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.

A shock flash breaking out of a dusty red supergiant.

Shock-breakout emission is light that arises when a shockwave, generated by the core-collapse explosion of a massive star, passes through its outer envelope. Hitherto, the earliest detection of such a signal was at several hours after the explosion1, although a few others had been reported2-7. The temporal evolution of early light curves should provide insights into the shock propagation, including explosion asymmetry and environment in the vicinity, but this has been hampered by the lack of multiwavelength observations. Here we report the instant multiband observations of a type II supernova (SN 2023ixf) in the galaxy M101 (at a distance of 6.85 ± 0.15 Mpc; ref. 8), beginning at about 1.4 h after the explosion. The exploding star was a red supergiant with a radius of about 440 solar radii. The light curves evolved rapidly, on timescales of 1-2 h, and appeared unusually fainter and redder than predicted by the models9-11 within the first few hours, which we attribute to an optically thick dust shell before it was disrupted by the shockwave. We infer that the breakout and perhaps the distribution of the surrounding dust were not spherically symmetric.

Open-channel metal particle superlattices.

Although tremendous advances have been made in preparing porous crystals from molecular precursors1,2, there are no general ways of designing and making topologically diversified porous colloidal crystals over the 10-1,000 nm length scale. Control over porosity in this size range would enable the tailoring of molecular absorption and storage, separation, chemical sensing, catalytic and optical properties of such materials. Here, a universal approach for synthesizing metallic open-channel superlattices with pores of 10 to 1,000 nm from DNA-modified hollow colloidal nanoparticles (NPs) is reported. By tuning hollow NP geometry and DNA design, one can adjust crystal pore geometry (pore size and shape) and channel topology (the way in which pores are interconnected). The assembly of hollow NPs is driven by edge-to-edge rather than face-to-face DNA-DNA interactions. Two new design rules describing this assembly regime emerge from these studies and are then used to synthesize 12 open-channel superlattices with control over crystal symmetry, channel geometry and topology. The open channels can be selectively occupied by guests of the appropriate size and that are modified with complementary DNA (for example, Au NPs).

Colloidal quasicrystals engineered with DNA.

In principle, designing and synthesizing almost any class of colloidal crystal is possible. Nonetheless, the deliberate and rational formation of colloidal quasicrystals has been difficult to achieve. Here we describe the assembly of colloidal quasicrystals by exploiting the geometry of nanoscale decahedra and the programmable bonding characteristics of DNA immobilized on their facets. This process is enthalpy-driven, works over a range of particle sizes and DNA lengths, and is made possible by the energetic preference of the system to maximize DNA duplex formation and favour facet alignment, generating local five- and six-coordinated motifs. This class of axial structures is defined by a square-triangle tiling with rhombus defects and successive on-average quasiperiodic layers exhibiting stacking disorder which provides the entropy necessary for thermodynamic stability. Taken together, these results establish an engineering milestone in the deliberate design of programmable matter.

The polar amino acid in the TatA transmembrane helix is not strictly necessary for protein function.

The twin-arginine translocation (Tat) pathway utilizes the proton-motive force to transport folded proteins across cytoplasmic membranes in bacteria and archaea, as well as across the thylakoid membrane in plants and the inner membrane in mitochondria. In most species, the minimal components required for Tat activity consist of three subunits, TatA, TatB, and TatC. Previous studies have shown that a polar amino acid is present at the N terminus of the TatA transmembrane helix (TMH) across many different species. In order to systematically assess the functional importance of this polar amino acid in the TatA TMH in Escherichia coli, we examined a complete set of 19-amino-acid substitutions. Unexpectedly, although the polar amino acid is preferred overall, our experiments suggest that it is not necessary for a functional TatA. Hydrophilicity and helix-stabilizing properties of this polar amino acid were found to be highly correlated with the Tat activity. Specifically, change in charge status of the amino acid side chain due to pH resulted in a shift in hydrophilicity, which was demonstrated to impact the Tat transport activity. Furthermore, we identified a four-residue motif at the N terminus of the TatA TMH by sequence alignment. Using a biochemical approach, we found that the N-terminal motif was functionally significant, with evidence indicating a potential role in the preference for utilizing different proton-motive force components. Taken together, these findings yield new insights into the functionality of TatA and its potential role in the Tat transport mechanism.

A real-time analysis of protein transport via the twin arginine translocation pathway in response to different components of the protonmotive force.

The twin arginine translocation (Tat) pathway transports folded protein across the cytoplasmic membrane in bacteria, archaea, and across the thylakoid membrane in plants as well as the inner membrane in some mitochondria. In plant chloroplasts, the Tat pathway utilizes the protonmotive force (PMF) to drive protein translocation. However, in bacteria, it has been shown that Tat transport depends only on the transmembrane electrical potential (Δψ) component of PMF in vitro. To investigate the comprehensive PMF requirement in Escherichia coli, we have developed the first real-time assay to monitor Tat transport utilizing the NanoLuc Binary Technology in E. coli spheroplasts. This luminescence assay allows for continuous monitoring of Tat transport with high-resolution, making it possible to observe subtle changes in transport in response to different treatments. By applying the NanoLuc assay, we report that, under acidic conditions (pH = 6.3), ΔpH, in addition to Δψ, contributes energetically to Tat transport in vivo in E. coli spheroplasts. These results provide novel insight into the mechanism of energy utilization by the Tat pathway.

High Performance Thermoelectric Power of Bi0.5Sb1.5Te3 Through Synergistic Cu2GeSe3 and Se Incorporations.

Bi2Te3-based alloys are the benchmark for commercial thermoelectric (TE) materials, the widespread demand for low-grade waste heat recovery and solid-state refrigeration makes it imperative to enhance the figure-of-merits. In this study, high-performance Bi0.5Sb1.5Te3 (BST) is realized by incorporating Cu2GeSe3 and Se. Concretely, the diffusion of Cu and Ge atoms optimizes the hole concentration and raises the density-of-states effective mass (md *), compensating for the loss of "donor-like effect" exacerbated by ball milling. The subsequent Se addition further increases md *, enabling a total 28% improvement of room-temperature power factor (S2σ), reaching 43.6 µW cm-1 K-2 compared to the matrix. Simultaneously, the lattice thermal conductivity is also significantly suppressed by multiscale scattering sources represented by Cu-rich nanoparticles and dislocation arrays. The synergistic effects yield a peak ZT of 1.41 at 350 K and an average ZT of 1.23 (300-500 K) in the Bi0.5Sb1.5Te2.94Se0.06 + 0.11 wt.% Cu2GeSe3 sample. More importantly, the integrated 17-pair TE module achieves a conversion efficiency of 6.4%, 80% higher than the commercial one at ΔT = 200 K. These results validate that the facile composition optimization of the BST/Cu2GeSe3/Se is a promising strategy to improve the application of BST-based TE modules.

A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy.

Doxorubicin (DOX) is widely used as a chemotherapeutic agent for both hematologic and solid tumors and is a reasonable candidate for glioma treatment. However, its effectiveness is hindered by significant toxicity and drug resistance. Moreover, the presence of the blood-brain barrier (BBB) brings a crucial challenge to glioma therapy. In response, a GSH-responsive and actively targeted nanoprodrug delivery system (cRGD/PSDOX-Cur@NPs) are developed. In this system, a disulfide bond-bridged DOX prodrug (PEG-SS-DOX) is designed to release specifically in the high glutathione (GSH) tumor environment, markedly reducing the cardiotoxicity associated with DOX. To further address DOX resistance, curcumin, serving as a P-glycoprotein (P-gp) inhibitor, effectively increased cellular DOX concentration. Consequently, cRGD/PSDOX-Cur@NPs exhibited synergistic anti-tumor effects in vitro. Furthermore, in vivo experiments validated the superior BBB penetration and brain-targeting abilities of cRGD/PSDOX-Cur@NPs, showcasing the remarkable potential for treating both subcutaneous and orthotopic gliomas. This research underscores that this nanoprodrug delivery system presents a novel approach to inhibiting glioma while addressing resistance and systemic toxicity.

Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction.

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.

Role of STING in the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy.

Facet-Dependent Photocatalytic Behavior of Rutile TiO2 for the Degradation of Volatile Organic Compounds: In Situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy and Density Functional Theory Investigations.

In this study, a custom rutile titanium dioxide (TiO2) photocatalyst with a single exposed surface was utilized to investigate the facet-dependent photocatalytic mechanism of toluene. The degradation of toluene was dynamically monitored using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) technology coupled with theoretical calculations. The findings demonstrated that the photocatalytic degradation rate on the TiO2 (001) surface was nearly double that observed on the TiO2 (110) surface. This remarkable enhancement can be attributed to the heightened stability in the adsorption of toluene molecules and the concurrent reduction in the energy requirement for the ring-opening process of benzoic acid on the TiO2 (001) surface. Moreover, the TiO2 (001) surface generated a greater number of reactive oxygen species (ROS), thereby promoting the separation of photogenerated charge carriers and concurrently diminishing their recombination rates, amplifying the efficiency of photocatalysis. This research provides an innovative perspective for a more comprehensive understanding of the photocatalytic degradation mechanism of TiO2 and presents promising prospects for significant applications in environmental purification and energy fields.

What Determines the Critical Electric Field of AFE-to-FE in Pb(Zr,Sn,Ti)O3-Based Perovskites?

Electric-field-induced antiferroelectric-ferroelectric (AFE-FE) phase transition is a prominent feature of antiferroelectric (AFE) materials. The critical electric field of this phase transition is crucial for the device performance of AEFs in many applications, but the determining factor of the critical electric field is still unclear. Here, we have established the correlation between the underlying structure and the critical electric field by using in situ synchrotron X-ray diffraction and high-resolution neutron diffraction in Pb(Zr,Sn,Ti)O3-based antiferroelectrics. It is found that the critical electric field is determined by the angle between the average polarization vector in the incommensurate AFE state and the [111]P polarization direction in the rhombohedral FE state. A large polarization rotation angle gives rise to a large critical electric field. Further, density functional theory (DFT) calculations corroborate that the lower energy is required for driving a smaller angle polarization rotation. Our discovery will offer guidance to optimize the performance of AFE materials.

Hydrophobic mismatch is a key factor in protein transport across lipid bilayer membranes via the Tat pathway.

The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria, thylakoids, plant mitochondria, and archaea. In most species, the active Tat machinery consists of three independent subunits: TatA, TatB, and TatC. TatA and TatB possess short transmembrane alpha helices (TMHs), both of which are only 15 residues long in Escherichia coli. Such short TMHs cause a hydrophobic mismatch between Tat subunits and the membrane bilayer, although the functional significance of this mismatch is unclear. Here, we sought to address the functional importance of the hydrophobic mismatch in the Tat transport mechanism in E. coli. We conducted three different assays to evaluate the effect of TMH length mutants on Tat activity and observed that the TMHs of TatA and TatB appear to be evolutionarily tuned to 15 amino acids, with activity dropping off following any modification of this length. Surprisingly, TatA and TatB with as few as 11 residues in their TMHs can still insert into the membrane bilayer, albeit with a decline in membrane integrity. These findings support a model of Tat transport utilizing localized toroidal pores that form when the membrane bilayer is thinned to a critical threshold. In this context, we conclude that the 15-residue length of the TatA and TatB TMHs can be seen as a compromise between the need for some hydrophobic mismatch to allow the membrane to reversibly reach the threshold thinness required for toroidal pore formation and the permanently destabilizing effect of placing even shorter helices into these energy-transducing membranes.

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain.

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLAGlu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLAGlu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (ICGlu) to BLAGlu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MDGlu) to BLAGlu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into their paws. Optical inhibition of the ICGlu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MDGlu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the ICGlu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MDGlu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete ICGlu→BLA and MDGlu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.

Dynamic Metal-Phenolic Coordination Complexes for Versatile Surface Nanopatterning.

We report a general nanopatterning strategy that takes advantage of the dynamic coordination bonds between polyphenols and metal ions (e.g., Fe3+ and Cu2+) to create structures on surfaces with a range of properties. With this methodology, under acidic conditions, 29 metal-phenolic complex-based precursors composed of different polyphenols and metal ions are patterned using scanning probe and large-area cantilever free nanolithography techniques, resulting in a library of deposited metal-phenolic nanopatterns. Significantly, post-treatment of the patterns under basic conditions (i.e., ammonia vapor) triggers a change in coordination state and results in the in situ generation of more stable networks firmly attached to the underlying substrates. The methodology provides control over feature size, shape, and composition, almost regardless of substrate (e.g., Si, Au, and silicon nitride). Under reducing conditions (i.e., H2) at elevated temperatures (180-600 °C), the patterned features have been used as nanoreactors to synthesize individual metal nanoparticles. At room temperature, the ammonia-treated features can reduce Ag+ to form metal nanostructures and be modified with peptides, proteins, and thiolated DNA via Michael addition and/or Schiff base reaction. The generality of this technique should make it useful for a wide variety of researchers interested in modifying surfaces for catalytic, chemical and biological sensing, and template-directed assembly purposes.

The emergence of valency in colloidal crystals through electron equivalents.

Colloidal crystal engineering of complex, low-symmetry architectures is challenging when isotropic building blocks are assembled. Here we describe an approach to generating such structures based upon programmable atom equivalents (nanoparticles functionalized with many DNA strands) and mobile electron equivalents (small particles functionalized with a low number of DNA strands complementary to the programmable atom equivalents). Under appropriate conditions, the spatial distribution of the electron equivalents breaks the symmetry of isotropic programmable atom equivalents, akin to the anisotropic distribution of valence electrons or coordination sites around a metal atom, leading to a set of well-defined coordination geometries and access to three new low-symmetry crystalline phases. All three phases represent the first examples of colloidal crystals, with two of them having elemental analogues (body-centred tetragonal and high-pressure gallium), while the third (triple double-gyroid structure) has no known natural equivalent. This approach enables the creation of complex, low-symmetry colloidal crystals that might find use in various technologies.

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial.

BACKGROUND: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC. METHODS: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed. RESULTS: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%). CONCLUSION: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC. REGISTRATION NUMBER: ChiCTR1800019421.

Exploring the local work function of metallic materials at the nanoscale: the influence of neighboring phases.

This paper investigates the local work function distribution of a multi-phase metal material at the nanoscale and examines how it is influenced by its surrounding components. A formula is derived to express the relationship between the local work function and neighboring phases, taking into account the solid angle they form. The study's findings indicate a positive correlation between the local work function and the neighboring phases. Experimental results, DFT calculations, and previous theories are all used to verify the study's conclusions. Additionally, this paper offers predictions for the local work functions of a second phase surrounded by a matrix. These findings have practical implications for materials research at the nanoscale and offer a bridge between DFT calculations and nanoscale experimentation.

Changes in Serum Concentrations of Bone Turnover Markers in Healthy Pregnant Women.

Background: Changes in bone metabolism during pregnancy have not received sufficient attention because of the lack of effective screening tools. Bone turnover markers (BTMs) could reflect the changes of bone metabolism. Currently, reference intervals for bone metabolism during normal pregnancy are inconclusive. This study aimed to determine reference intervals for BTMs in pregnant women taking prenatal care and to facilitate clinical research on diseases affecting bone metabolism during pregnancy. Methods: We surveyed 120 low-risk pregnant women attending routine antenatal care from January 2020 to March 2020. The serum levels of procollagen type I N-propeptide (PINP), N-terminal osteocalcin (N-MID), and C-terminal telopeptide of type I collagen (ß-CTX) were measured in the first trimester (<13 weeks), second trimester (14-27 weeks), and third trimester (>28 weeks). Reference intervals for BTMs during pregnancy were analyzed. The Kruskal-Wallis test and paired t-test are used to analyze differences between groups. Spearman correlation coefficients expressed the measure of linear association. Results: The bone resorption marker ß-CTX in third trimester increases compared to the first trimester and the second trimester (P < 0.001, P < 0.001). The bone formation markers PINP and N-MID were decreased from the first trimester to the second trimester (P = 0.01, P < 0.001) and then raised from the second trimester to the third trimester (P < 0.001, P < 0.001). Two indices of bone turnover rate, ß-CTX/PINP and ß-CTX/N-MID, were increased from the first trimester to the second trimester (P < 0.001, P < 0.001) and then decreased from the second trimester to the third trimester (P = 0.02, P < 0.001). Conclusion: This study established reference intervals for BTMs in pregnant women and observed the changes in BTMs during the different trimesters of pregnancy. The present findings can help in clinical monitoring of the effects of pregnancy diseases on the bone metabolism of pregnant women.