Copper-coordinated nanoassemblies based on photosensitizer-chemo prodrugs and checkpoint inhibitors for enhanced apoptosis-cuproptosis and immunotherapy.

Cuproptosis is a recently identified copper-dependent form of nonapoptotic cell death and holds great prospect in cancer treatment. One of the most intriguing aspects of cuproptosis is its ability to synergize with apoptosis-based cancer treatments. Herein, we presented a novel approach using copper-coordinated nanoassemblies (CCNAs) that were constructed by incorporating a photosensitizer Zinc Phthalocyanine (ZnPc)-chemotherapeutic (DOX) prodrug with a thioketal (TK) spacer and an IDO inhibitor (1-methyl tryptophan, 1-MT) as building blocks for Cu2+-coordination self-assembly to achieve combinational apoptosis-cuproptosis and immunotherapy. Upon NIR laser irradiation, the ZnPc component of CCNAs exhibited a photodynamic effect that generated reactive oxygen species (ROS). This triggered the release of DOX, leading to enhanced tumor cell apoptosis. Additionally, the presence of Cu2+ in the CCNAs not only enhanced the photodynamic process by catalyzing oxygen generation but also promoted the aggregation of toxic mitochondrial proteins, leading to cell cuproptosis. Importantly, the intensified cuproptosis-apoptosis effect triggered an immunogenic cell death (ICD) response. The released 1-MT complemented this response by reversing the immunosuppressive tumor microenvironment (ITM), synergistically amplifying anti-tumor immunity and suppressing the growth of primary and distant tumors. The findings of this study provide a new perspective on potential cancer treatments based on cuproptosis-apoptosis synergistic immunotherapy and stimulate further research in the design of advanced metal-coordinated nanomedicines. STATEMENT OF SIGNIFICANCE: The combination of cuproptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. Here, copper-coordinated nanoassemblies (CCNAs) based on photosensitizer-chemo prodrugs and checkpoint inhibitors were constructed for mediating cuproptosis-apoptosis and subsequently promoting cancer immunotherapy. CCNAs not only promoted the photodynamic effect and activation of chemotherapy through catalyzing the generation of oxygen but also induced toxic mitochondrial protein aggregation, leading to cell cuproptosis. These synergistic antitumor effects triggered robust immune responses with the aid of immune checkpoint blockade, almost eradicating primary tumors and inhibiting distant tumors by around 83 % without systemic toxicity.

Discovery of COVID-19 Symptomatic Experience Reported by Twitter Users.

Since the beginning of the COVID-19 pandemic, patients shared their personal experiences of the viral infection on social media. Gathering their symptomatic experiences reported on Twitter may help better understand the infectious disease and supplement our knowledge of the disease gathered by healthcare workers. In this study, we identified personal experience tweets related to COVID-19 infection using a pre-trained and fine-tuned language model, and annotated the machine-identified tweets in order to extract the information of infection status, symptom concepts, and the days the symptomatic experience occurred. Our result shows that the top 10 most common symptoms mentioned in the collected Twitter data are in line with those published by WHO and CDC. The symptoms along with the day information appear to provide additional insight on how the infection progresses in infected individuals.

Free-Space QKD with Modulating Retroreflectors Based on the B92 Protocol.

Free-space quantum key distribution (QKD) has attracted considerable attention due to its lower channel loss and link flexibility. It allows two participants share theoretical unconditional secure keys, and can potentially be applied to air-to-ground quantum communication to establish a global quantum network. Free-space QKD using modulating retro-reflectors (MRR-QKD) significantly reduces the pointing requirement and simplifies the structure of the mobile terminal, therefore making it suitable for lightweight aircraft such as unmanned aerial vehicle and Cubesat, etc. Based on intensity modulation of two non-orthogonal states and the B92 protocol, we proposed a scheme to improve the previous work (Optics Express 2018, 26, 11331). Our scheme simplifies the optical structure and shows more robustness in equipment imperfection. The analysis and simulation show that the number of multiple quantum well modulators needed in our scheme decreases from eight to three with similar performance. Additionally, while the previous scheme cannot work due to low modulator extinction ratio or high optical misalignment, our scheme can still operate.

Factors affecting physicians using mobile health applications: an empirical study.

BACKGROUND: Mobile health applications (mHealth apps) have created innovative service channels for patients with chronic diseases. These innovative service channels require physicians to actively use mHealth apps. However, few studies investigate physicians' participation in mHealth apps. OBJECTIVE: This study aims to empirically explore factors affecting physicians' usage behaviors of mHealth apps. Based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) and mHealth apps features, we propose a research model including altruism, cognitive trust, and online ratings. METHODS: We collected data from physicians who have used mHealth apps and conducted a factor analysis to verify the convergence and discriminative effects. We used a hierarchical regression method to test the path coefficients and statistical significance of our research model. In addition, we adopted bootstrapping approach and further analyzed the mediating effects of behavioral intention between all antecedent variables and physicians' usage behavior. Finally, we conducted three robustness analyses to test the validity of results and tested the constructs to verify the common method bias. RESULTS: Our results support the effects of performance expectancy, effort expectancy, social influence, and altruism on the behavioral intentions of physicians using mHealth apps. Moreover, facilitating conditions and habits positively affect physicians using mHealth apps through the mediating effort of behavioral intention. Physicians' cognitive trust and online rating have significant effects on their usage behaviors through the mediating efforts of behavioral intention. CONCLUSIONS: This study contributes to the existing literature on UTAUT2 extension of physicians' acceptance of mHealth apps by adding altruism, cognitive trust, and online ratings. The results of this study provide a novel perspective in understanding the factors affecting physicians' usage behaviors on mHealth apps in China and provide such apps' managers with an insight into the promotion of physicians' active acceptance and usage behaviors.

Isorhynchophylline ameliorates stress-induced emotional disorder and cognitive impairment with modulation of NMDA receptors.

Introduction: Isorhynchophylline is one of the main active ingredients from Uncaria rhynchophylla, the effects and mechanisms of isorhynchophylline on stress-induced emotional disorders and cognitive impairment remain unclear. Methods: Long-term potentiation (LTP) in vivo was used for synaptic plasticity evaluation; chronic unpredictable mild stress (CUMS) model was used to evaluate the effect of isorhynchophylline on stress induced emotional disorders and cognitive impairment; sucrose preference test (SPT), open field test (OFT), and elevated plus maze (EPM) were used to evaluate emotional disorders; morris water maze (MWM) test was used to evaluate cognitive impairment; Western blotting (WB) was used to the expression of proteins; high performance liquid chromatography (HPLC) was used to quantify neurotransmitters; Nissl staining was used to identify pathological changes induced by stress. Results: In this study, we found that isorhynchophylline improved corticosterone-induced in vivo LTP impairment significantly, indicating positive effects on stress. Therefore, 28-day CUMS model was adopted to evaluate the anti-stress effects of isorhynchophylline. The results showed that isorhynchophylline improved CUMS-induced weight loss, anxiety- and depression-like behaviors, and spatial memory impairment. Isorhynchophylline reduced CUMS-induced corticosterone elevation. N-methyl-D-aspartic acid (NMDA) receptors play an important role in the process of emotion and memory. Glutamate and the expression of GluN2B increased in the CUMS mice, while D-serine and the expression of serine racemase (SR) decreased significantly, and isorhynchophylline restored these changes to normal level. Conclusion: These results indicated that isorhynchophylline ameliorated stress-induced emotional disorders and cognitive impairment, modulating NMDA receptors might be one of the underlying mechanisms.

High pressure laminates reinforced with electrospun cellulose acetate nanofibers.

In the work, the non-woven cellulose acetate (CA) nanofiber mats were prepared via electrospinning, and CA nanofiber were incorporated into the core layer of the high-pressure laminates (HPLs). When the concentration of CA was 16 wt%, SEM images demonstrated that the morphology of the CA nanofiber mat was the best, with an average diameter of 654±246 nm. When CA nanofiber mats were incorporated into the core layer of HPLs, the mechanical properties of the resulted HPLs composites were significantly improved. Specifically, the tensile strength and elongation at break of the nanofiber mats reinforced HPLs composites increased remarkably to 40.8 ±1.1 MPa and 27.9 ± 0.9 %, respectively, which were nearly 6 times and 4.4 times higher than those of the pure HPLs. Furthermore, the incorporation of the CA nanofiber mats also significantly improved the flame retardancy of the HPLs, which was revealed from the thermogravimetric analysis (TGA) results.

Size fractions of dust and amount of associated metals on leaf surface and inner wax of 15 plant species at Beijing roadside.

To provide more insight into the removal ability of urban air dust and associated metals by plant leaves, and thus guide urban green planning to improve air quality, 15 plant species leaves collected from Beijing roadside were analyzed for size fractions of leaf surface dust (SD) and inner wax dust (WD). Seven associated metals Cd, Cr, Cu, Fe, Mn, Pb and Zn were also measured. Metal Accumulation Index (MAI) was calculated for different species leaves at various dust sizes and soluble forms, respectively. Cluster analysis was used for the plant species and correlations between dust and metal concentrations and for inter-metal concentrations were calculated for both surface and inner wax dust. Mean leaf total dust TD (SD + WD), SD and WD were measured as 1159, 817 and 342 mg m-2, respectively, with the highest values observed all in Euonymus japonicus. Most species leaves collected larger ratios of SD than WD except Salix babylonica and Robinia pseudoacacia. While SD was presented at all particle size fractions for all plants, nearly all species leaves collected higher proportions of WD >10 µm. Mean metal levels of leaf TD of all species ranged from high to low as Fe > Cr > Zn > Pb > Cu > Mn > Cd, but with different orders for individual species. Metals were observed in all sizes of SD/WD, although the size distributions were various for certain metals. Intercorrelations of metal concentrations in leaf SD/WD were positively significant except Pb, which may have different emission sources. Species Prunus cerasifera f. atropurpurea, Syringa oblata, Malus micromalu, Koelreuteria paniculata and Robinia pseudoacacia may possess better overall metal collection ability due to their relatively higher MAI values, but species Euonymus japonicus, Malus micromalu, Ligustrum x vicaryi and Koelreuteria paniculata were identified as the best choices in removing air dust based on cluster analysis and suggested to be planted at heavy trafficked road site for air quality improvement.

Implicit Perceptions of Closeness From the Direct Eye Gaze.

Eye gaze plays an important role during social interaction. Specifically, different eye gaze directions may send different functional messages to the observers, who have the capacity to automatically interpret these signals. In the present study, we used the implicit association test (IAT) to investigate whether direct eye gaze sends a functional, automatically perceived signal about non-target interpersonal closeness. Results suggest that the direct gaze strongly signals close relationship, and this association cannot be accounted for by positive valence. The findings suggest that the direct gaze may function to uniquely communicate a generalized closeness without orientation. Discussion focuses on the implications of these findings for social functions of direct gaze during interpersonal interaction and the automatic nature of such associations.

Complete mitochondrial genome of the gray red-backed vole (Myodes rufocanus) and a complete estimate of the phylogenetic relationships in Cricetidae.

Myodes rufocanus belongs to the genera Myodes within the subfamily Cricetidae, its complete mitochondrial genome is 16 487 bp in length, containing 12S rRNA gene, 16S rRNA gene, 22 tRNA genes, 13 protein-coding genes and 1 control region as other Cricetidae species. Results of phylogenetic analysis showed that Myodes had close relationship with Eothenomys, and had distant relationship with Microtus, Cricetulus, Wiedomys, Akodon and other genera. This study verifies the evolutionary status of Myodes rufocanus in Myodes at the molecular level. The mitochondrial genome would be a significant supplement for the M. rufocanus genetic background analysis and experimental animalization.

De novo transcriptomic analysis and development of EST-SSR markers in the Siberian tiger (Panthera tigris altaica).

The Siberian tiger, Panthera tigris altaica, is an endangered species, and much more work is needed to protect this species, which is still vulnerable to extinction. Conservation efforts may be supported by the genetic assessment of wild populations, for which highly specific microsatellite markers are required. However, only a limited amount of genetic sequence data is available for this species. To identify the genes involved in the lung transcriptome and to develop additional simple sequence repeat (SSR) markers for the Siberian tiger, we used high-throughput RNA-Seq to characterize the Siberian tiger transcriptome in lung tissue (designated 'PTA-lung') and a pooled tissue sample (designated 'PTA'). Approximately 47.5 % (33,187/69,836) of the lung transcriptome was annotated in four public databases (Nr, Swiss-Prot, KEGG, and COG). The annotated genes formed a potential pool for gene identification in the tiger. An analysis of the genes differentially expressed in the PTA lung, and PTA samples revealed that the tiger may have suffered a series of diseases before death. In total, 1062 non-redundant SSRs were identified in the Siberian tiger transcriptome. Forty-three primer pairs were randomly selected for amplification reactions, and 26 of the 43 pairs were also used to evaluate the levels of genetic polymorphism. Fourteen primer pairs (32.56 %) amplified products that were polymorphic in size in P. tigris altaica. In conclusion, the transcriptome sequences will provide a valuable genomic resource for genetic research, and these new SSR markers comprise a reasonable number of loci for the genetic analysis of wild and captive populations of P. tigris altaica.

Pollution resistance assessment of existing landscape plants on Beijing streets based on air pollution tolerance index method.

Various plant species of green belt in urban traffic area help to reduce air pollution and beautify the city environment. Those plant species growing healthily under long-term atmospheric pollution environment are considered to be resilient. This study aims to identify plant species that are more tolerant to air pollution from traffic and to give recommendations for future green belt development in urban areas. Leaf samples of 47 plant species were collected from two heavy traffic roadside sites and one suburban site in Beijing during summer 2014. Four parameters in leaves were separately measured including relative water content (RWC), total chlorophyll content (TCH), leaf-extract pH (pH), and ascorbic acid (AA). The air pollution tolerance index (APTI) method was adopted to assess plants' resistance ability based on the above four parameters. The tolerant levels of plant species were classified using two methods, one by comparing the APTI value of individual plant to the average of all species and another by using fixed APTI values as standards. Tolerant species were then selected based on combination results from both methods. The results showed that different tolerance orders of species has been found at the three sampling sites due to varied air pollution and other environmental conditions. In general, plant species Magnolia denudata, Diospyros kaki, Ailanthus altissima, Fraxinus chinensis and Rosa chinensis were identified as tolerant species to air pollution environment and recommend to be planted at various location of the city, especially at heavy traffic roadside.