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Chronic nonspecific low back pain (cNLBP) accounts for approximately 90% of low back pain cases, affecting 65–80% of the population and significantly impacting life quality and productivity. This condition also leads to substantial financial burden. Although there have been advancements, a comprehensive understanding of the underlying etiology of cNLBP remains elusive, resulting in less than optimal treatment outcomes. This study aimed to examine the correlation between lipid variations and the development of cNLBP. The cohort consisted of 26 healthy volunteers (HV group) and 30 cNLBP patients, with an assessment of metabolites and lipid composition in both groups. Metabolomic results revealed significant alterations in lipid-associated metabolites between the HV and cNLBP groups. Subsequent lipid analysis revealed that monoacylglycerols (MAGs) increased approximately 1.2-fold (p = 0.016), diacylglycerols (DAGs) increased approximately 1.4-fold (p = 0.0003), and phosphatidylserine (PS) increased approximately 1.4-fold (p = 0.011). In contrast, triacylglycerol (TAG) decreased to about 0.7-fold (p = 0.035) in the cNLBP group compared to the HV group. The contrasting trends in MAG/DAG and TAG levels indicated that the imbalance between MAG/DAG and TAG may have an impact on the development of cNLBP. This study has provided new insights into the relationship between the progression of cNLBP and specific lipids, suggesting that these lipids could serve as therapeutic targets for cNLBP.

Abstract Background Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. Methods Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. Results A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). Conclusions The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES. Graphical Abstract

High-concentration tailings pastes are commonly encountered in the surface deposition and underground cemented paste backfill. It is necessary to forecast the pressure loss along the pipe and the flow behavior in the mined-out area when tailings pastes are transported in a pipeline or stored up in goaf. Traditionally, thixotropy has often been overlooked while designing tailings paste transport and disposal systems due to the complexity of thixotropy characterization. However, thixotropy plays an essential role in the rheology of tailings pastes. To achieve the accurate representation of thixotropy, a suitable constitutive model has to be selected in advance. Unfortunately, there is no current available thixotropic model for tailings pastes up to date. Moreover, tailings pastes exhibit complex thixotropy that is significantly affected by the particle size of tailings, though the relevant studies are not abundant. It is important to analyze quantitively the relationship between particle size and thixotropic parameters based on an appropriate constitutive model. In this work, the constitutive thixotropic model for tailings pastes proposed by Zhang et al. was adopted. To reveal the influence of particle size on the thixotropy of tailings pastes, samples of various mean particle sizes prepared from the same tailings were applied to constant shear rate experiments. Results show that the target tailings pastes display significant thixotropy, leading to shear thinning under steady shear rates. In the steady state, the static yield stress, dynamic yield stress, and Bingham viscosity appear to correlate linearly to the reciprocal of the square of the mean particle size. As for the transient state, the corresponding fit parameters show a strong linear dependence on the mean particle size. The proposed equilibrium and thixotropic models are valid. The forecasting models for equilibrium and transient shear stress are established based on data fit, which is attributed to the quantitative characterization of steady-state and transient rheology for thixotropic tailings pastes under the effect of particle size.

To investigate the early hydration and consolidation mechanism of superfine metal tailings powder in the CaO–CaSO4–H2O system, a clinker-free consolidation material based on iron tailings powder was prepared by superfine grinding lime, gypsum, and iron tailings. From 3 min to 24 h, the liquid phase of the hydrated slurry was extracted by centrifugation and high-pressure extraction. The changes in ion concentration and conductivity were tested, and the relationship between them was analyzed. The relationship between the formation mechanism of early hydration products of a consolidated body and the change of liquid phase characteristics is studied combined with the hydration exothermic rate curve, field emission scanning electron microscope (SEM), X-ray diffraction analysis (XRD), thermogravimetry-differential thermal analysis (TG–DSC), and other test methods. The results show that lime, gypsum, and amorphous components, which are on the surface of iron tailings powder, dissolve rapidly within a few minutes after solid-liquid mixing. The concentration of each ion in the liquid phase rises sharply, reaching the peak or saturated state successively in 10–30 min, and then decreases rapidly. After 180 min, the decline rate slows down but continues to decline. The liquid conductivity has a very high positive correlation with the total concentration of Ca2+, OH–， and SO42– ions; The first hydration exothermic peak of the consolidated material is concentrated within 0–15 min, which is mainly caused by the wetting and dissolution of soluble components in the consolidated material and the exothermic behavior of lime hydration; The starting and ending time of the second hydration exothermic behavior is 20–180 min, which is mainly caused by the phase change heat generated by the formation of hydration products. Increasing the grinding time significantly prolongs the termination time of the second exothermic behavior and increases its peak value; The phase analysis of hydration products showed that AFt characteristic peak and C–S–H endothermic peak could be seen in the slurry after hydration for 90 min. Research has proved that the amorphous SiO2 and Al2O3 on the surface of superfine iron tailings powder have the characteristics of rapid dissolution in alkaline solutions, and a hydration reaction can occur when lime and gypsum components are encountered. When the solubility product of hydration products is reached, hydration products AFt and C–S–H will be generated. The two hydration products are interspersed and cemented with each other, and the unhydrated iron tailings particles will be consolidated to form a hardened body. Prolonging the grinding time can effectively increase the system’s amorphous SiO2 and Al2O3 content and the proportion of superfine particles in iron tailings, thus improving the slurry hydration rate. While increasing the amount of the hydration product, the filling effect of the micro powder part is further increased, and the strength of the consolidated body is correspondingly improved.

In recent years, paste technology has been rapidly promoted in domestic mines. It is a key technology for realizing green mining because it can effectively solve environmental and safety problems caused by mining. With the progress in science and technology, the research level of paste technology is constantly improving. Thickening technology of tailings is the primary procedure of paste backfill technology in metal mines, which can significantly improve the efficiency of tailings dewatering and utilization rate of tailings. Tailings thickening technology is an important part of the green development of mines. This paper presented a summary of the development process of tailings thickening and dewatering technology, dividing the development stage of the thickener into three: (1) ordinary thickener stage, (2) high-efficiency thickener stage, and (3) paste thickener stage. The application status of the thickening process of tailings and several typical application cases at home and abroad were also described. In addition, this paper explored different theories, including the single flocculation theory, multiple flocculation theory, bed compression theory under static/dynamic compression, and gravity thickening theory, along with the corresponding latest research progress of each theory. This paper also presented the main research methods of thickening of tailings, namely the static settlement experiment, small-scale thickening experiment, and semi-industrial thickening experiment. Advanced observational methods such as focused beam reflection measurement technology (FBRM) and particle video microscope technology (PVM) were also introduced. Moreover, the paper expounded on the research status of numerical simulation of tailings thickening technology and highlighted that the tailings thickening and dewatering technology is still in the development stage with some underlying problems, such as the instability of the key parameters of tailings thickening, the untimely production control of tailings thickening, and the imperfect information platform of tailings thickening. Overall, the development of tailings thickening technology is still facing numerous challenges. Finally, the direction of the development of tailing thickening technology is proposed in terms of personalization, automation, and intelligence.

In the future, the output of ultrafine full tailings will explode due to the massive mining of low-grade deposits and demand for the recovery of useful minerals. The best way to dispose of ultrafine full tailings is to prepare them into the paste for filling underground voids or surface stacking. The deep cone thickening of ultrafine full tailings is a key link of tailings paste disposal technology. In the thickening process of ultrafine full tailings, slow sedimentation velocity, high dosage of flocculant, excessive overflow turbidity, and low underflow concentration are the bottlenecks that restrict the application of disposal technology for ultrafine full tailings paste. To investigate the thickening characteristics of ultrafine full tailings, the sedimentation test in measuring cylinder, the small-scale and semi-industrial deep cone dynamic thickening tests were carried out. Results show that the nonionic flocculant with a molecular weight of 12 million is most beneficial for the settlement of the tailings. With increasing flocculant dosage, the turbidity of overflow decreases and underflow concentration remains unchanged. Upon increasing the solid flux, the turbidity of overflow increases and underflow concentration decreases. In particular, when the solid flux is 0.4 t·m−2·h−1, the feeding solid mass fraction is 12%, flocculant dosage is 50 g·t−1, and average solid mass fraction of the underflow of the small-scale and semi-industrial dynamic thickening test is 62.8% and 74.4%, respectively. Mud height has a significant influence on the underflow concentration. The solid mass fraction of the underflow of the deep cone thickener increases with the increasing mud height, and this process conforms to the DoseResp function. This growth process can be divided into three stages: (1) slow growth (mud height 1–4 m), (2) rapid growth (mud height 4–7 m), and (3) basic stable (mud height over 7–8 m). This is related to the compression performance of the tailings flocs at different mud heights. According to the function relation between the underflow concentration and mud height, the mud height can be adjusted to meet the required underflow concentration for underground backfilling.

The real-time inline monitoring technologies of focused beam reflectance measurement (FBRM) and particle video microscopy (PVM) were used to analyze the aggregate structure evolution during the operation of a dynamic thickening system. The tailings dewatering studies were performed under two series of conditions: (i) rake rotation speeds of 0, 0.1, 1, and 10 r·min−1 and an initial mud bed height of 75 cm and (ii) initial mud bed heights of 75, 45, and 25 cm and a rake rotation speed of 0.1 r·min−1. The aggregate diameter, particle size distribution, and real-time images of the tailings thickening process were obtained. The results show that with the increase in the shearing time, the diameter and counts of aggregate first increase, then decrease, and then become stable. According to the aggregate diameter variation, the aggregate evolution can be divided into three stages: growth, reconstruction, and densification periods. The condition of a shear rate of 0.1 r·min−1 and an initial mud bed height of 75 cm has the best effects on the aggregate growth, structure breaking acceleration, aggregate reconstruction, and aggregate densification improvement, as determined in the laboratory; however, high shear rate has a degrading effect on the aggregate structure evolution. The aggregate diameter progressively decreases with the increase in the shear rate. The longer the aggregate growth period, the larger the maximum aggregate diameter, and a longer reconstruction period is observed at higher initial mud bed heights. Moreover, the aggregate diameter increases with the increase in the initial mud bed height. The fractal dimension of tailings aggregate reflects the change characteristics of the aggregate structure. According to the calculation of fractal dimension and porosity of the PVM image, the dynamic equilibrium relastionship between the breaking force and cohesive force of aggregates was analyzed, the influence on the aggregate breaking was analyzed. The aggregate densification rule in the tailings thickening process was revealed analyzed, based on the dynamic equilibrium relationship between the breaking force and cohesive force of aggregates.

ABSTRACT The yellow fever (YF) live attenuated vaccine strain 17D (termed 17D) has been widely used for the prevention and control of YF disease. However, 17D retains significant neurovirulence and viscerotropism in mice, which is probably linked to the increased occurrences of serious adverse events following 17D vaccination. Thus, the development of an updated version of the YF vaccine with an improved safety profile is of high priority. Here, we generated a viable bicistronic YF virus (YFV) by incorporating the internal ribosome entry site (IRES) from Encephalomyocarditis virus into an infectious clone of YFV 17D. The resulting recombinant virus, 17D-IRES, exhibited similar replication efficiency to its parental virus (17D) in mammalian cell lines, while it was highly restricted in mosquito cells. Serial passage of 17D-IRES in BHK-21 cells showed good genetic stability. More importantly, in comparison with the parental 17D, 17D-IRES displayed significantly decreased mouse neurovirulence and viscerotropism in type I interferon (IFN)-signaling-deficient and immunocompetent mouse models. Interestingly, 17D-IRES showed enhanced sensitivity to type I IFN compared with 17D. Moreover, immunization with 17D-IRES provided solid protection for mice against a lethal challenge with YFV. These preclinical data support further development of 17D-IRES as an updated version for the approved YF vaccine. This IRES-based attenuation strategy could be also applied to the design of live attenuated vaccines against other mosquito-borne flaviviruses. IMPORTANCE Yellow fever (YF) continually spreads and causes epidemics around the world, posing a great threat to human health. The YF live attenuated vaccine 17D is considered the most efficient vaccine available and helps to successfully control disease epidemics. However, side effects may occur after vaccination, such as viscerotropic disease (YEL-AVD) and neurotropic adverse disease (YEL-AND). Thus, there is an urgent need for a safer YF vaccine. Here, an IRES strategy was employed, and a bicistronic YFV was successfully developed (named 17D-IRES). 17D-IRES showed effective replication and genetic stability in vitro and high attenuation in vivo. Importantly, 17D-IRES induced humoral and cellular immune responses and conferred full protection against lethal YFV challenge. Our study provides data suggesting that 17D-IRES, with its prominent advantages, could be a vaccine candidate against YF. Moreover, this IRES-based bicistronic technology platform represents a promising strategy for developing other live attenuated vaccines against emerging viruses.

The high-concentration slurry prepared from full tailings used for mine backfilling can effectively eliminate the disasters caused by underground voids and tailing ponds. Using pipelines to transport filling slurry is the most efficient way, and the pipe resistance is one of the most important parameters. Presently, the loop test method for studying the pipe transportation parameters of filling slurry is closest to engineering reality. To determine the influence of the cement-sand ratio, concentration, and flow velocity of the high-concentration filling slurry prepared from full tailings on the pipe resistance and predict the resistance of industrial filling pipelines, pilot-scale loop tests were performed. A pipe resistance prediction model was established based on the relationship between the shear stress and the shear rate at the pipe wall. The gray correlation method was used to analyze the influence of various factors on the pipe resistance, and the rheological parameters of filling slurry were obtained by linear regression. The results show that the pipe resistance is most sensitive to the mass concentration of filling slurry and increases quadratically. The flow velocity of filling slurry has the second-greatest effect on pipe resistance, and the resistance increases linearly with flow velocity in laminar flow. The cement-sand ratio of filling slurry has a dual effect on the pipe resistance. When the cement-sand ratio is less than 1∶8, the cohesion effect of the cementing material is dominant and increases the pipe resistance. On the contrary, the lubrication effect of the cementing material is dominant and reduces the pipe resistance. The rheological parameters of filling slurry obtained by the loop test are much smaller than those obtained by the rheometer, and the loop test method is more reliable. The error of the pipe resistance prediction model is within 10%.

Dependence on glutamine and acceleration of fatty acid oxidation (FAO) are both metabolic characteristics of triple‐negative breast cancer (TNBC). With the rapid growth of tumors, accelerated glutamine catabolism depletes local glutamine, resulting in glutamine deficiency. Studies have shown that the use of alternative energy sources, such as fatty acids, enables tumor cells to continue to proliferate rapidly in a glutamine‐deficient microenvironment. However, the detailed mechanisms behind this metabolic change are still unclear. Herein, we identified HRD1 as a regulatory protein for FAO that specifically inhibits TNBC cell proliferation under glutamine‐deficient conditions. Furthermore, we observed that HRD1 expression is significantly downregulated under glutamine deprivation and HRD1 directly ubiquitinates and stabilizes CPT2 through K48‐linked ubiquitination. In addition, the inhibition of CPT2 expression dramatically suppresses TNBC cell proliferation mediated by HRD1 knockdown in vitro and in vivo. Finally, we found that the glutaminase inhibitor CB839 significantly inhibited TNBC cell tumor growth, but not in the HRD1 knock‐downed TNBC cells. These findings provide an invaluable insight into HRD1 as a regulator of lipid metabolism and have important implications for TNBC therapeutic targeting.

Abstract Objectives To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. Methods The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. Results The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47–10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P

Yellow fever virus (YFV) is a re-emerging flavivirus, which can lead to severe clinical manifestations and high mortality, with no specific antiviral therapies available. The live-attenuated yellow fever vaccine 17D (YF17D) has been widely used for over eighty years. However, the emergence of yellow fever vaccine-associated viscerotropic disease (YFL-AVD) and yellow fever vaccine-associated neurotropic disease (YFL-AND) raised non-negligible concerns. Additionally, the attenuation mechanism of YF17D is still unclear. Thus, the development of convenient models is crucial to understand the mechanisms behind YF17D attenuation and its adverse effects. In this work, we generated a reporter YF17D expressing nano-luciferase (NLuc). In vitro and in vivo characterization demonstrated that the NLuc-YF17D shared similar biological properties with its parental strain and the NLuc activity can reflect viral infectivity reliably. Combined with in vivo bioluminescence imaging, a series of mice models of YF17D infection was established, which will be useful for the evaluation of antiviral medicines and novel vaccine candidates. Especially, we demonstrated that intraperitoneally (i.p.) infection of NLuc-YF17D in type I interferon receptor-deficient mice A129 resulted in outcomes resembling YEL-AVD and YEL-AND, evidenced by viral replication in multiple organs and invasion of the central neuronal system. Finally, in vitro and in vivo assays based on this reporter virus were established to evaluate the antiviral activities of validated antiviral agents. In conclusion, the bioluminescent reporter virus described herein provides a powerful platform to study YF17D attenuation and vaccine-associated diseases as well as to develop novel countermeasures against YFV.

Abstract Background Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. Results The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = − 3.3 mm [5.31, − 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = − 4.39 ml [− 8.09, − 0.7]); the difference in the mean change in E/e′ between GLP-1 agonists and placebo (MD = − 1.05[− 1.78, − 0.32]); and the difference in the mean change in E/e′ between SGLT-2 inhibitors and placebo (MD = − 1.91[− 3.39, − 0.43]). Conclusions GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e′, SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′, and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

Background: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. Methods: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. Results: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). Conclusions: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

The mine tailings generated from metallic ore not only occupies a large area of surface resources but also easily causes mud-rock flow and tailings dam failure. Moreover, the existence of a large number of underground voids threatens the safety of underground mining operations and can induce mines earthquake and surface subsidence. The paste filling technology involves thickening the mine tailings into paste and placing the paste in underground voids. The technology has been widely accepted and applied around the world for its advantages in safety, environmental protection, economy, and high efficiency. The dewatering of mine tailings is a prerequisite for the paste filling process. In the paste backfill, after tailings thickening, the concentration increase is limited, the yield stress is increased, and fluidity is reduced with flocculant dosage. The flocculant dosage and thickening synergist work together to further increase unclassified tailings paste concentration and reduce slurry yield stress. The mechanism of the thickening synergist was researched from a microscopic point of view. The results show that the best addition method is to add thickening synergist after tailings settlement with flocculant dosage by settlement and rheological test. The solid mass fraction can be increased by 8.57%‒10.13%, and the yield stress can be reduced by 6.68‒12.85 Pa. The multi-component thickening synergist can not only reduce unit consumption and cost but also improve the compressive strength of the paste backfill material. The compressive strength of paste backfill material with thickening synergist and cement-tailings mass ratio of 1∶12 is 2.5 MPa at the age of 28 d. The difference is less than 20% compared with the compressive strength of the material with cement-tailings mass ratio of 1∶6 and without thickening synergist. By total organic carbon adsorption test and Zeta potential test, the synergist is found to have functions of adsorption and dispersion. It can destroy the flocculation structure and release the contained water, thereby increasing the tailings concentration and improving the fluidity of tailings particles.

To calculate the required strength of a cemented backfill with high aspect ratio, the confirmation of lateral pressure is fundamental and needs to be determined first. As for the backfill with a high aspect ratio of height to length, the shape of the slip surface is not straight when in the active state due to the limited space, which is different from the general backfill. For this reason, a formulation of the slip surface with a curved shape and a lateral pressure calculation method based on this curved slip surface were proposed. The proposed equation of the slip surface is affected by the geometry parameters of the backfill, internal friction angle of the backfill, and the friction angle of the backfill-rock interface. Then, by the combination of the minor principal stress trajectory method and the horizontal slice method, an ordinary differential equation of stresses was established and then solved numerically. Finally, the method based on Mitchell’s three-dimensional limit equilibrium model was used to calculate the required strength of the cemented backfill. The calculated results were compared with previous studies and validated with numerical models. The results showed good consistency for the backfills with high aspect ratios.

Given the recent Zika virus (ZIKV) epidemic, development of an effective vaccine is of high importance. Here, the authors use a licensed live-attenuated flavivirus vaccine backbone to develop a ZIKV vaccine and determine immunogenicity, safety and protection profiles in different animal models.

Zika virus (ZIKV) has evolved from an overlooked mosquito-borne flavivirus into a global health threat due to its astonishing causal link to microcephaly and other disorders. ZIKV has been shown to infect neuronal progenitor cells of the fetal mouse brain, which is comparable to the first-trimester human fetal brain, and result in microcephaly. However, whether there are different effects between the contemporary ZIKV strain and its ancestral strain in the neonatal mouse brain, which is comparable with the second-trimester human fetal brain, is unclear. Here we adopted a mouse model which enables us to study the postnatal effect of ZIKV infection. We show that even 100 pfu of ZIKV can replicate and infect neurons and oligodendrocytes in most parts of the brain. Compared with the ancestral strain from Cambodia (CAM/2010), infection of the ZIKV strain from Venezuela (VEN/2016) leads to much more severe microcephaly, accompanied by more neuronal cell death, abolishment of oligodendrocyte development, and a more dramatic immune response. The serious brain damage caused by VEN/2016 infection would be helpful to elucidate why the American strain resulted in severe neurovirulence in infants and will provide clinical guidance for the diagnosis and treatment of infection by different ZIKV strains.

Thickening performance is greatly influenced by aggregate densification and channelling development; however, the microstructures of aggregates and channelling are unable to directly observe because of high turbidity mud bed during thickening. Computed tomography scan imaging technique has been introduced to investigate the effects of aggregate densification and channelling in the mud bed samples during unclassified tailings thickening. The samples were prepared through deep-freezing and freeze-drying techniques, immediately after sampling from the operation of a pilot thickener. Based on the information of void ratio, pore-size distribution, and permeability, obtained from 3D reconstruction images of the aggregates structure, aggregate densification and channelling development have been characterized. Channelling patterns have been classified by the size and shape of the connection throat of the pore between aggregates. As the aggregate structure broke and densified, the void ratio and pore size of the mud bed were decreased. Thickening performance enhancement was predicted based on solid flux and permeability of mud bed, and the result indicated raking on aggregate densification and channelling apparently improves the unclassified tailings dewatering extent.

Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10 days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

Abstract Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer.

Retrospective analysis was performed on 30 patients of skull defect who underwent surgical repair. Intraoperative and postoperative curative effect was evaluated on those patients, and the results showed that the incidence rate of intraoperative dura mater defect (P = 0.001), early postoperative complications [new epilepsy (P = 0.035) and effusion (P = 0.021)] and late postoperative complications [foreign body sensation (P = 0.035) and dizziness and headache (P = 0.050)] in long-term skull defect group were all higher than those in control group. In conclusion, surgical repair of long-term skull defect incurring high risk and various complications will not be an ideal management. Therefore, early surgical treatment for skull defect is suggested. DOI: 10.3969/j.issn.1672-6731.2015.12.016