Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis.

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

Aggregation-Induced Emission-Based Macrophage-Like Nanoparticles for Targeted Photothermal Therapy and Virus Transmission Blockage in Monkeypox.

The recent prevalence of monkeypox has led to the declaration of a Public Health Emergency of International Concern. Monkeypox lesions are typically ulcers or pustules (containing high titers of replication-competent virus) in the skin and mucous membranes, which allow monkeypox virus to transmit predominantly through intimate contact. Currently, effective clinical treatments for monkeypox are lacking, and strategies for blocking virus transmission are fraught with drawbacks. Herein, this work constructs a biomimetic nanotemplate (termed TBD@M NPs) with macrophage membranes as the coat and polymeric nanoparticles loading a versatile aggregation-induced emission featured photothermal molecule TPE-BT-DPTQ as the core. In a surrogate mouse model of monkeypox (vaccinia-virus-infected tail scarification model), intravenously injected TBD@M NPs show precise tracking and near-infrared region II fluorescence imaging of the lesions. Upon 808 nm laser irradiation, the virus is eliminated by the photothermal effect and the infected wound heals rapidly. More importantly, the inoculation of treated lesion tissue suspensions does not trigger tail infection or inflammatory activation in healthy mice, indicating successful blockage of virus transmission. This study demonstrates for the first time monkeypox theranostics using nanomedicine, and may bring a new insight into the development of a viable strategy for monkeypox management in clinical trials.

The miR-302/367 cluster: Aging, inflammation, and cancer.

MicroRNAs (miRNAs) are a class of noncoding RNAs that occupy a significant role in biological processes as important regulators of intracellular homeostasis. First, we will discuss the biological genesis and functions of the miR-302/367 cluster, including miR-302a, miR-302b, miR-302c, miR-302d, and miR-367, as well as their roles in physiologically healthy tissues. The second section of this study reviews the progress of the miR-302/367 cluster in the treatment of cancer, inflammation, and diseases associated with aging. This cluster's aberrant expression in cells and/or tissues exhibits similar or different effects in various diseases through molecular mechanisms such as proliferation, apoptosis, cycling, drug resistance, and invasion. This article also discusses the upstream and downstream regulatory networks of miR-302/367 clusters and their related mechanisms. Particularly because studies on the upstream regulatory molecules of miR-302/367 clusters, which include age-related macular degeneration, myocardial infarction, and cancer, have become more prevalent in recent years. MiR-302/367 cluster can be an important therapeutic target and the use of miRNAs in combination with other molecular markers may improve diagnostic or therapeutic capabilities, providing unique insights and a more dynamic view of various diseases. It is noted that miRNAs can be an important bio-diagnostic target and offer a promising method for illness diagnosis, prevention, and treatment.

Investigation of the Degradation Mechanism of SiC MOSFET Subjected to Multiple Stresses.

The performance requirements for power devices in airborne equipment are increasingly demanding, while environmental and working stresses are becoming more diverse. The degradation mechanisms of devices subjected to multiple stresses become more complex. Most proposed degradation mechanisms and models in current research only consider a single stress, making it difficult to describe the correlation between multiple stresses and the correlation of failures. Then, a multi-physical field coupling model based on COMSOL is proposed. The influence relationship between temperature, moisture, electrical load, and vibration during device operation is considered, and a three-dimensional finite element model is built to investigate the multi-stress degradation mechanism under multi-physical field coupling. The simulation results show that, compared with single-stress models, the proposed multi-stress coupled model can more accurately simulate the degradation process of SiC MOSFET. This provides references for improving the reliability design of power device packaging.

Predicting post-laminoplasty kyphosis in cervical spondylotic myelopathy patients without preoperative kyphosis: a retrospective study.

BACKGROUND: This study aimed to determine potential risk factors for post-laminoplasty kyphosis and the effect of postoperative kyphosis on neurologic function recovery. METHODS: A total of 266 patients with cervical spondylotic myelopathy (CSM) underwent traditional cervical laminoplasty with a minimum of a 12-month follow-up period. The patients were divided into non-kyphosis (NK group) and kyphosis (K group) groups based on the postoperative C2-7 Cobb angle. Clinical and radiological measurements were collected preoperatively and at the final follow-up. RESULTS: Of the 266 patients, 26 (9.77%) developed postoperative kyphosis at the final follow-up. The postoperative Japanese Orthopedic Association score did not differ significantly between the NK and K groups (P > 0.05). The postoperative numeric rating scale (NRS) also showed no significant difference between the NK and K groups; however, postoperative NRS improved better than the preoperative values in the NK group (P < 0.001). Multivariate analysis revealed that the preoperative C2-7 extension Cobb angle and C2-7 Cobb angle were independent predictors of post-laminoplasty kyphosis. Cut-off values for predicting postoperative kyphosis were a C2-7 extension Cobb angle of 18.00° and a C2-7 Cobb angle of 9.30°. CONCLUSIONS: Low preoperative C2-7 extension Cobb angle and C2-7 Cobb angle may be associated with post-laminoplasty kyphosis in CSM patients without preoperative kyphosis. The cut-off value of the C2-7 extension Cobb angle and C2-7 Cobb angle were 18.00° and 9.30°, respectively.

No-tillage with straw mulching promotes the utilization of soil nitrogen by rice under wheat-rice and oilseed rape-rice cropping systems.

Introduction: To investigate the effects of no-tillage with straw mulching on the absorption and utilization of soil nitrogen (N), fertilizer N, and straw N by rice under paddy-upland rotations. Methods: A field experiment with three cropping systems: fallow-rice rotation without straw mulching (FRN), wheat-rice rotation with wheat mulching in rice season (WRS), and oilseed rape-rice rotation with oilseed rape straw mulching in rice season (ORS) was conducted from 2015 to 2017, along with a mini-plot experiment with 15N-labeled urea and straws, which was conducted in 2017. Results: No-tillage with straw reduced rice N uptake up to 20 days after transplanting, the total amount of fertilizer N uptake of WRS and ORS rice plants was 46.33 and 61.67 kg/ha, respectively, which was 9.02 and 45.10% higher than that of FRN plants. Soil N was the main source for rice growth, followed by fertilizer N. Soil N uptake by WRS and ORS rice plants was 21.75 and 26.82% higher than that of FRN plants, accounting for 72.37 and 65.47%, respectively, of the total N accumulated in rice plants. Straw mulching increased the N utilization efficiency of tillering, panicle, and total fertilizer by 2.84-25.30%; however, base fertilizer was dependent on straw mulching. The total amount of N released from WRS and ORS straw mulching in the rice season was 34.97 and 24.82 kg/ha, respectively; however, only 3.04 and 4.82% of it was absorbed by the rice plants, accounting for only 0.62 and 0.66% of the total accumulated N. Discussion: No-tillage with straw mulching under paddy-upland rotations increased the N utilization of rice, especially for the absorption of soil N. These results provide theoretical information for the effective utilization of straw and rational N application practices in rice-based cropping systems.

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways.

Background: Interstitial lung disease (ILD) is the major cause of morbidity and mortality in patients with various rheumatic diseases. However, more interventions need to be sought. Tripterine, an extract of Tripterygium wilfordii Hook. F, has been widely studied for its powerful anti-inflammatory effect. However, its mechanism of action in treating connective tissue disease-related (CTD)-ILD remains unclear. Purpose: To investigate the mechanism of tripterine in CTD-ILD treatment by combining network pharmacology and an in vivo experiment. Methods: The related targets of tripterine were obtained after searching the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, Comparative Toxicogenomics Database, GeneCards, Search Tool for Interacting Chemicals database, and SymMap database. Following this, Online Mendelian Inheritance in Man, GeneCards, Genebank, and DrugBank were used to screen the targets of CTD-ILD. A target-signalling pathway network was constructed using Cytoscape. Additionally, topological analysis was performed. Protein interaction analysis was performed using the STRING online analysis platform. Following this, Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathway enrichment analyses were performed. Subsequently, the molecular docking between tripterine and the core targets was verified. Finally, experimental verification was performed in bleomycin-induced model mice. Results: A total of 134 common targets and 10 core targets of tripterine, including signal transducer and activator of transcription 3, tumour necrosis factor (TNF), v-rel avian reticuloendotheliosis viral oncogene homolog A, protein kinase B (Akt) α (Akt1), mitogen-activated protein kinase (MAPK) 1, Jun transcription factor family, tumour protein 53, MAPK3, nuclear factor kappa B subunit 1, and caspase 8, were obtained. GO enrichment analysis revealed that, while treating CTD-ILD, tripterine was mainly involved in cytokine receptor binding, receptor-ligand activity, signal receptor activation, cytokine activity, protein ubiquitination, deoxyribonucleic acid transcriptase activity, etc. The KEGG pathway enrichment analysis revealed that the most significant signalling pathways were multiple viral infections and the phosphatidylinositol-3-kinase (PI3K)/Akt, TNF, and apoptosis signalling pathways. Molecular docking results revealed that tripterine had good docking activity with the core targets. Experimental studies also demonstrated that tripterine could inhibit the activation of PI3K/Akt, apoptosis, and TNF-α signalling pathways in lung tissue and significantly improve lung pathology and collagen deposition in the model mice. Conclusions: This study preliminarily revealed the potential molecular biological mechanism of tripterine while treating CTD-ILD might be related to inhibiting the PI3K/Akt, apoptosis, and TNF-α signalling pathways. Tripterygium wilfordii Hook. F. and its extract could be used clinically for treating CTD-ILD.

Trace Analysis of Emerging Virus: An Ultrasensitive ECL-Scan Imaging System for Viral Infectious Disease.

Emerging infectious diseases have brought a huge impact on human society in recent years. The outbreak of Zika virus (ZIKV) in the Americas resulted in a large number of babies born with microcephaly. More seriously, the Coronavirus Disease 2019 (COVID-19) was globally spread and caused immeasurable damages. Thus, the monitoring of highly pathogenic viruses is important to prevent and control emerging infectious diseases. Herein, a dendritic polymer probe-amplified ECL-scan imaging system was constructed to realize trace analysis of viral emerging infectious diseases. A dendritic polymer probe was employed as the efficient signal emitter component that could generate an amplified ECL signal on the integrated chip, and the signal was detected by a single-photon level charge coupled device-based ECL-scan imaging system. With this strategy, the ZIKV in a complex system of blood, urine, and saliva was detected. The results indicated that a high sensitivity of 50 copies and superior specificity were achieved. Furthermore, this strategy realized highly sensitive detection (10 copies) of the S and N protein gene sequence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov2) and spiked pseudovirus samples. Thus, the dendritic polymer probe-amplified ECL-scan imaging system suitably met the strict clinical requirements for trace analysis of an emerging virus, and thus has the potential to serve as a paradigm for monitoring emerging infectious diseases.

Nitrogen Application Rate Affects the Accumulation of Carbohydrates in Functional Leaves and Grains to Improve Grain Filling and Reduce the Occurrence of Chalkiness.

Chalkiness, which is highly affected by nitrogen (N) management during grain filling, is critical in determining rice appearance quality and consumer acceptability. We investigated the effects of N application rates 75 (N1), 150 (N2), and 225 (N3) kg ha-1 on the source-sink carbohydrate accumulation and grain filling characteristics of two indica hybrid rice cultivars with different chalkiness levels in 2019 and 2020. We further explored the relationship between grain filling and formation of chalkiness in superior and inferior grains. In this study, carbohydrates in the functional leaves and grains of the two varieties, and grain filling parameters, could explain 66.2%, 68.0%, 88.7%, and 91.6% of the total variation of total chalky grain rate and whole chalkiness degree, respectively. They were primarily concentrated in the inferior grains. As the N fertilizer application rate increased, the chalky grain rate and chalkiness degree of both the superior and inferior grains decreased significantly. This interfered with the increase in total chalky grain rate and chalkiness. Moreover, the carbohydrate content in the functional leaves increased significantly in N2 and N3 compared with that in N1. The transfer of soluble sugar from the leaves to the grains decreased the soluble sugar and increased total starch contents, accelerated the development of grain length and width, increased grain water content, and effectively alleviated the contradiction between source and sink. These changes promoted the carbohydrate partition in superior and inferior grains, improved their average filling rate in the middle and later stages, optimized the uniformity of inferior grain fillings, and finally led to the overall reduction in rice chalkiness.

Visualization of Zika Virus Infection via a Light-Initiated Bio-Orthogonal Cycloaddition Labeling Strategy.

Zika virus (ZIKV) is a re-emerging flavivirus that leads to devastating consequences for fetal development. It is crucial to visualize the pathogenicity activities of ZIKV ranging from infection pathways to immunity processes, but the accurate labeling of ZIKV remains challenging due to the lack of a reliable labeling technique. We introduce the photo-activated bio-orthogonal cycloaddition to construct a fluorogenic probe for the labeling and visualizing of ZIKV. Via a simple UV photoirradiation, the fluorogenic probes could be effectively labeled on the ZIKV. We demonstrated that it can be used for investigating the interaction between ZIKV and diverse cells and avoiding the autofluorescence phenomenon in traditional immunofluorescence assay. Thus, this bioorthogonal-enabled labeling strategy can serve as a promising approach to monitor and understand the interaction between the ZIKV and host cells.

Medium to long term follow-up of survival and quality of life in patients with primary tumors of the cervical spine: Experience From a large single center.

Objectives: To evaluate the survival and medium to long term health-related quality of life (HRQoL) of patients with primary cervical spinal tumors in a cross-sectional study and to identify any significant associations with demographic or clinical characteristics. Methods: Patients diagnosed with primary cervical spinal tumors were retrospectively enrolled and their clinical, radiologic, and follow-up data (specifically the EQ-5D questionnaire) were collected. Univariate and multivariate Cox time-dependent regression analyses were performed to examine the significance of certain variables on overall survival. Univariate and multivariate logistic regression analyses were conducted to identify variables significant for overall HRQoL and each dimension of the EQ-5D. Results: A total of 341 patients were enrolled in the study with a mean follow-up of 70 months. The diagnosis was benign in 246 cases, malignant in 84, and unconfirmed in 11. The 5-year overall survival rate was 86% and the 10-year overall survival rate was 65%. Multivariate analysis suggested that surgical treatment (P = 0.002, hazard ratio [HR] = 0.431, 95% CI. [0.254, 0.729]), benign and malignant tumors [P < 0.001, HR = 2.788, 95% CI. (1.721, 4.516)], tumor and surrounding normal tissue boundary [P = 0.010, HR = 1.950, 95% CI. (1.171, 3.249)], and spinal instability [P = 0.031, HR = 1.731, 95% CI. (1.051, 2.851)] still had significant effects on survival. Conclusions: In this cross-sectional study, we evaluated the survival period and medium and long-term health-related quality of life of patients with primary tumors of the cervical spine, and analyzed the significant related factors of tumor clinical characteristics. Surgery, myelopathy, malignancy, spinal pain relieved by lying down or supine position, and tumor infiltration on MRI were significant predictors for overall survival. Enneking stage and age were significant predictors for HRQoL.

TFAP2A inhibits microRNA-126 expression at the transcriptional level and aggravates ischemic neuronal injury.

Neuronal injury induced by cerebral ischemia poses a serious health risk globally, and there is no effective clinical therapy. This study was performed to investigate the role of transcription factor AP-2 alpha (TFAP2A) in cerebral ischemia, and the underlying mechanisms, using an in-vitro model (PC-12 cells) of oxygen-glucose deprivation (OGD), and an in-vivo model (rat) of transient global cerebral ischemia (tGCI). The results for CCK-8 and Hoechst staining showed that silencing of TFAP2A enhanced the viability and decreased the rate of apoptosis of PC12 cells subjected to OGD. ChIP assays were performed to evaluate the binding of TFAP2A to the promoter region of microRNA (miR)-126, and we found that TFAP2A inhibits the expression of miR-126. Further mechanistic investigation revealed that miR-126 targets polo like kinase 2 (PLK2), and that overexpression of PLK2 activates the IκBα-NF-κB signaling pathway and suppresses the growth of PC12 cells subjected to OGD. For our in-vivo assay, we used TTC staining to analyze the infarction area in the brain tissues of rats, and Nissl staining to evaluate the number of surviving brain neurons. The pathological conditions associated with neuronal injury in rat brain tissues were assessed by staining the tissues with hematoxylin-eosin. Our results indicate that TFAP2A downregulates miR-126, and thereby upregulates PLK2 and activates the IκBα-NF-κB pathway, which increased neuronal injury following cerebral ischemia.

Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2.

BACKGROUND: It has been documented that microRNAs (miRs) assume a pivotal role in the development of ischemic stroke (IS). However, it remains poorly identified about the role of miR-122 in IS. Herein, this study was intended to explore the mechanism of E2F1-orchestrated miR-122 in IS. PATIENTS AND METHODS: E2F1, miR-122, and SPRY2 expression in serum from patients with IS and oxygen-glucose deprivation (OGD)-treated N2a cells was detected by RT-qPCR. After gain- and loss-of-function approaches in OGD-induced N2a cells, GAFP staining, flow cytometry, and Western blot analysis were adopted to assess neuronal viability, cell cycle and apoptosis, and expression of apoptosis- and autophagy-related proteins, respectively. Meanwhile, mice with IS were induced, in which E2F1, miR-122, and SPRY2 were overexpressed, followed by evaluation of neurological deficit and cerebral infarction area. The MAPK pathway activity in tissues of mice and cells was determined. RESULTS: miR-122 was down-regulated, and E2F1 and SPRY2 were up-regulated in IS patients and OGD-induced N2a cells. E2F1 inhibited miR-122 transcription, while miR-122 targeted SPRY2. Overexpression (OE) of miR-122 or down-regulation of E2F1 or SPRY2 increased viability, but decreased apoptosis, cell cycle arrest, and autophagy in OGD-induced N2a cells. In IS mice, the neurological deficit score and cerebral infarction area were elevated, which was aggravated by up-regulating E2F1 or SPRY2 but attenuated by overexpressing miR-122. E2F1/miR-122/SPRY2 axis mediated the MAPK pathway in vivo and in vitro. CONCLUSION: Collectively, E2F1 reduced miR-122 transcription to up-regulate SPRY2, which inactivated MAPK pathway and promoted neurological deficit in IS.

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Understanding population quality and nitrogen utilization characteristics of direct seeding rice under water-nitrogen interaction could provide theoretical and practical basis for high yield and ample production of direct seeding rice. Hybrid rice F You 498 was used as the material. Three irrigation methods were set in this study: flooding irrigation (W1), dry-wet alternate irrigation (W2) and drying irrigation (W3), with different ratio of base fertilizer: tiller fertilizer: panicle fertilizer at 5:3:2 (N1), 3:3:4 (N2), 3:1:6 (N3), respectively. No nitrogen application (N0) was set as the control. We investigated the effects of water-nitrogen interaction on population quality and nitrogen utilization characteristics of direct seeding rice, with the aim to clarify the relationship between population quality construction, nitrogen utilization characteristics and yield of direct seeding rice. The results showed that irrigation and N rate significantly interacted to affect dry matter accumulation, rice harvest index, heading high-efficiency leaf (the upper three leaves) dry weight, light transmittance rate at maturity stage, total nitrogen accumulation (TNA), apparent nitrogen use efficiency (ANE), nitrogen partial factor productivity (NPFP), nitrogen physiology efficiency, and rice yield. Taking population quality, yield and N fertilizer utilization characteristics into consideration, suitable panicle N-fertilizer under each irrigation mode was 20%-40% (N1-N2). Panicle N-fertilizer reached 60% (N3) and W3 treatment would significantly reduce population quality, yield, nitrogen agronomy efficiency (NAE), NPFP of direct seeding rice. Yield and nitrogen utilization characteristics of direct seeding rice were significantly correlated with effective panicles, dry matter accumulation at maturity stage, other leaf (except the upper three leaves) dry weight reduction, total leaf dry weight reduction, and middle part and basel part light-receiving rate under water-nitrogen interaction. The dry-wet alternative (W2) treatment could increase the rate of production til-lers, dry matter accumulation, rice harvest index, TNA, NAE and rice yield. W2 combined with N2 could improve population quality of direct seeding rice and realized the coordination and unification of high yield and efficient utilization of nitrogen, which is the best combination in this experiment.

Near-infrared light controlled fluorogenic labeling of glycoengineered sialic acids in vivo with upconverting photoclick nanoprobe.

Sialic acid serves as an important determinant for profiling cell activities in diverse biological and pathological processes. The precise control of sialic acid labeling to visualize its biological pathways under endogenous conditions is significant but still challenging due to the lack of reliable methods. Herein, we developed an effective strategy to spatiotemporally label thesialic acids with a near-infrared (NIR) light activated upconverting nanoprobe (Tz-UCNP). With this photoclickable nanoprobe and a stable N-alkene-d-mannosamine (Ac4ManNIPFA), metabolically synthesized alkene sialic acids on the cell surface were labeled and imaged in real time through fluorogenic cycloaddition. More importantly, we achieved spatially selective visualization of sialic acids in specific tumor tissues of the mice under NIR light activation in a spatially controlled manner. This in situ controllable labeling strategy thus enables the metabolic labeling of specific sialic acids in complex biological systems.

Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS­stimulated human periodontal ligament cells via the downregulation of miR­302b.

Periodontitis is the main cause of tooth or tissue loss. Human periodontal ligament stem cells (hPDLSCs), which have high proliferative, self­renewal and multi­differentiation abilities, are vital for the restoration of periodontitis­induced injuries. The anti­inflammatory and anti­apoptotic agent, tetramethylpyrazine (TMP), is a promising agent used for the protection of PDLSCs from apoptosis and inflammation induced by periodontitis. The aim of the present study was to investigate the effects of TMP on lipopolysaccharide (LPS)­stimulated hPDLSCs. LPS­stimulated hPDLSCs were established as the cell model. CCK­8 assay was performed to evaluate cell viability, western blot analysis was performed to measure protein expression and flow cytometry was performed to detect cell apoptosis levels. Detection kits were used to evaluate the levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and IL­6. Reverse transcription­quantitative PCR analysis was performed to detect gene expression. TMP alleviated the effects of LPS on cell viability, inflammation levels and cell apoptosis. TMP downregulated microRNA (miR)­302b levels in LPS­stimulated cells. Transfection with miR­302b mimic reversed the anti­inflammatory and anti­apoptotic effects of TMP on LPS­stimulated cells. TMP reduced inflammation and the apoptosis of LPS­stimulated human periodontal ligament cells via the downregulation of miR­302b. The anti­inflammatory and anti­apoptotic effects exerted by TMP render it a promising agent for the protection of PDLSCs from injuries induced by periodontitis. The findings of the present study may aid in the development of a novel strategy for the treatment of periodontitis and may pave the way for further research.

Salvianolic Acid C Attenuates LPS-Induced Inflammation and Apoptosis in Human Periodontal Ligament Stem Cells via Toll-Like Receptors 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND Periodontitis is a chronic inflammatory disease that causes gingival detachment and disintegration of alveolar bone. Salvianolic acid C (SAC) is a polyphenol compound with anti-inflammatory and antioxidant activities that is isolated from Danshen, a traditional Chinese medicine made from the roots of Salvia miltiorrhiza Bunge. The aim of this study was to investigate the mechanisms of underlying its protective effects and its inhibition effect on inflammation and apoptosis in human periodontal ligament stem cells (hPDLSCs). MATERIAL AND METHODS LPS-induced hPDLSCs, as a model mimicking an inflammatory process of periodontitis in vivo, were established to investigate the therapeutic effect of SAC in periodontitis. The inflammatory cytokines secretion and oxidative stress status were measured by use of specific commercial test kits. The hPDLSCs viability was analyzed by Cell Counting Kit-8 assay. The cell apoptosis and cell cycle were assayed with flow cytometry. Expressions levels of proteins involved in apoptosis, osteogenic differentiation, and TLR4/NF-kappaB pathway were evaluated by Western blotting. Alkaline phosphatase (ALP) activity was detected by ALP assay kit and ALP staining. The mineralized nodules formation of hPDLSCs was checked by Alizarin Red S staining. RESULTS Our results showed that LPS induced increased levels of inflammatory cytokines and oxidative stress and mediated the phosphorylation and nuclear translocation of NF­kappaB p65 in hPDLSCs. SAC reversed the abnormal secretion of inflammatory cytokines and inhibited the TLR4/NF­kappaB activation induced by LPS. SAC also upregulated cell viability, ALP activity, and the ability of osteogenic differentiation. The anti-inflammation and TLR4/NF­kappaB inhibition effects of SAC were reversed by TLR4 overexpression. CONCLUSIONS Taken together, our results revealed that SAC effectively attenuates LPS-induced inflammation and apoptosis via the TLR4/NF-kappaB pathway and that SAC is effective in treating periodontitis.

Trends of surgical treatment for spinal degenerative disease in China: a cohort of 37,897 inpatients from 2003 to 2016.

PURPOSE: Given the aging Chinese population and the inevitable degenerative process of the spine, more elderly patients with spinal degenerative disease (SDD) are surgical candidates, placing a significant burden on health care resources. Few studies have investigated recent trends in hospital admissions and procedures for SDD in China. This study aimed to identify the trends, if any, in the number of surgical procedures undertaken for SDD in a large patient cohort. MATERIALS AND METHODS: This retrospective cohort analysis used data from inpatient medical records at Peking University Third Hospital between 2003 and 2016. Descriptive statistical analysis, regression models, and a Holt-Winters seasonal model were used to analyze trends. RESULTS: Altogether, 38,676 surgery records from 37,897 SDD patients who had undergone surgical treatment were included in our study, among whom 49.60%, 47.81%, and 2.59% were treated because of cervical, lumbar, and thoracic degenerative disease, respectively. There was an increasing trend for spinal surgery performance with an increasing mean age at surgery, from 50.65 years of age in 2003 to 55.29 years in 2016. We also revealed interesting seasonal variation in our study - that is, most of the spinal procedures were performed during the winter and spring months. CONCLUSION: Our study showed a significantly increasing surgical workload for addressing SDD in China. Both the public and the health care system should be aware of this increase in chronic degenerative disease in the aging population.