bluuebunny/crossref_metadata_2025 huggingface dataset:
VPS41 recruits biosynthetic LAMP-positive vesicles through interaction with Arl8b
Authors: Sanzà Paolo , van der Beek Jan , Draper Derk , de Heus Cecilia , Veenendaal Tineke , Brink Corlinda ten , Farías Ginny G. , Liv Nalan , Klumperman Judith
Published: January 2025

Vacuolar protein sorting 41 (VPS41), a component of the homotypic fusion and protein sorting (HOPS) complex for lysosomal fusion, is essential for the trafficking of lysosomal membrane proteins via lysosome-associated membrane protein (LAMP) carriers from the trans-Golgi network (TGN) to endo/lysosomes. However, the molecular mechanisms underlying this pathway and VPS41’s role herein remain poorly understood. Here, we investigated the effects of ectopically localizing VPS41 to mitochondria on LAMP distribution. Using electron microscopy, we identified that mitochondrial-localized VPS41 recruited LAMP1- and LAMP2A-positive vesicles resembling LAMP carriers. The retention using selective hooks (RUSH) system further revealed that newly synthesized LAMPs were specifically recruited by mitochondrial VPS41, a function not shared by other HOPS subunits. Notably, we identified the small GTPase Arl8b as a critical factor for LAMP carrier trafficking. Arl8b was present on LAMP carriers and bound to the WD40 domain of VPS41, enabling their recruitment. These findings reveal a unique role of VPS41 in recruiting TGN-derived LAMP carriers and expand our understanding of VPS41–Arl8b interactions beyond endosome–lysosome fusion, providing new insights into lysosomal trafficking mechanisms.
TBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis
Authors: Zhai Denghui , Li Lamei , Wang Difei , Wang Weishu , Zhao Siyang , Wang Xue , Chen Cheng , Zhu Zixuan , Bu Weiwen , Yang Mulin , Yin Hanxiao , Shan Ying , Zhao Huijie , Westlake Christopher J. , Lu Quanlong , Zhou Jun
Published: January 2025

TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells. Further investigations reveal enhanced Rab11–MICAL1 interaction upon TBC1D20 loss, activating the monooxygenase domain of MICAL1 and inducing F-actin depolymerization around the centrosome. This actin network reorganization facilitates vesicle trafficking and docking, ultimately promoting ciliogenesis. In summary, our work uncovers a coordinated ciliogenesis initiation mechanism via Rab11 activation. These findings underscore a pivotal role for TBC1D20 in early ciliogenesis, advancing our understanding of its spatiotemporal regulation and offering insights into the disease pathogenesis associated with TBC1D20 mutations.
Association of preoperative frailty with short- and long-term outcomes after hepatic resection for elderly patients with hepatocellular carcinoma: multicentre analysis
Authors: Diao Yong-Kang , Li Dan , Wu Han , Yang Yi-Fan , Wang Nan-Ya , Gu Wei-Min , Chen Ting-Hao , Li Jie , Wang Hong , Zhou Ya-Hao , Liang Ying-Jian , Wang Xian-Ming , Lin Kong-Ying , Gu Li-Hui , Xu Jia-Hao , Pawlik Timothy M , Lau Wan-Yee , Shen Feng , Yang Tian
Published: January 2025

Background

The growing demand for surgical resection in elderly patients with hepatocellular carcinoma highlights the need to understand the impact of preoperative frailty on surgical outcomes. The aim of this multicentre cohort study was to investigate the association between frailty and short- and long-term outcomes after hepatic resection among elderly patients with hepatocellular carcinoma.

Methods

A multicentre analysis was conducted on elderly patients with hepatocellular carcinoma (aged greater than or equal to 70 years) who underwent curative-intent resection at ten Chinese hospitals from 2012 to 2021. Frailty was assessed using the Clinical Frailty Scale (with frailty defined as a Clinical Frailty Scale score greater than or equal to 5). The primary outcomes were overall survival and recurrence-free survival; secondary outcomes encompassed postoperative 30-day morbidity and mortality, and 90-day mortality. The outcomes between patients with and without preoperative frailty were compared.

Results

Of the 488 elderly patients, 148 (30.3%) were considered frail. Frail patients experienced significantly higher 30-day morbidity (68.9% (102 of 148) versus 43.2% (147 of 340)), 30-day mortality (4.1% (6 of 148) versus 0.6% (2 of 340)), and 90-day mortality (6.1% (9 of 148) versus 0.9% (3 of 340)) compared with non-frail patients (all P < 0.010). During a median follow-up of 37.7 (interquartile range 20.4–57.8) months, frail patients demonstrated significantly worse median overall survival (41.6 (95% c.i. 32.0 to 51.2) versus 69.7 (95% c.i. 55.6 to 83.8) months) and recurrence-free survival (27.6 (95% c.i. 23.1 to 32.1) versus 42.7 (95% c.i. 34.6 to 50.8) months) compared with non-frail patients (both P < 0.010). Multivariable Cox regression analysis revealed frailty as an independent risk factor for decreased overall survival (HR 1.61; P = 0.001) and decreased recurrence-free survival (HR 1.32; P = 0.028).

Conclusion

Frailty is significantly associated with adverse short-term and long-term outcomes after resection in elderly patients with hepatocellular carcinoma. The findings suggest that frailty assessment should be incorporated into perioperative and postoperative evaluation for elderly patients undergoing hepatocellular carcinoma resection.
Safety of Triple-Dose Rifampin in Tuberculosis Treatment: A Systematic Review and Meta-Analysis
Authors: Arbiv Omri A , Holmes Thomas , Kim Marie JeongMin , Yan Marie , Romanowski Kamila , Brode Sarah K , Burman William J , Menzies Dick , Johnston James C
Published: January 2025

Background

Recent studies suggest that triple-dose rifampin (TDR; ≥30 mg/kg/d) may be unsafe. We updated a systematic review to investigate the safety and efficacy of TDR.

Methods

We searched Embase, MEDLINE, Cochrane CENTRAL, Cochrane Database for Systematic Reviews, and clinicaltrials.gov for randomized, controlled trials from 1 January 1965 to 10 February 2024 that compared standard-dose rifampin (SDR) with TDR and/or double-dose rifampin (DDR) in human tuberculosis treatment. The primary outcome was pooled incidence rate ratio (IRR) of severe adverse events (SevAEs) between participants who received TDR and those who received SDR. Pooled relative risk (RR) of death was a key secondary outcome. Meta-analysis was performed using the inverse variance method. Heterogeneity was assessed using I2, and bias was assessed using Cochrane Risk of Bias 2. The protocol was prospectively registered (osf.io/kfn5a).

Results

Of the 11 315 articles identified, 17 met inclusion criteria, enrolling 2313 SDR participants (17 studies), 2238 receiving DDR (12 studies), and 1199 receiving TDR (11 studies). Six studies had a high risk of bias. There was an increase in pooled SevAEs among participants who received TDR compared with those who received SDR (IRR, 1.48; 95% confidence interval [CI], 1.12–1.96; I2, 23%), driven by hepatic events (IRR, 1.96; 95% CI, 1.21–3.18). Death did not differ between participants who received TDR and SDR (RR, 1.19; 95% CI, .71–1.99). One limitation is that only 2 included studies were blinded.

Conclusions

Regimens that used TDR were associated with an increase in SevAEs, raising concerns regarding safety of TDR regimens.
Educational needs of informal caregivers in cardiac rehabilitation: a mixed-methods study
Authors: Bomtempo Ana Paula Delgado , Ghisi Gabriela Lima de Melo
Published: January 2025

Aims

Informal caregivers play a crucial role in supporting individuals with cardiovascular disease (CVD) during cardiac rehabilitation (CR), yet their specific educational needs are often overlooked. Understanding these needs is essential for developing targeted interventions that enhance informal caregiver support and improve patient outcomes in CR. This study aimed to explore the educational needs of informal caregivers supporting individuals with CVD attending CR.

Methods and results

A mixed-methods approach was used to explore the educational needs of informal caregivers. Quantitative data were collected through an online cross-sectional survey completed by 86 informal caregivers. The survey assessed sociodemographic characteristics, quality of life (WHOQOL-BREF), and educational needs. Most respondents had not received formal education or training related to caregiving, although their knowledge of CVD was rated as moderate to high. Many reported difficulties accessing reliable information and resources. Qualitative data were gathered through semi-structured interviews with 16 informal caregivers, and four key themes were determined: Helpful Resources, Empowerment, Lived Experience Network, and Psychological Support. Informal caregivers expressed a desire for practical resources, more direct access to healthcare professionals, and both emotional and peer support. They also highlighted the importance of managing stress and balancing their well-being alongside caregiving responsibilities.

Conclusion

The findings suggest that educational interventions for informal caregivers should be comprehensive and flexible, incorporating practical caregiving strategies as well as social and emotional support. Such programmes could enhance the effectiveness of CR by better equipping informal caregivers to support patient recovery while maintaining their own health.
New Opportunities, Rising Constraints: Assessing the Gendered Opportunity Structure of Myanmar’s Resistance Movement
Authors: Haines Rebecca
Published: January 2025

In a global context of rising right-wing governance, feminist and gender equality actors are facing the reversal of hard-won gains and the deterioration of what they view to be the conditions for advancing gender equality. While these shifts are not failures of feminism, they do represent devastating setbacks that fundamentally challenge the strategies and tactics of gender equality movements. In response, gender equality actors are joining with a range of others in broad resistance coalitions, often with regime change goals. Although this is a common strategy of gender equality actors under similar political conditions, scholars do not typically analyze how joining with these broad coalitions impacts opportunities to work on gender equality. In other words, it is not common to examine within-movement opportunity structures and how gender equality actors are impacted by them. To contribute to addressing this gap, in this article I build on the concept of “gendered opportunity structure” to analyze the within-movement gender dynamics of Myanmar’s resistance movement and how gender equality actors are responding to them. My findings indicate that, while the current gendered opportunity structure of the movement provides some openings for the expanded participation of individual well-established gender equality actors and gender-diverse people, critical shifts in the within-movement opportunity structure have had the net effect of narrowing the objectives and strategies of gender equality actors. Via this case analysis, I propose that the concept “within-movement gendered opportunity structure” may be generative in helping scholars and practitioners better think about how gender equality actors are enabled and constrained by joining heterogeneous resistance movements. This concept, along with the suggested framework and model of analysis worked through in this article, could be adapted for analysis of other relevant cases. More consistent casework on the experiences of gender equality actors within broad-based resistance movements would help build knowledge about the conditions under which resistance movements of this kind may support gender equality outcomes.
A patient similarity-embedded Bayesian approach to prognostic biomarker inference with application to thoracic cancer immunity
Authors: Yu Duo , Huang Meilin , Kane Michael J , Hobbs Brian P
Published: January 2025

This paper introduces a novel statistical methodology integrating machine learning (ML) and Bayesian modelling to facilitate personalized prognostic predictions with application to oncology. Utilizing power priors, we construct ‘patient-similarity embeddings’ that identify localized patterns of prognosis. The methodology is applied to study the prognostic value of markers of anticancer immunity within the tumour microenvironment of nonsmall cell lung cancer while adjusting for established clinical characteristics. The method outperforms traditional regression and ML models, while accurately identifying subgroup patterns, thereby enhancing statistical inference and hypothesis testing.
Smullyan’s truth and provability
Authors: Kurahashi Taishi , Tominaga Kohei
Published: January 2025

We revisit Smullyan’s paper ‘Truth and Provability’ (2013) for three purposes. First, we introduce the notion of Smullyan models to give a precise definition for Smullyan’s framework discussed in that paper. Second, we clarify the relationship between three theorems proved by Smullyan and other newly introduced properties for Smullyan models in terms of both implications and non-implications. Third, we construct two Smullyan models based on arithmetical ideas and show the correspondence between the properties of these Smullyan models and those concerning truth and provability in arithmetic.
TCR clonality and TCR clonal expansion in thein situmicroenvironment of non-small cell lung cancer
Authors: Yu Hui , Magoulopoulou Anastasia , Amini Rose-Marie , Chatzinikolaou Maria Paraskevi , Horie Masafumi , Lindberg Amanda , Mezheyeuski Artur , Backman Max , Metousis Andreas , Brunström Hans , Zuniga Millaray Marincevic , Botling Johan , Mattsson Johanna Sofia Margareta , Kärre Klas , Leandersson Karin , Nilsson Mats , Strell Carina , Micke Patrick
Published: January 2025

T-cell activation and clonal expansion are essential for the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) patients. Since the distribution of T-cell clones might provide insights into immunogenic mechanisms, we determined the α/β TCR clonality using RNA-sequencing from frozen tumor tissue of 182 NSCLC patients and paired the results with extensivein situimage and sequence analyses of the immune microenvironment of NSCLC. TCR clonality (Gini index) patterns ranged from high T-cell clone diversity with high evenness (Gini index low) to clonal dominance with low evenness (Gini index high). TCR clonality in cancer tissue was lower than in matched normal lung (p=0.021). High Gini index correlated strongly with distinct mutations (EGFR, P53), tumor mutation burden (p<0.001), and inflamed tumor phenotypes (PRF1, GZMA, GZMB, INFG) with exhaustion signatures (LAG3, TIGIT, IDO1, PD-1, PD-L1). Correspondingly, PD-1+, CD3+, CD8A+, CD163+, and CD138+ immune cells infiltrated cancer tissue with high TCR clonality.In situsequencing revealed that dominant T-cell clones were more often of CD8-subtype and tended to approximate the tumor cell compartment (p<0.03). In a checkpoint inhibitor-treated NSCLC patient cohort, high TCR clonality was associated with therapy response (p=0.016) and prolonged survival (p=0.003, median survival 13.8 vs 2.9 months).

Our robust analysis pipeline revealed diverse TCR repertoires related to genotypes and immune phenotypes. Thein situpositioning of expanded T-cell clones indicated functional impact, which was clinically confirmed in NSCLC patients receiving immunotherapy.

One sentence summary

T-cell clone expansion in NSCLC is associated with genetic mutations, immune phenotypes, immunotherapy response, and patient survival.
Alveolar metabolite availability facilitates secondary infection byPseudomonas aeruginosain acutely injured lungs
Authors: Baker Jennifer M. , Flott Thomas L. , McLellan Laura A. , Bustos Ingrid G. , Guerrero Jose L. , Mendez Lina M. , Petouhoff Annastasia M. , Ranjan Piyush , Metcalf Joseph D. , McDonald Roderick A. , Falkowski Nicole R. , He Ying , Cala Mónica P. , Huffnagle Gary B. , Sjoding Michael W. , Reyes Luis F. , Stringer Kathleen A. , Dickson Robert P.
Published: January 2025

Secondary bacterial pneumonia is a frequent complication of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Prior efforts to explain increased pneumonia risk in ALI/ARDS have focused on impaired immunity and bacterial virulence, but have overlooked the potential contribution of ecological factors within acutely injured lungs. Here, we show that lung injury profoundly alters the alveolar metabolic microenvironment, a change that can be exploited by a common pneumonia pathogen. In mice and humans, we found that growth ofPseudomonas aeruginosa(the most prominent respiratory pathogen in a retrospective cohort of patients with ARDS) is enhanced by increased alveolar concentrations of multiple ALI/ARDS-associated metabolites, which are derived from the blood and cross the compromised alveolar-capillary barrier during alveolar leak. Collectively, this work reveals an ecological mechanism by which pathogens may survive in the injured lung microenvironment and identifies new potential targets for secondary pneumonia prevention and treatment.
Branched and Linear F-actin Networks Control Directional Migration Switching Behavior on Aligned Collagen Fibrils
Authors: Foroozandehfar Azarnoosh , Tohidi Shayan , Siddiqui Shafayet Ahmed , Namanda Fred Rogers , Schneider Ian
Published: January 2025

Directed cell migration is essential in biological processes like embryonic development, wound healing and cancer metastasis and is driven by a variety of directional cues, including aligned fibrils in the extracellular matrix (ECM), a phenomenon known as contact guidance. How different cells respond to aligned fibrils and how external factors like ECM stiffness and internal regulators like formins and Arp2/3 control contact guidance across different type of cells is unknown. In this study, a unique system to assemble aligned collagen fibrils on mica and to transfer them onto substrates with specified stiffness is used to probe how external factors and internal regulators affect contact guidance. This system reveals distinct contact guidance behaviors: mesenchymal cells exhibit high-fidelity contact guidance, amoeboid cells ignore cues and epithelial cells use a mixture of both parallel and perpendicular migration on aligned collagen fibrils. Formins and Arp2/3 exert reciprocal control over contact guidance across a variety of cell types, where formins mediators of linear F-actin structures enhance contact guidance and Arp2/3 a mediator of branched F-actin structures diminishes contact guidance. This controlled materials system reveals important external and internal mechanisms of how contact guidance directs cell migration across a variety of different cell types.
Short-Term Arcade-Action Video Gaming Enhances Working Memory Precision
Authors: Asgari Ali , Vahabie Abdol-Hossein , Rezayat Ehsan
Published: January 2025

Objective

Action video games are increasingly recognized for their potential to enhance cognitive capacities, including working memory (WM). However, most studies require extensive training or prior gaming experience. We examined whether a single, short-term session of “Snail Mail,” an arcade-action video game, could boost WM precision compared to a passive control condition.

Method

Thirty-six healthy adults (18–34 years) were randomly assigned to either play “Snail Mail” (Intervention) or watch episodes of “Shaun the Sheep” (Control) for 30 minutes. Two participants were excluded for unstable performance, yielding a final sample of 34. Participants completed a face emotion recognition memory task before and after the intervention, wherein the absolute error served as the primary metric of WM precision. A mixture model further characterized memory precision, and random guessing.

Results

The Intervention group showed a significant reduction in absolute error from pre- to post-test, whereas the Control group exhibited a negative effect size, indicating worsened post-test performance. Mixture-model results revealed a significant increase in precision for the Intervention group.

Conclusion

These findings indicate that a 30-minute arcade-action game session can meaningfully enhance WM precision, highlighting the feasibility of brief, targeted gaming interventions. Future research should explore longer-term outcomes, generalizability to other cognitive tasks, and optimal intervention protocols for sustained benefits.
Intercellular signaling stabilizes single-cell level phenotypic transitions and accelerates the reestablishment of equilibrium of heterogeneous cancer cell populations
Authors: Lopez Daniel , Tyson Darren R , Hong Tian
Published: January 2025

Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood. In particular, the role of intercellular communications in phenotypic plasticity remains elusive. In this study, we employ a multiscale inference-based approach using single-cell RNA sequencing (scRNA-seq) data to explore how intercellular interactions influence phenotypic dynamics of cancer cells, particularly cancers undergoing epithelial-mesenchymal transition. Our inference approach reveals that signaling interactions between cancerous cells in small cell lung cancer (SCLC) result in seemingly contradictory behaviors, reinforcing the cellular phenotypes and maintaining population-level intratumoral heterogeneity. Additionally, we find a recurring signaling pattern across multiple types of cancer in which the mesenchymal-like subtypes utilize signals from other subtypes to reinforce its phenotype, further promoting the intratumoral heterogeneity. We use a mathematical model based on ordinary differential equations to show that inter-subtype communication accelerates the development of heterogeneous tumor populations. Our work highlights the critical role of intercellular signaling in sustaining intratumoral heterogeneity, and our approach of computational analysis of scRNA-seq data can infer inter- and intra-cellular signaling networks in a holistic manner.
Development of Proton Density Fat Fraction Micro-MRI for Non-Invasive Quantitative Assessment of Bone Marrow Changes with Age and Radiation in Mouse Models
Authors: Ghimire Hemendra , Malekzadeh Malakeh , Lim Ji Eun , Madabushi Srideshikan Sargur , Zampini Marco Andrea , Camacho Angela , Hu Weidong , Storme Guy , Malki Monzr M. Al , Hui Susanta K.
Published: January 2025

Background/Objectives

Bone marrow (BM) adipocytes are critical in progressing solid tumor metastases and hematological malignancies across pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including hematologic malignancies, but are limited in capturing the full complexity of loco-regional and global BM microenvironments. Non-invasive imaging techniques like Magnetic Resonance Imaging (MRI), could offer valuable alternatives for real-time evaluation of BM diseases in both preclinical translational and clinical studies.

Methods

We developed a preclinical proton density fat fraction (PDFF) MRI technique for quantitative BM composition assessment, focusing on fat fraction (FF) within mouse femurs. We validated this method using aging mice and young mice subjected to 10 Gy X-ray irradiation, compared with young unirradiated mice as controls. Water-fat phantoms (0% to 100% fat content) were used to optimize the imaging sequence, and immunohistochemical (IHC) staining with H&E validates equivalent adipose content in the femur BM regions.

Results

Significant differences in FF were observed across age groups (p = 0.001 for histology and p = 0.0002 for PDFF) and between irradiated and control mice (p = 0.005 for histology and p = 0.002 for PDFF). A strong correlation (R2∼ 0.84) between FF values from PDFF and histology validates the accuracy of the technique.

Conclusions

These findings demonstrate the potential of PDFF MRI as a non-invasive real-time imaging biomarker for quantifying BM fat fraction in preclinical mice model studies, particularly in evaluating the effects of aging, disease progression, and irradiation therapy in pediatric and translational oncology research.
Hydrogen-bonded organic framework nanotransducers enabled sono-optogenetics for Parkinsonian rats
Authors: Wang Wenliang , Pyatnitskiy Ilya , Shi Yanshu , Tang Kai Wing Kevin , Xie Yi , Wynn Thomas , Liu Xiangping , Hsieh Ju-Chun , Jeong Jinmo , He Weilong , Artman Brinkley , Lozano Anakaren Romero , Shi Xi , Sangani Arjun , Fenno Lief , Santacruz Samantha , Chen Banglin , Wang Huiliang
Published: January 2025

Cell-type-specific activation of parvalbumin (PV)-expressing neurons in the external globus pallidus (GPe) through optogenetics has shown promise in facilitating long-lasting movement dysfunction recovery in mice with Parkinson’s disease. However, its translational potential is hindered by adverse effects stemming from the invasive implantation of optical fibers into the brain. In this study, we have developed a non-invasive optogenetics approach, utilizing focused ultrasound-triggered mechanoluminescent nanotransducers to enable remote photon delivery deep in the brain for genetically targeted neuromodulation. These mechanoluminescent nanotransducers consist of sonosensitized hydrogen-bonded frameworks and chemiluminescent L012, serving as a nanoscale light source through ultrasound-induced cascade reactions. This system offers high ultrasound-triggered brightness and long-lasting light emission, facilitating repeatable deep brain stimulation. Our sono-optogenetics technology demonstrated effective modulation in the mouse motor cortex for limb motion control and activation of PV-GPe neurons for rescuing movement dysfunction over time in dopamine-depleted Parkinson’s disease rats. This approach demonstrates the pathway for achieving genetically targeted and non-invasive neuromodulation for long-lasting treatment of Parkinson’s disease, towards non-human primate models and clinical applications.
Drastic genome reduction driven by parasitic lifestyle: Two complete genomes of endosymbiotic bacteria possibly hosted by a dinoflagellate
Authors: Nakayama Takuro , Harada Ryo , Yabuki Akinori , Nomura Mami , Shiba Kogiku , Inaba Kazuo , Inagaki Yuji
Published: January 2025

Bacteria with endosymbiotic lifestyles often exhibit dramatic genome reduction. While the reduction of genomes in intracellular symbionts of animals, including parasitic bacteria, has been extensively studied, less is known about such bacteria associated with single-celled eukaryotes. Here, we report the genomes of two novel gammaproteobacterial lineages, RS3 and XS4, identified as putative parasitic endosymbionts of the dinoflagellateCitharistes regius. Phylogenetic analyses suggest that RS3 and XS4 belong to the family Fastidiosibacteraceae within the order Beggiatoales, forming independent lineages therein. The genomes of RS3 and XS4 are 529 Kbp and 436 Kbp in size, respectively, revealing drastic genome reduction compared to related bacterial genomes. XS4, which has a particularly reduced genome with low GC content, uses an alternative genetic code, in which UGA assigned tryptophan. The small genomes of RS3 and XS4 encode a limited number of proteins, retaining only approximately 20% of the predicted ancestral proteome. Metabolic reconstruction suggests that RS3 and XS4 are energy parasites, heavily dependent on their host for essential metabolites. Furthermore, we found that the ancestor of both genomes likely acquired an ADP:ATP antiporter gene via horizontal gene transfer, an event that may have enabled their evolution as energy parasites by facilitating the acquisition of ATP from their host. These observations on novel bacteria with highly reduced genomes expand our understanding of the phylogenetic and genomic diversity of endosymbiotic bacteria in protists.
High-pressure Golgi neuronal staining for X-ray whole-brain imaging
Authors: Tang Qiaowei , Cai Xiaoqing , Liu Yu , Zhang Yu , Yan Xin , Zhou Feng , Zhang Jichao , Li Qian , Li Ke , Deng Biao , Wang Lihua , Li Jiang , Zhu Ying , Fan Chunhai , Hu Jun
Published: January 2025

Whole-brain imaging has revolutionized neuroscience research, providing comprehensive insights into neural networks across the entire brain. This powerful approach has greatly advanced our understanding of brain functions and the mechanisms underlying various diseases. One primary challenge in whole-brain imaging technology is to achieve high-resolution observation of neural networks at large scales. Although Golgi method allows labeling random neurons in their entirety in the brain, visualizing individual dendritic trees, and tracing long-distance axonal projections, the lengthy processing time pose a limit on its use, i.e., staining a mouse whole-brain sample of just 300 mm³ takes over two weeks. Here, we developed a rapid staining technique for whole-brain neurons using high-pressure assisted Golgi (HP Golgi). This method significantly reduced the staining time for mouse whole-brain neurons from 16 days to only 4 days. We demonstrated the broad applicability of the HP Golgi method across various model organisms, achieving whole-brain neuronal staining in zebrafish, mice, and rats. Further, we successfully performed rapid staining of hippocampal neurons in an intact pig brain, which is difficult to achieve with the classic Golgi-Cox method. We also demonstrated that the combination of the HP Golgi method with synchrotron-based X-ray microscopy for high-resolution imaging of whole-brain neurons in mice. This HP Golgi method enables fast and high-resolution neuronal imaging in large model organisms, showcasing its broad applicability for diverse applications.
Thriving big data artificial intelligence: entrepreneurial leadership, proactive personality and affective commitment to innovate micro and small family businesses
Authors: Nusrat Ayesha , Zongming Zhang , Li Jie , Muhammad Muneeb Farhan
Published: January 2025

Purpose

This study examines the impact of entrepreneurial leadership (EL) on Chinese micro and small family businesses’ (MSFBs) innovativeness. Drawing on the resource-based view, this research study further explores the intermediary roles of proactive personality (PP) and affective commitment (AC) between ELs’ and MSFBs’ innovativeness. Besides this, the present work proposes a novel contingency impact of big data-powered artificial intelligence (BDAI) between EL, PP and AC, which indirectly spurs MSFBs’ innovativeness.

Design/methodology/approach

This study proposed a moderated mediation model using multi-wave, multi-source, time-lagged datasets of 380 employees from 190 Chinese MSFBs. We tested our hypotheses using structural equation modeling through the PLS technique.

Findings

The findings reveal a significant impact of EL on MSFB innovativeness, underscoring the pivotal intermediary roles of EL in driving MSFB innovativeness. Furthermore, BDAI emerges as a critical contingency factor, amplifying the effects of EL on both PP and AC to spur MSFBs’ innovativeness.

Practical implications

Our research offers several practical implications for Chinese MSFBs aiming to enhance innovativeness and competitive advantage. Firstly, understanding the direct impact of EL on MSFBs’ innovativeness provides valuable guidance for MSFB leaders. Secondly, recognizing the mediating roles of PP and AC underscores the importance of human and social capital in driving innovation within Chinese MSFBs. Thirdly, leveraging BDAI as a contingency factor can further augment the effects of EL on both PP and AC, thereby enhancing innovation outcomes. Thus, managers can capitalize on BDAI to gain actionable insights to increase MSFBs’ innovativeness.

Originality/value

This study enlightened how EL can develop MSFBs innovativeness through PP and AC. Our findings reveal that MSFBs can increase their innovation by leveraging PP and AC, leading to higher proactive provision in employees’ behavior. Subsequently, our results synchronized the exploration of BDAI as a novel insight for MSFB innovativeness. This shed light on a highly notable contribution to understanding BDAI to benefit MSFBs, acting as a critical contingency between EL, PP and AC.
Leader–member exchange and work–family conflict; the moderating role of emotional intelligence and supervisory support
Authors: Adu Isaac Nyarko , Darko Nana Yaa , Kyei-Frimpong Michael , Yeboah-Kordee Nana Serwah
Published: January 2025

Purpose

This study sought to examine the interactional effect of emotional intelligence (EI) and supervisory support (SS) in the relationship between leader–member exchange (LMX) and work–family conflict (WFC).

Design/methodology/approach

The study adopted the survey research design, where 286 employees in the Ghanaian financial services sector were sampled for this study. The data retrieved from the respondents were quantitatively analyzed using descriptive and inferential statistics with the aid of IBM SPSS Statistics (Version 26.0), SmartPLS (Version 4.0) and the Hayes PROCESS macro.

Findings

As hypothesized, this study revealed that LMX positively and significantly relates to WFC, while EI and SS significantly moderated the relationship between LMX and WFC.

Practical implications

The findings of this study revealed the need for organizations to develop and implement policies that promote good leadership among employees.

Originality/value

This study fills the research gap in the Ghanaian financial service sector regarding the moderating effect of supervisory support and emotional intelligence in the nexus between leader–member exchange and employees’ work–family conflict.
Information seeking in a time of war: coping with stress in Lithuania during the Russia/Ukraine war
Authors: Wilson Thomas D. , Maceviciute Elena
Published: January 2025

Purpose

The aim of the research reported here was to determine how Lithuanian citizens engaged in information-seeking behaviour in response to the stress caused by the Russian invasion of Ukraine.

Design/methodology/approach

An interview survey was designed, using a semi-structured interview schedule. A convenience sample of 21 participants was obtained and the interviews lasted between 20 and 70 min. The schedule design was guided by the transactional theory of stress and coping and employed the Perceived Stress Scale.

Findings

A majority of participants experienced moderate to high levels of stress associated with the war in Ukraine. Information seeking and discussing information found with family members and friends played a significant role in helping to moderate stress. Most of the participants understood more than one language and, consequently, were able to compare local information sources with international sources. Only five participants were active users of social media, the rest were critical of these sources. All participants valued those sources they believed to be reliable and truthful.

Research limitations/implications

The small convenience sample of educated urban participants limits generalizability but provides indicative findings for future investigations into information behaviour during prolonged international conflicts.

Practical implications

The study highlights the importance of media literacy in managing psychological stress during geopolitical tensions, demonstrating how strategic information seeking and social support can serve as effective coping mechanisms.

Social implications

The research reveals psychological impacts of war beyond direct conflict zones, illustrating how communities develop collective emotional resilience through informed, critically engaged information practices.

Originality/value

The study provides unique insights by examining war-related stress in a neighbouring country not directly experiencing conflict, applying stress-coping theory to understand intricate information-seeking behaviours during a geopolitical crisis.
Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice
Authors: Luna Adrian , Chou Kai‐Neng , Wragg Kathleen M. , Worley Matthew J. , Paruchuri Nikhil , Zhou Xiaofeng , Blin Muriel G. , Moore Bethany B. , Salmon Morgan , Goldstein Daniel R. , Deng Jane C.
Published: January 2025

Aging is a major risk factor for poor outcomes following respiratory infections. In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced lung damage and increased survival, little is known about the role that senescent cells play in the outcome of influenza A viral (IAV) infections in aged mice. Here, we tested if the aged mice survival or weight loss IAV infections could be improved using three different senolytic regimens. We found that neither dasatinib plus quercetin, fisetin, nor ABT‐263 improved outcomes. Furthermore, both dasatanib plus quercetin and fisetin treatments further suppressed immune infiltration than aging alone. Additionally, our data show that the short‐term senolytic agents do not reduce senescent markers in our aged mouse model. These findings suggest that acute senolytic treatments do not universally reverse aging related immune phenotype against all respiratory viral infections.
Characteristics of Soluble PD‐L1 and PD‐1 Expression and Their Correlations With Immune Status and Prognosis in Advanced Lung Cancer
Authors: Li Ran , Liang Hongge , Shang Ying , Yang Zhengwu , Wang Keqiang , Yang Donghong , Bao Jing , Xi Wen , Zhou Dexun , Ni Wentao , Gao Zhancheng , Mu Xinlin
Published: January 2025

Purpose

Our study aims to evaluate the characteristics of serum soluble PD‐1 (sPD‐1) and soluble PD‐L1 (sPD‐L1) levels and their correlations with immune status and prognosis in advanced lung cancer patients.

Methods

Patients diagnosed with advanced lung cancer based on histology or cytology in Peking University People's Hospital from July 2020 to November 2021 were enrolled. Clinicopathological data were recorded and analyzed. Treatment efficacy was evaluated according to RESIST 1.1 criteria. The serum levels of sPD‐L1 and sPD‐1 were detected by enzyme‐linked immunosorbent assay (ELISA). Lymphocyte subsets were measured by flow cytometry to evaluate the immune status of the patients.

Results

A total of 65 patients with advanced lung cancer were enrolled. sPD‐L1 level in lung cancer patients (15.67 ± 11.09 pg/mL, p = 0.001) was significantly higher than those in healthy controls (5.21 ± 4.46 pg/mL). sPD‐1 level did not show a significant difference between patients with lung cancer and healthy controls. sPD‐L1 level in patients with progressive disease (PD) was significantly higher than those with partial response (PR) (20.94 ± 8.91 vs. 13.14 ± 12.66 pg/mL, p = 0.033). In treatment‐naïve patients, sPD‐L1 level was negatively correlated with the lymphocyte ratio (correlation coefficient = −0.452, p = 0.014). Kaplan–Meier survival analysis showed that patients with low sPD‐L1 level had a significantly longer progression‐free survival (PFS) (10.4 vs. 5.7 months, p = 0.023). However, sPD‐1 level did not correlate with lymphocyte subsets or prognosis in overall patients with lung cancer. Subgroup analysis showed that prolonged PFS in patients with low sPD‐L1 level was exclusively shown in the NSCLC subgroup, not in the SCLC subgroup. In the subgroups of patients who subsequently received immunotherapy, low sPD‐L1 level was correlated with longer PFS in the overall patients and NSCLC patients, and low sPD‐1 level was correlated with longer PFS exclusively in NSCLC patients.

Conclusion

Serum sPD‐L1 level was higher in patients with advanced lung cancer than healthy individuals, which was negatively correlated with the proportion of lymphocytes and prognosis. Serum sPD‐1 level did not show significant difference between patients with lung cancer and healthy individuals, which showed no correlation with lymphocyte subsets and the prognosis of overall patients, except NSCLC patients receiving immunotherapy.
Beyond the screen: Dissecting the nexus of victimization and cyberhate among adolescents through excessive internet use, online interactions with strangers and parental restrictions
Authors: Korol Liliia , Blaya Catherine
Published: January 2025

Prior research has established that being a target of offline and online victimization might function as a significant risk factor that increases the likelihood of adolescents' involvement in cyberhate. Yet, relatively little is known about the mediating and moderating mechanisms underlying this relationship. To fill this important gap in knowledge, the present study aims to examine (1) whether excessive Internet use and contact with unknown people online act as sequential mediators in the relationship between overall victimization and youth's involvement in cyberhate; and (2) whether restrictive parental mediation has any role to play in moderating this relationship. The findings suggest that adolescents who experience victimization are more likely to turn to using the Internet excessively, and consequently interact with strangers online, which in turn makes them more prone to becoming victim to cyberhate or spreading hateful content online themselves. Moreover, restrictive parental mediation was shown to exacerbate the link between excessive Internet use and adolescents' contacts with unknown people online, thereby putting them at higher risk of cyberhate involvement. The current study emphasizes the need for a balanced approach to parental mediation – one that fosters open communication, trust and the development of digital literacy skills.
Testing the Effectiveness of Synthetic Chemical Lures to Increase Fruit Bat‐Mediated Seed Dispersal in a Tropical Forest
Authors: Gelambi Mariana , Coto‐Pereira Yoselyn Pamela , Morales‐M Estefania , Whitehead Susan R.
Published: January 2025

Tropical deforestation is occurring at alarming rates, creating an urgent need for global prioritization of restoration efforts. One potential forest recovery strategy is to boost seed‐dispersing animal activity (e.g., fruit‐eating bats) to increase seed availability in degraded areas. In this study, we investigated the efficacy of synthetic chemical lures in attracting fruit bats and enhancing seed rain in northeastern Costa Rica. The chemical lures were composed of a few volatile organic compounds commonly found in ripe bat‐dispersed fruits. Daily deployment of the chemical lures resulted in a significant increase in the capture of Carollia spp., a key neotropical seed disperser, but no detectable effect on other fruit bats. The 15‐day deployment of chemical lures also increased the average of total seeds collected in seed traps. However, the effect of lures explained only a small portion of the total variance in seed rain, highlighting the potential context‐dependency of these results. Still, in contrast to the previously studied essential oil‐based lures, synthetic lures hold the potential to be applied across a broader spectrum of restoration initiatives due to simplified manufacturing and improved reproducibility. Although additional research is essential to understand the full potential for use in restoration efforts, our study demonstrates the effectiveness of synthetic chemical lures in attracting fruit bats and potentially augmenting seed rain.
Integrated Mendelian Randomization and Single‐Cell Transcriptomics Analysis Identifies Critical Blood Biomarkers and Potential Mechanisms in Epilepsy
Authors: Shi Jianwei , Xie Jing , Yang Yanfeng , Fu Bin , Ye Zuliang , Tang Ting , Liu Quanlei , Xu Jinkun , Wei Penghu , Shan Yongzhi , Zhao Guoguang
Published: January 2025

Background

Epilepsy has a genetic predisposition, yet causal factors and the dynamics of the immune environment in epilepsy are not fully understood.

Methods

We analyzed peripheral blood samples from epilepsy patients, identifying key genes associated with epilepsy risk through Mendelian randomization, using eQTLGen and genome‐wide association studies. The peripheral immune environment's composition in epilepsy was explored using CIBERSORT. An epilepsy mouse model was established to validated the expression of key genes at the transcriptomic and proteomic levels through single‐cell analysis. Relevant pathways were verified. Finally, we developed a predictive model for antiepileptic drug response in epilepsy patients.

Results

We found that CDC25B, DNMT1, GZMA, MTX1, and SSH2 expression decreases epilepsy risk, whereas FGD3, RAF1, and SH3BP5L increase it. Epilepsy patients exhibited an altered peripheral immune profile, notably with increased activated mast cells and decreased CD4 memory activated T cells and γδ T cells. Eight genes were significantly related to this immune environment. In the animal model, FGD3, SSH2, and DNMT1 were upregulated at both mRNA and protein levels in the hippocampus. FGD3 and SSH2 are specifically elevated in microglia and are primarily associated with actin regulation. The trained predictive model was deployed on an online platform.

Conclusions

This study elucidates key genes linked to epilepsy, delineates the epilepsy immune landscape, and highlights the interaction between these domains, providing insights into potential epilepsy mechanisms and treatments.
Peripheral Single‐Cell Immune Characteristics Contribute to the Diagnosis of Alzheimer's Disease and Dementia With Lewy Bodies
Authors: Qiu Conglong , Zhang Danhua , Wang Majie , Mei Xi , Chen Wei , Yu Haihang , Yin Weiwei , Peng Guoping , Hu Shaohua
Published: January 2025

Objective

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD.

Methods

We utilized time‐of‐flight mass cytometry (CyTOF) with single‐cell resolution to quantitatively analyze peripheral PBMCs, identifying 1228 immune characteristics. Based on the top‐selected immune features, we constructed immunological elastic net (iEN) models.

Results

These models demonstrated high diagnostic efficacy in distinguishing diseased samples from healthy donors as well as distinguishing AD and DLB cases. The selected features reveal that the primary peripheral immune characteristic of AD is a decrease in total T cells, while DLB is characterized by low expression of I‐kappa‐B‐alpha (IKBα) in the classical monocyte subset.

Conclusions

These findings suggest that peripheral immune characteristics could serve as potential biomarkers, facilitating the diagnosis of neurodegenerative diseases.