Bioorthogonal "Click and Release" Reaction-Triggered Aggregation of Gold Nanoparticles Combined with Released Lonidamine for Enhanced Cancer Photothermal Therapy.

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)-based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade-off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone-lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs-based two-component nanoplatform consisting of prodrug-loaded AuNPs-ImLND and tumor-targeting peptide RGD-conjugated AuNPs-DBCO-RGD is designed. In the therapeutic regimen, AuNPs-DBCO-RGD are intravenously injected first for tumor-specific enrichment and retention. Once the arrival of AuNPs-ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT.

A PD-L1-targeting Regulator for Metabolic Reprogramming to Enhance Glutamine Inhibition-Mediated Synergistic Antitumor Metabolic and Immune Therapy.

Inhibition of glutamine metabolism in tumor cells can cause metabolic compensation-mediated glycolysis enhancement and PD-L1 upregulation-induced immune evasion, significantly limiting the therapeutic efficacy of glutamine inhibitors. Here, inspired by the specific binding of receptor and ligand, a PD-L1-targeting metabolism and immune regulator (PMIR) are constructed by decorating the glutaminase inhibitor (BPTES)-loading zeolitic imidazolate framework (ZIF) with PD-L1-targeting peptides for regulating the metabolism within the tumor microenvironment (TME) to improve immunotherapy. At tumor sites, PMIR inhibits glutamine metabolism of tumor cells for elevating glutamine levels within the TME to improve the function of immune cells. Ingeniously, the accompanying PD-L1 upregulation on tumor cells causes self-amplifying accumulation of PMIR through PD-L1 targeting, while also blocking PD-L1, which has the effects of converting enemies into friends. Meanwhile, PMIR exactly offsets the compensatory glycolysis, while disrupting the redox homeostasis in tumor cells via the cooperation of components of the ZIF and BPTES. These together cause immunogenic cell death of tumor cells and relieve PD-L1-mediated immune evasion, further reshaping the immunosuppressive TME and evoking robust immune responses to effectively suppress bilateral tumor progression and metastasis. This work proposes a rational strategy to surmount the obstacles in glutamine inhibition for boosting existing clinical treatments.

New Wine in an Old Bottle? Exposure to Bullying-Related Media and Bullying Perpetration Behavior in Daily Life Among Adolescents.

Although the effect of media violence on aggression has garnered major attention, little is known about the link between bullying-related media exposure and bullying behaviors. Across three studies, we examined this association among Chinese adolescents. Study 1 used a large sample of adolescents (n=10,391, 51.4% boys) to investigate the link between bullying-related media exposure and bullying perpetration. Using another adolescent sample (n=3,125, 49.5% boys), Study 2 replicated the findings from Study 1 and extended the investigation from traditional bullying to cyberbullying perpetration. Study 3 examined the longitudinal associations between bullying-related media exposure and (cyber)bullying perpetration 6 months later (n = 2,744, 47.0% boys). The results suggested a positive, albeit small, association between exposure to bullying-related media and (cyber)bullying perpetration. Importantly, personal anti-bullying attitudes moderated this link, with a significant association observed among adolescents holding weak anti-bullying attitudes. Findings are discussed with respect to the media's effect on bullying behaviors.

Engineering metal-based hydrogel-mediated tertiary lymphoid structure formation via activation of the STING pathway for enhanced immunotherapy.

Tertiary lymphoid structures (TLSs) primarily constructed by multiple immune cells can effectively enhance tumor immune responses, but expediting the formation of TLSs is still an enormous challenge. Herein, a stimulator of interferon gene (STING)-activating hydrogel (ZCCG) was elaborately developed by coordinating Zn2+ with 4,5-imidazole dicarboxylic acid, and simultaneously integrating chitosan (a stimulant of STING pathway activation) and CpG (an agonist of toll-like receptor 9, TLR9) for initiating and activating cGAS-STING and TLR9 pathway-mediated immunotherapy. Moreover, the dual-pathway activation could effectively enhance the infiltration of immune cells and the expression of lymphocyte-recruiting chemokines in the tumor microenvironment (TME), thereby promoting the formation of TLSs and further strengthening tumoricidal immunity. Local administration of the hydrogel could prime systemic immune responses and long-term immune memory and improve the therapeutic effects of programmed death-1 antibody (αPD-1) to inhibit tumor progression, metastasis and recurrence. The engineered hydrogel lays the foundation for tumor immunotherapy strategies based on the enhanced formation of TLSs via the activation of the cGAS-STING and TLR9 pathways.

A Domain Generative Graph Network for EEG-Based Emotion Recognition.

Emotion is a human attitude experience and corresponding behavioral response to objective things. Effective emotion recognition is important for the intelligence and humanization of brain-computer interface (BCI). Although deep learning has been widely used in emotion recognition in recent years, emotion recognition based on electroencephalography (EEG) is still a challenging task in practical applications. Herein, we proposed a novel hybrid model that employs generative adversarial networks to generate potential representations of EEG signals while combining graph convolutional neural networks and long short-term memory networks to recognize emotions from EEG signals. Experimental results on DEAP and SEED datasets show that the proposed model achieved the promising emotion classification performance compared with the state-of-the-art methods.

The Effect of Everyday Moral Sensitivity on Bullying Bystander Behavior: Parallel Mediating Roles of Empathy and Moral Disengagement.

The higher moral sensitivity to bullying a student has, the more likely they are to help the victim or inhibit bullying rather than ignore it. Research has mainly focused on particular sensitivity to bullying, and it remains unknown whether sensitivity to everyday moral issues functions similarly. The present study aimed to examine the effect of everyday moral sensitivity (EMS) on bullying bystander behaviors. We included a range of school children (n = 1,655, Grades 3-12, 27.6% girls) in Southwest China. The results show 6.10% have been a victim-only, 0.48% have been a bully-only, 0.85% have been the bullying victim, 92.57% have been neither a bully nor a bullying victim, and 45.86% have observed bullying. Students in lower grades are more likely to be bullied. After controlling for covariates (i.e., gender, grade, and social desirability), EMS is positively associated with positive bystander behaviors. Moreover, empathy and moral disengagement (MD) play a mediating role in the relationship between EMS and positive bystander behaviors. The results reveal two parallel processes of EMS influenced bystander behaviors (i.e., empathy and MD). The findings indicate the possibility of cultivating EMS and highlight the role of morality development in preventing school bullying.

Dissociating the Multiple Psychological Processes in Everyday Moral Decision-Making with the CAN Algorithm.

In previous research frameworks, researchers used an everyday dilemma to test people's altruistic versus egoistic inclination. However, there are at least three different psychological processes that could induce altruistic over egoistic decisions, i.e., stronger altruistic sensitivity, weaker egoistic sensitivity, and stronger overall action versus inaction preference. To dissociate these different psychological processes, we developed new materials and applied the CAN algorithm from traditional moral dilemma research in two studies. In Study 1, we designed scenarios varying with a 2 (egoistic/non-egoistic) × 2 (non-altruistic/altruistic) structure. Then, we recruited 209 participants to validate the scenarios and filtered six scene frameworks with 24 scenarios in total. In Study 2, we recruited 747 participants to judge whether they would conduct behavior that is simultaneously altruistic (or non-altruistic) and egoistic (or non-egoistic) in the filtered scenarios obtained from Study 1. They also filled in the Social Isolation Scale, Distress Disclosure Scale, and some other demographic information. As we dissociated the psychological processes using the CAN algorithm, significant correlations between social isolation and distress disclosure and three parameters (i.e., altruistic tendency, egoistic tendency, and overall action/inaction preference) underlying the altruistic choice were revealed to varying degrees. Other individual differences in the psychological processes in everyday moral decision-making were further demonstrated. Our study provided materials and methodological protocols to dissociate the multiple psychological processes in everyday moral decision-making. It promotes our insights on everyday moral decisions from a differential psychological processes perspective.

People Cheat on Task Performance When They Feel Bored: The Mediating Role of State Self-Efficacy.

It is unclear whether the state of boredom is related to morality. The present study investigated how state boredom influenced cheating behaviors on task performance. In Study 1 (N = 104), participants were induced to feel bored, and then reported whether they had finished an anagram task (two sentences in the task were unsolvable). The results found that people with higher boredom showed more cheating behaviors than those with lower boredom on task performance. In Study 2 (N = 139), participants completed the Multidimensional State Boredom Scale, and then completed the same anagram task as in Study 1, as well as a state self-efficacy scale. The results revealed that state self-efficacy mediated the effect of state boredom on cheating behaviors on task performance. In other words, a higher level of state boredom leads to a lower level of state self-efficacy, and the lower state self-efficacy then results in more cheating behaviors. The present study provides empirical evidence that state boredom has its moral function through state self-efficacy.

Resolving the Limitations of the CNI Model in Moral Decision Making Using the CAN Algorithm: A Methodological Contrast.

The CNI model generates C, N, and I parameters to measure people's mental processes-consequence sensitivity (C), norm sensitivity (N), and generalized inaction/action preferences (I)-in moral decision making. Given the limitations of the CNI model, the CAN algorithm was developed to depict the consequence sensitivity (C), overall action versus inaction preferences (A), norm sensitivity (N), and perverse responses with the other three parameters. However, no studies have clarified whether and how the CAN algorithm can solve the limitations of the CNI model. The present study systematically uncovers the limitations of the CNI model and the solutions provided by the CAN algorithm: (a) the CNI model does not consider negative values of the parameters, but the CAN algorithm does; (b) the sequential processing assumption of the CNI model is biased, the CAN algorithm proposes a parallel calculation strategy to fix this problem; (c) the calculation of the I parameter of the CNI model is inaccurate, so the CAN algorithm proposes the A parameter to replace it; (d) the CNI model has a problem measuring perverse responses, while the CAN algorithm develops three parameters to measure these. We examined some of our points on the basis of a reanalysis of the foreign language effect (FLE) by comparing the parameters from the CAN algorithm with those from the CNI model. We found that consequence and norm sensitivity were estimated to be greater using the CNI model than with the CAN algorithm. Consequently, these overestimations significantly (consequence sensitivity) and marginally (norm sensitivity) interfered with the FLE, making the FLE more likely to return a false positive result. In addition, the CAN algorithm was able to measure the extent of perverse responses, indicating that foreign language (compared to a native language) leads to more perverse responses. The present study demonstrates that the CNI model magnifies the Type I error of conclusions and that the CAN algorithm (compared to the CNI model) provides more insights regarding moral decision making.

Fully Inkjet-Printed Chemiresistive Sensor Array Based on Molecularly Imprinted Sol-Gel Active Materials.

The fabrication of chemiresistive sensors by inkjet printing is recognized as a breakthrough in gas-sensing applications. One challenge of this technology, however, is how to enhance the cross-selectivity of the sensor array. Herein, we present a ketjen black (KB) ink and molecularly imprinted sol-gel (MISG) inks to support the fabrication of a fully inkjet-printed chemiresistive sensor array, enabling the highly accurate recognition of volatile organic acids (VOAs) on the molecular level. The MISG/KB sensor array was prepared on a glossy photographic paper with a three-layer structure: a circuit layer by a commercial silver ink, a conductive layer by a KB ink, and an active selective layer by MISG inks imprinted by different templates. Hexanoic acid (HA), heptanoic acid, and octanoic acid were used as templates to prepare the MISGs and as targets to evaluate the detection and discrimination performance of the sensor array. Three resultant MISG/KB sensors exhibited high sensitivity and selectivity to VOA vapors. The limit of detection and imprinting factor were 0.018 ppm and 7.82, respectively, for HA-MISG/KB sensors to the corresponding target. With linear discriminant analysis of the gas responses, the MISG/KB sensor array can realize high discrimination to VOAs in single and binary mixtures. Furthermore, the proposed sensor array showed strong sensor robustness with excellent consistency, durability, bending, and humidity resistance. This work developed a fully inkjet-printed chemiresistive sensor array, enabling the realization of high cross-selectivity detection, achieving low-cost, scalable, and highly reproducible sensor fabrication, moving it closer to reliable, commercial, and wearable multi-analyte human body odor analysis potential.

Identification of discriminating chemical compounds in banana species and their odor characterization using GC-MS, statistical, and clustering analysis.

The study aims identification of discriminating chemical constituents in the banana odor grown in Philippines and Ecuador using GC-MS characterization. Ester is recognized as a major chemical class in selected banana odor. Odors discriminating compounds like, 2-hexenal, ethyl acetate, and hexanoic acid, ethyl ester, etc. have been identified. Besides, other odors generating chemical compounds (alcohols, esters, aldehydes, and ketones) have been recognized. Furthermore, principal component analysis (PCA) and hierarchical cluster analysis were implemented to differentiate banana odors. PCA achieved 100% discrimination of selected bananas odors using the peak area information about recognizing chemical compounds. Odor identity and discrimination of selected bananas have been achieved successfully. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05298-9.

Relationship between Depression and Cognitive Inhibition in Men with Heroin or Methamphetamine Use Disorder in First-Time Mandatory Detoxification.

Previous studies have shown that males with substance use disorder (SUD) in their first mandatory detoxification experience high rates of depression. It is unknown whether this high depression incidence contributes to impaired inhibition. In this work, two studies were undertaken to examine the role of depression in cognitive inhibition in heroin and methamphetamine withdrawal. We used the Beck Depression Inventory (BDI) and the self-control scale (SCS) to explore the relationship between depression and impulse inhibition in patients participating in mandatory drug treatment for the first time (Study 1). The results showed that depression negatively predicted impulse inhibition. The Stroop color-word interference task was used to explore the role of patients' depression in their inhibitory abilities (Study 2). The results showed that the high-depression group had weaker inhibition performances in the Stroop color-word interference task compared to the low-depression group. This study shows that cognitive inhibition is weaker in people with high-depression addiction than in those with low depression. This result suggests that attention should be paid to the role of depressive comorbidity when conducting working memory training treatment for substance addiction.

Hybrid Vesicles Based on Autologous Tumor Cell Membrane and Bacterial Outer Membrane To Enhance Innate Immune Response and Personalized Tumor Immunotherapy.

Tumor heterogeneity, often leading to metastasis, limits the development of tumor therapy. Personalized therapy is promising to address tumor heterogeneity. Here, a vesicle system was designed to enhance innate immune response and amplify personalized immunotherapy. Briefly, the bacterial outer membrane vesicle (OMV) was hybridized with the cell membrane originated from the tumor (mT) to form new functional vesicles (mTOMV). In vitro experiments revealed that the mTOMV strengthened the activation of innate immune cells and increased the specific lysis ability of T cells in homogeneous tumors. In vivo experiments showed that the mTOMV effectively accumulated in inguinal lymph nodes, then inhibited lung metastasis. Besides, the mTOMV evoked adaptive immune response in homologous tumor rather than the heterogeneous tumor, reversibly demonstrating the effects of personalized immunotherapy. The functions to inhibit tumor growth and metastasis accompanying good biocompatibility and simple preparation procedure of mTOMV provide their great potential for clinical applications.

A smart municipal waste management system based on deep-learning and Internet of Things.

A proof-of-concept municipal waste management system was proposed to reduce the cost of waste classification, monitoring and collection. In this system, we utilize the deep learning-based classifier and cloud computing technique to realize high accuracy waste classification at the beginning of garbage collection. To facilitate the subsequent waste disposal, we subdivide recyclable waste into plastic, glass, paper or cardboard, metal, fabric and the other recyclable waste, a total of six categories. Deep-learning convolution neural networks (CNN) were applied to realize the garbage classification task. Here, we investigate seven state-of-the-art CNNs and data pre-processing methods for waste classification, whose accuracies of nine categories range from 91.9 to 94.6% in the validation set. Among these networks, MobileNetV3 has a high classification accuracy (94.26%), a small storage size (49.5 MB) and the shortest running time (261.7 ms). Moreover, the Internet of Things (IoT) devices which implement information exchange between waste containers and waste management center are designed to monitor the overall amount of waste produced in this area and the operating state of any waste container via a set of sensors. According to monitoring information, the waste management center can schedule adaptive equipment deployment and maintenance, waste collection and vehicle routing plans, which serves as an essential part of a successful municipal waste management system.

Stand up to action: The postural effect of moral dilemma decision-making and the moderating role of dual processes.

Previous studies have demonstrated the possibility that when people are in standing rather than sitting postures, they have a stronger cognitive control propensity, making them inclined to agree more to sacrificing one innocent person and saving more people. Furthermore, this postural effect can be moderated by dual processes. In three studies, participants read dilemma scenarios followed by a proposed behavior to sacrifice one innocent person and save five or more people. The participants in sitting or standing postures were asked whether the described action was morally acceptable (moral judgment) and whether they would perform the described action (moral action). The results demonstrated that participants were more approving of the behavioral proposal in the moral action perspective than in the moral judgment perspective across the three studies. The hypothesized postural effect was found in a field study (Study 1) and replicated in a preregistered replication study (Study 2), and was further supported in an experimental study (Study 3). Compared with those in sitting postures, participants in standing postures expressed higher approval of the behavioral proposal compared to their sitting counterparts. Furthermore, the postural effect was dismissed when participants made moral decisions with a dual task to increase cognitive load, and it was reversed when they made moral decisions after deliberate consideration of the behavioral proposal (Study 3). The present research supports and extends the dual-process morality theory by demonstrating that body posture can affect moral decision-making; it also offers novel evidence revealing the moderating role of dual process on embodiment effects. It enriches our knowledge that morality is evolutionarily embodied in postures and that the dual process can moderate embodiment effects.

Non-depleting reformation of immunosuppressive myeloid cells to broaden the application of anti-PD therapy.

Traditional methods of depleting tumor-associated myeloid cells via chemotherapy can easily lead to the re-recruitment of them, eventually resulting in chemo-resistance and presenting obstacles in immunotherapy. Herein, we report a nano-educator (NE) that when loaded with all trans retinoic acid (ATRA) and anti-PD-1 antibodies (aPD-1) instructs myeloid cells to assist T cells towards revitalizing anti-PD-1 therapy. In vivo, ATRA converts myeloid-derived suppressor cells (MDSCs) into dendritic cells (DCs), which are essential for anti-PD-1 therapy, while intervening in the polarization of macrophages. Furthermore, aPD-1-armed T cells reboot anti-tumor immunity after suppression relief, which exposes tumor-specific antigens and in turn promotes the maturation of transformed DCs. The nano-platform provides shelter for vulnerable immunomodulatory agents and durable drug release to stimulate intensive immune modulation. We established three types of tumor-bearing mice models with different myeloid cell contents to show the spatiotemporal complementarity of ATRA and aPD-1. The NE re-educates the tumor's guard to assist T cells in enhanced immunotherapy, broadening the application of aPD-1 in the treatment of anti-PD-1-resistant tumors.

The Outlook of the Development of Innovative Products from Biocompatible Natural Spider Silk in the Beauty Thread-Lifting Industry.

Embedding thread lift rhytidectomy, also known as "thread lifting" in China, with the natures of simple operation, less trauma and quick recovery, is progressively used in clinical practice as a new technology of face lifting. Herewith, a brief introduction of the previous advances of thread lifting techniques and materials in the facial beauty industry, combined with the discussion on various types of sutures, common complications, and the site of actions were provided. The main limitations of present thread lifting material include: (1) the use of non-absorbable sutures is liable to cause allergies and a series of complications; (2) the absorbable sutures are easily degradation, and people need to reshape in a relatively short period. Therefore, the high biocompatible spider silk was proposed as a novel material of thread lifting suture and related devices, the advantages and preliminary achievements on spider silk were also addressed.

Multifunctional peptides for tumor therapy.

Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent developed peptide-based multifunctional nanomaterials for tumor therapy.

Molecularly imprinted sol-gel/Au@Ag core-shell nano-urchin localized surface plasmon resonance sensor designed in reflection mode for detection of organic acid vapors.

A molecularly imprinted sol-gel (MISG)/Au@Ag core-shell NU sensor is proposed for organic vapor detection in an optical fiber-based reflection mode. The compact structure design of the system in the reflection model is promising for practical use as a portable and rapid responsivity sensing probe. Volatile organic acids (OAs) are analogs to biogenetic volatile organic vapors related to specific human diseases. Here, Au@Ag core-shell nano-urchins exhibiting branched tips were synthesized and deposited on indium tin oxide (ITO) glass in small dimer and trimmer clusters to generate an enhanced electric field. A MISG solution was then spin-coated on the substrate to fabricate MISG-LSPR sensors, and three types of MISGs were developed for the detection of hexanoic acid, heptanoic acid and octanoic acid. The normalized spectral response indicated selectivity of the MISG-LSPR sensors for the corresponding template OAs. With Native Bayes and linear discriminant analysis of the sensor responses, where the latter were detected by the proposed system, single- and mixed-OA vapors could be classified into separate clusters. This signified that the proposed MISG-LSPR sensor can be applied toward pattern recognition of single vapors or multiple vapor mixtures.

Near-Infrared Light Responsive Nanoreactor for Simultaneous Tumor Photothermal Therapy and Carbon Monoxide-Mediated Anti-Inflammation.

Photothermal therapy (PTT) is an effective treatment modality with high selectivity for tumor suppression. However, the inflammatory responses caused by PTT may lead to adverse reactions including tumor recurrence and therapeutic resistance, which are regarded as major problems for PTT. Here, a near-infrared (NIR) light-responsive nanoreactor (P@DW/BC) is fabricated to simultaneously realize tumor PTT and carbon monoxide (CO)-mediated anti-inflammatory therapy. Defective tungsten oxide (WO3) nanosheets (DW NSs) are decorated with bicarbonate (BC) via ferric ion-mediated coordination and then modified with polyethylene glycol (PEG) on the surface to fabricate PEG@DW/BC or P@DW/BC nanosheets. Upon 808 nm NIR laser irradiation, the DW content in P@DW/BC can serve as not only a photothermal agent to realize photothermal conversion but also a photocatalyst to convert carbon dioxide (CO2) to CO. In particular, the generated heat can also trigger the decomposition of BC to produce CO2 near the NSs, thus enhancing the photocatalytic CO generation. Benefiting from the efficient hyperthermia and CO generation under single NIR laser irradiation, P@DW/BC can realize effective thermal ablation of tumor and simultaneous inhibition of PTT-induced inflammation.