bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Diabetes Mellitus on Left Ventricular Mechanics and Long‐Term Outcome in Patients with Hypertrophic Cardiomyopathy
Authors: Badran Hala Mahfouz , Helmy John Anis , Ahmed Nagalaa Fahem , Yacoub Magdi
Published: December 2024

Background

Type 2 diabetes mellitus (T2DM) intensifies the clinical symptoms of heart diseases and leads to a worse prognosis in heart failure patients. Although hypertrophic cardiomyopathy (HCM) and DM rarely co‐occur, particularly in older individuals, the impact of DM on cardiac function and outcomes in individuals with HCM remains insufficiently understood.

Methods

A total of 421 HCM patients were included and followed up in a prospective cohort study (mean 68.7 months). In the diabetic HCM group (n = 47), patients had a mean age of 47 ± 17 years, and 31 (66%) were male, while the non‐diabetic HCM group (n = 374) had a mean age of 44 ± 14 years, and 246 (65%) were male. At study entry, all patients underwent echocardiographic evaluation, encompassing left ventricular (LV) regional and global longitudinal strain (GLS), as well as strain rate (SR) analysis.

Results

In diabetic HCM, there was a greater prevalence of hypertension (p < 0.0001), while the ratio of septal to posterior wall thickness (PWT) (p < 0.003) and E' value were lower (p < 0.009) compared to non‐diabetic HCM. No significant difference between groups in NYHA class or cardiac phenotype. Diabetic HCM exhibited notable reductions in GLS (p < 0.02), systolic SR (SRsys) (p < 0.04), and early diastolic SR (SRe) p < 0.006. Additionally, there was a significant inverse correlation between LVGLS and HbA1c levels (r = −0.58, p < 0.0001), and the duration of diabetes (r = −0.39, p < 0.006). Hospitalization rates were greater in the diabetic HCM than in the non‐diabetic group (44.7% vs.19.5%, p < 0.001). Among all demographic characteristics, phenotypic data, conventional echocardiographic measurements, and LV mechanics, diabetes emerged as the sole determinant of hospitalization among HCM patients. The presence of diabetes nearly tripled the odds of hospitalization (odds ratio: 2.813 [1.448–5.465], p < 0.002). However, diabetes did not negatively affect long‐term survival, and age remained the only independent predictor of all‐cause mortality.

Conclusions

In HCM, T2DM is linked to more deterioration of cardiac mechanics and contributes to unfavorable consequences by frequent hospitalization on its own, independent of age, comorbidities, or phenotype.
Acoustic Features, Syllable Usage, and Song Rates of Male and Female Songs in a Tropical Island Songbird, the Puerto Rican Oriole
Authors: Moyer Michelle J. , Ocasio Michael D. , Lehnert Emerson F. , Nieves Colón Noelia A. , Osorio Eriberto , Bare Ellie K. , de León Laguna Alberic Ponce , Molake Bukola A. , Costas Sabatier Miguel J. , Evans Brian S. , Morales Pérez Alcides L. , Omland Kevin E.
Published: December 2024

Our understanding of elaborate signaling behaviors, such as bird song, has been hindered by historical biases towards male animals. Bird song has been shown to serve important functions like defending territories or attracting mates in both males and females, and singing in both sexes is likely the ancestral trait for songbirds. Female song is strongly associated with year‐round territory defense, especially in the tropics. However, more studies of both male and female songs are needed to better understand the selection pressures acting on this elaborate signal trait. The common ancestor of the New World orioles (Icterus) was likely a nonmigratory tropical species, with both males and females singing and defending year‐round territories. The Puerto Rican Oriole (Icterus portoricensis) has these natural history characteristics, but little is known about how each sex uses song in this understudied Caribbean endemic. We found that while male and female songs were significantly different acoustically, they were indistinguishable in the field, and showed no sex‐specific pattern in syllable usage. Males sang at higher rates than females during the dawn chorus, but females sang frequently during the day. Song is likely evolving as a unified trait in this species, reflecting the characteristics of the common ancestor, but may serve different functions for each sex. In the future, playback studies and rate observations throughout the full day and throughout the year will provide additional insight into how males and females of this tropical songbird may be using their songs.
Social Determinants as Mediators of the Emotional State of People With Type 2 Diabetes and/or Hypertension During the COVID‐19 Pandemic in Ecuador and Spain
Authors: Sanchís‐Ramón María José , Chilet‐Rosell Elisa , Peralta Andrés , Puig‐García Marta , Rivadeneira María Fernanda , Caicedo Cintia , Benazizi‐Dahbi Ikram , Lumbreras Blanca , Nicols Montse , Cebrián Ana , Ricart Wifredo , Lopez‐Miras Ester , Parker Lucy A.
Published: December 2024

Introduction

We aimed to explore the impact of the COVID‐19 pandemic and the resulting restrictions on the emotional state of people with type 2 diabetes mellitus (T2DM) and/or hypertension in Ecuador and Spain. Given the differences in sociopolitical and socioeconomic contexts between these two countries, the research focused on how these diverse environments and their management of social policies and pandemic strategies influenced the emotional well‐being of individuals with chronic illnesses.

Methods

We conducted 36 semi‐structured telephone interviews between August and December 2020 with adults diagnosed with T2DM and/or hypertension (19 in Ecuador, 17 in Spain). The interviews were recorded, anonymized and transcribed for thematic analysis. This approach allowed us to systematically identify and analyse themes related to the participants' emotional experiences during the pandemic.

Results

The results revealed a significant deterioration in the emotional state of participants, attributable to the stress generated by the health crisis and concerns related to their chronic illnesses. The situation elicited a range of emotions among participants, from boredom and apathy to fear, uncertainty and depression. The study highlighted how the impact on emotional well‐being was shaped by the interplay between conjunctural determinants (measures to control COVID‐19 infections) and structural factors driving inequalities (social class, gender, ethnicity).

Conclusion

We developed a conceptual framework illustrating how measures to control COVID‐19 infections directly influenced economic, health and social determinants, which interacted with pre‐existing inequalities and had a differential impact on individuals' emotional well‐being. This framework can be useful for designing more effective and equitable social policies during future health crises, ensuring they address social needs and safeguard psychological and emotional well‐being, particularly among vulnerable groups such as those with chronic illnesses.

Patient and Public Contribution

Thirty‐six participants diagnosed with T2DM and/or hypertension (19 in Ecuador, 17 in Spain) contributed to the study by sharing their emotional experiences during the pandemic. Their detailed accounts enriched the research by providing valuable insights into how the pandemic affected their emotional well‐being. There was no additional involvement or contribution from the public in the design, conduct, analysis or interpretation of the study, nor in the preparation of the manuscript.
Lock‐In Effects in Online Labor Markets
Authors: Ciotti Fabrizio , Hornuf Lars , Stenzhorn Eliza
Published: December 2024

Online platforms that implement reputation mechanisms typically prevent the transfer of ratings to other platforms, leading to lock‐in effects and high switching costs for users. Platforms are able to capitalize on this arrangement, for example, by charging their users higher fees. In this paper, we theoretically and experimentally investigate the effects of platform pricing on workers' switching behavior in online labor markets and analyze whether a policy regime with reputation portability could mitigate lock‐in effects and reduce the likelihood of worker capitalization by the platform. We examine switching motives in depth, differentiating between monetary motives and fairness preferences. We provide theoretical evidence for the existence of switching costs if reputation mechanisms are platform‐specific. Our model predicts that reputation portability lowers switching costs, eliminating the possibility for platforms to capitalize on lock‐in effects. We test our predictions using an online lab‐in‐the‐field experiment. The results are in line with our theoretical model and show that platforms can capitalize on lock‐in effects more effectively in a policy regime without reputation portability. We also find that reputation portability has a positive impact on worker mobility and the wages of highly rated workers. The data further show that the switching of workers is primarily driven by monetary motives, but perceiving the platform fee as unfair also plays a significant role for workers.
Drivers of consumption of plant‐based meat alternatives and their nutritional contributions: A mixed methods approach
Authors: Cooper Deborah , Craddock Joel C. , Beck Eleanor J.
Published: December 2024

Background

Plant‐based meat alternatives (PBMA) are considered an alternative to animal products. We aimed to understand the patterns and drivers of consumption of PBMA and their nutritional contributions using dietary modelling, whilst also considering the relevance of processing.

Methods

This study used a mixed methods exploratory sequential approach. Semistructured online interviews (n = 19) with consumers and nonconsumers of PBMA were conducted. Thematic analysis of interviews considered drivers of PBMA consumption, with content used to develop personas to represent key concepts driving incorporation (or lack of intake) into dietary patterns. Diets were modelled for personas, based on recommended and typical population intake and with variations in processed foods based on the Nova food classification system, including PBMA. Diets were analysed against nutrient reference values.

Results

The main drivers of PBMA consumption were animal welfare, health improvement and environmental concerns. Convenience, cost, taste, processing and thoughts that the nutritional value of PBMA was lesser than meats were all described. Six personas were identified from the interview content. The three most disparate personas (age, dietary pattern and nutrient requirements) were used for dietary modelling. Nutrient analyses showed diets predominantly meeting reference values, with deficiencies more likely when modelled on food choices typical of population intake and diets excluding processed foods.

Conclusions

This study found that PBMA may have beneficial nutritional qualities such as lower saturated fat and higher dietary fibre when compared to their meat equivalents. PBMA may have a place in a healthy diet, whilst alleviating animal welfare and environmental concerns which were identified as key drivers of consumption.
The effect of temperature on rates of dissolved organic carbon (DOC) release by the kelp Ecklonia radiata (phylum Ochrophyta): Implications for the future coastal ocean carbon cycle
Authors: Bennett Eloise , Paine Ellie R. , Britton Damon , Schwoerbel Jakop , Hurd Catriona L.
Published: December 2024

Dissolved organic carbon (DOC) released by macroalgae is an intrinsic component of the coastal ocean carbon cycle, yet knowledge of how future ocean warming may influence this is limited. Temperature is one of the primary abiotic regulators of macroalgal physiology, but there is minimal understanding of how it influences the magnitude and mechanisms of DOC release. To investigate this, we examined the effect of a range of temperatures on DOC release rates and physiological traits of Ecklonia radiata, the most abundant and widespread kelp in Australia that represents a potentially significant contribution to coastal ocean carbon cycling. Juvenile sporophytes were incubated at eight temperatures (4–28°C) for 14 days, after which time, DOC concentrations and physiological traits (growth, photosynthesis, respiration, Fv/Fm, photosynthetic pigment content, and carbon, and nitrogen content) were analyzed using thermal performance curves (TPCs) or regression analyses. Thermal optima were 15.63°C for growth and 25.84°C for photosynthesis, highlighting vulnerability to future ocean warming. Dissolved organic carbon concentrations increased when the temperature was above ~22°C, being greatest at the highest temperature tested (28°C), which was likely driven by photosynthetic overflow and thermal stress. Mean Fv/Fm, total chlorophyll, and total fucoxanthin content were lowest at 28°C. The C:N ratio of blades increased linearly with temperature from 23.9 ± 1.30 at 4°C to 33.0 ± 1.22 at 28°C. We demonstrate increased DOC release by E. radiata under elevated seawater temperatures and discuss potential implications for coastal carbon cycling under future ocean warming given the complex and uncertain fate of macroalgal DOC in the marine environment.
XopM, An FFAT Motif‐Containing Type III Effector Protein From Xanthomonas, Suppresses MTI Responses at the Plant Plasma Membrane
Authors: Brinkmann Charlotte , Bortlik Jennifer , Raffeiner Margot , González‐Fuente Manuel , Börnke Linus F. , Üstün Suayib , Börnke Frederik
Published: December 2024

Many gram‐negative pathogenic bacteria use type III effector proteins (T3Es) as essential virulence factors to suppress host immunity and to cause disease. However, in many cases the molecular function of T3Es remains unknown. The plant pathogen Xanthomonas campestris pv. vesicatoria (Xcv) is the causal agent of bacterial spot disease on tomato and pepper plants and is known to translocate around 36 T3Es into its host cell, which collectively suppress plant defence and promote infection. XopM is an Xcv core T3E with unknown function that has no similarity to any other known protein. We found that XopM interacts with vesicle‐associated membrane protein (VAMP)‐associated proteins (VAPs) in an isoform‐specific manner. The endoplasmic reticulum (ER) integral membrane protein VAP is a common component of membrane contact sites involved in both tethering and lipid transfer by binding directly to proteins containing an FFAT (two phenylalanines [FF] in an acidic tract [AT]) motif. Sequence analyses revealed that XopM displays two FFAT motifs that cooperatively mediated the interaction of XopM with VAP. When expressed in plants, XopM supported growth of a nonpathogenic bacterial strain and dampened the production of reactive oxygen species, indicating its ability to suppress plant immunity. Further analyses revealed that the interaction with VAP and the ability to suppress microbe‐associated molecular pattern‐triggered immunity (MTI) are structurally and functionally separable, although XopM requires localisation to the host membrane system for full MTI suppression activity. We discuss a working model in which XopM uses FFAT motifs to target the membrane to interfere with early MTI responses.
Knowledge About Sexually Transmitted Infections and Associated Factors Among Brazilian Riverside People
Authors: Pinho Ellen Christiane Correa , Galvão José Jorge Da Silva , Martins Wenderson Melo , Goncalves Flavine Evangelista , Aben‐Athar Cintia Yolette Urbano Pauxis , da Silva Richardson Augusto Rosendo , Botelho Eliã Pinheiro , Cunha Carlos Leonardo Figueirdo , Ferreira Glenda Roberta Oliveira Naiff
Published: December 2024

Riverside populations in the Amazon are considered vulnerable due to their living conditions, social aspects, and access to health services; therefore, they may be more exposed to sexually transmitted infections. The objective of this study is to analyze knowledge about STI and associated factors in the riverside population of a metropolis from the Brazilian Amazon. A cross‐sectional study carried out in the Combú environmental protection area. The participants were individuals aged at least 18 years old living in the study area. A questionnaire on knowledge about STI was applied, in addition to another one on associated factors. Multiple binary logistic regression was performed in Minitab 22. A total of 325 riverside dwellers participated in the study. Participants with low schooling levels, incomes below one minimum wage and who had never taken any rapid HIV tests are twice as likely to having low knowledge about STI. Those who live with more people in the same household are more likely to presenting low knowledge levels. The social factors exerted a greater impact on low knowledge about STI.
Colder Climates and Dementia: An Ecological Analysis of Climate‐Patterned Temperature's Influence on Neurological Health
Authors: You Wenpeng
Published: December 2024

Countries with lower climate‐patterned temperatures (Tcp), typically colder, have not been consistently correlated with higher dementia risk in population studies. This study explores Tcp's influence on global and regional dementia rates. Country‐specific Tcp data was analyzed alongside dementia incidence using bivariate analysis, partial correlation, and multiple linear regression. Factors like life expectancy (Life e(0)), economic affluence, genetic predisposition (Biological State Index), and urbanization were considered. Both Pearson's r and nonparametric tests revealed a significant inverse correlation between Tcp and dementia incidence, holding true even after adjusting for life expectancy, affluence, genetic predisposition, and urbanization. Multiple linear regression identified Tcp as a key predictor of dementia incidence, ranking second after life expectancy. Affluence, genetic predisposition, and urbanization did not significantly predict dementia rates. Tcp's predictive power was consistent across different country groups, with minor correlation variations between developing versus developed countries and LMICs versus high‐income nations. Countries with colder climate (lower Tcp) may experience higher dementia rates, a correlation robust across major risk factors. Including Tcp in dementia studies is crucial for understanding its public health implications.
Disguised Blessings: A Mechanistic Understanding of the Beneficial Outcomes Triggered by Partial K Replacement With Na in Two Eucalyptus Species Under Drought Stress
Authors: Mateus Nikolas Souza , Florentino Antonio Leite , Moreira Gabriel Luis Lima Soares , Nogueira Marina Lima , Ferreira Maria Eduarda Pena , Rossi Monica Lanzoni , Linhares Francisco Scaglia , Lavres Jose
Published: December 2024

While not essential for most plants, sodium (Na+) can partially substitute for potassium (K+) in some metabolic functions. Thus, understanding the mechanisms underlying K+ and Na+ uptake, transport, utilization, and ion replacement is crucial to sustain forest production. A pot experiment was designed with 6 K/Na ratios (100/0, 85/15, 70/30, 55/45, 40/60, and 0/0%) and two water conditions (well‐watered, W+; and water‐stressed, W−) on two Eucalyptus species with contrasting drought tolerance. In a multi‐level analysis, we measured morphological, nutritional, physiological, biochemical, molecular, and anatomical traits. Low to moderate K replacement with Na (85/15%–55/45%) provided partial and faster stomatal closure (lower δ13C), thereby enhancing plants' water status (WUE, RLWC, ΨPD, ΨMD), photosynthetic capacity (gs, E, A, Ci/Ca), photoprotection (NPQ, qP, ETR, Fv/FM, ΦPSII), and growth (height, collar diameter, LA, TDM) relative to exclusive K supply. The 70/30% K/Na replacement was defined as the ideal ratio, upregulating K+ and water uptake (overexpression of AKT1, PIP2;5, PIP2;7 and TIP1;3), maximizing enzymatic antioxidant performance and biomass production, and reducing oxidative stress. High K replacement with Na (40/60%) and K deficiency (0/0%) led to incomplete stomatal closure reduced water status, photosynthetic capacity, photoprotection, and growth, especially in the species with low drought tolerance.
MangroveDB: A Comprehensive Online Database for Mangroves Based on Multi‐Omics Data
Authors: Xu Chaoqun , Song Ling‐Yu , Li Jing , Zhang Lu‐Dan , Guo Ze‐Jun , Ma Dong‐Na , Dai Ming‐Jin , Li Qing‐Hua , Liu Jin‐Yu , Zheng Hai‐Lei
Published: December 2024

Mangroves are dominant flora of intertidal zones along tropical and subtropical coastline around the world that offer important ecological and economic value. Recently, the genomes of mangroves have been decoded, and massive omics data were generated and deposited in the public databases. Reanalysis of multi‐omics data can provide new biological insights excluded in the original studies. However, the requirements for computational resource and lack of bioinformatics skill for experimental researchers limit the effective use of the original data. To fill this gap, we uniformly processed 942 transcriptome data, 386 whole‐genome sequencing data, and provided 13 reference genomes and 40 reference transcriptomes for 53 mangroves. Finally, we built an interactive web‐based database platform MangroveDB (https://github.com/Jasonxu0109/MangroveDB), which was designed to provide comprehensive gene expression datasets to facilitate their exploration and equipped with several online analysis tools, including principal components analysis, differential gene expression analysis, tissue‐specific gene expression analysis, GO and KEGG enrichment analysis. MangroveDB not only provides query functions about genes annotation, but also supports some useful visualization functions for analysis results, such as volcano plot, heatmap, dotplot, PCA plot, bubble plot, population structure, and so on. In conclusion, MangroveDB is a valuable resource for the mangroves research community to efficiently use the massive public omics datasets.
Does the implementation status of gender provisions affect the implementation of a peace agreement? Evidence from Colombia's 2016 peace agreement implementation process
Authors: Joshi Madhav
Published: December 2024

In 2016, the Colombian government and the leftist insurgency group FARC (Fuerzas Armadas Revolucionarias de Colombia – Ejército del Pueblo) signed an agreement that ensures women's greater participation in the peace implementation process, their access to benefits from the programs, and their ability to reform initiatives in the agreement. While applauded for adhering to the UNSCR 1325 normative commitments on women's roles in peace processes, it's unclear how adopting a gender perspective affects the entire agreement's implementation success. This article analyzes monthly data on the implementation of 578 stipulations and 70 subthemes (reforms or programs) and evaluates peace implementation from a gender perspective. The findings from the stipulation level analysis reveal an implementation gap between gender and gender‐neutral or non‐gender provisions. The subtheme level analyses further confirm this finding that gender provisions alone do not contribute to the overall peace implementation success; rather, implementing those provisions is foundational for advancing the overall peace implementation.
Intramuscular blood flow and muscle oxygenation of the vastus lateralis response to intermittent incremental muscle contractions
Authors: Izumi Kazuma , Yamamori Keisuke , Katayama Keisho , Kano Yutaka , Tanaka Noriko , Akima Hiroshi
Published: December 2024

Power Doppler ultrasonography is used to measure blood flow within a given muscle, otherwise known as intramuscular blood flow. However, it is not fully understood how intramuscular blood flow and muscle oxygenation change with repetitive muscle contraction. The present study was conducted to assess changes in intramuscular blood flow and muscle oxygenation of the vastus lateralis (VL) during intermittent and incremental contractions. Fifteen healthy male subjects (21.7 ± 2.6 years) performed intermittent (5 s contraction, 5 s relaxation) and incremental isometric knee extensions at 30%, 40%, 50%, 60% and 70% of maximal voluntary contraction (MVC) until task failure. Intramuscular blood flow and muscle oxygen saturation () were simultaneously measured using power Doppler ultrasonography and near‐infrared spectroscopy, respectively, from the right VL of the mid‐thigh. Intramuscular blood flow was increased from 0.5 ± 0.5% at rest to 13.9 ± 9.5% at task failure. Intramuscular blood flow significantly increased from rest to 30% and 40% MVC (P = 0.001), and significantly decreased from 30% to 70% MVC (P = 0.004). These results indicate that intramuscular blood flow and show different patterns of change, suggesting that the contribution of intramuscular blood flow to oxygen supply decreases within the VL at moderate and higher exercise intensities.
Influence of Prematch Perceived Wellness on High-Intensity Locomotor Activities of Professional Soccer Players During in-Season Matches
Authors: Marqués-Jiménez Diego , Quílez-Larrayad Pablo , Izquierdo José M.
Published: December 2024

Purpose: The aim of this study was to determine the influence of prematch perceived wellness on high-intensity locomotor activities of professional soccer players during in-season matches. Methods: Twenty male soccer players (26.74 [3.27] y; 179.77 [6.06] cm; 76.72 [9.33] kg), members of a professional soccer team, participated in this longitudinal study. Data collection was conducted during the competitive period of 1 season and involved the 34 league official matches. Perceived wellness was assessed individually 3 hours before each match using a 5-point Likert questionnaire, and external loads during matches were monitored using global navigation satellite system devices. Each wellness item (ie, fatigue, delayed-onset muscle soreness [DOMS], sleep, and stress) was considered as an individual wellness component and analyzed as raw score, team z score, and individualized z score. Different random forest regression models and linear mixed models were carried out for statistical analysis. Results: Individualized z scores should be considered the most important variables to estimate the proportion of external-load variation during match play, but the proportion of the variance that may be explained from the prematch perceived wellness suggests a limited capacity in relation to external-load measures. Only individualized z scores of DOMS showed significant effects on sprint running distance (>24.0 km·h−1) and number of sprints (>24.0 km·h−1) during matches (P < .05). Conclusions: Sprint performance of professional soccer players during in-season matches may be slightly influenced by the players’ day-to-day variation of prematch perceived DOMS.
High-throughput single-cell sorting by stimulated Raman-activated cell ejection
Authors: Zhang Jing , Lin Haonan , Xu Jiabao , Zhang Meng , Ge Xiaowei , Zhang Chi , Huang Wei E. , Cheng Ji-Xin
Published: December 2024

Raman-activated cell sorting isolates single cells in a nondestructive and label-free manner, but its throughput is limited by small spontaneous Raman scattering cross section. Coherent Raman scattering integrated with microfluidics enables high-throughput cell analysis, but faces challenges with small cells (<3 μm) and tissue sections. Here, we report stimulated Raman-activated cell ejection (S-RACE) that enables high-throughput single-cell sorting by integrating stimulated Raman imaging, in situ image decomposition, and laser-induced cell ejection. S-RACE allows ejection of live bacteria or fungi guided by their Raman signatures. Furthermore, S-RACE successfully sorted lipid-rich
Rhodotorula glutinis
cells from a cell mixture with a throughput of ~13 cells per second, and the sorting results were confirmed by downstream quantitative polymerase chain reaction. Beyond single cells, S-RACE shows high compatibility with tissue sections. Incorporating a closed-loop feedback control circuit further enables real-time SRS imaging-identification-ejection. In summary, S-RACE opens exciting opportunities for diverse single-cell sorting applications.
Identification of the Wnt signal peptide that directs secretion on extracellular vesicles
Authors: Gurriaran-Rodriguez Uxia , Datzkiw David , Radusky Leandro G. , Esper Marie , Javandoost Ehsan , Xiao Fan , Ming Hong , Fisher Solomon , Marina Alberto , De Repentigny Yves , Kothary Rashmi , Azkargorta Mikel , Elortza Felix , Rojas Adriana L. , Serrano Luis , Hierro Aitor , Rudnicki Michael A.
Published: December 2024

Wnt proteins are hydrophobic glycoproteins that are nevertheless capable of long-range signaling. We found that Wnt7a is secreted long distance on the surface of extracellular vesicles (EVs) following muscle injury. We defined a signal peptide region in Wnts required for secretion on EVs, termed exosome-binding peptide (EBP). Addition of EBP to an unrelated protein directed secretion on EVs. Palmitoylation and the signal peptide were not required for Wnt7a-EV secretion. Coatomer was identified as the EV-binding protein for the EBP. Analysis of cocrystal structures, binding thermodynamics, and mutagenesis found that a dilysine motif mediates EBP binding to coatomer with a conserved function across the Wnt family. We showed that EBP is required for Wnt7a bioactivity when expressed in vivo during regeneration. Overall, our study has elucidated the structural basis and singularity of Wnt secretion on EVs, alternatively to canonical secretion, opening avenues for innovative therapeutic targeting strategies and systemic protein delivery.
Deep and dynamic metabolic and structural imaging in living tissues
Authors: Liu Kunzan , Cao Honghao , Shashaty Kasey , Yu Li-Yu , Spitz Sarah , Pramotton Francesca Michela , Wan Zhengpeng , Kan Ellen L. , Tevonian Erin N. , Levy Manuel , Lendaro Eva , Kamm Roger D. , Griffith Linda G. , Wang Fan , Qiu Tong , You Sixian
Published: December 2024

Label-free imaging through two-photon autofluorescence of NAD(P)H allows for nondestructive, high-resolution visualization of cellular activities in living systems. However, its application to thick tissues has been restricted by its limited penetration depth within 300 μm, largely due to light scattering. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to more than 700 μm in living engineered human multicellular microtissues by adopting multimode fiber-based, low repetition rate, high peak power, three-photon excitation of NAD(P)H at 1100 nm. This is achieved by having more than 0.5 megawatts peak power at the band of 1100 ± 25 nm through adaptively modulating multimodal nonlinear pulse propagation with a compact fiber shaper. Moreover, the eightfold increase in pulse energy enables faster imaging of monocyte behaviors in the living multicellular models. These results represent a substantial advance for deep and dynamic imaging of intact living biosystems. The modular design is anticipated to allow wide adoption for demanding imaging applications, including cancer research, immune responses, and tissue engineering.
From oxide epitaxy to freestanding membranes: Opportunities and challenges
Authors: Choo Sooho , Varshney Shivasheesh , Liu Huan , Sharma Shivam , James Richard D. , Jalan Bharat
Published: December 2024

Motivated by the growing demand to integrate functional oxides with dissimilar materials, numerous studies have been undertaken to detach a functional oxide film from its original substrate, effectively forming a membrane, which can then be affixed to the desired host material. This review article is centered on the synthesis of functional oxide membranes, encompassing various approaches to their synthesis, exfoliation, and transfer techniques. First, we explore the characteristics of thin-film growth techniques with emphasis on molecular beam epitaxy. We then examine the fundamental principles and pivotal factors underlying three key approaches of creating membranes: (i) chemical lift-off, (ii) the two-dimensional layer–assisted lift-off, and (iii) spalling. We review the methods of exfoliation and transfer for each approach. Last, we provide an outlook into the future of oxide membranes, highlighting their applications and emerging properties.
Turing covalent organic framework membranes via heterogeneous nucleation synthesis for organic solvent nanofiltration
Authors: Yang Fan , Guo Jing , Han Chengzhe , Huang Junhui , Zhou Zhiwei , Sun Shi-Peng , Zhang Yanqiu , Shao Lu
Published: December 2024

Although covalent organic frameworks (COFs) demonstrate notable potential for developing advanced separation membranes, contemporary COF membranes still lack controlled stacking and highly efficient sieving. Here, Turing-architecture COF membranes were constructed by engineering a reaction-diffusion assembly process via heterogeneous nucleation synthesis with tannic acid (TA). TA covalently binds with amine monomers to form a composite precursor with increased reactivity and decreased diffusivity. This altered the pathway of Schiff base reactions with aldehyde monomers, fulfilling suitable reaction-diffusion conditions, and ultimately formed the labyrinthine stripe or spot-patterned Turing COF film with controlled stacking and uniform pore structure. This endows our COF membrane with highly efficient molecule sieving ability for organic solvent nanofiltration while exhibiting a flux that is 621% greater than that of commercial membranes. Thus, this study provides a paradigm for the in situ synthesis of highly efficient COF membranes for diversely sustainable separations.
Sustainable high-entropy materials?
Authors: Han Liuliu , Mu Wangzhong , Wei Shaolou , Liaw Peter K. , Raabe Dierk
Published: December 2024

High-entropy materials (HEMs) show inspiring structural and functional properties due to their multi-elemental compositions. However, most HEMs are burdened by cost-, energy-, and carbon-intensive extraction, synthesis, and manufacturing protocols. Recycling and reusing HEMs are challenging because their design relies on high fractions of expensive and limited-supply elements in massive solid solutions. Therefore, we review the basic sustainability aspects of HEMs. Solutions include using feedstock with lower carbon and energy footprints, sustainable primary synthesis routes from minerals, attenuation of the equimolar alloying rule, and a preference for scrap and dumped waste for secondary and tertiary synthesis. The high solubility, compositional flexibility, and chemical robustness of HEMs offer pathways for using higher fractions of mixed and contaminated scrap and waste feedstocks, which are not admissible for synthesizing conventional materials. We also discuss thermodynamic and kinetic design strategies to reconcile good material properties with high impurity tolerance and variable compositions.
Imaging-guided bioresorbable acoustic hydrogel microrobots
Authors: Han Hong , Ma Xiaotian , Deng Weiting , Zhang Junhang , Tang Songsong , Pak On Shun , Zhu Lailai , Criado-Hidalgo Ernesto , Gong Chen , Karshalev Emil , Yoo Jounghyun , You Ming , Liu Ann , Wang Canran , Shen Hao K. , Patel Payal N. , Hays Claire L. , Gunnarson Peter J. , Li Lei , Zhang Yang , Dabiri John O. , Wang Lihong V. , Shapiro Mikhail G. , Wu Di , Zhou Qifa , Greer Julia R. , Gao Wei
Published: December 2024

Micro- and nanorobots excel in navigating the intricate and often inaccessible areas of the human body, offering immense potential for applications such as disease diagnosis, precision drug delivery, detoxification, and minimally invasive surgery. Despite their promise, practical deployment faces hurdles, including achieving stable propulsion in complex in vivo biological environments, real-time imaging and localization through deep tissue, and precise remote control for targeted therapy and ensuring high therapeutic efficacy. To overcome these obstacles, we introduce a hydrogel-based, imaging-guided, bioresorbable acoustic microrobot (BAM) designed to navigate the human body with high stability. Constructed using two-photon polymerization, a BAM comprises magnetic nanoparticles and therapeutic agents integrated into its hydrogel matrix for precision control and drug delivery. The microrobot features an optimized surface chemistry with a hydrophobic inner layer to substantially enhance microbubble retention in biofluids with multiday functionality and a hydrophilic outer layer to minimize aggregation and promote timely degradation. The dual-opening bubble-trapping cavity design enables a BAM to maintain consistent and efficient acoustic propulsion across a range of biological fluids. Under focused ultrasound stimulation, the entrapped microbubbles oscillate and enhance the contrast for real-time ultrasound imaging, facilitating precise tracking and control of BAM movement through wireless magnetic navigation. Moreover, the hydrolysis-driven biodegradability of BAMs ensures its safe dissolution after treatment, posing no risk of long-term residual harm. Thorough in vitro and in vivo experimental evidence demonstrates the promising capabilities of BAMs in biomedical applications. This approach shows promise for advancing minimally invasive medical interventions and targeted therapeutic delivery.
Accelerating the pace of innovation in robotics by fostering diversity and inclusive leadership
Authors: Macari Daniela , Fratzl Alex , Keplinger Ksenia , Keplinger Christoph
Published: December 2024

Diverse and inclusive teams are not merely a moral imperative but also a catalyst for scientific excellence in robotics. Drawing from literature, a comprehensive citation analysis, and expert interviews, we derive seven main benefits of diversity and inclusion and propose a leadership guide for roboticists to reap these benefits.
Development of a fibrin-targeted theranostic for gastric cancer
Authors: Esfahani Shadi A. , Ma Li , Krishna Shriya , Ma Hua , Raheem Shvan J. , Shuvaev Sergey , Rotile Nicholas J. , Weigand-Whittier Jonah , Boice Avery T. , Borges Nicholas , Treaba Constantina A. , Deffler Caitlin , Diyabalanage Himashinie , Humblet Valerie , Sosnovik David E. , Mahmood Umar , Heidari Pedram , Shih Angela , Catana Ciprian , Strickland Matthew R. , Klempner Samuel J. , Caravan Peter
Published: December 2024

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores. First-in-human
64
Cu-FBP8 fibrin–targeted positron emission tomography (PET) imaging in seven patients with gastric or gastroesophageal junction cancer showed high probe uptake in all target lesions with tumor-to-background (muscle) uptake ratios of 9.9 ± 6.6 in primary (
n
= 7) and 11.2 ± 6.6 in metastatic (
n
= 45) tumors. Using two mouse models of human GCa, one fibrin-high (SNU-16) and one fibrin-low (NCI-N87), we showed that PET imaging with a related fibrin-specific peptide, CM500, labeled with copper-64 (
64
Cu-CM500) specifically bound to and precisely quantified tumor fibrin in both models. We then labeled the fibrin-specific peptide CM600 with yttrium-90 and showed that
90
Y-CM600 effectively decreased tumor growth in these mouse models. Mice carrying fibrin-high SNU-16 tumors experienced tumor growth inhibition and prolonged survival in response to either a single high dosage or fractionated lower dosage of
90
Y-CM600, whereas mice carrying fibrin-low NCI-N87 tumors experienced prolonged survival in response to a fractionated lower dosage of
90
Y-CM600. These results lay the foundation for a fibrin-targeted theranostic that may expand options for patients with advanced GCa.
Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation
Authors: Zhang Youran R. , Keshari Swapnil , Kurihara Kazuo , Liu James , McKendrick Lindsay M. , Chen Chien-Sin , Yang Yufan , Falo Louis D. , Das Jishnu , Sumpter Tina L. , Kaplan Daniel H.
Published: December 2024

Activation of dermal mast cells through the Mas-related G protein–coupled receptor B2 receptor (MrgprB2 in mice and MrgprX2 in humans) is a key component of numerous inflammatory skin diseases, including dermatitis and rosacea. Sensory neurons actively suppress mast cell activation through the regulated release of glutamate, resulting in reduced expression of
Mrgprb2
as well as genes associated with proteins found in mast cell granules. To determine whether exogenous glutamate receptor agonism could suppress mast cell function, we determined that mast cells have relatively selective expression of the glutamate receptor ionotropic, kainate 2 (GluK2). A GluK2-specific agonist, SYM2081, effectively inhibited mast cell degranulation in response to MrgprB2 agonism in both murine mast cells and human skin explants in vitro as well as in vivo after both intradermal and topical administration of SYM2081 to mice. Analyses of transcriptomic datasets from SYM2081-treated mast cells using standard differential expression approaches and an interpretable machine learning technique revealed a previously unrecognized cellular program coordinately regulated by GluK2 agonism. GluK2 agonism suppressed the expression of
Mrgprb2
and genes associated with mast cell proliferation. Suppression of mast cell proliferation by SYM2081 exposure was confirmed on the basis of reduced Ki-67 expression and BrdU incorporation in vitro and in vivo. Last, pretreatment with SYM2081 reduced skin inflammation in murine models of dermatitis and rosacea. Thus, agonism of GluK2 represents a promising approach to suppress mast cell activation and may prove beneficial as therapy for inflammatory diseases in which mast cell activation is pathogenic.
Assembly and engineering of BioBricks to develop an efficient NADH regeneration system
Authors: Cheng Feng , Wang Cheng-Jiao , Gong Xiao-Xiao , Sun Ke-Xiang , Liang Xi-Hang , Xue Ya-Ping , Zheng Yu-Guo
Published: December 2024

The cofactor regeneration system plays a crucial role in redox biocatalysis for organic synthesis and the pharmaceutical industry. The alcohol dehydrogenase (ADH)-based regeneration system offers a promising solution for the
in situ
regeneration of NAD(P)H. However, its widespread use is hindered by low activity and poor expression of ADH in
Escherichia coli
. Herein, the BioBricks (promoter, ribosome binding site [RBS], functional gene, and terminator) were assembled and engineered to constitute an efficient NADH regeneration system. The semi-rational design was employed to enhance the catalytic efficiency of
Gst
ADH (an ADH from
Geobacillus stearothermophilus
), resulting in a beneficial
Gst
ADH variant with a 2.1-fold increase in catalytic efficiency. Furthermore, the RBS optimization was used to increase the expression of ADH genes, leading to the identification of an RBS with a 3.2-fold increased translation rate. Using this developed system, the NADH generating velocity reached more than 2 s
−1
even toward 0.1 mM NAD
+
, indicating that it is the most promising NADH regeneration so far. Finally, the engineered system was utilized for the asymmetric biosynthesis of
l-
phosphinothricin (a chiral herbicide), with a high yield (>95%).

IMPORTANCE

The alcohol dehydrogenase (ADH)-based coenzyme regeneration system serves as a useful tool in redox biocatalysis. This system effectively replenishes NAD(P)H by utilizing isopropanol as a substrate, with the added advantage of easily separable acetone as a by-product. Previous studies focused on discovering new
adh
genes and engineering the ADH protein for higher catalytic efficiency, neglecting the optimization of other gene components. In this study, a remarkably efficient NADH regeneration system was developed using BioBricks assembly for system initialization. The ADH engineering was used to enhance catalytic efficiency, and RBS optimization for elevated ADH expression, which resulted in not only a 2.1-fold increase in catalytic efficiency but also a 3.2-fold increase in translation rate. Together, these improvements resulted in an overall 6.7-fold enhancement in performance. This system finds application in a wide range of NADH-dependent biocatalysis processes and is particularly advantageous for the biosynthesis of fine chemicals.
A new target of multiple lysine methylation in bacteria
Authors: Inoue Shori , Yoshimoto Shogo , Hori Katsutoshi
Published: December 2024

The methylation of ε-amino groups in protein lysine residues is an important posttranslational modification in eukaryotes. This modification plays a pivotal role in the regulation of diverse biological processes, including epigenetics, transcriptional control, and cellular signaling. Recent research has begun to reveal the potential role of methylation in modulating bacterial immune evasion and adherence to host cells. In this study, we analyzed the cell surface proteins of the toluene-degrading bacterium
Acinetobacter
sp. Tol 5 by label-free liquid chromatography‒mass spectrometry and found multiple lysine methylation in its trimeric autotransporter adhesin (TAA), AtaA. Over 130 lysine residues of AtaA, consisting of 3,630 amino acids and containing 234 lysine residues, were methylated. We identified that the outer membrane protein lysine methyltransferase (OM PKMT) of Tol 5, KmtA, specifically methylates the lysine residues of AtaA. In the KmtA-deficient mutant, most lysine methylations on AtaA were absent, indicating that KmtA is responsible for the methylation of multiple lysine residues throughout AtaA. Bioinformatic analysis revealed that the OM PKMT genes were widely distributed among Gram-negative bacteria, including pathogens with TAAs that promote infectivity, such as
Burkholderia mallei
and
Haemophilus influenzae
. Although KmtA has sequence similarities to the OM PKMTs of
Rickettsia
involved in infectivity, KmtA-like PKMTs formed a distinct cluster from those of the
Rickettsia
type according to the clustering analysis, suggesting that they are new types of OM PKMTs. Furthermore, the deletion of Tol 5 KmtA led to an increase in AtaA on the cell surface and enhanced bacterial adhesion, resulting in slower growth.

IMPORTANCE

Lysine methylation has been underexplored in prokaryotes, and information on it is limited to some pathogens. Our finding is the second case of multiple lysine methylation of bacterial outer membrane (OM) proteins, following that of OmpB of
Rickettsia
. The newly found target of methylation, AtaA, a trimeric autotransporter adhesin family protein of
Acinetobacter
sp. Tol 5 isolated from activated sludge, extends our understanding of OM protein methylation to non-pathogenic environmental strains. The newly identified enzyme KmtA shows higher specificity than rickettsial lysin methylases, protein lysine methyltransferases, and methylates more lysine residues of the target, which raises interest in the mechanism underlying its biological specificity. The widespread presence of KmtA-like PKMTs throughout Gram-negative bacteria suggests that lysine methylation functions more extensively in bacterial physiology than previously recognized.
Erratum to: Preparation of High-Labeled Graphene Oxide by Tritium Thermal Activation Method Application for in the Betavoltaic Cell of a Nuclear Battery
Authors: Badun G. A. , Bunyaev V. A. , Chernysheva M. G.
Published: December 2024

Erratum