Self-Delivery Nanobooster to Enhance Immunogenic Cell Death for Cancer Chemoimmunotherapy.

Inducing immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Shikonin (SHK), a naphthoquinone compound from Lithospermum erythrorhizon, can stimulate antitumor immunity by inducing ICD. Nevertheless, the immunogenicity of tumor cells killed by SHK is weak. Endoplasmic reticulum (ER) stress is an important intracellular pathway of the ICD effect. Curcumin (CUR) can directly induce ER stress by disrupting Ca2+ homeostasis, which might enhance SHK-induced ICD effect. A self-delivery ICD effect nanobooster (CS-PEG NPs) was developed by the self-assembly of SHK (ICD inducer) and CUR (ICD enhancer) with the assistance of DSPE-PEG2K for cancer chemoimmunotherapy. CS-PEG NPs possessed effective CT26 tumor cell cellular uptake and tumor accumulation ability. Moreover, enhanced cytotoxicity against tumor cells and apoptosis promotion were achieved due to the synergistic effect of CUR and SHK. Notably, CS-PEG NPs induced obvious Ca2+ homeostasis disruption, ER stress, and ICD effect. Subsequently, the neoantigens produced by the robust ICD effect in vivo promoted dendritic cell maturation, which further recruited and activated cytotoxic T lymphocytes. Superior antitumor efficacy and systemic antitumor immunity were observed in the CT26-bearing BALB/c mouse model without side effects in major organs. This study offers a promising self-delivery nanobooster to induce strong ICD effect and antitumor immunity for cancer chemoimmunotherapy.

Symbol-level fiber-longitudinal power profile estimation.

Symbol-level fiber-longitudinal power profile estimation (PPE) greatly reduces the implementation complexity compared with the waveform-level PPE using oversampled data. However, symbol-rate data cannot account for the inter-sample interaction, which leads to inaccuracy of the absolute power estimation. To realize an accurate symbol-level PPE, we provide an in-depth analysis of the differences between symbol-level and waveform-level perturbation matrices and propose a power calibration method based on the trace of the inverse matrix. Evaluated in the probabilistic constellation shaping (PCS) 64QAM 130 Gbaud 5 × 50 km optical links, the root mean squared error (RMSE) of the symbol-level PPE decreases by 0.98 and 0.62 dB at erbium-doped fiber amplifier (EDFA) positions and all estimated positions with the aid of matrix calibration.

Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex.

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

Effect of platelet-rich plasma on healing of lower extremity diabetic skin ulcers: A meta-analysis.

The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.

Largely Enhanced Service Life and Energy Harvesting Stability of Dielectric Elastomer Generator by Designing and Optimizing Compliance of Electrodes.

Dielectric elastomer generator (DEG), which consists of a dielectric elastomer (DE) film sandwiched between two flexible electrodes (FEs), has the advantages of lightweight, high energy density, and high energy conversion efficiency, providing a simple and feasible solution for harvesting energy from human motion or nature. As crucial constituents of DEG, FEs are expected to possess excellent conductivity and compliance. Nevertheless, there is currently no quantitative characterization method for FE compliance. In addition, the impact mechanism of FE compliance on the energy harvesting performance and fatigue life of the DEG remains unclear. In this study, the dynamic mechanical property (DMP) was used to assess the compliance of FEs, and the quantitative characterization method of FE compliance was proposed. A series of silicone rubber electrodes (SREs) with different DMPs and compliance were designed and prepared, and the impact mechanism of FE compliance on the energy harvesting stability and fatigue life of the DEG was investigated. The results indicate that the key to achieving excellent FE compliance lies in reducing the difference in the magnitude of the complex modulus and phase angle between the FEs and DE, which can significantly reduce interfacial friction and extend the fatigue life of DEG. Benefiting from the enhanced FE compliance, the fatigue life and full-life energy density of the DEG device increase by 20.3 times and 26.4 times, respectively, compared with those of the commonly used carbon-based electrodes.

Integrated transcriptome and proteome analysis provides insights into CpFPA1 for floral induction in Chimonanthus praecox (Magnoliidae) without FLC in genome.

KEY MESSAGE: We used transcriptomic and proteomic association analysis to reveal the critical genes/proteins at three key flower bud differentiation stages and overexpression of CpFPA1 in Arabidopsis resulted in earlier flowering. Wintersweet (Chimonanthus praecox), a rare winter-flowering woody plant, is well known for its unique blooming time, fragrance and long flowering period. However, the molecular mechanism of flowering in C. praecox remains poorly unclear. In this study, we used transcriptomic and proteomic association analysis to reveal the critical genes/proteins at three key flower bud (FB) differentiation stages (FB.Apr, FB.May and FB.Nov) in C. praecox. The results showed that a total of 952 differential expressed genes (DEGs) and 40 differential expressed proteins (DEPs) were identified. Gene ontology (GO) enrichment revealed that DEGs in FB.Apr/FB.May comparison group were mainly involved in metabolic of biological process, cell and cell part of cellular component and catalytic activity of molecular function. In the EuKaryotic Orthologous Groups (KOG) functional classification, DEPs were predicted mainly in the function of general function prediction only (KOG0118), post-translational modification, protein turnover and chaperones. The autonomous pathway genes play an essential role in the floral induction. Based on transcriptome and proteome correlation analysis, six candidate genes associated with the autonomous pathway were identified, including FPA1, FPA2a, FPA2b, FCA, FLK, FY. Furthermore, CpFPA1 was isolated and functionally characterized, and ectopic expression of CpFPA1 in Arabidopsis Columbia (Col-0) resulted in earlier flowering. These data could contribute to understand the function of CpFPA1 for floral induction and provide information for further research on the molecular mechanisms of flowering in wintersweet.

Comparing two unitisation manipulations: effects on familiarity, recollection-based recognition, and semantic interference.

The recognition of associative memory can be significantly influenced by the use of an encoding strategy known as unitisation, which has been implemented through various manipulations. However, [Shao, H., Opitz, B., Yang, J., & Weng, X. (2016). Recollection reduces unitised familiarity effect. Memory (Hove, England), 24(4), 535-547. https://doi.org/10.1080/09658211.2015.1021258] found intriguing distinctions between two common manipulations, the compound task and the imagery task, leading to a dispute. We propose that differences in levels of processing in the imagery task may account for these discrepancies. This study tested our hypothesis using two approaches. The first two experiments utilised the R/K paradigm to investigate the effects of these methods on familiarity-based and recollection-based recognition. The results demonstrated that familiarity was increased in the compound task, while recollection was increased in the imagery task. In the subsequent two experiments, an interference paradigm was employed to examine differences in semantic processing within the two tasks. The results showed that the compound task did not impact participants' inclination towards lures, while the imagery task led to a bias towards semantic lures over episodic lures, suggesting that the two encodings in the imagery task involve different levels of semantic processing. These results support our hypothesis and underscore the importance of carefully choosing comparisons that account for other variables in the study of unitisation.

Novel quantitative immunohistochemistry method using histone H3, family 3B as the internal reference standard for measuring human epidermal growth factor receptor 2 expression in breast cancer.

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.

Superstretchable Liquid-Metal Electrodes for Dielectric Elastomer Transducers and Flexible Circuits.

Dielectric elastomer transducers (DETs), with a dielectric elastomer (DE) film sandwiched between two compliant electrodes, are highly sought after in the fields of soft robotics, energy harvesting, and human-machine interaction. To achieve a high-performance DET, it is essential to develop electrodes with high conductivity, strain-insensitive resistance, and adaptability. Herein, we design an electrode (Supra-LMNs) based on multiple dynamic bond cross-linked supramolecular networks (Ns) and liquid metal (LM), which realizes high conductivity (up to 16,000 S cm-1), negligible resistance changes at high strain (1.3-fold increase at 1000% strain), instantaneous self-healability at ambient temperature, and rapid recycling. The conductive pathway can be activated through simple friction by transmitting stress through the silver nanowires (AgNWs) and cross-linking sites of LM particles. This method is especially attractive for printing circuits on flexible substrates, especially DE films. Utilized as dielectric elastomer generator (DEG) electrodes, it reduces the charge loss by 3 orders of magnitude and achieves high generating energy density and energy conversion efficiency on a low-resistance load. Additionally, serving as sensor (DES) and actuator (DEA) electrodes, it enables a highly sensitive sensing capability and complex interaction.

Descriptions of two new stick insect species of Cnipsomorpha Hennemann, Conle, Zhang & Liu (Phasmatodea) from China based on integrative taxonomy.

Accurate taxonomical identification is an extremely important basis for stick insect research, including evolutionary biology but also applied biology such as pest control. In addition, genetic methods are a valuable identification auxiliary technology at present. Therefore, this paper used morphological and molecular data to investigate five stick insect specimens from the genus Cnipsomorpha in Yunnan, successfully identifying two new species: Cnipsomorphayunnanensis Xu, Jiang & Yang, sp. nov. and C.yuxiensis Xu, Jiang & Yang, sp. nov. A phylogenetic tree was constructed through their 28S and COI genes in order to infer the phylogenetic position of the two new species. Photographs of the new species and a key to all known Cnipsomorpha species are provided.

Relationship Between Empathy and Interpersonal Distress of Chinese Left-Behind Children: The Role of Emotion Regulation and Gender.

Introduction: Interpersonal relationship serve as crucial of social support and a sense of security for left-behind children, playing a compensatory role in mitigating the absence of familial affection. Interpersonal distress can significantly impact their mental well-being. Although previous research has established a connection between empathy and interpersonal distress, the mechanisms by which empathy triggers interpersonal distress, as well as potential gender-based variations in this relationship, remain elusive. To bridge this gap in knowledge, this study investigates the mediating influence of emotion regulation and the moderating impact of gender in the relationship between empathy and interpersonal distress. Methods: A total of 713 rural left-behind children completed the Interpersonal Reactivity Index scale, Emotion Regulation Competence Scale, and Interpersonal Relationship Assessment Scale. Results: Pearson correlation analyses suggested strong significant correlations among empathy, emotion regulation ability, and interpersonal distress. Path analyses indicated that emotion regulation ability mediated the relationship between empathy and interpersonal distress. Furthermore, hierarchical regression analyses suggest a moderating effect of gender in the relationship between empathy and emotion regulation ability. Discussion: The present study reveals the role of emotion regulation ability and gender in the relationship between empathy and interpersonal distress, which has important theoretical and practical implications for the prevention and intervention of interpersonal distress in left-behind children. Moreover, it may strengthen the relationship between peer and teacher at school, and improve the quality of parent-child communication at home.

Wulfenioidins D-N, Structurally Diverse Diterpenoids with Anti-Zika Virus Activity Isolated from Orthosiphon wulfenioides.

Eleven diterpenoids, wulfenioidins D-N (1-11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC50 values of 8.07 and 8.50 µM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 µM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.

A High-Rigidity Organic-Inorganic Metal Halide Hybrid Enabling Reversible and Enhanced Self-Trapped Exciton Emission under High Pressure.

Zero-dimensional organic-inorganic metal halide hybrids provide ideal bulk-crystal platforms for exploring the pressure engineering of electron-phonon coupling (EPC) and self-trapped exciton (STE) emission at the molecular level. However, the low stiffness of inorganic clusters hinders the reversible tuning of these physical properties. Herein, we designed a Sb3+-doped metal halide with a high emission yield (89.4%) and high bulk modulus (35 GPa) that enables reversible and enhanced STE emission (20-fold) under pressure. The high lattice rigidity originates from the corner-shared cage-structured inorganic tetramers and ring-shaped organic ligands. Further, we reveal that the pressure-enhanced emission regime below 4.5 GPa is owing to the lattice hardening and preferably EPC strength reducing, while the pressure-insensitive emission regime within 4.5-8.5 GPa results from the enhanced intercluster Coulombic attraction force that resists intracluster compression. These results provide insights into the structure-property relation and molecular engineering of zero-dimensional metal halides toward wide-band and pressure-sensitive light sources.

Euphopias G - J, macrocyclic diterpenes with anti-zika virus activity from Euphorbia helioscopia L.

Four new diterpenoids (1-4) and sixteen known diterpenoids (5-20) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were rhamofolane diterpenoids with a 5/7/6 tricyclic systems, compound 3 was a lathyranes diterpenoid, and compound 4 was a jathophanes diterpenoid. The isolated compounds were tested for their cytotoxicity and anti-Zika virus properties, and compounds 9 and 15 showed low cytotoxicity and strong anti-Zika virus properties with EC50 2.63 and 5.94 µM, respectively. Further, the inhibitory effects of compounds on protein levels were determined using Western blotting and immunofluorescence assays.

Probing Anisotropic Deformation and Near-Infrared Emission Tuning in Thin-Layered InSe Crystal under High Pressure.

Indium selenide (InSe) exhibits high lattice compressibility and an extraordinary capability of tailoring the optical band gap under pressure beyond other 2D materials. Herein, by applying hydrostatic pressure via a diamond anvil cell, we revealed an anisotropic deformation dynamic and efficient manipulation of near-infrared light emission in thin-layered InSe strongly correlated to layer numbers (N = 5-30). As N > 20, the InSe lattice is compressed in all directions, and the intralayer compression leads to widening of the band gap, resulting in an emission blue shift (∼120 meV at 1.5 GPa). In contrast, as N ≤ 15, an efficient emission red shift is observed from band gap shrinkage (rate of 100 meV GPa-1), which is attributed to the predominant uniaxial interlayer compression because of the high strain resistance along the InSe-diamond interface. These findings advance the understanding of pressure-induced lattice deformation and optical transition evolution in InSe and could be applied to other 2D materials.

High Energy Harvesting Performances Silicone Elastomer via Filling Soft Dielectric with Stretching Deformability.

Dielectric elastomer generators (DEGs) with high generated energy density and high conversion efficiency are of great interest. Among several dielectric elastomers (DEs), silicone elastomer filled with ceramic fillers have been extensively studied for their high elasticity, insulation, and permittivity. However, the stretched breakdown strength (Ebs ) of such composites decreases significantly under large strain, thus sharply reduces its energy harvesting performances. In this study, a polar rubber-based dielectric (GNBR) is synthetized and creatively used as "soft filler" for silicone elastomer. Benefiting from the deformability under stretching and its inherent strong interface bonding with silicone elastomer, this soft filler effectively avoids the formation of weak interface under large strain and reduces the local field strength of interface area. As expected, the composite filled with soft filler (GNBR/PMVS) shows enhanced Ebs of 2.8 times that of composite with traditional hard filler (TiO2 /PMVS) under equibiaxial strain of 200%. As a result, GNBR/PMVS composite exhibits maximum energy density of 130.5 mJ g-1 with up-to-date highest power conversion efficiency of reported DEG (44.5%). The findings will provide new insights in the rational design of DE composites characterized by high stretched breakdown strength for advanced energy harvesting system.

Metacognitive Illusions: A Positivity Effect in Judgments of Learning for Older but Not Younger Adults.

The positivity effect for metacognitive judgments (judgments of learning, JOLs) of emotional words in recognition memory was shown in older adults, in contrast to younger adults, who typically displayed the emotional salience effect. This is compatible with the socioemotional selection theory, which suggests the presence of a positive stimulus bias in older adults' cognitive processes. This study examined whether the positivity effect and age-related differences could be extended to a picture study to determine whether the positivity effect in older adults is robust in the metacognitive domain. Younger and older adults studied negative, positive, and neutral pictures, followed by JOLs and then a recognition test that asked participants to judge whether the picture was shown in the studying stage or not. Age-related differences were found not only in recognition memory performance for emotional pictures but also in JOLs and their accuracy. Younger adults showed an emotional salience effect for both memory performance and JOLs. Older adults' JOLs showed a positivity effect, but their actual memory performance was influenced by emotion, and this inconsistency between metacognitive judgments and memory performance is a metacognitive illusion. These findings support the cross-material replicability of a positivity bias in older adults in the metacognitive domain and suggest that we should be cautioned about the detrimental effects of this metacognitive illusion in older adults. It illustrates an age difference in the effect of emotion on individual metacognitive monitoring ability.

Effect of Radial Artery Compression with a Novel Automatic Pressure-Controlled Radial Compression Device: A Short-Term Prospective Interventional Pilot Study.

This study was conducted to design a novel radial compression device with the function of automatic pressure control and evaluate the feasibility and safety of this new technique. Patients who underwent transradial access (TRA) coronary angiography and percutaneous coronary intervention (PCI) in the First Hospital of Jiaxing between August 2021and October 2021 were prospectively enrolled in this pilot interventional study. The patients were grouped in a 1 : 1 ratio to receive compression with a novel device (the experimental group) or a conventional device without pressure control (the control group). The primary endpoint was the compression time, and the main secondary endpoints were rebleeding, upper-limb swelling, radial artery occlusion (RAO), and device-related pressure injury (DPI). Eighty-four patients were enrolled in this study. No significant differences were found in the baseline clinical characteristics between the two groups. Compared with the control group, the compression time in the experimental group was significantly reduced (207.4 ± 15.5 vs. 378.1 ± 19 min, p < 0.001). Besides, the rate of upper-limb swelling was also significantly lower in the novel device group (2.4% vs. 85.7%, p < 0.001), as well as the rate of DPI (19.05% vs. 100%, p = 0.005). Furthermore, the pain score in the experimental group was significantly lower than in the control group (0.79 ± 0.42 vs. 1.83 ± 0.58, p < 0.001). There were no significant differences in the rate of rebleeding (7.1% vs. 14.3, p = 0.48) between the two groups. In addition, no RAO occurred in any of the groups. The novel automatic pressure-controlled radial compression device could reduce the hemostasis time and decrease the rate of adverse complications. It might be a promising and effective compression device in TRA coronary invasive procedures.

Small RNA and Degradome Sequencing in Floral Bud Reveal Roles of miRNAs in Dormancy Release of Chimonanthus praecox.

Chimonanthus praecox (wintersweet) is highly valued ornamentally and economically. Floral bud dormancy is an important biological characteristic in the life cycle of wintersweet, and a certain period of chilling accumulation is necessary for breaking floral bud dormancy. Understanding the mechanism of floral bud dormancy release is essential for developing measures against the effects of global warming. miRNAs play important roles in low-temperature regulation of flower bud dormancy through mechanisms that are unclear. In this study, small RNA and degradome sequencing were performed for wintersweet floral buds in dormancy and break stages for the first time. Small RNA sequencing identified 862 known and 402 novel miRNAs; 23 differentially expressed miRNAs (10 known and 13 novel) were screened via comparative analysis of breaking and other dormant floral bud samples. Degradome sequencing identified 1707 target genes of 21 differentially expressed miRNAs. The annotations of the predicted target genes showed that these miRNAs were mainly involved in the regulation of phytohormone metabolism and signal transduction, epigenetic modification, transcription factors, amino acid metabolism, and stress response, etc., during the dormancy release of wintersweet floral buds. These data provide an important foundation for further research on the mechanism of floral bud dormancy in wintersweet.

Reward Uncertainty and Expected Value Enhance Generalization of Episodic Memory.

Previous research has revealed some mechanisms underlying the generalization of reward expectation of generalization stimuli, but little is known about the generalization of episodic memory for rewarding events, its consolidation, and how reward components such as expected value and reward uncertainty affect it. Participants underwent a Pavlovian reward-conditioning task to test whether reward conditioning would enhance episodic memory generalization and which reward components would directly affect it. Counterbalanced across participants, one semantic category was paired with a reward, while the other was never paired. Following a delay of either 5 min or 24 h, participants took a memory test consisting of old, highly similar, and new items. We found that participants were more likely to falsely recognize lure items as old in the reward-paired category after 5 min and 24 h delays. These results indicate that reward conditioning enhanced the generalization of episodic memory, but this effect was not necessarily dependent on consolidation. The composite score and raw data of generalization further showed that the uncertainty and expected value enhanced generalization. Together, these findings revealed an effect of reward conditioning on episodic memory generalization and supported the enhancement effects of expected value and uncertainty.