Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and [177Lu]Lu-trastuzumab-based RLT can enhance the therapeutic efficacy of HER2-targeted RLT in drug-resistant gastric cancers. We demonstrate that lovastatin elevates cell surface HER2 levels and increases the tumor-absorbed radiation dose of [177Lu]Lu-DOTA-trastuzumab. Furthermore, lovastatin-modulated [177Lu]Lu-DOTA-trastuzumab RLT durably inhibits tumor growth and prolongs overall survival in mice bearing NCI-N87 gastric tumors and HER2-positive patient-derived xenografts (PDXs) of known clinical resistance to trastuzumab therapy. Statins also exhibit a radioprotective effect, reducing radiotoxicity in a mice cohort given the combination of statins and [177Lu]Lu-DOTA-trastuzumab. Since statins are commonly prescribed to patients, our results strongly support the feasibility of clinical studies that combine lovastatin with HER2-targeted RLT in HER2-postive patients and trastuzumab-resistant HER2-positive patients.

Two-dimensional electronic-vibrational sum frequency spectroscopy for interactions of electronic and nuclear motions at interfaces.

Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic-vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic-vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active (E)-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air-water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S2, is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm-1 Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S2 state to the lower excited state S1 We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces.

STE20 phosphorylation of AMPK-related kinases revealed by biochemical purifications combined with genetics.

We have recently purified mammalian sterile 20 (STE20)-like kinase 3 (MST3) as a kinase for the multifunctional kinases, AMP-activated protein kinase-related kinases (ARKs). However, unresolved questions from this study, such as remaining phosphorylation activities following deletion of the Mst3 gene from human embryonic kidney cells and mice, led us to conclude that there were additional kinases for ARKs. Further purification recovered Ca2+/calmodulin-dependent protein kinase kinases 1 and 2 (CaMKK1 and 2), and a third round of purification revealed mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5) as potential kinases of ARKs. We then demonstrated that MST3 and MAP4K5, both belonging to the STE20-like kinase family, could phosphorylate all 14 ARKs both in vivo and in vitro. Further examination of all 28 STE20 kinases detected variable phosphorylation activity on AMP-activated protein kinase (AMPK) and the salt-inducible kinase 3 (SIK3). Taken together, our results have revealed novel relationships between STE20 kinases and ARKs, with potential physiological and pathological implications.

Biochemical purification uncovers mammalian sterile 3 (MST3) as a new protein kinase for multifunctional protein kinases AMPK and SIK3.

The AMP-activated protein kinase (AMPK) and AMPK-related kinase salt-inducible kinase 3 (SIK3) regulate many important biological processes ranging from metabolism to sleep. Liver kinase B1 is known to phosphorylate and activate both AMPK and SIK3, but the existence of other upstream kinases was unclear. In this study, we detected liver kinase B1-independent AMPK-related kinase phosphorylation activities in human embryonic kidney cells as well as in mouse brains. Biochemical purification of this phosphorylation activity uncovered mammalian sterile 20-like kinase 3 (MST3). We demonstrate that MST3 from human embryonic kidney cells could phosphorylate AMPK and SIK3 in vivo. In addition, recombinant MST3 expressed in and purified from Escherichia coli could directly phosphorylate AMPK and SIK3 in vitro. Moreover, four other members of the MST kinase family could also phosphorylate AMPK or SIK3. Our results have revealed new kinases able to phosphorylate and activate AMPK and SIK3.

A novel toolbox for precise regulation of gene expression and metabolic engineering in Bacillus licheniformis.

Despite industrial bio-manufacturing progress using Bacillus licheniformis, the absence of a well-characterized toolbox allowing precise regulation of multiple genes limits its expansion for basic research and application. Here, a novel gene expression toolbox (GET) was developed for precise regulation of gene expression and high-level production of 2-phenylethanol. Firstly, we established a novel promoter core region mosaic combination model to combine, characterize and analyze different core regions. Characterization and orthogonal design of promoter ribbons allowed convenient construction of an adaptable and robust GET, gene gfp expression intensity was 0.64%-16755.77%, with a dynamic range of 2.61 × 104 times, which is the largest regulatory range of GET in Bacillus based on modification of promoter P43. Then we verified the protein and species universality of GET using different proteins expressed in B. licheniformis and Bacillus subtilis. Finally, the GET for 2-phenylethanol metabolic breeding, resulting in a plasmid-free strain producing 6.95 g/L 2-phenylethanol with a yield and productivity of 0.15 g/g glucose and 0.14 g/L/h, respectively, the highest de novo synthesis yield of 2-phenylethanol reported. Taken together, this is the first report elucidating the impact of mosaic combination and tandem of multiple core regions to initiate transcription and improve the output of proteins and metabolites, which provides strong support for gene regulation and diversified product production in Bacillus.

Global Minimum Search and Bonding Analysis of Tl2 Hx and Tl3 Hy (x=0-6; y=0-5) Series.

A remarkable distinction between boron and carbon hydrides lies in their extremely different bonding patterns and chemical reactivity, resulting in diverse areas of application. Particularly, carbon, characterized by classical two-center - two-electron bonds, gives rise to organic chemistry. In contrast, boron forms numerous exotic and non-intuitive compounds collectively called non-classical structures. It is reasonable to anticipate that other elements of Group 13 exhibit their own unusual bonding patterns; however, our knowledge of the hydride chemistry for other elements in Group 13 is much more limited, especially for the heaviest stable element, thallium. In this work, we performed a conformational analysis of Tl2 Hx and Tl3 Hy (x=0-6, y=0-5) series via Coalescence Kick global minimum search algorithm, DFT, and ab initio quantum chemistry methods; we investigated the bonding pattern using the AdNDP algorithm, thermodynamic stability, and stability toward electron detachment. All found global minimum structures are classified as non-classical structures featuring at least one multi-center bond.

In Situ Probing of the Surface Properties of Droplets in the Air.

Surface properties of nanodroplets and microdroplets are intertwined with their immense applicability in biology, medicine, production, catalysis, the environment, and the atmosphere. However, many means for analyzing droplets and their surfaces are destructive, non-interface-specific, not conducted under ambient conditions, require sample substrates, conducted ex situ, or a combination thereof. For these reasons, a technique for surface-selective in situ analyses under any condition is necessary. This feature article presents recent developments in second-order nonlinear optical scattering techniques for the in situ interfacial analysis of aerosol droplets in the air. First, we describe the abundant utilization of such droplets across industries and how their unique surface properties lead to their ubiquitous usage. Then, we describe the fundamental properties of droplets and their surfaces followed by common methods for their study. We next describe the fundamental principles of sum-frequency generation (SFG) spectroscopy, the Langmuir adsorption model, and how they are used together to describe adsorption processes at planar liquid and droplet surfaces. We also discuss the history of developments of second-order scattering from droplets suspended in dispersive media and introduce second-harmonic scattering (SHS) and sum-frequency scattering (SFS) spectroscopies. We then go on to outline the developments of SHS, electronic sum-frequency scattering (ESFS), and vibrational sum-frequency scattering (VSFS) from droplets in the air and discuss the fundamental insights about droplet surfaces that the techniques have provided. Finally, we describe some of the areas of nonlinear scattering from airborne droplets which need improvement as well as potential future directions and utilizations of SHS, ESFS, and VSFS throughout environmental systems, interfacial chemistry, and fundamental physics. The goal of this feature article is to spread knowledge about droplets and their unique surface properties as well as introduce second-order nonlinear scattering to a broad audience who may be unaware of recent progress and advancements in their applicability.

Hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane.

Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) is a noninvasive metabolic-imaging modality that probes carbon flux in tissues and infers the state of metabolic reprograming in tumors. Prevailing models attribute elevated hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in aggressive tumors to enhanced glycolytic flux and lactate dehydrogenase A (LDHA) activity (Warburg effect). By contrast, we find by cross-sectional analysis using genetic and pharmacological tools in mechanistic studies applied to well-defined genetically engineered cell lines and tumors that initial hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates as well as global conversion were highly dependent on and critically rate-limited by the transmembrane influx of [1-13C]pyruvate mediated predominately by monocarboxylate transporter-1 (MCT1). Specifically, in a cell-encapsulated alginate bead model, induced short hairpin (shRNA) knockdown or overexpression of MCT1 quantitatively inhibited or enhanced, respectively, unidirectional pyruvate influxes and [1-13C]pyruvate-to-[1-13C]lactate conversion rates, independent of glycolysis or LDHA activity. Similarly, in tumor models in vivo, hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion was highly dependent on and critically rate-limited by the induced transmembrane influx of [1-13C]pyruvate mediated by MCT1. Thus, hyperpolarized [1-13C]pyruvate MRSI measures primarily MCT1-mediated [1-13C]pyruvate transmembrane influx in vivo, not glycolytic flux or LDHA activity, driving a reinterpretation of this maturing new technology during clinical translation. Indeed, Kaplan-Meier survival analysis for patients with pancreatic, renal, lung, and cervical cancers showed that high-level expression of MCT1 correlated with poor overall survival, and only in selected tumors, coincident with LDHA expression. Thus, hyperpolarized [1-13C]pyruvate MRSI provides a noninvasive functional assessment primarily of MCT1 as a clinical biomarker in relevant patient populations.

Excess exogenous pyruvate inhibits lactate dehydrogenase activity in live cells in an MCT1-dependent manner.

Cellular pyruvate is an essential metabolite at the crossroads of glycolysis and oxidative phosphorylation, capable of supporting fermentative glycolysis by reduction to lactate mediated by lactate dehydrogenase (LDH) among other functions. Several inherited diseases of mitochondrial metabolism impact extracellular (plasma) pyruvate concentrations, and [1-13C]pyruvate infusion is used in isotope-labeled metabolic tracing studies, including hyperpolarized magnetic resonance spectroscopic imaging. However, how these extracellular pyruvate sources impact intracellular metabolism is not clear. Herein, we examined the effects of excess exogenous pyruvate on intracellular LDH activity, extracellular acidification rates (ECARs) as a measure of lactate production, and hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates across a panel of tumor and normal cells. Combined LDH activity and LDHB/LDHA expression analysis intimated various heterotetrameric isoforms comprising LDHA and LDHB in tumor cells, not only canonical LDHA. Millimolar concentrations of exogenous pyruvate induced substrate inhibition of LDH activity in both enzymatic assays ex vivo and in live cells, abrogated glycolytic ECAR, and inhibited hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in cellulo. Of importance, the extent of exogenous pyruvate-induced inhibition of LDH and glycolytic ECAR in live cells was highly dependent on pyruvate influx, functionally mediated by monocarboxylate transporter-1 localized to the plasma membrane. These data provided evidence that highly concentrated bolus injections of pyruvate in vivo may transiently inhibit LDH activity in a tissue type- and monocarboxylate transporter-1-dependent manner. Maintaining plasma pyruvate at submillimolar concentrations could potentially minimize transient metabolic perturbations, improve pyruvate therapy, and enhance quantification of metabolic studies, including hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging and stable isotope tracer experiments.

A crucial role for Arf6 in the response of commissural axons to Slit.

A switch in the response of commissural axons to the repellent Slit is crucial for ensuring that they cross the ventral midline only once. However, the underlying mechanisms remain to be elucidated. We have found that both endocytosis and recycling of Robo1 receptor are crucial for modulating Slit sensitivity in vertebrate commissural axons. Robo1 endocytosis and its recycling back to the cell surface maintained the stability of axonal Robo1 during Slit stimulation. We identified Arf6 guanosine triphosphatase and its activators, cytohesins, as previously unknown components in Slit-Robo1 signalling in vertebrate commissural neurons. Slit-Robo1 signalling activated Arf6. The Arf6-deficient mice exhibited marked defects in commissural axon midline crossing. Our data showed that a Robo1 endocytosis-triggered and Arf6-mediated positive-feedback strengthens the Slit response in commissural axons upon their midline crossing. Furthermore, the cytohesin-Arf6 pathways modulated this self-enhancement of the Slit response before and after midline crossing, resulting in a switch that reinforced robust regulation of axon midline crossing. Our study provides insights into endocytic trafficking-mediated mechanisms for spatiotemporally controlled axonal responses and uncovers new players in the midline switch in Slit responsiveness of commissural axons.

A Tale of Two Sites: Neighboring Atomically Dispersed Pt Sites Cooperatively Remove Trace H2 in CO-Rich Stream.

Single-atom catalysts (SACs) exhibit distinct catalytic behavior compared with nano-catalysts because of their unique atomic coordination environment without the direct bonding between identical metal centers. How these single atom sites interact with each other and influence the catalytic performance remains unveiled as designing densely populated but stable SACs is still an enormous challenge to date. Here, a fabrication strategy for embedding high areal density single-atom Pt sites via a defect engineering approach is demonstrated. Similar to the synergistic mechanism in binuclear homogeneous catalysts, from both experimental and theoretical results, it is proved that electrons would redistribute between the two oxo-bridged paired Pt sites after hydrogen adsorption on one site, which enables the other Pt site to have high CO oxidation activity at mild-temperature. The dynamic electronic interaction between neighboring Pt sites is found to be distance dependent. These new SACs with abundant Pt-O-Pt paired structures can improve the efficiency of CO chemical purification.

Correcting the wavelength-induced phase deviation of Pancharatnam-Berry lenses.

Liquid-crystal-based Pancharatnam-Berry optical elements are widely used in virtual reality and augmented reality. However, the mismatch between exposure wavelength and operating wavelength leads to an undesirable phase deviation to the lenses, which in turn causes severe aberration especially when the f-number is small. To overcome the mismatched wavelength problem and to obtain a nearly ideal lens phase profile, a new exposure method using two template lenses with different focal lengths is proposed and experimentally validated. Our results indicate that such a lens indeed exhibits a better imaging performance than that fabricated by traditional interference method.

Ultracompact virtual reality system with a Pancharatnam-Berry phase deflector.

We propose an ultracompact virtual reality (VR) system with three optical components: a lenslet array, a Pancharatnam-Berry phase deflector (PBD), and a deflector array. The lenslet array aims to collect and collimate the input light from the display panel. The PBD steers the deviated beams after the lenslet array toward the optical axis so that the image uniformity and angular resolution can be enhanced, which plays a key role to enable this ultracompact design. Finally, the deflector array deflects the collimated beam from each lenslet to the exit pupil to widen the field of view. Such an ultracompact design is particularly attractive for next-generation glasses-like, lightweight VR headsets.

In Situ Detection of Chemical Compositions at Nanodroplet Surfaces and In-Nanodroplet Phases.

Small-volume nanodroplets play an increasingly common role in chemistry and biology. Such nanodroplets are believed to have unique chemical and physical properties at the interface between a droplet and its surrounding medium, however, they are underexamined. In this study, we present the novel technique of vibrational sum frequency scattering (VSFS) spectroscopy as an interface-specific, high-performance method for the in situ investigation of nanodroplets with sub-micron radii; as well as the droplet bulk through simultaneous hyper-Raman scattering (HRS) spectroscopy. We use laboratory-generated nanodroplets from aqueous alcohol solutions to demonstrate this technique's ability to separate the vibrational phenomena which take place at droplet surfaces from the underlying bulk phase. In addition, we systemically examine interfacial spectra of nanodroplets containing methanol, ethanol, 1-propanol, and 1-butanol through VSFS. Furthermore, we demonstrate interfacial differences between such nanodroplets and their analogous planar surfaces. The sensitivity of this technique to probe droplet surfaces with few-particle density at standard conditions validates VSFS as an analytical technique for the in situ investigation of small nanodroplets, providing breakthrough information about these species of ever-increasing relevance.

Ag nanoplatelets as efficient photosensitizers for TiO2 nanorods.

The lifetime for injecting hot electrons generated in Ag nanoplatelets to nearby TiO2 nanorods was measured with ultrafast transient IR absorption to be 13.1 ± 1.5 fs, which is comparable to values previously reported for much smaller spherical Ag nanoparticles. Although it was shown that the injection rate decreases as the particle size increases, this observation can be explained by the facts that (1) the platelet has a much larger surface to bulk ratio and (2) the platelet affords a much larger surface area for direct contact with the semiconductor. These two factors facilitate strong Ag-TiO2 coupling (as indicated by the observed broadened surface plasmon resonance band of Ag) and can explain why Ag nanoplatelets have been found to be more efficient than much smaller Ag nanoparticles as photosensitizers for photocatalytic functions. The fast injection rate, together with a stronger optical absorption in comparison with Au and dye molecules, make Ag nanoplatelets a preferred photosensitizer for wide bandgap semiconductors.

Quantitative Proteomic Analysis Reveals the Key Molecular Events Driving Phaeocystis globosa Bloom and Dissipation.

Phaeocystis globosa is a marine-bloom-forming haptophyte with a polymorphic life cycle alternating between free-living cells and a colonial morphotype, that produces high biomass and impacts ecological structure and function. The mechanisms of P. globosa bloom formation have been extensively studied, and various environmental factors are believed to trigger these events. However, little is known about the intrinsic biological processes that drive the bloom process, and the mechanisms underlying P. globosa bloom formation remain enigmatic. Here, we investigated a P. globosa bloom occurring along the Chinese coast and compared the proteomes of in situ P. globosa colonies from bloom and dissipation phases using a tandem mass tag (TMT)-based quantitative proteomic approach. Among the 5540 proteins identified, 191 and 109 proteins displayed higher abundances in the bloom and dissipation phases, respectively. The levels of proteins involved in photosynthesis, pigment metabolism, nitrogen metabolism, and matrix substrate biosynthesis were distinctly different between these two phases. Ambient nitrate is a key trigger of P. globosa bloom formation, while the enhanced light harvest and multiple inorganic carbon-concentrating mechanisms support the prosperousness of colonies in the bloom phase. Additionally, colonies in the bloom phase have greater carbon fixation potential, with more carbon and energy being fixed and flowing toward the colonial matrix biosynthesis. Our study revealed the key biological processes underlying P. globosa blooms and provides new insights into the mechanisms behind bloom formation.

A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.

The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.

Symmetry-Breaking Enhanced Herzberg-Teller Effect with Brominated Polyacenes.

Molecular symmetry is vital to the selection rule of vibrationally resolved electronic transition, particularly when the nuclear dependence of electronic wave function is explicitly treated by including Franck-Condon (FC) factor, Franck-Condon/Herzberg-Teller (FC/HT) interference, and Herzberg-Teller (HT) coupling. Our present study investigated the light absorption spectra of highly symmetric tetracene, pentacene, and hexacene molecules of point-group D2h, as well as their monobrominated derivatives with a lower Cs symmetry. It was found that the symmetry-breaking monobromination allows more vibrational normal modes and their pairs to contribute to FC/HT interference and HT coupling, respectively. Through a projection of a molecule's vibrational normal modes to its irreducible representations, a linear relationship between the FC/HT intensity to the polyacene's size was deduced alongside a quadratic dependence of the HT intensity. Both theoretically derived correlations were well justified by our numerical simulations, which also demonstrated an approximately 20% improvement on the agreement with experimental line shape if the HT theory is adopted to replace the FC approximation. Moreover, for these low-symmetry monobrominated polyacenes, the FC intensity was even weaker than its FC/HT and HT counterparts at some excitation energies, making the HT theory imperative to decipher vibronic coupling, a fundamental driving force behind numerous chemical, biological, and photophysical processes.

[Biofilm Eradication Four-Step Strategy: Study of Using Self-Assembled Azithromycin/Rhamnolipid Nanoparticles for Removing Pseudomonas aeruginosa Biofilm].

OBJECTIVE: To investigate the in vitro eradicative effect of self-assembled azithromycin/rhamnolipid nanoparticles (AZI-RHL NPs) on P seudomonas aeruginosa ( P. aeruginosa) biofilm. METHODS: AZI-RHL NPs were prepared and characterized. The minimum inhibitory concentration (MIC) of AZI-RHL NPs on planktonic P. aeruginosa was measured by the broth microdilution method. The eradicative effect of AZI-RHL NPs on P. aeruginosa biofilm was evaluated via crystal violet staining and SYTO 9/PI live/dead staining. Fluorescence labeling was used to measure the eradicative effect of NPs on extracellular polymeric substances (EPS). In addition, crystal violet staining was performed to evaluate the inhibitory effect of AZI-RHL NPs on the adhesion of P. aeruginosa on human bronchial epithelial BEAS-2B cells. To investigate the ability of AZI-RHL NPs to penetrate mucus, the interaction between NPs and mucin was measured via particle size changes after co-incubation with mucin solution. RESULTS: The AZI-RHL NPs had a particle size of about 121 nm and were negatively charged on the surface, displaying a high encapsulation efficiency and a high drug loading capacity of 96.72% and 45.08% for AZI, respectively and 99.38% and 53.07% for RHL, respectively. The MIC of AZI-RHL NPs on planktonic P. aeruginosa was half of that of using AZI alone. AZI-RHL NPs displayed the capacity to effectively destroy the biofilm structure and remove the proteins and polysaccharides in EPS, eradicating biofilms in addition to reducing the survival rate of bacteria in the biofilm. AZI-RHL NPs were shown to have inhibited P. aeruginosa adhesion on BEAS-2B cells and prevented the residual bacteria from forming a new biofilm. There was no significant change in the particle size of NPs after co-incubation with mucin solution, indicating a weak interaction between NPs and mucin, and suggesting that NPs could penetrate the mucus and reach the P. aeruginosa infection sites. CONCLUSION: AZI-RHL NPs were able to effectively enhance the removal of P. aeruginosa biofilm through a four-step strategy of biofilm eradication, including penetrating the mucus, disintegrating the biofilm structure, killing the bacteria dispersed from biofilm, and preventing the adhesion of residual bacteria. We hope that this study will provide a replicable common strategy for the treatment of refractory infections caused by P. aeruginosa and other types of biofilms.

Reducing Defects Density and Enhancing Hole Extraction for Efficient Perovskite Solar Cells Enabled by π-Pb2+ Interactions.

Molecular doping is an of significance approach to reduce defects density of perovskite and to improve interfacial charge extraction in perovskite solar cells. Here, we show a new strategy for chemical doping of perovskite via an organic small molecule, which features a fused tricyclic core, showing strong intermolecular π-Pb2+ interactions with under-coordinated Pb2+ in perovskite. This π-Pb2+ interactions could reduce defects density of the perovskite and suppress the nonradiative recombination, which was also confirmed by the density functional theory calculations. In addition, this doping via π-Pb2+ interactions could deepen the surface potential and downshift the work function of the doped perovskite film, facilitating the hole extraction to hole transport layer. As a result, the doped device showed high efficiency of 21.41 % with ignorable hysteresis. This strategy of fused tricyclic core-based doping provides a new perspective for the design of new organic materials to improve the device performance.