bluuebunny/crossref_metadata_2025 huggingface dataset:
The complete mitochondrial genome of Brachytarsina amboinensis (Diptera: Hippoboscoidea: Streblidae) provides new insights into phylogenetic relationships of Hippoboscoidea
Authors: Yang Jinting , Wang Yujuan , Yang Huijuan , Huang Xiaobin
Published: December 2024

The family Streblidae is a significant grouping of dipteran insects within the superfamily Hippoboscoidea, which parasitizes the body surface of bats. With the global spread of bat-related pathogens in recent years, Streblidae has gained increasing attention due to its potential for pathogen transmission. A sample of Brachytarsina amboinensis was sequenced on the B. amboinensis were obtained, compared with available Streblidae mitogenomes, and the phylogeny of Hippoboscoidea was reconstructed. The results indicate that the mitochondrial genome of B. amboinensis exhibits a relatively high degree of conservation, with an identical gene count, arrangement, and orientation as the ancestral insect's genome. Base composition analysis revealed a strong bias towards A and T in the base composition. Selection pressure analysis indicated strong purifying selection acting on cox1. Pairwise genetic distance analysis showed that cox1 evolved at a relatively slow rate. Regarding phylogenetic relationships, the constructed phylogenetic trees using Bayesian inference and Maximum Likelihood methods supported the monophyly of the Hippoboscoidea, Glossinidae, Hippoboscidae, and Nycteribiidae clades, with high nodal support values. Our research confirmed the paraphyly of the families Streblidae. In the familial relations between Nycteribiidae and Streblidae, New World Streblidae share a closer kinship with Nycteribiidae. This contrasts with prior findings which indicated that Old World Streblidae share a closer kinship with Nycteribiidae. This study not only enhances the molecular database for bat flies but also provides a valuable reference for the identification and phylogenetic analysis of Streblidae.
The sectional curvature of the infinite dimensional manifold of Hölder equilibrium probabilities
Authors: Lopes Artur O. , Ruggiero Rafael O.
Published: December 2024

Here we consider the discrete time dynamics described by a transformation

$T:M \to M$

, where T is either the action of shift

$T=\sigma$

on the symbolic space

$M=\{1,2, \ldots,d\}^{\mathbb{N}}$

, or, T describes the action of a d to 1 expanding transformation

$T:S^1 \to S^1$

of class

$C^{1+\alpha}$

(for example

$x \to T(x) =\mathrm{d} x $

(mod 1)), where

$M=S^1$

is the unit circle. It is known that the infinite-dimensional manifold

$\mathcal{N}$

of Hölder equilibrium probabilities is an analytical manifold and carries a natural Riemannian metric. Given a certain normalized Hölder potential A denote by

$\mu_A \in \mathcal{N}$

the associated equilibrium probability. The set of tangent vectors X (functions

$X: M \to \mathbb{R}$

) to the manifold

$\mathcal{N}$

at the point µA (a subspace of the Hilbert space

$L^2(\mu_A)$

) coincides with the kernel of the Ruelle operator for the normalized potential A. The Riemannian norm

$|X|=|X|_A$

of the vector X, which is tangent to

$\mathcal{N}$

at the point µA, is described via the asymptotic variance, that is, satisfies

$ |X|^2 = \langle X, X \rangle = \lim_{n \to \infty}
\frac{1}{n} \int (\sum_{i=0}^{n-1} X\circ T^i )^2 \,\mathrm{d} \mu_A$

.

Consider an orthonormal basis Xi,

$i \in \mathbb{N}$

, for the tangent space at µA. For any two orthonormal vectors X and Y on the basis, the curvature

$K(X,Y)$

is

\begin{equation*}K(X,Y) = \frac{1}{4}[ \sum_{i=1}^\infty (\int X Y X_i \,\mathrm{d} \mu_A)^2 - \sum_{i=1}^\infty \int X^2 X_i \,\mathrm{d} \mu_A \int Y^2 X_i \,\mathrm{d} \mu_A ].\end{equation*}

When the equilibrium probabilities µA is the set of invariant Markov probabilities on

$\{0,1\}^{\mathbb{N}}\subset \mathcal{N}$

, introducing an orthonormal basis

$\hat{a}_y$

, indexed by finite words y, we show explicit expressions for

$K(\hat{a}_x,\hat{a}_z)$

, which is a finite sum. These values can be positive or negative depending on A and the words x and z. Words

$x,z$

with large length can eventually produce large negative curvature

$K(\hat{a}_x,\hat{a}_z)$

. If

$x, z$

do not begin with the same letter, then

$K(\hat{a}_x,\hat{a}_z)=0$

.
Toward a Strategy for More Spatial Control: The Politics of MLK Street (Re)naming
Authors: HANAFI ELYES
Published: December 2024

While the bulk of the study of the burgeoning movement to (re)name streets for Martin Luther King Jr. (MLK) has predominantly been centered on the creation of a new geography of commemoration honoring the leader's legacy and philosophy, little work has explicitly addressed the spatial motivations undergirding Black communities’ insistence on quickening the pace of such a process. This study strives to bring this point further by proposing to analyze the growing phenomenon of street naming for King in terms of Black communities’ relentless determination to challenge and reformulate the long-established practices shaping the MLK toponymic streetscape, especially in the southern part of the United States. On a deeper level, the paper reveals that Black communities and leaders use the spatial commemoration of King as a conduit for the acquisition of a more equitable share of and control over the urban landscape with their white counterparts. The politics of street naming thus lays bare the history and legacy of racial segregation in the South, the unfinished journey of the march for socio-spatial justice, and the rising power of Black communities.
Environmental drivers of seed persistence and seedling trait variation in two Neltuma species (Fabaceae)
Authors: Renzi Juan P. , Quintana Matías , Bruna Matías , Reinoso Omar
Published: December 2024

The endemic tree Neltuma caldenia Burk. and the shrub Neltuma flexuosa var depressa F.A. Roig (Fabaceae; subfam: Mimosoideae) are two promising species from the central region of Argentina, with high potential for use in the restoration of disturbed environments, for extensive livestock grazing and apiculture. Both species have seeds with physical dormancy. Ecological study of native species is important from the point of view of rehabilitation of degraded areas by natural regeneration or via seed-based programmes. The objective of this study was to evaluate soil seed bank persistence and seedling traits to understand variation among different populations of each of the study species growing along an ecological gradient and to identify potential components driving this variation. Home environments influenced seed bank persistence, which was higher in populations originating from more arid and unpredictable environments where it could act as a bet-hedging strategy between years and seasons. We also observed differences associated with seedling growth traits between the species and populations. Populations with higher seed persistence were associated with greater seedling growth in N. caldenia. The rapid elongation rate of N. caldenia seedlings growing in large populations and unstable environments could help their ability to escape drought by accessing deeper soil moisture and would confer a high relative competitive ability. In contrast, N. f. var depressa displayed higher seed persistence, which was associated with more arid and unstable conditions and correlated with lower seedling growth, possibly due to an inbreeding depression effect, resulting from the presence of mother plants in low-densities or being isolated from other individuals. There was no effect of population size on seed persistence. To better understand seed persistence and associated seedling trait variation, future studies need to consider the genotype, environment and landscape conditions.
To stay civil during the carnage: Feeling rules for soldiers in British military memoirs from the Napoleonic Wars (1803–15)
Authors: Pahl Kerstin Maria
Published: December 2024

During the Napoleonic Wars (1803–15), an unprecedented number of soldiers wrote “military memoirs,” firsthand accounts of the “first total war.” Next to private forms of recording experiences and keeping contact with those at home, such as letters or diaries, these memoirs were part of a larger shift in the relations between the army and civil society: soldiers wrote, at least partly, to change what non-combatants thought about them. As Britain did not see battles on home soil, war was both omnipresent and far away. Moreover, the reputation of the British armed forces was notorious, with common soldiers famously called “the scum of the earth” by Wellington. In conveying the battlefield experience to a sheltered audience, military memoirs, especially those written during or shortly after the wars, aimed at bridging the emotional divide between military and civil life, between the callous soldier and the compassionate citizen. Soldiers, too, these texts argued, were men of feeling, able to preserve a moral sense of respectability despite all the killing, blood, and trauma. Many memoirs communicated viscerally and in graphic detail about the horrors of war, both to make the traumatizing experience understandable and to show the heights of their emotional self-discipline. Bringing together the history of biography, reading, and emotions, this article argues that, by writing frankly about their horrific experiences, British soldiers fighting during the Napoleonic Wars contributed to changing civil society’s feeling rules about the army, reproaching the civilians’ contempt, and soliciting their compassion.
Thermal Adaptation of Enzyme‐Mediated Processes Reduces Simulated Soil CO2 Fluxes Upon Soil Warming
Authors: Van de Broek Marijn , Riley William J. , Tang Jinyun , Frey Serita D. , Schmidt Michael W. I.
Published: December 2024

Understanding factors influencing carbon effluxes from soils to the atmosphere is important in a world experiencing climatic change. Two important uncertainties related to soil organic carbon (SOC) stock responses to a changing climate are (a) whether soil microbial communities acclimate or adapt to changes in soil temperature and (b) how to represent this process in SOC models. To further explore these issues, we included thermal adaptation of enzyme‐mediated processes in a mechanistic SOC model (ReSOM) using the macromolecular rate theory. Thermal adaptation is defined here to encompass all potential responses of soil microbes and microbial communities following a change in temperature. To assess the effects of thermal adaptation of enzyme‐mediated processes on simulated SOC losses, ReSOM was applied to data collected from a 13‐year soil warming experiment. Results show that a model omitting thermal adaptation of enzyme‐mediated processes substantially overestimates observed CO2 effluxes during the initial years of soil warming. The bias against observed CO2 effluxes was lower for models including thermal adaptation of enzyme‐mediated processes. In addition, for a simulated linear 3°C soil warming over 100 years, models including thermal adaptation of enzyme‐mediated processes simulated SOC losses of a factor of three smaller than models omitting this process. As thermal adaptation of microbial community characteristics is generally not included in models simulating feedback between the soil, biosphere and atmosphere, we encourage future studies to assess the potential impact that microbial adaptation has on soil carbon – climate feedback representations in models.
Improving the rehabilitation of individuals admitted to England’s National Spinal Injuries Centre with traumatic brain injury
Authors: Falshaw Lawson , King Nigel , Cotter Imogen
Published: December 2024

Study design

Mixed methods service improvement project. Retrospective analysis of clinical documentation and qualitative focus group with clinicians.

Objectives

Although traumatic brain injury (TBI) and spinal cord injury (SCI) often co-occur, many barriers have been found to identifying TBI in SCI rehabilitation and adapting treatment accordingly. This study aimed to compare the number of individuals with a TBI detected at England’s National Spinal Injuries Centre to figures found in previous research and understand the barriers to adapting SCI rehabilitation in the presence of TBI.

Setting

England’s National Spinal Injuries Centre at Stoke Mandeville Hospital.

Methods

This mixed methods study assessed the documentation at each stage of 88 patients’ treatment where a TBI could be detected and used to inform rehabilitation, and subsequently, a focus group was conducted with staff to explore the barriers to detecting TBI and adapting SCI rehabilitation.

Results

Results suggested that data related to TBI were inconsistently recorded, the number of individuals recorded as having a TBI at the centre was lower than a recent study, and several barriers were interpreted from the focus group.

Conclusions

TBI in SCI populations may be an invisible unmet need. Several barriers may exist which prevent clinicians from detecting TBI in this population and adapting rehabilitation accordingly. Findings have implications for rehabilitation for individuals with TBI and SCI admitted to the service.
Oleanolic acid combined with aspirin plays antitumor roles in colorectal cancer via the Akt/NFκB/IκBα/COX2 pathway
Authors: Zhou Yulv , Lin Shengnan , Zhong Xinzhu , Huang Fang , Huang Jinxiang , Xu Luning
Published: December 2024

Among the common malignancies, colorectal cancer (CRC) is often resistant to chemotherapy because of drug resistance and severe toxicity. Currently, aspirin is one of the most promising CRC chemopreventive drugs, both for primary prevention and for reducing the chance of recurrence and metastasis following radical surgery in patients with early-stage CRC. Oleanolic acid is a potential antineoplastic drug that has an antagonistic effect on many kinds of tumors. Network pharmacology, molecular docking, and in vitro experiments were performed to investigate whether OA combined with aspirin can enhance the anticancer effects of aspirin. As indicated by the network pharmacology results, oleanolic acid and aspirin can regulate multiple signaling pathways through multiple target proteins, including NFκB1\IκBα\PTGS2\MAPK3\PIK3CA. A series of cellular experiments demonstrated for the first time that oleanolic acid synergistically enhances aspirin to inhibit the proliferation and invasion of HCT116 and HT29 cells and induce S-phase arrest by regulating Akt/NFκB/IκBα/COX2 signaling pathway, thus synergistically enhancing the ability of aspirin to promote apoptosis of colorectal cancer cells. This study provides a novel approach to the use of fresh medications for the treatment of colorectal cancer and offers a theoretical foundation for the potential creation of aspirin derivatives based on oleanolic acid.
GALNTL5, which is restricted to mouse spermatids, impairs endoplasmic reticulum (ER) function through direct interaction with ER chaperone proteins
Authors: Takasaki Nobuyoshi , Koya Yoshihiro , Yamashita Mamoru , Nawa Akihiro
Published: December 2024

Polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5) was identified as a pp-GalNAc-T family gene. Nevertheless, GALNTL5 has no glycosyltransferase activity. In mice, Galntl5 expression is restricted to differentiating spermatids, and haploinsufficiency leads to immotile spermatozoa with an aberrant protein composition. Moreover, heterozygotic deletions of human GALNTL5 have been detected in patients diagnosed with asthenozoospermia (low sperm motility). Although these findings indicate that GALNTL5 is a functional molecule essential for mature sperm formation in mammals, the exact function of GALNTL5 in spermiogenesis remains unknown. To clarify this role, we established the mouse spermatocyte cell line GC-2spd(ts), which exhibits drug-inducible GALNTL5 expression. Interestingly, continuous GALNTL5 expression in the resultant cell lines caused apoptosis with cell shrinkage, and GALNTL5 was localized in the endoplasmic reticulum (ER) and was associated with two ER-resident chaperone proteins, calnexin and BiP (GRP78). Calnexin recognized and strongly bound to the N-glycans on GALNTL5 molecules modified in the ER. In contrast, ER-resident BiP likely attached to GALNL5 regardless of its glycosylation. GALNTL5 expression abolished the binding between calnexin and misfolded substrate proteins, indicating that GALNTL5 directly blocks calnexin function. Furthermore, the interaction between GALNTL5 and calnexin decreased the level of BiP protein, and consequently also the expression levels of proteins that are resident in the ER, Golgi apparatus, and cytoplasm. These reduced protein levels were confirmed by loss of calnexin or BiP function in the GC-2spd(ts) cell line using siRNA knockdown. Further, sustained expression of GALNTL5 resulted in cell structure changes, including the position of the cis-Golgi apparatus and alterations in the ER network. These results strongly suggest that GALNTL5 contributes to alteration of the cell structure specific to differentiating spermatids by blocking ER function.
Phytochemical-mediated efferocytosis and autophagy in inflammation control
Authors: Vafadar Asma , Tajbakhsh Amir , Hosseinpour-Soleimani Fatemeh , Savardshtaki Amir , Hashempur Mohammad Hashem
Published: December 2024

Efferocytosis, the clearance of apoptotic cells, is a critical process that maintains tissue homeostasis and immune regulation. Defective efferocytosis is linked to the development of chronic inflammatory conditions, including atherosclerosis, neurological disorders, and autoimmune diseases. Moreover, the interplay between autophagy and efferocytosis is crucial for inflammation control, as autophagy enhances the ability of phagocytic cells. Efficient efferocytosis, in turn, regulates autophagic pathways, fostering a balanced cellular environment. Dysregulation of this balance can contribute to the pathogenesis of various disorders. Phytochemicals, bioactive compounds found in plants, have emerged as promising therapeutic agents owing to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to highlight the pivotal role of phytochemicals in enhancing efferocytosis and autophagy and explore their potential in the prevention and treatment of related disorders. This study examines how phytochemicals influence key aspects of efferocytosis, including phagocytic cell activation, macrophage polarization, and autophagy induction. The therapeutic potential of phytochemicals in atherosclerosis and neurological diseases is highlighted, emphasizing their ability to enhance efferocytosis and autophagy and reduce inflammation. This review also discusses innovative approaches, such as nanoformulations and combination therapies to improve the targeting and bioavailability of phytochemicals. Ultimately, this study inspires further research and clinical applications in phytochemical-mediated efferocytosis enhancement for managing chronic inflammatory and autoimmune conditions.
USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer
Authors: Shin Ji Hye , Kim Mi-Jeong , Kim Ji Young , Choi Bongkum , Kang Yeeun , Kim Seo Hyun , Lee Ha-Jeong , Kwon Dohee , Cho Yong Beom , Kim Kyeong Kyu , Chun Eunyoung , Lee Ki-Young
Published: December 2024

The emerging role of ubiquitin-specific peptidase 21 (USP21) in stabilizing Fra-1 (FOSL1) highlights its involvement in promoting colorectal cancer (CRC) metastasis. Additionally, a reciprocal link between EGFR signaling and Fra-1 activation has been identified, mediated through matrix metalloproteinases (MMPs). However, the functional implications of the USP21-EGFR signaling axis in metastatic CRC (mCRC) are not fully understood. To investigate the clinical correlation between USP21 and EGFR expression, RNA-Seq data from tumor tissues (n = 27) and matched normal tissues (n = 27) of 27 mCRC patients were analyzed. Functional studies were performed, including the use of CRISPR/Cas9 to generate USP21-knockout (USP21-KO) CRC cells, in vitro assays for cancer progression and tumor formation, in vivo xenograft assays in NSG mice. Additionally, the therapeutic effect of the USP21 inhibitor, BAY-805, was evaluated. We found that elevated levels of USP21 and EGFR expression in mCRC patients were associated with poorer survival outcomes. Mechanistically, USP21 was found to enhance EGFR stability by deubiquitinating EGFR, leading to reduced EGFR degradation. USP21-KO colon cancer cells exhibited significantly reduced proliferation, migration, colony formation, and 3D tumor spheroid formation in response to EGF. Furthermore, the tumorigenic activity in vivo was markedly diminished in NSG mice xenografted with USP21-KO colon cancer cells. Importantly, BAY-805 demonstrated a notable inhibitory effect on the formation of 3D tumor spheroids in colorectal cancer cells stimulated with EGF. These findings suggest that USP21 could be a valuable therapeutic target and predictive biomarker for managing mCRC driven by EGF.
SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis
Authors: Wang Ganggang , Jin Wenzhi , Zhang Lianmei , Dong Meiyuan , Zhang Xin , Zhou Zhijie , Wang Xiaoliang
Published: December 2024

Metabolic reprogramming has been found to be closely associated with the occurrence and development of hepatocellular carcinoma (HCC). The relationship between SLC50A1, a member of the SLC family involved in glucose transmembrane transport, and HCC remains unclear. This study aims to investigate the function and underlying mechanisms of SLC50A1 in the occurrence and progression of HCC. Based on bioinformatics analysis and clinical sample testing, we observed a significant upregulation of SLC50A1 in HCC, which is correlated with unfavorable prognosis in HCC patients. Additionally, there is a noticeable correlation between the expressions of SLC50A1 and METTL3. Further in vitro and in vivo experiments confirmed that SLC50A1 can regulate cellular glycolysis and the cell cycle, thereby promoting the proliferation of HCC cells while reducing apoptosis. Moreover, our findings indicate that SLC50A1 enhances resistance of HCC cells to DOX and 2-DG. Furthermore, we discovered that the m6A methyltransferase METTL3 mediates the methylation modification of SLC50A1. The recognition and binding of the modified SLC50A1 by IGF2BP2 subsequently promote its stability and translational expression. Consequently, our research identifies the METTL3/SLC50A1 axis as a novel therapeutic target in the context of HCC.
Cardiocutaneous syndrome is caused by aggregation of iASPP mutants
Authors: Lotz Rebecca , Osterburg Christian , Schäfer Birgit , Lu Xin , Dötsch Volker
Published: December 2024

The ASPP (apoptosis-stimulating protein of p53) family of proteins is involved in many cellular interactions and is starting to emerge as a major scaffolding hub for numerous proteins involved in cancer biology, inflammation and cellular integrity. It consists of the three members ASPP1, ASPP2 and iASPP which are best known for modulating the apoptotic function of p53, thereby directing cell fate decision. Germline mutations in iASPP have been shown to cause cardiocutaneous syndromes, a combination of heart and skin defects usually leading to death before the age of five. Mutations in iASPP causing these syndromes do not cluster in hot spots but are distributed throughout the protein. To understand the molecular mechanism(s) of how mutations in iASPP cause the development of cardiocutaneous syndromes we analysed the stability and solubility of iASPP mutants, characterized their interaction with chaperones and investigated their influence on NF-ĸB activity. Here we show that three different mechanisms are responsible for loss of function of iASPP: loss of the complete C-terminal domain, mutations resulting in increased auto-inhibition and aggregation due to destabilization of the C-terminal domain. In contrast to these germline mutations causing cardiocutaneous syndromes, missense mutations found in cancer do not result in aggregation.
Role of N6-methyladenosine methylation in nasopharyngeal carcinoma: current insights and future prospective
Authors: Zhao YaYan , Li Jie , Dian MeiJuan , Bie YaNan , Peng ZhiTao , Zhou Ying , Zhou BingQian , Hao WeiChao , Wang XiCheng
Published: December 2024

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck squamous cell carcinoma prevalent in Southern China, Southeast Asia, and North Africa. Despite advances in treatment options, the prognosis for advanced NPC remains poor, underscoring the urgent need to explore its underlying mechanisms and develop novel therapeutic strategies. Epigenetic alterations have been shown to play a key role in NPC progression. Recent studies indicate that dysregulation of RNA modifications in NPC specifically affects tumor-related transcripts, influencing various oncogenic processes. This review provides a comprehensive overview of altered RNA modifications and their regulators in NPC, with a focus on m6A and its regulatory mechanisms. We discuss how m6A RNA modification influences gene expression and affects NPC initiation and progression at the molecular level, analyzing its impact on cancer-related biological functions. Understanding these modifications could reveal new biomarkers and therapeutic targets for NPC, offering promising directions for future research and precision medicine.
Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3
Authors: Yang Nianhui , Dong Zexuan , Xiao Weihao , Deng Suqi , Li Yizhen , Hua Lei , Li Yue , Wu Yingying , Huang Kexiu , Zhou Wei , Wang Hua , Li Yonghua , Du Juan , Zeng Hui
Published: December 2024

Multiple myeloma (MM) is the second common hematological malignancy characterized by the abnormal proliferation of plasma cells. Although advances in the past decades have led to improved outcomes and longer survival, MM remains largely incurable. New targets and targeted therapy may help to achieve better outcomes. Proton exporter NHE1 is highly expressed by tumor cells to maintain pH gradient for their survival and its inhibitor Hexamethylene amiloride (HA) has been demonstrated anti-tumor effect. However, whether HA could inhibit MM remains unknown. In this study, we firstly demonstrated that elevated expression level of NHE1 is associated with poor prognosis of MM. Moreover, the NHE1 inhibitor HA inhibited growth and induced apoptosis effectively in both MM cell lines and primary bone marrow cells from MM patients. Mechanistically, inhibitory effect was achieved partially through TFE3-mediated lysosomal production. With a MM xenograft mouse model, we verified that HA has a significant anti MM effect in vivo. Importantly, HA induced apoptosis of the carfilzomib-resistant MM cells and enhanced the effect of carfilzomib in MM. In summary, we demonstrated that NHE1 inhibitor HA can effectively inhibit MM growth both in vitro and in vivo, providing a new therapeutic strategy for improved outcome of de novo and resistant MM.
Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases
Authors: Harary Paul M. , Rajaram Sanjeeth , Chen Maggie S. , Hori Yusuke S. , Park David J. , Chang Steven D.
Published: December 2024

Radiotherapy remains a key treatment modality for both primary and metastatic brain tumors. Significant technological advances in precision radiotherapy, such as stereotactic radiosurgery and intensity-modulated radiotherapy, have contributed to improved clinical outcomes. Notably, however, molecular genetics is not yet widely used to inform brain radiotherapy treatment. By comparison, genetic testing now plays a significant role in guiding targeted therapies and immunotherapies, particularly for brain metastases (BM) of lung cancer, breast cancer, and melanoma. Given increasing evidence of the importance of tumor genetics to radiation response, this may represent a currently under-utilized means of enhancing treatment outcomes. In addition, recent studies have shown potentially actionable mutations in BM which are not present in the primary tumor. Overall, this suggests that further investigation into the pathways mediating radiation response variability is warranted. Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral heterogeneity. We then discuss advances in tumor sampling methods, such as a collection of cell-free DNA and RNA, as well as progress in genomic analysis. We further consider how these tools may be applied to provide personalized radiotherapy for BM, including patient stratification, detection of radiotoxicity, and use of radiosensitization agents. In addition, we describe recent developments in preclinical models of BM and consider their relevance to investigating radiation response. Given the increase in clinical trials evaluating the combination of radiotherapy and targeted therapies, as well as the rising incidence of BM, it is essential to develop genomically informed approaches to enhance radiation response.
Overexpression of PDSS2-Del2 in HCC promotes tumor metastasis by interacting with macrophages
Authors: Li Guanghui , Suo Daqin , Ma Yuanzhen , Zeng Tingting , Zhan Jiarong , Yuan Yunfei , Guan Xin-Yuan , Li Yan
Published: December 2024

Hepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide. According to the Global Cancer Statistics 2020, liver cancer remains the third cause of cancer death globally. Despite significant advances in systemic therapy, HCC still has one of the worst prognoses due to its frequent recurrence and metastasis. Previously we found that PDSS2-Del2 (prenyl diphosphate synthase subunit 2 with exon 2 deletion), a novel variant of PDSS2, could promote HCC metastasis and angiogenesis via activating NF-κB. In this study, we elucidate a novel mechanism by which PDSS2-Del2 enhances HCC metastasis. The overexpression of PDSS2-Del2 in HCC cells promotes the ubiquitination and degradation of SKOR1, consequently heightening SMAD3 phosphorylation. Subsequently, the expression and secretion of MST1 (macrophage stimulatory protein 1) are upregulated, resulting in enhanced recruitment of macrophages into tumor tissues where they differentiate into M2-type macrophages. Co-culture with PDSS2-Del2 overexpressed HCC cells activated the PI3K/AKT signaling pathway in macrophages, and more MMP2 and MMP9 were secreted, which facilitated HCC cell dissemination. Our study elucidates a novel molecular mechanism by which PDSS2-Del2 promotes HCC metastasis, which may contribute to the development of effective HCC clinical treatment and prevent tumor metastasis. Furthermore, MST1 could be a potential therapeutic target, and MST1 inhibitors might be integrated into clinical practice for HCC patients with high expression of PDSS2-Del2.
How human–AI feedback loops alter human perceptual, emotional and social judgements
Authors: Glickman Moshe , Sharot Tali
Published: December 2024

Artificial intelligence (AI) technologies are rapidly advancing, enhancing human capabilities across various fields spanning from finance to medicine. Despite their numerous advantages, AI systems can exhibit biased judgements in domains ranging from perception to emotion. Here, in a series of experiments (n = 1,401 participants), we reveal a feedback loop where human–AI interactions alter processes underlying human perceptual, emotional and social judgements, subsequently amplifying biases in humans. This amplification is significantly greater than that observed in interactions between humans, due to both the tendency of AI systems to amplify biases and the way humans perceive AI systems. Participants are often unaware of the extent of the AI’s influence, rendering them more susceptible to it. These findings uncover a mechanism wherein AI systems amplify biases, which are further internalized by humans, triggering a snowball effect where small errors in judgement escalate into much larger ones.
Tidally driven remelting around 4.35 billion years ago indicates the Moon is old
Authors: Nimmo Francis , Kleine Thorsten , Morbidelli Alessandro
Published: December 2024

The last giant impact on Earth is thought to have formed the Moon1. The timing of this event can be determined by dating the different rocks assumed to have crystallized from the lunar magma ocean (LMO). This has led to a wide range of estimates for the age of the Moon between 4.35 and 4.51 billion years ago (Ga), depending on whether ages for lunar whole-rock samples2–4 or individual zircon grains5–7 are used. Here we argue that the frequent occurrence of approximately 4.35-Ga ages among lunar rocks and a spike in zircon ages at about the same time8 is indicative of a remelting event driven by the Moon’s orbital evolution rather than the original crystallization of the LMO. We show that during passage through the Laplace plane transition9, the Moon experienced sufficient tidal heating and melting to reset the formation ages of most lunar samples, while retaining an earlier frozen-in shape10 and rare, earlier-formed zircons. This paradigm reconciles existing discrepancies in estimates for the crystallization time of the LMO, and permits formation of the Moon within a few tens of million years of Solar System formation, consistent with dynamical models of terrestrial planet formation11. Remelting of the Moon also explains the lower number of lunar impact basins than expected12,13, and allows metal from planetesimals accreted to the Moon after its formation to be removed to the lunar core, explaining the apparent deficit of such materials in the Moon compared with Earth14.
Ancient genomes reveal a deep history of Treponema pallidum in the Americas
Authors: Barquera Rodrigo , Sitter T. Lesley , Kirkpatrick Casey L. , Ramirez Darío A. , Kocher Arthur , Spyrou Maria A. , Couoh Lourdes R. , Talavera-González Jorge A. , Castro Mario , von Hunnius Tanya , Guevara Evelyn K. , Hamilton W. Derek , Roberts Patrick , Scott Erin , Fabra Mariana , Da Peña Gabriela V. , Pacheco Aryel , Rodriguez Mónica , Aspillaga Eugenio , Tiliakou Anthi , Nelson Elizabeth A. , Giffin Karen L. , Bianco Raffaela A. , Rohrlach Adam B. , de los Ángeles García Martínez María , Ballesteros Solís Fabiola A. , Sajantila Antti , Saunders Shelley R. , Nores Rodrigo , Herbig Alexander , Krause Johannes , Bos Kirsten I.
Published: December 2024

Human treponemal infections are caused by a family of closely related Treponema pallidum that give rise to the diseases yaws, bejel, pinta and, most notably, syphilis1. Debates on a common origin for these pathogens and the history of syphilis itself have weighed evidence for the ‘Columbian hypothesis’2, which argues for an American origin, against that for the ‘pre-Columbian hypothesis’3, which argues for the presence of the disease in Eurasia in the Medieval period and possibly earlier. Although molecular data has provided a genetic basis for distinction of the typed subspecies4, deep evolution of the complex has remained unresolved owing to limitations in the conclusions that can be drawn from the sparse palaeogenomic data that are currently available. Here we explore this evolutionary history through analyses of five pre- and peri-contact ancient treponemal genomes from the Americas that represent ancient relatives of the T. pallidum subsp. pallidum (syphilis), T. pallidum subsp. pertenue (yaws) and T. pallidum subsp. endemicum (bejel) lineages. Our data indicate unexplored diversity and an emergence of T. pallidum that post-dates human occupation in the Americas. Together, these results support an American origin for all T. pallidum characterized at the genomic level, both modern and ancient.
Chromosome-scale genome assembly and de novo annotation of Alopecurus aequalis
Authors: Wright Jonathan , Baker Kendall , Barker Tom , Catchpole Leah , Durrant Alex , Fraser Fiona , Gharbi Karim , Harrison Christian , Henderson Suzanne , Irish Naomi , Kaithakottil Gemy , Leitch Ilia J. , Li Jun , Lucchini Sacha , Neve Paul , Powell Robyn , Rees Hannah , Swarbreck David , Watkins Chris , Wood Jonathan , McTaggart Seanna , Hall Anthony , MacGregor Dana
Published: December 2024

Alopecurus aequalis is a winter annual or short-lived perennial bunchgrass which has in recent years emerged as the dominant agricultural weed of barley and wheat in certain regions of China and Japan, causing significant yield losses. Its robust tillering capacity and high fecundity, combined with the development of both target and non-target-site resistance to herbicides means it is a formidable challenge to food security. Here we report on a chromosome-scale assembly of A. aequalis with a genome size of 2.83 Gb. The genome contained 33,758 high-confidence protein-coding genes with functional annotation. Comparative genomics revealed that the genome structure of A. aequalis is more similar to Hordeum vulgare rather than the more closely related Alopecurus myosuroides.
Monitoring measles infections using flight passenger dynamics in Europe: A data-driven approach
Authors: Romano Chiara , Branda Francesco , Scarpa Fabio , Lasinio Giovanna Jona , Ciccozzi Massimo
Published: December 2024

This paper presents an open-access repository collecting information on measles virus infections and flight passenger movements in European countries from 2011 to 2023. It provides a comprehensive overview of reported measles cases and measles-mumps-rubella (MMR) vaccination coverage from authoritative organizations such as the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC). In addition, the dataset includes detailed data on passenger movements between countries, facilitating analysis of cross-border disease transmission. This resource enables more precise spatial analyses for monitoring and forecasting measles outbreaks, underscoring the importance of adequate vaccination coverage and sustained international surveillance to prevent the spread of the disease.
Aperiodic and oscillatory systems underpinning human domain-general cognition
Authors: Lu Runhao , Dermody Nadene , Duncan John , Woolgar Alexandra
Published: December 2024

Domain-general cognitive systems are essential for adaptive human behaviour, supporting various cognitive tasks through flexible neural mechanisms. While fMRI studies link frontoparietal network activation to increasing demands across various tasks, the electrophysiological mechanisms underlying this domain-general response to demand remain unclear. Here, we used MEG/EEG, and separated the aperiodic and oscillatory components of the signals to examine their roles in domain-general cognition across three cognitive tasks using multivariate analysis. We found that both aperiodic (broadband power, slope, and intercept) and oscillatory (theta, alpha, and beta power) components coded task demand and content across all subtasks. Aperiodic broadband power in particular strongly coded task demand, in a manner that generalised across all subtasks. Source estimation suggested that increasing cognitive demand decreased aperiodic broadband power across the brain, with the strongest modulations overlapping with the frontoparietal network. In contrast, oscillatory activity showed more localised patterns of modulation, primarily in frontal or occipital regions. These results provide insights into the electrophysiological underpinnings of human domain-general cognition, highlighting the critical role of aperiodic broadband power.
Predicting emergence of crystals from amorphous precursors with deep learning potentials
Authors: Aykol Muratahan , Merchant Amil , Batzner Simon , Wei Jennifer N. , Cubuk Ekin Dogus
Published: December 2024

Crystallization of amorphous precursors into metastable crystals plays a fundamental role in the formation of new matter, from geological to biological processes in nature to the synthesis and development of new materials in the laboratory. Reliably predicting the outcome of such a process would enable new research directions in these areas, but has remained beyond the reach of molecular modeling or ab initio methods. Here we show that candidates for the crystallization products of amorphous precursors can be predicted in many inorganic systems by sampling the local structural motifs at the atomistic level using universal deep learning interatomic potentials. We show that this approach identifies, with high accuracy, the most likely crystal structures of the polymorphs that initially nucleate from amorphous precursors, across a diverse set of material systems, including polymorphic oxides, nitrides, carbides, fluorides, chlorides, chalcogenides and metal alloys.
Mineral-ecological cropping systems mitigate biodiversity-productivity trade-offs of the organic vs. conventional farming dichotomy
Authors: Kasten Marit Kinga , Witte Felix , Sponagel Christian , Bahrs Enno , Köhler Thomas , Morinière Jérôme , Grass Ingo
Published: December 2024

Conventional agriculture significantly reduces biodiversity, while organic farming promotes it, but often yields half as much. Addressing this biodiversity-productivity trade-off is crucial for future agriculture. Mineral-ecological cropping systems (MECS) have been suggested as an alternative, blending organic and conventional methods by avoiding chemical-synthetic pesticides and using mineral fertilizers. In a German experiment with 168 parcels, we compared MECS, conventional, and organic systems in terms of ecological and economic performance. Arthropod diversity was measured through standardized species collections and DNA-metabarcoding. Productivity was assessed via yields and economic profits. MECS showed similar arthropod diversity to other farming systems, achieved 90% of conventional crop yields, and produced 1.8 times of the organic yield. Profits from MECS were on average 37% higher than the conventional system with a short wheat-maize-soy crop rotation. Further farm-level studies are needed, but MECS could be a reasonable alternative to both organic and conventional farming and can mitigate biodiversity-productivity trade-offs.
Legacy effects of crop diversity on weed-crop competition in maize production
Authors: Menalled Uriel D. , Ann Bybee-Finley K. , Smith Richard G. , DiTommaso Antonio , Darby Heather M. , Pethybridge Sarah J. , Ryan Matthew R.
Published: December 2024

The legacy effects of crop diversity on maize (Zea mays L.) tissue nutrient composition, weed community structure, and intensity of weed-crop competition were assessed through a field experiment at two sites in the northeastern United States. Fields were conditioned with crop diversity gradients from summer 2016 to spring 2019. The crop diversity gradients ranged from a single cultivar to sixteen intercropped cultivars (four species, four cultivars per species) and were established in organic annual and perennial cropping systems. Following the three-year conditioning phase, maize was planted across the entire experiment, and each conditioning-phase diversity treatment was split into weed-free, ambient-weed, moderate-weed, and heavy-weed treatments. Within each cropping system, the effect of crop diversity legacy on weed-crop competition was negligible. In contrast, weed-crop competition varied between the maize grown in soil conditioned by the annual and perennial cropping systems.
Transcriptomic analysis of circulating extracellular vesicles during the perioperative period of Fontan and Glenn surgery
Authors: Takaesu Felipe , Yasseen Khalid , Yang Evan , Park Hyun-Ji , Kelly John M. , Breuer Christopher K. , Davis Michael E.
Published: December 2024

Single-ventricle defects are treated with the Glenn and Fontan procedures, which offer lifesaving relief but result in lifelong complications. To address the lack of outcome predictors, we conducted an untargeted transcriptomic analysis to identify RNA biomarkers in serum and circulating sEVs from 25 Glenn or Fontan patients with three samples exclusively used for experimental assays. Unsupervised analysis revealed a distinction between pre-op and post-op samples in both surgical groups. Differential gene expression and pathway analysis showed enrichment for pro-angiogenic cargo in post-op sEVs compared to pre-op sEVs. Wound healing assays revealed post-op Fontan sEVs induce a stronger pro-angiogenic response than pre-op Fontan sEVs. A PLSR-guided approach revealed MAPK6, GLE1, hsa-miR-340-5p, and hsa-miR-199b-5p as key transcripts in the observed wound healing response. Lastly, EV-Origin revealed decreased secretion of sEV from cardiac tissue and increased secretion from brain tissue for both Fontan and Glenn samples. This work demonstrates the potential of sEV RNAs as biomarkers for patients with Fontan physiology, enabling quicker diagnosis for Fontan-associated complications.
Tuning interfacial charge transport via Ti–O–Sn bonds for efficient CO2 conversion
Authors: Yin Shikang , Zhou Fan , Zhou Yiying , Sun Yuming , Li Binrong , Qin Yingying , Yan Yan , Huo Pengwei
Published: December 2024

Hierarchical structures with ohmic contact junctions: the strong built-in electric field constructed through an ohmic contact realizes the directional movement and rapid migration of photogenerated charges, significantly improving CO2 conversion.
Thermodynamics and transport in molten chloride salts and their mixtures
Authors: Cockrell C. , Withington M. , Devereux H. L. , Elena A. M. , Todorov I. T. , Liu Z. K. , Shang S. L. , McCloy J. S. , Bingham P. A. , Trachenko K.
Published: December 2024

Relationship between thermophysical properties and phonon mean free path. Heat capacity, viscosity, and thermal conductivity in ionic liquids decrease as mean free path decreases and dynamics become less “solid-like” and collect motion diminishes.
Necrosis inducing tetranuclear Ru(ii)–Re(i) metal complex for anticancer therapy
Authors: Schleisiek Julia , Michaltsis Eleni , Mayer Stephan , Montesdeoca Nicolás , Karges Johannes
Published: December 2024

This study reports on the chemical synthesis and biological evaluation of a tetranuclear Ru(ii)–Re(i) complex as a chemotherapeutic agent.
High-performance multi-functional solar panel coatings: recent advances, challenges, strategies and industrial aspects
Authors: Padhan Anil Kumar , Singh Vaishakhi , Ray Saptarshi , Voolapalli Ravi Kumar
Published: December 2024

This review highlights multi-functional solar panel coatings, including anti-reflective, superhydrophobic, selfcleaning, anti-fogging, self-healing and self-stratifying features.
Green synthesis of biocompatible silver nanoparticles using Trillium govanianum rhizome extract: comprehensive biological evaluation and in silico analysis
Authors: Manzoor Syed Ifrah , Jabeen Farhat , Patel Rajan , Alam Rizvi M. Moshahid , Imtiyaz Khalid , Malik Maqsood Ahmad , Dar Tanveer A.
Published: December 2024

Green synthesized Trillium govanianum rhizome-mediated nanoparticles, characterized by spectroscopic and electron microscopic studies, exhibited potential activities including antioxidant, anti-inflammatory, anticancer and DNA damage protection.
Highly efficient electroplating of (220)-oriented nano-twinned copper in methanesulfonic copper baths
Authors: Wei Hsiang-Sheng , Tsou Hsu , Ku Hao-Yu , Lai Chi-Yu , Chen Shih-Hua , Lin Chun-Cheng , Liu Shang-Tzu , Huang Hung-Yi , Lu Ming-Kun , Liu Kuan-Ling , Hu Chi-Chang
Published: December 2024

The formation of a high-density nanotwinned structure in copper deposits is presently acknowledged as a paramount goal for enhancing the material characteristics of copper.
MAX phase coatings: synthesis, protective performance, and functional characteristics
Authors: Ma Guanshui , Zhang Anfeng , Wang Zhenyu , Wang Kaihang , Zhang Jiayue , Xu Kaixuan , Xu Yuxi , Zhou Shenghao , Wang Aiying
Published: December 2024

This paper reviews the historical development of MAX-phase materials, fabrication techniques for MAX-phase coatings, their protective performance and functional characteristics, and provides an outlook on future trends of MAX-phase coatings.
Mechanochemical generation of nitrogen-centred radicals for the formation of tertiary amines in polymers
Authors: Storch Sonja , Campagna Davide , Aydonat Simay , Göstl Robert
Published: December 2024

Carbamoylketoximes of N-pentenyl-substituted secondary amines give access to cyclic tertiary amine bases by a subsequent 5-exo-trig cyclization after homolytic bond scission of the mechanophore induced through polymer mechanochemistry.