Engineered Macrophage Membrane-Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death.

Spinal cord injury (SCI) is a severe neurological disorder characterized by significant disability and limited treatment options. Mitigating the secondary inflammatory response following the initial injury is the primary focus of current research in the treatment of SCI. CCL2 (C─C motif chemokine ligand 2) serves as the primary regulator responsible for inflammatory chemotaxis of the majority of peripheral immune cells, blocking the CCL2-CCR2 (C─C chemokine receptor type 2) axis has shown considerable therapeutic potential for inflammatory diseases, including SCI. In this study, it presents a multifunctional biomimetic nanoplatform (CCR2-MM@PLGA/Cur) specifically designed to target the CCL2-CCR2 axis, which consisted of an engineered macrophage membrane (MM) coating with enhanced CCR2 expression and a PLGA (poly (lactic-co-glycolic acid)) nanoparticle that encapsulated therapeutic drugs. CCR2 overexpression on MM not only enhanced drug-targeted delivery to the injury site, but also attenuated macrophage infiltration, microglia pro-inflammatory polarization, and neuronal apoptosis by trapping CCL2. Consequently, it facilitated neural regeneration and motor function recovery in SCI mice, enabling a comprehensive treatment approach for SCI. The feasibility and efficacy of this platform are confirmed through a series of in vitro and in vivo assays, offering new insights and potential avenues for further exploration in the treatment of SCI.

Near-Infrared Light-Excited Quinolinium-Carbazole Small Molecule as Two-Photon Fluorescence Nucleic Acid Probe.

This article reports three new two-photon absorption (TPA) materials that are quinolinium-carbazole derivates. They are 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (M4), 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H2), and 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H4). Their TPA cross-sections are 491, 515, and 512 GM, respectively. Under the excitation of near-infrared light, their fluorescence emission is about 650 nm. The compounds can stain nucleic acid DNA with the same level of nuclear localization as Hoechst 33342. Under continuous irradiation with a near-infrared laser, the three new compounds showed less fluorescence decay than DAPI, and the average fluorescence decay rates were 0.016%/s, 0.020%/s, and 0.023%/s. They are expected to become new two-photon fluorescent probes of nucleic acid DNA because of their excellent performance.

Semiparametric additive time-varying coefficients model for longitudinal data with censored time origin.

Statistical analysis of longitudinal data often involves modeling treatment effects on clinically relevant longitudinal biomarkers since an initial event (the time origin). In some studies including preventive HIV vaccine efficacy trials, some participants have biomarkers measured starting at the time origin, whereas others have biomarkers measured starting later with the time origin unknown. The semiparametric additive time-varying coefficient model is investigated where the effects of some covariates vary nonparametrically with time while the effects of others remain constant. Weighted profile least squares estimators coupled with kernel smoothing are developed. The method uses the expectation maximization approach to deal with the censored time origin. The Kaplan-Meier estimator and other failure time regression models such as the Cox model can be utilized to estimate the distribution and the conditional distribution of left censored event time related to the censored time origin. Asymptotic properties of the parametric and nonparametric estimators and consistent asymptotic variance estimators are derived. A two-stage estimation procedure for choosing weight is proposed to improve estimation efficiency. Numerical simulations are conducted to examine finite sample properties of the proposed estimators. The simulation results show that the theory and methods work well. The efficiency gain of the two-stage estimation procedure depends on the distribution of the longitudinal error processes. The method is applied to analyze data from the Merck 023/HVTN 502 Step HIV vaccine study.

A semiparametric Cox-Aalen transformation model with censored data.

We propose a broad class of so-called Cox-Aalen transformation models that incorporate both multiplicative and additive covariate effects on the baseline hazard function within a transformation. The proposed models provide a highly flexible and versatile class of semiparametric models that include the transformation models and the Cox-Aalen model as special cases. Specifically, it extends the transformation models by allowing potentially time-dependent covariates to work additively on the baseline hazard and extends the Cox-Aalen model through a predetermined transformation function. We propose an estimating equation approach and devise an expectation-solving (ES) algorithm that involves fast and robust calculations. The resulting estimator is shown to be consistent and asymptotically normal via modern empirical process techniques. The ES algorithm yields a computationally simple method for estimating the variance of both parametric and nonparametric estimators. Finally, we demonstrate the performance of our procedures through extensive simulation studies and applications in two randomized, placebo-controlled human immunodeficiency virus (HIV) prevention efficacy trials. The data example shows the utility of the proposed Cox-Aalen transformation models in enhancing statistical power for discovering covariate effects.

Poaceae Chloroplast Genome Sequencing: Great Leap Forward in Recent Ten Years.

The first complete chloroplast genome of rice (Oryza sativa) was published in 1989, ushering in a new era of studies of chloroplast genomics in Poaceae. Progresses in Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) technologiesand in the development of genome assembly software, have significantly advanced chloroplast genomics research. Poaceae is one of the most targeted families in chloroplast genome research because of its agricultural, ecological, and economic importance. Over the last 30 years, 2,050 complete chloroplast genome sequences from 40 tribes and 282 genera have been generated, most (97%) of them in the recent ten years. The wealth of data provides the groundwork for studies on species evolution, phylogeny, genetic transformation, and other aspects of Poaceae chloroplast genomes. As a result, we have gained a deeper understanding of the properties of Poaceae chloroplast genomes. Here, we summarize the achievements of the studies of the Poaceae chloroplast genomes and envision the challenges for moving the area ahead.

Resistance to Masks During the COVID-19 Pandemic: How User Comments Drive Psychological Reactance to Health Campaigns.

Campaigns for mask-wearing have become widespread on digital platforms during the COVID-19 outbreak and have garnered varied responses in the form of comments. The present study conducts a 2 (comment position: pro-mask wearing vs. anti-mask wearing) × 2 (comment tone: civil vs. uncivil) between-subjects experiment to investigate whether and how the position and tone of comments accompanying a health campaign on social media affect people's psychological reactance toward the campaign. The results show that although anti-mask wearing comments following a social media mask-promoting post provoke individuals' perception about others' disapproval of the post, the perception did not trigger the individuals' psychological reactance to the post. Nevertheless, uncivil comments elicit anger, which arouses reactance and cause persuasion failure.

Tracking the Influence of Misinformation on Elderly People's Perceptions and Intention to Accept COVID-19 Vaccines.

In this study, we surveyed low-income elderly people in Hong Kong and their family or friends to test a dual-path model with which we identified how misinformation in the media reached elderly people and how the elderly people's perception and acceptance of coronavirus disease 2019 (COVID-19) vaccines were influenced. The findings suggest that elderly people's own exposure to erroneous information regarding vaccines and COVID-19 in the media was positively associated with their misperceptions. In addition, their family or friends, who also received misinformation from the media, were found to relay the misleading or erroneous information to the elderly people, indicating a two-step flow of media influence. While previous studies have predominantly focused on the direct influence of misinformation in the media, our study suggests that social influence can also mediate the influence of misinformation in the media and negatively impacts elderly people's perceptions of COVID-19 vaccines.

How Exposure to Online Parenting Content Relates to Mothers' Self-Discrepancy and Postpartum Mental Health.

Postpartum mental health problems are common and have deleterious effects on new mothers and their babies. This study developed a theoretically informed model of the relationship between exposure to images of motherhood in online parenting content and mothers' postpartum mental health. The model was tested using survey data collected from 509 Chinese mothers during their 12-month postpartum period. The results revealed that greater exposure to online public parenting content was indirectly related to lower levels of shame among new mothers via two mediators: the presumed influence of parenting media content on their partners, and the mothers' perceptions of the discrepancy between their actual selves as mothers and their partners' expectations of an ideal mother (i.e. actual/own - ideal/partner self-discrepancy). In contrast, increased exposure to online private parenting content shared by peers was indirectly related to increased levels of shame among new mothers via the mediation of social comparison with parenting media images, and of the mothers' perceptions of the discrepancy between their actual selves as mothers and their own expectations of an ideal mother (i.e. actual/own - ideal/own self-discrepancy). Additionally, new mothers were more likely to experience depressive symptoms and shame if they felt that they fell short of their partners' expectations of an ideal mother. However, increased social support reduced the anxiety and shame that stemmed from this belief.

A Pilot Human Cadaveric Study on Accuracy of the Augmented Reality Surgical Navigation System for Thoracolumbar Pedicle Screw Insertion Using a New Intraoperative Rapid Registration Method.

To evaluate the feasibility and accuracy of AR-assisted pedicle screw placement using a new intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy in cadavers. Five cadavers with intact thoracolumbar spines were employed in this study. Intraoperative registration was performed using anteroposterior and lateral views of preoperative CT scanning and intraoperative 2D fluoroscopic images. Patient-specific targeting guides were used for pedicle screw placement from Th1-L5, totaling 166 screws. Instrumentation for each side was randomized (augmented reality surgical navigation (ARSN) vs. C-arm) with an equal distribution of 83 screws in each group. CT was performed to evaluate the accuracy of both techniques by assessing the screw positions and the deviations between the inserted screws and planned trajectories. Postoperative CT showed that 98.80% (82/83) screws in ARSN group and 72.29% (60/83) screws in C-arm group were within the 2-mm safe zone (p < 0.001). The mean time for instrumentation per level in ARSN group was significantly shorter than that in C-arm group (56.17 ± 3.33 s vs. 99.22 ± 9.03 s, p < 0.001). The overall intraoperative registration time was 17.2 ± 3.5 s per segment. AR-based navigation technology can provide surgeons with accurate guidance of pedicle screw insertion and save the operation time by using the intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy.

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates, with application to analysis of biomarker correlates in vaccine trials.

This article studies generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly-robust augmented inverse probability weighted complete-case (AIPW) approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.

Insérer votre résumé ici. We will supply a French abstract for those authors who can't prepare it themselves.

How Misinformation and Rebuttals in Online Comments Affect People's Intention to Receive COVID-19 Vaccines: The Roles of Psychological Reactance and Misperceptions.

This study investigated how exposure to negative and misleading online comments about the COVID-19 vaccination persuasive messages and the ensuing corrective rebuttals of these comments affected people's attitudes and intentions regarding vaccination. An online experiment was performed with 344 adults in the United States. The results showed that rebuttals by the Centers for Disease Control and Prevention, rather than those by social media users, indirectly increased people's willingness to receive the vaccine by reducing their psychological reactance to persuasive messages and their belief in the misinformation contained in the comments. Rebuttals by social media users became more effective in reducing reactance when people initially had stronger pro-vaccination attitudes.

The highly enhanced Cr(VI) photoreduction removal by oxalic acid coordinated with iron-loaded waste Loofah.

In order to remove high toxic Cr(VI) from the water with low cost and high efficiency, iron-loaded Loofah (Loofah-Fe) was prepared from agriculture waste Loofah and was applied in the Cr(VI) photoreduction remvoal by oxalic acid (Ox). The Cr(VI) removal of Loofah-Fe/Ox/UV system were investigated by the effect of initial Cr(VI) concentration, Ox concentration and Loofah-Fe dosage. The Cr(VI) removal mechanism in Loofah-Fe/Ox/UV system were discussed through the study of initial pH, the change (pH, Ox concentration, Fe(II) and Fe(III) concentration) in solution during the reaction, and the free radicals scavenging test. The role of Loofah-Fe in Loofah-Fe/Ox/UV system was further deduced by the analysis of XPS, EIS and Mott-Schottky. The results showed that Loofah-Fe remarkably enhanced the Cr(VI) photoreduction by Ox, 1 mM of Cr(VI) in aqueous solution was completely removed in 30 min by Loofah-Fe/Ox/UV system at pH = 3.0. The loaded Fe(III) and the contained SiO2 on Loofah-Fe played an important synergized photocatalytic role for Cr(VI) removal in Loofah-Fe/Ox/UV system. Fe(II) and CO2·-, which was continuously generated by photoactive Fe(III)-(C2O4)3 formed between Ox and Fe(III) dissolved from Loofah-Fe, reduced a large amounts of Cr(VI) in solution. The separated electron (e-) and the produced CO2·-, generated from the oxidized Ox by the hole (h+) through photoactive SiO2 on Loofah-Fe, also reduced part of Cr(VI).

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. RESULTS: Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. CONCLUSIONS: We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

The Role of Influence of Presumed Influence and Anticipated Guilt in Evoking Social Correction of COVID-19 Misinformation.

Misinformation on social media pertaining to COVID-19 poses a great threat to public health. The active correction of misinformation by social media users and an understanding of the drivers of such behavior can help solve this ongoing issue. Drawing on the influence of presumed influence model and cognitive appraisal theory, an online experiment (N = 400) was conducted to examine how exposure to corrective messages with regard to COVID-19 misinformation induced individuals' threat appraisals of the influence of the misinformation on others and how these threat appraisals and the corresponding emotional responses motivated individuals to take corrective actions. The results suggested that people's perceptions of the severity of the influence of misinformation on others engendered anticipated guilt, which, in turn, strengthened their intentions to correct misinformation related to COVID-19. The study offers guidance on how to effectively craft a corrective message to encourage audiences to counter misinformation together.

The Battle is On: Factors that Motivate People to Combat Anti-Vaccine Misinformation.

This study proposes a theory-driven model to concurrently examine the cognitive and emotional factors that motivate vaccine supporters to combat erroneous online anti-vaccination information. The model was tested using data from a web survey of 599 vaccination supporters in the United States. The vaccine supporters reported greater support for government regulation of misinformation when they perceived greater susceptibility among the general public to the influence of misinformation. Surprisingly, the perceived severity of the influence was inversely related to respondents' intention to correct misinformation. In addition, perceived susceptibility to the influence of anti-vaccine misinformation and perceived severity of its influence on others induced negative emotions that included anticipated guilt and anger. The negative emotions in turn motivate vaccine supporters to attitudinally support government's media restriction or behaviorally correct the online misinformation.

Semiparametric regression analysis of partly interval-censored failure time data with application to an AIDS clinical trial.

Failure time data subject to various types of censoring commonly arise in epidemiological and biomedical studies. Motivated by an AIDS clinical trial, we consider regression analysis of failure time data that include exact and left-, interval-, and/or right-censored observations, which are often referred to as partly interval-censored failure time data. We study the effects of potentially time-dependent covariates on partly interval-censored failure time via a class of semiparametric transformation models that includes the widely used proportional hazards model and the proportional odds model as special cases. We propose an EM algorithm for the nonparametric maximum likelihood estimation and show that it unifies some existing approaches developed for traditional right-censored data or purely interval-censored data. In particular, the proposed method reduces to the partial likelihood approach in the case of right-censored data under the proportional hazards model. We establish that the resulting estimator is consistent and asymptotically normal. In addition, we investigate the proposed method via simulation studies and apply it to the motivating AIDS clinical trial.

The synergistic effect of attapulgite in the highly enhanced photoreduction of Cr(VI) by oxalic acid in aqueous solution.

Attapulgite (ATP), a widely existed clay in nature, was firstly and successfully applied to enhance the photoreduction of highly toxic Cr(VI) by oxalic acid (Ox). In ATP + Ox + UV system, batch effects (Ox concentration, initial Cr(VI) concentration, ATP dosage, and reusability of ATP) were investigated. By studying the impact of the initial pH in the solution, the change of pH and Fe species concentration as well as Ox concentration during the reaction, the free radical scavenging test, and the role of ATP, the mechanism of Cr(VI) removal by ATP + Ox + UV system was revealed. The methyl orange (MO) removal of ATP + Ox + UV system was also inspected. The results indicated that ATP showed the obvious enhancement in efficient photoreduction of Cr(VI) by Ox in water. The Fe and Si components in ATP played an important role in Cr(VI) removal by ATP + Ox + UV system: most of Cr(VI) was reduced by Fe(II) and CO2•‒ produced by the Fe(III)-Ox complex from the dissolved Fe component in ATP under UV irradiation. Some of Cr(VI) was reduced by e- and CO2•‒ from the oxidation of Ox by h+ generated by the photocatalyzed SiO2 in ATP. Furthermore, ATP + Ox + UV system also showed excellent MO removal performance, indicating the great potential in practical applications.

Analysis of the time-varying Cox model for the cause-specific hazard functions with missing causes.

This paper studies the Cox model with time-varying coefficients for cause-specific hazard functions when the causes of failure are subject to missingness. Inverse probability weighted and augmented inverse probability weighted estimators are investigated. The latter is considered as a two-stage estimator by directly utilizing the inverse probability weighted estimator and through modeling available auxiliary variables to improve efficiency. The asymptotic properties of the two estimators are investigated. Hypothesis testing procedures are developed to test the null hypotheses that the covariate effects are zero and that the covariate effects are constant. We conduct simulation studies to examine the finite sample properties of the proposed estimation and hypothesis testing procedures under various settings of the auxiliary variables and the percentages of the failure causes that are missing. These simulation results demonstrate that the augmented inverse probability weighted estimators are more efficient than the inverse probability weighted estimators and that the proposed testing procedures have the expected satisfactory results in sizes and powers. The proposed methods are illustrated using the Mashi clinical trial data for investigating the effect of randomization to formula-feeding versus breastfeeding plus extended infant zidovudine prophylaxis on death due to mother-to-child HIV transmission in Botswana.

Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data.

The generalized semiparametric mixed varying-coefficient effects model for longitudinal data can accommodate a variety of link functions and flexibly model different types of covariate effects, including time-constant, time-varying, and covariate-varying effects. The time-varying effects are unspecified functions of time and the covariate-varying effects are nonparametric functions of a possibly time-dependent exposure variable. A semiparametric estimation procedure is developed that uses local linear smoothing and profile weighted least squares, which requires smoothing in the two different and yet connected domains of time and the time-dependent exposure variable. The asymptotic properties of the estimators of both nonparametric and parametric effects are investigated. In addition, hypothesis testing procedures are developed to examine the covariate effects. The finite-sample properties of the proposed estimators and testing procedures are examined through simulations, indicating satisfactory performances. The proposed methods are applied to analyze the ACTG 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV-infected patients before and after developing the T215Y antiretroviral drug resistance mutation.

Insérer votre résumé ici. We will supply a French abstract for those authors who can't prepare it themselves. La revue canadienne de statistique : 1­25; 2011.

Weighted Estimating Equations for Additive Hazards Models with Missing Covariates.

This paper presents simple weighted and fully augmented weighted estimators for the additive hazards model with missing covariates when they are missing at random. The additive hazards model estimates the difference in hazards and has an intuitive biological interpretation. The proposed weighted estimators for the additive hazards model use incomplete data nonparametrically and have close-form expressions. We show that they are consistent and asymptotically normal, and are more efficient than the simple weighted estimator which only uses the complete data. We illustrate their finite-sample performance through simulation studies and an application to study the progression from mild cognitive impairment to dementia using data from the Alzheimer's Disease Neuroimaging Initiative as well as an application to the mouse leukemia study.