bluuebunny/crossref_metadata_2025 huggingface dataset:
(Pre)diabetes and a higher level of glycaemic measures are continuously associated with corneal neurodegeneration assessed by corneal confocal microscopy: the Maastricht Study
Authors: Mokhtar Sara B. A. , van der Heide Frank C. T. , Oyaert Karel A. M. , van der Kallen Carla J. H. , Berendschot Tos T. J. M. , Scarpa Fabio , Colonna Alessia , de Galan Bastiaan E. , van Greevenbroek Marleen M. J. , Dagnelie Pieter C. , Schalkwijk Casper G. , Nuijts Rudy M. M. A. , Schaper Nicolaas C. , Kroon Abraham A. , Schram Miranda T. , Webers Carroll A. B. , Stehouwer Coen D. A.
Published: August 2023

Aims/hypothesis

To assess the associations between glucose metabolism status and a range of continuous measures of glycaemia with corneal nerve fibre measures, as assessed using corneal confocal microscopy.

Methods

We used population-based observational cross-sectional data from the Maastricht Study of N=3471 participants (mean age 59.4 years, 48.4% men, 14.7% with prediabetes, 21.0% with type 2 diabetes) to study the associations, after adjustment for demographic, cardiovascular risk and lifestyle factors, between glucose metabolism status (prediabetes and type 2 diabetes vs normal glucose metabolism) plus measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, skin autofluorescence [SAF] and duration of diabetes) and composite Z-scores of corneal nerve fibre measures or individual corneal nerve fibre measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length and fractal dimension). We used linear regression analysis, and, for glucose metabolism status, performed a linear trend analysis.

Results

After full adjustment, a more adverse glucose metabolism status was associated with a lower composite Z-score for corneal nerve fibre measures (β coefficients [95% CI], prediabetes vs normal glucose metabolism −0.08 [−0.17, 0.03], type 2 diabetes vs normal glucose metabolism −0.14 [−0.25, −0.04]; linear trend analysis showed a p value of 0.001), and higher levels of measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, SAF and duration of diabetes) were all significantly associated with a lower composite Z-score for corneal nerve fibre measures (per SD: −0.09 [−0.13, −0.05], −0.07 [−0.11, −0.03], −0.08 [−0.11, −0.04], −0.05 [−0.08, −0.01], −0.09 [−0.17, −0.001], respectively). In general, directionally similar associations were observed for individual corneal nerve fibre measures.

Conclusions/interpretation

To our knowledge, this is the first population-based study to show that a more adverse glucose metabolism status and higher levels of glycaemic measures were all linearly associated with corneal neurodegeneration after adjustment for an extensive set of potential confounders. Our results indicate that glycaemia-associated corneal neurodegeneration is a continuous process that starts before the onset of type 2 diabetes. Further research is needed to investigate whether early reduction of hyperglycaemia can prevent corneal neurodegeneration.

Graphical Abstract
Detection of botanical adulterants in saffron powder
Authors: Ryparova Kvirencova Jana , Navratilova Klara , Hrbek Vojtech , Hajslova Jana
Published: August 2023

Saffron is a unique spice obtained by drying stigmas of saffron flowers (Crocus sativus L.). Due to its high price, economically motivated adulteration occurs relatively often. The presented study aimed to develop an effective strategy for the detection of the following potential botanical adulterants used for a saffron substitution or dilution: safflower (Carthamus tinctorius L.), calendula (Calendula officinalis L.), turmeric (Curcuma longa L.), achiote (Bixa orellana L.), red pepper (Capsicum spp.), mountain arnica (Arnica montana L.), beet (Beta vulgaris L.), and pomegranate (Punica granatum L.). A non-target screening strategy based on ultra-high performance reverse-phase liquid chromatography coupled to tandem high-resolution mass spectrometry (UHPLC-HRMS/MS) was employed for the analysis of an aqueous ethanol plant extract. By using multivariate statistical methods, principal components analysis (PCA), and partial least squares discriminant analysis (PLS-DA), for processing the generated “chemical fingerprints,” metabolites unique to the investigated plants could be identified. To enable routine saffron authenticity control by target screening, an internal spectral database was developed; currently, it involves 82 unique markers. In this way, the detection addition as low as 1% (w/w) of all analyzed botanical adulterants in admixture with saffron was possible. The developed method was used to control 7 saffron powder samples from the Czech market, and none of the monitored adulterants were confirmed.
Customized poly (aniline-co-o-aminobenzoic acid) by functionalizing with n/p dopants and its application in symmetrical redox supercapacitor
Authors: Manikandan G. , Sudhakar Y. N. , Selvakumar M. , Pitchumani S. , Renganathan N. G.
Published: August 2023

The chemically synthesized poly (aniline-co-o-aminobenzoic acid) copolymer was functionalized electrochemically by cationic and anionic doping and tailored its property for suitable redox behavior. The mechanism during this process has been proposed using cyclic voltammetry studies, and the doping was confirmed in FTIR and UV studies. In the electrochemical impedance spectroscopy, undoped and doped behavior revealed the possibility of fine-tuning of conditions that are required for redox supercapacitor. A symmetrical supercapacitor was fabricated with an optimized doped co-polymer-based electrode and the specific capacitance values were 107 Fg−1 for n-doped polymer and 140 Fg−1 for p-doped polymer. The electrochemical characterization of n/p 1 cm2 cells in terms of specific power, specific energy, specific capacitance, columbic efficiency, IR drop, and ESR was calculated from charge/discharge studies. Data were analyzed in terms of complex power versus complex capacitance, and hence, active region of n/p supercapacitor was obtained. This concept paves way for future tailoring of dopants during the synthesis of conducting polymer and its copolymers.

Graphical abstract
Neural network architecture with intermediate distribution-driven layer for classification of multidimensional data with low class separability
Authors: Borek-Marciniec Weronika , Ksieniewicz Pawel
Published: August 2023

Simple neural network classification tasks are based on performing extraction as transformations of the set simultaneously with optimization of weights on individual layers. In this paper, the Representation 7 architecture is proposed, the primary assumption of which is to divide the inductive procedure into separate blocks – transformation and decision – which may lead to a better generalization ability of the presented model. Architecture is based on the processing context of the typical neural network and unifies datasets into a shared, generically sampled space. It can be applicable in the case of difficult problems – defined not as imbalance or streaming data but by low-class separability and a high dimensionality. This article has tested the hypothesis that – in such conditions – the proposed method could achieve better results than reference algorithms by comparing the R7 architecture with state-of-the-art methods, raw mlp and Tabnet architecture. The contributions of this work are the proposition of the new architecture and complete experiments on synthetic and real datasets with the evaluation of the quality and loss achieved by R7 and by reference methods.
Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability
Authors: Nelson Louisa , Barnes Bethany M. , Tighe Anthony , Littler Samantha , Coulson-Gilmer Camilla , Golder Anya , Desai Sudha , Morgan Robert D. , McGrail Joanne C. , Taylor Stephen S.
Published: August 2023

Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% — largely due to late diagnosis and rapid development of drug resistance, e.g., via CIN-driven ABCB1 translocations. However, CIN is also a cell cycle vulnerability that can be exploited to specifically target tumour cells, illustrated by the success of PARP inhibitors to target homologous recombination deficiency (HRD). However, a lack of appropriate models with ongoing CIN has been a barrier to fully exploiting disease-specific CIN mechanisms. This barrier is now being overcome with the development of patient-derived cell cultures and organoids. In this review, we describe our progress building a Living Biobank of over 120 patient-derived ovarian cancer models (OCMs), predominantly from HGSOC. OCMs are highly purified tumour fractions with extensive proliferative potential that can be analysed at early passage. OCMs have diverse karyotypes, display intra- and inter-patient heterogeneity and mitotic abnormality rates far higher than established cell lines. OCMs encompass a broad-spectrum of HGSOC hallmarks, including a range of p53 alterations and BRCA1/2 mutations, and display drug resistance mechanisms seen in the clinic, e.g., ABCB1 translocations and BRCA2 reversion. OCMs are amenable to functional analysis, drug-sensitivity profiling, and multi-omics, including single-cell next-generation sequencing, and thus represent a platform for delineating HGSOC-specific CIN mechanisms. In turn, our vision is that this understanding will inform the design of new therapeutic strategies.
Causal link between thyroid function and schizophrenia: a two-sample Mendelian randomization study
Authors: Freuer Dennis , Meisinger Christa
Published: August 2023

Schizophrenia is a chronic psychiatric disorder with inconsistent behavioral and cognitive abnormalities with profound effects on the individual and the society. Individuals with schizophrenia have altered thyroid function, but results from observational studies are conflicting. To date, it remains unclear whether and in which direction there is a causal relationship between thyroid function and schizophrenia. To investigate causal paths, a bidirectional two-sample Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies including up to 330,132 Europeans. Thyroid function was described by the normal-range thyroid-stimulating hormone (TSH) and free thyroxine levels as well as an increased and decreased TSH status. The iterative radial inverse-variance weighted approach with modified second order weights was used as the main method. Based on a discovery and replication sample for schizophrenia, pooled effect estimates were derived using a fixed-effect meta-analysis. Robustness of results was assessed using both a range of pleiotropy robust methods and a network analysis that clustered genetic instruments potentially responsible for horizontal pleiotropy. Genetic liability for hypothyroidism was inversely associated with schizophrenia ($$\beta =-0.06$$; 95% CI: (-0.10; -0.02); $$P=0.004$$). No notable associations were observed between other thyroid parameters and schizophrenia. Furthermore, no associations could be detected in the reverse direction. Our results suggest that an elevated level of TSH reduce the risk for schizophrenia. The role of thyroid function and the hypothalamic-pituitary-thyroid axis in the development of schizophrenia should be subject of further research.
First implementation of a new cross-disciplinary observation strategy for heavy precipitation events from formation to flooding
Authors: Wieser Andreas , Güntner Andreas , Dietrich Peter , Handwerker Jan , Khordakova Dina , Ködel Uta , Kohler Martin , Mollenhauer Hannes , Mühr Bernhard , Nixdorf Erik , Reich Marvin , Rolf Christian , Schrön Martin , Schütze Claudia , Weber Ute
Published: August 2023

Heavy Precipitation Events (HPE) are the result of enormous quantities of water vapor being transported to a limited area. HPE rainfall rates and volumes cannot be fully stored on and below the land surface, often leading to floods with short forecast lead times that may cause damage to humans, properties, and infrastructure. Toward an improved scientific understanding of the entire process chain from HPE formation to flooding at the catchment scale, we propose an elaborated event-triggered observation concept. It combines flexible mobile observing systems out of the fields of meteorology, hydrology and geophysics with stationary networks to capture atmospheric transport processes, heterogeneous precipitation patterns, land surface and subsurface storage processes, and runoff dynamics. As part of the Helmholtz Research Infrastructure MOSES (Modular Observation Solutions for Earth Systems), the effectiveness of our observation strategy is illustrated by its initial implementation in the Mueglitz river basin (210 km2), a headwater catchment of the Elbe in the Eastern Ore Mountains with historical and recent extreme flood events. Punctual radiosonde observations combined with continuous microwave radiometer measurements and back trajectory calculations deliver information about the moisture sources, and initiation and development of HPE. X-band radar observations calibrated by ground-based disdrometers and rain gauges deliver precipitation information with high spatial resolution. Runoff measurements in small sub-catchments complement the discharge time series of the operational network of gauging stations. Closing the catchment water balance at the HPE scale, however, is still challenging. While evapotranspiration is of less importance when studying short-term convective HPE, information on the spatial distribution and on temporal variations of soil moisture and total water storage by stationary and roving cosmic ray measurements and by hybrid terrestrial gravimetry offer prospects for improved quantification of the storage term of the water balance equation. Overall, the cross-disciplinary observation strategy presented here opens up new ways toward an integrative and scale-bridging understanding of event dynamics.
Associations of attention-deficit/hyperactivity disorder with inflammatory diseases. Results from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS)
Authors: Boemanns Lena , Staab Julia , Meyer Thomas
Published: August 2023

Background

Despite conflicting data, some studies have suggested a pathophysiological relationship between inflammation and attention-deficit/hyperactivity disorder (ADHD).

Methods

Using data from the nationwide and representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS; n = 6922 study participants aged 11–17 years), this post hoc analysis assessed the associations between ADHD and three common inflammatory diseases.

Results

Results showed univariate associations between ADHD and lifetime inflammatory diseases including atopic dermatitis (p = 0.002), otitis media (p = 0.001), and herpes simplex infection (p = 0.032). In logistic regression models adjusted for clinically relevant confounders, we found that ADHD remained a significant predictor of all three inflammatory diseases (atopic dermatitis, Exp(β) = 1.672, 95% confidence interval [CI] 1.239–2.257, p = 0.001; otitis media, Exp(β) = 1.571, 95% CI 1.209–2.040, p = 0.001; herpes simplex, Exp(β) = 1.483, 95% CI 1.137–1.933, p = 0.004).

Conclusion

Our findings demonstrate a positive link between ADHD and peripheral inflammatory diseases, including atopic dermatitis, otitis media, and herpes simplex infection. Further studies are needed to understand the exact pathophysiological mechanisms underlying these associations.
AI art in architecture
Authors: Ploennigs Joern , Berger Markus
Published: August 2023

Recent diffusion-based AI art platforms can create impressive images from simple text descriptions. This makes them powerful tools for concept design in any discipline that requires creativity in visual design tasks. This is also true for early stages of architectural design with multiple stages of ideation, sketching and modelling. In this paper, we investigate how applicable diffusion-based models already are to these tasks. We research the applicability of the platforms Midjourney, DALL$$\cdot$$
·
E 2 and Stable Diffusion to a series of common use cases in architectural design to determine which are already solvable or might soon be. Our novel contributions are: (i) a comparison of the capabilities of public AI art platforms; (ii) a specification of the requirements for AI art platforms in supporting common use cases in civil engineering and architecture; (iii) an analysis of 85 million Midjourney queries with Natural Language Processing (NLP) methods to extract common usage patterns. From this we derived (iv) a workflow for creating images for interior designs and (v) a workflow for creating views for exterior design that combines the strengths of the individual platforms.
Improving the light stability of perovskite solar cell with new hole transport material based on spiro[fluorene-9,9′-xanthene]
Authors: Luo Huiming , Zhang Zheng , Yuan Ligang , Wang Jiarong , Li Bin , Wang Sijing , Abdi-Jalebi Mojtaba , Shi Lei , Zhang Wenjun , Guo Kunpeng , Ding Liming , Yan Keyou
Published: August 2023

Development of suitable hole transport materials is vital for perovskite solar cells (PSCs) to diminish the energy barrier and minimize the potential loss. Here, a low-cost hole transport molecule named SFX-POCCF3 (23.72 $/g) is designed with a spiro[fluorene-9,9'-xanthene] (SFX) core and terminated by trifluoroethoxy units. Benefiting from the suitable energy level, high hole mobility, and better charge extraction and transport, the PSCs based on SFX-POCCF3 exhibit improved open-circuit voltage by 0.02 V, therefore, the PSC device based on SFX-POCCF3 exhibits a champion PCE of 21.48%, which is comparable with the control device of Spiro-OMeTAD (21.39%). More importantly, the SFX-POCCF3 based PSC possesses outstanding light stability, which retains 95% of the initial efficiency after about 1,000 h continuous light soaking, which is in accordance with the result continuous output at maximum power point. Whereas, Spiro-OMeTAD witnesses a rapid decrease to 80% of its original efficiency after 100 h light soaking. This work demonstrated that an efficient alignment of energy levels between HTL and perovskite will lead to significant highly efficient PSCs with remarkably enhanced light stability.
Differential gene expression profile evaluation between uterine leiomyoma and leiomyosarcoma using a machine learning approach
Authors: Upadhyay Sonal , Bhushan Ravi , Tripathi Anima , Chaubey Lavina , Diwakar Amita , Dubey Pawan K.
Published: August 2023

Objective

The objective of this study is to differentiate between uterine leiomyomas (ULM) and uterine leiomyosarcomas (ULMS) by conducting molecular differential analysis and identifying potential prognostic biomarkers for diagnosis.

Methods

The microarray datasets (GSEID: GSE64763 and GSE185543) were retrieved from the Gene Expression Omnibus database. Data preprocessing and differential gene expressions (DEGs) analysis were performed. The DEGs were further intersected to find the common DEGs in ULM and ULMS and further validation of selected DEGs were performed. Further, a machine learning classifier was also applied in the selection of biomarkers. Protein-protein interaction network based upon STRING v 10.5, was constructed. Additionally, Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were also performed to dissect possible functions and pathways.

Results

A total of 50 significant DEGs for ULM while 321 DEGs for ULMS have been identified with their official gene symbol. Between ULM and ULMS, a total of 14 common DEGs were identified of which 8 were up-regulated while 6 were down-regulated. The DEGs of (GSE185543) were also analyzed and the significant genes were retrieved common in both datasets for further analysis. Using a machine learning approach, 10 feature genes were identified. Using the expression profiles of these genes, a sequential minimal optimization (SMO) prediction model was built on the training set, and it accurately and reliably classified features expression in ULM and ULMS in the independent test set. Furthermore, Co- Enrichment analysis was also performed.

Conclusion

The study identified several DEGs, including ZNF365, EPYC, COL11A1, SHOX2, MMP13, TNN, GPM6A, and GATA2, through cross-validation, machine learning classifier, and Co- Enrichment analysis. These candidate disease genes may provide valuable insight into the underlying mechanisms and could be used as potential diagnostic biomarkers for ULM and ULMS. However, further validation of these genes is necessary to better understand their roles in the pathogenesis of ULM and ULMS.
Commemorating the Past and Performing Power: Parades of Ancestors on Caligula's Coinage
Authors: McIntyre Gwynaeth
Published: August 2023

This article explores the interconnection between Caligula's rehabilitation of his family and the performance of imperial power through processions as presented on three of his coin types. It argues that Caligula used the depictions of processions in connection with coin types celebrating his father, mother, and brothers to create a ‘parade of ancestors’. These coins served as portable visual reminders (monumenta) of Germanicus’pompa triumphalisof 17 CE, the inclusion of Agrippina's image into thepompa circensisas part of the honours granted to Caligula's family members upon his accession, and the likely inclusion of Nero and Drusus’ images at the head of thetransvectio equitumduring the early years of Caligula's reign. By parading his family members on his coins in this way, Caligula was able to propel himself forward by looking to and commemorating the past, thereby creating permanentmonumentaof these public performances of power.
A 7-year analysis of attributable costs of healthcare-associated infections in a network of community hospitals in the southeastern United States
Authors: Zhang Helen L. , Crane Linda , Cromer Andrea Lynn , Green Amanda , Padgette Polly , Payne Valerie C. , Roach Linda , Wood Brittain , Anderson Deverick J.
Published: August 2023

We calculated the attributable cost of several healthcare-associated infections in a community hospital network: central-line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-onset Clostridioides difficile infections (CDI-HOs) (43 hospitals); surgical site infections (SSIs) (40 hospitals). From 2016 to 2022, the total cost of CLABSIs, CAUTIs, CDI-HOs, and SSIs was $420,012,025.
Effects of monolaurin on intestinal barrier, blood biochemical profile, immunity and antioxidant function in porcine epidemic diarrhoea virus-infected piglets
Authors: Wang Chao , Zhang Qian , Ji Changzheng , Hu Yuyan , Yi Dan , Wu Tao , Wang Lei , Zhao Di , Hou Yongqing
Published: August 2023

The effects of monolaurin (ML) on the health of piglets infected with porcine epidemic diarrhoea virus (PEDV) have not been fully understood. This study aimed to investigate its role in blood biochemical profile, intestinal barrier function, antioxidant function and the expression of antiviral genes in piglets infected with PEDV. Thirty-two piglets were randomly divided into four groups: control group, ML group, PEDV group and ML + PEDV group. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 d before PEDV infection. Results showed that PEDV infection significantly decreased D-xylose content and increased intestinal fatty acid-binding protein content, indicating that PEDV infection destroyed intestinal barrier and absorption function. While it could be repaired by ML administration. Moreover, ML administration significantly decreased plasma blood urea nitrogen and total protein content upon PEDV infection. These results suggested ML may increase protein utilisation efficiency. ML administration significantly decreased the number of large unstained cells and Hb and increased the number of leucocytes and eosinophils in the blood of PEDV-infected piglets, indicating ML could improve the immune defense function of the body. In the presence of PEDV infection, ML administration significantly increased superoxide dismutase and catalase activities in blood and colon, respectively, indicating ML could improve antioxidant capacity. Besides, ML administration reversed the expression of ISG15, IFIT3 and IL-29 throughout the small intestine and Mx1 in jejunum and ileum, indicating the body was in recovery from PEDV infection. This study suggests that ML could be used as a kind of feed additive to promote swine health upon PEDV infection.
Higher energy flux may improve short-term appetite control in adolescents with obesity: the NEXT study
Authors: Siroux Julie , Pereira Bruno , Fillon Alicia , Moore Halim , Dionnet Céline , Julian Valérie , Finlayson Graham S. , Duclos Martine , Boirie Yves , Isacco Laurie , Thivel David
Published: August 2023

Recent evidence suggests better appetite control in states of high-energy flux (HEF) in adults and lean children. Nevertheless, it is unknown whether this extends to youth with obesity. This study compares the effects of low, moderate or HEF on short-term appetitive control in adolescents with obesity. Sixteen adolescents with obesity (12–16 years, Tanner stages 3–5, 11 females) randomly completed three conditions: (i) low-energy flux (LEF); (ii) moderate energy flux (MEF; + 250 kcal) and (iii) HEF (HEF; + 500 kcal). Energy flux was achieved in MEF and HEF through elevated energy intake (EI) and concomitant increase in energy expenditure using cycling exercise (65 % VO2peak). Ad libitum EI, macronutrient intake and relative EI were assessed at dinner, subjective appetite sensations taken at regular intervals and food reward measured before dinner. Ad libitum EI at dinner was greater in LEF compared with HEF (P = 0·008), and relative EI (REI) was higher in LEF compared with MEF (P = 0·003) and HEF (P < 0·001). The absolute consumption of carbohydrates was lower in LEF compared with MEF (P = 0·047) and HEF (P < 0·001). Total AUC for hunger and desire to eat was lower in HEF compared with LEF (P < 0·001) and MEF (P = 0·038). Total AUC for prospective food consumption was lower on HEF compared with LEF (P = 0·004). Food choice sweet bias was higher in HEF (P = 0·005) compared with LEF. To conclude, increasing energy flux may improve short-term appetite control in adolescents with obesity.
The Challenge of Old Legal Manuscripts in Modern Law Libraries
Authors: Tearle Barbara
Published: August 2023

On the few occasions that old manuscripts are encountered in modern practice they may raise problems of reading old handwriting and identifying the place of the document in the legal process. This article by Barbara Tearle gives advice on why specialist help is needed and where to obtain it.
Raiders of the lost archive
Authors: Breslin Mike , Breslin Jas
Published: August 2023

In the second in our series of regular articles reviewing archived issues of Legal Information Management and The Law Librarian – as the journal was once known – the LIM editors travel back in time to 1983.
Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates
Authors: Burdo Tricia H. , Chen Chen , Kaminski Rafal , Sariyer Ilker K. , Mancuso Pietro , Donadoni Martina , Smith Mandy D. , Sariyer Rahsan , Caocci Maurizio , Liao Shuren , Liu Hong , Huo Wenwen , Zhao Huaqing , Misamore John , Lewis Mark G. , Simonyan Vahan , Thompson Elaine E. , Xu Ethan Y. , Cradick Thomas J. , Gordon Jennifer , Khalili Kamel
Published: August 2023

In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 1012, 1.4 × 1013 and 1.4 × 1014 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.
Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome
Authors: Zhai Lixiang , Xiao Haitao , Lin Chengyuan , Wong Hoi Leong Xavier , Lam Yan Y. , Gong Mengxue , Wu Guojun , Ning Ziwan , Huang Chunhua , Zhang Yijing , Yang Chao , Luo Jingyuan , Zhang Lu , Zhao Ling , Zhang Chenhong , Lau Johnson Yiu-Nam , Lu Aiping , Lau Lok-Ting , Jia Wei , Zhao Liping , Bian Zhao-Xiang
Published: August 2023

The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.
Streamlining the synthesis of amides using Nickel-based nanocatalysts
Authors: Gao Jie , Ma Rui , Poovan Fairoosa , Zhang Lan , Atia Hanan , Kalevaru Narayana V. , Sun Wenjing , Wohlrab Sebastian , Chusov Denis A. , Wang Ning , Jagadeesh Rajenahally V. , Beller Matthias
Published: August 2023

The synthesis of amides is a key technology for the preparation of fine and bulk chemicals in industry, as well as the manufacture of a plethora of daily life products. Furthermore, it constitutes a central bond-forming methodology for organic synthesis and provides the basis for the preparation of numerous biomolecules. Here, we present a robust methodology for amide synthesis compared to traditional amidation reactions: the reductive amidation of esters with nitro compounds under additives-free conditions. In the presence of a specific heterogeneous nickel-based catalyst a wide range of amides bearing different functional groups can be selectively prepared in a more step-economy way compared to previous syntheses. The potential value of this protocol is highlighted by the synthesis of drugs, as well as late-stage modifications of bioactive compounds. Based on control experiments, material characterizations, and DFT computations, we suggest metallic nickel and low-valent Ti-species to be crucial factors that makes this direct amide synthesis possible.
High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription
Authors: Bressin Annkatrin , Jasnovidova Olga , Arnold Mirjam , Altendorfer Elisabeth , Trajkovski Filip , Kratz Thomas A. , Handzlik Joanna E. , Hnisz Denes , Mayer Andreas
Published: August 2023

Gene transcription by RNA polymerase II (Pol II) is under control of promoters and distal regulatory elements known as enhancers. Enhancers are themselves transcribed by Pol II correlating with their activity. How enhancer transcription is regulated and coordinated with transcription at target genes has remained unclear. Here, we developed a high-sensitive native elongating transcript sequencing approach, called HiS-NET-seq, to provide an extended high-resolution view on transcription, especially at lowly transcribed regions such as enhancers. HiS-NET-seq uncovers new transcribed enhancers in human cells. A multi-omics analysis shows that genome-wide enhancer transcription depends on the BET family protein BRD4. Specifically, BRD4 co-localizes to enhancer and promoter-proximal gene regions, and is required for elongation activation at enhancers and their genes. BRD4 keeps a set of enhancers and genes in proximity through long-range contacts. From these studies BRD4 emerges as a general regulator of enhancer transcription that may link transcription at enhancers and genes.
Rapid self-heating synthesis of Fe-based nanomaterial catalyst for advanced oxidation
Authors: Yu Fengbo , Jia Chao , Wu Xuan , Sun Liming , Shi Zhijian , Teng Tao , Lin Litao , He Zhelin , Gao Jie , Zhang Shicheng , Wang Liang , Wang Shaobin , Zhu Xiangdong
Published: August 2023

Iron-based catalysts are promising candidates for advanced oxidation process-based wastewater remediation. However, the preparation of these materials often involves complex and energy intensive syntheses. Further, due to the inherent limitations of the preparation conditions, it is challenging to realise the full potential of the catalyst. Herein, we develop an iron-based nanomaterial catalyst via soft carbon assisted flash joule heating (FJH). FJH involves rapid temperature increase, electric shock, and cooling, the process simultaneously transforms a low-grade iron mineral (FeS) and soft carbon into an electron rich nano Fe0/FeS heterostructure embedded in thin-bedded graphene. The process is energy efficient and consumes 34 times less energy than conventional pyrolysis. Density functional theory calculations indicate that the electron delocalization of the FJH-derived heterostructure improves its binding ability with peroxydisulfate via bidentate binuclear model, thereby enhancing ·OH yield for organics mineralization. The Fe-based nanomaterial catalyst exhibits strong catalytic performance over a wide pH range. Similar catalysts can be prepared using other commonly available iron precursors. Finally, we also present a strategy for continuous and automated production of the iron-based nanomaterial catalysts.
Microdiversity of the vaginal microbiome is associated with preterm birth
Authors: Liao Jingqiu , Shenhav Liat , Urban Julia A. , Serrano Myrna , Zhu Bin , Buck Gregory A. , Korem Tal
Published: August 2023

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. The vaginal microbiome has been associated with PTB, yet the mechanisms underlying this association are not fully understood. Understanding microbial genetic adaptations to selective pressures, especially those related to the host, may yield insights into these associations. Here, we analyze metagenomic data from 705 vaginal samples collected during pregnancy from 40 women who delivered preterm spontaneously and 135 term controls from the Multi-Omic Microbiome Study-Pregnancy Initiative. We find that the vaginal microbiome of pregnancies that ended preterm exhibited unique genetic profiles. It was more genetically diverse at the species level, a result which we validate in an additional cohort, and harbored a higher richness and diversity of antimicrobial resistance genes, likely promoted by transduction. Interestingly, we find thatGardnerellaspecies drove this higher genetic diversity, particularly during the first half of the pregnancy. We further present evidence thatGardnerellaspp. underwent more frequent recombination and stronger purifying selection in genes involved in lipid metabolism. Overall, our population genetics analyses reveal associations between the vaginal microbiome and PTB and suggest that evolutionary processes acting on vaginal microbes may play a role in adverse pregnancy outcomes such as PTB.
In-plane reorientation induced single laser pulse magnetization reversal
Authors: Peng Y. , Salomoni D. , Malinowski G. , Zhang W. , Hohlfeld J. , Buda-Prejbeanu L. D. , Gorchon J. , Vergès M. , Lin J. X. , Lacour D. , Sousa R. C. , Prejbeanu I. L. , Mangin S. , Hehn M.
Published: August 2023

Single Pulse All Optical Switching represents the ability to reverse the magnetization of a nanostructure using a femtosecond single laser pulse without any applied field. Since the first switching experiments carried out on GdFeCo ferrimagnets, this phenomena has been only recently extended to a few other materials, MnRuGa alloys and Tb/Co multilayers with a very specific range of thickness and composition. Here, we demonstrate that single pulse switching can be obtained for a large range of rare earth–transition metal multilayers, making this phenomenon much more general. Surprisingly, the threshold fluence for switching is observed to be independent of the laser pulse duration. Moreover, at high laser intensities, concentric ring domain structures are induced. These striking features contrast to those observed in Gd based materials pointing towards a different reversal mechanism. Concomitant with the demonstration of an in-plane magnetization reorientation, a precessional reversal mechanism explains all the observed features.
Thin, soft, wearable system for continuous wireless monitoring of artery blood pressure
Authors: Li Jian , Jia Huiling , Zhou Jingkun , Huang Xingcan , Xu Long , Jia Shengxin , Gao Zhan , Yao Kuanming , Li Dengfeng , Zhang Binbin , Liu Yiming , Huang Ya , Hu Yue , Zhao Guangyao , Xu Zitong , Li Jiyu , Yiu Chun Ki , Gao Yuyu , Wu Mengge , Jiao Yanli , Zhang Qiang , Tai Xuecheng , Chan Raymond H. , Zhang Yuanting , Ma Xiaohui , Yu Xinge
Published: August 2023

Continuous monitoring of arterial blood pressure (BP) outside of a clinical setting is crucial for preventing and diagnosing hypertension related diseases. However, current continuous BP monitoring instruments suffer from either bulky systems or poor user-device interfacial performance, hampering their applications in continuous BP monitoring. Here, we report a thin, soft, miniaturized system (TSMS) that combines a conformal piezoelectric sensor array, an active pressure adaptation unit, a signal processing module, and an advanced machine learning method, to allow real wearable, continuous wireless monitoring of ambulatory artery BP. By optimizing the materials selection, control/sampling strategy, and system integration, the TSMS exhibits improved interfacial performance while maintaining Grade A level measurement accuracy. Initial trials on 87 volunteers and clinical tracking of two hypertension individuals prove the capability of the TSMS as a reliable BP measurement product, and its feasibility and practical usability in precise BP control and personalized diagnosis schemes development.
Global analysis of ocean phytoplankton nutrient limitation reveals high prevalence of co-limitation
Authors: Browning Thomas J. , Moore C. Mark
Published: August 2023

Nutrient availability limits phytoplankton growth throughout much of the global ocean. Here we synthesize available experimental data to identify three dominant nutrient limitation regimes: nitrogen is limiting in the stratified subtropical gyres and in the summertime Arctic Ocean, iron is most commonly limiting in upwelling regions, and both nutrients are frequently co-limiting in regions in between the nitrogen and iron limited systems. Manganese can be co-limiting with iron in parts of the Southern Ocean, whilst phosphate and cobalt can be co-/serially limiting in some settings. Overall, an analysis of experimental responses showed that phytoplankton net growth can be significantly enhanced through increasing the number of different nutrients supplied, regardless of latitude, temperature, or trophic status, implying surface seawaters are often approaching nutrient co-limitation. Assessments of nutrient deficiency based on seawater nutrient concentrations and nutrient stress diagnosed via molecular biomarkers showed good agreement with experimentally-assessed nutrient limitation, validating conceptual and theoretical links between nutrient stoichiometry and microbial ecophysiology.
A nuclear receptor HR96-related gene underlies large trans-driven differences in detoxification gene expression in a generalist herbivore
Authors: Ji Meiyuan , Vandenhole Marilou , De Beer Berdien , De Rouck Sander , Villacis-Perez Ernesto , Feyereisen René , Clark Richard M. , Van Leeuwen Thomas
Published: August 2023

The role, magnitude, and molecular nature of trans-driven expression variation underlying the upregulation of detoxification genes in pesticide resistant arthropod populations has remained enigmatic. In this study, we performed expression quantitative trait locus (eQTL) mapping (n = 458) between a pesticide resistant and a susceptible strain of the generalist herbivore and crop pest Tetranychus urticae. We found that a single trans eQTL hotspot controlled large differences in the expression of a subset of genes in different detoxification gene families, as well as other genes associated with host plant use. As established by additional genetic approaches including RNAi gene knockdown, a duplicated gene with a nuclear hormone receptor HR96-related ligand-binding domain was identified as causal for the expression differences between strains. The presence of a large family of HR96-related genes in T. urticae may enable modular control of detoxification and host plant use genes, facilitating this species’ known and rapid evolution to diverse pesticides and host plants.
Skin-like cryogel electronics from suppressed-freezing tuned polymer amorphization
Authors: Zhang Xiansheng , Yan Hongwei , Xu Chongzhi , Dong Xia , Wang Yu , Fu Aiping , Li Hao , Lee Jin Yong , Zhang Sheng , Ni Jiahua , Gao Min , Wang Jing , Yu Jinpeng , Ge Shuzhi Sam , Jin Ming Liang , Wang Lili , Xia Yanzhi
Published: August 2023

The sole situation of semi-crystalline structure induced single performance remarkably limits the green cryogels in the application of soft devices due to uncontrolled freezing field. Here, a facile strategy for achieving multifunctionality of cryogels is proposed using total amorphization of polymer. Through precisely lowering the freezing point of precursor solutions with an antifreezing salt, the suppressed growth of ice is achieved, creating an unusually weak and homogenous aggregation of polymer chains upon freezing, thereby realizing the tunable amorphization of polymer and the coexistence of free and hydrogen bonding hydroxyl groups. Such multi-scale microstructures trigger the integrated properties of tissue-like ultrasoftness (Young’s modulus <10 kPa) yet stretchability, high transparency (~92%), self-adhesion, and instantaneous self-healing (<0.3 s) for cryogels, along with superior ionic-conductivity, antifreezing (−58 °C) and water-retention abilities, pushing the development of skin-like cryogel electronics. These concepts open an attractive branch for cryogels that adopt regulated crystallization behavior for on-demand functionalities.
Inactivation kinetics of horseradish peroxidase (HRP) by hydrogen peroxide
Authors: Morales-Urrea Diego , López-Córdoba Alex , Contreras Edgardo M.
Published: August 2023

In recent years, the peroxidase enzymes have generated wide interest in several industrial processes, such as wastewater treatments, food processing, pharmaceuticals, and the production of fine chemicals. However, the low stability of the peroxidases in the presence of hydrogen peroxide (H2O2) has limited its commercial use. In the present work, the effect of H2O2 on the inactivation of horseradish peroxidase (HRP) was evaluated. Three states of HRP (E0, E2, and E3) were identified. While in the absence of H2O2, the resting state E0 was observed, in the presence of low and high concentrations of H2O2, E2, and E3 were found, respectively. The results showed that HRP catalyzed the H2O2 decomposition, forming the species Ex, which was catalytically inactive. Results suggest that this loss of enzymatic activity is an intrinsic characteristic of the studied HRP. A model from a modified version of the Dunford mechanism of peroxidases was developed, which was validated against experimental data and findings reported by the literature.
Genetic variation among elite inbred lines suggests potential to breed for BNI-capacity in maize
Authors: Petroli César D. , Subbarao Guntur V. , Burgueño Juan A. , Yoshihashi Tadashi , Li Huihui , Franco Duran Jorge , Pixley Kevin V.
Published: August 2023

Biological nitrification inhibition (BNI) is a plant function where root systems release antibiotic compounds (BNIs) specifically aimed at suppressing nitrifiers to limit soil-nitrate formation in the root zone. Little is known about BNI-activity in maize (Zea mays L.), the most important food, feed, and energy crop. Two categories of BNIs are released from maize roots; hydrophobic and hydrophilic BNIs, that determine BNI-capacity in root systems. Zeanone is a recently discovered hydrophobic compound with BNI-activity, released from maize roots. The objectives of this study were to understand/quantify the relationship between zeanone activity and hydrophobic BNI-capacity. We assessed genetic variability among 250 CIMMYT maize lines (CMLs) characterized for hydrophobic BNI-capacity and zeanone activity, towards developing genetic markers linked to this trait in maize. CMLs with high BNI-capacity and ability to release zeanone from roots were identified. GWAS was performed using 27,085 SNPs (with unique positions on the B73v.4 reference genome, and false discovery rate = 10), and phenotypic information for BNI-capacity and zeanone production from root systems. Eighteen significant markers were identified; three associated with specific BNI-activity (SBNI), four with BNI-activity per plant (BNIPP), another ten were common between SBNI and BNIPP, and one with zeanone release. Further, 30 annotated genes were associated with the significant SNPs; most of these genes are involved in pathways of “biological process”, and one (AMT5) in ammonium regulation in maize roots. Although the inbred lines in this study were not developed for BNI-traits, the identification of markers associated with BNI-capacity suggests the possibility of using these genomic tools in marker-assisted selection to improve hydrophobic BNI-capacity in maize.