bluuebunny/crossref_metadata_2025 huggingface dataset:
A Membrane‐Targeted Photosensitizer Prevents Drug Resistance and Induces Immune Response in Treating Candidiasis
Authors: Wu Ming‐Yu , Xu Xiaoyu , Hu Rui , Chen Qingrong , Chen Luojia , Yuan Yuncong , Li Jie , Zhou Li , Feng Shun , Wang Lianrong , Chen Shi , Gu Meijia
Published: October 2023

Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP‐QY has a high molar absorption coefficient and an excellent ability to generate 1O2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP‐QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP‐QY‐mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole‐resistant strains. Moreover, TBTCP‐QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.
Enhanced Chemo‐Immunotherapy Strategy Utilizing Injectable Thermosensitive Hydrogel for The Treatment of Diffuse Peritoneal Metastasis in Advanced Colorectal Cancer
Authors: Wang Meng , Hu DanRong , Yang Yun , Shi Kun , Li JiaNan , Liu QingYa , Li YiCong , Li Ran , Pan Meng , Mo Dong , Chen Wen , Li XiCheng , Qian ZhiYong
Published: October 2023

Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first‐line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti‐tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.
Nanomaterials‐Based Bioinspired Next Generation Wearable Sensors: A State‐of‐the‐Art Review
Authors: Sengupta Debarun , Kottapalli Ajay Giri Prakash
Published: October 2023

With a constantly growing percentage of the population having access to high‐quality healthcare facilities, preventable pathogenic illnesses have been nearly eradicated in the developed parts of the world, which has led to a significant rise in the average human life expectancy over the last few decades. In such a highly developed world, age‐related illnesses will lead to an immense burden on healthcare providers. Remote health monitoring enabled by wearable sensors will play a significant role in the growth and evolution of Health 3.0 by providing intimate and valuable information to healthcare providers regarding the progression of disease in patients with critical life‐altering conditions. Especially, in the case of people suffering from neurodegenerative disorders, inexpensive and user‐friendly wearable sensors can enable physiotherapists monitor real‐time physiological parameters to design patient‐specific treatment plans. This review provides a comprehensive overview of the recent advances and emerging trends at the convergence of biomimicry and nanomaterial sensors, with a specific focus on wearable skin‐inspired mechanical sensors for applications in IoT‐enabled human physiological parameters monitoring. Skin‐inspired wearable mechanical sensors with relevance to the most common types of sensing mechanisms including piezoresistive, piezocapacitive, and triboelectric sensing are discussed along with their current challenges and possible future opportunities.
New insights into protein–polysaccharide complex coacervation: Dynamics, molecular parameters, and applications
Authors: Zheng Jiabao , Van der Meeren Paul , Sun Weizheng
Published: October 2023

For more than a decade, the discovery of liquid–liquid phase separation within living organisms has prompted colloid scientists to understand the connection between coacervate functionality, phase behavior, and dynamics at a multidisciplinary level. Although the protein–polysaccharide was the first system in which the coacervation phenomenon was discovered and is widely used in food systems, the phase state and relaxation dynamics of protein–polysaccharide complex coacervates (PPCC) have rarely been discussed previously. Consequently, this review aims to unravel the relationship between PPCC dynamics, thermodynamics, molecular architecture, applications, and phase states in past studies. Looking ahead, solving the way molecular architecture spreads to macro‐functionality, that is, establishing the relationship between molecular architecture–dynamics–application, will catalyze novel advancements in PPCC research within the field of foods and biomaterials.
Macronutrient composition of milk from captive southern pig‐tailed macaques (Macaca nemestrina)
Authors: Glick Virginia J. , Power Michael L.
Published: October 2023

Milk composition is a fundamental aspect of mammalian reproduction. Differences in milk composition between species may reflect phylogeny, dietary ecology, lactation strategy, and infant growth patterns, but may also vary within a species due to maternal body condition. This study presents the first published data on milk macronutrient composition of southern pig‐tailed macaques (Macaca nemestrina) and compares the results with data on two other Cercopithecine species. Milk samples were obtained from five dams at 10‐ and 14‐weeks postparturition. Macronutrient composition was determined at the Smithsonian's National Zoo and Conservation Biology Institute using proven methods developed over 30 years. On average (±SEM), the milk contained 83.9 ± 0.4% water, 6.7 ± 0.4% fat, 7.6 ± 0.1% sugar, 1.8 ± 0.1% protein, and 0.22 ± 0.01% mineral content. The Ca:P ratio was 1.8; concentrations of Ca and protein were correlated. Mean gross energy was 1.02 ± 0.03 kcal/g with most of the energy coming from fat (59.6 ± 1.5%), followed by sugar (29.9 ± 1.4%) and protein (10.5 ± 0.5%). The milks at 14 weeks of infant age were higher in energy than the milks at 10 weeks, with an increase in energy from fat (p = 0.005) and decrease in energy from sugar (p = 0.018). The energy from protein did not change (p = 0.272). Compared to captive rhesus macaque (Macaca mulatta) and olive baboon (Papio anubis) milk assayed by identical methods, captive pig‐tailed macaque milk was higher in energy, but after accounting for the higher milk energy there was no difference in the proportions of milk energy from protein, fat, and sugar. The captive pig‐tailed dams were significantly heavier than reported values for wild pig‐tailed macaques, suggesting high body condition. High body condition in captive Cercopithecines appears to result in milk higher in energy, with more energy coming from fat and less from sugar. However, variation in the proportion of milk energy from protein in captive Cercopithecine milks appears relatively constrained.
Supracluster Assembly of Archimedean Cages with 72 Hydrogen Bonds for the Aldol Addition Reaction
Authors: Liu Ya‐Jie , Su Hai‐Feng , Sun Yi‐Fan , Wang San‐Tai , Zhang Cheng‐Yang , Fang Wei‐Hui , Zhang Jian
Published: October 2023

Clusters that can be experimentally precisely characterized and theoretically accurately calculated are essential to understanding the relationship between material structure and function. Here, we propose the concept of “supraclusters”, which aim to connect “supramolecules” and “suprananoparticles” as well as reveal the unique assembly behavior of “supraclusters” with nanoparticle size at the molecular level. The implementation of supraclusters is full of challenges due to the difficulty in satisfying the ordered connectivity of clusters due to their abundant and dispersed hydrogen bonding sites. By solvothermal synthesis under a high catechol (H2CATs) content, we successfully isolated a series of triangular {Al6M3} cluster compounds possessing brucite‐like structural features. Interestingly, eight {Al6M3} clusters form 72‐fold strong hydrogen bonding truncatedhexahedron Archimedean {Al6M3}8 supracluster cage (abbreviated as H‐tcu). Surprisingly, the solution stability of the H‐tcu was further proved by electrospray ionization mass spectrometry (ESI‐MS) characterization. Therefore, it is not difficult to explain the reason for assembly of H‐tcu into edge‐directed and vertex‐directed isomers. These porous supraclusters can be obtained by scale‐up synthesis and exhibit a noticeable catalysis effect towards the condensation of acetone and p‐nitrobenzaldehyde. As an intermediate state of supramolecule and suprananoparticle, the supracluster assembly can enrich the cluster chemistry and bring new structural types.
Exploration of Chemical Diversity in Intercellular Quorum Sensing Signalling Systems in Prokaryotes
Authors: Jonkergouw Christopher , Savola Pihla , Osmekhina Ekaterina , van Strien Joeri , Batys Piotr , Linder Markus B.
Published: October 2023

Quorum sensing (QS) serves as a vital means of intercellular signalling in a variety of prokaryotes, which enables single cells to act in multicellular configurations. The potential to control community‐wide responses has also sparked numerous recent biotechnological innovations. However, our capacity to utilize intercellular communication is hindered due to a scarcity of complementary signalling systems and a restricted comprehension of interconnections between these systems caused by variations in their dynamic range. In this study, we utilize uniform manifold approximation and projection and extended‐connectivity fingerprints to explore the available chemical space of QS signalling molecules. We investigate and experimentally characterize a set of closely related QS signalling ligands, consisting of N‐acyl homoserine lactones and the aryl homoserine lactone p‐coumaroyl, as well as a set of more widely diverging QS ligands, consisting of photopyrones, dialkylresorcinols, 3,5‐dimethylpyrazin‐2‐ol and autoinducer‐2, and define their performance. We report on a set of six signal‐ and promoter‐orthogonal intercellular QS signalling systems, significantly expanding the toolkit for engineering community‐wide behaviour. Furthermore, we demonstrate that ligand diversity can serve as a statistically significant tool to predict much more complicated ligand‐receptor interactions. This approach highlights the potential of dimensionality reduction to explore chemical diversity in microbial dynamics.
Inspecting the anti‐tuberculosis, antimicrobial, and anti‐inflammatory efficiency of newly synthesized Co (II), Ni (II), Cu (II) and Zn (II) complexes of hydrazone ligands: Characterization and computational studies
Authors: Kumar Binesh , Devi Jai , Dubey Amit , Tufail Aisha , Arora Tanisha
Published: October 2023

In the current research, we have reported the synthesis of eight new Co (II), Ni (II), Cu (II) and Zn (II) metal complexes from aldehyde derivatives and 3,5‐dichlorobenzohydrazide‐based hydrazone ligands (HL1HL2) in an effort to identify a combating agent for infectious ailments. Further, numerous physical and spectral studies were carried out to characterize the compounds and the spectral analysis indicates octahedral geometry around central metal ions in the complexes. The anti‐tuberculosis (TB) activity indicates that the complexes (3–10) are highly active for TB ailment and Zn (II) complex (10) has double efficacy to control the TB dysfunction with MIC value (0.006 ± 0.001 μmol/mL) in comparison with streptomycin (0.010 ± 0.001 μmol/mL) while complexes (6), (8), and (9) are comparably active (0.013 ± 0.001–0.014 ± 0.002 μmol/mL MIC) to inhibit the TB malformation. The antimicrobial investigation affirmed that zinc complex (10) has higher efficacy to control the microbial ailments with 0.0064–0.0129 μmol/mL MIC value. The anti‐inflammatory activity also revealed that the complexes (3–10) are highly active for inflammation and the Zn complex (10) has comparable IC50 value (7.58 ± 0.02 μM) with diclofenac sodium to hinder the inflammation diseases. Furthermore, the computational techniques such as molecular docking, density functional theory, molecular electrostatic potential and absorption, distribution, metabolism, excretion and toxicity studies were conducted against highly active ligand (2) and its complexes (7–10) which advocates that the biological activity of the hydrazone ligands was increased on complexation and the complex (10) has higher potency to control infectious ailments that behave as effective infection inhibitor without any toxic effects. Hence, the present research gives a new insight for in vivo investigation.
An online sequential training package to teach citation formatting: Within and across participant analyses
Authors: Guinness Kendra E. , Parry‐Cruwys Diana , Atkinson Ryan S. , MacDonald Jacquelyn M.
Published: October 2023

When teaching complex skills in higher education settings, different individuals may require different levels of instruction to achieve mastery. The current study replicated and extended Parry‐Cruwys et al. (2022) by evaluating the effects of an online sequential training package on accuracy of APA citations with graduate students in behavior analysis. The intervention consisted of (a) a checklist of APA citation criteria, (b) online modules based on principles of behavioral instruction, and (c) email feedback. All components were delivered remotely through course management software and introduced sequentially such that participants experienced only the intervention necessary to meet the mastery criterion. Of 13 participants, seven required the checklist only, two required the checklist and online modules, and four required the checklist, modules, and feedback. An across participant acquisition analysis revealed additional response patterns that could inform the refinement of future training materials. This evaluation demonstrates an efficient mechanism for assessing skill acquisition at the level of the individual learner in the context of higher education.
What qualities do lifelong friends and good leaders have in common?
Authors: Hodges Dawn Z.
Published: October 2023

Earlier this summer I traveled to Lake Athens, Texas, just outside Dallas, for another gathering of five high school friends. We graduated high school together and set about earning college degrees, building careers, marrying, and raising children. We kept up with each other here and there, but for the most part, we lived separate lives. With the advent of Facebook, we all reconnected. In 2015, with careers firmly established and children raised and gone, we decided to have our own little high school reunion at a lake house belonging to one of the friends. We’ve met up six times since then. We also did weekly Zoom calls during the pandemic and set up a group text. We communicate with each other often.
Did court dismiss Title IX erroneous outcome claim?
Authors: Lyerly Eric
Published: October 2023

John Doe was a Stonehill College football player. While at the college, John Doe developed a friendship with a female student, Jane Roe. On three separate occasions, John Doe and Jane Roe engaged in consensual sexual contact.
Implantation depth of balloon‐expandable transcatheter heart valves and risks for permanent pacemaker implantation and midterm adverse events
Authors: Pellegrini Costanza , Freißmuth Markus , Rheude Tobias , Graas David , Mayr N. Patrick , Syryca Finn , Alvarez‐Covarrubias Hector A. , Fetcu Andrei , Hübner Judith , Lennerz Carsten , Schunkert Heribert , Kastrati Adnan , Xhepa Erion , Joner Michael
Published: October 2023

Background

Permanent pacemaker implantation (PPI) remains a relevant complication after transcatheter aortic valve implantation (TAVI) and its impact on outcome remains controversial.

Aims

This study aimed to analyze the effects of implantation depth on PPI at 30 days and assess its impact on outcome with the balloon‐expandable Sapien 3 (S3) prosthesis.

Methods

Between 2014 and 2018, 849 patients without previous pacemaker undergoing transfemoral TAVI with the S3 were included. Prosthesis implantation depth was measured and divided into Quintiles. An ordinal logistic regression was used to assess its association with PPI, while a multivariate logistic regression was performed to identify predictors of PPI. Survival analyses were performed with the Kaplan−Meier method and a multivariable Cox regression was performed to ascertain the impact of PPI on mortality.

Results

Overall, incidence of PPI at 30 days was 9.7%. Implantation depth decreased consistently from a median of 6.7 mm [5.55−8.00] in 2014 to 2.7 mm [2.30−3.50] in 2018 (p < 0.001). When considering Quintiles of implantation depth, incidence of PPI was significantly higher in upper Quintiles and risk for PPI was significantly lower for the 1. Quintile compared to the 5. Quintile (OR: 0.34, 95% CI: [0.16−0.73]; p = 0.003). In the adjusted multivariable logistic regression implantation depth persisted ad independent predictor of PPI at 30 days. Patients requiring PPI at 30 days displayed significantly higher mortality at 4 years compared to patients without PPI (49.5% vs. 40.0%; log‐rank = 0.022). In a multivariate analysis, increased logistic EuroScore, diabetes mellitus, and history of atrial fibrillation, were independent predictors of all‐cause mortality at 2 years.

Conclusions

Higher prosthesis implantation relative to the virtual aortic annulus was significantly associated with reduced risk for PPI at 30 days. Patients with PPI at 30 days exhibited higher mortality during follow‐up, however, only logistic EuroScore, diabetes mellitus, and history of atrial fibrillation were identified as independent predictors of mortality at 2 years.
Pressure‐Assisted Synthesis of Highly Crystalline 1T′′‐LixMoS2
Authors: Schwarzmüller Stefan , Wurst Klaus , Heymann Gunter , Huppertz Hubert
Published: October 2023

LixMoS2 is not only a lithium battery material, but is also an important precursor for the synthesis of MoS2 nanomaterials. Current syntheses of MoS2, such as in n‐butyllithium/LiBH4 or electrochemically, are not satisfying in terms of defined stoichiometry and crystallinity, so an accurate experimental crystal structure determination of this important and widely used material has been long awaited. A high‐pressure/high‐temperature synthesis yielded highly crystalline 1T′′‐LixMoS2 (x=1, 1.333). 1T′′‐LiMoS2 crystallizes in the space group P
with a=6.2482(3) Å, b=6.6336(3) Å, c=6.7480(3) Å, α=119.321(2)°, β=90.010(2)° and γ=90.077(2)°. The arrangement of Mo atoms within the b‐c‐plane confirmed a predicted Peierls distortion. A similar atom distribution pattern to that of Mo is also observed for the lithium atoms. Calculation of bond valence site energies gave an activation barrier of 1.244 eV for 2D lithium‐ion migration. For x=1.333, a phase‐pure synthesis was achieved.
Cryoballoon ablation for atrial fibrillation in patients with heart failure and reduced left ventricular ejection fraction: A systematic review and meta‐analysis
Authors: Taha Amira M. , Hendi Nada I. , Elwekel Ahmed B. , Atia Ahmed , Taha Nouran A. , Shrestha Abhigan B. , Elbanna Mohamed
Published: October 2023

The coexistence of atrial fibrillation (AF) with heart failure (HF) is prevalent, leading to severe complications. This review aimed to investigate the success rate and efficacy of cryoballoon ablation (CBA) by measuring the improvement in the New York Heart Association (NYHA) classification and the effect on the left ventricular systolic function in patients with AF accompanied by heart failure with reduced ejection fraction (HFrEF). Electronic databases search included PubMed, Web of Science, and Scopus in January 2023. Outcomes addressed the following: left ventricular ejection fraction (LVEF) improvement, AF recurrence, NYHA classification improvement, and mortality. STATA 17.0 software was used for data analysis. The effect size for the studies was a standard mean difference (SMD) with a 95% confidence interval (CI) for outcomes. Proportion analysis with 95% CI was used for freedom from early AF and AF after 2 years and all‐cause death. We included six studies, including 1699 HF patients with 365 HFrEF patients. The SMD of postoperative LVEF compared to preoperative LVEF in HFrEF was 0.99 ([95% CI: 0.60, 1.39], p = .00), and for NYHA was −1.12 ([95% CI: −1.36, −0.87], p = .00). The analysis results in HFrEF patients for freedom from AF after 1 year was 65% ([95% CI: 0.55, 0.75], and after 2 years was 39% ([95% CI: 0.10, 0.67]). Proportional analysis was conducted for all‐cause death, resulting in 3% mortality ([95% CI: −0.01, 0.07]). Cryoablation of AF accompanied by HFrEF appeared safe as it reduced AF recurrence and enhanced clinical outcomes.
Post‐Synthetic Modification of Triplex‐Forming Oligonucleotides Containing 2‐Aminoethyl‐2′‐Deoxynebularine Derivatives
Authors: Notomi Ryotaro , Sasaki Shigeki , Taniguchi Yosuke
Published: October 2023

This article describes the detailed synthetic protocol for the preparation of oligonucleotides containing 2‐guanidinoethyl‐2′‐deoxynebularine and 2‐ureidoethyl‐2′‐deoxynebularine nucleoside derivatives. These derivatives are obtained by a post‐synthetic modification of triplex‐forming oligonucleotides (TFOs) containing 2‐aminoethyl‐2′‐deoxynebularine, which is useful for forming stable triplex DNA with duplex DNA sequences containing 5mCG and CG interrupting sites. The hydroxyl groups of the sugar moiety of commercially available 2′‐deoxyguanosine are acetyl‐protected, the 6‐position is chlorinated and reduced to give a 2‐substituted nebularine derivative, and then the sugar moiety is deprotected. The hydroxyl groups of the sugar moiety are silyl‐protected and the amino group at the 2‐position is iodinated before being coupled with diethyl malonate. The ethyl ester is reduced and the resulting alcohol converted to an amino group for protection. The compound is then converted to a phosphoramidite unit and incorporated into a TFO. Subsequent modification of the aminoethyl group on the TFO completes the synthesis of the oligonucleotides containing 2‐guanidinoethyl‐2′‐deoxynebularine and 2‐ureidoethyl‐2′‐deoxynebularine. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Preparation of the phosphoramidite unit of the 2‐aminoethyl‐2′‐deoxynebularine derivative (14)

Basic Protocol 2: Post‐synthetic modification of oligonucleotides containing 2‐aminoethyl‐2′‐deoxynebularine derivatives

Basic Protocol 3: Determination of the triplex‐forming ability of oligonucleotides containing 2‐aminoethyl‐2′‐deoxynebularine derivatives
Correlations between different protein species of oral rinse MMP‐8 and patient‐related factors
Authors: Leppilahti Jussi M. , Tervahartiala Taina , Kautiainen Hannu , Räisänen Ismo , Ahonen Minna‐Maija , Uitto Veli‐Jukka , Sorsa Timo , Mäntylä Päivi
Published: October 2023

Objectives

The aim of this study is to examine correlations between different oral rinse matrix metalloproteinase (MMP)‐8 protein species in western blot (WB) analysis, quantitative MMP‐8 measurements, and patient‐related factors. Elevated activated MMP‐8 (aMMP‐8) associate with periodontitis and a diagnostic point‐of‐care technology has been developed based on aMMP‐8. In WB, different MMP‐8 protein species can be analyzed. Relative abundancy of fragmented 20–25 kDa forms in WB has been associated with and reflects MMP‐8 activation and related fragmentation and elevated quantitative aMMP‐8 measurements.

Material and Methods

A random sample of 192 participants from a periodontal disease screening study was used for this study. Oral rinse samples for biomarker analyses were collected before clinical periodontal examinations. aMMP‐8 immunofluorometric (IFMA) and WB analysis (utilizing the same monoclonal antibody, 8708), polymorphonuclear leukocyte (PMN) elastase activity test and tissue inhibitor of metalloproteinases (TIMP)‐1 ELISA levels were performed from the oral rinse samples. Distinct MMP‐8 protein species were differentiated in the WB analysis. Principal component (PC) analysis was conducted to explore correlation patterns between the different species. Adjusted correlation analysis between the extracted PCs of WB and aMMP‐8 IFMA levels and multilevel regression analysis were conducted to explore if the other periodontal disease‐related biomarkers and clinical surrogate measures and patient‐related factors are co‐variating with the extracted components.

Results

Distinct correlation patterns between the MMP‐8 protein species were observed. The first four PCs explained 89% of the whole variance in PC analysis. Statistically significant correlation (p < 0.05) were observed as follows: PC1 positively with 21 kDa (r = .69) and 25 kDa fragments (r = .55) and negatively with 150 kDa complexes (r = −.46). PC2 correlated with 45 (r = .70) and 55 kDa (r = .65) activated forms, PC3 with 70–80 kDa latent proforms (r = .63) and 90–100 kDa complexes (r = .67), and PC4 with 35 kDa fragments (r = .81). There were significant correlations between quantitative (IFMA) aMMP‐8 measurements and PC1 (p < 0.001), PC2 (<0.05) and PC3 (<0.05) but not with PC4. In multilevel regression models age, PMN elastase activity, TIMP‐1 levels, and a number of 4–5 mm periodontal pockets were associated with PC1, nonsmoking with PC2, age and PMN elastase activity with PC3, and age and smoking with PC4.

Conclusions

Relative abundancy of fragmented 21–25 kDa protein species was correlated with the quantitative aMMP‐8 (IFMA) measurements, which is in line with previous results. Different patient‐related factors (smoking, age, proteolytic activity) may modify the formation of different MMP‐8 protein species in oral rinse samples and may cause variability in quantitative aMMP‐8 measurement.
Parkin regulates IGF2BP3 through ubiquitination in the tumourigenesis of cervical cancer
Authors: Sun Xin , Ye Guiqin , Li Jiuzhou , Shou Huafeng , Bai Gongxun , Zhang Jianbin
Published: October 2023

Background

Insulin‐like growth Factor 2 mRNA‐binding protein 3 (IGF2BP3) is a highly conserved RNA‐binding protein and plays a critical role in regulating posttranscriptional modifications.

Methods

Immunoprecipitation was used to examine the interaction of Parkin and IGF2BP3. Mass spectrometry was performed to identify the ubiquitination sites of IGF2BP3. RNA‐immunoprecipitation was conducted to examine the target genes of IGF2BP3. Xenograft mouse model was constructed to determine the tumorigenesis of IGF2BP3.

Results

IGF2BP3 expression is negatively correlated with Parkin expression in human cervical cancer cells and tissues. Parkin directly interacts with IGF2BP3, and overexpression of Parkin causes the proteasomal degradation of IGF2BP3, while knockdown of PARK2 increases the protein levels of IGF2BP3. Mechanistically, in vivo and in vitro ubiquitination assays demonstrated that Parkin is able to ubiquitinate IGF2BP3. Moreover, the ubiquitination site of IGF2BP3 was identified at K213 in the first KH domain of IGF2BP3. IGF2BP3 mutation results in the loss of its oncogenic function as an m6A reader, resulting in the inactivation of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) signalling pathways. In addition, IGF2BP3 mutation results in the attenuation of Parkin‐mediated mitophagy, indicating its inverse role in regulating Parkin. Consequently, the tumourigenesis of cervical cancer is also inhibited by IGF2BP3 mutation.

Conclusion

IGF2BP3 is ubiquitinated and regulated by the E3 ubiquitin ligase Parkin in human cervical cancer and ubiquitination modification plays an important role in modulating IGF2BP3 function. Thus, understanding the role of IGF2BP3 in tumourigenesis could provide new insights into cervical cancer therapy.
Neighborhood greenspace and neighborhood income associated with white matter grade worsening: Cardiovascular Health Study
Authors: Besser Lilah M. , Lovasi Gina S. , Zambrano Joyce Jimenez , Camacho Simone , Dhanekula Devi , Michael Yvonne L. , Garg Parveen , Hirsch Jana A. , Siscovick David , Hurvitz Philip M. , Biggs Mary L. , Galvin James E. , Bartz Traci M. , Longstreth W. T.
Published: October 2023

INTRODUCTION

We examined whether a combined measure of neighborhood greenspace and neighborhood median income was associated with white matter hyperintensity (WMH) and ventricle size changes.

METHODS

The sample included 1260 cognitively normal ≥ 65‐year‐olds with two magnetic resonance images (MRI; ≈ 5 years apart). WMH and ventricular size were graded from 0 (least) to 9 (most) abnormal (worsening = increase of ≥1 grade from initial to follow‐up MRI scans). The four‐category neighborhood greenspace–income measure was based on median neighborhood greenspace and income values at initial MRI. Multivariable logistic regression tested associations between neighborhood greenspace–income and MRI measures (worsening vs. not).

RESULTS

White matter grade worsening was more likely for those in lower greenspace–lower income neighborhoods than higher greenspace–higher income neighborhoods (odds ratio = 1.73; 95% confidence interval = 1.19–2.51).

DISCUSSION

The combination of lower neighborhood income and lower greenspace may be a risk factor for worsening white matter grade on MRI. However, findings need to be replicated in more diverse cohorts.

HIGHLIGHTS

Population‐based cohort of older adults (≥ 65 years) with greenspace and MRI data

Combined measure of neighborhood greenspace and neighborhood income at initial MRI

MRI outcomes included white matter hyperintensities (WMH) and ventricular size

Longitudinal change in MRI outcomes measured approximately 5 years apart

Worsening WMH over time more likely for lower greenspace‐lower income neighborhoods
Design, synthesis, and in‐silico study of novel triarylethylene analogs with dual anti‐estrogenic and serotonergic activity
Authors: Mostafa Tammy , Albeir Miriam , Wober Jannette , Abadi Ashraf , Salama Ismail , Ahmed Nermin S.
Published: October 2023

Estrogen receptor is an important target in breast cancer. Serotonin receptors (5‐HT2A and 5‐HT2C, in particular) were investigated for a potential role in development and progression of breast cancer. Ligands that interact with estrogenic receptors influence the emotional state of females. Thus, designing selective estrogen receptor modulator (SERM) analogs with potential serotonergic activity is a plausible approach. The dual ligands can augment cytotoxic effect of SERMs, help in both physical and emotional menopausal symptom relief, enhance cognitive function and support bone health. Herein, we report triarylethylene analogs as potential candidates for treatment of breast cancer. Compound 2e showed (ERα relative β‐ galactosidase activity = 0.70), 5‐HT2A (Ki = 0.97 µM), and 5‐HT2C (Ki = 3.86 µM). It was more potent on both MCF‐7 (GI50 = 0.27 µM) and on MDA‐MB‐231 (GI50 = 1.86 µM) compared to tamoxifen (TAM). Compound 4e showed 40 times higher antiproliferative activity on MCF‐7 and 15 times on MDA‐MBA compared to TAM. Compound 4e had higher average potency than TAM on all nine tested cell line panels. Our in‐silico model revealed the binding interactions of compounds 2 and 2e in the three receptors; further structural modifications are suggested to optimize binding to the ERα, 5‐HT2A, and 5‐HT2C.
Plant provenance can influence the impacts of temperature and moisture on intraspecific competition in Pseudoroegneria spicata
Authors: Donnelly Sabina , Akin‐Fajiye Morodoluwa , Fraser Lauchlan H.
Published: October 2023

Warming and changing precipitation can alter the performance of native grasses that are essential to grassland ecosystems. Native grasses may respond to changing climate by phenotypic plasticity or lose their current ranges. Establishing plant species from southern, warmer provenances may reduce the likelihood of biodiversity loss and improve restoration success in cool, northern locations that are undergoing warming. We conducted competition trials for Pseudoroegneria spicata (bluebunch wheatgrass), a native grass commonly found in western North American grasslands, to understand the impact of temperature and moisture on plant–plant interactions. We obtained seeds from three locations along a latitudinal gradient in North America, two in British Columbia (BC), Canada, and one in California, USA. We compared the effects of warming, changing water inputs, and competitor provenance on pairwise competitive interactions among Pseudoroegneria spicata plants grown from seeds obtained from the three locations. We quantified interactions using the relative interaction intensity, which has values from −1 (complete competition) to +1 (complete facilitation). Target plants from northern British Columbia, the location with the coldest summer temperature, were generally more competitively suppressed when competing with plants from California, which had the warmest summer temperature and lowest summer precipitation. Competitive suppression of target plants from northern British Columbia and southern British Columbia was more intense when competitor provenance was more geographically distant from target plant provenance. Finally, plants from northern British Columbia and southern British Columbia were more suppressed at higher temperatures, indicating some local adaptation, while plants from California were not affected by competitors, temperature, or water input. Plants grown from seeds obtained from warm and dry locations appear to be more tolerant to competition at higher temperatures, compared to plants from cooler regions. Native plant diversity and restoration success in grasslands subjected to climate change may be preserved or improved by assisted migration of seeds from warm to cooler but warming locations.
Root‐centric β diversity reveals functional homogeneity while phylogenetic heterogeneity in a subtropical forest
Authors: Luo Wenqi , Wang Youshi , Cahill James F. , Luan Fucheng , Zhong Yonglin , Li Yuanzhi , Li Buhang , Chu Chengjin
Published: October 2023

Root‐centric studies have revealed fast taxonomic turnover across root neighborhoods, but how such turnover is accompanied by changes in species functions and phylogeny (i.e., β diversity) remains largely unknown. As β diversity can reflect the degree of community‐wide biotic homogenization, such information is crucial for better inference of below‐ground assembly rules, community structuring, and ecosystem processes. We collected 2480 root segments from 625 0–30 cm soil profiles in a subtropical forest in China. Root segments were identified into 138 species with DNA‐barcoding with six root morphological and architectural traits measured per species. By using the mean pairwise (Dpw) and mean nearest neighbor distance (Dnn) to quantify species ecological differences, we first tested the non‐random functional and phylogenetic turnover of root neighborhoods that would lend more support to deterministic over stochastic community assembly processes. Additionally, we examined the distance‐decay pattern of β diversity, and finally partitioned β diversity into geographical and environmental components to infer their potential drivers of environmental filtering, dispersal limitation, and biotic interactions. We found that functional turnover was often lower than expected given the taxonomic turnover, whereas phylogenetic turnover was often higher than expected. Phylogenetic Dpw (e.g., interfamily species) turnover exhibited a distance‐decay pattern, likely reflecting limited dispersal or abiotic filtering that leads to the spatial aggregation of specific plant lineages. Conversely, both functional and phylogenetic Dnn (e.g., intrageneric species) exhibited an inverted distance‐decay pattern, likely reflecting strong biotic interactions among spatially and phylogenetically close species leading to phylogenetic and functional divergence. While the spatial distance was generally a better predictor of β diversity than environmental distance, the joint effect of environmental and spatial distance usually overrode their respective pure effects. These findings suggest that root neighborhood functional homogeneity may somewhat increase forest resilience after disturbance by exhibiting an insurance effect. Likewise, root neighborhood phylogenetic heterogeneity may enhance plant fitness by hindering the transmission of host‐specific pathogens through root networks or by promoting interspecific niche complementarity not captured by species functions. Our study highlights the potential role of root‐centric β diversity in mediating community structures and functions largely ignored in previous studies.
Zhenjiang aromatic vinegar prevents the alcohol liver disease in mice via autophagy
Authors: Zhao Yuxuan , Xia Ting , Qiang Xiao , Wang Yongqi , Kang Chaoyan , Meng Yuan , Cheng Yan , Wang Min , Xiao Jianbo
Published: October 2023

Alcoholic liver disease (ALD) is an ignored global issue of public health. It is urgent for searching bioactive foods to prevent ALD. Zhenjiang aromatic vinegar (ZAV) contained antioxidant compounds, including polyphenols, flavonoids, and melanoidins. The mechanism of ZAV on preventing acute liver injury was evaluated in alcohol‐treated mice. Our results showed that ZAV ameliorated morphological damage by hematoxylin and eosin and Oil Red O staining in alcohol‐treated liver. ZAV relieved symptoms of ALD, which presented as decreased serum triacylglycerol, total cholesterol, alanine transaminase, and aspartate aminotransferase levels. In addition, ZAV treatment inhibited hepatic oxidative stress levels by downregulating reactive oxygen species generation, and the oxidative products (malonaldehyde, 4‐hydroxynonenal, and 8‐hydroxydeoxyguanosine), and upregulating catalase, superoxide dismutase, glutathione, and glutathione peroxidase. ZAV further reduced production of tumor necrosis factor‐α and monocyte chemoattractant protein‐1, and elevated levels of interleukin‐4 and transforming growth factor‐β indicating the inhibition of alcohol‐induced inflammation. Furthermore, ZAV treatment increased expression levels of autophagy‐associated proteins in ALD mice by western blot, which participated in anti‐ALD effect of ZAV. These findings demonstrate that ZAV could be an alternative for ALD intervention by regulating oxidative stress and autophagy.
Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation
Authors: Kouranos Vasileios , Khattar Rajdeep S. , Okafor Joseph , Ahmed Raheel , Azzu Alessia , Baksi John Arun , Wechalekar Kshama , Cowie Martin R. , Wells Athol Umfrey , Lüscher Thomas F. , Sharma Rakesh
Published: October 2023

Aims

Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients.

Methods and results

Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and 18F‐flourodeoxyglucose positron emission tomography (FDG‐PET) at baseline. The composite endpoint consisted of all‐cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow‐up of 2.2 years (range: 1 month–11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5‐ and 10‐year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34–4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94–0.98, p < 0.0001) and maximum standardized uptake value of FDG‐PET (HR 1.11, 95% CI 1.04–1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups.

Conclusion

Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes.
Electrodeposited folic acid platinum electrode for rapid detection of human hepatocellular carcinoma cells
Authors: Dhayal Marshal , Srivastava Shubhangi , Jaiswal Juhi
Published: October 2023

Folic acid (FA) was successfully adhered onto the surface of platinum through an electrochemical process without hindering its functional capability to bind with human hepatocellular carcinoma (HepG2) cells. The CV response of FA‐deposited platinum electrode showed distinct oxidation and reduction peaks, which decreased gradually by varying the concentrations of FA. The electrochemically deposited FA/Pt electrode was used to detect HepG2 cells in the electrolyte, and a linear response in DPV peak current was observed with a sensitivity of ∼ 3 nA/cells mL−1 in the range of 5×103 to 25×103 cells mL−1.
Mental workload evaluation model of receiver aircraft pilots based on multiple resource theory
Authors: Pei Huining , Ma Yujie , Li Wenhua , Liu Xinyu , Zhang Chuyi
Published: October 2023

Aerial refueling is an extender of air combat capability that has received widespread attention with the development of the military field, particularly the mental workload of the pilot performing the aerial refueling task, as it is the key to the aerial refueling success rate. Therefore, this study analyzes the behavior of receiver aircraft pilots from rendezvous to the separation phase and constructs a mental workload model to improve the aerial refueling success rate. First, the time‐channel‐action unit network was constructed based on Petri net and multiple resource theory (MRT). Second, the mental workload evaluation model was constructed from three dimensions: conventional resource occupation, additional resource occupation, and time occupation. Finally, a simulated experiment was conducted, and the results showed that the mental workload obtained by the model constructed in this study exhibits a high positive correlation with subjective mental workload, pupil diameter, and blink rate, surpassing the accuracy of the traditional MRT model.
Gender bias in pediatric care: Health professionals' opinions and perceptions
Authors: Carrilero Neus , Pérez‐Jover Virtudes , Guilabert‐Mora Mercedes , García‐Altés Anna
Published: October 2023

Introduction

Gender bias in healthcare is understood as a misconception of the differences between males and females that may generate healthcare disparities and discrimination against one sex. However, is not well known how this implicit bias is manifested in pediatric clinical praxis. Thus, the goal of this study is to explore and analyse the attitudes of health personnel toward a possible gender bias in pediatric care in Catalonia.

Methods

We undertake a descriptive and exploratory study applying a qualitative research methodology based on hermeneutic phenomenology and Grounded Theory using the focus group technique. The opinions collected were classified into four categories and 22 subcategories, and subsequently analyzed.

Results

Three main ideas stood out regarding situations that might be affected by gender bias: (1) attitudes of health personnel and perceptions with regard to mental health problems and (to a lesser extent) to physical health problems; (2) the role of the child's family and the professional's assessment of this role; and (3) the professional's attention to children of the opposite sex, especially in the case of genital examinations.

Discussion

The results stand out that differential attitudes depending on the gender of the child have been observed in clinical practice in pediatrics, which may have an impact on health inequality. Hence, academic training that includes the study and prevention of implicit biases in professional activity, campaigns aimed at the general population on how to detect implicit biases and promoting gender equity in education, should help to avoid the negative consequences of these misconceptions.
Low‐dose oral isotretinoin in the treatment of recalcitrant facial flat warts: A clinical case and review of literature
Authors: Olguín‐García María Guadalupe , Peralta‐Pedrero María Luisa , Jurado‐Santa Cruz Fermín , Vega‐Memije Elisa , Morales‐Sánchez Martha Alejandra
Published: October 2023

Background and Aims

The treatment of recalcitrant facial flat warts has always been challenging for dermatologists. The pain related to the application of the different treatments, side effects and costs are determining factors in the choice of therapy. To date, it is known that oral isotretinoin administered at a dose of 0.5 mg/kg/day is effective and safe; However, the different adverse effects reported have a dose‐dependent behavior and they could limit their use. Our aim is to assess the effect of low‐doses of oral isotretinoin to reducing side effects in the complete removal of recalcitrant facial flat warts and the current evidence in this regard.

Methods

An extensive literature review was conducted to identify articles relating to low doses of oral isotretinoin for recalcitrant flat warts treatment, regardless of design up to May 2023.

Results

The literature search yielded eight articles of 324 reviewed meeting criteria. Isotretinoin was administered in doses of 0.1–0.5 mg/kg/day. Complete elimination of the lesions occurred in 65.13% of the patients and a partial response in 19.26%. Four relapses were documented at the 4‐month follow‐up. The most frequent adverse effect was cheilitis.

Conclusion

We might consider low doses of oral isotretinoin for the treatment of recalcitrant facial flat warts in which side effects need to be reduced. However, current published works have several limitations, including small sample sizes, lack of control group and follow‐up periods. Larger, randomized, controlled studies are needed to verify the efficacy and safety of different doses of isotretinoin.