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Hydrogen can be used to reduce the concentration of reactive oxygen species (ROS), but its delivery to diseased tissues is challenging due to its low solubility. Here the authors develop a photosynthesis-inspired FRET nanocomplex to detect and scavenge local excess of ROS in the tissue using photocatalytic hydrogen production.

Aims: Cranioplasty and ventriculoperitoneal shunt (VPS) are common procedures for patients who undergo decompressive craniectomy. The ideal time for these two procedures remains controversial. Settings and Design: This is a retrospective, single institute, chart review comparing the complications associated with simultaneous and staged cranioplasty and VPS. Materials and Methods: From January 2012 to December 2017, 56 patients who underwent both cranioplasty and VPS surgery at our hospital were separated into simultaneous or staged operation groups. We compared the demographic data and complications, including infections, subdural or epidural hemorrhage, and revision surgery between the groups. Statistical Analysis Used: Independent Student's t-test was used for analysis of continuous variables, and Fisher's exact test was used for categorical data. MedCalc (version: 18.11) was used to perform all analysis. Results: Nineteen patients underwent simultaneous cranioplasty and VPS, whereas 37 underwent staged operation. Etiologies for craniectomy included traumatic brain injury, infarction, spontaneous subarachnoid hemorrhage, and spontaneous intracerebral hemorrhage. There were no significant differences in the baseline characteristics between the groups. The overall complication rate was 14.3%. Three (15.8%) patients experienced complications in the simultaneous group: One (5.3%) with skin infection and two (10.5%) with overdrainage. Five (13.5%) patients experienced complications in the staged group: three (10.8%) with skin infections, one with central nervous system (CNS) infections, and one with both skin and CNS infections. Overall complications, wound infections, CNS infections, overdrainage, and revision surgery showed no significant differences between the groups. Conclusions: Simultaneous cranioplasty and VPS showed complication rates similar to those of staged operation.

Integer-valued data are frequently encountered in time series studies. A pth-order mixed dependence-driven random coefficient integer-valued autoregressive time series model (Po-MDDRCINAR(p)) in view of binomial and negative binomial operators, where the innovation sequence follows a Poisson distribution, is investigated to provide meaningful theoretical explanations. Strict stationary and ergodicity of the model are demonstrated. Furthermore, the conditional least-squares and conditional maximum-likelihood methods are adopted to estimate the parameters, where the asymptotic characterization of the estimators is derived. Finite-sample properties of the conditional maximum-likelihood estimator are examined in relation to the widely used conditional least-squares estimator. The conclusion is that, if the Poisson assumption of the innovation sequence can be justified, conditional maximum-likelihood method performs better in terms of MADE and MSE. Finally, the practical performance of the model is illustrated by a set of COVID-19 data of suspected cases in China with a comparison with relevant models that exist so far in the literature.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

Highlights An overview of the superhydrophobic surface -assisted strategies for fabricating microspheres and supraparticles are presented. The applications of microspheres and supraparticles fabricated using SHS-assisted strategies are discussed in detail. NCrucial challenges facing the development of microspheres and supraparticles fabricated through SHS-assisted strategies are analysed.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). Methods: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. Results: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. Conclusions: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

Abstract Backgroud Endoscopic surgery can be used as the main treatment for advanced recurrent nasopharyngeal carcinoma (rNPC). However, there is a huge clinical controversy about the need for consolidated immunotherapy after surgery. Methods We performed a retrospective propensity score-matched analysis (1:2) of patients with locally advanced rNPC who underwent endoscopic nasopharyngectomy (ENPG) combined with anti-programmed cell death protein-1 (PD-1) monotherapy or ENPG alone. The survival rate was analyzed by Kaplan–Meier method. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Potential surgical-related complications and immune-related adverse events (AEs) were also assessed. Results We recruited 10 patients receiving ENPG plus anti-PD-1 monotherapy and 20 receiving ENPG alone. During the mean follow-up of 23.8 months, a significant improvement in the 2-year PFS was detected in the consolidation immunotherapy group compared to the ENPG alone group (80.0% vs. 40.0%; HR = 0.258; 95% CI: 0.09–0.72; p = 0.04), while the 2-year OS in the consolidation immunotherapy group was not significantly longer than that in the ENPG alone group (90.0% vs. 75.0%; HR = 0.482; 95% CI: 0.08–3.00; p = 0.50). The incidence of surgical-related complications in the consolidation immunotherapy group and ENPG alone group was 70.0 and 60.0%, respectively. Immune-related AEs were similar between the toripalimab arm (75.0%) and the camrelizumab arm (66.7%). Surgical-related complications depend on symptomatic treatments. Immune-related AEs were mild and tolerable. Conclusions Consolidation immunotherapy regimen for patients with advanced rNPC after ENPG compared to ENPG alone provides a superior PFS rate with a manageable safety profile.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that develops in the nasopharynx. It has a distinct ethnic and geographical distribution, and emerging evidence suggests that it is an ecological disease. Most patients respond well to radiation combined with chemotherapy as the primary treatment for NPC. However, some patients will eventually develop radio resistance and chemoresistance, resulting in recurrence and metastasis, which is a primary cause of poor prognosis. The processes underlying radio resistance and chemoresistance in NPC are complex and unknown. MicroRNAs (miRNAs) are endogenic non-coding RNA molecules. They play a role in a variety of cell functions as well as development of disease such as cancer. There has been considerable data demonstrating the existence of numerous aberrant miRNAs in cancer tissues, cells, and biofluids, which indicates the importance of studying the influence of miRNAs on NPC. Therefore, this review comprehensively analyzes the elaborate mechanisms of miRNAs affecting the radio resistance and chemoresistance of NPC. Multiple tumor-specific miRNAs can be employed as therapeutic and prognostic biological indicators.

Objective This study aimed to explore the impacts of the changing national fertility policy on maternal and fetal characteristics, and birth timing patterns and provide a basis for the management of the obstetric and midwifery workforce.Design Retrospective cohort study.Setting Data from medical register of a tertiary referral centre in Beijing, China.Participants We included 20 334 births with a gestational age more than 28 weeks during January 2013–September 2023.Main outcomes The main outcomes included birth numbers, maternal age, parity, birth modes, premature rates, neonatal birth weight, and birth timings.Results The birth rates showed a general rising trend before 2016. Afterwards, the birth rates kept decreasing and reached the bottom level in 2022. The caesarean section rates showed a declining trend, while the assisted birth rates were progressively rising, especially among primiparous women. From 2013 to 2022, the proportions of multiparous women (increasing from 9.3% to 36.6%) and women with advanced maternal age (increasing from 11.4% to 34.5%) were on the rise, together with increasing rates of premature birth (increasing from 5.7% to 8.5%) and neonatal low birth weight (rising from 4.3% to 7.2%) in this population. This study found a significant peak of births between 14:00 and 15:00, which remained unchanged despite shifts in the fertility policy (p

While overdispersion is a common phenomenon in univariate count time series data, its exploration within bivariate contexts remains limited. To fill this gap, we propose a bivariate integer-valued autoregressive model. The model leverages a modified binomial thinning operator with a dispersion parameter ρ and integrates random coefficients. This approach combines characteristics from both binomial and negative binomial thinning operators, thereby offering a flexible framework capable of generating counting series exhibiting equidispersion, overdispersion, or underdispersion. Notably, our model includes two distinct classes of first-order bivariate geometric integer-valued autoregressive models: one class employs binomial thinning (BVGINAR(1)), and the other adopts negative binomial thinning (BVNGINAR(1)). We establish the stationarity and ergodicity of the model and estimate its parameters using a combination of the Yule–Walker (YW) and conditional maximum likelihood (CML) methods. Furthermore, Monte Carlo simulation experiments are conducted to evaluate the finite sample performances of the proposed estimators across various parameter configurations, and the Anderson-Darling (AD) test is employed to assess the asymptotic normality of the estimators under large sample sizes. Ultimately, we highlight the practical applicability of the examined model by analyzing two real-world datasets on crime counts in New South Wales (NSW) and comparing its performance with other popular overdispersed BINAR(1) models.

The emulation of the biological synapses is essential for brain-inspired computing which is expected to overcome the traditional von Neumann bottleneck. Thus, synaptic memristor with analog resistive switching (RS) is highly desirable in non-volatile memristors for future neuromorphic computing. Herein, the co-existence of digital and analog RS can be observed in two-dimensional (2D) layered BiOI nanosheets sandwiched by the top and bottom Pt electrodes. The vertical Pt/BiOI/Pt memristors demonstrate typical bipolar RS behaviors with a large ON/OFF ratio of 1.0 × 103 and long retention time up to 1.6 × 104 s under a relatively large operation voltage. When the operation voltages are reduced to 1 V, analog RS behaviors with a series of tunable resistance states can be observed. The adjustable resistance states can be utilized to emulate “learning-forgetting” experience of human brain. Repeatable long-term potentiation (LTP) and long-term depression (LTD) cycles can be implemented based on the synaptic memristors, which can be used for simulation of artificial neural network for image recognition with accuracy up to 91.15 %. Moreover, Pavlov’s dog experiment is successfully emulated based on the synaptic memristors. This study suggests good prospects of the synaptic memristors based on BiOI nanosheets for future neuromorphic computing.

Abstract Objective Sinonasal melanoma (SMM) is a rare but aggressive malignancy with 5‐year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SMM remain undefined. We aimed to establish a model to predict the survival outcomes of SMM. Methods We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SMM between 1975 and 2016. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. We also developed and validated a nomogram for OS, and compared its performance with that of conventional staging systems. Results Overall, 305 SMM patients were included in this population‐based study. Multivariate Cox regression showed that primary site, American Joint Committee on Cancer stage, radiotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C‐indices, areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis demonstrated reliable performance of the nomogram. Conclusion The nomogram predicting survival outcomes of SMM patients based on clinical information showed good discriminative ability and prognostic accuracy compared with conventional stage classifications. Our nomogram could be used to predict the survival probabilities for SMM patients at different timepoints. Level of Evidence 2b.

Abstract Background To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. Methods Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random‐effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non‐RCT design, and insufficient participants or follow‐up were excluded. Results In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT‐22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. Conclusions In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head‐to‐head trials and real‐world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.

In this paper, a time-varying first-order mixture integer-valued threshold autoregressive process driven by explanatory variables is introduced. The basic probabilistic and statistical properties of this model are studied in depth. We proceed to derive estimators using the conditional least squares (CLS) and conditional maximum likelihood (CML) methods, while also establishing the asymptotic properties of the CLS estimator. Furthermore, we employed the CLS and CML score functions to infer the threshold parameter. Additionally, three test statistics to detect the existence of the piecewise structure and explanatory variables were utilized. To support our findings, we conducted simulation studies and applied our model to two applications concerning the daily stock trading volumes of VOW.

This paper proposes a new time-varying integer-valued autoregressive (TV-INAR) model with a state vector following a logistic regression structure. Since the autoregressive coefficient in the model is time-dependent, the Kalman-smoothed method is applicable. Some statistical properties of the model are established. To estimate the parameters of the model, a two-step estimation method is proposed. In the first step, the Kalman-smoothed estimation method, which is suitable for handling time-dependent systems and nonstationary stochastic processes, is utilized to estimate the time-varying parameters. In the second step, conditional least squares is used to estimate the parameter in the error term. This proposed method allows estimating the parameters in the nonlinear model and deriving the analytical solutions. The performance of the estimation method is evaluated through simulation studies. The model is then validated using actual time series data.

Introduction. Circadian rhythm is involved in multiple biological activities and implicated in cancer development. However, the role of circadian rhythm in head and neck squamous cell carcinoma (HNSCC) has not been fully interpreted yet. Herein, the present study set out to explore the significance of circadian regulator genes (CRGs) in HNSCC. Materials and Methods. The molecular landscape and clinical significance of 13 CRGs in HNSCC were explored based on The Cancer Genome Atlas (TCGA). The biological functions of PER3, a key CRG, were validated by cellular experiments. The correlation of CRGs with microenvironment, pathway activities, and prognosis was determined by bioinformatic algorithms. A novel circadian score was introduced to evaluate the circadian modification pattern of each patient and further validated in an independent cohort from the Gene Expression Omnibus (GEO) dataset. Results. CRGs presented high heterogeneity in HNSCC at both genomic and transcriptomic levels. Specifically, PER3 indicated a better prognosis and inhibited HNSCC cell proliferation. Moreover, HNSCC tissues displayed three circadian regulator patterns with distinct clinical outcomes, transcriptomic characteristics, and microenvironment features. Circadian score was an independent risk factor and exhibited excellent predictive efficiency in both the training cohort from the TCGA database and the validation cohort from the GEO database. Conclusions. CRGs played an indispensable role in HNSCC development. An in-depth exploration of circadian rhythm would improve the understanding of HNSCC carcinogenesis and confer novel insights for future clinical practices.

Repelling liquid drops from engineering surfaces has attracted great attention in a variety of applications. To achieve efficient liquid shedding, delicate surface textures are often introduced to sustain air pockets at the liquid–solid interface. However, those surfaces are prone to suffer from mechanical failure, which may bring reliability issues and thus limits their applications. Here, inspired by the aerodynamic Leidenfrost effect, we present that impacting drops are directionally repelled from smooth surfaces supplied with an exogenous air layer. Our theoretical analysis reveals that the synchronized nonwetting and oblique bouncing behavior is attributed to the aerodynamic force arising from the air layer. The versatility and practicability of our approach allow for drop repellency without the aid of any surface wettability treatment and also avoid the consideration of mechanical stability issues, which thereby provides a promising candidate for the applications that necessitate liquid shedding, e.g., resolve the problem of tiny raindrop adhesion on the automobile side window during driving.

To broaden the application of ultra-high performance concrete (UHPC) in engineering fields with high-early-strength requirements, accelerators were used to accelerate the setting and hardening of UHPC. This study investigated how alkaline accelerator (NA) and alkali-free accelerator (AS) influence the strength, hydration and microstructure characteristics of UHPC. To achieve the proposed objective, the terms of setting time, strength, released ionic concentration, isothermal calorimetry, X-ray diffraction, scanning electron microscope, energy dispersive X-ray and mercury intrusion porosimetry were performed. The results show that NA and AS significantly increase the setting and hardening rate of UHPC, and their optimal dosages are 2% and 4%, respectively. 2% NA increases the 1 d compressive, splitting tensile and flexural strengths of UHPC by 55.8%, 62.2% and 56.5%, respectively, while 4% AS increases by 10.8%, 21.6% and 21.0%, respectively. However, their later strengths decrease slightly. The first exothermic peak values of NA-2% and AS-4% are about 3 times higher than the reference paste, and their main hydration peaks appear earlier by 38.2 and 23.3 h, respectively. NA and AS contribute to the rapid formation of hydration products and refine the pore structure of pastes.

Objective: The aim of this study was to report 6 cases of sinonasal/basicranial myxofibrosarcoma and review demographic data, clinical symptoms, diagnostic methods, therapeutic methods, and prognosis on this subject in the literature. Methods: We conducted a retrospective analysis of six patients referred to our hospital during a 10-year period from 2010 to 2020. Results: In this series, there were four males and two females. The tumours originated from the maxillary sinus in all six cases. The symptoms were nonspecific, and all patients underwent endoscopic resection alone or combined with open resection. The postoperative period was uneventful. All patients were diagnosed with myxofibrosarcoma. After a median follow-up period of 36 (6–52) months, the recurrence rate of MFS was 66.7% (4/6), and the mortality rate was 50% (3/6). Conclusion: Sinonasal/basicranial MFS is a rare neoplasm, and the most common primary site is the maxillary sinus. When diagnosing MFS, osteolysis may help rule out benign lesions. So far surgery is the mainstay of treatment for sinonasal/basicranial MFS. Our surgical strategy using endoscopic resection or endoscopic resection combined with open resection to achieve a negative surgical margin and using re-excision operations to treat relapsed cases may be recommended to rhinologists who treat MFS. Prospective randomised trials are needed to study the role of chemotherapy, radiotherapy, and our surgical strategy for sinonasal/basicranial MFS. Diagnosing patients at an earlier stage and better patient compliance with follow-up plans may improve the prognosis of patients.

We investigate the complete convergence for weighted sums of sequences of negative dependence (ND) random variables and p-th moment convergence for weighted sums of sequences of ND random variables under sublinear expectation space. Using moment inequality and truncation methods, we prove the equivalent conditions of complete convergence for weighted sums of sequences of ND random variables and p-th moment convergence for weighted sums of sequences of ND random variables under sublinear expectation space.

We are interested in the linear processes generated by dependent sequences under sub-linear expectation. Using the Beveridge–Nelson decomposition of linear processes and the inequalities, the moderate deviation principle for linear processes produced by an m-dependent sequence is established. We also prove the upper bound of the moderate deviation principle for linear processes produced by negatively dependent sequences via different methods from m-dependent sequences. These conclusions promote and improve the corresponding results from the traditional probability space to the sub-linear expectation space.

In this article, we consider the nonparametric inference for the time-varying coefficient double-threshold generalized autoregressive conditional heteroscedastic models. The quasi-maximum exponential likelihood estimators (QMELEs) of the model’s parameters and the asymptotic properties of the estimators are obtained. The simulation study implies that the distribution of the estimators is asymptotically normal. A real data application to stock returns is given. Both the simulations and real data example imply that the model and the QMELE are proper, compatible and accurately fit the financial time series data of the Nikkei 225.

Abstract Background Femoral neck fractures are common fractures in the elderly. Common treatment options include internal fixation (IF) and hemiarthroplasty (HA). However, the clinical application of these two options is always controversial due to the potential clinical trauma, postoperative function, early complications, and other factors. Materials and methods Randomized controlled trials and cohort studies comparing screw fixation and hemiarthroplasty in elderly patients with displaced femoral neck fractures were extracted from databases such as PubMed, Web of Science, EMBASE, and Cochrane. The revised Jadad scale or NOS treatment evaluation form was used to evaluate the quality of the included studies. After extracting the data, the standard deviation of continuous data and the relative risk of binary data were used. The operation time, blood loss during operation, EQ-5D (EuroQol-5 Dimension) score, mortality rate, reoperation rate, and postoperative common complications were reviewed using Review Manager software (RevMan 5.3) were compared. Results There were 7 randomized controlled trials and 5 cohort studies. The results showed that the operation time, intraoperative blood loss, and short-term EQ-5D score of the internal fixation group were lower than those of the hemi-hip replacement group, but the reoperation rate was higher. There was no statistically significant difference in mortality and common complications such as deep vein thrombosis, pulmonary embolism, infection, and pressure sores during short-term follow-up. Conclusions In the treatment of elderly femoral neck fractures, the screw internal fixation group has shorter operation time and less intraoperative bleeding, and the perioperative advantage is more obvious. However, the hemi-hip replacement group had more advantages in postoperative functional scoring and reoperation.

Abstract We study a covariate-adjusted regression(CAR) model that is proposed for such situations where both predictors and response in a regression model are not directly observable but are distorted by a multiplicative factor that is determined by an unknown function of some observable covariate. By establishing a connection to varying-coefficient models, we present the local linear L 1 $L_{1}$ -estimation method when the underlying error distribution deviates from a normal distribution. The robust estimators of parameters are proposed in the underlying regression model. The consistency and asymptotic normality of the robust estimators are investigated. Since the limit distribution depends on the unknown components of the errors, an empirical likelihood ratio method based on L 1 $L_{1}$ estimator is proposed. The confidence intervals for the regression coefficients are constructed. Simulation results demonstrate the superiority of the proposed estimators over other classical estimators when the underlying errors have heavy tails. Pima Indian diabetes data set is conducted to illustrate the performance of the proposed method, where the response and predictors are potentially contaminated by body mass index.

Objective. To investigate the protective effect of laminarin on PC12 cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and its molecular mechanism. Methods. PC12 cells in the logarithmic phase were randomly divided into the control group, OGD/R group, and OGD/R+laminarin (0.5, 2.5, and 5 μg/ml) group. CCK-8 activity assay kit was used to detect cell viability. ELISA kit was performed to examine the levels of proinflammatory factors (TNF-α, IL-1β, and IL-6) and oxidative stress markers (ROS, LDH, and MPO). In addition, flow cytometry was employed to determine cell cycle and apoptosis. The expression of cell proliferation-related proteins (PCNA and Ki67), apoptosis-related proteins (Bcl-2, Bax, and Caspase-3), and PTEN/PI3K/AKT pathway-related proteins was evaluated by Western blot. Results. Compared with the control group, the cell viability was decreased significantly in the OGD/R group. CCK-8 results showed that laminarin could attenuate the damage of PC12 cell viability induced by OGD/R in a concentration-dependent manner. Meanwhile, the highest concentration of 5 μg/ml laminarin could significantly promote the viability of PC12 cells and the expression of PCNA and Ki67 than the OGD/R group. Additionally, ELISA assays showed that laminarin significantly inhibited the expression of proinflammatory factors (TNF-α, IL-1β, and IL-6) and the levels of oxidative stress markers (ROS, LDH, and MPO). Flow cytometry results demonstrated that laminarin promoted the cell cycle. And laminin upregulated the expression of apoptotic protein Bcl-2, while downregulated the expression of apoptotic proteins Bax and Caspase-3. Finally, laminarin significantly suppressed the expression of PTEN and facilitated the expression of PI3K and p-AKT compared to the OGD/R group. Conclusion. Laminarin could alleviate the OGD/R-induced PC12 cell neuronal injury via promoting cell activity and cycle and inhibiting inflammation, oxidative stress, and apoptosis. The mechanism may be related to the downregulation of PTEN protein and the activation of the PI3K/AKT pathway.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC.Materials and MethodsBased on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments.ResultsAmong CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC.ConclusionCollectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for HNSCC patients.

Abstract High‐resolution fluid dispensing techniques play a critical role in modern digital microfluidics, micro‐biosensing, and advanced fabrication. Though most of existing dispensers can achieve precise and high‐throughput fluid dispensing, they suffer from some inherent problems, such as specially fabricated dispensing micronozzles/microtips, large operating systems, low volume tunability, and poor performance for low surface tension liquids and liquids containing solid/liquid additives. Herein, the authors propose a facile, low‐frequency micro dispensing technique based on the Rayleigh–Plateau instability of singular liquid jets, which are stimulated by the air cavity collapse arising in the impact of microliter drops on non‐wetting surfaces. This novel dispensing strategy is capable to produce single microdrops of low‐viscosity liquids with a tunable volume from picoliters to nanoliters, and the operational surface tension range covers most laboratory solvents. The dispensing function is implemented without using small‐dimension nozzles/tips and enables handling diverse complex liquids. Moreover, the rather simple operating platform allows the integration of the whole dispensing function into a handy portable device with a low cost. Employing this microdispensing technique, the authors have controlled microchemical reactions, handled liquid samples in biological analysis, and fabricated smart materials and devices. The authors envision that this rational microdrop generator would find applications in various research areas.

BackgroundSalvage endoscopic nasopharyngectomy has better survival prognosis and fewer complications in the management of early stage rNPC, compared to re-irradiation. However, the treatment modality of advanced recurrent nasopharyngeal carcinoma (rNPC) remains controversial. Thus, the purpose of this study was to investigate the demographics, clinical outcomes, and prognostic factors associated with salvage endoscopic nasopharyngectomy in advanced rNPC.MethodsThis study conducted a retrospective analysis of advanced rNPC patients who underwent salvage surgery betweenm January 2014 and December 2019. The overall survival (OS) and progression-free survival (PFS) were analyzed. Univariable and multivariable analyses of OS and PFS were performed using the Cox regression model. The predicted values of the parameters were determined by means of the receiver operating characteristic (ROC) curve analysis.ResultsAmong the 120 patients included, there were 75 patients with rT3 stage and 45 patients with rT4 stage. With the median follow-up time of 18 months,the 3 -year OS and PFS were 55.2% and 29.4%, respectively. Multivariate analyses showed that the rNPC patients with older age, low BMI (Body Mass Index), rT4 stage, tumor necrosis, and tumor invasion into the ICA was predictive of worse OS, whereas low BMI and rT4 stage were associated with worse PFS. In addition, the rT stage was identified as a better predictor of OS (area under the ROC curve: 0.669; P=0.003) than the other clinical features.ConclusionsSalvage treatment using endoscopic nasopharyngectomy appears to be an effective treatment in the management of patients with advanced rNPC. In addition, case matching studies and prospective studies with larger clinical samples are required to further evaluate the efficacy of endoscopic surgery compared with re-irradiation in advanced rNPC.

Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic strategy. Patients with allergic rhinitis (n = 6) and healthy controls (n = 6) were enrolled, and gut microbiome composition analysis was performed by 16S rDNA sequencing. We also established an ovalbumin (OVA)-induced allergic airway inflammation murine model. Dysbiosis of the gut flora was observed in both AAD patients and the mice, with the decrease of the biodiversity and the quantity of the Bacteroidetes phylum. Oral application of Bacteroides (B.) thetaiotaomicron ameliorated the symptoms of OVA-induced airway hyperresponsiveness (AHR) and attenuated the airway inflammation in mice. In addition, nasal lavage fluid (NALF) and bronchoalveolar lavage fluid (BALF) from AAD mice orally administered with B. thetaiotaomicron showed reduced numbers of immune cells, and diminished secretion of T helper (Th)-2 cytokines (IL-4, IL-5, and IL-13) compared with the corresponding control mice, whereas the levels of Th1 cytokineIFN-γ was not changed in both the groups. When B. thetaiotaomicron was co-administered with metronidazole in AAD mice, the immunomodulatory effect was weakened and the allergic inflammatory response was aggravated. The ratios of CD4+Foxp3+ cells, CD4+ICOS+ T cells, CD4+ICOS+ Foxp3+ regulatory T cells, and IL-10-expressing CD4+Foxp3+ cells were increased in lymphocytes of spleen, mesenteric, and cervical lymph nodes of AAD mice administrated with B. thetaiotaomicron. Therefore, our data indicate that oral administration of B. thetaiotaomicron effectively inhibited the development of AAD in murine model; inhibition was mediated by the activation of Tregs and inhibition of Th2 response without promoting a Th1 response.

Summary: In this paper, we report a finding that substrate affects the adhesion of charged super-repellent surfaces. Water droplet impacting on a super-repellent surface produces surface charge, whose expression depends on the substrate. The charged super-repellent surface is sticky to droplets for a suspended substrate made of dielectric materials, while it has low adhesion for a conducting substrate or stage attached at the bottom because of electrostatic induction. Theoretical analysis and simulation are conducted to elucidate the mechanism of substrate effect on surface adhesion. Finally, we develop a new approach to reversibly tune the adhesion of super-repellent surface by combining surface-charge-induced adhesion increase and electrostatic-induction-regulated express of net surface charge. As a proof-of-concept experiment, we demonstrate that droplet sorting and manipulations can be realized by using this controllable surface adhesion tuning approach, which has potential applications in advanced lab-on-a-drop platform.

BackgroundTransnasal endoscopic nasopharyngectomy (TEN) has become increasingly used for recurrent nasopharyngeal carcinoma (rNPC); however, there is no report on the definitive resectable contour for TEN according to the latest staging system for nasopharyngeal carcinoma. The aim of this study was to establish the types of TEN for rNPC.Materials and MethodsA total of 101 rNPC patients underwent TEN from January 2016 to April 2019 at the authors’ institution. TEN was categorized into four types, which included type I (n=40) with resection of the nasopharynx and sinuses; type II (n=10) with lateral extension to the parapharyngeal space; type III (n=40) with lateral extension to the floor of the middle cranial fossa and the infratemporal fossa and superior extension to the orbital apex and the cavernous sinus back to the prevertebral region; and type IV (n=11) with the resection of the involved internal carotid artery following type III. The 2-year overall survival rate (OS) and local recurrence-free survival rate (LRFS) were assessed.ResultsThe median time of follow-up was 20 months. Twenty-five patients reoccurred. Nineteen patients died. Independent predictors of outcome on multivariate analysis were recurrent T stage (P = 0.039), types of TEN (P = 0.002) and surgical margin (P = 0.003). The 2-year OS and LRFS was 76.2% and 53.6%, respectively.ConclusionsThe result of TEN in the treatment of rNPC is promising. The types of TEN will provide effective guideline for surgical treatment of rNPC.

It is well known that supplementary cementitious materials (SCMs) have obvious effects on the properties of concrete. In order to understand the relationship between cementitious materials and properties of ultrahigh strength concrete (UHSC), the cementitious compositions of UHSC were designed by the simple-centroid design method. The effects of cementitious compositions on the properties of UHSC were investigated. It was found that the incorporation of silica fume (SF) improved the flowability and strength of UHSC, but it decreased the time of acceleration period, calcium hydroxide (CH) content, and porosity of UHSC at a certain content. The incorporation of fly ash (FA) increased the flowability, time of acceleration period, and porosity of UHSC, but it decreased the strength and CH content of UHSC. The relationships between cement, silica fume, and fly ash and the properties of UHSC were calculated based on the simple-centroid design method.

Background: Olfactory neuroblastoma (ONB) is a rare malignancy arising in the nasal vault. Endoscopic resection has been reported to improve overall survival (OS). At present, clinicopathological predictors of the prognosis of ONB remain undefined. Methods: Data including demographics, clinical characteristics and follow-up information of ONB patients treated with endoscopic surgery were collected. Risk factors on OS rates were investigated by LASSO and Cox analyses. A nomogram was developed and evaluated with internal validation. Risk groups were established according to patients’ points in the nomogram. Findings: 154 ONB patients treated with surgery were included in this single center study. A nomogram based on multivariate Cox regression model including multiple tumor history, orbital invasion, carotid canal invasion, modified Kadish stage, delivery sequence of RT and surgery, sequence of chemotherapy and surgery was developed. The bias-corrected C-index (0.886 [95% CI: 0.843-0.943]) was significantly higher than of conventional staging classifications. The AUC of nomogram regarding 1-, 2- and 5-year OS probabilities reached 0.912, 0.929 and 0.957, respectively. The risk levels based on nomogram points were more discriminative than conventional classifications. Interpretation: Validation analysis showed good predictive accuracy and discriminative ability of the nomogram. Therefore, the nomogram could be utilized to individually predict survival probability for ONB patients after endoscopic resection. Funding: This study was funded by the Chinese Academy of Medical Sciences (No. 2019-I2M-5-003), the Shanghai Science and Technology Commission (No. 19411950600), the Shanghai Hospital Development Center (No. SHDC12018118) and the Eye, Ear, Nose and Throat Hospital of Fudan University (No. SYB202006).

Background: This study aimed to assess the effect of endoscopic nasopharyngectomy in patients with recurrent nasopharyngeal carcinoma (NPC) on site-specific and sinonasal-related quality of life (QoL) before and after surgery using validated instruments.Methods: Consecutive adult patients with recurrent NPC, who were treated via salvage endoscopic nasopharyngectomy, were prospectively enrolled at a single institution from January 2018 to December 2019. Each patient completed the Anterior Skull Base Questionnaire (ASBQ) and the 22-Item Sino-Nasal Outcome Test (SNOT-22) preoperatively, and then at regular intervals after surgery to assess their perceived QoL.Results: Forty patients fulfilled the inclusion criteria. The median follow-up was 12 months (range, 2–24 months). Overall scores on the ASBQ and SNOT-22 at 3 or 12 weeks after surgery decreased significantly compared with before surgery (p < 0.05). At 6 months and 1 year postoperatively, there was no significant difference from the preoperative score. Subtotal resection was associated with worse overall ASBQ scores at 6 months and 1 year after endoscopic nasopharyngectomy (p < 0.05). Worse QoL was also associated with advanced T stage (rT3 and rT4) and pathological World Health Organization type III. Sex, age (

Abstract It is widely acknowledged that splash impact can be suppressed by increasing the viscosity of the impinging drop. In this work, however, by imposing a highly viscous drop to a low‐viscosity drop, it is demonstrated that the splash of the low‐viscosity part of this Janus drop on superamphiphobic surfaces can be significantly promoted. The underlying mechanism is that the viscous stress exerted by the low‐viscosity component drives the viscous component moving in the opposite direction, enhancing the spreading of the low‐viscosity side and thereby its rim instability. The threshold velocity, above which splashing occurs, can be tuned by varying the viscosity ratio of the Janus drop. Moreover, the impact of the Janus drop can be employed to verify the mechanism of splash.

The preparation of ultra-high-performance concrete (UHPC) with both high-early-strength and good workability contributes to further promotion of its development and application. This study investigated the effects of different accelerators (SM, alkaline powder accelerator; SF, alkaline powder accelerator containing fluorine; and AF, alkali-free liquid accelerator containing fluorine) on the workability and strength properties of UHPC. The microstructure of UHPC was also characterized by using XRD and SEM. Several dosage levels of accelerators (2%, 4%, 6%, and 8% by mass) were selected. The results indicate that the setting time and fluidity of UHPC are gradually decreased with an increase in accelerators dosage. Compared with fluorine-containing SF/AF, fluorine-free SM evidently facilitates UHPC early strength gain speed. However, the fluorine-containing accelerators have a higher 28 d strength ratio, especially AF. The maximum compressive and flexural strength ratios are obtained at a dosage of 6%, which are 95.5% and 98.3%, respectively. XRD and SEM tests further reveal the effect of different accelerators on the macroscopic properties of UHPC from the micro level.

In view of the complexity and asymmetry of finite range multi-state integer-valued time series data, we propose a first-order random coefficient multinomial autoregressive model in this paper. Basic probabilistic and statistical properties of the model are discussed. Conditional least squares (CLS) and weighted conditional least squares (WCLS) estimators of the model parameters are derived, and their asymptotic properties are established. In simulation studies, we compare these two methods with the conditional maximum likelihood (CML) method to verify the proposed procedure. A real example is applied to illustrate the advantages of our model.

This paper considers the periodic self-exciting threshold integer-valued autoregressive processes under a weaker condition in which the second moment is finite instead of the innovation distribution being given. The basic statistical properties of the model are discussed, the quasi-likelihood inference of the parameters is investigated, and the asymptotic behaviors of the estimators are obtained. Threshold estimates based on quasi-likelihood and least squares methods are given. Simulation studies evidence that the quasi-likelihood methods perform well with realistic sample sizes and may be superior to least squares and maximum likelihood methods. The practical application of the processes is illustrated by a time series dataset concerning the monthly counts of claimants collecting short-term disability benefits from the Workers’ Compensation Board (WCB). In addition, the forecasting problem of this dataset is addressed.

Abstract In this paper, we consider a size-dependent renewal risk model with stopping time claim-number process. In this model, we do not make any assumption on the dependence structure of claim sizes and inter-arrival times. We study large deviations of the aggregate amount of claims. For the subexponential heavy-tailed case, we obtain a precise large-deviation formula; our method substantially relies on a martingale for the structure of our models.

In this research, we consider monitoring mean and correlation changes from zero-inflated autocorrelated count data based on the integer-valued time series model with random survival rate. A cumulative sum control chart is constructed due to its efficiency, the corresponding calculation methods of average run length and the standard deviation of the run length are given. Practical guidelines concerning the chart design are investigated. Extensive computations based on designs of experiments are conducted to illustrate the validity of the proposed method. Comparisons with the conventional control charting procedure are also provided. The analysis of the monthly number of drug crimes in the city of Pittsburgh is displayed to illustrate our current method of process monitoring.

Abstract In this paper, we consider a perturbed compound Poisson risk model with stochastic premiums and constant interest force. We obtain the upper bound and Lundberg-Cramér approximation for the infinite-time ruin probability, and consider the asymptotic formula for the finite-time ruin probability when the claim size is heavy-tailed. We show that the model in our paper has similar results to the classical risk process and some existing generalized models.

The aim of the present study was to investigate the effects of Lycium barbarum polysaccharides (LBP) on cisplatin-induced hair cell damage in the organ of Corti explant. The neonatal (P2-3) rat organ of Corti explant was exposed to cisplatin (20 μM; 48 h) with or without LBP pretreatment (150 and 600 μg/mL; 24 h). Hair cell loss was indicated by FITC-labeled phalloidin staining. The level of reactive oxygen species (ROS) and alteration of mitochondrial membrane potential (ΔΨm) in hair cells were analyzed using fluorescent probes 2′,7′-dichlorofluorescein diacetate and JC-1, respectively. The results showed that LBP significantly attenuated hair cell loss (p < 0.01). Hair cells pretreated with LBP showed significant reduction in ROS production and the decline of ΔΨm compared with cisplatin alone group (p < 0.01), indicating the protective effect of LBP on cisplatin-induced hair cell loss. Taken together, these results indicate that LBP was effective in attenuating cisplatin-induced hair cell loss by reducing the production of ROS and maintaining mitochondrial ΔΨm.

In this study, we designed and synthesized three N-terminal deletion analogs of human beta-defensin 3 (hBD-3), namely, hBD-3Δ4, hBD-3Δ7, and hBD-3Δ10, to determine the effect of N-terminal residues on the antibacterial activity and salt resistance of these peptides. The antibacterial activities and salt resistance of hBD-3 and its analogs were tested against a broad range of standard and clinically isolated strains. The deletion of nine N-terminal residues significantly reduced the antibacterial activity of hBD-3 against most of tested strains, particularly Klebsiella pneumonia. Compared with hBD-3 and other analogs, the analog with a deletion of three residues, hBD-3Δ4, exhibited significantly higher antimicrobial activity against almost all the tested strains, especially Escherichia coli and Enterococcus faecium, at high NaCl concentrations. Given its broad spectrum of antimicrobial activity and high salt resistance, hBD-3Δ4 could serve as a promising template for new therapeutic antimicrobial agents.

New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme was stable even in extremely alkaline buffer (pH 11) and reached its highest activity at a low temperature (15°C), which was different from other MBLs. The 50% inhibition concentration of EDTA against NDM-1 was 412 nM, which showed that NDM-1 was more susceptible to EDTA than other MBLs. The effects of zinc on NDM-1 differed between cephem and carbapenem complexes, but inhibition at high Zn(2+) concentration was observed for all of tested β-lactam compounds.

In this paper, a novel velocimeter based on laser self-mixing Doppler technology has been developed for speed measurement. The laser employed in our experiment is a distributed feedback (DFB) fiber laser, which is an all-fiber structure using only one Fiber Bragg Grating to realize optical feedback and wavelength selection. Self-mixing interference for optical velocity sensing is experimentally investigated in this novel system, and the experimental results show that the Doppler frequency is linearly proportional to the velocity of a moving target, which agrees with the theoretical analysis commendably. In our experimental system, the velocity measurement can be achieved in the range of 3.58 mm/s–2216 mm/s with a relative error under one percent, demonstrating that our novel all-fiber configuration velocimeter can implement wide-range velocity measurements with high accuracy.

Based on the cooperative virulence index ( c.f. ) and LC 50 of fipronil, the interaction effect between short-term heat pretreatment and fipronil on 2 nd instar larvae of diamondback moth (DBM), Plutella xylostella (Linnaeus), was assessed. The results suggested that pretreatment of the tested insects at 30 °C for 2, 4 and 8h could somewhat decrease the toxicity of fipronil at all set concentrations. The LC 50 values of fipronil increased after heat pretreatment and c.f. values in all these treatments were below zero. These results indicated that real mortalities were less than theoretical ones and antagonism was found in the treatments of fipronil at 0.39 and 0.78 mg/L after heat pretreatment at 30°C at 2, 4 and 8 h. However, pretreatment at 30°C for 12h could increase the toxicity of fipronil at all set concentrations, the LC 50 of fipronil decreased after heat pretreatment and c.f. values in all these treatments were above zero, which indicated real mortalities were higher than theoretical ones. Pretreatment of the tested insects at 35 °C for 2, 4, 8 and 12h was found to increase the toxicity of fipronil at all set concentrations which resulted in the decrease of LC 50 values of fipronil and c.f. above zero in all treatments with only one exception. Most interactions were assessed as synergism. The results indicated that cooperative virulence index (c.f.) may be adopted in hormetic effect assessment.

Based on the cooperative virulence index ( c.f .), the interaction effect between short-term heat pretreatment and avermectin on 2 nd instar larvae of diamondback moth (DBM), Plutella xylostella (Linnaeus), was assessed. The results suggested that the interaction results between short-term heat pretreatment and avermectin on the tested insects varied with temperature level as well as its duration and avermectin concentration. Interaction between heat pretreatment at 30°C and avermectin mainly resulted in addition. Meanwhile, pretreatment at 35°C for 2 or 4 h could antagonize the toxicity of avermectin at lower concentrations, which indicated a hormetic effect occurred. The results indicate that cooperative virulence index ( c.f .) may be adopted in hormetic effect assessment.