TMK-based cell-surface auxin signalling activates cell-wall acidification.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.

Author Correction: Autophagy maintains tumour growth through circulating arginine.

In this Letter, 'released' should have been 'regulated' in the sentence starting: 'Deletion of Atg5 in the host similarly regulated circulating arginine and suppressed tumorigenesis...' This has been corrected online.

Crystalline C3N3H3 tube (3,0) nanothreads.

Carbon nanothread (CNTh) is a "one-dimensional diamond polymer" that combines high tensile strength and flexibility, but it severely suffers from intrathread disorder. Here, by modifying the reactivity and the stacking ordering of the aromatic precursor, crystalline C3N3H3 CNTh with perfect hexagonal orientation and stacking was synthesized at 10.2 GPa and 573 K from s-triazine. By Rietveld refinement of X-ray diffraction data, gas chromatography mass spectrometry investigation, and theoretical calculation, we found that synthesized CNTh has a tube (3,0) structure, with the repeating s-triazine residue connected solely by C­N bonds along the thread. A "peri-cage" reaction, the concerted bonding between six C and N atoms, instead of [4 + 2] or [1,4] addition reactions, was concluded for the formation of CNThs, and the critical bonding distance between the nearest intermolecular C and N was ∼2.9 Å. The formation of a "structure-specific" crystalline CNTh with C and N orderly distributed highlighted the importance of reaction selectivity and stacking order of reactant molecules, which have great significance for understanding the polymerization of aromatic molecules under high pressure and developing new crystalline CNThs.

N-3-Methylbutyl-benzisoselenazol-3(2H)-one Exerts Antifungal Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis.

In the present work, we evaluated the antifungal activities of two novel ebselen analogs, N-allyl-benzisoselenazol-3(2H)-one (N-allyl-bs) and N-3-methylbutylbenzisoselenazol-3(2H)-one (N-3mb-bs). Colorimetric and turbidity assays were performed to determine the minimum inhibitory concentration (MIC) of these compounds in S1 (fluconazole-sensitive) and S2 (fluconazole-resistant) strains of C. albicans. N-3mb-bs was more active than the N-allyl-bs compound. It is noteworthy that the concentration of N-3mb-bs observed to inhibit fungal growth by 50% (18.2 µM) was similar to the concentration observed to inhibit the activity of the yeast plasma membrane H+-ATPase (Pma1p) by 50% (19.6 µM). We next implemented a mouse model of vulvovaginal candidiasis (VVC) using the S1 strain and examined the mouse and yeast proteins present in the vaginal lavage fluid using proteomics. The yeast proteins detected were predominately glycolytic enzymes or virulence factors associated with C. albicans while the mouse proteins present in the lavage fluid included eosinophil peroxidase, desmocollin-1, and gasdermin-A. We then utilized the N-3mb-bs compound (12.5 mg/kg) in the mouse VVC model and observed that it significantly reduced the vaginal fungal burden, histopathological changes in vagina tissue, and expression of myeloperoxidase (MPO). All in all, the present work has identified a potentially promising drug candidate for VVC treatment.

Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Bayesian sample size determination in basket trials borrowing information between subsets.

Basket trials are increasingly used for the simultaneous evaluation of a new treatment in various patient subgroups under one overarching protocol. We propose a Bayesian approach to sample size determination in basket trials that permit borrowing of information between commensurate subsets. Specifically, we consider a randomized basket trial design where patients are randomly assigned to the new treatment or control within each trial subset ("subtrial" for short). Closed-form sample size formulae are derived to ensure that each subtrial has a specified chance of correctly deciding whether the new treatment is superior to or not better than the control by some clinically relevant difference. Given prespecified levels of pairwise (in)commensurability, the subtrial sample sizes are solved simultaneously. The proposed Bayesian approach resembles the frequentist formulation of the problem in yielding comparable sample sizes for circumstances of no borrowing. When borrowing is enabled between commensurate subtrials, a considerably smaller trial sample size is required compared to the widely implemented approach of no borrowing. We illustrate the use of our sample size formulae with two examples based on real basket trials. A comprehensive simulation study further shows that the proposed methodology can maintain the true positive and false positive rates at desired levels.

Allosteric inhibitor of SHP2 enhances macrophage endocytosis and bacteria elimination by increasing caveolae activation and protects against bacterial sepsis.

The uncontrolled bacterial infection-induced cytokine storm and sequential immunosuppression are commonly observed in septic patients, which indicates that the activation of phagocytic cells and the efficient and timely elimination of bacteria are crucial for combating bacterial infections. However, the role of dysregulated immune cells and their disrupted function in sepsis remains unclear. Here, we found that macrophages exhibited the impaired endocytosis capabilities in sepsis by Single-cell RNA sequencing and bulk RNA sequencing. Caveolae protein Caveolin-1 (Cav-1) of macrophages was inactivated by SHP2 rapidly during Escherichia coli (E.coli) infection. Allosteric inhibitor of SHP2 effectively maintains Cav-1 phosphorylation to enhance macrophage to endocytose and eliminate bacteria. Additionally, TLR4 endocytosis of macrophage was also enhanced upon E.coli infection by SHP099, inducing an increased and rapidly resolved inflammatory response. In vivo, pretreatment or posttreatment with inhibitor of SHP2 significantly reduced the bacterial burden in organs and mortality of mice subjected E.coli infection or CLP-induced sepsis. The cotreatment of inhibitor of SHP2 with an antibiotic conferred complete protection against mortality in mice. Our findings suggest that Cav-1-mediated endocytosis and bacterial elimination may play a critical role in the pathogenesis of sepsis, highlighting inhibitor of SHP2 as a potential therapeutic agent for sepsis.

Autophagy maintains tumour growth through circulating arginine.

Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly regulated [corrected] circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.

The correlation between sperm percentage with a small acrosome and unexplained in vitro fertilization failure.

PURPOSE: Since the unexplained in vitro fertilization failure occurs frequently, it is of great importance and clinical value to identify potential underlying predictors. This study aimed to explore whether the percentage of sperm with a small acrosome was correlated with unexplained in vitro fertilization failure. METHODS: A new acrosomal function evaluation index (the percentage of sperm with a small acrosome) was introduced into the analysis of sperm morphology. The association between the index and acrosome function by acrosin activity detection test and acrosome reaction test was investigated. In addition, the correlation with unexplained in vitro fertilization failure was further explored. Finally, the ROC curve was used to analyze the diagnostic efficacy on the failure of in vitro fertilization and the cutoff value was calculated. RESULTS: As the increasing of the percentage of sperm with a small acrosome, the value of acrosin activity, acrosome reaction rate, and in vitro fertilization rate were reduced, with a statistically significant difference (P < 0.05). The index in the low fertilization rate group was significantly higher than that in the normal fertilization rate group (P < 0.05). Finally, the results of ROC curve found that when the index was 43.5%, the sensitivity and specificity were 74.2% and 95.3%, respectively. CONCLUSION: The percentage of sperm with a small acrosome was positively correlated with unexplained in vitro fertilization failure, which could be potentially used as a prognostic index for the failure of in vitro fertilization. TRIAL REGISTRATION: [Ethics review acceptance No IIT20210339B].

Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic-pituitary-thyroid axis.

Fasting induces profound changes in the hypothalamic-pituitary-thyroid (HPT) axis. After binding thyroid hormone (TH), the TH receptor beta 2 isoform (THRB2) represses Trh and Tsh subunit genes and is the principle negative regulator of the HPT axis. Using mass spectrometry, we identified a major phosphorylation site in the AF-1 domain of THRB2 (serine 101, S101), which is conserved among many members of the nuclear hormone receptor superfamily. More than 50% of THRB2 is phosphorylated at S101 in cultured thyrotrophs (TαT1.1) and in the mouse pituitary. All other THR isoforms lack this site and exhibit limited overall levels of phosphorylation. To determine the importance of THRB2 S101 phosphorylation, we used the TαT1.1 cell line and S101A mutant knock-in mice (Thrb2S101A ). We found that TH promoted S101 THRB2 phosphorylation and was essential for repression of the axis at physiologic TH concentrations. In mice, THRB2 phosphorylation was also increased by fasting and mimicked Trh and Tshb repression by TH. In vitro studies demonstrated that a master metabolic sensor, AMP-activated kinase (AMPK) induced phosphorylation at the same site and caused Tshb repression independent of TH. Furthermore, we identified cyclin-dependent kinase 2 (CDK2) as a direct kinase phosphorylating THRB2 S101 and propose that AMPK or TH increase S101 phosphorylation through the activity of CDK2. This study provides a physiologically relevant function for THR phosphorylation, which permits nutritional deprivation and TH to use a common mechanism for acute suppression of the HPT axis.

Mycobacterium tuberculosis VapC4 toxin engages small ORFs to initiate an integrated oxidative and copper stress response.

The Mycobacterium tuberculosis (Mtb) VapBC4 toxin-antitoxin system is essential for the establishment of Mtb infection. Using a multitier, systems-level approach, we uncovered the sequential molecular events triggered by the VapC4 toxin that activate a circumscribed set of critical stress survival pathways which undoubtedly underlie Mtb virulence. VapC4 exclusively inactivated the sole transfer RNACys (tRNACys) through cleavage at a single site within the anticodon sequence. Depletion of the pool of tRNACys led to ribosome stalling at Cys codons within actively translating messenger RNAs. Genome mapping of these Cys-stalled ribosomes unexpectedly uncovered several unannotated Cys-containing open reading frames (ORFs). Four of these are small ORFs (sORFs) encoding Cys-rich proteins of fewer than 50 amino acids that function as Cys-responsive attenuators that engage ribosome stalling at tracts of Cys codons to control translation of downstream genes. Thus, VapC4 mimics a state of Cys starvation, which then activates Cys attenuation at sORFs to globally redirect metabolism toward the synthesis of free Cys. The resulting newly enriched pool of Cys feeds into the synthesis of mycothiol, the glutathione counterpart in this pathogen that is responsible for maintaining cellular redox homeostasis during oxidative stress, as well as into a circumscribed subset of cellular pathways that enable cells to defend against oxidative and copper stresses characteristically endured by Mtb within macrophages. Our ability to pinpoint activation or down-regulation of pathways that collectively align with Mtb virulence-associated stress responses and the nonreplicating persistent state brings to light a direct and vital role for the VapC4 toxin in mediating these critical pathways.

Microalgae Octapeptide IIAVEAGC Alleviates Oxidative Stress and Neurotoxicity in 6-OHDA-Induced SH-SY5Y Cells by Regulating the Nrf2/HO-1and Jak2/Stat3 Pathways.

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.

Cerebrospinal Fluid Protein Biomarker Discovery in CLN3.

Syndromic CLN3-Batten is a fatal, pediatric, neurodegenerative disease caused by variants in CLN3, which encodes the endolysosomal transmembrane CLN3 protein. No approved treatment for CLN3 is currently available. The protracted and asynchronous disease presentation complicates the evaluation of potential therapies using clinical disease progression parameters. Biomarkers as surrogates to measure the progression and effect of potential therapeutics are needed. We performed proteomic discovery studies using cerebrospinal fluid (CSF) samples from 28 CLN3-affected and 32 age-similar non-CLN3 individuals. Proximal extension assay (PEA) of 1467 proteins and untargeted data-dependent mass spectrometry [MS; MassIVE FTP server (ftp://MSV000090147@massive.ucsd.edu)] were used to generate orthogonal lists of protein marker candidates. At an adjusted p-value of <0.1 and threshold CLN3/non-CLN3 fold-change ratio of 1.5, PEA identified 54 and MS identified 233 candidate biomarkers. Some of these (NEFL, CHIT1) have been previously linked with other neurologic conditions. Others (CLPS, FAM217B, QRICH2, KRT16, ZNF333) appear to be novel. Both methods identified 25 candidate biomarkers, including CHIT1, NELL1, and ISLR2 which had absolute fold-change ratios >2. NELL1 and ISLR2 regulate axonal development in neurons and are intriguing new candidates for further investigation in CLN3. In addition to identifying candidate proteins for CLN3 research, this study provides a comparison of two large-scale proteomic discovery methods in CSF.

Ordered Van der Waals Hetero-nanoribbon from Pressure-Induced Topochemical Polymerization of Azobenzene.

Pressure-induced topochemical polymerization of molecular crystals with various stackings is a promising way to synthesize materials with different co-existing sub-structures. Here, by compressing the azobenzene crystal containing two kinds of intermolecular stacking, we synthesized an ordered van der Waals carbon nanoribbon (CNR) heterostructure in one step. Azobenzene polymerizes via a [4 + 2] hetero-Diels-Alder (HDA) reaction of phenylazo-phenyl in layer A and a para-polymerization reaction of phenyl in layer B at 18 GPa, as evidenced by in situ Raman and IR spectroscopies, X-ray diffraction, as well as gas chromatography-mass spectrometry and the solid-state nuclear magnetic resonance of the recovered products. The theoretical calculation shows that the obtained CNR heterostructure has a type II (staggered) band gap alignment. Our work highlights a high-pressure strategy to synthesize bulk CNR heterostructures.

Borrowing of information across patient subgroups in a basket trial based on distributional discrepancy.

Basket trials have emerged as a new class of efficient approaches in oncology to evaluate a new treatment in several patient subgroups simultaneously. In this article, we extend the key ideas to disease areas outside of oncology, developing a robust Bayesian methodology for randomized, placebo-controlled basket trials with a continuous endpoint to enable borrowing of information across subtrials with similar treatment effects. After adjusting for covariates, information from a complementary subtrial can be represented into a commensurate prior for the parameter that underpins the subtrial under consideration. We propose using distributional discrepancy to characterize the commensurability between subtrials for appropriate borrowing of information through a spike-and-slab prior, which is placed on the prior precision factor. When the basket trial has at least three subtrials, commensurate priors for point-to-point borrowing are combined into a marginal predictive prior, according to the weights transformed from the pairwise discrepancy measures. In this way, only information from subtrial(s) with the most commensurate treatment effect is leveraged. The marginal predictive prior is updated to a robust posterior by the contemporary subtrial data to inform decision making. Operating characteristics of the proposed methodology are evaluated through simulations motivated by a real basket trial in chronic diseases. The proposed methodology has advantages compared to other selected Bayesian analysis models, for (i) identifying the most commensurate source of information and (ii) gauging the degree of borrowing from specific subtrials. Numerical results also suggest that our methodology can improve the precision of estimates and, potentially, the statistical power for hypothesis testing.

CALCIUM-DEPENDENT PROTEIN KINASE32 regulates cellulose biosynthesis through post-translational modification of cellulose synthase.

Cellulose is an essential component of plant cell walls and an economically important source of food, paper, textiles, and biofuel. Despite its economic and biological significance, the regulation of cellulose biosynthesis is poorly understood. Phosphorylation and dephosphorylation of cellulose synthases (CESAs) were shown to impact the direction and velocity of cellulose synthase complexes (CSCs). However, the protein kinases that phosphorylate CESAs are largely unknown. We conducted research in Arabidopsis thaliana to reveal protein kinases that phosphorylate CESAs. In this study, we used yeast two-hybrid, protein biochemistry, genetics, and live-cell imaging to reveal the role of calcium-dependent protein kinase32 (CPK32) in the regulation of cellulose biosynthesis in A. thaliana. We identified CPK32 using CESA3 as a bait in a yeast two-hybrid assay. We showed that CPK32 phosphorylates CESA3 while it interacts with both CESA1 and CESA3. Overexpressing functionally defective CPK32 variant and phospho-dead mutation of CESA3 led to decreased motility of CSCs and reduced crystalline cellulose content in etiolated seedlings. Deregulation of CPKs impacted the stability of CSCs. We uncovered a new function of CPKs that regulates cellulose biosynthesis and a novel mechanism by which phosphorylation regulates the stability of CSCs.

Multi-mode strong coupling in Fabry-Pérot cavity-WS2 photonic crystal hybrid structures.

Optical microcavities embedded with transition metal dichalcogenide (TMDC) membranes have been demonstrated as excellent platforms to explore strong light-matter interactions. Most of the previous studies focus on strong coupling between excitons of unpatterned TMDC membranes and optical resonances of various microcavities. It is recently found that TMDC membranes patterned into photonic crystal (PhC) slabs can sustain guided-mode resonances that can be excited and probed by far-fields. Here, we present a comprehensive theoretical and numerical study on optical responses of Fabry-Pérot (F-P) cavity-WS2 PhC hybrid structures to investigate the multi-mode coupling effects between excitons, guided-mode resonances and F-P modes. We show that both the exciton resonance and the guide-mode resonance of the WS2 PhC can strongly interact with F-P modes of the cavity to reach strong coupling regime. Moreover, a Rabi splitting as large as 63 meV is observed for the strong coupling between the guided-mode resonance and the F-P mode, which is much larger than their average dissipation rate. We further demonstrate that it is even possible to realize a triple mode strong coupling by tuning the guide-mode resonances spectrally overlapped with the exciton resonance and the F-P modes. The hybrid polariton states generated from the triple mode coupling exhibit a Rabi splitting of 120 meV that greatly exceeds the criterion of a triple mode strong coupling (∼29.3 meV). Our results provide that optical microcavities embedded with TMDC PhCs can serve as promising candidates for polariton devices based on multi-mode strong coupling.

Multiple surface lattice resonances of overlapping nanoparticle arrays with different lattice spacing.

Multiple surface lattice resonances generated with nanoparticle arrays are promising to enhance light-matter interactions at different spectral positions simultaneously, and it is important to tailor these resonances to desired frequencies for practical applications such as multi-modal nanolasing. To this end, this study proposes to generate multiple surface lattice resonances using overlapping nanoparticle arrays with different lattice spacing. Both full-wave numerical simulations and analytical coupled dipole approximation calculations reveal that for the overlapping structures composed with two different gold nanosphere arrays, both surface lattice resonances for the element structures are effectively excited. Considering that the optical responses are governed by the dipole-dipole interactions between the nanoparticles, it is interesting to find that the multiple surface lattice resonances are almost invariant by adjusting the relative shifts between the two arrays, which can be useful to tailor the high-quality factor resonances to desired spectral positions. In addition, due to the same reason, it is also shown that the multiple surface lattice resonances can be further finely tuned by selectively removing specific nanoparticles in the array. We anticipate that the tolerance to generate multiple surface lattice resonances and the flexible tunability make the overlapping nanoparticle arrays useful to design high performance linear and nonlinear nanophotonic devices.

Resonance coupling between chiral quasi-BICs and achiral molecular excitons in dielectric metasurface J-aggregate heterostructures.

The realization of flexible tuning and enhanced chiral responses is vital for many applications in nanophotonics. This study proposes to manipulate the collective optical responses with heterostructures consisting of chiral dielectric metasurfaces and achiral J-aggregates. Owing to the resonance coupling between the chiral quasi-bound states in the continuum (QBICs) and the achiral exciton mode, large mode splitting and anticrossing are observed in both the transmission and circular dichroism (CD) spectra, which indicates the formation of hybrid chiral eigenmodes and the realization of the strong coupling regime. Considering that the radiative and dissipative damping of the hybrid eigenmodes depends on the coherent energy exchange, the chiral resonances can be flexibly tuned by adjusting the geometry and optical constants for the heterostructure, and the CD of the three hybrid eigenmodes approach the maximum (∼1) simultaneously when the critical coupling conditions are satisfied, which can be promising for enhanced chiral light-matter interactions.

Mechanism of lnRNA-ICL involved in lung cancer development in COPD patients through modulating microRNA-19-3p/NKRF/NF-κB axis.

The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.