bluuebunny/crossref_metadata_2025 huggingface dataset:
A multimodal deep learning approach for the prediction of cognitive decline and its effectiveness in clinical trials for Alzheimer’s disease
Authors: Wang Caihua , Tachimori Hisateru , Yamaguchi Hiroyuki , Sekiguchi Atsushi , Li Yuanzhong , Yamashita Yuichi ,   for Alzheimer’s Disease Neuroimaging Initiative
Published: February 2024

Alzheimer’s disease is one of the most important health-care challenges in the world. For decades, numerous efforts have been made to develop therapeutics for Alzheimer’s disease, but most clinical trials have failed to show significant treatment effects on slowing or halting cognitive decline. Among several challenges in such trials, one recently noticed but unsolved is biased allocation of fast and slow cognitive decliners to treatment and placebo groups during randomization caused by the large individual variation in the speed of cognitive decline. This allocation bias directly results in either over- or underestimation of the treatment effect from the outcome of the trial. In this study, we propose a stratified randomization method using the degree of cognitive decline predicted by an artificial intelligence model as a stratification index to suppress the allocation bias in randomization and evaluate its effectiveness by simulation using ADNI data set.
Update on the management of relapsed/refractory chronic lymphocytic leukemia
Authors: Bennett Rory , Seymour John F.
Published: February 2024

Chronic lymphocytic leukemia (CLL) predominantly affects older adults, characterized by a relapsing and remitting pattern with sequential treatments available for many patients. Identification of progressive/relapsed CLL should prompt close monitoring and early discussion about the next therapies when treatment indications are present. The intervening period represents an opportunity to optimize patient health, including establishing adequate vaccination and surveillance for second primary malignancies, and treating non-CLL-related comorbidities which may impact well-being and CLL therapy. We now see patients with relapsed/refractory (RR) CLL in the clinic who have been previously treated with chemoimmunotherapy (CIT) and/or one or more novel therapies. Continuous covalent inhibitors of Bruton’s tyrosine kinase (cBTKi) and fixed-duration venetoclax (Ven)-anti-CD20 monoclonal antibody (mAb) are preferred over CIT given the survival advantages associated with these therapies, although have never been evaluated head-to-head. While both classes are effective for RR CLL, potential side effects and the logistics of administration differ. Few randomized data demonstrate the sequential use of cBTKi and fixed-duration Ven-anti-CD20 mAb; however, they may be used in either sequence. Newer non-covalent BTKi, active against BTK C481 resistance mutations emerging with continuous cBTKi exposure, and novel approaches such as BTK degraders, bispecific antibodies, and chimeric antigen receptor T-cell therapies demonstrate impressive efficacy. In this review of RR CLL we explore relevant investigations, consideration of broader CLL- and non-CLL-related health needs, and evidence for efficacy and safety of B-cell receptor inhibitors and Ven, including available data to support drug sequencing or switching. We describe novel approaches to RR CLL, including rechallenging with fixed-duration therapies, allogeneic stem cell transplant indications in the novel therapy era, and highlight early data supporting the use of T-cell directing therapies and novel drug targets.
nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus
Authors: Wan Chaofan , Xia Yucen , Yan Jinglan , Lin Weipeng , Yao Lin , Zhang Meng , Gaisler-Salomon Inna , Mei Lin , Yin Dong-Min , Chen Yongjun
Published: February 2024

Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.
Ferroptotic alveolar epithelial type II cells drive TH2 and TH17 mixed asthma triggered by birch pollen allergen Bet v 1
Authors: Ma Linyi , He Ying , Xie Huancheng , Wang Jing , Chen Jiaqian , Song Shijie , Zhang Le , Li Linmei , Lai He , Liu Yongping , Chen Huifang , Zhang Xueyan , Liu Xueting , Zou Zehong , Zhang Qingling , Yan Jie , Tao Ailin
Published: February 2024

Asthma is a common allergic disease characterized by airway hypersensitivity and airway remodeling. Ferroptosis is a regulated death marked by iron accumulation and lipid peroxidation. Several environmental pollutants and allergens have been shown to cause ferroptosis in epithelial cells, but the relationship between birch pollinosis and ferroptosis in asthma is poorly defined. Here, for the first time, we have identified ferroptosis of type II alveolar epithelial cells in mice with Bet v 1-induced asthma. Further analysis revealed that treatment with ferrostatin-1 reduced TH2/TH17-related inflammation and alleviated epithelial damage in mice with Bet v 1-induced asthma. In addition, ACSL4-knocked-down A549 cells are more resistant to Bet v 1-induced ferroptosis. Analysis of clinical samples verified higher serum MDA and 4-HNE concentrations compared to healthy individuals. We demonstrate that birch pollen allergen Bet v 1 induces ferroptosis underlaid TH2 and TH17 hybrid asthma. Lipid peroxidation levels can be considered as a biomarker of asthma severity, and treatment with a specific ferroptosis inhibitor could be a novel therapeutic strategy.
Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
Authors: Gonzalez Galofre Zaniah N. , Kilpatrick Alastair M. , Marques Madalena , Sá da Bandeira Diana , Ventura Telma , Gomez Salazar Mario , Bouilleau Léa , Marc Yvan , Barbosa Ana B. , Rossi Fiona , Beltran Mariana , van de Werken Harmen J. G. , van IJcken Wilfred F. J. , Henderson Neil C. , Forbes Stuart J. , Crisan Mihaela
Published: February 2024

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2+Runx1+ perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2+ cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2+Runx1+ cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo.
A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria
Authors: Nhu Nguyen Thi Khanh , Rahman M. Arifur , Goh Kelvin G. K. , Kim Seung Jae , Phan Minh-Duy , Peters Kate M. , Alvarez-Fraga Laura , Hancock Steven J. , Ravi Chitra , Kidd Timothy J. , Sullivan Matthew J. , Irvine Katharine M. , Beatson Scott A. , Sweet Matthew J. , Irwin Adam D. , Vukovic Jana , Ulett Glen C. , Hasnain Sumaira Z. , Schembri Mark A.
Published: February 2024

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.
Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial
Authors: Bol Kalijn F. , Schreibelt Gerty , Bloemendal Martine , van Willigen Wouter W. , Hins-de Bree Simone , de Goede Anna L. , de Boer Annemiek J. , Bos Kevin J. H. , Duiveman-de Boer Tjitske , Olde Nordkamp Michel A. M. , van Oorschot Tom G. M. , Popelier Carlijn J. , Pots Jeanne M. , Scharenborg Nicole M. , van de Rakt Mandy W. M. M. , de Ruiter Valeska , van Meeteren Wilmy S. , van Rossum Michelle M. , Croockewit Sandra J. , Koeneman Bouke J. , Creemers Jeroen H. A. , Wortel Inge M. N. , Angerer Caroline , Brüning Mareke , Petry Katja , Dzionek Andrzej , van der Veldt Astrid A. , van Grünhagen Dirk J. , Werner Johanna E. M. , Bonenkamp Johannes J. , Haanen John B. A. G. , Boers-Sonderen Marye J. , Koornstra Rutger H. T. , Boomsma Martijn F. , Aarntzen Erik H. J. , Gotthardt Martin , Nagarajah James , de Witte Theo J. M. , Figdor Carl G. , de Wilt Johannes H. W. , Textor Johannes , de Groot Jan Willem B. , Gerritsen Winald R. , de Vries I. Jolanda M.
Published: February 2024

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88−1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73−2.38; p = 0.44). Grade 3−4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed.
Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci
Authors: Lopez Soriano Victor , Dueñas Rey Alfredo , Mukherjee Rajarshi ,   Genomics England Research Consortium, Inglehearn Chris F. , Coppieters Frauke , Bauwens Miriam , Willaert Andy , De Baere Elfride
Published: February 2024

Cross-species genome comparisons have revealed a substantial number of ultraconserved non-coding elements (UCNEs). Several of these elements have proved to be essential tissue- and cell type-specific cis-regulators of developmental gene expression. Here, we characterize a set of UCNEs as candidate CREs (cCREs) during retinal development and evaluate the contribution of their genomic variation to rare eye diseases, for which pathogenic non-coding variants are emerging. Integration of bulk and single-cell retinal multi-omics data reveals 594 genes under potential cis-regulatory control of UCNEs, of which 45 are implicated in rare eye disease. Mining of candidate cis-regulatory UCNEs in WGS data derived from the rare eye disease cohort of Genomics England reveals 178 ultrarare variants within 84 UCNEs associated with 29 disease genes. Overall, we provide a comprehensive annotation of ultraconserved non-coding regions acting as cCREs during retinal development which can be targets of non-coding variation underlying rare eye diseases.
Anomalously bright single-molecule upconversion electroluminescence
Authors: Luo Yang , Kong Fan-Fang , Tian Xiao-Jun , Yu Yun-Jie , Jing Shi-Hao , Zhang Chao , Chen Gong , Zhang Yang , Zhang Yao , Li Xiao-Guang , Zhang Zhen-Yu , Dong Zhen-Chao
Published: February 2024

Efficient upconversion electroluminescence is highly desirable for a broad range of optoelectronic applications, yet to date, it has been reported only for ensemble systems, while the upconversion electroluminescence efficiency remains very low for single-molecule emitters. Here we report on the observation of anomalously bright single-molecule upconversion electroluminescence, with emission efficiencies improved by more than one order of magnitude over previous studies, and even stronger than normal-bias electroluminescence. Intuitively, the improvement is achieved via engineering the energy-level alignments at the molecule−substrate interface so as to activate an efficient spin-triplet mediated upconversion electroluminescence mechanism that only involves pure carrier injection steps. We further validate the intuitive picture with the construction of delicate electroluminescence diagrams for the excitation of single-molecule electroluminescence, allowing to readily identify the prerequisite conditions for producing efficient upconversion electroluminescence. These findings provide deep insights into the microscopic mechanism of single-molecule upconversion electroluminescence and organic electroluminescence in general.
Motility of an autonomous protein-based artificial motor that operates via a burnt-bridge principle
Authors: Korosec Chapin S. , Unksov Ivan N. , Surendiran Pradheebha , Lyttleton Roman , Curmi Paul M. G. , Angstmann Christopher N. , Eichhorn Ralf , Linke Heiner , Forde Nancy R.
Published: February 2024

Inspired by biology, great progress has been made in creating artificial molecular motors. However, the dream of harnessing proteins – the building blocks selected by nature – to design autonomous motors has so far remained elusive. Here we report the synthesis and characterization of the Lawnmower, an autonomous, protein-based artificial molecular motor comprised of a spherical hub decorated with proteases. Its “burnt-bridge” motion is directed by cleavage of a peptide lawn, promoting motion towards unvisited substrate. We find that Lawnmowers exhibit directional motion with average speeds of up to 80 nm/s, comparable to biological motors. By selectively patterning the peptide lawn on microfabricated tracks, we furthermore show that the Lawnmower is capable of track-guided motion. Our work opens an avenue towards nanotechnology applications of artificial protein motors.
Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy
Authors: Hoogenboezem Ella N. , Patel Shrusti S. , Lo Justin H. , Cavnar Ashley B. , Babb Lauren M. , Francini Nora , Gbur Eva F. , Patil Prarthana , Colazo Juan M. , Michell Danielle L. , Sanchez Violeta M. , McCune Joshua T. , Ma Jinqi , DeJulius Carlisle R. , Lee Linus H. , Rosch Jonah C. , Allen Ryan M. , Stokes Larry D. , Hill Jordan L. , Vickers Kasey C. , Cook Rebecca S. , Duvall Craig L.
Published: February 2024

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.
Design of target specific peptide inhibitors using generative deep learning and molecular dynamics simulations
Authors: Chen Sijie , Lin Tong , Basu Ruchira , Ritchey Jeremy , Wang Shen , Luo Yichuan , Li Xingcan , Pei Dehua , Kara Levent Burak , Cheng Xiaolin
Published: February 2024

We introduce a computational approach for the design of target-specific peptides. Our method integrates a Gated Recurrent Unit-based Variational Autoencoder with Rosetta FlexPepDock for peptide sequence generation and binding affinity assessment. Subsequently, molecular dynamics simulations are employed to narrow down the selection of peptides for experimental assays. We apply this computational strategy to design peptide inhibitors that specifically targetβ-catenin and NF-κB essential modulator. Among the twelveβ-catenin inhibitors, six exhibit improved binding affinity compared to the parent peptide. Notably, the best C-terminal peptide bindsβ-catenin with an IC50of 0.010 ± 0.06 μM, which is 15-fold better than the parent peptide. For NF-κB essential modulator, two of the four tested peptides display substantially enhanced binding compared to the parent peptide. Collectively, this study underscores the successful integration of deep learning and structure-based modeling and simulation for target specific peptide design.
Global evaluation of lineage-specific human papillomavirus capsid antigenicity using antibodies elicited by natural infection
Authors: Kamuyu Gathoni , Coelho da Silva Filomeno , Tenet Vanessa , Schussler John , Godi Anna , Herrero Rolando , Porras Carolina , Mirabello Lisa , Schiller John T. , Sierra Mónica S. , Kreimer Aimée R. , Clifford Gary M. , Beddows Simon
Published: February 2024

Human Papillomavirus (HPV) type variants have been classified into lineages and sublineages based upon their whole genome sequence. Here we have examined the specificity of antibodies generated following natural infection with lineage variants of oncogenic types (HPV16, 18, 31, 33, 45, 52 and 58) by testing serum samples assembled from existing archives from women residing in Africa, The Americas, Asia or Europe against representative lineage-specific pseudoviruses for each genotype. We have subjected the resulting neutralizing antibody data to antigenic clustering methods and created relational antigenic profiles for each genotype to inform the delineation of lineage-specific serotypes. For most genotypes, there was evidence of differential recognition of lineage-specific antigens and in some cases of a sufficient magnitude to suggest that some lineages should be considered antigenically distinct within their respective genotypes. These data provide compelling evidence for a degree of lineage specificity within the humoral immune response following natural infection with oncogenic HPV.
Quantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction
Authors: Pinzi Luca , Conze Christian , Bisi Nicolo , Torre Gabriele Dalla , Soliman Ahmed , Monteiro-Abreu Nanci , Trushina Nataliya I. , Krusenbaum Andrea , Dolouei Maryam Khodaei , Hellwig Andrea , Christodoulou Michael S. , Passarella Daniele , Bakota Lidia , Rastelli Giulio , Brandt Roland
Published: February 2024

Tauopathies such as Alzheimer’s disease are characterized by aggregation and increased phosphorylation of the microtubule-associated protein tau. Tau’s pathological changes are closely linked to neurodegeneration, making tau a prime candidate for intervention. We developed an approach to monitor pathological changes of aggregation-prone human tau in living neurons. We identified 2-phenyloxazole (PHOX) derivatives as putative polypharmacological small molecules that interact with tau and modulate tau kinases. We found that PHOX15 inhibits tau aggregation, restores tau’s physiological microtubule interaction, and reduces tau phosphorylation at disease-relevant sites. Molecular dynamics simulations highlight cryptic channel-like pockets crossing tau protofilaments and suggest that PHOX15 binding reduces the protofilament’s ability to adopt a PHF-like conformation by modifying a key glycine triad. Our data demonstrate that live-cell imaging of a tauopathy model enables screening of compounds that modulate tau-microtubule interaction and allows identification of a promising polypharmacological drug candidate that simultaneously inhibits tau aggregation and reduces tau phosphorylation.
4D printed hydrogel scaffold with swelling-stiffening properties and programmable deformation for minimally invasive implantation
Authors: Liu Bo , Li Hui , Meng Fengzhen , Xu Ziyang , Hao Liuzhi , Yao Yuan , Zhu Hao , Wang Chenmin , Wu Jun , Bian Shaoquan , Lu Willima W. , Liu Wenguang , Pan Haobo , Zhao Xiaoli
Published: February 2024

The power of three-dimensional printing in designing personalized scaffolds with precise dimensions and properties is well-known. However, minimally invasive implantation of complex scaffolds is still challenging. Here, we develop amphiphilic dynamic thermoset polyurethanes catering for multi-material four-dimensional printing to fabricate supportive scaffolds with body temperature-triggered shape memory and water-triggered programmable deformation. Shape memory effect enables the two-dimensional printed pattern to be fixed into temporary one-dimensional shape, facilitating transcatheter delivery. Upon implantation, the body temperature triggers shape recovery of the one-dimensional shape to its original two-dimensional pattern. After swelling, the hydrated pattern undergoes programmable morphing into the desired three-dimensional structure because of swelling mismatch. The structure exhibits unusual soft-to-stiff transition due to the water-driven microphase separation formed between hydrophilic and hydrophobic chain segments. The integration of shape memory, programmable deformability, and swelling-stiffening properties makes the developed dynamic thermoset polyurethanes promising supportive void-filling scaffold materials for minimally invasive implantation.
Spontaneous crystallization of strongly confined CsSnxPb1-xI3 perovskite colloidal quantum dots at room temperature
Authors: Zhang Louwen , Zhou Hai , Chen Yibo , Zheng Zhimiao , Huang Lishuai , Wang Chen , Dong Kailian , Hu Zhongqiang , Ke Weijun , Fang Guojia
Published: February 2024

The scalable and low-cost room temperature (RT) synthesis for pure-iodine all-inorganic perovskite colloidal quantum dots (QDs) is a challenge due to the phase transition induced by thermal unequilibrium. Here, we introduce a direct RT strongly confined spontaneous crystallization strategy in a Cs-deficient reaction system without polar solvents for synthesizing stable pure-iodine all-inorganic tin-lead (Sn-Pb) alloyed perovskite colloidal QDs, which exhibit bright yellow luminescence. By tuning the ratio of Cs/Pb precursors, the size confinement effect and optical band gap of the resultant CsSnxPb1-xI3 perovskite QDs can be well controlled. This strongly confined RT approach is universal for wider bandgap bromine- and chlorine-based all-inorganic and iodine-based hybrid perovskite QDs. The alloyed CsSn0.09Pb0.91I3 QDs show superior yellow emission properties with prolonged carrier lifetime and significantly increased colloidal stability compared to the pristine CsPbI3 QDs, which is enabled by strong size confinement, Sn2+ passivation and enhanced formation energy. These findings provide a RT size-stabilized synthesis pathway to achieve high-performance pure-iodine all-inorganic Sn-Pb mixed perovskite colloidal QDs for optoelectronic applications.
Evolution and expression patterns of the neo-sex chromosomes of the crested ibis
Authors: Xu Lulu , Ren Yandong , Wu Jiahong , Cui Tingting , Dong Rong , Huang Chen , Feng Zhe , Zhang Tianmin , Yang Peng , Yuan Jiaqing , Xu Xiao , Liu Jiao , Wang Jinhong , Chen Wu , Mi Da , Irwin David M. , Yan Yaping , Xu Luohao , Yu Xiaoping , Li Gang
Published: February 2024

Bird sex chromosomes play a unique role in sex-determination, and affect the sexual morphology and behavior of bird species. Core waterbirds, a major clade of birds, share the common characteristics of being sexually monomorphic and having lower levels of inter-sexual conflict, yet their sex chromosome evolution remains poorly understood. Here, by we analyse of a chromosome-level assembly of a female crested ibis (Nipponia nippon), a typical core waterbird. We identify neo-sex chromosomes resulting from fusion of microchromosomes with ancient sex chromosomes. These fusion events likely occurred following the divergence of Threskiornithidae and Ardeidae. The neo-W chromosome of the crested ibis exhibits the characteristics of slow degradation, which is reflected in its retention of abundant gametologous genes. Neo-W chromosome genes display an apparent ovary-biased gene expression, which is largely driven by genes that are retained on the crested ibis W chromosome but lost in other bird species. These results provide new insights into the evolutionary history and expression patterns for the sex chromosomes of bird species.
Enhancing phosphate-solubilising microbial communities through artificial selection
Authors: Faller Lena , Leite Marcio F. A. , Kuramae Eiko E.
Published: February 2024

Microbial communities, acting as key drivers of ecosystem processes, harbour immense potential for sustainable agriculture practices. Phosphate-solubilising microorganisms, for example, can partially replace conventional phosphate fertilisers, which rely on finite resources. However, understanding the mechanisms and engineering efficient communities poses a significant challenge. In this study, we employ two artificial selection methods, environmental perturbation, and propagation, to construct phosphate-solubilising microbial communities. To assess trait transferability, we investigate the community performance in different media and a hydroponic system withChrysanthemum indicum. Our findings reveal a distinct subset of phosphate-solubilising bacteria primarily dominated byKlebsiellaand Enterobacterales. The propagated communities consistently demonstrate elevated levels of phosphate solubilisation, surpassing the starting soil community by 24.2% in activity. The increased activity of propagated communities remains consistent upon introduction into the hydroponic system. This study shows the efficacy of community-level artificial selection, particularly through propagation, as a tool for successfully modifying microbial communities to enhance phosphate solubilisation.
General synthesis and atomic arrangement identification of ordered Bi–Pd intermetallics with tunable electrocatalytic CO2 reduction selectivity
Authors: Guo Wenjin , Li Guangfang , Bai Chengbo , Liu Qiong , Chen Fengxi , Chen Rong
Published: February 2024

Intermetallic compounds (IMCs) with fixed chemical composition and ordered crystallographic arrangement are highly desirable platforms for elucidating the precise correlation between structures and performances in catalysis. However, diffusing a metal atom into a lattice of another metal to form a controllably regular metal occupancy remains a huge challenge. Herein, we develop a general and tractable solvothermal method to synthesize the Bi-Pd IMCs family, including Bi2Pd, BiPd, Bi3Pd5, Bi2Pd5, Bi3Pd8 and BiPd3. By employing electrocatalytic CO2 reduction as a model reaction, we deeply elucidated the interplay between Bi-Pd IMCs and key intermediates. Specific surface atomic arrangements endow Bi-Pd IMCs different relative surface binding affinities and adsorption configuration for *OCHO, *COOH and *H intermediate, thus exhibiting substantially selective generation of formate (Bi2Pd), CO (BiPd3) and H2 (Bi2Pd5). This work provides a comprehensive understanding of the specific structure-performance correlation of IMCs, which serves as a valuable paradigm for precisely modulating catalyst material structures.
Liquid metal-embraced photoactive films for artificial photosynthesis
Authors: Zhen Chao , Chen Xiangtao , Chen Ruotian , Fan Fengtao , Xu Xiaoxiang , Kang Yuyang , Guo Jingdong , Wang Lianzhou , Lu Gao Qing , Domen Kazunari , Cheng Hui-Ming , Liu Gang
Published: February 2024

The practical applications of solar-driven water splitting pivot on significant advances that enable scalable production of robust photoactive films. Here, we propose a proof-of-concept for fabricating robust photoactive films by a particle-implanting technique (PiP) which embeds semiconductor photoabsorbers in the liquid metal. The strong semiconductor/metal interaction enables resulting films efficient collection of photogenerated charges and superior photoactivity. A photoanode of liquid-metal embraced BiVO4 can stably operate over 120 h and retain ~ 70% of activity when scaled from 1 to 64 cm2. Furthermore, a Z-scheme photocatalyst film of liquid-metal embraced BiVO4 and Rh-doped SrTiO3 particles can drive overall water splitting under visible light, delivering an activity 2.9 times higher than that of the control film with gold support and a 110 h stability. These results demonstrate the advantages of the PiP technique in constructing robust and efficient photoactive films for artificial photosynthesis.
Tracing the origin of Argentine Malbec wines by sensometrics
Authors: Urvieta Roy , Heymann Hildegarde , Cantu Annegret , Catania Aníbal , Buscema Fernando , Bottini Rubén , Fontana Ariel
Published: February 2024

The study of terroir, increasingly popular in scientific circles, remains a challenging field, particularly in terms of sensory analysis. This paper summarizes our own contribution to the field—an approach for tracing the typicity of wines by sensometrics, using the Malbec variety as a case study. This large-scale research fingerprinted 81 wines from 29 parcels from highly contrasting environments (varying climate, elevation, and soils), produced under standardized conditions in three consecutive vintages. Wines were evaluated through descriptive sensory analysis (DA) by a trained panel, and sensory descriptors were associated with different size geographic scales (zones, departments, and Geographic Indications (GIs)). The application of different sensometric tools allowed us to describe the typicity of wines and discriminate each region, proposing a novel methodology for the comprehensive evaluation of terroir from a sensory viewpoint. The vintage effect was very strong at the departmental and GI level, with aroma, taste and mouthfeel descriptors varying annually. However, certain origin descriptors remained consistent, providing insight into the typicity of Malbec. Considering the extension of the experimental study performed, this methodology provides a proof of concept for understanding both terroir and vintage effects from a sensorial perspective, offering wine producers and consumers a clear message backed by scientific evidence.
High-resolution land use/cover forecasts for Switzerland in the 21st century
Authors: Bütikofer Luca , Adde Antoine , Urbach Davnah , Tobias Silvia , Huss Matthias , Guisan Antoine , Randin Christophe
Published: February 2024

We present forecasts of land-use/land-cover (LULC) change for Switzerland for three time-steps in the 21st century under the representative concentration pathways 4.5 and 8.5, and at 100-m spatial and 14-class thematic resolution. We modelled the spatial suitability for each LULC class with a neural network (NN) using > 200 predictors and accounting for climate and policy changes. We improved model performance by using a data augmentation algorithm that synthetically increased the number of cells of underrepresented classes, resulting in an overall quantity disagreement of 0.053 and allocation disagreement of 0.15, which indicate good prediction accuracy. These class-specific spatial suitability maps outputted by the NN were then merged in a single LULC map per time-step using the CLUE-S algorithm, accounting for LULC demand for the future and a set of LULC transition rules. As the first LULC forecast for Switzerland at a thematic resolution comparable to available LULC maps for the past, this product lends itself to applications in land-use planning, resource management, ecological and hydraulic modelling, habitat restoration and conservation.
A dataset of genetic diversity studies in the China Seas
Authors: Ming Yaqian , Ni Gang
Published: February 2024

Genetic diversity, a fundamental aspect of biodiversity, greatly influences the ecological and evolutionary characteristics of populations and species. Compiling genetic data is crucial as the initial step in comprehending and applying genetic resources; however, regional collating work is still insufficient, especially in marine ecosystems. Here, by conducting a thorough literature search and quality-control procedures, we provide a dataset of genetic diversity studies on marine species in the China Seas. The final dataset comprised a total of 746 studies (encompassing 840 data sets and 3658 populations) across 343 species from 1998 to 2022. For each data set, information including publication year, publication language, studied species, belonged taxonomic group, applied molecular markers, and sampling strategies (number of populations, total number of individuals, etc.) was collated to analyse the scope, strengths, and omissions of these works. This dataset offers a comprehensive overview of genetic diversity studies in the China Seas, which may help to adjust future research focuses, promote conservation and macrogenetics studies in this region, and also facilitate regional cooperation.
Single image super-resolution with denoising diffusion GANS
Authors: Xiao Heng , Wang Xin , Wang Jun , Cai Jing-Ye , Deng Jian-Hua , Yan Jing-Ke , Tang Yi-Dong
Published: February 2024

Single image super-resolution (SISR) refers to the reconstruction from the corresponding low-resolution (LR) image input to a high-resolution (HR) image. However, since a single low-resolution image corresponds to multiple high-resolution images, this is an ill-posed problem. In recent years, generative model-based SISR methods have outperformed conventional SISR methods in performance. However, the SISR methods based on GAN, VAE, and Flow have the problems of unstable training, low sampling quality, and expensive computational cost. These models also struggle to achieve the trifecta of diverse, high-quality, and fast sampling. In particular, denoising diffusion probabilistic models have shown impressive variety and high quality of samples, but their expensive sampling cost prevents them from being well applied in the real world. In this paper, we investigate the fundamental reason for the slow sampling speed of the SISR method based on the diffusion model lies in the Gaussian assumption used in the previous diffusion model, which is only applicable for small step sizes. We propose a new Single Image Super-Resolution with Denoising Diffusion GANS (SRDDGAN) to achieve large-step denoising, sample diversity, and training stability. Our approach combines denoising diffusion models with GANs to generate images conditionally, using a multimodal conditional GAN to model each denoising step. SRDDGAN outperforms existing diffusion model-based methods regarding PSNR and perceptual quality metrics, while the added latent variable Z solution explores the diversity of likely HR spatial domain. Notably, the SRDDGAN model infers nearly 11 times faster than diffusion-based SR3, making it a more practical solution for real-world applications.
Neighbour–stranger discrimination in an African wood dove inhabiting equatorial rainforest
Authors: Niśkiewicz Małgorzata , Szymański Paweł , Zampa Lia , Budka Michał , Osiejuk Tomasz S.
Published: February 2024

We investigated within- and between-individual song variation and song-based neighbour-stranger discrimination in a non-learning bird species, the blue-headed wood-dove (Turtur brehmeri), which inhabits lowland rainforests of West and Central Africa. We found that songs of this species are individually specific and have a high potential for use in individual recognition based on the time–frequency pattern of note distribution within song phrases. To test whether these differences affect behaviour, we conducted playback experiments with 19 territorial males. Each male was tested twice, once with the songs of a familiar neighbour and once with the songs of an unfamiliar stranger. We observed that males responded more aggressively to playback of a stranger’s songs: they quickly approached close to the speaker and spent more time near it. However, no significant differences between treatments were observed in the vocal responses. In addition, we explored whether responses differed based on the song frequency of the focal male and/or that of the simulated intruder (i.e., playback), as this song parameter is inversely related to body size and could potentially affect males’ decisions to respond to other birds. Song frequency parameters (of either the focal male or the simulated intruder) had no effect on the approaching response during playback. However, we found that the pattern of response after playback was significantly affected by the song frequency of the focal male: males with lower-frequency songs stayed closer to the simulated intruder for a longer period of time without singing, while males with higher-frequency songs returned more quickly to their initial song posts and resumed singing. Together, these results depict a consistently strong response to strangers during and after playback that is dependent on a male’s self-assessment rather than assessment of a rival’s strength based on his song frequency. This work provides the first experimental evidence that doves (Columbidae) can use songs for neighbour-stranger discrimination and respond according to a “dear enemy” scheme that keeps the cost of territory defence at a reasonable level.
Experimental and simulation study of inert gas mixture inhibiting coal spontaneous combustion
Authors: Wang Xinning , Wang Lei , Li Weidong , Liu Dongyang
Published: February 2024

To explore the mechanism of inhibiting spontaneous combustion of coal by mixed gases, the low-temperature oxidation characteristics of coal under different components of mixed gases were analyzed. ESR and FTIR experiments were used to investigate the effects of different gas mixtures on the activity of coal during low-temperature oxidation and the oxidation reaction of coal surface functional groups. The mechanism of chemical oxygen inhibition of mixed gas was studied by density functional theory. The results show that the larger the CO2 component in the mixed gas, the higher the ability to inhibit coal oxidation. The concentration of free radicals in coal under dry air condition is higher than that under inert mixed gas condition during oxidation heating at 30–230 °C. The oxidation ability of –CH3, –OH and oxygen-containing functional groups in the mixed gas reaction is inhibited. Through quantum chemistry calculation, it is found that the mixed gas increases the activation energy of free radicals and reduces the heat release of the reaction. This study provides theoretical reference for coal mine thermal disaster.
Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level
Authors: Perkiö Anna , Pradhan Barun , Genc Fatih , Pirttikoski Anna , Pikkusaari Sanna , Erkan Erdogan Pekcan , Falco Matias Marin , Huhtinen Kaisa , Narva Sara , Hynninen Johanna , Kauppi Liisa , Vähärautio Anna
Published: February 2024

Long interspersed nuclear elements (LINE-1s/L1s) are a group of retrotransposons that can copy themselves within a genome. In humans, it is the most successful transposon in nucleotide content. L1 expression is generally mild in normal human tissues, but the activity has been shown to increase significantly in many cancers. Few studies have examined L1 expression at single-cell resolution, thus it is undetermined whether L1 reactivation occurs solely in malignant cells within tumors. One of the cancer types with frequent L1 activity is high-grade serous ovarian carcinoma (HGSOC). Here, we identified locus-specific L1 expression with 3′ single-cell RNA sequencing in pre- and post-chemotherapy HGSOC sample pairs from 11 patients, and in fallopian tube samples from five healthy women. Although L1 expression quantification with the chosen technique was challenging due to the repetitive nature of the element, we found evidence of L1 expression primarily in cancer cells, but also in other cell types, e.g. cancer-associated fibroblasts. The expression levels were similar in samples taken before and after neoadjuvant chemotherapy, indicating that L1 transcriptional activity was unaffected by clinical platinum-taxane treatment. Furthermore, L1 activity was negatively associated with the expression of MYC target genes, a finding that supports earlier literature of MYC being an L1 suppressor.
Attenuated huntingtin gene CAG nucleotide repeat size in individuals with Lynch syndrome
Authors: Dalene Skarping Karin , Arning Larissa , Petersén Åsa , Nguyen Huu Phuc , Gebre-Medhin Samuel
Published: February 2024

DNA mismatch repair (MMR) is thought to contribute to the onset and progression of Huntington disease (HD) by promoting somatic expansion of the pathogenic CAG nucleotide repeat in the huntingtin gene (HTT). Here we have studied constitutional HTT CAG repeat size in two cohorts of individuals with Lynch syndrome (LS) carrying heterozygous loss-of-function variants in the MMR genes MLH1 (n = 12/60; Lund cohort/Bochum cohort, respectively), MSH2 (n = 15/88), MSH6 (n = 21/23), and controls (n = 19/559). The sum of CAG repeats for both HTT alleles in each individual was calculated due to unknown segregation with the LS allele. In the larger Bochum cohort, the sum of CAG repeats was lower in the MLH1 subgroup compared to controls (MLH1 35.40 CAG repeats ± 3.6 vs. controls 36.89 CAG repeats ± 4.5; p = 0.014). All LS genetic subgroups in the Bochum cohort displayed lower frequencies of unstable HTT intermediate alleles and lower HTT somatic CAG repeat expansion index values compared to controls. Collectively, our results indicate that MMR gene haploinsufficiency could have a restraining impact on constitutional HTT CAG repeat size and support the notion that the MMR pathway is a driver of nucleotide repeat expansion diseases.
Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB
Authors: Fróes Renata de Sá Brito , Andrade Adriana Ribas , Faria Mikaell Alexandre Gouvea , de Souza Heitor Siffert Pereira , Parra Rogério Serafim , Zaltman Cyrla , dos Santos Carlos Henrique Marques , Bafutto Mauro , Quaresma Abel Botelho , Santana Genoile Oliveira , Luporini Rafael Luís , de Lima Junior Sérgio Figueiredo , Miszputen Sender Jankiel , de Souza Mardem Machado , Herrerias Giedre Soares Prates , Junior Roberto Luiz Kaiser , do Nascimento Catiane Rios , Féres Omar , de Barros Jaqueline Ribeiro , Sassaki Ligia Yukie , Saad-Hossne Rogerio
Published: February 2024

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn’s Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.
Early differentiation of mesenchymal stem cells is reflected in their dielectrophoretic behavior
Authors: Tivig Ioan , Vallet Leslie , Moisescu Mihaela G. , Fernandes Romain , Andre Franck M. , Mir Lluis M. , Savopol Tudor
Published: February 2024

The therapeutic use of mesenchymal stem cells (MSCs) becomes more and more important due to their potential for cell replacement procedures as well as due to their immunomodulatory properties. However, protocols for MSCs differentiation can be lengthy and may result in incomplete or asynchronous differentiation. To ensure homogeneous populations for therapeutic purposes, it is crucial to develop protocols for separation of the different cell types after differentiation. In this article we show that, when MSCs start to differentiate towards adipogenic or osteogenic progenies, their dielectrophoretic behavior changes. The values of cell electric parameters which can be obtained by dielectrophoretic measurements (membrane permittivity, conductivity, and cytoplasm conductivity) change before the morphological features of differentiation become microscopically visible. We further demonstrate, by simulation, that these electric modifications make possible to separate cells in their early stages of differentiation by using the dielectrophoretic separation technique. A label free method which allows obtaining cultures of homogenously differentiated cells is thus offered.