Extracellular matrix physical properties govern the diffusion of nanoparticles in tumor microenvironment.

Nanoparticles (NPs) are confronted with limited and disappointing delivery efficiency in tumors clinically. The tumor extracellular matrix (ECM), whose physical traits have recently been recognized as new hallmarks of cancer, forms a main steric obstacle for NP diffusion, yet the role of tumor ECM physical traits in NP diffusion remains largely unexplored. Here, we characterized the physical properties of clinical gastric tumor samples and observed limited distribution of NPs in decellularized tumor tissues. We also performed molecular dynamics simulations and in vitro hydrogel experiments through single-particle tracking to investigate the diffusion mechanism of NPs and understand the influence of tumor ECM physical properties on NP diffusion both individually and collectively. Furthermore, we developed an estimation matrix model with evaluation scores of NP diffusion efficiency through comprehensive analyses of the data. Thus, beyond finding that loose and soft ECM with aligned structure contribute to efficient diffusion, we now have a systemic model to predict NP diffusion efficiency based on ECM physical traits and provide critical guidance for personalized tumor diagnosis and treatment.

The effect of top-down attention on empathy fatigue.

Prolonged exposure to others' suffering can lead to empathy fatigue, especially when individuals struggle to effectively regulate their empathic capacity. Shifting active attention away from emotional components toward cognitive components of others' suffering is an effective strategy for mitigating empathy fatigue. This research investigated how top-down attentional manipulation modulates empathy fatigue in both auditory (Study 1) and visual (Study 2) modalities. Participants completed two tasks in both studies: (i) the attention to cognitive empathy task (A-C task) and (ii) the attention to emotional empathy task (A-E task). Each task included three blocks (Time Block 1, Time Block 2, and Time Block 3) designed to induce empathy fatigue. Study 1 revealed that the A-C task reduced empathy fatigue and N1 amplitudes than the A-E task in Time Block 3, indicating that attention to cognitive empathy might decrease auditory empathy fatigue. Study 2 indicates that the A-C task caused a longer N2 latency than the A-E task, signifying a decelerated emotional empathic response when attention was on cognitive empathy in the visual modality. Overall, prioritizing cognitive empathy seems to conserve mental resources and reduce empathy fatigue. This research documented the relationship between top-down attention and empathy fatigue and the possible neural mechanism.

Probing the Impact of Surface Functionalization Module on the Performance of Mitoxantrone Prodrug Nanoassemblies: Improving the Effectiveness and Safety.

Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, WDSPE-mPEG2000/Wprodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.

Minor Changes in Response Modules Leading to a "U-Shaped" Conversion Rate of Docetaxel Prodrug Nanoassemblies.

The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification modules, and response modules. The response modules are crucial for facilitating the accurate conversion of prodrugs at specific sites. In this work, we opted for differentiated disulfide bonds as response modules to construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in response modules leads to a "U-shaped" conversion rate of DTX-prodrug nanoassemblies. Prodrug nanoassemblies with the least carbon numbers between the disulfide bond and ester bond (PDONα) offered the fastest conversion rate, resulting in powerful treatment outcomes with some unavoidable toxic effects. PDONß, with more carbon numbers, possessed a slow conversion rate and poor antitumor efficacy but good tolerance. With most carbon numbers in PDONγ, it demonstrated a moderate conversion rate and antitumor effect but induced a risk of lethality. Our study explored the function of response modules and highlighted their importance in prodrug development.

Structure-Activity Relationship of pH-Sensitive Doxorubicin-Fatty Acid Prodrug Albumin Nanoparticles.

Albumin has emerged as a versatile drug carrier. To harness albumin as a carrier for doxorubicin (DOX), we synthesized three acid-labile DOX prodrugs using stearic acid (SA), oleic acid (OA), and linoleic acid (LA) as the albumin-binding motif, respectively. Different from conventional albumin nanodrugs (such as Abraxane, with a drug loading of 10%), the DOX prodrugs assembled albumin nanoparticles (NPs) have an ultrahigh drug loading (>35%). Noteworthy, we demonstrated that the saturation of fatty acids exerted great influence on colloidal stability of prodrug NPs, thus affecting their in vivo pharmacokinetics, tumor accumulation and antitumor efficacy. Furthermore, the hydrazone bond-bridged DOX prodrugs could remain intact in the bloodstream but allow DOX to be released in the acidic tumor environment, resulting in improved antitumor efficacy and safety. Our work gives novel insights into the structure-to-efficacy relationship of albumin-bound fatty acid prodrugs and provides a simple strategy for advanced albumin-bound nanomedicines.

Rational Engineering Docetaxel Prodrug Nanoassemblies: Response Modules Guiding Efficacy Enhancement and Toxicity Reduction.

Prodrug-based nanoassemblies have been developed to solve the bottlenecks of chemotherapeutic drugs. The fabricated prodrugs usually consist of active drug modules, response modules, and modification modules. Among three modules, the response modules play a vital role in controlling the intelligent drug release at tumor sites. Herein, various locations of disulfide bond linkages were selected as response modules to construct three Docetaxel (DTX) prodrugs. Interestingly, the small structural difference caused by the length of response modules endowed corresponding prodrug nanoassemblies with unique characteristic. α-DTX-OD nanoparticles (NPs) possessed the advantages of high redox-responsiveness due to their shortest linkages. However, they were too sensitive to retain the intact structure in the blood circulation, leading to severe systematic toxicity. ß-DTX-OD NPs significantly improved the pharmacokinetics of DTX but may induce damage to the liver. In comparison, γ-DTX-OD NPs with the longest linkages greatly ameliorated the delivery efficiency of DTX as well as improved DTX's tolerance dose.

Transition Metal Selenide-Based Anodes for Advanced Sodium-Ion Batteries: Electronic Structure Manipulation and Heterojunction Construction Aspect.

In recent years, sodium-ion batteries (SIBs) have gained a foothold in specific applications related to lithium-ion batteries, thanks to continuous breakthroughs and innovations in materials by researchers. Commercial graphite anodes suffer from small interlayer spacing (0.334 nm), limited specific capacity (200 mAh g-1), and low discharge voltage (<0.1 V), making them inefficient for high-performance operation in SIBs. Hence, the current research focus is on seeking negative electrode materials that are compatible with the operation of SIBs. Many studies have been reported on the modification of transition metal selenides as anodes in SIBs, mainly targeting the issue of poor cycling life attributed to the volume expansion of the material during sodium-ion extraction and insertion processes. However, the intrinsic electronic structure of transition metal selenides also influences electron transport and sodium-ion diffusion. Therefore, modulating their electronic structure can fundamentally improve the electron affinity of transition metal selenides, thereby enhancing their rate performance in SIBs. This work provides a comprehensive review of recent strategies focusing on the modulation of electronic structures and the construction of heterogeneous structures for transition metal selenides. These strategies effectively enhance their performance metrics as electrodes in SIBs, including fast charging, stability, and first-cycle coulombic efficiency, thereby facilitating the development of high-performance SIBs.

The Empathy for Pain Stimuli System (EPSS): Development and preliminary validation.

We present the Empathy for Pain Stimuli System (EPSS): a large-scale database of stimuli for studying people's empathy for pain. The EPSS comprises five sub-databases. First, the Empathy for Limb Pain Picture Database (EPSS-Limb) provides 68 painful and 68 non-painful limb pictures, exhibiting people's limbs in painful and non-painful situations, respectively. Second, the Empathy for Face Pain Picture Database (EPSS-Face) provides 80 painful and 80 non-painful pictures of people's faces being penetrated by a syringe or touched by a Q-tip. Third, the Empathy for Voice Pain Database (EPSS-Voice) provides 30 painful and 30 non-painful voices exhibiting either short vocal cries of pain or neutral interjections. Fourth, the Empathy for Action Pain Video Database (EPSS-Action_Video) provides 239 painful and 239 non-painful videos of whole-body actions. Finally, the Empathy for Action Pain Picture Database (EPSS-Action_Picture) provides 239 painful and 239 non-painful pictures of whole-body actions. To validate the stimuli in the EPSS, participants evaluated the stimuli using four different scales, rating pain intensity, affective valence, arousal, and dominance. The EPSS is available to download for free at https://osf.io/muyah/?view_only=33ecf6c574cc4e2bbbaee775b299c6c1 .

Deep learning assisted plenoptic wavefront sensor for direct wavefront detection.

Traditional plenoptic wavefront sensors (PWFS) suffer from the obvious step change of the slope response, leading to poor wavefront detection performance. In order to solve this problem, in this paper, a deep learning model is proposed to restore phase maps directly from slope measurements of PWFS. Numerical simulations are employed to demonstrate our approach, and the statistical residual wavefront root mean square error (RMSE) of our method is 0.0810 ± 0.0258λ, which is much superior to those of modal algorithm (0.2511 ± 0.0587λ) and zonal approach (0.3584 ± 0.0487λ). The internal driving force of PWFS-ResUnet is investigated, and the slope response differences between sub-apertures and directions are considered as a probably key role to help our model to accurately restore the phase map. Additionally, the robustness of our model to turbulence strength and signal-to-noise ratio (SNR) level is also tested. The proposed method provides a new direction to solve the nonlinear problem of traditional PWFS.

Ultrastable Aluminum Nanoparticles with Enhanced Combustion Performance Enabled by a Polydopamine/Polyethyleneimine Nanocoating.

In national defense, aluminum nanoparticles (Al NPs) have better combustion performance than Al microparticles but are easily oxidized during processing, especially in oxidative liquids. Although some protective coatings have been reported, it is still challenging to obtain Al NPs stable in oxidative liquids (e.g., hot liquids) without scarifying combustion performance. Here, we report ultrastable Al NPs with enhanced combustion performance enabled by the crosslinked polydopamine/polyethyleneimine (PDA/PEI) nanocoating merely ∼15 nm in thickness and ∼0.24 wt % in mass. The Al@PDA/PEI NPs are fabricated by one-step rapid graft copolymerization of dopamine and PEI on Al NPs at room temperature. The formation mechanism of the nanocoating is discussed including reactions between dopamine and PEI and interactions of the nanocoating with Al NPs. The Al@PDA/PEI NPs show excellent stability in hot water, and the mechanism is interpreted by molecular dynamics simulation. The PDA/PEI nanocoating can also enhance the combustion heat and burning rate of Al NPs.

Guar Gum-Based Macroporous Hygroscopic Polymer for Efficient Atmospheric Water Harvesting.

Solar-driven atmospheric water harvesting technology has the advantage of not being limited by geography and has great potential in solving the freshwater crisis. Here, we first propose a purely natural and degradable superhydrophilic composite macroporous hygroscopic material by applying guar gum (GG) to atmospheric water harvesting. The material consists of GG-cellulose nanofibers (CNFs) as a porous substrate material, limiting the hygroscopic factor lithium chloride (LiCl) in its three-dimensional (3D) network structure, and carbon nanotubes (CNTs) play a photothermal conversion role. The composite material has a high light absorption rate of more than 95%, and the macroporous structure (20-60 µm) allows for rapid adsorption/desorption kinetics. At 35 °C and 90% relative humidity (RH), the moisture absorption capacity is as high as 1.94 g/g. Under 100 mW/cm2 irradiation, the absorbed water is almost completely desorbed within 3 h, and the water harvesting performance is stable in 10 cycles. Moreover, liquid water was successfully collected in an actual outdoor experiment. This work demonstrates the great potential of biomass materials in the field of atmospheric water collection and provides more opportunities for various energy and sustainable applications in the future.

Development of inferiority-compensation scale among high school students.

An increasing number of high school students are inflicted by different degrees of mental disorders in learning, such as moodiness, learning difficulties, test anxiety, difficulty coping with frustration, etc., which are one of the factors leading to the inferiority of students. In the present study, the initial scale of inferiority compensation for high school students was developed through literature searching, expert evaluation, interviews, and an open scale. 1187 high school students were tested in different periods, after deleting an invalid 83 scales, including 461 copies of valid scale of exploratory factor analysis in the first stage and 643 copies of valid scale of confirmatory factor analysis in the second stage. The results showed that the inferiority compensation scale for high school students consisted of two sub-scale: self-compensation and others-compensation, ach two were composed of five dimensions including academic performance, physical fitness, social communication, appearance, and self-esteem. Confirmatory factor analysis showed that the total scale and the two sub-scale all had good structural validity (RMSEA≤0.08; CFI&IFI ≥ 0.9), and the combined reliability and values (such as the correlation coefficient of each dimension) of the two sub-scale were within the ideal range. With good reliability and validity (Cronbacα&KMO ≥ 0.90), and meeting the requirements of psychometrics, the scale can be used in the relevant research and practice of inferiority compensation for high school students.

No-Reference Quality Assessment of Extended Target Adaptive Optics Images Using Deep Neural Network.

This paper proposes a supervised deep neural network model for accomplishing highly efficient image quality assessment (IQA) for adaptive optics (AO) images. The AO imaging systems based on ground-based telescopes suffer from residual atmospheric turbulence, tracking error, and photoelectric noise, which can lead to varying degrees of image degradation, making image processing challenging. Currently, assessing the quality and selecting frames of AO images depend on either traditional IQA methods or manual evaluation by experienced researchers, neither of which is entirely reliable. The proposed network is trained by leveraging the similarity between the point spread function (PSF) of the degraded image and the Airy spot as its supervised training instead of relying on the features of the degraded image itself as a quality label. This approach is reflective of the relationship between the degradation factors of the AO imaging process and the image quality and does not require the analysis of the image's specific feature or degradation model. The simulation test data show a Spearman's rank correlation coefficient (SRCC) of 0.97, and our method was also validated using actual acquired AO images. The experimental results indicate that our method is more accurate in evaluating AO image quality compared to traditional IQA methods.

Bioinspired Nanocomplexes Comprising Phenolic Acid Derivative and Human Serum Albumin for Cancer Therapy.

Inspired by the natural phenomenon of phenolic-protein interactions, we translate this "naturally evolved interaction" to a "phenolic acid derivative based albumin bound" technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids. Paclitaxel was selected as a model drug for an in-depth study. Three novel paclitaxel-phenolic acid conjugates have been synthesized. Molecular dynamics simulations provide insights into the self-assembled mechanisms of phenolic-protein nanocomplexes. The nanocomplexes show improved pharmacokinetics, elevated tolerability, decreased neurotoxicity, and enhanced anticancer efficacies in multiple murine xenograft models of breast cancer, in comparison with two clinically approved formulations, Taxol (polyoxyethylated castor oil-formulated paclitaxel) and Abraxane (nab-paclitaxel). Such a robust system provides a broadly applicable platform for the development of albumin-based nanomedicines and has great potential for clinical translation.

Identification of Candidate Biomarkers of Alzheimer's Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics.

Alzheimer's disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.

Superelastic Clay/Silicone Composite Sponges and Their Applications for Oil/Water Separation and Solar Interfacial Evaporation.

3D porous materials are of great interest in many areas of study, but it is still difficult to prepare those with high elasticity and low thermal conductivity via facile methods. Here, superelastic laponite/silicone (LS) composite sponges with low thermal conductivity are prepared via a simple approach. The LS sponges were analyzed by various characterization methods. The content of laponite nanosheets in LS sponges has a great influence on the microstructure, comprehensive mechanical properties, and thermal conductivity. LS sponges feature (i) high mechanical strength, compressibility, and elasticity, (ii) excellent superhydrophobicity/superoleophilicity, and (iii) low thermal conductivity. Consequently, LS sponges could be used for water purification, for example, oil/water separation and solar-driven interfacial evaporation in combination with carbon nanotubes (CNTs). The LS/CNTs solar evaporator has a remarkable evaporation rate of 1.77 kg m-2 h-1 for the 3.5 wt % NaCl aqueous solution under 1 kW m-2 irradiation and high salt resistance. We foresee that this study will promote the development of new 3D porous materials and their applications.

Tailoring patchy nanoparticle design to modulate serum albumin adsorption and membrane interaction.

When nanoparticles (NPs) enter into the biological system, a wide range of proteins will coat on their surfaces forming protein corona, which changes the initial synthetic characteristics of NPs to the biological identity, resulting in the loss of their targets or specially designed properties. Although pre-coating with proteins would reduce the protein corona formation, they may diminish the targeting moieties in the transport process. Patchy NPs can offer unique advantages of asymmetry, heterogeneity, and multi-functions. This has inspired us to use the asymmetry to realize the versatility of NPs, to accommodate stealth and targeting functions. In this study, we performed molecular dynamics simulations to investigate the adsorption mechanism between patchy NPs and human serum albumin, and the interaction mechanism between NP-HSA and the membrane. The results show that there is a high probability for HSA to interact with the hydrophobic, or charged brushes of patchy NPs. The adsorption sites, as calculated through the contact probability between NPs and the residues, depend on the NP surface properties. Furthermore, the HSA adsorption on NPs could improve the NP-membrane interaction. The simulation results provide deep understanding of the NP interaction mechanism, which would help the NP design for their biomedical applications.

Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies.

Additional Sex Combs-Like 1 (ASXL1) is mutated at a high frequency in all forms of myeloid malignancies associated with poor prognosis. We generated a Vav1 promoter-driven Flag-Asxl1Y588X transgenic mouse model, Asxl1Y588X Tg, to express a truncated FLAG-ASXL1aa1-587 protein in the hematopoietic system. The Asxl1Y588X Tg mice had an enlarged hematopoietic stem cell (HSC) pool, shortened survival, and predisposition to a spectrum of myeloid malignancies, thereby recapitulating the characteristics of myeloid malignancy patients with ASXL1 mutations. ATAC- and RNA-sequencing analyses revealed that the ASXL1aa1-587 truncating protein expression results in more open chromatin in cKit+ cells compared with wild-type cells, accompanied by dysregulated expression of genes critical for HSC self-renewal and differentiation. Liquid chromatography-tandem mass spectrometry and coimmunoprecipitation experiments showed that ASXL1aa1-587 acquired an interaction with BRD4. An epigenetic drug screening demonstrated a hypersensitivity of Asxl1Y588X Tg bone marrow cells to BET bromodomain inhibitors. This study demonstrates that ASXL1aa1-587 plays a gain-of-function role in promoting myeloid malignancies. Our model provides a powerful platform to test therapeutic approaches of targeting the ASXL1 truncation mutations in myeloid malignancies.

Adsorption of DNA by using polydopamine modified magnetic nanoparticles based on solid-phase extraction.

A polydopamine magnetic composite (PDA@Fe3O4) was prepared for the extraction of human genomic DNA and characterized by transmission electron microscopy, X-ray diffraction, FT-IR spectrometer, zeta potential and vibrating sample magnetometry. PDA@Fe3O4 based on magnetic solid phase extraction (MSPE) method have highly efficient capture of genomic deoxyribonucleic acid (DNA)and gene fragments ranging from about 100 bp to 200 bp. Compared with commercial beads (Shenggong, China) and spin column nucleic acid extraction kit (Tiangen, China), the PDA coated magnetic nanoparticles display superior genomic DNA extraction capacity (116 mg/g) and yield (90.2%). The isolation protocol used the solutions (composed of PEG and NaCl) with a specific pH for the binding and release of DNA. The procedure can be attributed to the charge switch of amino and hydroxyl groups on surface of the magnetic particle. The extracted DNA with high quality (A260/A280 = 1.82 ±â€¯0.04) can be directly used as template for polymerase chain reaction (PCR) followed by agarose gel electrophoresis. The results showed the new composite to be an ideal adsorbent for separation of DNA which had the advantage of its low cost, high extraction capacity and yield.

Multifunctional Tumor-Targeting Cathepsin B-Sensitive Gemcitabine Prodrug Covalently Targets Albumin in Situ and Improves Cancer Therapy.

We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting, and site-specific drug release are achieved, and as such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.