bluuebunny/crossref_metadata_2025 huggingface dataset:
Urine biomarkers in type 2 diabetes mellitus with or without microvascular complications
Authors: Zhang Chanyuan , Liu Tiebing , Wang Xiaoqian , Yang Jing , Qin Dongfang , Liang Yin , Wang Xuejing
Published: July 2024

Objective

To investigate the distribution of nine (9) urine biomarkers in people living with type 2 diabetes mellitus (T2DM), with or without microvascular complications.

Methods

In total, 407 people with T2DM were enrolled from 2021 to 2022. According to diabetic retinopathy (DR) and urinary albumin-creatinine ratio (UACR), the 407 people were divided into four (4) groups, DR(–)UACR(–), DR(+)UACR(–), DR(–)UACR(+), and DR( + )UACR(+). In addition, 112 healthy volunteers were enrolled during the same period. The nine (9) urine markers included α1-microglobulin (u-α1MG), immunoglobulin G (u-IgG), neutrophil gelatinase-associated lipid carrier protein (u-NGAL), cystatin C (u-CysC), retinol-binding protein (u-RBP), β2-microglobulin (u-β2MG), N-acetyl-β-D-glucosaminidase (u-NAG), transferrin (u-Trf), and collagen type IV (u-Col). For each marker, the respective level of 97.5 percentile in healthy volunteers was taken as an upper reference limit.

Results

Among the 407 people, 248 individuals (61%) were DR(–)UACR(–), 100 (25%) were DR(-)UACR(+), 37 (9%) were DR(+)UACR(–), and 22 (5%) were DR(+)UACR(+). The u-NAG/Cr biomarker level showed a significant difference between healthy participants and people with T2DM. In the DR(–)UACR(–)group, u-Trf/Cr showed the highest positive rate (21.37%), followed by u-IgG/Cr (14.52%); u-NAG/Cr (10.48%); u-β2MG/Cr (4.44%); u-CysC/Cr (4.03%); u-NGAL/Cr (4.03%); u-RBP/Cr (2.82%); u-α1MG/Cr (2.42%); 17.34% of people with T2DM showed multiple biomarkers positive (≥2 biomarkers). The positive rates of one biomarker (21.33%) and two biomarkers (18.67%) in people who have less than five (5) years of T2DM were almost close to those of the DR(–)UACR(–) group (21.37%, and 12.10%, respectively).

Conclusion

Renal tubule biomarkers may be used as an indicator in the early detection and monitoring of renal injury in diabetes mellitus. The u-NAG biomarker should be measured for the people with T2DM of the first-time diagnosis.
Developing and validating a Modified Cachexia Index to predict the outcomes for colorectal cancer after radical surgery
Authors: Yuan Qinggang , Liu Lixiang , Wang Kai , Zhou Shizhen , Miao Ji , Gao Bo , Ding Chao , Guan Wenxian
Published: July 2024

Background

It was reported that the cachexia index (CXI: $$\frac{{\rm{ALB}}* {\rm{SMI}}}{{\rm{NLR}}}$$

ALB
*
SMI

NLR

) was an essential index for predicting the prognosis of tumor patients. However, since for SMI needs to be measured by CT imaging methods and its calculation was inconvenient. Thus, we developed a modified cachexia index (mCXI: $$\frac{{\rm{ALB}}}{{\rm{NLR}}* {\rm{UCR}}}$$

ALB

NLR
*
UCR

). The purpose of this study was to evaluate the association between mCXI and prognosis in patients with colorectal cancer.

Methods

An analysis of 215 patients with newly diagnosed colorectal cancer was carried out retrospectively. An optimal cut-off value of mCXI was established by the receiver operating characteristic (ROC) curves for predicting prognosis. Prognostic implications of mCXI were investigated using Kaplan–Meier curves and Cox regression analysis. A comparative assessment of the predictive capacity between mCXI and the CXI was performed using time-dependent receiver operating characteristic analysis.

Results

Patients were classified into two groups based on the cut-off value of mCXI: the LOW mCXI group (n = 60) and the HIGH mCXI group (n = 155). The 3-year Overall survival (OS) (76.6% vs 96.7%, p < 0.01) and 3-year Recurrence-free survival (RFS) (68.3% vs 94.1%, p < 0.01) were significantly worse in the LOW mCXI group in contrast to that in the HIGH mCXI group. In Cox multivariate regression analysis, mCXI was an independent prognostic factor for OS (HR = 8.951, 95%CI: 3.105–25.807, <0.01). Moreover, compared with CXI (AUC = 0.723), mCXI (AUC = 0.801) has better predictive efficacy, indicating that mCXI is more suitable for prognostic assessment.

Conclusions

The mCXI significantly correlated with survival outcomes for colorectal cancer patients after radical surgery.
Evidence of thermophilization in Afromontane forests
Authors: Cuni-Sanchez Aida , Martin Emanuel H. , Uzabaho Eustrate , Ngute Alain S. K. , Bitariho Robert , Kayijamahe Charles , Marshall Andrew R. , Mohamed Nassoro A. , Mseja Gideon A. , Nkwasibwe Aventino , Rovero Francesco , Sheil Douglas , Tinkasimire Rogers , Tumugabirwe Lawrence , Feeley Kenneth J. , Sullivan Martin J. P.
Published: July 2024

Thermophilization is the directional change in species community composition towards greater relative abundances of species associated with warmer environments. This process is well-documented in temperate and Neotropical plant communities, but it is uncertain whether this phenomenon occurs elsewhere in the tropics. Here we extend the search for thermophilization to equatorial Africa, where lower tree diversity compared to other tropical forest regions and different biogeographic history could affect community responses to climate change. Using re-census data from 17 forest plots in three mountain regions of Africa, we find a consistent pattern of thermophilization in tree communities. Mean rates of thermophilization were +0.0086 °C·y−1 in the Kigezi Highlands (Uganda), +0.0032 °C·y−1 in the Virunga Mountains (Rwanda-Uganda-Democratic Republic of the Congo) and +0.0023 °C·y−1 in the Udzungwa Mountains (Tanzania). Distinct from other forests, both recruitment and mortality were important drivers of thermophilzation in the African plots. The forests studied currently act as a carbon sink, but the consequences of further thermophilization are unclear.
TSG-6+ cancer-associated fibroblasts modulate myeloid cell responses and impair anti-tumor response to immune checkpoint therapy in pancreatic cancer
Authors: Anandhan Swetha , Herbrich Shelley , Goswami Sangeeta , Guan Baoxiang , Chen Yulong , Macaluso Marc Daniel , Jindal Sonali , Natarajan Seanu Meena , Andrewes Samuel W. , Xiong Liangwen , Nagarajan Ashwat , Basu Sreyashi , Tang Derek Ng , Liu Jielin , Min Jimin , Maitra Anirban , Sharma Padmanee
Published: July 2024

Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. TSG-6 inhibition in combination with ICT improves therapy response and survival in pancreatic tumor-bearing mice by reducing macrophages expressing immunosuppressive phenotypes and increasing CD8 T cells. Overall, our findings propose TSG-6 as a therapeutic target to enhance ICT response in non-responsive tumors.
Primordial aqueous alteration recorded in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu
Authors: Takano Yoshinori , Naraoka Hiroshi , Dworkin Jason P. , Koga Toshiki , Sasaki Kazunori , Sato Hajime , Oba Yasuhiro , Ogawa Nanako O. , Yoshimura Toshihiro , Hamase Kenji , Ohkouchi Naohiko , Parker Eric T. , Aponte José C. , Glavin Daniel P. , Furukawa Yoshihiro , Aoki Junken , Kano Kuniyuki , Nomura Shin-ichiro M. , Orthous-Daunay Francois-Regis , Schmitt-Kopplin Philippe ,   Hayabusa2-initial-analysis SOM team, Furusho Aogu , Hashiguchi Minako , Fukushima Kazuhiko , Dan Aoki  , McLain Hannah L. , Elsila Jamie E. , Graham Heather V. , Eiler John M. , Hertkorn Norbert , Ruf Alexander , Wolters Cédric , Isa Junko , Vuitton Véronique , Thissen Roland , Sakai Saburo , Sugahara Haruna , Mita Hajime , Chikaraishi Yoshito , Yoshikawa Takaaki , Tanaka Satoru , Morita Mayu , Onose Morihiko , Araoka Daisuke , Kabashima Fumie , Fujishima Kosuke , Sato Hajime , Yamazaki Tomoya , Kimura Yuki , Yurimoto Hisayoshi , Nakamura Tomoki , Noguchi Takaaki , Okazaki Ryuji , Yabuta Hikaru , Sakamoto Kanako , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Nakazawa Satoru , Watanabe Sei-ichiro , Tsuda Yuichi , Tachibana Shogo
Published: July 2024

We report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu by the Hayabusa2 spacecraft of JAXA. Newly identified low-molecular-weight hydroxy acids (HO-R-COOH) and dicarboxylic acids (HOOC-R-COOH), such as glycolic acid, lactic acid, glyceric acid, oxalic acid, and succinic acid, are predominant in samples from the two touchdown locations at Ryugu. The quantitative and qualitative profiles for the hydrophilic molecules between the two sampling locations shows similar trends within the order of ppb (parts per billion) to ppm (parts per million). A wide variety of structural isomers, including α- and β-hydroxy acids, are observed among the hydrophilic molecules. We also identify pyruvic acid and dihydroxy and tricarboxylic acids, which are biochemically important intermediates relevant to molecular evolution, such as the primordial TCA (tricarboxylic acid) cycle. Here, we find evidence that the asteroid Ryugu samples underwent substantial aqueous alteration, as revealed by the presence of malonic acid during keto–enol tautomerism in the dicarboxylic acid profile. The comprehensive data suggest the presence of a series for water-soluble organic molecules in the regolith of Ryugu and evidence of signatures in coevolutionary aqueous alteration between water and organics in this carbonaceous asteroid.
Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation
Authors: Mohr Sarah M. , Dai Pra Rafael , Platt Maryann P. , Feketa Viktor V. , Shanabrough Marya , Varela Luis , Kristant Ashley , Cao Haoran , Merriman Dana K. , Horvath Tamas L. , Bagriantsev Sviatoslav N. , Gracheva Elena O.
Published: July 2024

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.
Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records
Authors: Venkatesh Samvida S. , Ganjgahi Habib , Palmer Duncan S. , Coley Kayesha , Linchangco Gregorio V. , Hui Qin , Wilson Peter , Ho Yuk-Lam , Cho Kelly , Arumäe Kadri ,   Million Veteran Program,   Estonian Biobank Research Team, Metspalu Andres , Milani Lili , Esko Tõnu , Mägi Reedik , Nelis Mari , Hudjashov Georgi , Wittemans Laura B. L. , Nellåker Christoffer , Vainik Uku , Sun Yan V. , Holmes Chris , Lindgren Cecilia M. , Nicholson George
Published: July 2024

Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 24.5 million primary-care health records in over 740,000 individuals in the UK Biobank, Million Veteran Program USA, and Estonian Biobank, to discover and validate the genetic architecture of adiposity trajectories. Using multiple BMI measurements over time increases power to identify genetic factors affecting baseline BMI by 14%. In the largest reported genome-wide study of adiposity-change in adulthood, we identify novel associations with BMI-change at six independent loci, including rs429358 (APOE missense variant). The SNP-based heritability of BMI-change (1.98%) is 9-fold lower than that of BMI. The modest genetic correlation between BMI-change and BMI (45.2%) indicates that genetic studies of longitudinal trajectories could uncover novel biology of quantitative traits in adulthood.
Wavelength-tunable high-fidelity entangled photon sources enabled by dual Stark effects
Authors: Chen Chen , Yan Jun-Yong , Babin Hans-Georg , Wang Jiefei , Xu Xingqi , Lin Xing , Yu Qianqian , Fang Wei , Liu Run-Ze , Huo Yong-Heng , Cai Han , Sha Wei E. I. , Zhang Jiaxiang , Heyn Christian , Wieck Andreas D. , Ludwig Arne , Wang Da-Wei , Jin Chao-Yuan , Liu Feng
Published: July 2024

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.
The cysteine-rich virulence factor NipA of Arthrobotrys flagrans interferes with cuticle integrity of Caenorhabditis elegans
Authors: Emser Jennifer , Wernet Nicole , Hetzer Birgit , Wohlmann Elke , Fischer Reinhard
Published: July 2024

Animals protect themself from microbial attacks by robust skins or a cuticle as in Caenorhabditis elegans. Nematode-trapping fungi, like Arthrobotrys flagrans, overcome the cuticle barrier and colonize the nematode body. While lytic enzymes are important for infection, small-secreted proteins (SSPs) without enzymatic activity, emerge as crucial virulence factors. Here, we characterized NipA (nematode induced protein) which A. flagrans secretes at the penetration site. In the absence of NipA, A. flagrans required more time to penetrate C. elegans. Heterologous expression of the fungal protein in the epidermis of C. elegans led to blister formation. NipA contains 13 cysteines, 12 of which are likely to form disulfide bridges, and the remaining cysteine was crucial for blister formation. We hypothesize that NipA interferes with cuticle integrity to facilitate fungal entry. Genome-wide expression analyses of C. elegans expressing NipA revealed mis-regulation of genes associated with extracellular matrix (ECM) maintenance and innate immunity.
Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing
Authors: Reedy Jennifer L. , Jensen Kirstine Nolling , Crossen Arianne J. , Basham Kyle J. , Ward Rebecca A. , Reardon Christopher M. , Brown Harding Hannah , Hepworth Olivia W. , Simaku Patricia , Kwaku Geneva N. , Tone Kazuya , Willment Janet A. , Reid Delyth M. , Stappers Mark H. T. , Brown Gordon D. , Rajagopal Jayaraj , Vyas Jatin M.
Published: July 2024

Respiratory infections caused by the human fungal pathogenAspergillus fumigatusare a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo.Aspergillus-derived melanin, a major constituent of the fungal cell wall, dampened airway epithelial chemokine secretion in response to fungi, bacteria, and exogenous cytokines. Furthermore, melanin muted pathogen-mediated calcium fluxing and hindered actin filamentation. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens.
Programmed cell death regulator BAP2 is required for IRE1-mediated unfolded protein response in Arabidopsis
Authors: Pastor-Cantizano Noelia , Angelos Evan R. , Ruberti Cristina , Jiang Tao , Weng Xiaoyu , Reagan Brandon C. , Haque Taslima , Juenger Thomas E. , Brandizzi Federica
Published: July 2024

Environmental and physiological situations can challenge the balance between protein synthesis and folding capacity of the endoplasmic reticulum (ER) and cause ER stress, a potentially lethal condition. The unfolded protein response (UPR) restores ER homeostasis or actuates programmed cell death (PCD) when ER stress is unresolved. The cell fate determination mechanisms of the UPR are not well understood, especially in plants. Here, we integrate genetics and ER stress profiling with natural variation and quantitative trait locus analysis of 350 natural accessions of the model species Arabidopsis thaliana. Our analyses implicate a single nucleotide polymorphism to the loss of function of the general PCD regulator BON-ASSOCIATED PROTEIN2 (BAP2) in UPR outcomes. We establish that ER stress-induced BAP2 expression is antagonistically regulated by the UPR master regulator, inositol-requiring enzyme 1 (IRE1), and that BAP2 controls adaptive UPR amplitude in ER stress and ignites pro-death mechanisms in conditions of UPR insufficiency.
Regulatory mechanism of cold-inducible diapause in Caenorhabditis elegans
Authors: Horikawa Makoto , Fukuyama Masamitsu , Antebi Adam , Mizunuma Masaki
Published: July 2024

Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms.
A diverse proteome is present and enzymatically active in metabolite extracts
Authors: House Rachel J. , Soper-Hopper Molly T. , Vincent Michael P. , Ellis Abigail E. , Capan Colt D. , Madaj Zachary B. , Wolfrum Emily , Isaguirre Christine N. , Castello Carlos D. , Johnson Amy B. , Escobar Galvis Martha L. , Williams Kelsey S. , Lee Hyoungjoo , Sheldon Ryan D.
Published: July 2024

Metabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types. By combining post-resuspension stable isotope addition and enzyme inhibitors, we demonstrate in-extract metabolite interconversions due to residual transaminase activity. We extend these findings with untargeted metabolomics where we observe extensive protein-mediated metabolite changes, including in-extract formation of glutamate dipeptide and depletion of total glutathione. Finally, we present a simple extraction workflow that integrates 3 kDa filtration for protein removal as a superior method for polar metabolomics. In this work, we uncover a previously unrecognized, protein-mediated source of observer effects in metabolomics experiments with broad-reaching implications across all research fields using metabolomics and molecular metabolism.
Whole exome sequencing analysis identifies genes for alcohol consumption
Authors: Kang Jujiao , Deng Yue-Ting , Wu Bang-Sheng , Liu Wei-Shi , Li Ze-Yu , Xiang Shitong , Yang Liu , You Jia , Gong Xiaohong , Jia Tianye , Yu Jin-Tai , Cheng Wei , Feng Jianfeng
Published: July 2024

Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.
Decreased ENSO post-2100 in response to formation of a permanent El Niño-like state under greenhouse warming
Authors: Geng Tao , Cai Wenju , Jia Fan , Wu Lixin
Published: July 2024

Under transient greenhouse warming, El Niño-Southern Oscillation (ENSO) is projected to increase pre-2100, accompanied by an easier establishment of atmospheric convection in the equatorial eastern Pacific, where sea surface temperature (SST) warms faster than surrounding regions. After 2100, how ENSO variability may change remains unknown. Here we find that under a high emission scenario, ENSO variability post-2100 reverses from the initial increase to an amplitude far smaller than that of the 20th century. The fast eastern warming persists and shrinks the equatorial Pacific non-convective area, such that establishing convection in the non-convective area, as during an El Niño, requires smaller convective anomaly, inducing weaker wind anomalies leading to reduced ENSO SST variability. The nonlinear ENSO response is thus a symptom of the persistent El Niño-like warming pattern. Therefore, the oscillatory ENSO impact could be replaced by that from the permanent El Niño-like mean condition with cumulative influences on affected regions.
On-demand transposition across light-matter interaction regimes in bosonic cQED
Authors: Valadares Fernando , Huang Ni-Ni , Chu Kyle Timothy Ng , Dorogov Aleksandr , Chua Weipin , Kong Lingda , Song Pengtao , Gao Yvonne Y.
Published: July 2024

The diverse applications of light-matter interactions in science and technology stem from the qualitatively distinct ways these interactions manifest, prompting the development of physical platforms that can interchange between regimes on demand. Bosonic cQED employs the light field of high-Q superconducting cavities coupled to nonlinear circuit elements, harnessing the rich dynamics of their interaction for quantum information processing. However, implementing fast switching of the interaction regime without deteriorating the cavity coherence is a significant challenge. We present an experiment that achieves this feat, combining nanosecond-scale frequency tunability of a transmon coupled to a cavity with lifetime of hundreds of microseconds. Our implementation affords a range of useful capabilities for quantum information processing; from fast creation of cavity Fock states using resonant interaction and interchanging tomography techniques at qualitatively distinct interaction regimes on the fly, to the suppression of unwanted cavity-transmon dynamics during idle evolution. By bringing flux tunability into the bosonic cQED toolkit, our work opens up the possibility to probe the full range of light-matter interaction dynamics within a single platform and provides valuable pathways towards robust and versatile quantum information processing.
Developmental trajectories of EEG aperiodic and periodic components in children 2–44 months of age
Authors: Wilkinson Carol L. , Yankowitz Lisa D. , Chao Jerry Y. , Gutiérrez Rodrigo , Rhoades Jeff L. , Shinnar Shlomo , Purdon Patrick L. , Nelson Charles A.
Published: July 2024

The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2–44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Developmental changes in periodic peaks include (1) the presence and then absence of a 9-10 Hz alpha peak between 2-6 months, (2) nonlinear changes in high beta peaks (20-30 Hz) between 4-18 months, and (3) the emergence of a low beta peak (12-20 Hz) in some infants after six months of age. We hypothesized that the emergence of the low beta peak may reflect maturation of thalamocortical network development. Infant anesthesia studies observe that GABA-modulating anesthetics do not induce thalamocortical mediated frontal alpha coherence until 10-12 months of age. Using a small cohort of infants (n = 23) with EEG before and during GABA-modulating anesthesia, we provide preliminary evidence that infants with a low beta peak have higher anesthesia-induced alpha coherence compared to those without a low beta peak.
Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis
Authors: Sun Jun , Chen Muxiong , Hu Zhen , Xu Ningqin , Wang Wenguang , Ping Zejun , Zhu Jiayi , Sun Desen , Zhu Zhehao , Li Hangyu , Ge Xiaolong , Luo Liang , Zhou Wei , Bai Rongpan , Xu Zhengping , Sheng Jinghao
Published: July 2024

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.
Population structure and antibiotic resistance of swine extraintestinal pathogenic Escherichia coli from China
Authors: Li Xudong , Hu Huifeng , Zhu Yongwei , Wang Taiquan , Lu Youlan , Wang Xiangru , Peng Zhong , Sun Ming , Chen Huanchun , Zheng Jinshui , Tan Chen
Published: July 2024

Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, blaCTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.
Polar confinement of a macromolecular machine by an SRP-type GTPase
Authors: Dornes Anita , Schmidt Lisa Marie , Mais Christopher-Nils , Hook John C. , Pané-Farré Jan , Kressler Dieter , Thormann Kai , Bange Gert
Published: July 2024

The basal structure of the bacterial flagellum includes a membrane embedded MS-ring (formed by multiple copies of FliF) and a cytoplasmic C-ring (composed of proteins FliG, FliM and FliN). The SRP-type GTPase FlhF is required for directing the initial flagellar protein FliF to the cell pole, but the mechanisms are unclear. Here, we show that FlhF anchors developing flagellar structures to the polar landmark protein HubP/FimV, thereby restricting their formation to the cell pole. Specifically, the GTPase domain of FlhF interacts with HubP, while a structured domain at the N-terminus of FlhF binds to FliG. FlhF-bound FliG subsequently engages with the MS-ring protein FliF. Thus, the interaction of FlhF with HubP and FliG recruits a FliF-FliG complex to the cell pole. In addition, the modulation of FlhF activity by the MinD-type ATPase FlhG controls the interaction of FliG with FliM-FliN, thereby regulating the progression of flagellar assembly at the pole.
Investigating the impact of poverty on mental illness in the UK Biobank using Mendelian randomization
Authors: Marchi Mattia , Alkema Anne , Xia Charley , Thio Chris H. L. , Chen Li-Yu , Schalkwijk Winni , Galeazzi Gian M. , Ferrari Silvia , Pingani Luca , Kweon Hyeokmoon , Evans-Lacko Sara , David Hill W. , Boks Marco P.
Published: July 2024

It is unclear whether poverty and mental illness are causally related. Using UK Biobank and Psychiatric Genomic Consortium data, we examined evidence of causal links between poverty and nine mental illnesses (attention deficit and hyperactivity disorder (ADHD), anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia). We applied genomic structural equation modelling to derive a poverty common factor from household income, occupational income and social deprivation. Then, using Mendelian randomization, we found evidence that schizophrenia and ADHD causally contribute to poverty, while poverty contributes to major depressive disorder and schizophrenia but decreases the risk of anorexia nervosa. Poverty may also contribute to ADHD, albeit with uncertainty due to unbalanced pleiotropy. The effects of poverty were reduced by approximately 30% when we adjusted for cognitive ability. Further investigations of the bidirectional relationships between poverty and mental illness are warranted, as they may inform efforts to improve mental health for all.
Incidence and intensity of catastrophic health expenditure and impoverishment among the elderly: an empirical evidence from India
Authors: Ahmad Fahimuddin , Mohanty Pratap Chandra
Published: July 2024

World health statistics (2022) report that about 1.4 billion people have incurred catastrophic health expenditure (CHE), and half of its population have pushed into extreme poverty due to healthcare payments. The elderly population faces a higher risk of ill health, and seeking treatment reflects in high out-of-pocket health spending (OOPHS) that results in CHE and further impoverishment. This study aims to investigate the incidence and intensity of OOPHS, CHE, and impoverishment among the older adults in India. Data utilizes from the 75th round of the national sample survey (NSS) based on household social consumption: health (schedule 25.0), 2018. The incidence and intensity of CHE and impoverishment among older adults in India estimated by using standard measures. The older adults spend about 17.4% of household consumption expenditure on healthcare services. The poorest older adults are spending the highest share of consumption expenditure (24.8%) on healthcare among economic quantiles. Similarly, the elderly from rural (20.3%), male (18.4%), scheduled castes (21.5%), and Hinduism (17.9%) show a larger share of consumption expenditure on healthcare services. The incidence and intensity of CHE among older adults are 46.5% and 16.1% at 10% threshold level of household consumption expenditure, respectively. However, as the threshold level rises the incidence and intensity of CHE decline. The estimates of normalized poverty gap using the poverty line of Tendulkar committee as well as Rangarajan committee show that the intensity of impoverishment among older adults are 56.4% and 57.9% respectively, which is quite high. Financial protection along with vision might mitigate the risk of CHE and impoverishment among older adults in India.
Effects of an OX2R agonist on migration and removal of tau from mouse brain
Authors: Terada Michiko , Mitsukawa Kayo , Nakakariya Masanori , Koike Tatsuki , Kimura Haruhide
Published: July 2024

Pathological proteins including tau are produced in neurons and released into interstitial fluid (ISF) in a neural activity-dependent manner during wakefulness. Pathological proteins in ISF can be removed from the brain via the glymphatic pathway during nighttime. Thus, in individuals with Alzheimer’s disease (AD) that have dysregulated sleep/wake rhythm, application of orexin receptor 2 (OX2R) agonists during daytime could recover the efflux of pathological proteins to ISF and indirectly promote the glymphatic pathway by improving the quality of nighttime sleep after proper daytime arousal, resulting in increased removal of these proteins from the brain. We investigated this hypothesis using OX-201, a novel OX2R-selective agonist with a 50% effective concentration of 8.0 nM. Diurnal rhythm of tau release into hippocampal ISF correlated well with neuronal activity and wakefulness in wild-type mice. In both wild-type and human P301S tau transgenic mice, OX-201 induced wakefulness and promoted tau release into hippocampal ISF. Human P301S tau transgenic mice, tested under our conditions, showed longer wakefulness time, which differs from individuals with AD. OX-201 treatment over 2 months did not alter hippocampal tau levels. Although further studies are required, at a minimum OX2R agonists may not exacerbate tau accumulation in individuals with tauopathy, including AD.
Effect of cold arid high-altitude environment on bioactive phytochemical compounds of organically grown Brassicaceae vegetables for nutri-health security in mountainous regions
Authors: Shukla Shardulya , Kumar Nitish , Bhardwaj Pushpender , Pandita Priyanka , Patel Manoj Kumar , Thakur Mohan Singh , Kumar Raj , Rawat Monisha , Saxena Shweta
Published: July 2024

High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter. The open field study was conducted as a two-factorial randomized block design. The first factor was treatment (T1-FYM, T2-Azotobacter, T3-FYM + Azotobacter, and T4-control) while the second was locations (HA and LA). Among all these treatments, the application of treatment T3 in HA-grown cabbage showed the highest total phenolic content (TPC; 9.56 μg/mg), total flavonoids content (TFC; 14.48 μg/mg), and antioxidant potential using 2,2-diphenyl-1-picrylhydrazyl (DPPH; 85.97%) and ferric reducing antioxidant power (FRAP; 30.77 μg/mg) compared to LA grown samples. Reverse Phase high performance liquid chromatography (RP-HPLC) analysis showed that treatment T3 at HA led to significantly high kaempferol (0.92 μg/mg) and sulforaphane (8.94 μg/mg) contents in cabbage whereas, indole-3-carbinol (1.31 μg/mg) was higher in HA grown cauliflower. The present study provides scientific evidence for the enrichment of health-promoting phytochemical compounds in Brassicaceae vegetables grown with T3 treatment specifically at HA.
Cross-cultural comparison of beauty judgments in visual art using machine learning analysis of art attribute predictors among Japanese and German speakers
Authors: Mikuni Jan , Spee Blanca T. M. , Forlani Gaia , Leder Helmut , Scharnowski Frank , Nakamura Koyo , Watanabe Katsumi , Kawabata Hideaki , Pelowski Matthew , Steyrl David
Published: July 2024

In empirical art research, understanding how viewers judge visual artworks as beautiful is often explored through the study of attributes—specific inherent characteristics or artwork features such as color, complexity, and emotional expressiveness. These attributes form the basis for subjective evaluations, including the judgment of beauty. Building on this conceptual framework, our study examines the beauty judgments of 54 Western artworks made by native Japanese and German speakers, utilizing an extreme randomized trees model—a data-driven machine learning approach—to investigate cross-cultural differences in evaluation behavior. Our analysis of 17 attributes revealed that visual harmony, color variety, valence, and complexity significantly influenced beauty judgments across both cultural cohorts. Notably, preferences for complexity diverged significantly: while the native Japanese speakers found simpler artworks as more beautiful, the native German speakers evaluated more complex artworks as more beautiful. Further cultural distinctions were observed: for the native German speakers, emotional expressiveness was a significant factor, whereas for the native Japanese speakers, attributes such as brushwork, color world, and saturation were more impactful. Our findings illuminate the nuanced role that cultural context plays in shaping aesthetic judgments and demonstrate the utility of machine learning in unravelling these complex dynamics. This research not only advances our understanding of how beauty is judged in visual art—considering self-evaluated attributes—across different cultures but also underscores the potential of machine learning to enhance our comprehension of the aesthetic evaluation of visual artworks.
Characterizing soluble immune checkpoint molecules and TGF-β1,2,3 in pleural effusion of malignant pleural mesothelioma
Authors: Okita Riki , Senoo Tomoya , Mimura-Kimura Yuka , Mimura Yusuke , Murakami Tomoyuki , Ikeda Eiji , Okada Masanori , Inokawa Hidetoshi , Aoe Keisuke
Published: July 2024

The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-β isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-β1, TGF-β2, and TGF-β3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-β2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-β1 and TGF-β3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.
Identification of tumor stemness and immunity related prognostic factors and sensitive drugs in head and neck squamous cell carcinoma
Authors: Ye Zhihua , Xiao Mintao , Zhang Yinping , Zheng Anfu , Zhang Duoli , Chen Jie , Du Fukuan , Zhao Yueshui , Wu Xu , Li Mingxing , Chen Yu , Deng Shuai , Shen Jing , Zhang Xinyi , Wen Qinglian , Zhang Junkai , Xiao Zhangang
Published: July 2024

The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.
Considerations for fatty acids in standardized reference diet for parthenogenetic marbled crayfish Procambarus virginalis model organism
Authors: Das Koushik , Roy Koushik , Mráz Jan , Buřič Miloš , Kouba Antonín
Published: July 2024

Fatty acid accumulation was studied in the parthenogenetic all-female marbled crayfish Procambarus virginalis using six arbitrarily designed experimental feeds and related to individuals with glair glands (sexual maturity) after 100 days of ad libitum feeding at 21 °C, including gravid females from the wild as a reference. Fatty acids 16:0 and 18:1n-9 comprised 40% of the total amount of fatty acids and tended to up-concentrate in bodies. Shorter chain 14:0 depleted from feed to body. Across diets, there was a concomitant decrease in precursor fatty acid and increase in product fatty acid, such as reinforcements in monounsaturated fatty acid (18:1n-9), eicosanoid precursors 20:4n-6 (arachidonic acid, ARA) and 20:5n-3 (eicosapentaenoic acid, EPA) in-vivo, but not 22:6n-3 (docosahexaenoic acid, DHA) except when deficient in CHI or CHI + SPI diets. Saturation kinetics modeling (R2 0.7–0.9, p < 0.05) showed that when the ARA share is ~ 1%, the EPA share is ~ 8%, and the DHA share is ~ 2% in the food lipids, the accumulation of fatty acids in body lipids levels off. The lowest DHA in the CHI (0% glair glands) or CHI + SPI (0–3.9% glair glands) diets, and the lowest ARA in SER (0% glair glands) or SER + SPI (0–3% glair glands) diets, were synchronous with negligible sexual maturity despite a wide range of observed specific growth rates (2.77–3.60% per day), body size (0.44–0.84 g), ≤ 5% crude lipid and 40–46% crude protein feed. The FISH and SHRIMP diets (56% protein, 11–14% lipid) with the highest ARA, EPA, and DHA together seem to be the most conducive diets for sexual maturity (up to 20% of individuals with glair glands). We propose a fatty acid profile mimicking the FISH or SHRIMP diets as a starting point for designing the lipid content required in the marbled crayfish standardized reference diet.