Single-cell transcriptomic analysis reveals heterogeneous features of myeloid-derived suppressor cells in newborns.

The transitory emergence of myeloid-derived suppressor cells (MDSCs) in infants is important for the homeostasis of the immune system in early life. The composition and functional heterogeneity of MDSCs in newborns remain elusive, hampering the understanding of the importance of MDSCs in neonates. In this study, we unraveled the maturation trajectory of polymorphonuclear (PMN)-MDSCs from the peripheral blood of human newborns by performing single-cell RNA sequencing. Results indicated that neonatal PMN-MDSCs differentiated from self-renewal progenitors, antimicrobial PMN-MDSCs, and immunosuppressive PMN-MDSCs to late PMN-MDSCs with reduced antimicrobial capacity. We also established a simple framework to distinguish these distinct stages by CD177 and CXCR2. Importantly, preterm newborns displayed a reduced abundance of classical PMN-MDSCs but increased late PMN-MDSCs, consistent with their higher susceptibility to infections and inflammation. Furthermore, newborn PMN-MDSCs were distinct from those from cancer patients, which displayed minimum expression of genes about antimicrobial capacity. This study indicates that the heterogeneity of PMN-MDSCs is associated with the maturity of human newborns.

PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/ß-catenin pathway.

Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.

NRP1 downregulation correlates with enhanced ILC2 responses during IL-33 challenge.

Group 2 innate lymphoid cells (ILC2s) play critical roles in driving the pathogenesis of allergic airway inflammation. The mechanisms underlying the regulation of ILC2s remain to be fully understood. Here, we identified neuropilin-1 (NRP1) as a surface marker of ILC2s in response to IL-33 stimulation. NRP1 was abundantly expressed in ILC2s from lung under steady state, which was significantly reduced upon IL-33 stimulation. ILC2s with high expression of NRP1 (NRP1high) displayed lower response to IL-33, as compared with NRP1low ILC2s. Transcriptional profiling and flow cytometric analysis showed that downregulation of AKT-mTOR signalling participated in the diminished functionality of NRP1high ILC2s. These observations revealed a potential role of NRP1 in ILC2s responses under allergic inflammatory condition.

Periodic changes of cyclin D1 mRNA stability are regulated by PC4 modifications in the cell cycle.

The cell cycle is a highly regulated process in which proteins involved in cell cycle progression exhibit periodic expression patterns, controlled by specific mechanisms such as transcription, translation, and degradation. However, the precise mechanisms underlying the oscillations of mRNA levels in cell cycle regulators are not fully understood. In this study, we observed that the stability of cyclin D1 (CCND1) mRNA fluctuates during the cell cycle, with increased stability during interphase and decreased stability during the M phase. Additionally, we identified a key RNA binding protein, positive coactivator 4 (PC4), which plays a crucial role in stabilizing CCND1 mRNA and regulating its periodic expression. Moreover, the binding affinity of PC4 to CCND1 mRNA is modulated by two cell cycle-specific posttranslational modifications: ubiquitination of K68 enhances binding and stabilizes the CCND1 transcript during interphase, while phosphorylation of S17 inhibits binding during the M phase, leading to degradation of CCND1 mRNA. Remarkably, PC4 promotes the transition from G1 to S phase in the cell cycle, and depletion of PC4 enhances the efficacy of CDK4/6 inhibitors in hepatocellular carcinoma, suggesting that PC4 could serve as a potential therapeutic target. These findings provide valuable insights into the intricate regulation of cell cycle dynamics.

Electroactive Bi-Functional Liquid Crystal Elastomer Actuators.

Liquid crystal elastomers (LCEs) with promising applications in the field of actuators and soft robotics are reported. However, most of them are activated by external heating or light illumination. The examples of electroactive LCEs are still limited; moreover, they are monofunctional with one type of deformation (bending or contraction). Here, the study reports on trilayer electroactive LCE (eLCE) by intimate combination of LCE and ionic electroactive polymer device (i-EAD). This eLCE is bi-functional and can perform either bending or contractile deformations by the control of the low-voltage stimulation. By applying a voltage of ±2 V at 0.1 Hz, the redox behavior and associated ionic motion provide a bending strain difference of 0.80%. Besides, by applying a voltage of ±6 V at 10 Hz, the ionic current-induced Joule heating triggers the muscle-like linear contraction with 20% strain for eLCE without load. With load, eLCE can lift a weight of 270 times of eLCE-actuator weight, while keeping 20% strain and affording 5.38 kJ·m-3 work capacity. This approach of combining two smart polymer technologies (LCE and i-EAD) in a single device is promising for the development of smart materials with multiple degrees of freedom in soft robotics, electronic devices, and sensors.

Eco-Friendly Zn-Ag-In-Ga-S Quantum Dots: Amorphous Indium Sulfide Passivated Silver/Sulfur Vacancies Achieving Efficient Red Light-Emitting Diodes.

I-III-VI quantum dots (QDs) and derivatives (I, III, and VI are Ag+/Cu+, Ga3+/In3+, and S2-/Se2-, respectively) are the ideal candidates to replace II-VI (e.g., CdSe) and perovskite QDs due to their nontoxicity, pure color, high photoluminescence quantum yield (PLQY), and full visible coverage. However, the chaotic cation alignment in multielement systems can easily lead to the formation of multiple surface vacancies, highlighted as VI and VVI, leading to nonradiative recombination and nonequilibrium carrier distribution, which severely limit the performance improvement of materials and devices. Here, based on Zn-Ag-In-Ga-S QDs, we construct an ultrathin indium sulfide shell that can passivate electron vacancies and convert donor/acceptor level concentrations. The optimized In-rich 2-layer indium sulfide structure not only enhances the radiative recombination rate by preventing further VS formation but also achieves the typical DAP emission enhancement, achieving a significant increase in PLQY to 86.2% at 628 nm. Moreover, the optimized structure can mitigate the lattice distortion and make the carrier distribution in the interior of the QDs more balanced. On this basis, red QD light-emitting diodes (QLEDs) with the highest external quantum efficiency (EQE; 5.32%) to date were obtained, providing a novel scheme for improving I-III-VI QD-based QLED efficiency.

The contribution of cultural identity to subjective well-being in collectivist countries: a study in the context of contemporary Chinese culture.

Introduction: Though the important effect of cultural identity on subjective well-being is widely acknowledged, the details of how different cultures' unique features influence well-being remain to be revealed. To address this issue in the context of Chinese culture, the present study investigates whether and how the prominent features of Chinese culture-collectivism and red culture-shape Chinese people's subjective well-being. Methods: The Red Cultural Identity Scale, Subjective Well-Being Scale, Collectivism Scale, and Perspective-Taking Scale were used to assess 1,045 Chinese residents. Results: The results showed that red cultural identity positively predicted participants' subjective well-being through the mediated role of collectivism. Furthermore, perspective-taking was found to moderate the mediating effect of collectivism. Discussion: These results demonstrate that the way cultural identity predicts subjective well-being is highly correlated to specific cultural features, e.g., the opinion of values, which was significant in practice with a cross-cultural background.

High-Temperature, Reversible, and Robust Thermochromic Fluorescence Based on Rb2 MnBr4 (H2 O)2 for Anti-Counterfeiting.

Thermochromic fluorescent materials (TFMs) characterized by noticeable emission color variation with temperature have attracted pervasive attention for their frontier application in stimulus-response and optical encryption technologies. However, existing TFMs typically suffer from weak PL reversibility as well as limited mild operating temperature and severe temperature PL quenching. PL switching under extreme conditions such as high temperature will undoubtedly improve encryption security, while it is still challenging for present TFMs. In this work, high-temperature thermochromic fluorescence up to 473 K and robust structural and optical reversibility of 80 cycles are observed in Rb2 MnBr4 (H2 O)2 and related crystals, which is seldom reported for PL changes at such a high temperature. Temperature-driven nonluminous, red and green light emission states can be achieved at specific temperatures and the modulation mechanism is verified by in situ optical and structural measurements and single particle transition. By virtue of this unique feature, a multicolor anti-counterfeiting label based on a broad temperature gradient and multidimensional information encryption applications are demonstrated. This work opens a window for the design of inorganic materials with multi-PL change and the development of advanced encryption strategies with extreme stimuli source.

Machine learning and density functional theory simulation of the electronic structural properties for novel quaternary semiconductors.

In order to accelerate the application of quaternary optoelectronic materials in the field of luminescence, it is crucial to develop new quaternary semiconductor materials with excellent properties. However, faced with vast alternative quaternary semiconductors, traditional trial-and-error methods tend to be laborious and inefficient. Here, we combined machine learning (ML) with density functional theory (DFT) calculation to predict the bandgaps of 2180 quaternary semiconductors, most of which were undeveloped but environmentally friendly. The evaluation coefficient (R2) of the model using a random forest algorithm was up to 0.93 in ML. Four novel quaternary semiconductors with direct bandgaps: Ag2InGaS4, AgZn2InS4, Ag2ZnSnS4, and AgZn2GaS4, were selected from the ML model. Then their electronic structures and optical properties were further verified and studied by DFT calculations, which demonstrated that the four quaternary semiconductors had direct bandgaps, a small effective mass, and a large exciton binding energy and Stokes shift. Our calculation could significantly speed up the discovery of novel optoelectronic semiconductors and has a certain reference value for the study of luminescent materials and devices.

Suppressing Nonradiative Recombination by Electron-Donating Substituents in 2D Conjugated Triphenylamine Polymers toward Efficient Perovskite Optoelectronics.

Highly efficient perovskite optoelectronics (POEs) have been limited by nonradiative recombination. We report a strategy to inhibit the nonradiative recombination of 2D triphenylamine polymers in the hole transport layer (HTL) via introducing electron-donating groups to enhance the conjugation effect and electron cloud density. The conjugated systems with electron-donating groups present smaller energy level oscillation compared to the ones with electron-absorbing groups, as confirmed by nonadiabatic molecular dynamics (NAMD) calculation. Further study reveals that the introduction of low-frequency phonons in the electron-donating group systems shortens the nonadiabatic coupling and inhibits the nonradiative recombination. Such electron-donating groups can decrease the valence band maximum of 2D polymers and promote hole transport. Our report provides a new design strategy to suppress nonradiative recombination in HTL for application in efficient POEs.

Dopamine inhibits group 2 innate lymphoid cell-driven allergic lung inflammation by dampening mitochondrial activity.

Neuronal signals have emerged as pivotal regulators of group 2 innate lymphoid cells (ILC2s) that regulate tissue homeostasis and allergic inflammation. The molecular pathways underlying the neuronal regulation of ILC2 responses in lungs remain to be fully elucidated. Here, we found that the abundance of neurotransmitter dopamine was negatively correlated with circulating ILC2 numbers and positively associated with pulmonary function in humans. Dopamine potently suppressed lung ILC2 responses in a DRD1-receptor-dependent manner. Genetic deletion of Drd1 or local ablation of dopaminergic neurons augmented ILC2 responses and allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired the mitochondrial oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effect of dopamine. Local administration of dopamine alleviated allergen-induced ILC2 responses and airway inflammation. These findings demonstrate that dopamine represents an inhibitory regulator of ILC2 responses in allergic airway inflammation.

Interfacial electronic properties of metal/CsSnBr3heterojunctions.

All-inorganic lead-free perovskite CsSnBr3, has been proved good stability and optoelectronic properties in theory and experiment. However, the interfacial electronic properties of metal/CsSnBr3are still unclear in electronic devices. Herein, we systematically investigate the interfacial properties of metal electrodes (Al, Ag and Au) and CsSnBr3with different atomic terminals (SnBr2-T and CsBr-T) through the first-principles calculation. SnBr2-T and CsBr-T have various contact types and Schottky barriers due to their different interaction strengths with metals. In particular, the moderate interlayer coupling strength with Al leads to the ultra-low Schottky barrier and tunneling barrier, which makes Al possess the best contact performance among the studied metals. Furthermore, the external electric field can be effective in regulating the Schottky barrier and realizing the Ohmic contact. These findings provide useful guidance for the design of perovskite-based nanoelectronic devices with high performance.

Positive Cofactor 4 as a Potential Radiation Biodosimeter for Early Assessment.

During a major radiation event, a large number of people need to be rapidly assessed for radiation damage to ensure effective medical treatment and efficient use of medical resources. However, current techniques cannot meet the requirement of rapid detection of large quantities of samples in an emergency. It is essential to develop rapid and accurate radiation biodosimeters in peripheral blood. Here, we identified radiation sensitive genes in mice by RNA sequencing and evaluated their utility as radiation biodosimeters in human cell lines. Mice were subjected to gamma-irradiation with different doses (0-8 Gy, .85 Gy/min), and the tail venous blood was analyzed by RNA sequencing. We have identified 5 genes with significantly differential expression after radiation exposure. We found that positive cofactor 4(PC4) had well correlation with radiation dose in human lymphoblastoid cell line after irradiation. The relative expression of PC4 gene showed a good linear correlation with the radiation dose after 1-5 Gy irradiation (.85 Gy/min). PC4 gene can be rapidly recruited to the DNA damage sites faster than γ-H2AX after radiation in immunofluorescence detection. In conclusion, PC4 may be represented as new radiation biological dosimeter for early assessment.

Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation.

Group 2 innate lymphoid cells (ILC2s) have emerged as critical mediators in driving allergic airway inflammation. Here, we identified angiotensin (Ang) II as a positive regulator of ILC2s. ILC2s expressed higher levels of the Ang II receptor AT1a, and colocalized with lung epithelial cells expressing angiotensinogen. Administration of Ang II significantly enhanced ILC2 responses both in vivo and in vitro, which were almost completely abrogated in AT1a-deficient mice. Deletion of AT1a or pharmacological inhibition of the Ang II-AT1 axis resulted in a remarkable remission of airway inflammation. The regulation of ILC2s by Ang II was cell intrinsic and dependent on interleukin (IL)-33, and was associated with marked changes in transcriptional profiling and up-regulation of ERK1/2 phosphorylation. Furthermore, higher levels of plasma Ang II correlated positively with the abundance of circulating ILC2s as well as disease severity in asthmatic patients. These observations reveal a critical role for Ang II in regulating ILC2 responses and airway inflammation.

Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation.

Group 2 innate lymphoid cells (ILC2s) play an important role in allergic airway inflammation. Despite recent advances in defining molecular mechanisms that control ILC2 development and function, the role of endogenous metabolites in the regulation of ILC2s remains poorly understood. Herein, we demonstrated that bilirubin, an end product of heme catabolism, was a potent negative regulator of ILC2s. Bilirubin metabolism was found to be significantly induced during airway inflammation in mouse models. The administration of unconjugated bilirubin (UCB) dramatically suppressed ILC2 responses to interleukin (IL)-33 in mice, including cell proliferation and the production of effector cytokines. Furthermore, UCB significantly alleviated ILC2-driven airway inflammation, which was aggravated upon clearance of endogenous UCB. Mechanistic studies showed that the effects of bilirubin on ILC2s were associated with downregulation of ERK phosphorylation and GATA3 expression. Clinically, newborns with hyperbilirubinemia displayed significantly lower levels of ILC2 with impaired function and suppressed ERK signaling. Together, these findings indicate that bilirubin serves as an endogenous suppressor of ILC2s and might have potential therapeutic value in the treatment of allergic airway inflammation.

Adenosine restrains ILC2-driven allergic airway inflammation via A2A receptor.

Although group 2 Innate Lymphoid Cells (ILC2s) play important roles in driving the pathogenesis of allergic airway inflammation, the molecular mechanisms regulating ILC2 responses remain to be fully elucidated. Adenosine signaling is emerging as an important factor to limit excessive inflammation and tissue damage, its role in ILC2-driven airway inflammation remains to be understood. Here we identify adenosine as a negative regulator of ILC2s and allergic airway inflammation. Elevation of adenosine was observed in lungs after protease papain challenge. Adenosine receptor A2A was abundantly expressed in lung ILC2s. The adenosine analog NECA significantly suppress ILC2s responses and relieved airway inflammation induced by IL-33 or papain. Conversely, blockage of adenosine synthesis by CD73 inhibitor APCP or deficiency of A2A aggravated murine airway inflammation. Adoptive transfer of ILC2s into immunodeficiency NCG mice demonstrated that the regulation of ILC2 by adenosine was cell intrinsic. Mechanistic studies showed that the effects of adenosine on ILC2s were associated with changes in transcriptional profiling, and the elevation of intracellular cAMP and resulted NF-κB downregulation. These observations indicate that adenosine-A2A signaling is a negative regulator of ILC2s, which confers protection against airway inflammation and represents a novel therapeutic target for controlling asthma.

Customizable Sophisticated Three-Dimensional Shape Changes of Large-Size Liquid Crystal Elastomer Actuators.

Stimuli-responsive liquid crystal elastomers (LCEs), which exhibit sophisticated and versatile shape variations and functions upon stimulations, have constantly interested material science researchers. To date, many challenges still exist in scaling up orientated LCEs with sophisticated physical shapes and multi-functions. Herein, LCEs with various customizable conventional and exotic three-dimensional (3D) shapes and with sizes larger than those previously reported have been prepared by combining magnetic field alignment and soft lithography technology. These LCEs have film, cylinder, ellipsoid, hemispheroid, tube, pyramid, triangle and rectangle frame, grid pattern, cubic frame, and spring shapes. Meanwhile, diversified deformation behaviors such as contraction, expansion, bending, and twisting have been achieved by effectively controlling the alignment directions. Finally, the LCE actuator with hemispheroid shape has been explored for its possible applications in dynamic Braille displays or lenses with adjustable focal length. The simple strategy reported here provides a convenient way to customize multimorphological large-size 3D LCE actuators and their stimuli-responsive deformations. These systems will considerably enlarge the potential applications of LCEs and benefit the development of LCE soft robots and the future special bionic systems.