2X-Rhodamine: A Bright and Fluorogenic Scaffold for Developing Near-Infrared Chemigenetic Indicators.

Chemigenetic fusion of synthetic dyes with genetically encoded protein tags presents a promising avenue for in vivo imaging. However, its full potential has been hindered by the lack of bright and fluorogenic dyes operating in the "tissue transparency" near-infrared window (NIR, 700-1700 nm). Here, we report 2X-rhodamine (2XR), a novel bright scaffold that allows for the development of live-cell-compatible, NIR-excited variants with strong fluorogenicity beyond 1000 nm. 2XR utilizes a rigidified π-skeleton featuring dual atomic bridges and functions via a spiro-based fluorogenic mechanism. This design affords longer wavelengths, higher quantum yield (ΦF = 0.11), and enhanced fluorogenicity in water when compared to the phosphine oxide-cored, or sulfone-cored rhodamine, the NIR fluorogenic benchmarks currently used. We showcase their bright performance in video-rate dynamic imaging and targeted deep-tissue molecular imaging in vivo. Notably, we develop a 2XR variant, 2XR715-HTL, an NIR fluorogenic ligand for the HaloTag protein, enabling NIR genetically encoded calcium sensing and the first demonstration of in vivo chemigenetic labeling beyond 1000 nm. Our work expands the library of NIR fluorogenic tools, paving the way for in vivo imaging and sensing with the chemigenetic approach.

Efficient and Stable NIR-II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single-Cell Tracking and Time-Resolved Imaging.

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 µs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93 %) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

NIR-II Dyad-Doped Ratiometric Nanosensor with Enhanced Spectral Fidelity in Biological Media for In Vivo Biosensing.

Ratiometric fluorescence nanosensors provide quantitative biological information. However, spectral shift and distortion of ratiometric nanosensors in biological media often compromise sensing accuracy, limiting in vivo applications. Here, we develop a fluorescent dyad (aBOP-IR1110) in the second near-infrared (NIR-II) window by covalently linking an asymmetric aza-BODIPY with a ONOO--responsive meso-thiocyanine. The dyad encapsulated in the PEGylated nanomicelle largely improves spectral fidelity in serum culture by >9.4 times compared to that of its noncovalent counterpart. The increased molecular weights (>1480 Da) and hydrophobicity (LogP of 7.87-12.36) lock dyads inside the micelles, which act as the shield against the external environment. ONOO--altered intramolecular Förster resonance energy transfer (FRET) generates linear ratiometric response with better serum tolerance, enabling us to monitor the dynamics of oxidative stress in traumatic brain injury and evaluate therapeutic efficiency. The results show high correlation with in vitro triphenyltetrazolium chloride staining, suggesting the potential of NIR-II dyad-doped nanosensor for in vivo high-fidelity sensing applications.

Polymethine Molecular Platform for Ratiometric Fluorescent Probes in the Second near-Infrared Window.

Visualizing biomolecules such as enzymes in the deep tissue of living organisms via molecular ratiometric fluorescent probes in the second near-infrared window (NIR-II) with a built-in self-calibration function can provide reliable information about relevant pathophysiological processes directly but so far is not feasible due to the lack of a fluorescence modulation strategy in the NIR-II window. Here we present a molecular platform Py-2 by integrating the rhodamine 6G scaffold and polymethine. The maximal emission wavelength of Py-2 was 1010 nm and blue-shifted to 945 nm when its secondary amine was acylated. Based on Py-2, two molecular ratiometric NIR-II fluorescent probes, nitroreductase-responsive Rap-N and ROS-responsive Rap-R, were constructed and successfully demonstrated in vitro and in vivo. Overall, this report presents a unique approach to developing ratiometric NIR-II molecular probes for in vivo biosensing.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Comprehensive metabolomics analysis of key taste components in different varieties of table grapes.

Grapes are one of the world's largest fruit crops, which are rich in nutrients and taste. Summer Black, Gui Fei, Kyoho Grape, Giant Rose, Shine Muscat, and Rosario Bianco are the six most popular table grapes in Wuxi city, Jiangsu province. Owing to the lack of comprehensive investigations of metabolites in table grapes, the metabolic causes of differences in their taste are unknown. In this study, metabolites of six table grapes were profiled using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry combined with multivariate analysis. Orthogonal partial least squares discriminant analysis discriminated among the metabolites of these varieties. Metabolic pathway analysis revealed that carbohydrate and amino acid metabolisms were highly conserved among these varieties. Our results suggest that the taste differences in the six table grape varieties can be explained by variations in composition and abundance of carbohydrates, organic acids, amino acids, and polyphenols. This study provides comprehensive insights into the underlying metabolic causes of taste variation in table grapes.

Counterion-Paired Bright Heptamethine Fluorophores with NIR-II Excitation and Emission Enable Multiplexed Biomedical Imaging.

Photon excitation and emission at the NIR-II spectral window enable high-contrast deep-tissue bioimaging. However, multiplexed imaging with NIR-II excitation and emission has been hampered by the limited chemical strategies to develop bright fluorophores with tunable absorption in this spectral regime. Herein, we developed a series of heptamethine cyanines (HCs) with varied absorption/emission maxima spanning from 1100 to 1600 nm through a physical organic approach. A bulky counterion paired to HCs was found to elicit substantial improvements in absorptivity (7-fold), brightness (14-fold), and spectral profiles in water, addressing a notorious quenching problem of NIR-II cyanines due to aggregation and polarization. We demonstrated the utilities of HC1222 and HC1342 for high-contrast dual-color imaging of circulatory system, lymphatic structures, tumor, and organ function in living mice under 1120 nm and 1319 nm excitation, showing HCs as a promising platform for non-invasive bioimaging.

Nitidumpeptins A and B, Cyclohexapeptides Isolated from Zanthoxylum nitidum var. tomentosum: Structural Elucidation, Total Synthesis, and Antiproliferative Activity in Cancer Cells.

Nitidumpeptins A and B (1 and 2), two novel cyclic hexapeptides, were isolated from the herb Zanthoxylum nitidum var. tomentosum. Their planar structures were elucidated based on NMR and MS spectrometric analysis, and the absolute configurations were determined by the Marfey's method. Structurally, 1 is a unique peptide with a backbone bearing a pyrrolidine-2,5-dione unit, which is the first occurrence moiety specifically in a naturally occurring cyclohexapeptide. The total synthesis of 1 and 2 was achieved by solution-phase in parallel with solid-phase peptide synthesis, and their absolute configurations were further confirmed. The combination of 2 with gefitinib exhibited synergistic antiproliferative activity in acquired gefitinib-resistant non-small cell lung cancer cells (HCC827-gef). The underlying mechanism for the antiproliferative activity of 2 was in part associated with the suppression of YAP expression in HCC827-gef cells.

[Two newly recorded species of plants in Jiangxi province].

Based on the investigation of wild medicinal plant resources in Dexing city, Jiangxi province, and the collected plant specimens, which were identified by taxonomy, two new record species of geographical distribution were found, which are Meehania zheminensis A. Takano, Pan Li & G.-H. Xia and Corydalis huangshanensis L.Q.Huang & H.S.Peng. The voucher specimens are kept in Dexing museum of traditional Chinese medicine. In this paper, the new distribution species were reported, which provides valuable information for further enriching and supplementing the species diversity of medicinal plant resources in Jiangxi province.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Radiomics analysis of multicenter CT images for discriminating mucinous adenocarcinoma from nomucinous adenocarcinoma in rectal cancer and comparison with conventional CT values.

OBJECTIVE: To investigate the value of CT-based radiomics signature for preoperatively discriminating mucinous adenocarcinoma (MA) from nomucinous adenocarcinoma (NMA) in rectal cancer and compare with conventional CT values. METHOD: A total of 225 patients with histologically confirmed MA or NMA of rectal cancer were retrospectively enrolled. Radiomics features were computed from the entire tumor volume segmented from the post-contrast phase CT images. The maximum relevance and minimum redundancy (mRMR) and LASSO regression model were performed to select the best preforming features and build the radiomics models using a training cohort of 155 cases. Then, predictive performance of the models was validated using a validation cohort of 70 cases and receiver operating characteristics (ROC) analysis method. Meanwhile, CT values in post- and pre-contrast phase, as well as their difference (D-values) of tumors in two cohorts were measured by two radiologists. ROC curves were also calculated to assess diagnostic efficacies. RESULTS: One hundred and sixty-three patients were confirmed by pathology as NMA and 62 cases were MA. The radiomics signature comprised 19 selected features and showed good discrimination performance in both the training and validation cohorts. The areas under ROC curves (AUC) are 0.93 (95% confidence interval [CI]: 0.89-0.98) in training cohort and 0.93 (95% CI: 0.87-0.99) in validation cohort, respectively. Three sets of CT values of MA in pre- and post-contrast phase, and their difference (D-value) (31±7.0, 51±12.6 and 20±9.3, respectively) were lower than those of NMA (37±5.6, 69±13.3 and 32±11.7, respectively). Comparing to the radiomics signature, using three sets of conventional CT values yielded relatively low diagnostic performance with AUC of 0.84 (95% CI: 0.78-0.88), 0.75 (95% CI: 0.69-0.81) and 0.78 (95% CI: 0.72-0.83), respectively. CONCLUSION: This study demonstrated that CT radiomics features could be utilized as a noninvasive biomarker to identify MA patients from NMA of rectal cancer preoperatively, which is more accurate than using the conventional CT values.

Single-cell transcriptome sequencing reveals that cell division cycle 5-like protein is essential for porcine oocyte maturation.

The brilliant cresyl blue (BCB) test is used in both basic biological research and assisted reproduction to identify oocytes likely to be developmentally competent. However, the underlying molecular mechanism targeted by the BCB test is still unclear. To explore this question, we first confirmed that BCB-positive porcine oocytes had higher rates of meiotic maturation, better rates of cleavage and development into blastocysts, and lower death rates. Subsequent single-cell transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes identified 155 genes that were significantly differentially expressed between BCB-negative and BCB-positive oocytes. These included genes such as cdc5l, ldha, spata22, rgs2, paip1, wee1b, and hsp27, which are enriched in functionally important signaling pathways including cell cycle regulation, oocyte meiosis, spliceosome formation, and nucleotide excision repair. In BCB-positive GV oocytes that additionally had a lower frequency of DNA double-strand breaks, the CDC5L protein was significantly more abundant. cdc5l/CDC5L inhibition by short interference (si)RNA or antibody microinjection significantly impaired porcine oocyte meiotic maturation and subsequent parthenote development. Taken together, our single-oocyte sequencing data point to a potential new role for CDC5L in porcine oocyte meiosis and early embryo development, and supports further analysis of this protein in the context of the BCB test.

Arabidopsis VAC14 Is Critical for Pollen Development through Mediating Vacuolar Organization.

Pollen viability depends on dynamic vacuolar changes during pollen development involving increases and decreases of vacuolar volume through water and osmolite accumulation and vacuolar fission. Mutations in FAB1A to FAB1D, the genes encoding phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]-converting kinases, are male gametophyte lethal in Arabidopsis (Arabidopsis thaliana) due to defective vacuolar fission after pollen mitosis I, suggesting a key role of the phospholipid in dynamic vacuolar organization. However, other genetic components that regulate the production of PI(3,5)P2 and its involvement in pollen germination and tube growth are unknown. Here, we identified and characterized Arabidopsis VAC14, a homolog of the yeast and metazoan VAC14s that are crucial for the production of PI(3,5)P2VAC14 is constitutively expressed and highly present in developing pollen. Loss of function of VAC14 was male gametophyte lethal due to defective pollen development. Ultrastructural studies showed that vacuolar fission after pollen mitosis I was compromised in vac14 mutant microspores, which led to pollen abortion. We further showed that inhibiting the production of PI(3,5)P2 or exogenous application of PI(3,5)P2 mimicked or rescued the pollen developmental defect of the vac14 mutant, respectively. Genetic interference and pharmacological approaches suggested a role of PI(3,5)P2 in pollen germination and tube growth. Our results provide insights into the function of VAC14 and, by inference, that of PI(3,5)P2 in plant cells.

Glechomanamides A-C, Germacrane Sesquiterpenoids with an Unusual Δ8-7,12-Lactam Moiety from Salvia scapiformis and Their Antiangiogenic Activity.

Three new germacrane sesquiterpenoid-type alkaloids with an unusual Δ8-7,12-lactam moiety, glechomanamides A-C (1-3), and two pairs of 7,12-hemiketal sesquiterpenoid epimers (4a/b, 5a/b) were isolated from Salvia scapiformis. Their structures were elucidated by spectroscopic methods including HRESIMS, IR, UV, and 1D and 2D NMR and also confirmed by single-crystal X-ray diffraction analysis. The chemical transformation of compounds 1-5 in a solution environment was analyzed by 2D NMR spectroscopy. The aza acetallactams (1-3) were stable in organic solvent, while single crystals of the hemiacetal esters (4a/b, 5a/b) underwent a tautomeric equilibrium after being dissolved. Single crystals of 4a, 4b, and 5a were obtained for the first time as their naturally occurring forms. Glechomanamide B (2) exhibited antiangiogenic activity by suppression of vascular endothelial growth factor (VEGF)-induced tube formation through modulation of VEGF receptor 2 (VEGFR2)-mediated signaling pathways in human umbilical vascular endothelial cells (HUVECs). In addition, compound 2 also showed the significant suppression of mRNA expression associated with glycolysis and angiogenesis biomarkers in high glucose (30 mM)-induced HUVECs. These findings suggest that compound 2 might be a potential lead compound candidate for the management of diabetic retinopathy.

The influence of diet quality and dietary behavior on health-related quality of life in the general population of children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: The association between diet quality, dietary behavior and health-related quality of life has been mostly examined in children and adolescents with specific chronic diseases. No systematic review has synthesized the influence of diet quality and dietary behavior on health-related quality of life in the general population of children and adolescents. The purpose of this study was to systematically review the primary studies that evaluated the association between diet quality, dietary behavior and health-related quality of life in the general population of children and adolescents and to synthesize the findings for the association. METHODS: A computer search in the databases of MEDLINE, EMBASE and PSYCINFO was performed to retrieve English language studies that were published from 1946 up to April 8, 2018. We also screened the PubMed-related articles and the reference lists of the existing relevant literature to identify other eligible studies. We synthesized the association between diet quality, dietary behavior and health-related quality of life using both a qualitative method and meta-analysis. We reported the review following up the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. RESULTS: Seventeen studies were included in the synthesis including twelve cross-sectional studies and five longitudinal studies. We found that diet quality and dietary behavior were associated with health-related quality of life in children and adolescents. The positive effect of healthy diets on health-related quality of life was observed for multiple domains of health-related quality of life, including physical, school and emotional functioning, and psychosocial quality of life. We observed a dose-response relationship between the diet exposure and health-related quality of life, where an unhealthy dietary behavior or lower diet quality was associated with decreased health-related quality of life among children and adolescents. CONCLUSION: The findings of the systematic review suggest the importance of promoting healthy diets and nutrition for good health-related quality of life among children and adolescents. Future research is needed to strengthen the evidence for prospective relationships and for the dose-response effect between diet quality, dietary behavior and health-related quality of life among children and adolescents.

Association of the rs1760944 polymorphism in the APEX1 base excision repair gene with risk of nasopharyngeal carcinoma in a population from an endemic area in South China.

BACKGROUND: Apurinic/apyrimidinic endonuclease 1 (APEX1) plays a central role in the repair of oxidative DNA lesions via base excision repair, and polymorphism in the APEX1 gene may affect susceptibility to carcinogenesis. METHODS: Here, we assessed possible relationships between single-nucleotide polymorphism at APEX1 rs1760944 and risk of nasopharyngeal carcinoma (NPC) in 477 NPC patients and 558 healthy controls from Guangxi province, which is the second largest NPC endemic area in South China. RESULTS: Genotype frequencies in controls were in Hardy-Weinberg equilibrium. Logistic regression analysis identified the genotypes GT or GG as associated with significantly lower risk than the genotype TT (adjusted odds ratio [OR] 0.745, 95% confidence interval [CI] 0.573-0.970). This apparent protective effect of GT/GG was even greater among those with no smoking history (adjusted OR 0.679, 95%CI 0.494-0.934). CONCLUSION: Our results suggest that APEX1 rs1760944 polymorphism may correlate with NPC susceptibility in a population from an endemic area in South China.

miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA.

BACKGROUND: Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. METHODS: miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. RESULTS: Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. CONCLUSIONS: Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.

Serine/threonine kinases 31(STK31) may be a novel cellular target gene for the HPV16 oncogene E7 with potential as a DNA hypomethylation biomarker in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a leading cause of mortality in females, especially in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (hrHPV), and hrHPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. STK31 gene of which the expression has been proven to be regulated by the methylation status of its promoter, is one of the novel cancer/testis (CT) genes and plays important roles in human cancers. Reasearches have indicated that viral infection is correlated to the methylation statuses of some genes. Herein, we detected methylation status of the STK31 gene in cervical tumors and explored its interaction with HPV16 or/and HPV18 (HPV16/18) infection. METHODS: Bisulfite genomic sequencing PCR (BGS) combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation statuses of the STK31 gene promoter/exon 1 region in HPV16/18-positive, HPV-negative CC cell lines; ectopically expressed HPV16 E6, -E7, and -E6/E7 CC cells; normal cervical tissues and cervical tumor tissues of different stages. The mRNA and protein expressions of STK31 were detected by RT-PCR and western blotting. RESULTS: The STK31 gene promoter/exon 1 was hypomethylated in the HPV16/18-positive cell lines HeLa, SiHa and CaSki, and the mRNA and protein expression were detected. In contrast, the STK31 gene exhibited hypermethylation and silenced expression in the HPV-negative CC cells C33A and HT-3. Compared with the primary HPV-negative CC cell lines, the STK31 methylation was downregulated, and STK31 expression was induced in the HPV16E7/E67 transfected cells. The methylation statuses and expressions of STK31 were verified in the cervical tumor samples at different stages. Additionally, chemotherapy treatment may influence STK31 expression by regulating its methylation status. CONCLUSIONS: STK31 may be a novel cellular target gene for the HPV16 oncogeneE7. The HPV16 oncogene E7 may affect STK31 expression through a methylation-mediated mechanism. The aberrant methylation of the STK31 promoter/exon 1 region may be a precursor of human cervical carcinogenesis and a potential DNA aberrant methylation biomarker of conditions ranging from precancerous disease to invasive cancer.

General monogamy relation for the entanglement of formation in multiqubit systems.

We prove exactly that the squared entanglement of formation, which quantifies the bipartite entanglement, obeys a general monogamy inequality in an arbitrary multiqubit mixed state. Based on this kind of exotic monogamy relation, we are able to construct two sets of useful entanglement indicators: the first one can detect all genuine multiqubit entangled states even in the case of the two-qubit concurrence and n-tangles being zero, while the second one can be calculated via quantum discord and applied to multipartite entanglement dynamics. Moreover, we give a computable and nontrivial lower bound for multiqubit entanglement of formation.

Brominated Quaternary Ammonium Salt-Assisted Hybrid Electron Transport Layer for High-Performance Conventional Organic Solar Cells.

Interlayer engineering is crucial for achieving efficient and stable organic solar cells (OSCs). Herein, by introducing a commercialized brominated quaternary ammonium salt, hexamethonium bromide (HB), into a perylene diimide (PDI)-structured electron transport layer (ETL), a PDINN:HB hybrid ETL with enhanced charge collection ability and environmental/operational stability is realized. Molecular dynamics simulations and Kelvin probe force microscopy indicate that strong polar bromine and amine groups can form extra interfacial dipoles in the hybrid interlayer, while X-ray photoelectron spectroscopy and electron paramagnetic resonance suggest the hybrid ETL can interact with the Ag cathode, thereby regulating the energy level arrangement at the interface. As for the results, the PDINN:HB hybrid ETL enables improved power conversion efficiency (PCE) from 17.8 to 18.4% and 18.8 to 19.4% in PM6:C5-16 bulk heterojunction- and PM6/L8-BO pseudobulk heterojunction-based OSCs, respectively. The versatility of this method is further verified by introducing a range of brominated quaternary ammonium salts into PDINN, in which a superior PCE and stability are all obtained compared to the reference device.