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SummaryThe aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of balloon kyphoplasty (BK), percutaneous vertebroplasty (PVP), and non-surgical treatment (NST) for patients with osteoporotic vertebral compression fractures (OVCFs). The results demonstrate that for pain and functional status, PVP was significantly better than NST, while the three treatments did not significantly differ in other outcomes.IntroductionBK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs.MethodsPubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis.ResultsOf the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland–Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) − 0.35 to 1.4), ODI (MD 0.11, 95% CrI − 13 to 13), and RMDQ (MD 1.2, 95% CrI − 2.7 to 5.4). The European Quality of Life–5 Dimensions (EQ–5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures.ConclusionPVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 ( SNORA42 ) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907 , in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.

We recently reported that shikonin and its analogs were a class of necroptotic inducers that could bypass cancer drug resistance. However, the molecular targets of shikonin are not known. Here, we showed that shikonin and its analogs are inhibitors of tumor-specific pyruvate kinase-M2 (PKM2), among which shikonin and its enantiomeric isomer alkannin were the most potent and showed promising selectivity, that is, shikonin and alkannin at concentrations that resulted in over 50% inhibition of PKM2 activity did not inhibit PKM1 and pyruvate kinase-L (PKL). Shikonin and alkannin significantly inhibited the glycolytic rate, as manifested by cellular lactate production and glucose consumption in drug-sensitive and resistant cancer cell lines (MCF-7, MCF-7/Adr, MCF-7/Bcl-2, MCF-7/Bcl-x L and A549) that primarily express PKM2. HeLa cells transfected with PKM1 showed reduced sensitivity to shikonin- or alkannin-induced cell death. To the best of our knowledge, shikonin and alkannin are the most potent and specific inhibitors to PKM2 reported so far. As PKM2 universally expresses in cancer cells and dictates the last rate-limiting step of glycolysis vital for cancer cell proliferation and survival, enantiomeric shikonin and alkannin may have potential in future clinical application.

Industrial processes prominently feature π-acidic gases, and an adsorbent capable of selectively interacting with these molecules could enable important chemical separations 1 – 4 . Biological systems use accessible, reducing metal centres to bind and activate weakly π-acidic species, such as N 2 , through backbonding interactions 5 – 7 , and incorporating analogous moieties into a porous material should give rise to a similar adsorption mechanism for these gaseous substrates 8 . Here, we report a metal–organic framework featuring exposed vanadium( ii ) centres capable of back-donating electron density to weak π acids to successfully target π acidity for separation applications. This adsorption mechanism, together with a high concentration of available adsorption sites, results in record N 2 capacities and selectivities for the removal of N 2 from mixtures with CH 4 , while further enabling olefin/paraffin separations at elevated temperatures. Ultimately, incorporating such π-basic metal centres into porous materials offers a handle for capturing and activating key molecular species within next-generation adsorbents. Nitrogenases use transition metals to selectively capture weak π acids such as N 2 by employing backbonding interactions. Here, a metal–organic framework with exposed vanadium sites is presented that uses this approach for selective capture of N 2 from CH 4 , with impressive selectivity and capacity.

Materials that combine magnetic order with other desirable physical attributes could find transformative applications in spintronics, quantum sensing, low-density magnets and gas separations. Among potential multifunctional magnetic materials, metal–organic frameworks, in particular, bear structures that offer intrinsic porosity, vast chemical and structural programmability, and the tunability of electronic properties. Nevertheless, magnetic order within metal–organic frameworks has generally been limited to low temperatures, owing largely to challenges in creating a strong magnetic exchange. Here we employ the phenomenon of itinerant ferromagnetism to realize magnetic ordering at TC = 225 K in a mixed-valence chromium(ii/iii) triazolate compound, which represents the highest ferromagnetic ordering temperature yet observed in a metal–organic framework. The itinerant ferromagnetism proceeds through a double-exchange mechanism, which results in a barrierless charge transport below the Curie temperature and a large negative magnetoresistance of 23% at 5 K. These observations suggest applications for double-exchange-based coordination solids in the emergent fields of magnetoelectrics and spintronics.The development of metal–organic magnets that combine tunable magnetic properties with other desirable physical properties remains challenging despite numerous potential applications. Now, a mixed-valent chromium–triazolate material has been prepared that exhibits itinerant ferromagnetism with a magnetic ordering temperature of 225 K, a high conductivity and large negative magnetoresistance (23%).

Infrared spectra of graphene deposited on a silicon oxide substrate suggest that many-body effects have a more significant role in determining its electronic behaviour than in free-standing graphene A remarkable manifestation of the quantum character of electrons in matter is offered by graphene, a single atomic layer of graphite. Unlike conventional solids where electrons are described with the Schrödinger equation, electronic excitations in graphene are governed by the Dirac hamiltonian 1 . Some of the intriguing electronic properties of graphene, such as massless Dirac quasiparticles with linear energy–momentum dispersion, have been confirmed by recent observations 2 , 3 , 4 , 5 . Here, we report an infrared spectromicroscopy study of charge dynamics in graphene integrated in gated devices. Our measurements verify the expected characteristics of graphene and, owing to the previously unattainable accuracy of infrared experiments, also uncover significant departures of the quasiparticle dynamics from predictions made for Dirac fermions in idealized, free-standing graphene. Several observations reported here indicate the relevance of many-body interactions to the electromagnetic response of graphene.

Studies have shown that the deformation of Ti alloys is due to the competition between hardening and softening effects under dynamic loading. However, there are limited indicators of this behaviour throughout the complete stress–strain process. This study aims to quantify the impact of strain rate and temperature on the hardening/softening behaviour of Ti-6Al-4V using a split-Hopkinson pressure bar system over a range of 2000 to 7000 s −1 strain rates and temperatures from 25 to 800°C. Firstly, this study proposes an evaluation index of material hardening/softening behaviour based on the complete stress–strain curve and energy evolution characteristic. Further, the dynamic mechanical properties of Ti-6Al-4V are investigated through the analysis of the stress–strain relationship and fracture morphology. Finally, the hardening/softening index is calculated and analysed. The findings revealed that the fracture surface of the impact specimen displayed dimple-like and smooth features, that are significantly influenced by both temperature and strain rate. The stress–strain curves demonstrated that Ti-6Al-4V exhibits remarkable strain-rate strengthening, plastic increasing, and strain work hardening behaviour. The hardening/softening index B r decreases with an increase in strain rate. For specific strain rates of 3000, 5000 and 7000 s −1 , B r increases as the loading temperature rises from 25 to 400°C, but decreases when the loading temperature is increased to 600°C. At a strain rate of 2000 s −1 , B r increases monotonically until the loading temperature reaches ∼ 800°C. These observations are found to be related to the microstructural evolution at varying temperatures and strain rates. Graphic Abstract

MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis. MiR-140-5p mimics and a negative control were transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used to detect the invasive ability of the cells, and the angiogenic ability was assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF-A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot analysis in vivo . VEGF-A was verified as a possible target gene of miR-140-5p, and corroborated by dual-luciferase reporter and ELISA. Taken together, the study elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer metastasis and angiogenesis, and provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for breast cancer patients.

Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.

The completion of the Arabidopsis thaliana genome sequence allows a comparative analysis of transcriptional regulators across the three eukaryotic kingdoms. Arabidopsis dedicates over 5% of its genome to code for more than 1500 transcription factors, about 45% of which are from families specific to plants. Arabidopsis transcription factors that belong to families common to all eukaryotes do not share significant similarity with those of the other kingdoms beyond the conserved DNA binding domains, many of which have been arranged in combinations specific to each lineage. The genome-wide comparison reveals the evolutionary generation of diversity in the regulation of transcription.