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Purpose This systematic review and meta-analysis aimed to determine the incidence of symptomatic spinal epidural hematoma (SSEH) following spine surgery. Methods We systematically searched for all relevant articles that mentioned the incidence of SSEH following the spine surgery published in the PubMed, Embase, and Cochrane Library databases through March 2022 and manually searched the reference lists of included studies. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. A fixed-effects or random-effects model was performed to calculate the pooled incidence of the totality and subgroups based on the heterogeneity. The potential publication bias was assessed by Egger's linear regression and a funnel plot. Sensitivity analysis was also conducted. Results A total of 40 studies were included in our meta-analysis based on our inclusion and exclusion criteria. The overall pooled incidence of SSEH was 0.52% (95% CI 0.004–0.007). In the subgroup analysis, the pooled incidence of SSEH in males and females was 0.86% (95% CI 0.004–0.023) and 0.68% (95% CI 0.003–0.017). Among the different indications, a higher incidence (2.9%, 95% CI 0.006–0.084) was found in patients with deformity than degeneration (1.12%, 95% CI 0.006–0.020) and tumor (0.30%, 95% CI 0.006–0.084). For different surgical sites, the incidences of SSEH in cervical, thoracic and lumbar spine were 0.32% (95% CI 0.002–0.005), 0.84% (95% CI 0.004–0.017) and 0.63% (95% CI 0.004–0.010), respectively. The incidences of SSEH in anterior and posterior approach were 0.24% (95% CI 0.001–0.006) and 0.70% (95% CI 0.004–0.011), respectively. The pooled incidence of SSEH was five times higher with minimally invasive surgery (1.94%, 95% CI 0.009–0.043) than with open surgery (0.42%, 95% CI 0.003–0.006). Delayed onset of SSEH had a lower incidence of 0.16% (95% CI 0.001–0.002) than early onset. There were no significant variations in the incidence of SSEH between patients who received perioperative anticoagulation therapy and those who did not or did not report getting chemopreventive therapy (0.44%, 95% CI 0.006–0.084 versus 0.42%, 95% CI 0.003–0.006). Conclusion We evaluated the overall incidence proportion of SSEH after spine surgery and performed stratified analysis, including sex, surgical indication, site, approach, minimally invasive surgery, and delayed onset of SSEH. Our research would be helpful for patients to be accurately informed of their risk and for spinal surgeons to estimate the probability of SSEH after spine surgery.

Neuroblastoma (NB) is one of the most common extracranial tumors with limited therapeutic options. Retinoic acid (RA) has been identified to play anticancer role against NB cells by inducing the differentiation and apoptosis of immature neuroblasts. However, silencing HoxC9 promoter by EZH2-induced H3K27me3 hypermethylation can lead to RA resistance. Previous studies have suggested that arsenic trioxide (ATO), an inhibitor of DNA methylation, could downregulate the expression of EZH2 in breast cancer cells.In our study, we attempted to obtain some insight into the mechanisms of differentiation of RA-resistant NB cells by detecting the expressions of HoxC9 and EZH2 in NB cells treated with ATO, so as to provide a basis for the subsequent treatment of RA-resistant NB by ATO.Two NB cell lines, SK-N-AS (retinoic acid-resistant neuroblastoma cells) and SK-N-SH (retinoic acid-sensitive neuroblastoma cells), were used in our experiments. Cell proliferation and apoptosis were respectively determined with Cell Counting Kit-8 (CCK-8) assay kit and Annexin V staining. The inverted phase contrast microscope was used to observe cell growth and measure the total length of nerve synapses. We employed label-free quantitative proteomic analysis to profile ATO-dependent changes in the proteome of NB cells. Western blot was used to detect the expressions of HoxC9, HoxD8 and EZH2.Arsenic trioxide inhibited the cell proliferation and increased apoptosis and total length of synapses in two NB cell lines. The expressions of HoxC9 and HoxD8 were upregulated, while the expression of EZH2 was downregulated in the SK-N-AS cell line. No significant changes in the 3 proteins mentioned above were observed in the SK-N-SH cell line after ATO treatment.Arsenic trioxide may reactivate the expression of HoxC9 by downregulating EZH2, which leads to restoring RA sensitivity and promoting the differentiation and apoptosis of RA-resistant NB cells.

Metal-based compounds with excellent photo-physical properties show good photochemotherapeutic performance. But, low in-depth tissue penetration of light limits their effectivity for deeply buried tumors. Encouraged by the sonosensitizing ability of the traditional organic photosensitizers, here, we developed AuNPs@Ir1 as a sonosensitizer by hybridizing an organometallic Ir(III) complex (Ir1) with ultrasmall gold nanoparticles (AuNPs) for efficient tumor sonodynamic therapy (SDT) for the first time. AuNPs@Ir1 rapidly entered the cancer cells, produced 1O2, and catalytically oxidized NADH to NAD+ under ultrasound (US) irradiation, thus resulted in cancer cells oncosis. Because of efficient passive retention in tumors post intravenous injection, AuNPs@Ir1 further efficiently inhibited the growth of tumors in-vivo under US stimulation without long-term toxicity to other organs. Overall, this work presents the excellent US triggered in-vitro and in-vivo anticancer profile of the novel AuNPs@Ir1. It is expected to increase the scope of SDT for metal-based anticancer drugs.

The sluggish charge transfer and poor intrinsic activity are the bottlenecks that hamper the further development of electrocatalysts for hydrogen evolution. A novel core-shell heterostructure of Cu3P@Ni is fabricated, which is composed of Cu3P nanorods covered by metallic Ni. The as-prepared Cu3P@Ni exhibits a durable and superior activity toward hydrogen evolution, with an overpotential of 42 mV to deliver 10 mA·cm−2 and a Tafel slope of 41 mV·dec−1. Charge redistribution is observed after successfully constructing the core-shell heterostructure, leading to the altered electronic structure. The theoretical calculations have manifested that Cu3P@Ni exhibits a zero bandgap and optimized adsorption strength of intermediates, which could give rise to the accelerated charge transfer as well as increased intrinsic activity. This work could shed light on the development of novel electrocatalysts with modulated electronic structure for highly efficient hydrogen evolution.

The high-frequency single side-band (HF-SSB) speech radio is an essential technique for long-distance speech transmission. However, the HF-SSB received speech is corrupted by both high-power noise and severe channel fading, and the typical speech enhancement methods only focus on the suppression of additive noise. In this letter, a two-stage hybrid approach is proposed to enhance the speech quality of the HF-SSB radio. In the anti-fading stage, we adopt the anti-fading convolution neural network (AF-CNN) to eliminate the effects of channel fading. In the noise suppression stage, noise suppression CNN (NS-CNN) subnet and unsupervised denoising block are used parallelly to further improve the performance and the generalization ability. In addition, we present the optimal topological relations of noise suppression and anti-fading modules by comparison and analysis. Experimental results show that applying the AF-CNN subnet before noise suppression can effectively help recover the weak speech components. Moreover, in terms of objective intelligibility and quality scores, the overall performance of the proposed method outperforms the typical methods that only consider noise suppression.

Translation activation of local synaptic mRNAs is critical to learning and memory1-3. Despite extensive studies on how phosphorylation of ribosomal proteins and translation factors enables timely response to exogenous stimuli4,our knowledge on molecular pathways utilized by RNA binding proteins (RBPs) to control translation of specific mRNAs remains incomplete. We have previously found that YTHDF1 regulates depolarization-induced protein synthesis by promoting translation ofN6-methyladenosine (m6A)-modified transcripts5. Here we report an unexpected mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Phosphorylation of FMRP serine 499 induced by neuronal depolarization alters the condensing behavior of prion-like protein YTHDF1. Unphosphorylated FMRP sequesters YTHDF1 away from the translation initiation complex, whereas the stimulation-induced FMRP phosphorylation releases YTHDF1 to form translational active condensates with the ribosome to activate translation of YTHDF1 target transcripts. In fragile X syndrome (FXS) models characterized by low FMRP expression, we observed YTHDF1-mediated hyperactive translation, which notably impacts FXS pathophysiology. Developmental defects in an FXS forebrain organoid model could be reversed by a selective small-molecule inhibitor of YTHDF1 which acts by suppressing its condensation in neurons. We characterized transcriptome-wide mRNA translation with inhibitor treatment in organoids and identified targets that explain alleviated FXS pathology. Our study thus reveals FMRP and its phosphorylation as an important regulator of the activity-dependent translation during neuronal development and stimulation, and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.

This article investigates the issues of state estimation and state estimation-based stabilization for Boolean control networks (BCNs). Unlike previous state observers, this article proposes an optimal state estimator by designing a particular input sequence for the first time, where the maximum-minimum method is employed such that the state of BCNs can be uniquely estimated in short time steps. A minimum reconstructible state set (MRSS) is constructed to determine this input sequence. Next, based on the estimated state, a finite-time stabilization scheme is proposed by constructing a switching controller consisting of three stages. A controller is first developed to estimate the state of BCNs in finite-time steps, and a state reachable controller is also provided to make the state of BCNs reachable to a given equilibrium point. Subsequently, a constant controller is further developed to stabilize the state of BCNs to the equilibrium point. Finally, an oxidative stress response model is used to illustrate the effectiveness of the proposed results.

Sepsis is a life-threatening organ dysfunction due to disturbance of the host's response to infection, and is often accompanied by shock. Timely and standardized hemodynamic management can effectively control disease progression. Mean arterial pressure (MAP) refers to tissue and organ perfusion and is one of the key factors for patient recovery. In this study, we focused on the relationship between MAP levels and 30-day mortality in patients with sepsis.This cohort study included 14,607 sepsis patients out of 38,597 adults admitted to Beth Israel Deaconess Medical Center in Boston between 2001 and 2012, according to the Sepsis 3.0 diagnostic criteria. According to the MAP value of the sepsis patients on the first day of intensive care unit (ICU) admission, they were divided into 5 groups (Q1 ≤67.4 mmHg, Q2 67.4-72.5 mmHg, Q3 72.5-77.6 mmHg, Q4 77.6-84.6 mmHg, Q5 ≥84.6 mmHg). At the same time, the baseline data of vital signs, critical illness score, comorbidities and laboratory examination were collected on the first day of admission to ICU. The 30-day mortality of the 5 groups of patients and the overall sepsis patients were recorded. Multivariate Cox regression analysis and smooth curve fitting were used to assess the independent association between MAP and 30-day mortality.A total of 14,607 sepsis patients were screened. The mean age of participants was 67.2±16.3 years, approximately 46.9% were women, and the overall 30-day mortality rate was 21.0%. Multivariate Cox regression models and smooth curve fitting revealed a non-linear association between MAP and 30-day mortality. The inflection point occurred at 68.6 mmHg. The left side effect size of each 10-unit change in the exposure factor was [hazard ratio (HR): 0.479, 95% confidence interval (CI): 0.403-0.569, P0.001]. To the right of the inflection point, the effect size was (HR: 0.996, 95% CI: 0.931-1.065, P0.9018).Our study demonstrated a non-linear relationship between MAP and 30-day mortality in patients with sepsis. When MAP was less than 68.6 mmHg, it was a strong predictor of the potential risk of sepsis death, which declined by 52.1% for every 10 mmHg growth in MAP.

Peroxidase-like nanozymes are nanoscale materials that can closely mimic the activity of natural peroxidase for a range of oxidation reactions. Surface coating with polymer nanogels has been considered to prevent the aggregation of nanozymes. For a long time, the understanding of polymer coating has been largely limited to its stabilization effect on the nanozyme in aqueous media, while little is known about how polymer coating plays a role in interaction with substrates and primary oxidants to dictate the catalytic process. This work reported a facile sequential modification of Fe3O4 nanoparticles to polyacrylamide coated nanozymes, and as low as 112 mg/L samples with only 5 mg/L Fe3O4 could nearly quantitatively (99%) remove a library of organic dyes with either H2O2 or Na2S2O8 as primary oxidants. The catalytic results and molecular simulation provide both experimental and computational evidence that the hydrogen bonding interaction between the reactant and nanozymes is key for the high local concentration hence catalytic efficiency. We envision that this work, for the first time, provides some insights into the role of polymer coating in enhancing the catalytic activity of nanozyme apart from the well-known water dispersity effect.

Owing to their anti-fouling properties, zwitterionic polypeptides demonstrate great advantage on protecting protein drugs. When conjugated to glucagon-like peptide-1 (GLP-1), a drug for type-II diabetes, zwitterionic polypeptides confer better pharmacokinetics than uncharged counterparts. However, its microscopic mechanism is still unclear due to the complicated conformational space. To address this challenge, this work explored the interaction modes of GLP-1 with the unconnected repeat units, instead of the full-length polypeptides. The three repeat units are two zwitterionic pentapeptides VPKEG and VPREG, and one uncharged control VPGAG. Our molecular simulations revealed that the helical conformation of GLP-1 was stabilized by adding 40 polypeptides. Both VPGAG and VPREG formed dense packing shells around GLP-1, but the driving forces were hydrophobic and electrostatic interactions, respectively. In contrast, the packing shell composed of VPKEG was most loose, while could still stabilize GLP-1. The moderate electrostatic interactions endowed VPKEG an anti-fouling property, thereby avoiding non-specific interaction with other amino acids. The strong electrostatic interactions exerted by arginine promoted atomic contacts between VPREG and other residues, making it as "hydrophobic" as VPGAG. In summary, the combination of hydrophobic and moderate electrostatic interactions in VPKEG brings about a subtle balance between stabilizing GLP-1 and avoiding non-specific interaction.

ObjectiveHip fracture is a prevalent condition with a significant death rate among the elderly. We sought to develop a nomogram-based survival prediction model for older patients with hip fracture.DesignA retrospective case–control study.SettingThe data from Medical Information Mart for Intensive Care III (MIMIC-III V.1.4).ParticipantsThe clinical features of elderly patients with hip fracture, including basic information, comorbidities, severity score, laboratory tests and therapy, were filtered out based on the MIMIC-III V.1.4.Methods and main outcome measuresAll patients included in the study were from critical care and randomly divided into training and validation sets (7:3). On the basis of retrieved data, the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression analysis were used to identify independent predictive variables of 1-year mortality, and then constructed a risk prediction nomogram. The predictive values of the nomogram model were evaluated by the concordance indexes (C-indexes), receiver operating characteristic curve, decision curve analysis (DCA) and calibration curve.ResultsA total of 341 elderly patients with hip fracture were included in this study; 121 cases died within 1 year. After LASSO regression and multiple logistic regression analysis, a novel nomogram contained the predictive variables of age, weight, the proportion of lymphocyte count, liver disease, malignant tumour and congestive heart failure. The constructed model proved satisfactory discrimination with C-indexes of 0.738 (95% CI 0.674 to 0.802) in the training set and 0.713 (95% CI 0.608 to 0.819) in the validation set. The calibration curve shows a good degree of fitting between the predicted and observed probabilities and the DCA confirms the model’s clinical practicability.ConclusionsThe novel prediction model provides personalised predictions for 1-year mortality in elderly patients with hip fractures. Compared with other hip fracture models, our nomogram is particularly suitable for predicting long-term mortality in critical patients.

The sluggish charge transfer and poor intrinsic activity are the obstacles that limit the development for electrocatalysts on hydrogen evolution. A novel core-shell heterostructure composed of Cu3P nanowires with supported CoO nanosheets was synthesized. Owing to numerous active sites and synergistic effect, the as-prepared Cu3P@CoO was highly efficient for hydrogen evolution and outperformed the single component. The theoretical calculations demonstrate that Cu3P@CoO had a zero bandgap for the incorporation of metallic Cu3P, which can greatly accelerate the charge transfer. Besides, the adsorption free energy of intermediates on Cu3P@CoO can also be optimized, leading to a small energy barrier in the reaction pathway, and thereby an increased intrinsic activity. This work highlights the significance of exploiting the synergistic effect of the heterostructure on the charge transfer and intrinsic activity when designing highly efficient electrocatalysts for hydrogen evolution.

Spectrum reconstruction with filter-free microspectrometers has attracted much attention owing to their promising potential in

Transition metal phosphides are regarded as promising cocatalysts for photocatalytic hydrogen evolution, although there are still many limitations, such as a relatively lower electrical conductivit...

Hydrogen fuel receives worldwide attention for the zero emission and high energy density. Production of hydrogen by electrochemical water splitting requires efficient electrocatalysts to boost the hydrogen evolution reaction (HER). Transition metal phosphides are regarded as promising substitutes for precious metals as HER electrocatalysts. This review focuses on the recent progress with respect to the advantages, common synthetic approaches and enhancement strategies of Fe, Co and Ni-based phosphides, with important works in each section elaborately introduced for researchers in the relevant area. After the rational design and fabrication, Fe, Co and Ni-based phosphides can become highly efficient, durable and cost-effective electrocatalysts, and thereby exhibit a great potential for the scale-up production of hydrogen fuel.

Water oxidation reaction often impedes the overall water splitting for the multi-step electron transfer process. Transition metal sulfides are earth abundant and widely studied for accelerating water splitting reactions. Cuprous sulfide, which is a common mineral and generally regarded as less active for oxygen evolution reaction, can also effectively promote water oxidation by introducing coarse surfaces on the as-prepared Cu2S nanorod arrays, with a largely increased double layer capacitance and thereby a greatly improved electrochemically active surface area, which only needs an overpotential of 360 mV to deliver 50 mA cm−2 and exhibits a rapid kinetics for oxygen evolution reaction. The fabrication strategy of creating coarse surfaces on pre-synthesized nanostructures for increased electrochemically active surface area can be promising for developing precious-metal-free electrocatalysts by providing more active sites and surface areas for water oxidation, and is also valuable for promoting the activity of less active but earth-abundant materials to achieve a better cost-effectiveness in scale-up application of water splitting technology.

As ubiquitous environmental pollutants, phenolic compounds are requested to be efficiently removed from wastewater. Enzymes, such as Horseradish peroxidase (HRP), have been demonstrated with great potential in removing phenolic compounds. Different from the general immobilization technology, the encapsulation of individual enzymes within nanogel has been employed in this work. Here we show that, the encapsulated HRP could remarkably enhance enzymatic performance, including thermostability, catalytic efficiency, environmental tolerance and, most importantly, the biodegradation of phenolic compounds. For instance, the removal efficiencies of phenol and BPA increased by 7-fold and 3.5-fold, respectively. On the other hand, the diverted removal efficiencies were obtained for a series of phenolic compounds. Based on molecular modelling, the biodegradabilities of phenolic compounds were rationalized according to their redox potentials and binding affinities with enzymes. In summary, our work indicates that the nanocapsulation of enzyme should be a promising strategy in removing different types of phenolic compounds from wastewater.

Increased plasma concentrations of lipoprotein(a) (Lp(a)) are associated with an increased risk for cardiovascular disease. Lp(a) is composed of apolipoprotein(a) (apo(a)) covalently bound to apolipoprotein B of low-density lipoprotein (LDL). Many of apo(a)'s potential pathological properties, such as inhibition of plasmin generation, have been attributed to its main structural domains, the kringles, and have been proposed to be mediated by their lysine-binding sites. However, available small-molecule inhibitors, such as lysine analogs, bind unselectively to kringle domains and are therefore unsuitable for functional characterization of specific kringle domains. Here, we discovered small molecules that specifically bind to the apo(a) kringle domains KIV-7, KIV-10, and KV. Chemical synthesis yielded compound AZ-05, which bound to KIV-10 with a K(d) of 0.8 μm and exhibited more than 100-fold selectivity for KIV-10, compared with the other kringle domains tested, including plasminogen kringle 1. To better understand and further improve ligand selectivity, we determined the crystal structures of KIV-7, KIV-10, and KV in complex with small-molecule ligands at 1.6–2.1 Å resolutions. Furthermore, we used these small molecules as chemical probes to characterize the roles of the different apo(a) kringle domains in in vitro assays. These assays revealed the assembly of Lp(a) from apo(a) and LDL, as well as potential pathophysiological mechanisms of Lp(a), including (i) binding to fibrin, (ii) stimulation of smooth-muscle cell proliferation, and (iii) stimulation of LDL uptake into differentiated monocytes. Our results indicate that a small-molecule inhibitor targeting the lysine-binding site of KIV-10 can combat the pathophysiological effects of Lp(a).

Many synthetic routes have been explored to make small molecule sulfonimidamides (SIAs), however, its introduction into larger molecules such as oligopeptides has not been studied before. We herein ...

The sluggish charge transfer and poor intrinsic activity are the obstacles that limit the development for electrocatalysts on hydrogen evolution. A novel core-shell heterostructure composed of Cu