Adult mice with noise-induced hearing loss exhibited temporal ordering memory deficits accompanied by microglia-associated neuroplastic changes in the medial prefrontal cortex.

Acquired peripheral hearing loss in midlife is considered the primary modifiable risk factor for dementia, while the underlying pathological mechanism remains poorly understood. Excessive noise exposure is the most common cause of acquired peripheral hearing loss in modern society. This study was designed to investigate the impact of noise-induced hearing loss (NIHL) on cognition, with a focus on the medial prefrontal cortex (mPFC), a brain region that is involved in both auditory and cognitive processes and is highly affected in patients with cognitive impairment. Adult C57BL/6 J mice were randomly assigned to a control group and seven noise groups: 0HPN, 12HPN, 1DPN, 3DPN, 7DPN, 14DPN, and 28DPN, which were exposed to broadband noise at a 123 dB sound pressure level (SPL) for 2 h and sacrificed immediately (0 h), 12 h, or 1, 3, 7, 14, or 28 days post-noise exposure (HPN, DPN), respectively. Hearing assessment, behavioral tests, and neuromorphological studies in the mPFC were performed in control and 28DPN mice. All experimental animals were included in the time-course analysis of serum corticosterone (CORT) levels and mPFC microglial morphology. The results illustrated that noise exposure induced early-onset transient serum CORT elevation and permanent moderate-to-severe hearing loss in mice. 28DPN mice, in which permanent NIHL has been verified, exhibited impaired performance in temporal order object recognition tasks concomitant with reduced structural complexity of mPFC pyramidal neurons. The time-course immunohistochemical analysis in the mPFC revealed significantly higher morphological microglial activation at 14 and 28 DPN, preceded by a remarkably higher amount of microglial engulfed postsynaptic marker PSD95 at 7 DPN. Additionally, lipid accumulation in microglia was observed in 7DPN, 14DPN and 28DPN mice, suggesting a driving role of lipid handling deficits following excessive phagocytosis of synaptic elements in delayed and sustained microglial abnormalities. These findings provide fundamentally novel information concerning mPFC-related cognitive impairment in mice with NIHL and empirical evidence suggesting the involvement of microglial malfunction in the mPFC neurodegenerative consequences of NIHL.

Factor reallocation and cost pass-through under the carbon emission trading policy: Evidence from Chinese metal industrial chain.

Piloted in 2013, the Carbon Emission Trading (CET) policy is the most practical tool for emission reduction in China, however, midstream firms increase capital investment to cope with compliance costs, resulting in more expensive intermediate commodities that may hurt export benefits of industrial chain terminal. Based on the A-shared listed firms of Chinese metal industrial chain during 2008-2018, this paper applies the difference-in-difference model to explore the effects of CET on chain reactions of corporate activities. After a set of robustness tests, the results show that midstream firms accelerate capital deepening in response to CET and become more capital-intensive, but gain losses of outputs both in revenue and in quantity, accompanying cost pass-through to downstream firms, which are all contributed by the external pressure imposed by stakeholders and internal incentive from senior managers. Then, affected by price fluctuation in markets of production factors and carbon-intensive commodities, CET increases the cleanliness standards of midstream firms and promote their export benefits immediately, and cost pass-through generates more expensive intermediate products and results in export contraction of downstream firms, but precision machine manufacturing has seen export growth, as their products are more sensitive to technological breakthroughs than material costs.

Does environmental regulation enhance firm's position in dual value chain? An analysis based on environmental information disclosure.

Climbing the dual value chain (DVC) of parallel development in global and domestic value chains is an important channel to get rid of bottom solidification. Based on the data of international input-output tables after embedding provinces and decomposing value-added flow during 2003-2012, this article provides measurement for downstream or upstream embedding and division position indexes of A-listed firms. Then, theoretical framework of environmental regulation affecting DVC embeddedness is constructed, and the Environmental Information Disclosure (EID) trial implemented in 2008 is regarded as a quasi-natural experiment. The results show that EID enhances corporate division position in DVC by weakening downstream embeddedness and increasing upstream embeddedness, domestic firms are gradually transforming from low-end manufacturers to high-end designers. The effect works with a year lag in downstream embeddedness and lags 2 years in others. Heterogeneity analysis confirms that enhancement of division position is more sensitive in resource-rich cities with high marketization or labor-intensive firms and manufacturing or service sectors. Besides, we find that environmental regulation such as EID induces technological innovation for process upgrade, product improvement for quality upgrade and allocation optimization for function upgrade to transform the role and degree of firms embedding DVC.

Non-linear effects of heterogeneous environmental regulations on industrial relocation: Do compliance costs work?

Reasonably designing environmental regulations for compliance-driven industrial relocation can avoid new pollution havens. The Cournot duopoly model simulates that the necessary condition for industrial relocation is differentiated market costs. Then, based on the province-industrial data of six Chinese pollution-intensive industries during 2005-2019, this study applies spatial Durbin model to explore the non-linear effects of heterogeneous environmental regulations on industrial relocation. Results shown that command-and-control environmental regulation manifests a U-shaped curve with local industrial relocation, with inverted U-shaped spillover effect radiating a road distance of 650 km, and both internal and external costs play the mediating roles; Market incentive environmental regulation has inverted U-shaped curves with industrial relocation in local and neighboring regions, it creates dual costs and works well in both short and long terms, which is the most potential regulatory tool to avoid pollution relocation accompanying industrial relocation; Voluntary environmental regulation exhibits inverted U-shaped relationships with industrial relocation in direct and spillover effects, and works through increased external cost rather than internal cost. Its spatial spillover radiates the longest 1250 km due to rapid spread of public opinions, but this effect takes more than 3 years to be effective.

H3K27ac-induced FOXC2-AS1 accelerates tongue squamous cell carcinoma by upregulating E2F3.

BACKGROUND: The important roles of lncRNAs have been reported in cancers, including tongue squamous cell carcinoma (TSCC). Here, we investigated the functional role and molecular mechanisms of lncRNA FOXC2-AS1 in TSCC. METHODS: The expression level of FOXC2-AS1 in TSCC was determined by RT-qPCR. Its biological role was evaluated through colony formation assay, flow cytometry, wound healing, transwell, and Western blot analyses. The interactions among gene were tested by mechanistic investigations. RESULTS: FOXC2-AS1 expression was high in TSCC tissues and cells. Functional assays in vitro showed that silencing FOXC2-AS1 restrained cell proliferation, cell cycle, migration, invasion, and EMT. In the mechanism, it was verified that H3K27 acetylation (H3K27ac) triggered an increase in FOXC2-AS1 expression. Furthermore, FOXC2-AS1 was identified as a cytoplasmic lncRNA and served as a ceRNA to upregulate E2F3 expression via sponging miR-6868-5p. CONCLUSION: H3K27ac-induced FOXC2-AS1 exhibits carcinogenic property in TSCC by the miR-6868-5p/E2F3 axis.

SREBP1-Induced Glutamine Synthetase Triggers a Feedforward Loop to Upregulate SREBP1 through Sp1 O-GlcNAcylation and Augments Lipid Droplet Formation in Cancer Cells.

Glutamine and lipids are two important components of proliferating cancer cells. Studies have demonstrated that glutamine synthetase (GS) boosts glutamine-dependent anabolic processes for nucleotide and protein synthesis, but the role of GS in regulating lipogenesis remains unclear. This study identified that insulin and glutamine deprivation activated the lipogenic transcription factor sterol regulatory element-binding protein 1 (SREBP1) that bound to the GS promoter and increased its transcription. Notably, GS enhanced the O-linked N-acetylglucosaminylation (O-GlcNAcylation) of the specificity protein 1 (Sp1) that induced SREBP1/acetyl-CoA carboxylase 1 (ACC1) expression resulting in lipid droplet (LD) accumulation upon insulin treatment. Moreover, glutamine deprivation induced LD formation through GS-mediated O-GlcNAc-Sp1/SREBP1/ACC1 signaling and supported cell survival. These findings demonstrate that insulin and glutamine deprivation induces SREBP1 that transcriptionally activates GS, resulting in Sp1 O-GlcNAcylation. Subsequently, O-GlcNAc-Sp1 transcriptionally upregulates the expression of SREBP1, resulting in a feedforward loop that increases lipogenesis and LD formation in liver and breast cancer cells.

Transformation of pollution control and green development: Evidence from China's chemical industry.

The Air Pollution Prevention and Control Action Plan (APCP) is an important pollution control policy formulated by the Chinese government to promote green development. However, there are few studies of its impact. Based on a province-level panel dataset from 2007 to 2017, we use a three-hierarchy meta-frontier slack-based data envelopment analysis (SBM-DEA) model and the global Malmquist (GM) index to estimate the green total factor productivity (GTFP) of China's chemical sub-industries. Next, we use the difference-in-differences (DID) method to explore the effect of the implementation of the APCP in 2013 on the GTFP of China's chemical industry. We find an increasing trend in the GTFP of China's chemical industry between 2007 and 2017. A decomposition of the change in GTFP shows that technical progress was the main driving factor and management inefficiency was the main inhibitory factor. The APCP had a significant positive effect on GTFP. Overall, in the post-implementation period, the increase in the GTFP of the treatment group was approximately 7.9% greater than in the control group. The APCP also significantly improved the technical efficiency change index. A dynamic effect analysis shows that the positive effect of the APCP on GTFP had an inverted U-shaped trend. A series of robustness tests, including counterfactual, re-grouping, and quasi-DID tests, suggest that our findings are reliable. In addition, changes in exports, capital deepening, and energy prices all significantly improved the GTFP of China's chemical industry.

Building-in-Briefcase: A Rapidly-Deployable Environmental Sensor Suite for the Smart Building.

A building’s environment has profound influence on occupant comfort and health. Continuous monitoring of building occupancy and environment is essential to fault detection, intelligent control, and building commissioning. Though many solutions for environmental measuring based on wireless sensor networks exist, they are not easily accessible to households and building owners who may lack time or technical expertise needed to set up a system and get quick and detailed overview of environmental conditions. Building-in-Briefcase (BiB) is a portable sensor network platform that is trivially easy to deploy in any building environment. Once the sensors are distributed, the environmental data is collected and communicated to the BiB router via the Transmission Control Protocol/Internet Protocol (TCP/IP) and WiFi technology, which then forwards the data to the central database securely over the internet through a 3G radio. The user, with minimal effort, can access the aggregated data and visualize the trends in real time on the BiB web portal. Paramount to the adoption and continued operation of an indoor sensing platform is battery lifetime. This design has achieved a multi-year lifespan by careful selection of components, an efficient binary communications protocol and data compression. Our BiB sensor is capable of collecting a rich set of environmental parameters, and is expandable to measure others, such as CO 2 . This paper describes the power characteristics of BiB sensors and their occupancy estimation and activity recognition functionality. We have demonstrated large-scale deployment of BiB throughout Singapore. Our vision is that, by monitoring thousands of buildings through BiB, it would provide ample research opportunities and opportunities to identify ways to improve the building environment and energy efficiency.

MapSentinel: Can the Knowledge of Space Use Improve Indoor Tracking Further?

Estimating an occupant's location is arguably the most fundamental sensing task in smart buildings. The applications for fine-grained, responsive building operations require the location sensing systems to provide location estimates in real time, also known as indoor tracking. Existing indoor tracking systems require occupants to carry specialized devices or install programs on their smartphone to collect inertial sensing data. In this paper, we propose MapSentinel, which performs non-intrusive location sensing based on WiFi access points and ultrasonic sensors. MapSentinel combines the noisy sensor readings with the floormap information to estimate locations. One key observation supporting our work is that occupants exhibit distinctive motion characteristics at different locations on the floormap, e.g., constrained motion along the corridor or in the cubicle zones, and free movement in the open space. While extensive research has been performed on using a floormap as a tool to obtain correct walking trajectories without wall-crossings, there have been few attempts to incorporate the knowledge of space use available from the floormap into the location estimation. This paper argues that the knowledge of space use as an additional information source presents new opportunities for indoor tracking. The fusion of heterogeneous information is theoretically formulated within the Factor Graph framework, and the Context-Augmented Particle Filtering algorithm is developed to efficiently solve real-time walking trajectories. Our evaluation in a large office space shows that the MapSentinel can achieve accuracy improvement of 31.3% compared with the purely WiFi-based tracking system.

BlueDetect: An iBeacon-Enabled Scheme for Accurate and Energy-Efficient Indoor-Outdoor Detection and Seamless Location-Based Service.

The location and contextual status (indoor or outdoor) is fundamental and critical information for upper-layer applications, such as activity recognition and location-based services (LBS) for individuals. In addition, optimizations of building management systems (BMS), such as the pre-cooling or heating process of the air-conditioning system according to the human traffic entering or exiting a building, can utilize the information, as well. The emerging mobile devices, which are equipped with various sensors, become a feasible and flexible platform to perform indoor-outdoor (IO) detection. However, power-hungry sensors, such as GPS and WiFi, should be used with caution due to the constrained battery storage on mobile device. We propose BlueDetect: an accurate, fast response and energy-efficient scheme for IO detection and seamless LBS running on the mobile device based on the emerging low-power iBeacon technology. By leveraging the on-broad Bluetooth module and our proposed algorithms, BlueDetect provides a precise IO detection service that can turn on/off on-board power-hungry sensors smartly and automatically, optimize their performances and reduce the power consumption of mobile devices simultaneously. Moreover, seamless positioning and navigation services can be realized by it, especially in a semi-outdoor environment, which cannot be achieved by GPS or an indoor positioning system (IPS) easily. We prototype BlueDetect on Android mobile devices and evaluate its performance comprehensively. The experimental results have validated the superiority of BlueDetect in terms of IO detection accuracy, localization accuracy and energy consumption.

A fast and precise indoor localization algorithm based on an online sequential extreme learning machine.

Nowadays, developing indoor positioning systems (IPSs) has become an attractive research topic due to the increasing demands on location-based service (LBS) in indoor environments. WiFi technology has been studied and explored to provide indoor positioning service for years in view of the wide deployment and availability of existing WiFi infrastructures in indoor environments. A large body of WiFi-based IPSs adopt fingerprinting approaches for localization. However, these IPSs suffer from two major problems: the intensive costs of manpower and time for offline site survey and the inflexibility to environmental dynamics. In this paper, we propose an indoor localization algorithm based on an online sequential extreme learning machine (OS-ELM) to address the above problems accordingly. The fast learning speed of OS-ELM can reduce the time and manpower costs for the offline site survey. Meanwhile, its online sequential learning ability enables the proposed localization algorithm to adapt in a timely manner to environmental dynamics. Experiments under specific environmental changes, such as variations of occupancy distribution and events of opening or closing of doors, are conducted to evaluate the performance of OS-ELM. The simulation and experimental results show that the proposed localization algorithm can provide higher localization accuracy than traditional approaches, due to its fast adaptation to various environmental dynamics.

Fusion of WiFi, smartphone sensors and landmarks using the Kalman filter for indoor localization.

Location-based services (LBS) have attracted a great deal of attention recently. Outdoor localization can be solved by the GPS technique, but how to accurately and efficiently localize pedestrians in indoor environments is still a challenging problem. Recent techniques based on WiFi or pedestrian dead reckoning (PDR) have several limiting problems, such as the variation of WiFi signals and the drift of PDR. An auxiliary tool for indoor localization is landmarks, which can be easily identified based on specific sensor patterns in the environment, and this will be exploited in our proposed approach. In this work, we propose a sensor fusion framework for combining WiFi, PDR and landmarks. Since the whole system is running on a smartphone, which is resource limited, we formulate the sensor fusion problem in a linear perspective, then a Kalman filter is applied instead of a particle filter, which is widely used in the literature. Furthermore, novel techniques to enhance the accuracy of individual approaches are adopted. In the experiments, an Android app is developed for real-time indoor localization and navigation. A comparison has been made between our proposed approach and individual approaches. The results show significant improvement using our proposed framework. Our proposed system can provide an average localization accuracy of 1 m.

Clinical usefulness of the baby vision test in young children and its correlation with the Snellen chart.

AIM: To investigate the efficacy of a new visual acuity (VA) screening method, the baby vision test for young children. METHODS: A total 105 eyes of 65 children aged 2-8y were included in the study. Acuity testing was conducted using a standardized recognition acuity chart (Snellen visual chart: at 3 m) and the baby vision model assessment. The baby vision device includes a screen, a near infrared camera and a computer. Children were seated at a measured distance of 33-40 cm from a display for testing. VA was estimated according to the highest resolution the children could follow. Decimal VA data were converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. The VA results for each child were recorded and analyzed for consistency. RESULTS: The mean VA measured using the Snellen visual chart was 0.62±0.32, and that assessed using the baby vision test was 0.66±0.27. The 95% limit of agreement was -0.609 to 0.695, with 95.2% (100/105) plots within the 95% limits of agreement. VA values of the baby vision test were significantly correlated with those of the Snellen chart (R=0.274, P=0.005). CONCLUSION: The baby vision test can be used as a relatively reliable method for estimating VA in young children. This new acuity assessment might be a valid predictor of optotype-measured acuity later in preverbal children.

Efficacy and Mechanism Study of 6S-5-Methyltetrahydrofolate-Calcium Against Telencephalon Infarction Injury in Zebrafish Model of Ischemic Stroke.

Ischemic stroke is a heterogeneous brain injury with complex pathophysiology and it is also a time sensitive neurological injury disease. At present, the treatment options for ischemic stroke are still limited. 6S-5-methyltetrahydrofolate-calcium (MTHF-Ca) is the calcium salt of the predominant form of dietary folate in circulation. MTHF-Ca has potential neuroprotective effect on neurocytes, but whether it can be used for ischemic stroke treatment remains unknown. We established zebrafish ischemic stroke model through photothrombotic method to evaluate the protective effect of MTHF-Ca on the ischemic brain injury of zebrafish. We demonstrated that MTHF-Ca reduced the brain damage by reducing motor dysfunction and neurobehavioral defects of zebrafish with telencephalon infarction injury. MTHF-Ca counteracted oxidative damages after Tel injury by increasing the activities of GSH-Px and SOD and decreasing the content of MDA. RNA-seq and RT-qPCR results showed that MTHF-Ca played a neuroprotective role by alleviating neuroinflammation, inhibiting blood coagulation, and neuronal apoptosis processes. Overall, we have demonstrated that MTHF-Ca has neuroprotective effect in ischemic stroke and can be used as a potential treatment for ischemic stroke.

Broadband Waterborne Multiphase Pentamode Metastructure with Simultaneous Wavefront Manipulation and Energy Absorption Capabilities.

Acoustic metastructures are artificial structures which can manipulate the wavefront in sub-wavelength dimensions, and previously proposed acoustic metastructures have been mostly realized with single materials. An acoustic metastructure with composite structure is proposed for underwater acoustic stealth considering both wavefront manipulation and sound absorption. The unit cells of the metastructure are composed of a metallic supporting lattice, interconnecting polymer materials and mass balancing columns. With the gradual modulations of equivalent physical properties along the horizontal direction of metastructure, the incident acoustic wave is reflected to other directions. Meanwhile, the polymer material inside the unit cells will dissipate the acoustic wave energy due to inherent damping properties. With the simultaneous modulations of reflected wave direction and scattering acoustic amplitude, significant improvement of the underwater stealth effect is achieved. Compared with single-phase metastructure, the Far-Field Sound Pressure Level (FFSPL) of multiphase metastructure decreases by 4.82 dB within the frequency range of 3 kHz~30 kHz. The linearized mean stress for multiphase metastructure is only 1/3 of that of single-phase metastructure due to it having much thicker struts and much more uniform stress distribution under the same hydrostatic pressure. The proposed composite structure possesses potential applications due to its acceptable thickness (80 mm) and low equivalent density (1100 kg/m3).

Suppression of lncRNA OIP5-AS1 Attenuates Apoptosis and Inflammation, and Promotes Proliferation by Mediating miR-25-3p Expression in Lipopolysaccharide-Induced Myocardial Injury.

Purpose: Long non-coding RNAs (LncRNAs) OIP5-AS1 and miR-25-3p play important roles in myocardial injury, whereas their roles in lipopolysaccharide (LPS)-induced myocardial injury remain unknown. The purpose of our study was to investigate the functional mechanisms of OIP5-AS1 and miR-25-3p in LPS-induced myocardial injury. Methods: Rats and H9C2 cells were treated with LPS to establish the model of myocardial injury in vivo and in vitro, respectively. The expression levels of OIP5-AS1 and miR-25-3p were determined by quantitative reverse transcriptase-polymerase chain reaction. Enzyme-linked immunosorbent assay was performed to measure the serum levels of IL-6 and TNF-α. The relationship between OIP5-AS1 and miR-25-3p/NOX4 was determined by luciferase reporter assay and/or RNA immunoprecipitation assay. The apoptosis rate was detected by flow cytometry, and cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Western blot was performed to detect the protein levels of Bax, Bcl-2, caspase3, c-caspase3, NOX4, and p-NF-κB p65/NF-κB p65. Results: OIP5-AS1 was up-regulated, and miR-25-3p was down-regulated in myocardial tissues of LPS-induced rats and LPS-treated H9C2 cells. Knockdown of OIP5-AS1 relieved the myocardial injury in LPS-induced rats. Knockdown of OIP5-AS1 also inhibited the inflammation and apoptosis of myocardial cells in vivo, which was subsequently confirmed by in vitro experiments. In addition, OIP5-AS1 targeted miR-25-3p. MiR-25-3p mimics reversed the effects of OIP5-AS1 overexpression on promoting cell apoptosis and inflammation and on inhibiting cell viability. Besides, miR-25-3p mimics blocked the NOX4/NF-κB signalling pathway in LPS-induced H9C2 cells. Conclusion: Silencing of lncRNA OIP5-AS1 alleviated LPS-induced myocardial injury by regulating miR-25-3p.

Advancing Imbalanced Domain Adaptation: Cluster-Level Discrepancy Minimization With a Comprehensive Benchmark.

Unsupervised domain adaptation methods have been proposed to tackle the problem of covariate shift by minimizing the distribution discrepancy between the feature embeddings of source domain and target domain. However, the standard evaluation protocols assume that the conditional label distributions of the two domains are invariant, which is usually not consistent with the real-world scenarios such as long-tailed distribution of visual categories. In this article, the imbalanced domain adaptation (IDA) is formulated for a more realistic scenario where both label shift and covariate shift occur between the two domains. Theoretically, when label shift exists, aligning the marginal distributions may result in negative transfer. Therefore, a novel cluster-level discrepancy minimization (CDM) is developed. CDM proposes cross-domain similarity learning to learn tight and discriminative clusters, which are utilized for both feature-level and distribution-level discrepancy minimization, palliating the negative effect of label shift during domain transfer. Theoretical justifications further demonstrate that CDM minimizes the target risk in a progressive manner. To corroborate the effectiveness of CDM, we propose two evaluation protocols according to the real-world situation and benchmark existing domain adaptation approaches. Extensive experiments demonstrate that negative transfer does occur due to label shift, while our approach achieves significant improvement on imbalanced datasets, including Office-31, Image-CLEF, and Office-Home.

Multi-threshold image segmentation of 2D OTSU inland ships based on improved genetic algorithm.

Waterway transportation is a crucial mode of transportation, but ensuring navigational safety in waterways requires effective guidance of ships by the Water Resources Bureau. However, supervisors may only be interested in the ship portion of a complex image and need to quickly obtain relevant ship information. Therefore, this paper proposes a two-dimensional OTSU inland ships multi-threshold image segmentation algorithm based on the improved genetic algorithm. The improved algorithm enhances search accuracy and efficiency, improving image thresholding accuracy and reducing algorithm time complexity. Experimental verification shows the algorithm has excellent evaluation indexes and can achieve real-time segmentation of complex images. This method can not only address the challenges of complex inland navigation environments and difficult acquisition of target data sets, but also be applied to optimization problems in other fields by combining various metaheuristic algorithms.

Tumor Niches: Perspectives for Targeted Therapies in Glioblastoma.

Significance: Glioblastoma (GBM), the most common and lethal primary brain tumor with a median survival rate of only 15 months and a 5-year survival rate of only 6.8%, remains largely incurable despite the intensive multimodal treatment of surgical resection and radiochemotherapy. Developing effective new therapies is an unmet need for patients with GBM. Recent Advances: Targeted therapies, such as antiangiogenesis therapy and immunotherapy, show great promise in treating GBM based upon increasing knowledge about brain tumor biology. Single-cell transcriptomics reveals the plasticity, heterogeneity, and dynamics of tumor cells during GBM development and progression. Critical Issues: While antiangiogenesis therapy and immunotherapy have been highly effective in some types of cancer, the disappointing results from clinical trials represent continued challenges in applying these treatments to GBM. Molecular and cellular heterogeneity of GBM is developed temporally and spatially, which profoundly contributes to therapeutic resistance and tumor recurrence. Future Directions: Deciphering mechanisms of tumor heterogeneity and mapping tumor niche trajectories and functions will provide a foundation for the development of more effective therapies for GBM patients. In this review, we discuss five different tumor niches and the intercellular and intracellular communications among these niches, including the perivascular, hypoxic, invasive, immunosuppressive, and glioma-stem cell niches. We also highlight the cellular and molecular biology of these niches and discuss potential strategies to target these tumor niches for GBM therapy. Antioxid. Redox Signal. 39, 904-922.

Acid-Responsive Aggregation of Gold Nanoparticles for the Photothermal Treatment of Bacterial Infections.

Photothermal therapy (PTT) is considered to be one of the promising methods to combat pathogenic bacteria. However, traditional PTT is prone to generate undesired temperature increase to surrounding normal tissues, which limits the application of PTT. Herein, an acid-responsive PTT system (Au nanoparticles system: AuNPs-S) was constructed based on the photothermal feature of spherical gold nanoparticles (AuNPs) and the low pH of the bacterial infected site. AuNPs-S is composed of two kinds of AuNPs: AuNPs modified with Asp-Asp-Asp-Asp-Asp-Cys (peptide A) were denoted as AuNPs-A; AuNPs modified with 2,3-dimethylmaleic anhydride (DA) grafted Lys-Gly-Gly-Lys-Gly-Gly-Lys-Cys (peptide B) were denoted as AuNPs-B/DA. AuNPs-B/DA with an acid-responsive moiety showed a charge-convertible feature. The negatively charged AuNPs-B/DA became positively charged AuNPs-B at low pH, aggregating with the negatively charged AuNPs-A via an electrostatic interaction, reaching the threshold to the interparticle plasmonic coupling effect among AuNPs, thereby killing bacteria precisely under the irradiation of near-infrared (NIR) light through the elevated temperature at the targeted area. This acid-responsive PTT strategy supplies an excellent mode for combating bacterial infections with no vital damage to normal tissues.