Outcomes in non-small cell lung cancer with uncommon epidermal growth factor receptor L858 substitutions under first-line epidermal growth factor receptor tyrosine kinase inhibitors: A large real-world cohort study.

Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression-free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFRL858Q/M patients showed enhanced first-line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFRL858R.

On-site filtration of large sample volumes improves the detection of opportunistic pathogens in drinking water distribution systems.

In this study, we compared conventional vacuum filtration of small volumes through disc membranes (effective sample volumes for potable water: 0.3-1.0 L) with filtration of high volumes using ultrafiltration (UF) modules (effective sample volumes for potable water: 10.6-84.5 L) for collecting bacterial biomass from raw, finished, and tap water at seven drinking water systems. Total bacteria, Legionella spp., Legionella pneumophila, Mycobacterium spp., and Mycobacterium avium complex in these samples were enumerated using both conventional quantitative PCR (qPCR) and viability qPCR (using propidium monoazide). In addition, PCR-amplified gene fragments were sequenced for microbial community analysis. The frequency of detection (FOD) of Legionella spp. in finished and tap water samples was much greater using UF modules (83% and 77%, respectively) than disc filters (24% and 33%, respectively). The FODs for Mycobacterium spp. in raw, finished, and tap water samples were also consistently greater using UF modules than disc filters. Furthermore, the number of observed operational taxonomic units and diversity index values for finished and tap water samples were often substantially greater when using UF modules as compared to disc filters. Conventional and viability qPCR yielded similar results, suggesting that membrane-compromised cells represented a minor fraction of total bacterial biomass. In conclusion, our research demonstrates that large-volume filtration using UF modules improved the detection of opportunistic pathogens at the low concentrations typically found in public drinking water systems and that the majority of bacteria in these systems appear to be viable in spite of disinfection with free chlorine and/or chloramine.IMPORTANCEOpportunistic pathogens, such as Legionella pneumophila, are a growing public health concern. In this study, we compared sample collection and enumeration methods on raw, finished, and tap water at seven water systems throughout the State of Minnesota, USA. The results showed that on-site filtration of large water volumes (i.e., 500-1,000 L) using ultrafiltration membrane modules improved the frequency of detection of relatively rare organisms, including opportunistic pathogens, compared to the common approach of filtering about 1 L using disc membranes. Furthermore, results from viability quantitative PCR (qPCR) with propidium monoazide were similar to conventional qPCR, suggesting that membrane-compromised cells represent an insignificant fraction of microorganisms. Results from these ultrafiltration membrane modules should lead to a better understanding of the microbial ecology of drinking water distribution systems and their potential to inoculate premise plumbing systems with opportunistic pathogens where conditions are more favorable for their growth.

Circulating tumor DNA assisting lymphoma genetic feature profiling and identification.

INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.

The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes.

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination.

Identifying latent subtypes of symptom trajectories in major depressive disorder patients and their predictors.

This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.

Giant Orbital-to-Spin Conversion for Efficient Current-Induced Magnetization Switching of Ferrimagnetic Insulator.

It has long been believed that the attachment of two heavy metals such as Ta and Pt with opposite spin Hall angles results in a weakened net torque generation efficiency in magnetization switching devices. Here, we report a giant orbital-to-spin conversion in Ta/Pt/Tm3Fe5O12 (TmIG) heterostructures. We show that the torque generation efficiency is enhanced by an order of magnitude in the Ta/Pt/TmIG trilayer compared to that in the Pt/TmIG bilayer. This enhancement is further evidenced by the fact that the critical current density for the magnetization switching of the Ta/Pt/TmIG is an order of magnitude smaller than that of the Pt/TmIG. It is found that the orbital current generated from Ta through the orbital Hall effect (OHE) is converted to the spin current in the interior of Pt. Our discovery offers an extraordinary approach to enhance the torque generation for magnetization switching of insulators and provides an important piece of information for orbitronics.

Robust Mutual Synchronization in Long Spin Hall Nano-oscillator Chains.

Mutual synchronization of N serially connected spintronic nano-oscillators boosts their coherence by N and peak power by N2. Increasing the number of synchronized nano-oscillators in chains holds significance for improved signal quality and emerging applications such as oscillator based unconventional computing. We successfully fabricate spin Hall nano-oscillator chains with up to 50 serially connected nanoconstrictions using W/NiFe, W/CoFeB/MgO, and NiFe/Pt stacks. Our experiments demonstrate robust and complete mutual synchronization of 21 nanoconstrictions at an operating frequency of 10 GHz, achieving line widths <134 kHz and quality factors >79,000. As the number of mutually synchronized oscillators increases, we observe a quadratic increase in peak power, resulting in 400-fold higher peak power in long chains compared to individual nanoconstrictions. While chains longer than 21 nanoconstrictions also achieve complete mutual synchronization, it is less robust, and their signal quality does not improve significantly, as they tend to break into partially synchronized states.

Flushing Temporarily Improves Microbiological Water Quality for Buildings Supplied with Chloraminated Surface Water but Has Little Effect for Groundwater Supplies.

Microbial communities in premise plumbing systems were investigated after more than 2 months of long-term stagnation, during a subsequent flushing event, and during post-flush stagnation. Water samples were collected from showers in buildings supplied with chlorinated groundwater, untreated groundwater, and chloraminated surface water. The building supplied with chlorinated groundwater generally had the lowest bacterial concentrations across all sites (ranging from below quantification limit to 5.2 log copies/L). For buildings supplied with untreated groundwater, bacterial concentrations (5.0 to 7.6 log copies/L) and microbial community diversity index (ACE) values were consistent throughout sampling. Nontuberculous mycobacteria (NTM) and Legionella pneumophila were not detected in any groundwater-supplied buildings. Total bacteria, Legionella spp., and NTM were abundant in the surface water-supplied buildings following long-term stagnation (up to 7.6, 6.2, and 7.6 log copies/L, respectively). Flushing decreased these concentrations by ∼1 to >4 log units and reduced microbial community diversity, but the communities largely recovered within a week of post-flush stagnation. The results suggest that buildings supplied with disinfected surface water are more likely than buildings supplied with treated or untreated groundwater to experience deleterious changes in microbiological water quality during stagnation and that the water quality improvements from flushing with chloraminated water, while substantial, are short-lived.

Obesity as a mediator linking sleep-disordered breathing to both impaired fasting glucose and type 2 diabetes.

PURPOSE: To examine whether or not associations between sleep-disordered breathing (SDB) and impaired fasting glucose and type 2 diabetes are mediated by obesity. METHODS: We used cross-sectional data including participants from the Multi-Ethnic Study of Atherosclerosis (MESA). SDB, including obstructive sleep apnea (OSA), hypoxia and sleep fragmentation, was evaluated by polysomnography. Further, five obesity measures related to overall obesity and central obesity were assessed. Mediation analysis was conducted to explore the mediating effect of obesity on these relationships between SDB and impaired fasting glucose and type 2 diabetes. RESULTS: Among 1615 participants, OSA and hypoxia, including apnea hypopnea index (AHI) ≥ 15, percent of total sleep time (TST) with SaO2 < 90% (TST90), oxygen desaturation index (ODI), and lowest oxygen saturation (SaO2), were significantly associated with impaired fasting glucose and type 2 diabetes. In addition, mean SaO2 was also associated with impaired fasting glucose. Mediation analysis showed that these relationships were significantly mediated by all five obesity measures, where central obesity had greater mediating effect than overall obesity. Proportion of mediation of obesity ranged from 21.5 to 62.5% for impaired fasting glucose and 25.85 to 71.6% for type 2 diabetes, with substantial differences found in the subgroup analysis by gender or race/ethnicity. The consistency of the mediating effect was demonstrated across multiple measures of SDB, obesity, and glucose metabolism. CONCLUSION: Obesity, especially central obesity, may play a critical role in the pathway where SDB, including OSA and hypoxia, increases the occurrence of impaired fasting glucose and type 2 diabetes. Weight management is important for patients with SDB to prevent type 2 diabetes.

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring.

BACKGROUND: Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. METHODS: We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. RESULTS: A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. CONCLUSIONS: Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.

Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis.

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3 ) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 µM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 µM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.

Novel deoxyribonucleic acid methylation perturbations in workers exposed to vinyl chloride.

To explore the epigenetic mechanism of deoxyribonucleic acid (DNA) damage induced by vinyl chloride (VC), we studied the micronuclei of peripheral blood lymphocytes in 193 subjects (92 in a VC exposure group employed in a chlorine-alkali plant; 101 in a control group employed in a power plant) and selected three pairs from the subjects (exposed and control) for whole-genome bisulfite sequencing (WGBS). The results showed that the rate of micronucleus formation in the VC exposure group was higher than that of control group (6.05 ± 3.28‰ vs. 2.01 ± 1.79‰). A total of 9534 differentially methylated regions (DMRs) were identified by WGBS, of which 4816 were hypomethylated and 4718 were hypermethylated. The Kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) analyses showed the top three KEGG pathways were cancer , neuroactive ligand-receptor interaction, and axon guidance, and the top three GO-BP pathways enriched were multicellular organismal process, developmental process, and anatomical structure development. In the most enriched DMR pathway (pathways in cancer), we found that BCL2, TJP2, TAOK1, PFKFB3, LIPI, and LIPH were hypermethylated, and the methylation levels of BNIP1 and GRPEL2 were decreased. The methylation of differentially methylated genes (DMGs) mentioned above were verified by methylation-specific PCR (MSP) and agarose gel electrophoresis (AGE) in 50 pairs of subjects, where the coincidence rate was 60-100%. In conclusion, the epigenetic perturbations of specific DMGs (BCL2, TJP2, TAOK1, PFKFB3, LIPI, LIPH, BNIP1, and GRPEL2) may be associated with DNA damage from vinyl chloride exposure.

Flushing of Stagnant Premise Water Systems after the COVID-19 Shutdown Can Reduce Infection Risk by Legionella and Mycobacterium spp.

There is concern about potential exposure to opportunistic pathogens when reopening buildings closed due to the COVID-19 pandemic. In this study, water samples were collected before, during, and after flushing showers in five unoccupied (i.e., for ∼2 months) university buildings with quantification of opportunists via a cultivation-based assay (Legionella pneumophila only) and quantitative PCR. L. pneumophila were not detected by either method; Legionella spp., nontuberculous mycobacteria (NTM), and Mycobacterium avium complex (MAC), however, were widespread. Using quantitative microbial risk assessment (QMRA), the estimated risks of illness from exposure to L. pneumophila and MAC via showering were generally low (i.e., less than a 10-7 daily risk threshold), with the exception of systemic infection risk from MAC exposure in some buildings. Flushing rapidly restored the total chlorine (as chloramine) residual and decreased bacterial gene targets to building inlet concentrations within 30 min. During the postflush stagnation period, the residual chlorine dissipated within a few days and bacteria rebounded, approaching preflush concentrations after 6-7 days. These results suggest that flushing can quickly improve water quality in unoccupied buildings, but the improvement may only last a few days.

Effects of chironomid larvae and Limnodrilus hoffmeisteri bioturbation on the distribution and flux of chromium at the sediment-water interface.

The impacts of chironomid larvae and the tubificid worm Limnodrilus hoffmeisteri on the distribution and flux of the heavy metal chromium (Cr) across the sediment-water interface were investigated with a 21-day laboratory microcosm experiment. The two studied species feature different bioturbation modes involving bioirrigation and upward bioconveyance. The Cr concentrations in the overlying water and pore water were measured and compared using treatments with bioturbation by a single species and by combinations of both species and a treatment with no organisms. The results indicated that both bioturbation modes significantly increased the Cr concentrations in the overlying water and pore water. The overlying water had lower Cr concentrations than the pore water. Little variation in the Cr concentrations was observed in the treatment without organisms. Both species enhanced the Cr flux from the pore water to the overlying water. The worm treatments had a great impact on the Cr concentration in the overlying water through intensive upward conveyance activity, while the chironomid larvae treatments exerted significant effects on the Cr variation in the pore water and Cr flux across the interface via bioirrigation activity. These findings reveal the importance of bioturbation in biogeochemical processes in freshwater ecosystems.

[Hamilton-Thorne Integrated Visual Optical System â (IVOSâ ) versus IVOS â ¡ for human sperm analysis].

OBJECTIVE: To compare the computer-assisted sperm analysis (CASA) systems Hamilton-Thorne Integrated Visual Optical System Ⅰ (IVOSⅠ) and IVOS Ⅱ after verifying the performance of the latter so as to ensure the accuracy of the results of analysis. METHODS: Based on the criteria established in the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO 5th Ed), we compared the main semen parameters obtained from IVOSⅠ with those generated by IVOS Ⅱ, and examined the consistency between the results of the two sperm analyzers. RESULTS: The linear relationship of the outlier test, bias estimation and scatter plot and the results of the outlier test of the two systems all met the requirements of comparison analysis and showed an obvious correlativity. The application scope of the results obtained from the apparatus indicated a reasonable value range, with r = 0.988 for sperm concentration, r = 0.975 for sperm progressive motility (PR), and r = 0.981 for total sperm motility. Evaluation of the acceptability of the predicted bias showed that the allowable total error (TEa) to be 6.67% with sperm concentration at 12 × 106 /ml and 2.34% with PR < 31%, their upper limit of the allowable error < 1/2. The results of IVOS Ⅱ conformed to the requirements of the WHO 5th Ed. CONCLUSIONS: The main parameters derived from IVOSⅠ and IVOS Ⅱ are comparable and consistent, indicating that both can be used for the examination of semen samples.

Iron Oxide Nanoparticles-Based Vaccine Delivery for Cancer Treatment.

Modern therapeutic cancer vaccines need simple and effective formulations to enhance both humoral and cellular immune responses. Nanoparticles have obtained more and more attention in the development of vaccine delivery platforms. Moreover, nanoparticles-based vaccine delivery platform has high potential for improving the immunogenicity of vaccine. The Food and Drug Administration (FDA) has approved many types of iron oxide nanoparticles for clinical use, such as treating iron deficiency, contrast agents for magnetic resonance imaging (MRI) and drug delivery platforms. In this study, we explored a novel combined use of iron oxide nanoparticles (superparamagnetic Fe3O4 nanoparticles) as a vaccine delivery platform and immune potentiator, and investigated how this formulation affected cytokine expression in macrophages and dendritic cells (DCs) in vitro and tumor growth in vivo. Comparing with soluble OVA alone and iron oxide nanoparticles alone, we found significant differences in immune responses and tumor inhibition induced by OVA formulated with iron oxide nanoparticles. Our iron oxide nanoparticles greatly promoted the activation of immune cells and cytokine production, inducing potent humoral and cellular immune responses. These results suggest that this nanoparticle-based delivery system has strong potential to be utilized as a general platform for cancer vaccines.

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration.

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

Advances in redox-responsive drug delivery systems of tumor microenvironment.

With the improvement of nanotechnology and nanomaterials, redox-responsive delivery systems have been studied extensively in some critical areas, especially in the field of biomedicine. The system constructed by redox-responsive delivery can be much stable when in circulation. In addition, redox-responsive vectors can respond to the high intracellular level of glutathione and release the loaded cargoes rapidly, only if they reach the site of tumor tissue or targeted cells. Moreover, redox-responsive delivery systems are often applied to significantly improve drug concentrations in targeted cells, increase the therapeutic efficiency and reduce side effects or toxicity of primary drugs. In this review, we focused on the structures and types of current redox-responsive delivery systems and provided a comprehensive overview of relevant researches, in which the disulfide bond containing delivery systems are of the utmost discussion.