Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier.

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.

Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT (OFT)) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor (BPTF) to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

Dynamics studies for the multi-well and multi-channel reaction of OH with C2H2 on a full-dimensional global potential energy surface.

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

Reversible Recognition-Based Boronic Acid Probes for Glucose Detection in Live Cells and Zebrafish.

Glucose, a critical source of energy, directly determines the homeostasis of the human body. However, due to the lack of robust imaging probes, the mechanism underlying the changes of glucose homeostasis in the human body remains unclear. Herein, diboronic acid probes with good biocompatibility and high sensitivity were synthesized based on an ortho-aminomethylphenylboronic acid probe, phenyl(di)boronic acid (PDBA). Significantly, by introducing the water-solubilizing group -CN directly opposite the boronic acid group and -COOCH3 or -COOH groups to the ß site of the anthracene in PDBA, we obtained the water-soluble probe Mc-CDBA with sensitive response (F/F0 = 47.8, detection limit (LOD) = 1.37 µM) and Ca-CDBA with the highest affinity for glucose (Ka = 4.5 × 103 M-1). On this basis, Mc-CDBA was used to identify glucose heterogeneity between normal and tumor cells. Finally, Mc-CDBA and Ca-CDBA were used for imaging glucose in zebrafish. Our research provides a new strategy for designing efficient boronic acid glucose probes and powerful new tools for the evaluation of glucose-related diseases.

Effect of miRNA-146a-mediated TLR4 Signal Pathway on the Pain of Lumbar Disc Herniation.

The current experiment was carried out to explore the effect of the miR-146a-mediated TLR4 signaling pathway on the lumbar disc herniation pains. For this aim, a total of 32 rats were divided randomly into 4 groups - the blank group (Group C), Model group (M), miR-146a overexpression group (agomiR-146a group) and negative control group (NC group), with 8 rats in each group. Rats in Group M were prepared for the construction of lumbar disc herniation models, while those in the agomiR-146a group or NC group, in addition to the model construction, would receive the intrathecal injection of agomiR-146a or agomiRNA-146a NC. Thereafter, a series of tests were performed for rats, including the mechanical pain test and heat pain test to measure the pain threshold, RT-PCR to detect the expression of miR-146a, and the transcription of TLR4, IRAK1, TRAF6, IL-6 and TNF-α, Western blot to determine the expression of IRAK1 and TRAF6 and ELISA to determine the expression of IL-6 and TNF-α. Results showed that as compared to the blank group, rats in Group M were more sensitive to the pains, presenting with declines in the thresholds in the pain, and upregulation in the TRL4 signaling pathway (TLR4, IRAK1 and TRAF6) and pro-inflammatory factors, including IL-6 and TNF-α. In comparison with Group M, intrathecal injection of agomiR-146a relieved the pains, with significant upregulation of miR-146a and downregulation of TLR4, IRAK1, TRAF6, IL-6 and TNF-α. Then upregulation of miR-146a could reduce the activity of the TLR4 signaling pathway and the release of pro-inflammatory factors, which may be a potential strategy for the treatment of lumbar disc herniation.

Fully quantum calculations of the line shape parameters for 1-0 P(22) and P(31) lines of CO perturbed by He or Ar.

This work reports the full quantum calculations of the spectral line shape parameters for the P(22) line of 13CO and the P(31) line of 12CO in the fundamental band perturbed by He or Ar from 20 to 1000 K for the first time. The generalized spectroscopic cross sections of CO-He/Ar indicate that the Dicke narrowing effect competes with the pressure broadening effect. The pressure broadening can be explained by the dynamic behaviors of intermolecular collisions. The intermolecular inelastic collisions contribute more than 95% to the pressure broadening in both CO-He and CO-Ar systems at high temperatures. Regarding the state-to-state inelastic contributions to pressure broadening, the maximum contribution out of the final state of a given line is close to that out of the initial state. The Dicke narrowing effect influences the line shape profile significantly at high temperatures, which suggests that it is indispensable for reproducing the spectral line profile. With the Dicke narrowing effect, the calculated pressure-broadening coefficients and spectral intensity distribution are in good agreement with the available experimental observations.

Cervical rotational osteotomy for correction of axial deformity in a patient with ankylosing spondylitis.

PURPOSE: Severe cervical axial deformity associated with ankylosing spondylitis (AS) is rare in clinic, and there are little concerns about surgical treatment of axial deformity associated with AS. The case study aims to show the surgical technique to perform cervical rotational osteotomy. METHODS: We present the case of a young AS patient whose neck was fixed in a left-rotational posture at 18°, requiring his trunk to be turned to the right to look forward visually. This made his gait appear to be limping, inconveniencing him with great difficulty. In order to correct this deformity, we performed a novel cervical rotational osteotomy through a one-stage posterior-anterior-posterior approach. Firstly, we performed laminectomies of C7 and T1, followed by a C7/T1 facetectomy with release of the bilateral C8 nerve roots. Next, we performed C7/T1 discectomy, bony resection of the lateral body and uncovertebral joints. The head of the patient was then rotated manually, so that both his face and torso were simultaneously facing frontward. Finally, rods spanning the screws from C6 to T2 were fixed. RESULTS: Postoperatively, the patient's axial malalignment was significantly improved, and he was able to walk normally. Surgical outcomes were well maintained at a 3-year follow-up. CONCLUSION: Through this case, we hope to draw the attention to spinal axial deformity and provide a reference point in the surgical treatment of spinal axial deformity.

Predictors for second-stage posterior direct decompression after lateral lumbar interbody fusion: a review of five hundred fifty-seven patients in the past five years.

PURPOSE: To analyze the predictors for second-stage posterior direct decompression (PDD) after lateral lumbar interbody fusion (LLIF) procedure. METHODS: We studied patients who underwent LLIF for degenerative lumbar spinal stenosis in the last five years, from July 2016 to June 2021. All surgical levels were grouped according to Schizas' central canal stenosis (CCS) classification, Pathria's facet joint degeneration (FJD) classification, Bartynski's lateral recess stenosis (LRS) classification, and Lee's foraminal stenosis (FS) classification. Second-stage PDD rates of each subgroup and their annual change were analyzed. Evaluation of risk factors associated with PDD was investigated. RESULTS: A total of 901 segments from 557 patients were included. The overall PDD rate was 29.97%. An overall PDD rate of 75.21% for grade D CCS, 29.74% for grade C CCS, 41.67% for grade 3 FJD, 37.61% for grade 3 LRS, and 40.70% for grade 3 FS was shown. While there was a continuous decline in annual PDD rate in the past four years, the annual PDD rate for grade D remained at very high levels. Logistic regression analysis had shown grade D CCS as the utmost risk factor for PDD (OR = 17.77). And grade 3 LRS (OR = 4.63), grade 3 FS (OR = 2.42), grade C CCS (OR = 2.41), and grade 3 FJD (OR = 2.04) were also moderately correlated with PDD, which meant they only moderately increased the risk of PDD. CONCLUSION: Extreme severe lumbar CCS (grade D) is the greatest determinant to perform the second-stage PDD procedure after LLIF.

Dissection of the Multichannel Reaction O(3P) + C2H2: Differential Cross-Sections and Product Energy Distributions.

The O(3P) + C2H2 reaction plays an important role in hydrocarbon combustion. It has two primary competing channels: H + HCCO (ketenyl) and CO + CH2 (triplet methylene). To further understand the microscopic dynamic mechanism of this reaction, we report here a detailed quasi-classical trajectory study of the O(3P) + C2H2 reaction on the recently developed full-dimensional potential energy surface (PES). The entrance barrier TS1 is the rate-limiting barrier in the reaction. The translation of reactants can greatly promote reactivity, due to strong coupling with the reaction coordinate at TS1. The O(3P) + C2H2 reaction progress through a complex-forming mechanism, in which the intermediate HCCHO lives at least through the duration of a rotational period. The energy redistribution takes place during the creation of the long-lived high vibrationally (and rotationally) excited HCCHO in the reaction. The product energy partitioning of the two channels and CO vibrational distributions agree with experimental data, and the vibrational state distributions of all modes of products present a Boltzmann-like distribution.

Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury.

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1ß, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.

Theoretical H + O3 rate coefficients from ring polymer molecular dynamics on an accurate global potential energy surface: assessing experimental uncertainties.

Thermal rate coefficients and kinetic isotope effects have been calculated for an important atmospheric reaction H/D + O3 → OH/OD + O2 based on an accurate permutation invariant polynomial-neural network potential energy surface, using ring polymer molecular dynamics (RPMD), quasi-classical trajectory (QCT) and variational transition-state theory (VTST) with multidimensional tunneling. The RPMD approach yielded results that are generally in better agreement with experimental rate coefficients than the VTST and QCT ones, especially at low temperatures, attributable to its capacity to capture quantum effects such as tunneling and zero-point energy. The theoretical results support one group of existing experiments over the other. In addition, rate coefficients for the D + O3 → OD + O2 reaction are also reported using the same methods, which will allow a stringent assessment of future experimental measurements, thus helping to reduce the uncertainty in the recommended rate coefficients of this reaction.

Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases.

SLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

Trends of epidemiological characteristics of traumatic spinal cord injury in China, 2009-2018.

OBJECTIVE: We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. METHODS: A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. RESULTS: There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0-46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2-67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7-8.8%). The elderly population (aged 65-74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8-134.3]). CONCLUSIONS: The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Cadaveric biomechanical analysis of multilevel lateral lumbar interbody fusion with and without supplemental instrumentation.

BACKGROUND: This study was to evaluate and compare the biomechanical features of multilevel lateral lumbar interbody fusion (LLIF) with or without supplemental instrumentations. METHODS: Six human lumbar specimens were tested under multidirectional nondestructive moments (7.5 N·m), with a 6 degree-of-freedom spine simulator. The overall and intervertebral range of motion (ROM) were measured optoelectronically. Each specimen was tested under the following conditions at L2-5 levels: intact; stand-alone; cage supplemented with lateral plate (LP); cage supplemented with unilateral or bilateral pedicle screw/rod (UPS or BPS). RESULTS: Compared with intact condition, the overall and intersegmental ROM were significantly reduced after multilevel stand-alone LLIF. The ROM was further reduced after using LP instrumentation. In flexion-extension (FE) and axial rotation (AR), pedicle screw/rod demonstrated greater overall ROM reduction compared to LP (P < 0.01), and bilateral greater than unilateral (P < 0.01). In lateral bending (LB), BPS demonstrated greater overall ROM reduction compared to UPS and LP (P < 0.01), however, UPS and LP showed similar reduction (P = 0.245). Intervertebral ROM reductions showed similar trend as the overall ones after using different types of instrumentation. However, at L2/3 (P = 0.57) and L3/4 (P = 0.097) levels, the intervertebral ROM reductions in AR were similar between UPS and LP. CONCLUSIONS: The overall and intervertebral stability increased significantly after multilevel LLIF with or without supplemental instrumentation. BPS provided the greatest stability, followed by UPS and LP. However, in clinical practice, less invasive adjunctive fixation methods including UPS and LP may provide sufficient biomechanical stability for multilevel LLIF.

Scar Tissue-Targeting Polymer Micelle for Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase-responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol-b-poly [2-(((4-acetyl-2-methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG-PAPO or PAPO) by activated microglia cells. A scar tissue-homing peptide (cysteine-alanine-glutamine-lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue-targeting ability. As a result, this CAQK-modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.

An injectable recombinant human milk fat globule-epidermal growth factor 8-loaded copolymer system for spinal cord injury reduces inflammation through NF-κB and neuronal cell death.

Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment. It is shown that the MFG-E8-loaded copolymer system can decrease pro-inflammatory cytokine expression and neuron death. In a rat model of crush-caused SCI, the copolymer system shows significant therapeutic efficacy by ameliorating inflammation, decreasing fibrotic scar, promoting myelin regeneration and suppressing overall SCI severity.

Osmolarity controls the differentiation of adipose-derived stem cells into nucleus pulposus cells via histone demethylase KDM4B.

Adipose-derived stem cells (ADSCs) are an ideal source of cells for intervertebral disc (IVD) regeneration, but the effect of an increased osmotic microenvironment on ADSC differentiation remains unclear. Here, we aimed to elucidate whether hyperosmolarity facilitates ADSC nucleus pulposus (NP)-like differentiation and whether histone demethylase KDM4B is involved in this process. ADSCs were cultured under standard and increased osmolarity conditions for 1-3 weeks, followed by analysis for proliferation and viability. Differentiation was then quantified by gene and protein analysis. Finally, KDM4B knockdown ADSCs were generated using lentiviral vectors. The results showed that increasing the osmolarity of the differentiation medium to 400 mOsm significantly increased NP-like gene expression and the synthesis of extracellular matrix (ECM) components during ADSC differentiation; however, further increasing the osmolarity to 500 mOsm suppressed the NP-like differentiation of ADSCs. KDM4B, as well as the IVD formation regulators forkhead box (Fox)a1/2 and sonic hedgehog (Shh), were found to be significantly upregulated at 400 mOsm. KDM4B knockdown reduced Foxa1/2, Shh, and NP-associated markers' expression, as well as the synthesis of ECM components. The reduction in NP-like differentiation caused by KDM4B knockdown was partially rescued by Purmorphamine, a specific agonist of Shh. Moreover, we found that KDM4B can directly bind to the promoter region of Foxa1/2 and decrease the content of H3K9me3/2. In conclusion, our results indicate that a potential optimal osmolarity window might exist for successful ADSC differentiation. KDM4B plays an essential role in regulating the osmolarity-induced NP-like differentiation of ADSCs by interacting with Foxa1/2-Shh signaling.

Theoretical Investigations of Rate Coefficients for H + O3 and HO2 + O Reactions on a Full-Dimensional Potential Energy Surface.

In this work, a machine learning method is used to construct a high-fidelity multichannel global reactive potential energy surface (PES) for the HO3 system from 21452 high-level ab initio calculations at the explicitly correlated multireference configuration interaction (MRCI-F12) level of theory. The permutation invariance of the PES with respect to the three identical oxygen atoms is enforced using permutation invariant polynomials (PIPs) in the input layer of a neural network (NN). This PIP-NN representation is highly faithful to the ab initio points, with a root-mean-square error of 0.20 kcal/mol. Using this PES, the kinetics of H + O3 → OH + O2 (R1) and HO2 + O → OH + O2 (R2) reactions were investigated using a quasi-classical trajectory method over a wide temperature range (200-2000 K). It was found that the calculated thermal rate coefficients of R1 and R2, exhibiting positive and negative temperature dependences, respectively, are in reasonably good agreement with most experimental measured values. These temperature dependences can be attributed to the presence and absence of an entrance channel potential barrier.

Radiographic and clinical outcome of lateral lumbar interbody fusion for extreme lumbar spinal stenosis of Schizas grade D: a retrospective study.

BACKGROUND: Extreme lumbar spinal stenosis was thought to be a relative contraindication for lateral lumbar interbody fusion (LLIF) and was excluded in most studies. This is a retrospective study to analyze the radiographic and clinical outcome of LLIF for extreme lumbar spinal stenosis of Schizas grade D. METHODS: For radiographic analysis, we included 181 segments from 110 patients who underwent LLIF between June 2017 and December 2018. Lumbar spinal stenosis was graded according to Schizas' classification. Anterior and posterior disc heights, disc angle, foramen height, spinal canal diameter and central canal area were measured on CT and MRI. For clinical analysis, 18 patients with at least one segment of grade D were included. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate clinical outcome. Continuous variables were compared using Student's t-test, with P-values < 0.05 considered to indicate statistically significant differences. RESULTS: Among the 181 segments included for radiological evaluation, there were 23 grade A segments, 37 grade B segments, 103 grade C segments and 18 grade D segments. Postoperatively, the average change of midsagittal canal diameter of grade D was significantly greater than that of grade A, and not significantly different compared to grades B and C. As to the average change of disc height, bilateral foraminal height, disc angle and central canal area (CCA), grade D was not significantly different from the others. The average postoperative CCA of grade D was significantly smaller than the average preoperative CCA of grade C. Eighteen patients with grade D stenosis were followed up for an average of 19.61 ± 6.32 months. Clinical evaluation revealed an average improvement in the ODI and VAS scores for back and leg pain by 20.77%, 3.67 and 4.15 points, respectively. Sixteen of 18 segments with grade D underwent posterior decompression. CONCLUSION: The radiographic decompression effect of LLIF for Schizas grade D segments was comparable with that of other grades. Posterior decompression was necessary for LLIF to achieve a satisfactory clinical outcome for extreme lumbar spinal stenosis of Schizas grade D.

Multiple-Color Platinum Complex with Super-Large Stokes Shift for Super-Resolution Imaging of Autolysosome Escape.

It is of great significance to track the platinum drugs in real time with super-resolution to elucidate their mechanism of action, such as their behavior and distribution in live cells. Such information is required for further drug development. However, it is always challenging to design platinum complexes suitable for such research. Herein, we design a luminescent building block (L) for metal complexes and a dinuclear platinum complex (Pt2 L) for super-resolution imaging. Because of its super-large Stokes shift and excellent photophysical properties, Pt2 L is capable of serving as an ideal candidate for super-resolution imaging with extremely low luminescence background and high photobleaching resistance. Moreover, upon light stimulation, a matter flux of Pt2 L escaping from autolysosomes to nucleus was observed, which represents a new transportation path. Utilizing the photoactivated escape properties, we can regulate the nuclear accessibility of Pt2 L form autolysosomes with photo-selectivity, which provides a new way to improve the targeting of platinum drugs.