bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation
Authors: Zhang Xiang , Zhang Dawei , Wei Chenyang , Wang Dehua , Lavendomme Roy , Qi Shuo , Zhu Yu , Zhang Jingshun , Zhang Yongya , Wang Jiachen , Xu Lin , Gao En-Qing , Yu Wei , Yang Hai-Bo , He Mingyuan
Published: May 2024

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.
A statistical resolution measure of fluorescence microscopy with finite photons
Authors: Li Yilun , Huang Fang
Published: May 2024

First discovered by Ernest Abbe in 1873, the resolution limit of a far-field microscope is considered determined by the numerical aperture and wavelength of light, approximately $$\frac{\lambda }{2{NA}}$$

λ

2
N
A

. With the advent of modern fluorescence microscopy and nanoscopy methods over the last century, this definition is insufficient to fully describe a microscope’s resolving power. To determine the practical resolution limit of a fluorescence microscope, photon noise remains one essential factor yet to be incorporated in a statistics-based theoretical framework. We proposed an information density measure quantifying the theoretical resolving power of a fluorescence microscope in the condition of finite photons. The developed approach not only allows us to quantify the practical resolution limit of various fluorescence and super-resolution microscopy modalities but also offers the potential to predict the achievable resolution of a microscopy design under different photon levels.
Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies
Authors: Deng Jian-Qun , Li Yi , Wang Yu-Jia , Cao Ya-Lin , Xin Si-Yu , Li Xin-Yu , Xi Rui-Min , Wang Feng-Shan , Sheng Ju-Zheng
Published: May 2024

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.
Carbon–nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes
Authors: Lu Hong , Zhang Yu , Wang Xiu-Hong , Zhang Ran , Xu Peng-Fei , Wei Hao
Published: May 2024

Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion into the C–C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.
EPB41L4A-AS1 is required to maintain basal autophagy to modulates Aβ clearance
Authors: Wang Ziqiang , Wang Ruomei , Niu Lixin , Zhou Xiaoyan , Han Jinxiang , Li Kun
Published: May 2024

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques. Aβ is generated from the cleavage of the amyloid precursor protein by β and γ-secretases and cleared by neuroglial cells mediated autophagy. The imbalance of the intracellular Aβ generation and clearance is the causative factor for AD pathogenesis. However, the exact underlying molecular mechanisms remain unclear. Our previous study reported that EPB41L4A-AS1 is an aging-related long non-coding RNA (lncRNA) that is repressed in patients with AD. In this study, we found that downregulated EPB41L4A-AS1 in AD inhibited neuroglial cells mediated-Aβ clearance by decreasing the expression levels of multiple autophagy-related genes. We found that EPB41L4A-AS1 regulates the expression of general control of amino acid synthesis 5-like 2, an important histone acetyltransferase, thus affecting histone acetylation, crotonylation, and lactylation near the transcription start site of autophagy-related genes, ultimately influencing their transcription. Collectively, this study reveals EPB41L4A-AS1 as an AD-related lncRNA via mediating Aβ clearance and provides insights into the epigenetic regulatory mechanism of EPB41L4A-AS1 in gene expression and AD pathogenesis.
Composition and state prediction of lithium-ion cathode via convolutional neural network trained on scanning electron microscopy images
Authors: Oh Jimin , Yeom Jiwon , Madika Benediktus , Kim Kwang Man , Liow Chi Hao , Agar Joshua C. , Hong Seungbum
Published: May 2024

High-throughput materials research is strongly required to accelerate the development of safe and high energy-density lithium-ion battery (LIB) applicable to electric vehicle and energy storage system. The artificial intelligence, including machine learning with neural networks such as Boltzmann neural networks and convolutional neural networks (CNN), is a powerful tool to explore next-generation electrode materials and functional additives. In this paper, we develop a prediction model that classifies the major composition (e.g., 333, 523, 622, and 811) and different states (e.g., pristine, pre-cycled, and 100 times cycled) of various Li(Ni, Co, Mn)O2 (NCM) cathodes via CNN trained on scanning electron microscopy (SEM) images. Based on those results, our trained CNN model shows a high accuracy of 99.6% where the number of test set is 3840. In addition, the model can be applied to the case of untrained SEM data of NCM cathodes with functional electrolyte additives.
Corrosion resistance of additively manufactured aluminium alloys for marine applications
Authors: Linder Clara , Mehta Bharat , Sainis Salil , Lindén Johan B. , Zanella Caterina , Nyborg Lars
Published: May 2024

Additive manufacturing opens new possibilities for designing light-weight structures using aluminium alloys. The microstructure of two Al alloys and their corrosion resistance in NaCl and natural seawater environments were investigated. The newly designed Al-Mn-Cr-Zr based alloy showed a higher corrosion resistance than reference AlSi10Mg alloy in both environments in as printed and heat-treated conditions. The corrosion initiated in the Al matrix along the precipitates in the alloys where the Volta potential difference was found the highest. The coarser microstructure and precipitate composition of the new Al-alloy led to the formation of a resistant passive film which extended the passivity region of the Al-Mn-Cr-Zr alloy compared to the AlSi10Mg alloy. The effect of heat treatment could be seen in the microstructure as more precipitates were found in between the melt pool boundaries, which affected the corrosion initiation and slightly the pitting resistance. Overall, this study shows that a newly designed Al-alloy for additive manufacturing has a suitable corrosion resistance for applications in marine environments.
RNA-sequencing suggests extracellular matrix and vasculature dysregulation could impair neurogenesis in schizophrenia cases with elevated inflammation
Authors: North Hayley F. , Weissleder Christin , Bitar Maina , Barry Guy , Fullerton Janice M. , Webster Maree J. , Weickert Cynthia Shannon
Published: May 2024

A subgroup of schizophrenia cases with elevated inflammation have reduced neurogenesis markers and increased macrophage density in the human subependymal zone (SEZ; also termed subventricular zone or SVZ) neurogenic niche. Inflammation can impair neurogenesis; however, it is unclear which other pathways are associated with reduced neurogenesis. This research aimed to discover transcriptomic differences between inflammatory subgroups of schizophrenia in the SEZ. Total RNA sequencing was performed on SEZ tissue from schizophrenia cases, designated into low inflammation (n = 13) and high inflammation (n = 14) subgroups, based on cluster analysis of inflammation marker gene expression. 718 genes were differentially expressed in high compared to low inflammation schizophrenia (FDR p < 0.05) and were most significantly over-represented in the pathway ‘Hepatic Fibrosis/Hepatic Stellate-Cell Activation’. Genes in this pathway relate to extracellular matrix stability (including ten collagens) and vascular remodelling suggesting increased angiogenesis. Collagen-IV, a key element of the basement membrane and fractones, had elevated gene expression. Immunohistochemistry revealed novel collagen-IV+ fractone bulbs within the human SEZ hypocellular gap. Considering the extracellular matrix’s regulatory role in SEZ neurogenesis, fibrosis-related alterations in high inflammation schizophrenia may disrupt neurogenesis. Increased angiogenesis could facilitate immune cell transmigration, potentially explaining elevated macrophages in high inflammation schizophrenia. This discovery-driven analysis sheds light on how inflammation may contribute to schizophrenia neuropathology in the neurogenic niche.
A high-resolution dataset of water bodies distribution over the Tibetan Plateau
Authors: Chen Zhengchao , Guo Linan , Wu Yanhong , Zhang Bing , Chen Pan , Yang Xuan , Guo Jiawei
Published: May 2024

Water body (WB) extraction is the basic work of water resources management. Tibetan Plateau is one of the largest alpine lake systems in the world. However, research on the characteristics of water bodies (WBs) is mainly focused on large and medium WBs due to spatial resolution. This research presents a dataset containing a 2-m resolution map of WBs in 2020 based on Gaofen-1 data, and morphometric and landscape indices of WBs across the Tibetan Plateau. The Swin-UNet model is well performed with overall accuracy at 98%. The total area of WBs is 56354.6 km2 across Tibetan Plateau in 2020. The abundance compared with that from size-abundance relationship indicate WBs in the Tibetan Plateau conformed to the classic power scaling law. We evaluate the influence of spatial-resolution in WB extraction, which shows the dataset could be valuable to fill the gap of existing WBs map, especially for small waters. The dataset is valuable for revealing the spatial patterns of WBs, and understanding the impacts of climate change on water resources in Plateau.
The impact of maxillary dimensions on determining surgical approach of fungal ball in the maxillary sinus
Authors: Lee Young-Ha , Cho Won Ki , Kim Dong Hyun , Kim Ji Heui
Published: May 2024

Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior–posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements—anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus—for guiding optimal surgical approaches in MS lesions.
Foot-and-mouth disease-associated myocarditis is age dependent in suckling calves
Authors: Deka Pankaj , Das Sangeeta , Hazarika Ritam , Kayaga Ray , Dutta Biswajit , Deka Abhijit , Barman Utpal , Ahmed Rofique , Islam Nazrul , Sarma Mihir , Deka Ilakshy , Rout Manoranjan , Sharma Krishna , Sharma Rajeev K.
Published: May 2024

Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype “O”. Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P < 0.001) in < 2 months old FMD-infected calves showing clinical signs suggestive of myocarditis (264.833 ± 4.16; 11.650 ± 0.34 and 1213.33 ± 29.06) than those without myocarditis (< 2 months old: 110.00 ± 0.00, 0.06 ± 0.00, 1050.00 ± 0.00; > 2 months < 4 months: 83.00 ± 3.00, 0.05 ± 0.02, 1159.00 ± 27.63) and healthy control groups (< 2 months old: 67.50 ± 3.10, 0.047 ± 0.01, 1120.00 ± 31.62; > 2 months < 4 months: 72.83 ± 2.09, 0.47 ± 0.00, 1160.00 ± 18.44). However, mean serum CK-MB did not differ significantly amongst the groups. Four calves under 2 months old died and a necropsy revealed the presence of a pathognomic gross lesion of the myocardial form of FMD known as “tigroid heart”. Histopathology confirmed myocarditis. This study also reports the relevance of clinical and histopathological findings and biochemical markers in diagnosing FMD-related myocarditis in suckling calves.
Reactive molecular dynamics simulations of lithium-ion battery electrolyte degradation
Authors: Mabrouk Y. , Safaei N. , Hanke F. , Carlsson J. M. , Diddens D. , Heuer A.
Published: May 2024

The development of reliable computational methods for novel battery materials has become essential due to the recently intensified research efforts on more sustainable energy storage materials. Here, we use a recently developed framework allowing to consistently incorporate quantum-mechanical activation barriers to classical molecular dynamics simulations to study the reductive solvent decomposition and formation of the solid electrolyte interphase for a graphite/carbonate electrolyte interface. We focus on deriving condensed-phase effective rates based on the elementary gas-phase reduction and decomposition energy barriers. After a short initial transient limited by the elementary barriers, we observe that the effective rate shows a transition to a kinetically slow regime influenced by the changing coordination environment and the ionic fluxes between the bulk electrolyte and the interface. We also discuss the impact of the decomposition on the ionic mobility. Thus, our work shows how elementary first-principles properties can be mechanistically leveraged to provide fundamental insights into electrochemical stability of battery electrolytes.
Transcriptional repression of the oncofetal LIN28B gene by the transcription factor SOX6
Authors: Pastori Valentina , Zambanini Gianluca , Citterio Elisabetta , Weiss Tamina , Nakamura Yukio , Cantù Claudio , Ronchi Antonella Ellena
Published: May 2024

The identification of regulatory networks contributing to fetal/adult gene expression switches is a major challenge in developmental biology and key to understand the aberrant proliferation of cancer cells, which often reactivate fetal oncogenes. One key example is represented by the developmental gene LIN28B, whose aberrant reactivation in adult tissues promotes tumor initiation and progression. Despite the prominent role of LIN28B in development and cancer, the mechanisms of its transcriptional regulation are largely unknown. Here, by using quantitative RT-PCR and single cell RNA sequencing data, we show that in erythropoiesis the expression of the transcription factor SOX6 matched a sharp decline of LIN28B mRNA during human embryo/fetal to adult globin switching. SOX6 overexpression repressed LIN28B not only in a panel of fetal-like erythroid cells (K562, HEL and HUDEP1; ≈92% p < 0.0001, 54% p = 0.0009 and ≈60% p < 0.0001 reduction, respectively), but also in hepatoblastoma HepG2 and neuroblastoma SH-SY5H cells (≈99% p < 0.0001 and ≈59% p < 0.0001 reduction, respectively). SOX6-mediated repression caused downregulation of the LIN28B/Let-7 targets, including MYC and IGF2BP1, and rapidly blocks cell proliferation. Mechanistically, Lin28B repression is accompanied by SOX6 physical binding within its locus, suggesting a direct mechanism of LIN28B downregulation that might contribute to the fetal/adult erythropoietic transition and restrict cancer proliferation.
Rapid online assessment of reading and phonological awareness (ROAR-PA)
Authors: Gijbels Liesbeth , Burkhardt Amy , Ma Wanjing Anya , Yeatman Jason D.
Published: May 2024

Phonological awareness (PA) is at the foundation of reading development: PA is introduced before formal reading instruction, predicts reading development, is a target for early intervention, and is a core mechanism in dyslexia. Conventional approaches to assessing PA are time-consuming and resource intensive: assessments are individually administered and scoring verbal responses is challenging and subjective. Therefore, we introduce a rapid, automated, online measure of PA—The Rapid Online Assessment of Reading—Phonological Awareness—that can be implemented at scale without a test administrator. We explored whether this gamified, online task is an accurate and reliable measure of PA and predicts reading development. We found high correlations with standardized measures of PA (CTOPP-2, r = .80) for children from Pre-K through fourth grade and exceptional reliability (α = .96). Validation in 50 first and second grade classrooms showed reliable implementation in a public school setting with predictive value of future reading development.
Beak and feather disease virus detected in the endangered Red Goshawk (Erythrotriorchis radiatus)
Authors: MacColl Christopher , Watson James E. M. , Leseberg Nicholas P. , Seaton Richard , Das Tridip , Das Shubhagata , Raidal Shane R.
Published: May 2024

We report the first detection and prevalence of Beak and feather disease virus (BFDV) in Australia’s Red Goshawk (Erythrotriorchis radiatus). This is a new host for this pervasive pathogen amongst a growing list of non-psittacine species including birds of prey from the orders Accipitriformes (hawks, eagles, kites), Falconiformes (falcons and caracas), and Strigiformes (owls). The Red Goshawk is the first non-psittacine species listed as Endangered to be diagnosed with BFDV. We report an initial case of infection discovered post-mortem in a dead nestling and subsequent surveillance of birds from across northern Australia. We reveal BFDV prevalence rates in a wild raptor population for the first time, with detections in 25% (n = 7/28) of Red Goshawks sampled. Prevalence appears higher in juveniles compared to adults, although not statistically significant, but is consistent with studies of wild psittacines. BFDV genotypes were associated with the Loriinae (lorikeets, budgerigar, and fig parrots), Cacatuini (Cockatoos), and Polytelini (long-tailed parrots) tribes; species which are preyed upon by Red Goshawks. A positive BFDV status may be associated with lower body mass but small sample sizes precluded robust statistical analysis. We postulate the possible impacts of the virus on Red Goshawks and discuss future research priorities given these preliminary observations.
Pre-analytical challenges from adsorptive losses associated with thiamine analysis
Authors: Edwards Katie A. , Randall Eileen A. , Wolfe Patricia C. , Kraft Clifford E. , Angert Esther R.
Published: May 2024

Thiamine (vitamin B1) is an essential vitamin serving in its diphosphate form as a cofactor for enzymes in the citric acid cycle and pentose-phosphate pathways. Its concentration reported in the pM and nM range in environmental and clinical analyses prompted our consideration of the components used in pre-analytical processing, including the selection of filters, filter apparatuses, and sample vials. The seemingly innocuous use of glass fiber filters, glass filter flasks, and glass vials, ubiquitous in laboratory analysis of clinical and environmental samples, led to marked thiamine losses. 19.3 nM thiamine was recovered from a 100 nM standard following storage in glass autosampler vials and only 1 nM of thiamine was obtained in the filtrate of a 100 nM thiamine stock passed through a borosilicate glass fiber filter. We further observed a significant shift towards phosphorylated derivatives of thiamine when an equimolar mixture of thiamine, thiamine monophosphate, and thiamine diphosphate was stored in glass (most notably non-silanized glass, where a reduction of 54% of the thiamine peak area was observed) versus polypropylene autosampler vials. The selective losses of thiamine could lead to errors in interpreting the distribution of phosphorylated species in samples. Further, some loss of phosphorylated thiamine derivatives selectively to amber glass vials was observed relative to other glass vials. Our results suggest the use of polymeric filters (including nylon and cellulose acetate) and storage container materials (including polycarbonate and polypropylene) for thiamine handling. Losses to cellulose nitrate and polyethersulfone filters were far less substantial than to glass fiber filters, but were still notable given the low concentrations expected in samples. Thiamine losses were negated when thiamine was stored diluted in trichloroacetic acid or as thiochrome formed in situ, both of which are common practices, but not ubiquitous, in thiamine sample preparation.
Recent and projected changes in climate patterns in the Middle East and North Africa (MENA) region
Authors: Francis Diana , Fonseca Ricardo
Published: May 2024

Observational and reanalysis datasets reveal a northward shift of the convective regions over northern Africa in summer and an eastward shift in winter in the last four decades, with the changes in the location and intensity of the thermal lows and subtropical highs also modulating the dust loading and cloud cover over the Middle East and North Africa region. A multi-model ensemble from ten models of the Coupled Model Intercomparison Project—sixth phase gives skillful simulations when compared to in-situ measurements and generally captures the trends in the ERA-5 data over the historical period. For the most extreme climate change scenario and towards the end of the twenty-first century, the subtropical highs are projected to migrate poleward by 1.5°, consistent with the projected expansion of the Hadley Cells, with a weakening of the tropical easterly jet in the summer by up to a third and a strengthening of the subtropical jet in winter typically by 10% except over the eastern Mediterranean where the storm track is projected to shift polewards. The length of the seasons is projected to remain about the same, suggesting the warming is likely to be felt uniformly throughout the year.
A psychometric assessment of a novel scale for evaluating vaccination attitudes amidst a major public health crisis
Authors: Cheng Linan , Kong Jianhui , Xie Xiaofeng , Zhang Fengying
Published: May 2024

Despite abundant scientific evidence supporting immunization benefits, vaccine hesitancy remains a significant global health concern, particularly during public health crises. Exploring public attitudes towards vaccination is crucial. This study aimed to develop and validate a tailored Public Vaccination Attitudes Scale specifically under the unique circumstances of a public health crisis. A psychometric evaluation was conducted using a cross-sectional study during the peak of a major public health crisis. The scale was developed and its psychometric properties validated using three approaches: (1) generating the item pool through literature research and focus group discussions; (2) assessing the items through expert consultation; and (3) evaluating construct validity, content validity, and internal consistency reliability through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Data from a total of 3921 respondents were randomly divided into two subsets, one for EFA (n = 1935) and the other for CFA (n = 1986). A 22-item draft scale with five factors was created after literature research and focus group discussion. The content validity of this scale ranged between 0.88 and 1.00. EFA showed a 17-item scale with four factors (Cronbach’s α > 0.7) accounting for 68.044% of the total variance. CFA showed that the values of the fit indices, including convergent validity and discriminant validity, were excellent or acceptable. The overall Cronbach’s α was 0.874, and each factor ranged from 0.726 to 0.885. This study introduces a valuable tool for assessing vaccination attitudes during public health crises, aiding researchers, policymakers, and nurses in combating vaccine hesitancy. Emphasizing the importance of fostering vaccine acceptance, it enhances disease control during emergencies, contributing to the knowledge needed for more effective public health strategies and crisis responses
SDPR expression in human trabecular meshwork and its potential role in racial disparities of glaucoma
Authors: Shui Ying-Bo , Liu Ying , Huang Andrew J. W. , Siegfried Carla J.
Published: May 2024

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM from Black vs White POAG patients’ surgical specimens, with no significant expression differences in other caveolae-associated genes, confirmed by qPCR analysis. No racial differences in SDPR gene expression were noted in healthy donor tissue by PCR analysis, but there was greater expression as compared to specimens from patients with glaucoma. Analysis of SDPR protein expression confirmed specific expression in the TM regions, but not in adjacent tissues. TEM studies of TM specimens from healthy donors did not demonstrate any racial differences in caveolar morphology, but a significant reduction of caveolae with normal morphology and immuno-gold staining of SDPR were noted in glaucomatous TM as compared to TM from healthy donors. Linkage of SDPR expression levels in TM, POAG development, and caveolar ultrastructural morphology may provide the basis for a novel pathway of exploration of the pathologic mechanisms of glaucoma. Differential gene expression of SDPR in TM from Black vs White subjects with glaucoma may further our understanding of the important public health implications of the racial disparities of this blinding disease.
Examining a 12-year experience within Kazakhstan’s national heart transplantation program
Authors: Semenova Yuliya , Shaisultanova Saule , Beyembetova Altynay , Asanova Aruzhan , Sailybayeva Aliya , Novikova Svetlana , Myrzakhmetova Gulzhan , Pya Yuriy
Published: May 2024

Kazakhstan has one of the lowest heart transplantation (HTx) rates globally, but there are no studies evaluating the outcomes of HTx. This study aimed to provide a comprehensive analysis of the national HTx program over a 12-year period (2012–2023). Survival analysis of the national HTx cohort was conducted using life tables, Kaplan‒Meier curves, and Cox regression methods. Time series analysis was applied to analyze historical trends in HTx per million population (pmp) and to make future projections until 2030. The number of patients awaiting HTx in Kazakhstan was evaluated with a regional breakdown. The pmp rates of HTx ranged from 0.06 to 1.08, with no discernible increasing trend. Survival analysis revealed a rapid decrease in the first year after HTx, reaching 77.0% at 379 days, with an overall survival rate of 58.1% at the end of the follow-up period. Among the various factors analyzed, recipient blood levels of creatinine and total bilirubin before surgery, as well as the presence of infection or sepsis and the use of ECMO after surgery, were found to be significant contributors to the survival of HTx patients. There is a need for public health action to improve the HTx programme.
High histone crotonylation modification in bovine fibroblasts promotes cell proliferation and the developmental efficiency of preimplantation nuclear transfer embryos
Authors: Zhao Xiaoyu , Du Mengxin , Wu Shanshan , Du Zhiwen , Liu Shuqin , Yang Lei , Ma Haoran , Zhang Liguo , Song Lishuang , Bai Chunling , Su Guanghua , Li Guangpeng
Published: May 2024

Lysine crotonylation (Kcr) is a recently discovered histone acylation modification that is closely associated with gene expression, cell proliferation, and the maintenance of stem cell pluripotency and indicates the transcriptional activity of genes and the regulation of various biological processes. During cell culture, the introduction of exogenous croconic acid disodium salt (Nacr) has been shown to modulate intracellular Kcr levels. Although research on Kcr has increased, its role in cell growth and proliferation and its potential regulatory mechanisms remain unclear compared to those of histone methylation and acetylation. Our investigation demonstrated that the addition of 5 mM Nacr to cultured bovine fibroblasts increased the expression of genes associated with Kcr modification, ultimately promoting cell growth and stimulating cell proliferation. Somatic cell nuclear transfer of donor cells cultured in 5 mM Nacr resulted in 38.1% blastocyst development, which was significantly greater than that in the control group (25.2%). This research is important for elucidating the crotonylation modification mechanism in fibroblast proliferation to promote the efficacy of somatic cell nuclear transfer.
Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy
Authors: Yan Judy , Mehta Shanti , Patel Keya , Dhupar Narisa , Little Ness , Ong Tone Stephan
Published: May 2024

Fuchs endothelial corneal dystrophy (FECD) is a complex corneal disease characterized by the progressive decline and morphological changes of corneal endothelial cells (CECs) that leads to corneal edema and vision loss. The most common mutation in FECD is an intronic CTG repeat expansion in transcription factor 4 (TCF4) that leads to its altered expression. Corneal endothelial wound healing occurs primarily through cell enlargement and migration, and FECD CECs have been shown to display increased migration speeds. In this study, we aim to determine whether TCF4 can promote cellular migration in FECD CECs. We generated stable CEC lines derived from FECD patients that overexpressed different TCF4 isoforms and investigated epithelial-to-mesenchymal (EMT) expression, morphological analysis and cellular migration speeds. We found that full length TCF4-B isoform overexpression promotes cellular migration in FECD CECs in an EMT-independent manner. RNA-sequencing identified several pathways including the negative regulation of microtubules, withTUBB4A(tubulin beta 4A class IVa) as the top upregulated gene. TUBB4A expression was increased in FECD ex vivo specimens, and there was altered expression of cytoskeleton proteins, tubulin and actin, compared to normal healthy donor ex vivo specimens. Additionally, there was increased acetylation and detyrosination of microtubules in FECD supporting that microtubule stability is altered in FECD and could promote cellular migration. Future studies could be aimed at investigating if targeting the cytoskeleton and microtubules would have therapeutic potential for FECD by promoting cellular migration and regeneration.
Sync fast and solve things—best practices for responsible digital health
Authors: Landers Constantin , Blasimme Alessandro , Vayena Effy
Published: May 2024

Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation.

To grant practical insight into best practices for responsible digital health innovation, we conducted a qualitative study based on an interactive engagement methodology. We engaged key stakeholders (n = 46) operating at the translational frontier of digital health. This approach allowed us to identify three clusters of governance and innovation best practices in digital health innovation: i) inclusive co-creation, ii) responsive regulation, and iii) value-driven innovation. Our study shows that realizing responsible digital health requires diverse stakeholders’ commitment to adapt innovation and regulation practices, embracing co-creation as the default modus operandi for digital health development. We describe these collaborative practices and show how they can ensure that innovation is neither slowed by overregulation, nor leads to unethical outcomes.
Artificial intelligence in digital pathology: a systematic review and meta-analysis of diagnostic test accuracy
Authors: McGenity Clare , Clarke Emily L. , Jennings Charlotte , Matthews Gillian , Cartlidge Caroline , Freduah-Agyemang Henschel , Stocken Deborah D. , Treanor Darren
Published: May 2024

Ensuring diagnostic performance of artificial intelligence (AI) before introduction into clinical practice is essential. Growing numbers of studies using AI for digital pathology have been reported over recent years. The aim of this work is to examine the diagnostic accuracy of AI in digital pathology images for any disease. This systematic review and meta-analysis included diagnostic accuracy studies using any type of AI applied to whole slide images (WSIs) for any disease. The reference standard was diagnosis by histopathological assessment and/or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model, with additional subgroup analyses also performed. Of 2976 identified studies, 100 were included in the review and 48 in the meta-analysis. Studies were from a range of countries, including over 152,000 whole slide images (WSIs), representing many diseases. These studies reported a mean sensitivity of 96.3% (CI 94.1–97.7) and mean specificity of 93.3% (CI 90.5–95.4). There was heterogeneity in study design and 99% of studies identified for inclusion had at least one area at high or unclear risk of bias or applicability concerns. Details on selection of cases, division of model development and validation data and raw performance data were frequently ambiguous or missing. AI is reported as having high diagnostic accuracy in the reported areas but requires more rigorous evaluation of its performance.
Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer’s disease
Authors: Sanchez-Rodriguez Lazaro M. , Bezgin Gleb , Carbonell Felix , Therriault Joseph , Fernandez-Arias Jaime , Servaes Stijn , Rahmouni Nesrine , Tissot Cécile , Stevenson Jenna , Karikari Thomas K. , Ashton Nicholas J. , Benedet Andréa L. , Zetterberg Henrik , Blennow Kaj , Triana-Baltzer Gallen , Kolb Hartmuth C. , Rosa-Neto Pedro , Iturria-Medina Yasser
Published: May 2024

Neuronal dysfunction and cognitive deterioration in Alzheimer’s disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.
Excessive endometrial PlGF- Rac1 signalling underlies endometrial cell stiffness linked to pre-eclampsia
Authors: Raja Xavier Janet P. , Rianna Carmela , Hellwich Emily , Nikolou Iliana , Lankapalli Aditya Kumar , Brucker Sara Y. , Singh Yogesh , Lang Florian , Schäffer Tilman E. , Salker Madhuri S.
Published: May 2024

Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton at the maternal interface. We explored the global effects of PlGF in endometrial stromal cells (EnSCs) using the concerted approach of proteomics, atomic force microscopy (AFM), and electrical impedance spectroscopy (EIS). Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization-associated proteins in EnSCs. Rac1 and PAK1 transcript levels, activity, and actin polymerization were significantly increased with PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF treatment. The additive effect of PlGF on actin polymerization was suppressed with siRNA-mediated inhibition of Rac1, PAK1, and WAVE2. Interestingly, the increase in cell stiffness by PlGF treatment was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion. Taken together, aberrant PlGF levels in the endometrium can contribute to an altered pre-pregnancy maternal microenvironment and offer a unifying explanation for the pathological changes observed in conditions such as pre-eclampsia (PE).
Synthetic dimensions for topological and quantum phases
Authors: Argüello-Luengo Javier , Bhattacharya Utso , Celi Alessio , Chhajlany Ravindra W. , Grass Tobias , Płodzień Marcin , Rakshit Debraj , Salamon Tymoteusz , Stornati Paolo , Tarruell Leticia , Lewenstein Maciej
Published: May 2024

The concept of synthetic dimensions works particularly well in atomic physics, quantum optics, and photonics, where the internal degrees of freedom (Zeeman sublevels of the ground state, metastable excited states, or motional states for atoms, and angular momentum states or transverse modes for photons) provide the synthetic space. In this Perspective article we report on recent progress on studies of synthetic dimensions, mostly, but not only, based on the research realized around the Barcelona groups (ICFO, UAB), Donostia (DIPC), Poznan (UAM), Kraków (UJ), and Allahabad (HRI). We describe our attempts to design quantum simulators with synthetic dimensions, to mimic curved spaces, artificial gauge fields, lattice gauge theories, twistronics, quantum random walks, and more.
Plasmonic chemistry for sustainable ammonia production
Authors: Choudhary Arsha , Halder Anubhab , Aggarwal Pooja , Govind Rao Vishal
Published: May 2024

The traditional Haber-Bosch process for ammonia production is energy-intensive and relies on harsh conditions. Plasmonic materials are considered a sustainable alternative to this process. In plasmonics, the ability to localize and enhance light fields beyond the diffraction limit offers a promising avenue for harnessing visible light for photocatalysis. Moreover, the integration of plasmonic metals with various catalysts presents a promising avenue to improve efficiency and selectivity. However, cost and stability challenges hinder large-scale applications. Researchers are actively exploring new materials, optimizing catalyst design, and improving stability to overcome these hurdles. This Review delves into the intricacies of plasmonic catalysis, including material design, co-catalyst selection, and the use of nanotechnologies for precise control of metal properties in plasmonic catalysis. It emphasizes understanding energy flow at material interfaces. Ultimately, the Review aims to establish a foundation for efficient nitrogen fixation through plasmonic photocatalysis, paving the way for a more sustainable future.
Anthropogenic eutrophication and stratification strength control hypoxia in the Yangtze Estuary
Authors: Sheng Hui , Darby Stephen E. , Zhao Ning , Liu Dongyan , Kettner Albert J. , Lu Xixi , Yang Yang , Gao Jianhua , Zhao Yaqing , Wang Ya Ping
Published: May 2024

Many large estuaries are threatened by intensifying hypoxia. However, due to the limited duration of available observations, uncertainties persist regarding the level of contemporary hypoxia intensity in a longer-term context and the relative contributions of climate versus human factors. Here we present sediment records for the hypoxia intensity and associated environmental parameters in the Yangtze Estuary over the past three centuries. The results show that the hypoxia intensity has been increasing during the last half century due to anthropogenic eutrophication, but the current hypoxia condition is not as severe as some preindustrial periods due to weaker stratification in the water column. Our findings suggest that if anthropogenic and climatic forcing coincide in the foreseeable future, the hypoxia intensity of the Yangtze Estuary may reach unprecedented levels.
Full use of lignocellulosic biomass for efficient synthesis of l-tyrosine and its analogues by engineering microbial consortia
Authors: Zhao Mingtao , Wu Xiaofeng , Tao Yankai , Xiao Yi
Published: May 2024

A glucose–xylose–phenolics (GXP) system was developed by engineering Escherichia coli–Escherichia coli consortia to achieve the full use of lignocellulosic biomass for efficient synthesis of l-tyrosine and its analogues.
Acidity-responsive polyphenol-coordinated nanovaccines for improving tumor immunotherapy via bidirectional reshaping of the immunosuppressive microenvironment and controllable release of antigens
Authors: Qiu Huimin , Wang Shuman , Huang Rimei , Liu Xingyu , Li Liqun , Liu Zheng , Wang Aihui , Ji Shichen , Liang Hong , Jiang Bang-Ping , Shen Xing-Can
Published: May 2024

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI).
6-Gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology
Authors: Li Wenwen , Zhang Yun , Wang Quyi , Wang Yu , Fan Yuwen , Shang Erxin , Jiang Shu , Duan Jinao
Published: May 2024

An integrated strategy of plasma metabolomics, network pharmacology, experimental verification, and molecular docking was used to elucidate that ferroptosis is involved in the amelioration of colitis by 6-G.
Facile synthesis of hyperbranched magnetic nanospheres for highly efficient removal of methyl orange
Authors: Song Jinting , Chen Sufang , Lyu Renliang , Zhang Daohong , Hong Jingping
Published: May 2024

Hyperbranched ATHP1 coated magnetic microspheres were successfully synthesized. Fe3O4@ATHP1 has an excellent adsorption ability for methyl orange. Fe3O4@ATHP1 exhibits easy separation and good recyclability.
A crystalline/amorphous FeCo alloy/FeCoNi-Pi bifunctional electrocatalyst for efficient overall water splitting
Authors: Li Haoyu , Xiao Yawei , Tian Xu , Xing Xinxin , Cao Minhua , Wang Yude
Published: May 2024

The crystalline/amorphous composite strategy proposed in this work presents a new concept for the rational design of FeCo alloy-based bifunctional electrocatalysts for efficient overall water splitting.