Stimuli-responsive mechanically interlocked molecules constructed from cucurbit[n]uril homologues and derivatives.

Cucurbit[n]uril supramolecular chemistry has developed rapidly since 2001 when different cucurbit[n]uril homologues (Q[n]) were successfully separated in pure form. The combination of Q[n] cavity size and various types of external stimuli has given birth to numerous types of Q[n]-based mechanically interlocked molecules (MIMs), including (pseudo)rotaxanes, catenanes, dendrimers and poly(pseudo)rotaxanes. In this review article, the important advances in the field of Q[n]-based MIMs over the past two decades are highlighted. This review also describes examples of heterowheel (pseudo)rotaxanes and poly(pseudo)rotaxanes involving Q[n]s, and reflects on the opportunities and challenges of constructing Q[n]-based stimuli-responsive MIMs.

Simple Nano-Luciferase-Based Assay for the Rapid and High-Throughput Detection of SARS-CoV-2 3C-Like Protease.

In this study, we described an easy-to-perform nano-luciferase (nLuc) sensor for the rapid detection of 3-chymotrypsin-like protease (3CLpro) encoded by SARS-CoV-2. The technology is based on the cleavage reaction of recombinant-nLuc via 3CLpro. The nLuc-based assay is a general, one-step method and is naturally specific in detection. The stability, sensitivity, detection range, and response time are fully characterized. The application of 3CLpro detection in artificial and human saliva as well as antiviral drug screening demonstrates that the method can quantify 3CLpro with high sensitivity in one step. With its unique features, the nLuc-based assay may find broad applications in the auxiliary diagnosis of SARS-CoV-2, as well as other types of coronavirus infection.

You are what you eat: nutrient and water relations between mistletoes and hosts.

Mistletoes play important roles in biogeochemical cycles. Although many studies have compared nutrient concentrations between mistletoes and their hosts, no general patterns have been found and the nutrient uptake mechanisms in mistletoes have not been fully resolved. To address the water and nutrient relations in mistletoes compared with their hosts, we measured 11 nutrient elements, two isotope ratios and two leaf morphological traits for 11 mistletoe and 104 host species from four sites across a large environmental gradient in southwest China. Mistletoes had significantly higher phosphorus, potassium, and boron concentrations, nitrogen isotope ratio, and lower carbon isotope ratio (δ13 C) indicative of lower water-use efficiency than hosts, but other elements were similar to those in hosts. Sites explained most of the variation in the multidimensional trait space. With increasing host nitrogen concentration, both mistletoe δ13 C and the difference between mistletoe and host δ13 C increased, providing evidence to support the 'nitrogen parasitism hypothesis'. Host nutrient concentrations were the best predictors for that of the mistletoe nutrient elements in most cases. Our results highlight the important roles of environmental conditions and host nutrient status in determining mistletoe nutrient pools, which together explain their trophic interactions with hosts in subtropical and tropical ecosystems.

Strategies of Managing Repeated Measures: Using Synthetic Random Forest to Predict HIV Viral Suppression Status Among Hospitalized Persons with HIV.

The HIV/AIDS epidemic remains a major public health concern since the 1980s; untreated HIV infection has numerous consequences on quality of life. To optimize patients' health outcomes and to reduce HIV transmission, this study focused on vulnerable populations of people living with HIV (PLWH) and compared different predictive strategies for viral suppression using longitudinal or repeated measures. The four methods of predicting viral suppression are (1) including the repeated measures of each feature as predictors, (2) utilizing only the initial (baseline) value of the feature as predictor, (3) using the last observed value as the predictors and (4) using a growth curve estimated from the features to create individual-specific prediction of growth curves as features. This study suggested the individual-specific prediction of the growth curve performed the best in terms of lowest error rate on an independent set of test data.

Simultaneous removal of phosphate and tetracycline using LaFeO3 functionalised magnetic biochar by obtained ultrasound-assisted sol-gel pyrolysis: Mechanisms and characterisation.

Excessive phosphate and tetracycline (TC) contaminants pose a serious risk to human health and the ecological environment. As such exploring the simultaneous adsorption of phosphate and TC is garnering increasing attention. In this study, an efficient lanthanum ferrate magnetic biochar (FLBC) was synthesised from crab shells using an ultrasound-assisted sol-gel method to study its performance and mechanisms for phosphate and TC adsorption in aqueous solutions in mono/bis systems. According to the Langmuir model, the developed exhibited a maximum adsorption capacity of 65.62 mg/g for phosphate and 234.1 mg/g for TC (pH:7.0 ± 0.1, and 25 °C). Further, it exhibited high resistance to interference and pH suitability. In practical swine wastewater applications, whereby the concentrations of phosphate and TC are 37 and 19.97 mg/L, respectively, the proposed material demonstrated excellent performance. In addition, electrostatic adsorption, chemical precipitation and ligand exchange were noted to be the main mechanisms for phosphate adsorption by FLBC, whereas hydrogen bonding and π-π interaction were the main adsorption mechanisms for TC adsorption. Therefore, this study successfully prepared a novel and efficient adsorbent for phosphate and TC.

Exploring Three Decades of Progress: A Comprehensive Visual Review of Intravoxel Incoherent Motion MRI Research (1988-2021).

BACKGROUND Despite an increasing number of published articles on intravoxel incoherent motion (IVIM) in the past decade, almost all have focused on the technique and clinical applications of IVIM, with little attention to the collective knowledge and scientific analysis of this field. The aim of the present study was to construct a knowledge framework and to explore hotspots and emerging trends concerning use of IVIM in humans. MATERIAL AND METHODS The articles concerning IVIM MRI published from 1988 to 2021 were retrieved from the Science Citation Index Expended of the Web of Science Core Collection on 17, August 2021. The downloaded data were imported into Excel 2016 and CiteSpace V for scientometric analysis. RESULTS A total of 921 articles were included in this study and most of them were published since 2012. China (n=392) was the most productive country and the Philips Healthcare (n=46) was the most productive institution. Christian Federau had the largest number of publications (n=18). An article by Andreou A et al (2013) was the most important reference with the most co-citations (n=100) and centrality (0.06). The 5 hotspots in IVIM were perfusion, diffusion-weighted imaging, intravoxel incoherent motion, apparent diffusion coefficient, and magnetic resonance imaging. The 2 frontier topics were "brain perfusion" and "accuracy". According to the clustering of co-citation analysis, "liver", "diffusion weighting", "pancreas", and "brain" were the main research directions. CONCLUSIONS Scientometric analysis of IVIM literature with CiteSpace software can provide researchers with valuable information about knowledge framework, hotspots, and emerging trends concerning IVIM in humans.

Estrogen and BRCA1 deficiency synergistically induce breast cancer mutation-related DNA damage.

Estrogen (E2) is crucial for the development of breast cancer caused by BRCA1 mutation, and can increase the DNA damage in BRCA1-deficient cells. However, the mechanisms through which BRCA1 deficiency and E2 synergistically induce DNA damage remains unclear. In this study, we analyzed the distribution of DNA damage in E2-treated BRCA1-deficient cells. We detected DNA lesions in the vicinity of genes that are transcriptionally activated by estrogen receptor-α (ER). Loss of BRCA1 altered chromatin binding by ER, which significantly affected the distribution of DNA damage. Moreover, these changes were associated with the established mutations in BRCA1-mutant breast cancer. Taken together, our findings reveal a new mechanism underlying the DNA damage in breast cancer cells that is synergistically induced by BRCA1 deficiency and E2.

Neighborhood Characteristics, Intersectional Discrimination, Mental Health, and HIV Outcomes Among Black Women Living With HIV, Southeastern United States, 2019‒2020.

Objectives. To examine the effects of within-neighborhood and neighboring characteristics on discrimination, stigma, mental health, and HIV outcomes among Black women living with HIV (BWLWH). Methods. A total of 151 BWLWH in a southeastern US city provided baseline data (October 2019‒January 2020) on experienced microaggressions and discrimination (race-, gender-, sexual orientation-, or HIV-related), mental health (e.g., depression, posttraumatic stress disorder), and HIV outcomes (e.g., viral load, antiretroviral therapy adherence). Neighborhood characteristics by census tract were gathered from the American Community Survey and the National Center for Charitable Statistics. Spatial econometrics guided the identification strategy, and we used the maximum likelihood technique to estimate relationships between a number of predictors and outcomes. Results. Within-neighborhood and neighboring characteristics (employment, education, crime, income, number of religious organizations, and low-income housing) were significantly related to intersectional stigma, discrimination, mental health, HIV viral load, and medication adherence. Conclusions. Policy, research, and interventions for BWLWH need to address the role of neighborhood characteristics to improve quality of life and HIV outcomes. (Am J Public Health. 2022;112(S4):S433-S443. https://doi.org/10.2105/AJPH.2021.306675).

Mirror image stimulation could reverse social-isolation-induced aggressiveness in the high-level subsocial lactating spider.

Conspecific aggressiveness often increases after social isolation for species that are not entirely solitary, and this increased aggression could also be reversed after resocialization. However, literature on this aggression plasticity refers to either permanently social or low-level subsocial species in invertebrates. Examinations of conspecific aggressiveness reversibility in high-level subsocial invertebrates, in which offspring cohabitate with parents for a certain period of time after sexual maturation, would enhance the understanding of the role of conspecific-aggression plasticity in social evolution. Here, using the lactating spider Toxeus magnus, which exhibits extremely high-level subsociality, we assessed three questions. (1) Is its conspecific aggression affected by social living and/or kinship? The results indicated that conspecific aggression increased after social isolation, while kinship did not affect aggressiveness. (2) Could the social-isolation-induced higher aggression be reversed after resocialization? The results showed that the increased aggression of the spiders could be reversed 3 days after resocialization. (3) What is the proximate mechanism that caused the aggression reversibility by resocialization? A simulated resocialization experiment in which single spider was provided with mirrors demonstrated that the visual cues of conspecifics alone could reverse the aggression after 6 days. These results indicate that the high-level subsocial invertebrate showed aggressiveness reversibility without chemical cues. This is more similar to permanently social species rather than to low-level subsocial species, and visual cues could be vital to induce aggression change. These results suggest that conspecific-aggression reversibility might play a key role in social evolution and may functionally enhance species' adaptiveness under variable conditions.

A light-responsive molecular switch based on cucurbit[7]uril and 1,1'-bis(benzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium dibromide displaying white light emission.

By using 1H NMR, ESI-MS and UV spectra, a novel light-responsive molecular switch constructed using 1,1'-bis(benzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium (12+) and cucurbit[7]uril (Q[7]) is demonstrated. The E- to Z-isomerization of the double bond in 12+ results in the transition of the switching states from the 1 : 2 complex E-12+@Q[7]2 to the stable 1 : 1 complex Z-12+@Q[7]. In particular, both the 1 : 2 complex and the 1 : 1 complex can emit cold white fluorescence under UV light.

An inclusion complex of cucurbit[7]uril with benzimidazolyl benzyl viologen exhibits fluorescence and photochromic properties.

In order to investigate the photochromic mechanism of photochromic materials based on supramolecular host-guest systems, we designed and synthesized a unique viologen derivative (benzimidazolyl benzyl viologen, guest 1·Cl3), which does not contain oxygen atoms. The binding interaction of guest 13+ with host cucurbit[7]uril (Q[7]) was investigated by various techniques. The obtained supramolecular host-guest complex 13+@Q[7] exhibits interesting fluorescence emission and reversible photochromism. The ESR and XPS experimental data suggest that the photochromic process of the complex 13+@Q[7] comes from the electron transfer from the carbonyl O atoms of the host Q[7] to the bipyridinium N atoms of the guest 13+.

Programmable DNA Framework Sensors for In Situ Cell-Surface pH Analysis.

The availability of strategies for developing sensors with a defined responsiveness as well as the ability to working in a biological environment is critical to the fields of bioanalysis, nanomedicine, and nanorobotics. Herein, we developed programmable pH sensors by employing a tetrahedral DNA framework (TDF) as a robust structural skeleton for the sensors in biological working scenes and DNA i-motif structures as proton-recognition probes. The sensors' response midpoint and dynamic range can be fine-tuned by deliberately altering the i-motif's sequence composition or by combining different sensors, affording pH response windows that are consecutively distributed in the biologically relevant pH range of 5.0-7.5. This controllable tunability was successfully employed for in situ cell-surface pH analysis after anchoring the i-motif-TDF nanosensor on the cell surface via a two-step anchoring strategy, providing a useful platform for the diagnostics of diseases associated with extracellular pH variations.

Marker controlled superpixel nuclei segmentation and automatic counting on immunohistochemistry staining images.

MOTIVATION: For the diagnosis of cancer, manually counting nuclei on massive histopathological images is tedious and the counting results might vary due to the subjective nature of the operation. RESULTS: This paper presents a new segmentation and counting method for nuclei, which can automatically provide nucleus counting results. This method segments nuclei with detected nuclei seed markers through a modified simple one-pass superpixel segmentation method. Rather than using a single pixel as a seed, we created a superseed for each nucleus to involve more information for improved segmentation results. Nucleus pixels are extracted by a newly proposed fusing method to reduce stain variations and preserve nucleus contour information. By evaluating segmentation results, the proposed method was compared to five existing methods on a dataset with 52 immunohistochemically (IHC) stained images. Our proposed method produced the highest mean F1-score of 0.668. By evaluating the counting results, another dataset with more than 30 000 IHC stained nuclei in 88 images were prepared. The correlation between automatically generated nucleus counting results and manual nucleus counting results was up to R2 = 0.901 (P < 0.001). By evaluating segmentation results of proposed method-based tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score of 0.331 ± 0.006. AVAILABILITY AND IMPLEMENTATION: The proposed method has been implemented as a plugin tool in ImageJ and the source code can be freely downloaded. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Daily Microaggressions and Related Distress among Black Women Living with HIV during the Onset of the COVID-19 Pandemic and Black Lives Matter Protests.

Black women living with HIV (BWLWH) in the U.S. face microaggressions based on race, gender, HIV-status, and sexual orientation. We examined changes in daily microaggressions and related distress among 143 BWLWH in Miami, FL. Microaggression-related distress increased from 52% at baseline/October, peaked at 70% during the holidays (November/December), declined to 55% in March when COVID-19 social distancing began, and peaked to 83% in June/July 2020 during widespread Black Lives Matters protests. Baseline viral suppression was associated with lower microaggressions across the 9-months. Microaggression-related distress may change due to social context and research is needed on microaggressions and viral load overtime.

RESUMEN: Las mujeres de raza negra que viven con el VIH (MNVV) en los EE. UU. enfrentan microagresiones basadas en la raza, el género, el estado serológico del VIH y la orientación sexual. Examinamos los cambios en las microagresiones diarias y el estrés relacionado entre 143 MNVV en Miami, FL. El estrés relacionado con la microagresión aumentó del 52% en la línea de base/octubre, alcanzó un máximo del 70% durante las vacaciones (noviembre/diciembre), disminuyó al 55% en marzo cuando comenzó el distanciamiento social por el COVID-19 y alcanzó un máximo del 83% en junio/julio de 2020 durante las protestas generalizadas de Black Lives Matters. La supresión viral inicial se asoció con menores microagresiones durante los 9 meses. El estrés relacionada con la microagresión puede cambiar debido al contexto social y se necesitan investigaciones sobre las microagresiones y la carga viral con el tiempo.

An electrogenerated chemiluminescence aptasensor for lysozyme based on the interaction between Ru(bpy)3 2+ and cucurbit[8]uril.

Strong anodic Ru(bpy)3 2+ electrogenerated chemiluminescence (ECL) was obtained at a cucurbil[8]uril (CB[8]) modified electrode in neutral conditions without the need of an additional coreactant. An ECL aptasensor was fabricated based on the strong ECL emission as well as the host-guest interaction between DNA and CB[8]. Firstly, amino group-terminated complementary DNA (DNA-NH2 ) was firmly immobilized on CB[8]/glass carbon electrode, which could further increase ECL intensity. Then, a ferrocene group-terminated lysozyme aptamer (Fc-DNA) was hybridized with complementary DNA. The inhibiting effect of ferrocene on Ru(bpy)3 2+ ECL resulted in the apparent decrease in ECL signal. When the modified electrode was incubated in lysozyme, specific binding between lysozyme and its aptamer could release the ferrocene group from the electrode surface, and the ECL emission was recovered. As a result, an 'on-off-on' mode ECL aptasensor for lysozyme was fabricated. In the range 0.14-140 pg ml-1 , the increased ECL intensities exhibited excellent linearity with the logarithm of lysozyme concentrations, and the detection limit was calculated as 0.093 pg ml-1 (3σ). The proposed ECL aptasensor exhibited satisfactory analytical performance, revealing the potential application of CB[n]s in an ECL sensing field.

[Preparation and Evaluation of Intranasal in situ Gel of Bupleuri Radix Volatile Oil and Baicalin].

OBJECTIVE: To prepare and evaluate a new formulation of thermosensitive and ion-sensitive in situ gel for nasal administration, using the volatile oil of Bupleuri radix and baicalin, the effective component extracted from Scutellariae radix . METHODS: Formulation of in situ nasal gel of Bupleuri radix volatile oil and baicalin was prepared by using poloxamer 407 and deacetylated gellan gum as the gel base, 10% pharmasolve and 2% polysorbate 80 as the solubilizer, and 0.8% triethanolamine as the pH regulator. The physical appearance, phase transition temperature, and baicalin release performance of the prepared gel were examined. The pharmacodynamic evaluation was done with the rat fever model developed with dry yeast and the mouse auricle swelling inflammation model. RESULTS: The phase transition temperature of the gel was optimized to be 36 ℃. The release of baicalin from the gel showed obvious features of sustained release, which accorded well the zero-order kinetics equation. The results of experiments with the rat dry yeast fever model and the mouse xylene auricle swelling inflammation model showed that the gel had significant antipyretic and anti-inflammatory effects that were significantly better than those of the groups treated with the blank gel base and the Bupleuri radix and Scutellariae radix granule. Results from the cilia toxicity test showed that the gel did not have obvious toxic effect on toad palate mucosal cilia. CONCLUSION: The in situ nasal gel of Bupleuri radix volatile oil and baicalin prepared in the study had a rapid onset time, high efficiency, and prolonged release of active ingredients, thus showing promises for further applicational development.

Fast Affinity Induced Reaction Sensor Based on a Fluorogenic Click Reaction for Quick Detection of Protein Biomarkers.

Despite numerous biosensors currently available, the routine biomarker detection still largely relies on traditional ELISA and Western blot. Those standard techniques are labor intensive and time-consuming. Herein we introduce a fast affinity induced reaction sensor (FAIRS) that overcomes a few limitations of traditional and emerging biosensors. FAIRS is a general, one-step method and is naturally specific in detection. FAIRS probes are composed of a sandwich ELISA antibody pair that is conjugated with two fluorogenic click chemicals. This technology leverages significant differences of antibody affinity and chemical reaction rate, which are characterized to guide probe design. The stability, sensitivity, detection range, and response time are fully characterized. Application to IL-6 detection using blood serum and cell culture medium demonstrates that FAIRS can quantify IL-6 with high sensitivity in one step. With the unique features, FAIRS probes may find broad applications in medical sciences and clinical diagnostics, where quick detection of biomarkers is demanded.

Disadvantages for non-Hispanic whites in gastric carcinoma survival in Florida.

PURPOSE: The prognosis for gastric carcinoma (GC) remains challenging with less than 35% of patients surviving 5 years. GC survival varies greatly by anatomical site, cardia and non-cardia. However, these important differences have not been thoroughly studied in relation to the increasing diversity in US populations such as Florida. In this study we examined, for the first time, the effect of race-ethnicity on risk of death from GC controlling for potential risk factors separately for cardia and non-cardia GCs. METHODS: Data on GCs diagnosed in Florida from 2005-2016 were obtained from the statewide cancer registry. Age-standardized GC-specific 5-year survival was computed by anatomical site and race-ethnicity. In addition, a competing risk analysis was performed to assess prognostic factors and to estimate subdistribution hazard ratios of death from GC. RESULTS: Whites had high proportions of cardia GC (43.9%) compared to all racial/ethnic minorities (10.9%, 19.6%, and 13.8% in Blacks, Hispanics, and Asians, respectively; p < .0001). Among 12,302 cases included, there were 7534 deaths from GC and 1179 from other causes. Age standardized GC-specific 5-year survival was significantly lower for Whites (28.0%) compared to Blacks (31.6%), Hispanics (37.6%), and Asians, (39.6%) and significantly lower for cardia GC (25.0%, 95% CI 23.4-26.6) compared to non-cardia GC (37.0%, 95% CI 35.5-38.4). Multivariable competing risk analysis in patients with non-cardia GC showed that Asians (sHR: 0.64, 95% CI 0.51-0.80), Hispanics (sHR 0.71, 95% CI 0.64-0.78), and Blacks (sHR 0.83, 95% CI 0.75-0.92) all had lower risks of death from GC compared to Whites. In patients with cardia GC, only Hispanics had statistically significant lower risk of death from GC than Whites (sHR 0.84, 95% CI 0.74-0.95, p = 0.005). CONCLUSIONS: The study of racial/ethnic survival disparities in patients with GC in Florida reveals Whites as the most disadvantaged group. Whites are more afflicted by cardia GC, which is associated with higher risk of death than non-cardia GC. However, even within non-cardia GC, Whites had higher risk of death than the other racial-ethnic groups. Commonly assessed survival determinants do not adequately explain these unusual disparities; thus, further investigation is warranted.

Symmetrical-Tetramethyl-Cucurbit[6]uril-Driven Movement of Cucurbit[7]uril Gives Rise to Heterowheel [4]Pseudorotaxanes.

Two novel heterowheel [4]pseudorotaxanes consisting of cucurbit[7]uril (Q[7]) and symmetrical-tetramethyl-cucurbit[6]uril (TMeQ[6]) were constructed via the multirecognition mechanism, in which Q[7] can rotate freely around the horizontal axis, while TMeQ[6] cannot. In the construction process, due to strong repulsive forces between carbonyl portals of two neighboring wheels, the dethreading and movement of the wheels along the axle was observed. The dissociation of the [4]pseudorotaxanes was also discussed.

Selective Recovery and Detection of Gold with Cucurbit[n]urils (n = 5-7).

Environmentally benign methods for gold recovery and detection are highly desirable for a sustainable future. Herein, we demonstrate a selective recovery and detection strategy of gold with cucurbit[n]urils (Q[n = 5-7]) by means of outer-surface interactions. Tetrachloroaurate anion ([AuCl4]-) is able to be rapidly precipitated with Q[n] in forms of supramolecular adducts. X-ray crystallography of four Q[n = 5-7]·[AuCl4]- complexes reveal that strong outer-surface interactions between Q[n = 5-7] and [AuCl4]- are the major driving force for the formation of Q[n = 5-7]·[AuCl4]- complexes. Impressively, each Q[6] macrocycle is surrounded by 12 [AuCl4]- anions. Each of these 12 [AuCl4]- anions is connected to four adjacent [AuCl4]- anions, leading to the formation of a three-dimensional supramolecular framework with tubular channels. In addition, we found an interesting inclusion complex [Au(OH2)4]3+⊂Q[7] in the Q[7]·[AuCl4]- complex, which is the first example of hydrated metal cation encapsulated inside the cavity of Q[n]. Spectroscopic data suggest that Q[n = 5-7] possess a high affinity and selectivity for [AuCl4]- even in the presence of other transition-metal ions. Q[n] modified electrodes are found to be an effective material for the detection of trace gold in dilute solutions.