bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4
Authors: Zeng Jianyao , Fang Yuan , Zhang Zixuan , Lv Zhenzhen , Wang Xiaodie , Huang Qian , Tian Zhidan , Li Jiaguo , Xu Wenfeng , Zhu Weimin , Yu Jing , Liu Tao , Qian Qijun
Published: May 2024

The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.
Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature
Authors: Mori Daisuke , Inami Chihiro , Ikeda Ryosuke , Sawahata Masahito , Urata Shinji , Yamaguchi Sho T. , Kobayashi Yohei , Fujita Kosuke , Arioka Yuko , Okumura Hiroki , Kushima Itaru , Kodama Akiko , Suzuki Toshiaki , Hirao Takashi , Yoshimi Akira , Sobue Akira , Ito Takahiro , Noda Yukikiro , Mizoguchi Hiroyuki , Nagai Taku , Kaibuchi Kozo , Okabe Shigeo , Nishiguchi Koji , Kume Kazuhiko , Yamada Kiyofumi , Ozaki Norio
Published: May 2024

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.
Nuclear factor-κB activation by transforming growth factor-β1 drives tumour microenvironment-mediated drug resistance in neuroblastoma
Authors: Louault Kévin , Blavier Laurence , Lee Men-Hua , Kennedy Rebekah J. , Fernandez G. Esteban , Pawel Bruce R. , Asgharzadeh Shahab , DeClerck Yves A.
Published: May 2024

Background

Intrinsic and extrinsic factors in the tumour microenvironment (TME) contribute to therapeutic resistance. Here we demonstrate that transforming growth factor (TGF)-β1 produced in the TME increased drug resistance of neuroblastoma (NB) cells.

Methods

Human NB cell lines were tested in vitro for their sensitivity to Doxorubicin (DOX) and Etoposide (ETOP) in the presence of tumour-associated macrophages (TAM) and mesenchymal stromal cells/cancer-associated fibroblasts (MSC/CAF). These experiments were validated in xenotransplanted and primary tumour samples.

Results

Drug resistance was associated with an increased expression of efflux transporter and anti-apoptotic proteins. Upregulation was dependent on activation of nuclear factor (NF)-κB by TGF-β-activated kinase (TAK1) and SMAD2. Resistance was reversed upon pharmacologic and genetic inhibitions of NF-κB, and TAK1/SMAD2. Interleukin-6, leukaemia inhibitory factor and oncostatin M were upregulated by this TGF-β/TAK1/NF-κB/SMAD2 signalling pathway contributing to drug resistance via an autocrine loop activating STAT3. An analysis of xenotransplanted NB tumours revealed an increased presence of phospho (p)-NF-κB in tumours co-injected with MSC/CAF and TAM, and these tumours failed to respond to Etoposide but responded if treated with a TGF-βR1/ALK5 inhibitor. Nuclear p-NF-κB was increased in patient-derived tumours rich in TME cells.

Conclusions

The data provides a novel insight into a targetable mechanism of environment-mediated drug resistance.
A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia
Authors: Edtmayer Sophie , Witalisz-Siepracka Agnieszka , Zdársky Bernhard , Heindl Kerstin , Weiss Stefanie , Eder Thomas , Dutta Sayantanee , Graichen Uwe , Klee Sascha , Sharif Omar , Wieser Rotraud , Győrffy Balázs , Poli Valeria , Casanova Emilio , Sill Heinz , Grebien Florian , Stoiber Dagmar
Published: May 2024

Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3β. While STAT3α is predominantly described as an oncogenic driver, STAT3β has been suggested to act as a tumor suppressor. To elucidate the role of STAT3β in AML, we established a mouse model of STAT3β-deficient, MLL-AF9-driven AML. STAT3β deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3β. Accordingly, STAT3β-deficient leukemia cells displayed enhanced sensitivity to blockade of IFN signaling through both an IFNAR1 blocking antibody and the JAK1/2 inhibitor Ruxolitinib. Analysis of human AML patient samples confirmed that elevated expression of IFN-inducible genes correlated with poor overall survival and low STAT3β expression. Together, our data corroborate the tumor suppressive role of STAT3β in a mouse model in vivo. Moreover, they provide evidence that its tumor suppressive function is linked to repression of the STAT1-mediated IFN response. These findings suggest that the STAT3β/α mRNA ratio is a significant prognostic marker in AML and holds crucial information for targeted treatment approaches. Patients displaying a low STAT3β/α mRNA ratio and unfavorable prognosis could benefit from therapeutic interventions directed at STAT1/IFN signaling.
The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis
Authors: Ryu Seungwon , Kim Kyung Ah , Kim Jinwoo , Lee Dong Hun , Bae Yong-Soo , Lee Hajeong , Kim Byoung Choul , Kim Hye Young
Published: May 2024

Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.
Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations
Authors: Szczesny Brooke , Boorgula Meher Preethi , Chavan Sameer , Campbell Monica , Johnson Randi K. , Kammers Kai , Thompson Emma E. , Cox Madison S. , Shankar Gautam , Cox Corey , Morin Andréanne , Lorizio Wendy , Daya Michelle , Kelada Samir N. P. , Beaty Terri H. , Doumatey Ayo P. , Cruz Alvaro A. , Watson Harold , Naureckas Edward T. , Giles B. Louise , Arinola Ganiyu A. , Sogaolu Olumide , Falade Adegoke G. , Hansel Nadia N. , Yang Ivana V. , Olopade Christopher O. , Rotimi Charles N. , Landis R. Clive , Figueiredo Camila A. , Altman Matthew C. , Kenny Eimear , Ruczinski Ingo , Liu Andrew H. , Ober Carole , Taub Margaret A. , Barnes Kathleen C. , Mathias Rasika A.
Published: May 2024

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10−9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10−16 and CPA3; p = 2.39 × 10−14) and wound healing (FN1; p = 7.63 × 10−9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes – increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response – that may play a critical role in asthma within the African Diaspora.
Multi-source connectivity as the driver of solar wind variability in the heliosphere
Authors: Yardley Stephanie L. , Brooks David H. , D’Amicis Raffaella , Owen Christopher J. , Long David M. , Baker Deb , Démoulin Pascal , Owens Mathew J. , Lockwood Mike , Mihailescu Teodora , Coburn Jesse T. , Dewey Ryan M. , Müller Daniel , Suen Gabriel H. H. , Ngampoopun Nawin , Louarn Philippe , Livi Stefano , Lepri Sue , Fludra Andrzej , Haberreiter Margit , Schühle Udo
Published: May 2024

The ambient solar wind that fills the heliosphere originates from multiple sources in the solar corona and is highly structured. It is often described as high-speed, relatively homogeneous, plasma streams from coronal holes and slow-speed, highly variable, streams whose source regions are under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify solar wind sources and understand what drives the complexity seen in the heliosphere. By combining magnetic field modelling and spectroscopic techniques with high-resolution observations and measurements, we show that the solar wind variability detected in situ by Solar Orbiter in March 2022 is driven by spatio-temporal changes in the magnetic connectivity to multiple sources in the solar atmosphere. The magnetic field footpoints connected to the spacecraft moved from the boundaries of a coronal hole to one active region (12961) and then across to another region (12957). This is reflected in the in situ measurements, which show the transition from fast to highly Alfvénic then to slow solar wind that is disrupted by the arrival of a coronal mass ejection. Our results describe solar wind variability at 0.5 au but are applicable to near-Earth observatories.
An fNIRS dataset for driving risk cognition of passengers in highly automated driving scenarios
Authors: Zhang Xiaofei , Wang Qiaoya , Li Jun , Gao Xiaorong , Li Bowen , Nie Bingbing , Wang Jianqiang , Zhou Ziyuan , Yang Yingkai , Wang Hong
Published: May 2024

For highly autonomous vehicles, human does not need to operate continuously vehicles. The brain-computer interface system in autonomous vehicles will highly depend on the brain states of passengers rather than those of human drivers. It is a meaningful and vital choice to translate the mental activities of human beings, essentially playing the role of advanced sensors, into safe driving. Quantifying the driving risk cognition of passengers is a basic step toward this end. This study reports the creation of an fNIRS dataset focusing on the prefrontal cortex activity in fourteen types of highly automated driving scenarios. This dataset considers age, sex and driving experience factors and contains the data collected from an 8-channel fNIRS device and the data of driving scenarios. The dataset provides data support for distinguishing the driving risk in highly automated driving scenarios via brain-computer interface systems, and it also provides the possibility of preventing potential hazards in some scenarios, in which risk remains at a high value for an extended period, before hazard occurs.
The psychology of Mona Lisa’s smile
Authors: Soranzo Alessandro
Published: May 2024

Mona Lisa’s ambiguous expression, oscillating between melancholy and contentment, has captivated viewers for centuries, prompting diverse explanations. This article proposes a novel interpretation grounded in the psychological theory of perceptual organisation. Central to the investigation is the “Ambiguity-Nuance”, a subtly shaded, blended region framing the upper part of the lips, hypothesised to influence perceived expression due to perceptual organization. Through carefully crafted artwork and systematic manipulations of Mona Lisa reproductions, experiments reveal how alterations in the perceptual relationships of the Ambiguity-Nuance yield significant shifts in perceived expression, explaining why Mona Lisa’s appearance changes and under which conditions she looks content versus melancholic based on perceptual organization. These findings underscore the pivotal role of psychological principles in shaping ambiguous expressions in the Mona Lisa, and extend to other Leonardo’s portraits, namely La Bella Principessa and Scapigliata. This study sheds light on the intersection of psychology and art, offering new perspectives on timeless masterpieces.
Multidisciplinary design optimisation of lattice-based battery housing for electric vehicles
Authors: Wang Jier , Schutzeichel Maximilian , Plaumann Benedikt , Kletschkowski Thomas , Panesar Ajit
Published: May 2024

Batteries with high energy densities become essential with the increased uptake of electric vehicles. Battery housing, a protective casing encapsulating the battery, must fulfil competing engineering requirements of high stiffness and effective thermal management whilst being lightweight. In this study, a graded lattice design framework is developed based on topology optimisation to effectively tackle the multidisciplinary objectives associated with battery housing. It leverages the triply periodic minimal surfaces lattices, aiming for high mechanical stiffness and efficient heat dissipation considering heat conduction and convection. The effectiveness of the proposed framework was demonstrated through the battery housing design, showcasing its ability to address multidisciplinary objectives as evidenced by the analysis of the Pareto front. This study identifies the potential of lattices in lightweight applications incorporating multiphysics and offers an efficient lattice design framework readily extended to other engineering challenges.
Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth–seventh century BC, central Italy)
Authors: Bagnasco G. , Marzullo M. , Cattaneo C. , Biehler-Gomez L. , Mazzarelli D. , Ricciardi V. , Müller W. , Coppa A. , McLaughlin R. , Motta L. , Prato O. , Schmidt F. , Gaveriaux F. , Marras G. B. , Millet M. A. , Madgwick R. , Ballantyne R. , Makarewicz C.A. , Trentacoste A. , Reimer P. , Mattiangeli V. , Bradley D. G. , Malone C. , Esposito C. , Breslin E. M. , Stoddart S.
Published: May 2024

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.
Synergistic role of MoS2 in gelation-induced fabrication of graphene oxide films
Authors: Choi Minah , Lim Joonwon , Yang Jieun
Published: May 2024

Supporting materials for electrocatalysts must exhibit relative chemical inertness to facilitate unimpeded movement of gas, and demonstrate electrical conductivity to promote efficient electron transfer to the catalyst. Conventional catalyst electrodes, such as glassy carbon, carbon cloths, or Ni foam, are commonly employed. However, the challenge lies in the limited stability observed during testing due to the relatively weak adhesion between the catalyst and the electrode. Addressing this limitation is crucial for advancing the stability and performance of catalyst-electrode systems in various applications. Here, we suggest a novel fabrication method for a freestanding conducting film, accomplished through gelation, incorporating 1T-MoS2 and graphene oxide. 1T-MoS2 nanosheets play a crucial role in promoting the reduction of graphene oxide (GO) on the Zn foil. This contribution leads to accelerated film formation and enhanced electrical conductivity in the film. The synergistic effect also enhances the film’s stability as catalyst supports. This study provides insights into the effective utilization of MoS2 and graphene oxide in the creating of advanced catalyst support systems with potential applications in diverse catalytic reaction.
A nationwide study on new onset atrial fibrillation risk factors and its association with hospital mortality in sepsis patients
Authors: Liu Yi-wei , Wang Yi-fan , Chen Yan , Dong Run , Li Shan , Peng Jin-min , Liufu Rong , Weng Li , Xu Yang , Du Bin
Published: May 2024

Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.
Exercise derived myokine irisin as mediator of cardiorespiratory, metabolic and thermal adjustments during central and peripheral chemoreflex activation
Authors: Bernardes-Ribeiro Mariana , Patrone Luis Gustavo A. , Cristina-Silva Caroline , Bícego Kênia C. , Gargaglioni Luciane H.
Published: May 2024

Exercise elicits physiological adaptations, including hyperpnea. However, the mechanisms underlying exercise-induced hyperpnea remain unresolved. Skeletal muscle acts as a secretory organ, releasing irisin (IR) during exercise. Irisin can cross the blood–brain barrier, influencing muscle and tissue metabolism, as well as signaling in the central nervous system (CNS). We evaluated the effect of intracerebroventricular or intraperitoneal injection of IR in adult male rats on the cardiorespiratory and metabolic function during sleep–wake cycle under room air, hypercapnia and hypoxia. Central IR injection caused an inhibition on ventilation (VE) during wakefulness under normoxia, while peripheral IR reduced VE during sleep. Additionally, central IR exacerbates hypercapnic hyperventilation by increasing VE and reducing oxygen consumption. As to cardiovascular regulation, central IR caused an increase in heart rate (HR) across all conditions, while no change was observed following peripheral administration. Finally, central IR attenuated the hypoxia-induced regulated hypothermia and increase sleep episodes, while peripheral IR augmented CO2-induced hypothermia, during wakefulness. Overall, our results suggest that IR act mostly on CNS exerting an inhibitory effect on breathing under resting conditions, while stimulating the hypercapnic ventilatory response and increasing HR. Therefore, IR seems not to be responsible for the exercise-induced hyperpnea, but contributes to the increase in HR.
Imidazole[1,5-a]pyridine derivatives as EGFR tyrosine kinase inhibitors unraveled by umbrella sampling and steered molecular dynamics simulations
Authors: Truong Duc Toan , Ho Kiet , Nhi Huynh Thi Yen , Nguyen Van Ha , Dang Tuan Thanh , Nguyen Minh Tho
Published: May 2024

Although the use of the tyrosine kinase inhibitors (TKIs) has been proved that it can save live in a cancer treatment, the currently used drugs bring in many undesirable side-effects. Therefore, the search for new drugs and an evaluation of their efficiency are intensively carried out. Recently, a series of eighteen imidazole[1,5-a]pyridine derivatives were synthetized by us, and preliminary analyses pointed out their potential to be an important platform for pharmaceutical development owing to their promising actions as anticancer agents and enzyme (kinase, HIV-protease,…) inhibitors. In the present theoretical study, we further analyzed their efficiency in using a realistic scenario of computational drug design. Our protocol has been developed to not only observe the atomistic interaction between the EGFR protein and our 18 novel compounds using both umbrella sampling and steered molecular dynamics simulations, but also determine their absolute binding free energies. Calculated properties of the 18 novel compounds were in detail compared with those of two known drugs, erlotinib and osimertinib, currently used in cancer treatment. Inspiringly the simulation results promote three imidazole[1,5-a]pyridine derivatives as promising inhibitors into a further step of clinical trials.
Spatiotemporal variations of ecosystem services in the Aral Sea basin under different CMIP6 projections
Authors: He Jing , Yu Yang , Sun Lingxiao , Li Chunlan , Zhang Haiyan , Malik Ireneusz , Wistuba Malgorzata , Yu Ruide
Published: May 2024

The Aral Sea, located in Central Asia, has undergone significant reduction in surface area owing to the combined impacts of climate change and human activities. This reduction has led to a regional ecological crisis and profound repercussions on ecosystem services. Investigating the spatiotemporal variations and synergistic trade-offs of ESs in the Aral Sea basin is crucial for fostering the integrated development of the region’s socioeconomic ecology. This study utilizes the Future Land-Use Simulation and InVEST models to analyze future land-use scenarios, integrating CMIP6 projections to assess the quality of four key ecosystem services: water production, soil conservation, carbon storage, and habitat quality over two timeframes: the historical period (1995–2020) and the projected future (2021–2100). Employing Spearman correlation, the study explores the trade-offs and synergies among these ecosystem services. Findings reveal that the primary forms of land-use change in the Aral Sea basin are the reduction in water area (− 49.59%) and the rapid expansion of urban areas (+ 504.65%). Temporally, habitat quality exhibits a declining trend, while carbon storage shows an increasing trend, and water production and soil retention fluctuate initially decreasing and then increasing. Spatially, water production and carbon storage demonstrate an increasing trend from the northwest to the southeast. Habitat quality exhibits a higher spatial pattern in the southeast and south, contrasting with lower spatial patterns in the north and west. Low-level soil conservation is predominantly distributed in the northwest, while medium to low-level soil conservation is prevalent in the east of the basin. The trade-off and synergy analysis indicates that between 1995 and 2020, a trade-off relationship existed between carbon storage and habitat quality and water production, whereas synergies were observed between soil conservation and carbon storage, water production and habitat quality, and soil conservation. The correlation between water production and soil conservation emerges as the strongest, whereas the correlation between carbon storage and habitat quality appears to be the weakest. The dynamic spatiotemporal changes, trade-offs, and collaborative relationships of ESs constitute major aspects of ecosystem service research, holding substantial implications for the effective management of the regional ecological environment.
Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells
Authors: Wu Jiale , Li Wanyu , Su Junyu , Zheng Jiamin , Liang Yanwen , Lin Jiansuo , Xu Bilian , Liu Yi
Published: May 2024

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development.
Clear surgical margins as a prognostic indicator for disease recurrence, with no impact on survival rates in patients with myxofibrosarcoma
Authors: Tomáš Tomáš , Apostolopoulos Vasileios , Pazourek Lukáš , Kubíček Marián , Staniczková Zambo Iva , Adámková Dagmar , Šlampa Pavel , Mahdal Michal
Published: May 2024

Myxofibrosarcoma presents an infiltrating growth pattern that results in a high tendency for local recurrence. Clear margin resection is challenging because of microscopic infiltration. The purpose of the present study was to analyze the overall and disease-free survival rates of patients with myxofibrosarcoma and the prognostic factors that determine both survival and disease recurrence. Among the 111 patients included in our study, the 5-year overall survival rate was 65.5%. An age of more than 65 years (hazard ratio [HR] 1.9 [95% confidence interval (CI) 1.4–5.6]; p < 0.001), a tumor size of more than 5 cm (HR 2.8 [95% CI 0.9–8.1]; p = 0.049) and the G3 tumor grade (HR 14.1 [95% CI 2.1–105.0]; p < 0.001) negatively affected overall survival. The 5-year recurrence-free survival rate was 49.4%. R1/R2-type resection (HR 2.4 [95% CI 1.0–5.6]; p = 0.048) had a detrimental effect on tumor recurrence. Clear margins had a positive impact on recurrence-free survival, but did not significantly affect overall patient survival, suggesting that other factors may play a more significant role in determining patient outcomes. A surgical margin of 2 mm was not sufficient to significantly influence the incidence of recurrence. Consequently, a wider surgical margin may be necessary to reduce the risk of myxofibrosarcoma recurrence.
Proteomics and metabolic burden analysis to understand the impact of recombinant protein production in E. coli
Authors: Rajacharya Girish H. , Sharma Ashima , Yazdani Syed Shams
Published: May 2024

The impact of recombinant protein production (RPP) on host cells and the metabolic burden associated with it undermine the efficiency of the production system. This study utilized proteomics to investigate the dynamics of parent and recombinant cells induced at different time points for RPP. The results revealed significant changes in both transcriptional and translational machinery that may have impacted the metabolic burden, growth rate of the culture and the RPP. The timing of protein synthesis induction also played a critical role in the fate of the recombinant protein within the host cell, affecting protein and product yield. The study identified significant differences in the expression of proteins involved in fatty acid and lipid biosynthesis pathways between two E. coli host strains (M15 and DH5⍺), with the E. coli M15 strain demonstrating superior expression characteristics for the recombinant protein. Overall, these findings contribute to the knowledge base for rational strain engineering for optimized recombinant protein production.
A cooperative control method and application for series multivariable coupled system
Authors: Yu Yongchuan , Yang Haonan , Wan Shuo , Liu Qiusheng , Yan Jianzhuo
Published: May 2024

Series multivariable coupled system is a typical controlled object in process control industry. The interaction of various state variables between multiple inputs and outputs in the system forms a complex series multivariable coupled structure. This coupled structure makes the control of a controlled object in the system affect the controlled object in the upper and lower control loop. As a result, it is difficult to control one or more control loops in the system without changing the state of other links in the system. In this paper, a cooperative control method for series multivariable coupled system is proposed. A decoupling controller is designed to remove the coupling effect caused by the interaction between stages, and the system is decoupled into several independent control loops. Differential leading PI (proportional-integral) error compensation method is introduced to ensure the following performance of the controller without static error. The proposed cooperative control method satisfies the Lyapunov stability, and has been successfully applied in the simulation experiment of cascade pumping station system of Beijing East-to-West water transfer project. The proposed method reduces the difficulty to controlling the water level of forebay of each pumping station and ensures the efficient operation of the cascade pumping station system.
Temperature-dependent differences in mouse gut motility are mediated by stress
Authors: Han Alvin , Hudson-Paz Courtney , Robinson Beatriz G. , Becker Laren , Jacobson Amanda , Kaltschmidt Julia A. , Garrison Jennifer L. , Bhatt Ami S. , Monack Denise M.
Published: May 2024

Researchers have advocated elevating mouse housing temperatures from the conventional ~22 °C to the mouse thermoneutral point of 30 °C to enhance translational research. However, the impact of environmental temperature on mouse gastrointestinal physiology remains largely unexplored. Here we show that mice raised at 22 °C exhibit whole gut transit speed nearly twice as fast as those raised at 30 °C, primarily driven by a threefold increase in colon transit speed. Furthermore, gut microbiota composition differs between the two temperatures but does not dictate temperature-dependent differences in gut motility. Notably, increased stress signals from the hypothalamic–pituitary–adrenal axis at 22 °C have a pivotal role in mediating temperature-dependent differences in gut motility. Pharmacological and genetic depletion of the stress hormone corticotropin-releasing hormone slows gut motility in stressed 22 °C mice but has no comparable effect in relatively unstressed 30 °C mice. In conclusion, our findings highlight that colder mouse facility temperatures significantly increase gut motility through hormonal stress pathways.
Bacillamide D produced by Bacillus cereus from the mouse intestinal bacterial collection (miBC) is a potent cytotoxin in vitro
Authors: Hohmann Maximilian , Brunner Valentina , Johannes Widya , Schum Dominik , Carroll Laura M. , Liu Tianzhe , Sasaki Daisuke , Bosch Johanna , Clavel Thomas , Sieber Stephan A. , Zeller Georg , Tschurtschenthaler Markus , Janßen Klaus-Peter , Gulder Tobias A. M.
Published: May 2024

The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine (www.dsmz.de/miBC), which was predicted to encode a thiazol(in)e substructure. Cloning and heterologous expression of this BGC revealed that it produces bacillamide D. In-depth functional evaluation showed potent cytotoxicity and inhibition of cell migration using the human cell lines HCT116 and HEK293, which was validated using primary mouse organoids. This work establishes the bacillamides as selective cytotoxins from a bacterial gut isolate that affect mammalian cells. Our targeted structure-function-predictive approach is demonstrated to be a streamlined method to discover deleterious gut microbial metabolites with potential effects on human health.
Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish
Authors: Lai Shaohong , Shiraishi Hiroshi , Sebastian Wulan Apridita , Shimizu Nobuyuki , Umeda Ryohei , Ikeuchi Mayo , Kiyota Kyoko , Takeno Takashi , Miyazaki Shuya , Yano Shinji , Shimada Tatsuo , Yoshimura Akihiko , Hanada Reiko , Hanada Toshikatsu
Published: May 2024

SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9oi7/oi7) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9oi7/oi7 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9oi7/oi7 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9oi7/oi7 zebrafish. Spermidine oxidase (Smox) is increased in smg9oi7/oi7 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.
Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy
Authors: Karbon Gerlinde , Schuler Fabian , Braun Vincent Z , Eichin Felix , Haschka Manuel , Drach Mathias , Sotillo Rocio , Geley Stephan , Spierings Diana CJ , Tijhuis Andrea E , Foijer Floris , Villunger Andreas
Published: May 2024

Interference with microtubule dynamics in mitosis activates the spindle assembly checkpoint (SAC) to prevent chromosome segregation errors. The SAC induces mitotic arrest by inhibiting the anaphase-promoting complex (APC) via the mitotic checkpoint complex (MCC). The MCC component MAD2 neutralizes the critical APC cofactor, CDC20, preventing exit from mitosis. Extended mitotic arrest can promote mitochondrial apoptosis and caspase activation. However, the impact of mitotic cell death on tissue homeostasis in vivo is ill-defined. By conditional MAD2 overexpression, we observe that chronic SAC activation triggers bone marrow aplasia and intestinal atrophy in mice. While myelosuppression can be compensated for, gastrointestinal atrophy is detrimental. Remarkably, deletion of pro-apoptotic Bim/Bcl2l11 prevents gastrointestinal syndrome, while neither loss of Noxa/Pmaip or co-deletion of Bid and Puma/Bbc3 has such a protective effect, identifying BIM as rate-limiting apoptosis effector in mitotic cell death of the gastrointestinal epithelium. In contrast, only overexpression of anti-apoptotic BCL2, but none of the BH3-only protein deficiencies mentioned above, can mitigate myelosuppression. Our findings highlight tissue and cell-type-specific survival dependencies in response to SAC perturbation in vivo.
Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate
Authors: Karmakar Pratik , Finnegan Tyler J. , Rostam Darian C. , Taneja Sagarika , Uçar Sefa , Hansen Alexandar L. , Moore Curtis E. , Hadad Christopher M. , Pratumyot Kornkanya , Parquette Jon R. , Badjić Jovica D.
Published: May 2024

We describe synthesis, conformational dynamics and assembly characteristics of novel and tribenzotriquinacene-based hosts in water. These biocompatible molecules form stable inclusion complexes with toxic and anticancer drug methotrexate.
Paper-based sensing of phytotoxicant gossypol in aqueous media through turn-on visible-light emitting lanthanide-luminescence
Authors: Biswas Ananya , Maitra Uday
Published: May 2024

An inexpensive paper-based sensor through turn-on visible light emitting Tb3+-luminescence was developed for the first time to detect phytotoxin gossypol in aqueous solution and commercial cotton-seed oil with a lower nanomolar detection limit.
A novel approach for estimating the strength of argentophilic and aurophilic interactions using QTAIM parameters
Authors: Burguera Sergi , Bauzá Antonio , Frontera Antonio
Published: May 2024

Our manuscript presents a convenient method for estimating the strength of argentophilic (Ag⋯Ag) and aurophilic (Au⋯Au) interactions using QTAIM parameters.
Tuning energetic properties through co-crystallisation – a high-pressure experimental and computational study of nitrotriazolone: 4,4′-bipyridine
Authors: Christopher Imogen L. , Liu Xiaojiao , Lloyd Hayleigh J. , Bull Craig L. , Funnell Nicholas P. , Portius Peter , Michalchuk Adam A. L. , Kennedy Stuart R. , Pulham Colin R. , Morrison Carole A.
Published: May 2024

A highly piezochromic co-crystal of the energetic molecule NTO with bipyridine. Colour change attributed to direct compresion of the crystal lattice. No phase transition observed between 0–8 GPa. Impact sensitivity reduced compared to NTO.
Uncovering the crystallography and formation mechanism of nanoscale clusters in Sb-rich SPPs of a p-type (Bi, Sb)2Te3 alloy
Authors: Ren Jie , Wang Qichen , Han Fuzhou , Guo Wenbin , Cao Yi , Li Songbin , Li Geping , Ali Muhammad , Hu Jianan
Published: May 2024

The crystallography and formation of the Sb-rich SPPs in the (Bi, Sb)2Te3 alloy were systematically studied. When the (Bi, Sb)2Te3 alloy cooled down from the liquid state, nanosized Sb particles preferentially precipitated and aggregated, leading to the formation of Sb-rich clusters.
Hyperfine couplings between the paramagnetic moment and nuclei in the metallic phase of low silica X zeolite loaded with potassium
Authors: Igarashi Mutsuo , Shimizu Tadashi , Goto Atsushi , Hashi Kenjiro , Yamamichi Keiko , Nakano Takehito
Published: May 2024

Hyperfine coupling constants with the paramagnetic moment have been estimated for 23Na and 27Al in the metallic phase of the Na-K form of the low silica X (LSX) zeolite loaded with a saturating amount of potassium, 9.0 atoms per supercage.
Enhanced performance of a Na3.5Co4[Bi2Co2W19.75O70(H2O)6]/porous graphitic carbon nitride heterojunction based photocatalyst realized by the addition of copper sulfide nanoparticles
Authors: Jiang Qiushuang , Liu Zhuopeng , Wang Xinming , Ma Huiyuan , Pang Haijun
Published: May 2024

Photocatalytic hydrogen (H2) evolution can effectively solve the global energy problem, in which the key factor is the synthesis of efficient photocatalytic materials.
Two histidine-templated metal phosphate-oxalates: solvent-free synthesis, luminescence, and proton-conducting properties
Authors: Li Ying , Wang Yulin , Cheng Juan , Huang Ling , Gao Daojiang , Zou Guohong , Zhao Yan , Lin Zhien
Published: May 2024

Two luminescent and proton-conducting metal phosphate-oxalates have been synthesized using histidine as the organic template under solvent-free conditions.
Wood-derived Fe cluster-reinforced asymmetric single-atom catalysts and weather-resistant organohydrogel for wide-temperature flexible Zn–air batteries
Authors: Chen Jiachuan , Qiu Chenglong , Zhang Lei , Wang Baobin , Zhao Penghua , Zhao Yu , Wang Huanlei , Yang Guihua , Sun Aoran , Fan Jiaming , Xv Qixi , Rojas Orlando J.
Published: May 2024

All wood-based wide-temperature flexible Zn–air battery.
Challenges and perspectives on using acidic ionic liquids for biodiesel production via reactive distillation
Authors: Qi Zhaoyang , Cui Rongkai , Lin Hao , Ye Changshen , Chen Jie , Qiu Ting
Published: May 2024

Biodiesel, known as a renewable fuel, is an environmentally friendly energy source derived from animal and vegetable oils, as well as recycled oil.
Post-SELEX modifications with locked nucleic acids (LNA) of a SEA-specific DNA aptamer assisted by in silico modelling
Authors: Oliveira Ricardo , Pinho Eva , Azevedo Nuno Filipe , Almeida Carina
Published: May 2024

Post-SELEX modifications assisted by in silico modelling are powerful tools to improve the performance of aptamers, by providing a rational approach for the selection of modified-versions.
One-pot fabrication of vanadium-doped ordered mesoporous zirconium oxophosphate catalyst for the synthesis of carbonyl compounds
Authors: Xu Weichuan , Huang Hong , Bi Lingling , Xu Haimei , Miao Zhichao , Wu Mei
Published: May 2024

V/M-ZrPO composites as promising heterogeneous catalysts for sustainable carbonyl production.
Triazole-based nano-objects by polymerization induced self-assembly and modification of triazole motifs
Authors: Kumano Chiharu , Miyakawa Hirotsugu , Masuko Kazunori , Mori Hideharu
Published: May 2024

The rational design of self-assembled architectures with reactive and functional units via polymerization-induced self-assembly (PISA) has attracted growing interest. We demonstrate the design and synthesis of triazole-based nano-objects via PISA.
Boosting the electrocatalytic activity of 2D ultrathin BiOX/rGO (X = F, Cl, Br, and I) nanosheets as sulfur hosts: insight into the electronegativity effect of halogenated elements on the electrochemical performances of lithium–sulfur batteries
Authors: Wang Meili , Han Yumiao , Peng Huaiqi , Jin Ziqian , Guan Hui , Ma Shiyu , Li Xin , Ren Yunlai , Xie Lixia , Zheng Xianfu , Zhang Jianmin , Dong Yutao
Published: May 2024

Ultrathin BiOX/rGO (X = F, Cl, Br, and I) nanosheets serve as novel sulfur hosts in Li–S batteries. The influence of X on the electrochemical performance and redox mechanism is elucidated through in situ Raman/XRD characterization and DFT analysis.
Mechanical force-driven multi-state memory in WO3–δ thin films
Authors: Yang Mingdi , Lv Zonglin , Li Shan , Li Jiaqi , Cao Jinpeng , Chen Junjie , Wang Yilin , Lin Kun , Li Qiang , Miao Jun , Xing Xianran
Published: May 2024

Mechanical force successfully induced multi-level resistance states in WO3–δ thin films through large inhomogeneous strain and lattice distortion.
Engineered π⋯π interactions favour supramolecular dimers X@[FeL3]2 (X = Cl, Br, I): solid state and solution structure
Authors: Risa Arnau , Barrios Leoní A. , Diego Rosa , Roubeau Olivier , Aleshin Dmitry Y. , Nelyubina Yulia , Novikov Valentin , Teat Simon J. , Ribas-Ariño Jordi , Aromí Guillem
Published: May 2024

The engineered supramolecular recognition of coordination complexes achieved by ligand design is shown in the solid state and in solution via X-ray diffraction and paramagnetic H-NMR spectroscopy.
Correction: Tuning quantum interference through molecular junctions formed from cross-linked OPE-3 dimers
Authors: Alanazi Bashayr , Alajmi Asma , Al-Jobory Alaa A. , Lambert Colin , Ismael Ali
Published: May 2024

Correction for ‘Tuning quantum interference through molecular junctions formed from cross-linked OPE-3 dimers’ by Bashayr Alanazi et al., J. Mater. Chem. C, 2024, 12, 6905–6910, https://doi.org/10.1039/D4TC00611A.