micro-Raman spectroscopic measurement, and the distribution of compressive stress in the fault zone was estimated by the frequency shifts of the 464 cm-1 vibrational mode of quartz grains in the veins. It was showed that the 464 cm-1 peak arising from the quartz grains in the veins near the fault plane shifts by 3. 29 cm-1 , and the corresponding compressive stress is 368. 63 MPa, which is significantly lower than the stress accumulation on both sides due to multi-stage events. Stress accumulation increased with moving away from the fault plane in the footwall with the offset of the 464 cm-1 peak arising from the quartz grains in the veins increasing, which can reach 494. 77 MPa at a distance of 21 m with a high offset of 4. 40 cm-1 of the 464 cm-1 peak. The compressive stress gets the maximum value of 519.87 MPa at a distance of 10 m from the fault plane in the hanging wall with the offset of the 464 cm-1 peak arising from the quartz grains in the veins being 4. 62 cm-1, followed by a sudden drop in stress accumulation, and it drops to 359. 59 MPa at a distance of 17 m. Because of moving away from the foult plane at the edge of the foult zone, the stress drops to 359. 59 MPa with a small value of 464 cm-1 peak offset 3. 21 cm-1 at a distance of 27 m from the fault plane in the hanging wall due to the little effect by the fault activity. Therefore, the stress of Wenchuan earthquake fault zone is partially released, but the rest of the stress distribution is uneven, and there is also a high stress accumulation in somewhere in the fault zone, which reflects that the mechanical properties of the rocks in the fault zone have a characteristic of unevenness in space.

Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara, Oryza glaberrima, Oryza barthii, Oryza glumaepatula, and Oryza meridionalis. Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.

Objectives: This study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients., Methods: Six hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed., Results: The PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6-386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis., Conclusions: Circumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.

Objective: To identify the optimal ratio of free femur for minimizing the risks of periprosthetic fracture., Methods: Three dimensional models of the femur with hip and knee stem elongation were constructed. With the distal femoral condylar surface fixed in a three dimensional model, the femoral head loading was performed according to the methods described by Huiskes and van Rietbergen in the models of hip replacement, knee replacement with or without hip stem or knee stem elongation. The maximum principal stress (MPS) and maximum principal elastic strain (MPES) of the femur were recorded and their relationships to the free femur ratio were analyzed using Pearson's correlation analysis., Results: There were no obvious changes in MPS and MPES with hip stem elongation from 100 to 180 mm. In ipsilateral hip and knee replacement, the MPS and MPES had a tendency to decrease with knee and hip stem elongation. The MPS and MPES were mainly located in the anterior medial side of the middle to distal femur post-hip replacement and distalized with stem elongation. When the knee stem had been elongated more than 120 mm, the stress and strain concentrated strongly in the middle of the femoral shaft. There was a positive correlation between MPS and MPES to the free femur ratio (P < 0.01); however, no optimal ratio of free femur that would minimize the risks of periprosthetic fracture was identified., Conclusion: Positive correlations were found between implant free femur and stress and strain changes in total knee arthroplasty, total hip arthroplasty and ipsilateral hip and knee replacement., (© 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.)

Objective: To evaluate the clinical effects of the early use of recombinant human erythropoietin (rhEPO) on the neurointelligence development in very low birth weight infants (VLBWI)., Methods: Seventy-eight VLBWI were divided into rhEPO treatment group (n=35) and control group (n=43) according to the choice of their parents. Neonatal behavioral neurological assessment (NBNA) was performed at 40 weeks of corrected gestational age. The Gesell Developmental Schedules were used for neurodevelopmental evaluation at 3, 6, and 12 months of corrected age. The abnormal rates of auditory brainstem response (ABR) and cranial ultrasound were evaluated at 6 months of corrected age., Results: The rhEPO treatment group had significantly higher NBNA scores at 40 weeks of corrected gestational age than the control group (P<0.05). The adaptability at 3 months of corrected age, the gross motor, adaptability, and sociability at 6 months, and the gross motor, adaptability, fine motor, sociability, and language at 12 months were significantly better in the rhEPO treatment group than in the control group (P<0.05). The abnormal rates of ABR and cranial ultrasound in the rhEPO treatment group were significantly lower than in the control group at 6 months of corrected age (P<0.05)., Conclusions: Early use of rhEPO can promote the early recovery of neurological symptoms and improve the cognitive, motor, and language abilities in VLBWI due to its protective effects on the nervous system.

The melting and recrystallizing experiments of alkali basalt powder and mixture of pure oxides mixed as stoichiometry were performed at 3 GPa and 1 200 degrees C. Electronic microprobe analysis and Raman spectra showed that the recrystallized products were omphacites, the FWHM (full width at half maximum) of the Raman peak was narrow and its shape was sharp, which is attributed to the stable Si-O tetrahedral structure and the high degree of order in omphacite. Based on the results of previous studies, the influencing factors of omphacite genesis and its primary magma were discussed. The results showed that the formation of omphacite could be affected by many factors, such as the composition of parent rocks, the concentration of fluid in the system and the conditions of pressure and temperature. This result could support some experimental evidences on the genesis studies of omphacite and eclogite.

Background: Patellar fracture and cruciate ligament injury are a common consequence of traumatic knee injury. Patellar fracture combined with cruciate ligament injury is rarely reported, although the mechanisms of two things are similar. This study aimed to evaluate the incidence of closed patella fracture combined with cruciate ligament injury., Methods: From 2012 March 1 to June 30, magnetic resonance images of 60 patients with unilateral closed patellar fracture were studied in our institution. The mean age of the patients at presentation was 40.2 years (range, 13-64 years) and 48 patients were men. First, patients were divided according to the cause of injury. Twenty-eight patients had high-energy trauma from a falling injury or motor vehicle accident, and 32 patients had low-energy trauma resulting from a tumbling injury. Second, according to the fracture pattern, 31 patients had a transverse fracture and 29 patients had a comminuted fracture., Results: We found seven cases of closed patellar fracture combined with cruciate ligament injury among 60 patients, including two cases of a completely ruptured posterior cruciate ligament, two with a partially torn posterior cruciate ligament, and three with a partially torn anterior cruciate ligament. The percentage of this combined injury was 11.6% (7/60). The incidence of a combined injury of the cruciate ligament with a comminuted fracture (6/29, 20.7%) was significantly higher than that with a transverse fracture (1/31, 3.2%, P < 0.05). The most common mechanism of injury in patellar fracture combined with cruciate ligament injury was high-energy trauma from road traffic accidents (94%), whereas in the patellar fracture alone, it was tumbling (62%). The incidence of combined injury with high-energy trauma (6/28, 21.4%) was significantly higher than that with low-energy trauma (1/32, 3.1%, P < 0.05)., Conclusions: These data suggest that high-energy trauma often results in a comminuted patellar fracture, which is often combined with cruciate ligament injury. Traffic accidents are the main risk factor for this combined injury. Understanding the relationship between patellar fracture and cruciate ligament injury for diagnosis and treatment is important.

Objectives: Oral squamous cell carcinoma (OSCC) accounts for>90% oral cancer which is a leading cause of cancer death worldwide. Early diagnosis may well offer an opportunity to increase survival to this neoplasm. Micro(mi)RNA-interfered cancer progression is crucial, yet its migration machinery of OSCC is still unknown. To access whether the possible miRNA prognostic markers and underlying mechanisms, we developed a highly migratory TW2.6 MS-10 cells from TW2.6 cells to investigate the issue., Materials and Methods: miRNA profiling was performed on TW2.6 and TW2.6 MS-10. Target miRNA was correlated to pathological status in OSCC patients by real-time RT-PCR. A downstream effector was identified using a bioinformatics analysis, and a 3'-untranslated region (UTR) reporter assay was used., Results: An miRNA cluster, miR-17-92, including miR-17, miR-19b, miR-20a, and miR-92a, was found to be significantly down-regulated in TW2.6 MS-10 compared to TW2.6 cells. Overexpression of this cluster decreased the migratory ability of OSCC cell lines. We further demonstrated that miR-17 and miR-20a are the main miRNAs of miR-17-92 cluster which modulate OSCC migration. Clinically, miR-17/20a showed negative correlation with TNM stage and lymphatic metastasis. Through a bioinformatics screening analysis and 3'UTR reporter assay, we confirmed the integrin (ITG) β8 as a direct target of miR-17/20a, and knockdown of ITGβ8 reduced cell migratory capability of OSCC., Conclusions: miR-17/20a acts as a prognostic predictor of OSCC patients' outcome and a tumor migration suppressor miRNA., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this study was to compare monotonic biomechanical properties of gourd-shaped LCP fixation with LCP fixation of human tibial shaft in gap fracture mode. Twenty paired fresh cadaveric human tibias were randomly divided into 4 groups (5 pairs each): (1) axial loading single cycle to failure testing, (2) torsion single cycle to failure testing, (3) 4-point bending single cycle to failure testing, and (4) dynamic 4-point bending testing. A 7-hole 4.5 mm gourd-shaped LCP was secured on the anteromedial surface of 1 randomly selected bone from each pair, respectively, using 6 locking screws in the 1st, 2nd, 3rd, 5th, 6th and 7th hole with the middle hole unfilled and just located at the mid-diaphysis of the tibia. A 7-hole 4.5 mm LCP was secured on the other bone with the same method. Standard AO/ASIF techniques were used. After fixation finished, a 10 mm gap in the mid-diaphysis of tibia was created, centrally located at the unfilled hole. The axial, torsional, and bending stiffness and failure strengths were calculated from the collected data in static testings and statistically compared using paired Student's t-test. The 4-point bending fatigue lives of the two constructs were calculated from the dynamic testing data and also statistically compared using paired Student's t-test. Failure modes were recorded and visually analyzed. P<0.05 was considered significant. Results showed that the axial, torsional and bending stiffness of gourd-shaped LCP construct was greater (4%, 19%, 12%, respectively, P<0.05) than that of the LCP construct, and the axial, torsional and bending failure strengths of gourd-shaped LCP construct were stronger (10%, 46%, 29%, respectively, P<0.05) than those of the LCP construct. Both constructs failed as a result of plate plastic torsional deformation. After axial loading and 4-point bending testings, LCP failed in term of an obvious deformation of bent apex just at the unfilled plate hole, while the gourd-shaped LCP failed in term of a deformation of bent arc between the 3rd and 5th holes, which indicated a more consistent stress distribution on gourd-shaped LCP. Fatigue life of gourd-shaped LCP construct was significantly greater than LCP construct (153 836±2 228 vs. 132 471±6 460 cycles, P<0.01). All constructs failed as a result of fracture of the plate through the compression hole of the unfilled combination screw hole. The biomechanical testing showed that gourd-shaped LCP can provide greater stiffness and strength, and longer fatigue life than LCP. The gourd-shaped LCP may be more advantageous mechanically and may reduce the plate breakage rate clinically.

Quantitative Image Analysis (QIA) of digitized whole slide images for morphometric parameters and immunohistochemistry of breast cancer antigens was used to evaluate the technical reproducibility, biological variability, and intratumoral heterogeneity in three transplantable mouse mammary tumor models of human breast cancer. The relative preservation of structure and immunogenicity of the three mouse models and three human breast cancers was also compared when fixed with representatives of four distinct classes of fixatives. The three mouse mammary tumor cell models were an ER+/PR+ model (SSM2), a Her2+ model (NDL), and a triple negative model (MET1). The four breast cancer antigens were ER, PR, Her2, and Ki67. The fixatives included examples of (1) strong cross-linkers, (2) weak cross-linkers, (3) coagulants, and (4) combination fixatives. Each parameter was quantitatively analyzed using modified Aperio Technologies ImageScope algorithms. Careful pre-analytical adjustments to the algorithms were required to provide accurate results. The QIA permitted rigorous statistical analysis of results and grading by rank order. The analyses suggested excellent technical reproducibility and confirmed biological heterogeneity within each tumor. The strong cross-linker fixatives, such as formalin, consistently ranked higher than weak cross-linker, coagulant and combination fixatives in both the morphometric and immunohistochemical parameters.

Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in tumor development and progression. The aim of this study was to investigate the role of TWEAK in colorectal cancer (CRC) progression., Methods: To investigate the involvement of TWEAK in the progression of human CRC, normal, and tumor specimens from 174 patients were analyzed immunohistochemically for the expression of TWEAK. TWEAK recombinant protein treatment, transfection of expression plasmids, and small interfering RNA to knockdown TWEAK expression were performed to test invasive ability with a Boyden chamber. The mRNA expression profile in recombinant TWEAK treatment was compared to a control group by microarray analysis. To identify downstream effectors, Raf kinase inhibitor (RKIP) and its correlation with TWEAK in vitro and in vivo were examined by quantitative real-time polymerase chain reaction and invasion assays., Results: CRC patients whose tumors displayed high TWEAK expression had a statistically significantly higher overall survival and a disease-free advantage over those with a low TWEAK expression. In in vitro invasion assays, alterations in TWEAK expression in CRC cell lines inversely modulated their invasive ability. By means of integrated genomics, we identified RKIP as a downstream effector in TWEAK-mediated invasion inhibition. Knockout of RKIP expression in HCT116 cells by short hairpin RNA (shRKIP) resulted in increased invasiveness. Clinically, RKIP and TWEAK mRNA expression showed strong positive correlations in CRC patient samples., Conclusions: Our results implicate TWEAK as a key regulator of CRC invasion, and it appears to be a useful prognostic factor for patients with CRC.

Variation of crystal structure of oligoclase with pressure was investigated by the approach of diamond anvil cell (DAC) and in situ micro-Raman spectroscopic measurement at room temperature and under pressures from 1.0 to 4.4 GPa. At 2.9 GPa a new peak round 517 cm(-1) appeared, and a new phase was produced. Near 3.4 GPa a major discontinuity occurs in the pressure dependence of 288 cm(-1) peak arising from the stretching mode of M-O, and 517 cm(-1) peak disappeared, it implied that the oligoclase underwent triclinic to monoclinic phase transition completely at about 3.4 GPa. The peaks at 458 and 516 cm(-1) peaks arising from flexural vibrational mode of Si-O-Si shifted linearly with the increasing pressures, the pressure-related slopes are 1.667 cm(-1)/GPa and 3.560 cm(-1)/GPa, respectively, whereas, the flexural vibrational mode of Al-O-Al at 480 cm(-1) did not shifted linearly with the increasing pressures. The position of 288 cm(-1) peak did not change obviously in comparision with 458, 516 and 480 cm(-1) peaks, which shifted to lower frequency during decompression. The phase transition pressure of feldspar relates to the species of cation in the octatomic rings.

Surgical decision making for femoral neck fractures is currently based on factors such as patient age, fracture type, and medical condition, lacking a quantitative standard. The treatment protocol based on such qualitative assessment has poor operability, greatly affected by the surgeon's subjective factors. As a result, a quantitative score system (QSS) focusing on 5 factors--age, fracture type, bone mineral density, activities of daily living, and medical comorbidities--with a total score of 25 is designed to deal with adult femoral neck fractures. The higher the score, the worse the patient's physiological condition. According to our clinical experience, patients with 1 to 11 points should be treated with internal fixation; patients with 12 to 17 points with total hip arthroplasty (THA), and patients with 18 to 22 points with hemiarthroplasty. Patients with 22 to 25 points should be treated with internal fixation due to the high surgical risk of arthroplasty caused by poor physiological condition. Three hundred seventy-five adult femoral neck fractures were treated on the basis of QSS for this 2-year prospective study. Of these, 242 were treated with low-score internal fixation, 60 with THA, 55 with hemiarthroplasty, and 18 with high-score internal fixation. The revision rates 2 years postoperatively in the low-score internal fixation, THA, and hemiarthroplasty groups were 15.3%, 5.0%, and 5.5%, respectively, which were lower than those from a meta-analysis (internal fixation, 35%; THA, 16%). This QSS helps surgical decision making regarding the treatment choice for adult patients with femoral neck fractures, and good results in preliminary clinical practice have been achieved., (Copyright 2012, SLACK Incorporated.)

Background: Histone deacetylase 2 (HDAC2) expressions in oral squamous cell carcinoma (OSCC) had been implicated in advanced stage and poor prognosis. It suggests a possible link between the migration/invasion potential of oral cancer cells and the prevalent expression of HDAC2., Methods: Five head and neck cancer (HNC) cell lines, including Ca9-22, Cal-27, HSC-3, SAS, and TW2.6, were used. Cells stably overexpressing HDAC2 and shRNA against HDAC2 were established to investigate migration/invasion ability in vitro and tumorigenesis and progression in vivo., Results: We found that alterations in the HDAC2 level in OSCC cell lines modulated their invasive ability with a positive correlation. Animal model also showed that knockdown of HDAC2 expression in SAS cells, originally containing high endogenous HDAC2 expression, resulted in decrease in tumor initiation and progression. Using high-throughput transcriptome analysis, numerous genes involved in HIF-1α-associated pathways were found. At the mechanism levels, using agents to block de novo protein synthesis or prevent protein degradation by ubiquitination, we found the stability of hypoxia inducible factor 1α (HIF-1α) protein was maintained in OSCC cells with HDAC2 overexpression. In addition, co-immunoprecipitation assay also revealed that HDAC2-mediated HIF-1α protein stability is because of direct interaction of HIF-1α with von Hippel-Lindau (VHL) protein., Conclusions: Our work demonstrates that HDAC2 maintains HIF-1α stability, probably at the level of protein modification, which in turn leads to the increase in cell invasion/migration ability in oral cancer progression. These findings implicate the potential of HDAC inhibitors for oral cancer therapy., (© 2011 John Wiley & Sons A/S.)