Effects of "fixation-fusion" sequence of lumbar surgery on surgical outcomes for patients with lumbar spinal stenosis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. METHODS AND ANALYSIS: This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis populations in the study. CONCLUSION: This study is designed to investigate the clinical outcomes of modified LIF sequences in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified "fixation-fusion" sequence of LIF surgery is effective in treating lumbar spinal stenosis. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507.

Self-wavelength shifting in two-dimensional perovskite for sensitive and fast gamma-ray detection.

Lead halide perovskites have recently emerged as promising X/γ-ray scintillators. However, the small Stokes shift of exciton luminescence in perovskite scintillators creates problems for the light extraction efficiency and severely impedes their applications in hard X/γ-ray detection. Dopants have been used to shift the emission wavelength, but the radioluminescence lifetime has also been unwantedly extended. Herein, we demonstrate the intrinsic strain in 2D perovskite crystals as a general phenomenon, which could be utilized as self-wavelength shifting to reduce the self-absorption effect without sacrificing the radiation response speed. Furthermore, we successfully demonstrated the first imaging reconstruction by perovskites for application of positron emission tomography. The coincidence time resolution for the optimized perovskite single crystals (4 × 4 × 0.8 mm3) reached 119 ± 3 ps. This work provides a new paradigm for suppressing the self-absorption effect in scintillators and may facilitate the application of perovskite scintillators in practical hard X/γ-ray detections.

Reduction of Adolescent Idiopathic Scoliosis and Improved Z-Axis Alignment of the Entire Spine When Treating a Symptomatic Patient Using a Multidisciplinary Approach: A Case Report.

Background: This study presents findings on improvements of both the X-axis and Z-axis posture in a young female with adolescent idiopathic, scoliosis suffering from pain complaints who was treated with a multidisciplinary approach. Case Presentation: The 15-year-old patient reported low back pain for several months. Full spine radiographic assessment revealed a cervical kyphosis, forward head translation, a right ribcage translation, a left higher shoulder, and a dextroconvex lumbar scoliosis with a Cobb angle of 23°. The patient was treated with novel ASPINE Systems treatment protocols incorporating posture exercises, muscle balancing exercises, spinal 3D traction, and spinal manipulation. Results: Assessment after 50 treatment sessions over 32 weeks revealed a dramatic improvement in postural distortions. The cervical kyphosis was reduced by 9° and was accompanied by a reduction in forward head posture, centering of the thoracic spine, leveling off her shoulders, and a reduction in the dextroconvex scoliosis by 10°. The lower back pain was relieved. Conclusion: A reduction of postural distortions including idiopathic adolescent scoliosis resulted from a multidisciplinary approach utilizing ASPINE Systems.

MiR-135a-5p suppresses trophoblast proliferative, migratory, invasive, and angiogenic activity in the context of unexplained spontaneous abortion.

BACKGROUND: Spontaneous abortions (SA) is amongst the most common complications associated with pregnancy in humans, and the underlying causes cannot be identified in roughly half of SA cases. We found miR-135a-5p to be significantly upregulated in SA-associated villus tissues, yet the function it plays in this context has yet to be clarified. This study explored the function of miR-135a-5p and its potential as a biomarker for unexplained SA. METHOD: RT-qPCR was employed for appraising miR-135a-5p expression within villus tissues with its clinical diagnostic values being assessed using ROC curves. The effects of miR-135a-5p in HTR-8/SVneo cells were analyzed via wound healing, Transwell, flow cytometry, EdU, CCK-8, and tube formation assays. Moreover, protein expression was examined via Western blotting, and interactions between miR-135a-5p and PTPN1 were explored through RIP-PCR, bioinformatics analyses and luciferase reporter assays. RESULTS: Relative to normal pregnancy (NP), villus tissue samples from pregnancies that ended in unexplained sporadic miscarriage (USM) or unexplained recurrent SA (URSA) exhibited miR-135a-5p upregulation. When this miRNA was overexpressed in HTR-8/SVneo cells, their migration, proliferation, and cell cycle progression were suppressed, as were their tube forming and invasive activities. miR-135a-5p over-expression also downregulated the protein level of cyclins, PTPN1, MMP2 and MMP9. In RIP-PCR assays, the Ago2 protein exhibited significant miR-135a-5p and PTPN1 mRNA enrichment, and dual-luciferase reporter assays indicated PTPN1 to be a bona fide miR-135a-5p target gene within HTR-8/SVneo cells. CONCLUSION: miR-135a-5p may suppress trophoblast migratory, invasive, proliferative, and angiogenic activity via targeting PTPN1, and it may thus offer value as a biomarker for unexplained SA.

MYB43 as a novel substrate for CRL4PRL1 E3 ligases negatively regulates cadmium tolerance through transcriptional inhibition of HMAs in Arabidopsis.

Controlled stability of proteins is a highly efficient mechanism to direct diverse processes in plants. A key regulatory system for protein stability is given by the CULLIN-RING E3 ligases (CRLs). In this work, MYB43 is identified as a novel target of a CUL4-DDB1-PRL1 (PLEIOTROPIC REGULATORY LOCUS 1)-RING E3 ligase (CRL4PRL1 E3 ligase). Its stability depends on the presence of PRL1, a WD40-containing protein functioning as a substrate receptor of the CRL4 E3 ligases. Genetic studies have indicated that MYB43 is a negative regulator of cadmium (Cd) tolerance in Arabidopsis by transcriptional inhibition of important Cd transporters (HMA2, HMA3 and HMA4), while PRL1 and CUL4 positively regulate Cd tolerance. Expression of CUL4 and PRL1 was enhanced in response to Cd stress, and PRL1 can interact with and target MYB43 for degradation depending on assembly of CRL4PRL1 E3 ligase, and consequently increase the expression of HMA2, HMA3 and HMA4 through attenuating the transcriptional inhibition. HMA2 and HMA4 are shown to transport cadmium ion (Cd2+ ) from the roots of plants to the shoots through the xylem, ultimately increasing the plants' tolerance to Cd stress.

Chemical Potential Diagram Guided Rational Tuning of Electrical Properties: A Case Study of CsPbBr3 for X-ray Detection.

Controlling the carrier polarity and concentration underlies most electronic and optoelectronic devices. However, for the intensively studied lead halide perovskites, the doping tunability is inefficient. In this work, taking CsPbBr3 as an example, it is revealed that the coexistence of metallic Pb or CsBr3 /Br2 , rather than the precursor ratio, can provide Pb-rich/Br-poor or Br-rich/Pb-poor chemical conditions, enabling the tunability of electrical properties from weak n-type, intrinsic, to moderate p-type. Experimentally, under Br2 -exposure treatment, a shift of the Fermi level as large as 1.00 eV is achieved, which is one of the highest value among all kinds of doping methods. The X-ray detector based on the intrinsic CsPbBr3 exhibits excellent performance, with a negligible dark-current drift of 7.1 × 10-4 nA cm-1 s-1 V-1 , a low detection limit of 103.6 nGyair s-1 , and a high sensitivity of 9085 µC Gyair -1 cm-2 . This work provides a critical understanding and guidance for tuning the electrical properties of lead halide perovskites, which establishes good foundations for achieving intrinsic perovskite semiconductors and also constructing potential homojunction devices.

Lead halide perovskite for efficient optoacoustic conversion and application toward high-resolution ultrasound imaging.

Lead halide perovskites have exhibited excellent performance in solar cells, LEDs and detectors. Thermal properties of perovskites, such as heat capacity and thermal conductivity, have rarely been studied and corresponding devices have barely been explored. Considering the high absorption coefficient (104~105 cm-1), low specific heat capacity (296-326 J kg-1 K-1) and small thermal diffusion coefficient (0.145 mm2 s-1), herein we showcase the successful use of perovskite in optoacoustic transducers. The theoretically calculated phonon spectrum shows that the overlap of optical phonons and acoustic phonons leads to the up-conversion of acoustic phonons, and thus results in experimentally measured low thermal diffusion coefficient. The assembled device of PDMS/MAPbI3/PDMS simultaneously achieves broad bandwidths (-6 dB bandwidth: 40.8 MHz; central frequency: 29.2 MHz), and high conversion efficiency (2.97 × 10-2), while all these parameters are the record values for optoacoustic transducers. We also fabricate miniatured devices by assembling perovskite film onto fibers, and clearly resolve the fine structure of fisheyes, which demonstrates the strong competitiveness of perovskite based optoacoustic transducers for ultrasound imaging.

The effect of ABRE BINDING FACTOR 4-mediated FYVE1 on salt stress tolerance in Arabidopsis.

FYVE1 encodes a protein that is localized to the peripheral membrane of late endosomal compartments, and is involved in the regulation of mulitivesicular/prevacuolar compartment protein sorting. It was found that FYVE1 attenuates ABA signaling through degrading ABA receptors PYR1 and PYL4 by ESCRT pathway, and also interacts with transcription factors ABF4 and ABI5 to transcriptionally inhibit ABA signaling pathway by reducing their binding to the cis-regulatory sequences of their downstream genes. However, the mechanisms underlying the transcriptional regulation of FYVE1 and its biological function in salt stress are largely unknown. Here, we show that fyve1 knockdown-mutants show enhanced tolerance to salt stress, while overexpression of FYVE1 results in increased sensitivity to salt stress. Further analysis shows that FYVE1 negatively regulates salt stress tolerance, which is associated with ABA signaling pathway. ABRE BINDING FACTOR 4 (ABF4) directly binds to promoter of FYVE1 to activate its transcription. Moreover, FYVE1 interacts with and promotes degradation of all ABA PYR/PYL receptors. Thus, our results suggest that FYVE1 negatively modulates salt stress tolerance in Arabidopsis via a negative feedback loop.

Hot-Pressed CsPbBr3 Quasi-Monocrystalline Film for Sensitive Direct X-ray Detection.

An X-ray detector with high sensitivity would be able to increase the generated signal and reduce the dose rate; thus, this type of detector is beneficial for applications such as medical imaging and product inspection. The inorganic lead halide perovskite CsPbBr3 possesses relatively larger density and a higher atomic number in contrast to its hybrid counterpart. Therefore, it is expected to provide high detection sensitivity for X-rays; however, it has rarely been studied as a direct X-ray detector. Here, a hot-pressing method is employed to fabricate thick quasi-monocrystalline CsPbBr3 films, and a record sensitivity of 55 684 µC Gyair -1 cm-2 is achieved, surpassing all other X-ray detectors (direct and indirect). The hot-pressing method is simple and produces thick quasi-monocrystalline CsPbBr3 films with uniform orientations. The high crystalline quality of the CsPbBr3 films and the formation of self-formed shallow bromide vacancy defects during the high-temperature process result in a large µτ product and, therefore, a high photoconductivity gain factor and high detection sensitivity. The detectors also exhibit relatively fast response speed, negligible baseline drift, and good stability, making a CsPbBr3 X-ray detector extremely competitive for high-contrast X-ray detections.

Effect of age at first use of oral contraceptives on breast cancer risk: An updated meta-analysis.

BACKGROUND: We evaluated the relationship between the age at first use of oral contraceptives (OC) and breast cancer (BC) risk. METHODS: We searched PubMed, Embase, and related reviews published through June 28, 2018, and used summary relative risk (RR) and 95% confidence intervals (CIs) to evaluate the cancer risks, and fixed-effects dose-response meta-analysis to assess potential linear and non-linear dose-response relationships. RESULTS: We included 10 studies, with 8585 BC cases among 686,305 participants. The pooled RR for BC was 1.24 (95% CI: 1.10-1.41), with moderate heterogeneities (I = 66.5%, P < .001). No significant publication bias was found (P = .584 for Begg test, P = .597 for Egger test). A linear dose-response relationship between the age at first OC use and BC risk was detected (P = .518 for non-linearity). Subgroup analyses were restricted to studies done by BC subtypes, region, sample size, follow-up time and study quality. Inconsistent consequences with no statistical significance were explored when limited to studies from Western countries, study quality <7, sample size <10,000, follow-up time <5 years, and BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression status in tumor tissue. Sensitivity analyses indicated that our results were stable and reliable after removing each study in turn and omitting studies of adjusted unreported variables. CONCLUSION: A significant linear relationship between the age at first OC use and BC risk was confirmed. No further consistent differences are noted in multiple aspects of BC subtypes defined by progesterone or ER status.

Heteroepitaxial passivation of Cs2AgBiBr6 wafers with suppressed ionic migration for X-ray imaging.

X-ray detectors are broadly utilized in medical imaging and product inspection. Halide perovskites recently demonstrate excellent performance for direct X-ray detection. However, ionic migration causes large noise and baseline drift, limiting the detection and imaging performance. Here we largely eliminate the ionic migration in cesium silver bismuth bromide (Cs2AgBiBr6) polycrystalline wafers by introducing bismuth oxybromide (BiOBr) as heteroepitaxial passivation layers. Good lattice match between BiOBr and Cs2AgBiBr6 enables complete defect passivation and suppressed ionic migration. The detector hence achieves outstanding balanced performance with a signal drifting one order of magnitude lower than all previous studies, low noise (1/f noise free), a high sensitivity of 250 µC Gy air-1 cm-2, and a spatial resolution of 4.9 lp mm-1. The wafer area could be easily scaled up by the isostatic-pressing method, together with the heteroepitaxial passivation, strengthens the competitiveness of Cs2AgBiBr6-based X-ray detectors as next-generation X-ray imaging flat panels.

Photophysical Pathways in Highly Sensitive Cs2 AgBiBr6 Double-Perovskite Single-Crystal X-Ray Detectors.

The sensitive detection of X-rays embodies an important research area, being motivated by a common desire to minimize the radiation doses required for detection. Among metal halide perovskites, the double-perovskite Cs2 AgBiBr6 system has emerged as a promising candidate for the detection of X-rays, capable of high X-ray stability and sensitivity (105 µC Gy-1 cm-2 ). Herein, the important photophysical pathways in single-crystal Cs2 AgBiBr6 are detailed at both room (RT) and liquid-nitrogen (LN2 T) temperatures, with emphasis made toward understanding the carrier dynamics that influence X-ray sensitivity. This study draws upon several optical probes and an RT excitation model is developed which is far from optimal, being plagued by a large trap density and fast free-carrier recombination pathways. Substantially improved operating conditions are revealed at 77 K, with a long fundamental carrier lifetime (>1.5 µs) and a marked depopulation of parasitic recombination pathways. The temperature dependence of a single-crystal Cs2 AgBiBr6 X-ray detecting device is characterized and a strong and monotonic enhancement to the X-ray sensitivity upon cooling is demonstrated, moving from 316 µC Gy-1 cm-2 at RT to 988 µC Gy-1 cm-2 near LN2 T. It is concluded that even modest cooling-via a Peltier device-will facilitate a substantial enhancement in device performance, ultimately lowering the radiation doses required.

RNA binding protein HuR promotes osteosarcoma cell progression via suppressing the miR-142-3p/HMGA1 axis.

The present study aimed to study the roles and underlying mechanisms of human antigen R (HuR) in osteosarcoma (OS) cell progression. It was determined that the HuR mRNA and protein levels were significantly upregulated in OS tissues, compared with that in normal adjacent tissues. HuR expression was negatively associated with miR-142-3p expression, but positively with High Mobility Group AT-Hook 1 (HMGA1). Additionally, knockdown of HuR inhibited OS cells viability, epithelial-mesenchymal transition and promoted cell apoptosis. HuR was determined to harbor binding sites on HMGA1, directly binding to HMGA1, increasing HMGA1 mRNA stability and expression. Notably, the promotion of HuR on HMGA1 expression was attenuated via miR-142-3p overexpression, and miR-142-3p could directly bind to HMGA1 3'untranslated region (UTR). Furthermore, HMGA1 3'UTR with a mutated miR-142-3p binding site did not respond to HuR alterations. Finally, the inhibition of HuR knockdown was attenuated or even reversed via HMGA1 overexpression; therefore, the results of the present study indicated that RNA binding protein HuR may facilitate OS cell progression via competitively binding to HMGA1 with miR-142-3p.

RNA binding protein Lin28A promotes osteocarcinoma cells progression by associating with the long noncoding RNA MALAT1.

OBJECTIVES: To explore the effects of Lin28A on progression of osteocarcinoma (OS) cells. RESULTS: Lin28A mRNA and protein expressions were significantly increased in OS tissues compared with that in normal adjacent tissues. Expressions of Lin28A and long noncoding RNA MALAT1 were positively correlated. Patients with higher Lin28A expression had shorter overall survival. Moreover, Lin28A knockdown inhibited OS cells proliferation, migration, invasion and promoted cell apoptosis; Lin28A was found to harbor binding sites on MALAT1 sequences and associated with MALAT1, and increased MALAT1 stability and expression. Notably, the inhibition of Lin28A knockdown was attenuated or even reversed by MALAT1 overexpression. CONCLUSIONS: RNA binding protein Lin28A could facilitate OS cells progression by associating with the long noncoding RNA MALAT1.

High-Pressure Band-Gap Engineering in Lead-Free Cs2 AgBiBr6 Double Perovskite.

Novel inorganic lead-free double perovskites with improved stability are regarded as alternatives to state-of-art hybrid lead halide perovskites in photovoltaic devices. The recently discovered Cs2 AgBiBr6 double perovskite exhibits attractive optical and electronic features, making it promising for various optoelectronic applications. However, its practical performance is hampered by the large band gap. In this work, remarkable band gap narrowing of Cs2 AgBiBr6 is, for the first time, achieved on inorganic photovoltaic double perovskites through high pressure treatments. Moreover, the narrowed band gap is partially retainable after releasing pressure, promoting its optoelectronic applications. This work not only provides novel insights into the structure-property relationship in lead-free double perovskites, but also offers new strategies for further development of advanced perovskite devices.

catena-Poly[[[diaqua-copper(II)]-µ-2,2'-{[p-phenyl-enebis(oxymethyl-ene)]bis-(pyridinium-3,1-di-yl)}diacetate] dibromide].

The title centrosymmetric coordination polymer, {[Cu(C(22)H(20)N(2)O(6))(H(2)O)(2)]Br(2)}(n), formed by the reaction of the flexible double betaine ligand 2,2'-{[p-phenyl-enebis(oxymethyl-ene)]bis-(pyridine-3,1-di-yl)}diacetic acid with CuBr(2), contains a Cu(II) atom ( symmetry) which is surrounded by two water molecules and bridged by two anions in a square-planar coordination. In the crystal, polymeric zigzag chains are linked via O-H⋯Br inter-actions, forming a two-dimensional network extending parallel to (011).

catena-Poly[[[tetra-aqua-cadmium(II)]-µ-3,3'-[p-phenyl-enebis(oxymethyl-ene)]bis-(1-pyridinioacetate)] dinitrate hemihydrate].

In the title polymeric coordination complex, {[Cd(C(22)H(20)N(2)O(6))(H(2)O)(4)](NO(3))(2)·0.5H(2)O}(n), obtained from the self-assembly of the flexible double betaine 3,3'-[p-phenyl-enebis(oxymethyl-ene)]bis-(1-pyridinioacetate) with cadmium nitrate, both the octa-hedrally coordinated Cd(II) cation and the substituted betaine ligand lie on inversion centres. The chains constructed through the trans-related acetate groups of the ligand are inter-connected via O-H⋯O hydrogen bonds involving coordinated aqua ligands, the nitrate anions and the partial-occupancy (0.25) water mol-ecule of solvation, forming a three-dimensional structure.

1-Carboxymethyl-1'-carboxylatomethyl-3,3'-[p-phenylenebis(oxymethylene)]dipyridinium bromide dihydrate.

In the crystal structure of the title salt, C(22)H(21)N(2)O(6) (+)·Br(-)·2H(2)O, pairs of betaine mol-ecules are bridged by protons (the bridging proton is disordered), forming strong and symmetrical O-H⋯O hydrogen bonds, leading to an infinite chain along the b axis. The water mol-ecules are linked to the betaine mol-ecule and the bromide ion through O-H⋯O and O-H⋯Br inter-actions. The central ring, located on an inversion centre, makes dihedral angles of 1.2 (2)° with the outer rings. One of the carboxylic acid groups is deprotonated.