bluuebunny/crossref_metadata_2025 huggingface dataset:
E3 Siah ubiquitin ligase regulates dichotomous spermatogenesis in Sitotroga cerealella
Authors: Shah Sakhawat , Shi Chun-Mei , Elgizawy Karam Khamis , Yan Wen-Han , Wu Gang , Wang Xiao-Ping , Yang Feng-Lian
Published: January 2025

Spermatogenesis in Lepidoptera holds significant importance due to its unique process of dichotomous spermatogenesis, yielding eupyrene and apyrene spermatozoa through a complex molecular mechanism. While E3 ubiquitin ligases are known to play vital roles in spermatogenesis across various processes, their functions in dichotomous spermatogenesis remain less known. We utilized the RNAi, biochemical and microscopic procedures to unravel the function of ScE3 Siah in dichotomous spermatogenesis of adult Sitotroga cerealella. In S. cerealella E3 ligase Siah predominantly expressed in adult tissues. Knockdown of ScE3 Siah leads to disruptions in testes and sperm morphology, affecting the structure of eupyrene and apyrene sperm bundles and causing defective ultrastructure in eupyrene sperm. This disruption results in a reduction in the number of dichotomous sperms and significantly reduces their motility. Moreover, ScE3 Siah knockdown inhibits the transfer and motility of dichotomous sperm, impacting spermatophore formation in females and ultimately reducing egg production. Understanding the role of ScE3 Siah is not only crucial for comprehending the complex processes involved in dichotomous spermatogenesis and fertilization but also provides an avenue for sustainable pest control management.
A genetically encoded fluorescent biosensor for sensitive detection of cellular c-di-GMP levels in Escherichia coli
Authors: Li He , Quan Shu , He Wei
Published: January 2025

Cyclic di-guanosine monophosphate (c-di-GMP) acts as a second messenger regulating bacterial behaviors including cell cycling, biofilm formation, adhesion, and virulence. Monitoring c-di-GMP levels is crucial for understanding these processes and designing inhibitors to combat biofilm-related antibiotic resistance. Here, we developed a genetically encoded biosensor, cdiGEBS, based on the transcriptional activity of the c-di-GMP-responsive transcription factor MrkH. Notably, cdiGEBS can detect both low and high cellular c-di-GMP levels, with a high fluorescence dynamic change of 23-fold. Moreover, it can detect subtle changes in c-di-GMP concentrations due to variations in the expression of c-di-GMP synthesis or degradation enzymes and can distinguish different synthesis activities among WspR mutants. These capabilities allow us to apply cdiGEBS for identifying new diguanylate cyclases and evaluating chemicals that modulate c-di-GMP levels, highlighting its potential as a high-throughput tool for screening inhibitors of c-di-GMP synthesis enzymes. Overall, cdiGEBS enhances the study of c-di-GMP-regulated functions and holds the potential for screening antimicrobials targeting c-di-GMP or its synthesis enzymes.
Nanogenerators for gas sensing applications
Authors: Zhen Ye-Xuan , Wang Gong , Li Yun-Fei , Yu Yu
Published: January 2025

Gas sensors are now widely employed in many industries due to the rapid speed of industrialization and the growth of the Internet of Things. However, the wearability and mobility of traditional gas sensors are limited by their high reliance on external power sources. Nanogenerators (NGs) can compensate for their power source limitations when paired with gas sensors by transforming the environment’s widely dispersed low-frequency energy into electrical energy, allowing for self-powered gas detection. The paper thoroughly examines the advancements made in the field of NG-based self-powered gas sensor research in recent years. A systematic description is given of the two main types of NG-based self-powered gas sensors. Lastly, the evolution of sensor use in a few typical gas sensing applications is highlighted, and the field’s future development trend is anticipated.
Exploring mosquito virome dynamics within São Paulo Zoo: insights into mosquito-virus-environment interactions
Authors: Guimarães Lilian de Oliveira , Ribeiro Geovani de Oliveira , da Couto Roseane , Ramos Endrya do Socorro Foro , Morais Vanessa dos Santos , Telles-de-Deus Juliana , Helfstein Vanessa Christe , Santos Jesus Maia dos , Deng Xutao , Delwart Eric , Pandey Ramendra Pati , de Camargo-Neves Vera Lucia Fonseca , da Costa Antonio Charlys , Kirchgatter Karin , Leal Élcio
Published: January 2025

Background

Mosquito-borne diseases have a significant public health threat worldwide, with arboviruses accounting for a high proportion of infectious diseases and mortality annually. Brazil, in particular, has been suffering outbreaks of diseases transmitted by mosquito viruses, notably those of the Aedes genus, such as dengue, Zika, and chikungunya. Against this background, the São Paulo Zoo is an intriguing ecological niche to explore the virome of mosquitoes, potentially shedding light on the dynamics of arbovirus transmission within a confined setting.

Methods

In this study, we conducted a comprehensive metagenomic analysis of mosquitoes collected from diverse habitats within the zoo, focusing on the Aedes, Anopheles, and Culex genera. From 1,039 contigs of viral origin, we identified 229 viral species infecting mosquitoes, with the orders Picornavirales, Nodamuvirales and Sobelivirales being the most prevalent and abundant. The difference in virome composition was primarily driven by mosquito host species rather than specific collection sites or trap height.

Results

Despite environmental disparities, the virome remained remarkably uniform across different areas of the zoo, emphasizing the strong association between mosquito species and their viral communities. Furthermore, we identified a core virome shared among mosquito species, highlighting potential cross-species transmission events and underscoring the need for targeted surveillance and control measures.

Conclusion

These results contribute to our understanding of the interplay between mosquitoes, the environment, and viruses, providing valuable insights for disease intervention strategies in mosquito-borne diseases.
Effect of hyperhomocysteinemia on the prognostic value of triglyceride glucose index in patients with acute coronary syndrome
Authors: Kan Yi , Ma Xiaoteng , Zhao Zehao , Dong Shutong , Xu Yinxiao , Sun Yan , Cheng Yujing , Zhang Dai , Liu Yuyang , Liu Xiaoli , Shi Dongmei , Zhou Yujie
Published: January 2025

Background

The prognostic value of triglyceride-glucose (TyG) has been well described in patients with coronary artery disease (CAD). Hyperhomocysteinemia (HHcy) promotes insulin resistance and has also been regarded as a potential risk factor for cardiovascular disease. However, the prognostic value of TyG in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the interaction between TyG and HHcy remain unclear.

Methods

A total of 1,734 ACS patients undergoing PCI were continuously enrolled between June 2016 and November 2017 at Beijing Anzhen Hospital. Patients were categorized into four groups based on HHcy status and the optimal cut-off value of TyG. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization.

Results

Over a median follow-up of 927 days, 358 patients (20.6%) experienced MACE. The Kaplan-Meier curves showed significant differences in the cumulative incidence of MACE among prespecified groups (p < 0.001). Multivariable Cox regression analysis revealed that higher TyG was significantly associated with an increased risk of MACE in patients without HHcy (HR: 2.36, 95% CI: 1.53–3.64, p < 0.001), but not in patients with HHcy (HR: 1.31, 95% CI: 0.60–2.87, p = 0.503). Restricted cubic splines only demonstrated the prognostic value of TyG in patients without HHcy. A significant interaction was observed for MACE between TyG and HHcy (p for interaction = 0.01).

Conclusions

The prognostic value of TyG was modified by HHcy in ACS patients undergoing PCI. Higher TyG was only associated with an increased risk of MACE in ACS patients without HHcy, but not in ACS patients with HHcy.
Management of a pediatric patient with dental anomalies and its effect on psychosocial status: a case report
Authors: Damanhouri Wesam , Moussa Kholoud , Bathallath Joudi , Alsomali Zohour , Bakor Abeer , Attar Moaz
Published: January 2025

Managing multiple dental anomalies in the anterior region of the dental arch presents unique and complex challenges. This case report describes using a multidisciplinary approach to manage a child with not only a fused tooth with a supernumerary but also the presence of other supernumerary teeth in the same place. In this case, deviation from the standard management of a fused permanent anterior tooth, an anchor for aesthetics, by extracting it because of crown root complexity and allowing a supernumerary to erupt into its place made the difference in the successful outcome. However, this condition required multidisciplinary management that necessitated the involvement of the psychiatric department. Continuous assessment of the patient's psychosocial function using the Social Avoidance and Distress Scale (SADS) allowed appropriate guidance to manage the patient's behavior. This case report added a different perspective on managing a fused tooth with a supernumerary to the literature. It showed how dental aesthetics can have an adverse effect on children's psychology.
Inventory of landslide relics in Zhenxiong County based on human-machine interactive visual interpretation, Yunnan Province, China
Authors: Xue Zhiwen , Xu Chong , Zhang Zhiqiang , Feng Liye , Li Hao , Zhang Hourong , Zhu Dengjie , Sun Jingjing , Wang Peng , Li Lei , Chen Jingyu
Published: January 2025

Introduction

Landslides occur frequently in Zhenxiong County, posing significant threats to residents’ lives and property. A comprehensive understanding of the development patterns of landslide disasters in this region is crucial for disaster prevention, land-use planning, and risk assessment.

Methods

This study utilized high-resolution satellite imagery from the Google Earth Pro platform and employed a human-machine interactive visual interpretation approach to investigate landslide occurrences. A comprehensive landslide inventory comprising 3,979 landslide outlines was established through extensive literature review and data cleaning techniques. The spatial distribution characteristics and statistical patterns of landslides were analyzed.

Results

The total landslide-affected area is 319.20 km2, with the largest landslide covering 4.55 km2 and the smallest measuring 1,779 m2. The average landslide area is 80,215 m2, with the majority (73.54%) classified as medium-sized landslides. The landslide area percentage (LAP) is 8.64%, and the landslide number density (LND) is 1.077 landslides per km2, with the highest recorded landslide density being 3.380 landslides per km2. Landslides are predominantly concentrated in four key areas: the confluence of the Baishui River and Yanxi River, Dashuigou Reservoir, both sides of the valley from Heitang Village to Hongyan Village, and Xiaogou Village. These areas are characterized by well-developed water systems, middle and low mountains, and heavily dissected landscapes.

Discussion

The landslide database established in this study provides essential scientific data for analyzing the spatial distribution of landslide disasters in Zhenxiong County. It offers valuable insights for local governments and relevant authorities in disaster prevention, land-use planning, and risk assessment. The findings highlight the significant impact of complex terrain and developed water systems in middle and low mountain regions on landslide disasters. Future studies should further integrate geological and meteorological factors for deeper analysis.
The relationship between ethical leadership, teacher motivation, and commitment in public schools in Portugal
Authors: Neves Maria de Lurdes Gomes
Published: January 2025

In the current educational context, transformations are continuous, and the ethical dimension of leadership has become one of the main concerns of school cluster directors, given its direct influence on teachers’ motivation. This study, conducted with a sample of 204 teachers from public schools in Portugal, aimed to investigate the relationship between ethical leadership, motivation, and commitment. The results revealed that ethical leadership is positively correlated with intrinsic motivation and organizational commitment (OC). On the other hand, despotic leadership exhibits a negative correlation with OC and intrinsic motivation. Furthermore, it was found that commitment plays a mediating role in the effect of ethical leadership on teachers’ intrinsic motivation. These findings underscore the importance of promoting ethical leadership in schools, not only to foster teachers’ motivation but also to strengthen their commitment to the institution. Conversely, the need to avoid despotic practices is emphasized, as they can adversely affect not only teachers’ motivation but also their commitment to the educational organization. These conclusions further highlight, as future research avenues, the importance of promoting ethical leadership in educational institutions to ensure a healthy and productive work environment for teachers.
Using data to promote inclusion through early childhood mental health consultation
Authors: Clayback Kelsey A. , Partee Ann M. , Williford Amanda P. , Downer Jason T. , Parker Kyra , Lhospital Ann S.
Published: January 2025

Introduction

Early childhood educators continue to need support to build their capacity to promote positive social and emotional development and address challenging behavior when it occurs, without resorting to exclusion. One approach to improve the experiences and outcomes of young children through better support to educators is Early Childhood Mental Health Consultation (ECMHC). ECMHC is an evidence-based intervention that pairs a mental health professional (i.e., “consultant”) with early childhood educators to build the capacity of providers to promote inclusion by supporting young children's social and emotional development.

Methods

In this paper, we describe a model of ECMHC that combines data-driven action planning and an individualized approach to build educators' capacity to implement social and emotional teaching practices with fidelity. The model begins with in-context classroom observations of child engagement and teaching practices, as well as a teacher-report of child behavior. Based on this observational baseline data, a standardized formula selects a personalized set of social and emotional teaching strategies recommended for the focus of consultation, based on the strengths and challenges of the teacher and child. Strategies included foundational strategies (e.g., fostering strong teacher-child relationships), flexible strategies (e.g., using cues and visuals), and targeted strategies (e.g., supporting problem-solving skills). Consultants and teachers then collaboratively work together to select strategies to focus on in consultation, allowing for flexibility and individualization based on individual teacher and child strengths and challenges.

Results

We address the following two aims: (1) examine teaching practices and children's behavior at the beginning of consultation and how these data resulted in different recommended teaching strategies, based on our standardized formula, (2) present three case examples to further illustrate how these data guided consultation to improve social and emotional teaching practices during the 2023 to 2024 school year. We found that this baseline data collection and the subsequent data-driven process for selecting strategies was feasible in that all consultants and teachers served by ECMHC were able to use it. We also found variability in baseline data and the associated ECMHC teaching strategies recommended, suggesting that the measures were sensitive to unique classroom needs and individualized recommended strategies accordingly.

Discussion

We discuss how this approach allowed consultants to tailor ECMHC services to the unique strengths and challenges of each child and teacher dyad, while being firmly grounded in empirical research and previously validated assessments.
Evaluating the impact of visceral fat on the outcomes of frozen embryo transfer via bioelectrical impedance analysis
Authors: Ni Danyu , Wei Yi , Xie Qijun , Wang Xinyu , Yu Kaidi , Jiang Wei , Yang Ye , Ling Xiufeng
Published: January 2025

Objectives

The increasing prevalence of obesity underscores the need to explore its impact on assisted reproductive technology (ART) outcomes. This study aims to evaluate the association between visceral fat area (VFA), measured by bioelectrical impedance analysis (BIA), and pregnancy outcomes following frozen embryo transfer (FET).

Methods

In this retrospective clinical study, the data of 1,510 patients who underwent FET between April 2022 and April 2023 were analyzed. The VFA was measured by BIA, and patients were categorized into low and high VFA groups based on a threshold of 65 cm². Pregnancy outcomes were compared between the two groups. Univariable and multivariate logistic regression analyses, along with restricted cubic spline (RCS) modeling, were used to adjust for age, body mass index (BMI), and basal estradiol (E2) levels to determine the relationship between VFA and FET outcomes.

Results

There were significant differences in baseline characteristics and outcomes between the two groups. The high VFA group was characterized by older age and a lower basal estradiol (E2) level. The biochemical pregnancy rate, implantation rate, clinical pregnancy rate (CPR), and live birth rate (LBR) were significantly lower in the high VFA group. Logistic regression revealed a significant negative correlation between the high VFA group and both CPR and LBR. The RCS model demonstrated that the VFA was nonlinearly correlated with CPR and LBR. Subgroup analysis showed that among individuals under 35 years of age or with a BMI < 24, high VFA was significantly associated with poorer CPR and LBR.

Conclusions

High VFA is associated with poorer pregnancy outcomes after FET in female patients with infertility, with both CPR and LBR decreasing as VFA increases. Clinicians should consider VFA as an important reference for targeted fat management interventions to optimize reproductive success, especially when VFA exceeds 65 cm².
Association between neutrophil-to-lymphocyte ratio and left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus
Authors: Yang Xueyang , Shi Yinze , Zhang Huan , Huang Liying , Zhang Jiaoyue , Min Jie , Chen Lulu
Published: January 2025

Background

Diabetes has become a global pandemic, posing a sustained threat to human health, primarily due to its associated complications. Left ventricular diastolic dysfunction (LVDD) is a prevalent cardiac complication among patients with diabetes. Since most patients are asymptomatic and lack relevant biomarkers, LVDD has not attracted significant attention from clinicians. The neutrophil-to-lymphocyte ratio (NLR) is a widely studied inflammation biomarker that has been suggested to be linked to various medical conditions, including cardiac diseases. However, its association with LVDD among patients with type 2 diabetes mellitus (T2DM) has not been explored.

Aim

To clarify the relationship between NLR and LVDD among patients with type 2 diabetes.

Methods

We conducted a cross-sectional study using medical records from 855 patients diagnosed with T2DM who were admitted to the Endocrinology department at Wuhan Union Hospital. According to the ASE/EACVI 2016 recommendations, these patients were categorized into two groups based on sonographic parameters: patients with normal left ventricular diastolic function (the non-LVDD group) and patients with LVDD (the LVDD group). NLR values were calculated and divided into three different levels. Statistical analysis was conducted to evaluate the correlation between NLR levels and the prevalence of LVDD.

Results

The prevalence of LVDD among hospitalized patients with T2DM in our study was 47.8% (409/855). The mean NLR value of the LVDD group was significantly higher compared with the non-LVDD group [1.60 (1.24-2.05) vs 1.85 (1.44-2.31), P<0.001]. The prevalence of LVDD in the three different NLR levels was 35.51% (76/214), 49.27% (203/412), and 56.77% (130/229), respectively. Unjustified logistic analysis showed that NLR levels were positively associated with the prevalence of LVDD (P <0.001). Compared to the low level of NLR, the unadjusted odds ratios (OR) of LVDD at the medium and high levels were 1.764 (1.255-2.478, P=0.001) and 2.384 (1.626-3.497, P<0.001), respectively (P for trend <0.001).

Conclusion

Our findings suggest that the NLR is a potential indicator for assisting clinicians in identifying LVDD in patients with T2DM. Patients with elevated NLR levels may be at a greater risk of developing LVDD than those with lower NLR levels, which may require attention and interventions to prevent patients from progressing into heart failure.
Distributed emergency control method for integrated energy system in industrial park based on alternating direction multiplier method
Authors: Li Wenbin , Jia Lijing , Xu Baoyu , Lu Rongfei , Huang Yu
Published: January 2025

With the rapid development of integrated energy systems (IES), the extensive integration of dis-tributed energy and the increasing coupling of multiple energy systems need higher requirements for the coordinated control methods of IESs. This paper proposes a distributed emergency control method for integrated energy systems of industrial parks based on the alternating direction multiplier method (ADMM). Firstly, an optimization scheduling model is established for the integrated energy system in industrial parks. On the basis of minimizing operating costs, the model takes into account the operational constraints of each energy equipment. Secondly, considering the shortage of energy supply, in order to achieve energy transfer between users, a distributed optimization scheduling model for IES of the industrial park is established based on the typical energy structure of users. And a distributed optimization scheduling algorithm for the comprehensive energy system of the industrial park based on ADMM is proposed. Finally, the proposed emergency control method is verified under typical fault scenarios.
What do stakeholders perceive as success in large scale environmental monitoring design?
Authors: Dai Xiaoyan , Webb J. Angus , Horne Avril C.
Published: January 2025

The decline in global freshwater biodiversity demands urgent action. Governments are attempting to use environmental management to partly restore degraded ecosystems through targeted interventions. Designing monitoring programs to assess the success of these large-scale management programs is challenging. There is much literature addressing the technical challenges of monitoring program design, and many of these studies acknowledge limitations in current implementation. In this study, we examine the perspectives of those managers and scientists involved in designing a large-scale monitoring program and their understanding of what makes a monitoring program successful. We focus on an environmental flow monitoring program (the Flow Monitoring, Evaluation and Research program—Flow-MER—in Australia). Through semi-structured interviews and surveys, we aimed to identify what those involved consider to be “success” for monitoring projects. The outcomes highlight that—consistent with literature—clear objectives are considered pivotal to project success. However, despite this recognition, challenges in establishing clear objectives were identified as a pressing concern for the Flow-MER program. The survey results included a recurring emphasis from participants on the importance of consistent, long-term datasets. There was less clarity around how to balance monitoring design to both demonstrate management success and address key scientific uncertainties as part of adaptive management and monitoring. The findings show that while there is broadly a common understanding of success for large monitoring design, major monitoring programs such as Flow-MER continue to fall short in successful design. The approach to surveying those involved in the monitoring program, along with their articulated understanding of program shortfalls, both provide insights on how to improve design and implementation of future large-scale monitoring programs. In particular, we highlight the need for managers to establish clear objectives and invest in effective communication strategies.
Analysis of rainwater quality in a quarry site in southwestern Nigeria
Authors: Taiwo Temitope Mary , Ogunbode Timothy Oyebamiji
Published: January 2025

Introduction

Water has been of paramount importance to humanity throughout history. Understanding the factors contributing to water pollution, particularly those that compromise its quality and sustainability, is essential. This study investigates the impact of quarry activities on the portability of rainwater within a quarry site, focusing on the relationship between quarry operations, heavy metals, and the physicochemical properties of rainwater.

Methods

The study was conducted at Sanlong Quarry Industry in Ifelodun, Southwestern Nigeria. Rainwater samples were collected along a 15–150 m transect within the quarry for analysis of heavy metals and physicochemical contents. Five heavy metals cadmium (Cd), chromium (Cr), zinc (Zn), lead (Pb), and magnesium (Mg) were determined using Atomic Absorption Spectrophotometer (AAS). Additionally, eight physicochemical properties, including electrical conductivity, pH, total solids, suspended solids, total dissolved solids, nitrate, turbidity, and total phosphorus, were analyzed using standard procedures. Variance and correlation analysis of the rainwater’s physicochemical parameters was conducted using Statistical Product for Service Solutions (SPSS).

Results

The analysis indicated general compliance with water quality standards. However, elevated levels of Pb and Cd in certain areas exceeded WHO, NAFDAC, and US-EPA limits, while Cr, Zn, and Mg were found to have minimal impact on rainwater quality.

Discussion

Rainwater collected at Sanlong Quarry may not be safe for consumption due to heavy metal contamination, particularly Pb and Cd. This finding underscores the need for alternative clean water sources for both quarry staff and the surrounding community. Quarry management must prioritize the provision of clean water and raise awareness among personnel about the risks associated with consuming contaminated rainwater.
A review and meta-analysis of the efficacy of arbuscular mycorrhizal fungi in remediating toxic metals in mine-affected soils
Authors: Banerjee Sonali , Mandal Jajati , Sarkar Dibyendu , Datta Rupali , Bhattacharyya Pradip
Published: January 2025

Mines are natural reservoirs of various minerals, metals, and metalloids. Several heavy metals (HMs), such as Pb, Cd, Cr, Cu, and Ni, are major anthropogenic pollutants that cause severe environmental pollution. The accumulation of these toxic HMs in soils has raised several concerns for crop growth, food safety, and marketing. Physiological and biochemical processes in plants are severely impacted by HMs, disrupting normal metabolic activities and reducing biomass production. Phytoremediation plays a pivotal role in addressing HM contamination by offering an eco-friendly, economical, and holistic solution. Similarly, arbuscular mycorrhizal fungi (AMF) play a significant role by forming a symbiotic relationship with plant roots. In this association, plants provide root exudates, while AMF enhance plant growth under heavy metal stress by supplying essential nutrients, minerals, and water. These fungi also improve nutrient status, soil quality, and ecosystem stability. The present review and meta-analysis encompass an examination of the global distribution of toxic HMs in mining-affected areas. Furthermore, the study highlights the role of various plant species and microbes, particularly AMF, in mitigating HM stress and its impact on plant growth and nutrition. The meta-analysis also evaluates the efficacy of AMF as a remediation strategy for HM-impacted mine soils.
Changes in forest ecosystem stability under climate change in a temperate landscape
Authors: Wijenayake Pavithra Rangani , Shitara Takuto , Hirata Akiko , Matsui Tetsuya , Kubota Yasuhiro , Masaki Takashi
Published: January 2025

Climate change poses significant threats to forests globally. Understanding the relationship between environmental variables and species distribution is crucial for evaluating the vulnerability of tree species assemblies to anticipated climate change. Here, we address whether projected future changes in climate suitability are related to the structural stability of the old-growth forest community in Japan. We hypothesize that even with the expected changes in climate, the structural stability of the species assembly will remain unchanged until the end of this century. We modeled the influence of climate change on the spatial distribution of major tree species in a temperate deciduous forest reserve using local and regional presence data. We used the Maxent model and QGIS software to project potential habitat changes. Focusing on the period 2081–2,100, we used the MRI-ESM2-O general circulation model under baseline (SSP5–8.5) and mitigation (SSP1–2.6) future climate scenarios. This revealed that winter temperature is the most crucial factor affecting the distribution of tree species in the temperate landscape. Canopy tree species such as Acer pictum and Castanea crenata are projected to remain stable under SSP5–8.5 in 2100. Our results also suggest that the distribution of Quercus serrata, the dominant species in the forest studied, will expand, particularly under extreme climate conditions in 2100. However, there may be potential reductions in the abundance of subcanopy species, indicating a change in the structure of the forest stand. In this sense, the stability of forest ecosystems and local species diversity may be vulnerable under future climate change scenarios. Exploring the future species distribution and stand structure can improve understanding of habitat changes in temperate landscapes and requires more focused research efforts.
Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes
Authors: Sato Ayaka , Nagai Hodaka , Suzuki Ayano , Ito Aya , Matsuyama Shimpei , Shibui Nagito , Morita Masashi , Hikosaka-Kuniishi Mari , Ishii Naoto , So Takanori
Published: January 2025

OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on the surface of activated T cells. Upon interaction with its cognate ligand, OX40L, OX40 transmits costimulatory signals to antigen-primed T cells, promoting their activation, differentiation, and survival—processes essential for the establishment of adaptive immunity. Although the OX40-OX40L interaction has been extensively studied in the context of disease treatment, developing a substitute for the naturally expressed membrane-bound OX40L, particularly a multimerized OX40L trimers, that effectively regulates OX40-driven T cell responses remains a significant challenge. In this study, we successfully engineered soluble OX40L-fusion proteins capable of robustly activating OX40 on T cells. This was achieved by incorporating functional multimerization domains into the TNF homology domain of OX40L. These OX40L proteins bound to OX40, subsequently activated NF-κB signaling, and induced cytokine production by T cells in vitro. In vivo, mice treated with one of the OX40L-fusion proteins—comprising a single-chain OX40L trimer linked to the C-terminus of the human IgG1 Fc domain, forming a dimer of trimers—exhibited significantly enhanced clonal expansion of antigen-specific CD4+ T cells during the primary phase of the immune response. A comparable antibody-fusion single-chain TNF protein incorporating 4-1BBL, CD70 (CD27L), or GITRL in place of OX40L elicited similar in vivo T cell responses. Thus, we propose that optimizing the multimerization of OX40L proteins through innovative design strategies may facilitate the development of more effective agonists for targeted immunotherapies.
CD56neg CD16+ cells represent a distinct mature NK cell subset with altered phenotype and are associated with adverse clinical outcome upon expansion in AML
Authors: Wlosik Julia , Orlanducci Florence , Richaud Manon , Demerle Clemence , Amara Amira Ben , Rouviere Marie-Sarah , Livrati Philippe , Gorvel Laurent , Hospital Marie-Anne , Dulphy Nicolas , Devillier Raynier , Vey Norbert , Olive Daniel , Chretien Anne-Sophie
Published: January 2025

Introduction

Acute myeloid leukemia (AML) is a rare haematological cancer with poor 5-years overall survival (OS) and high relapse rate. Leukemic cells are sensitive to Natural Killer (NK) cell mediated killing. However, NK cells are highly impaired in AML, which promote AML immune escape from NK cell immune surveillance. We made the first report of CD56neg CD16+ NK cells expansion in AML. This unconventional subset has been reported to expand in some chronic viral infections. Although it is unclear whether CD56neg NK cells expansion mechanism is common across diseases, it seems more relevant than ever to further investigate this subset, representing a potential therapeutic target.

Methods

We used PBMCs from AML patients and HV to perform mass cytometry, spectral flow cytometry, bulk RNA-seq and in vitro assays in order to better characterize CD56neg CD16+ NK cells that expand in AML.

Results

We confirmed that CD56neg CD16+ NK cells represent a unique NK cell subset coexpressing Eomes and T-bet. CD56neg CD16+ NK cells could recover CD56 expression in vitro where they displayed unaltered NK cell functions. We previously demonstrated that CD56neg CD16+ NK cells expansion at diagnosis was associated with adverse clinical outcome in AML. Here, we validated our findings in a validation cohort of N=38 AML patients. AML patients with CD56neg CD16+ NK cells expansion at diagnosis had decreased overall survival (HR[CI95]=5.5[1.2-24.5], p=0.0251) and relapse-free survival (HR[CI95]=13.1[1.9-87.5], p=0.0079) compared to AML patients without expansion after 36 months follow-up. RNA-seq unveiled that CD56neg CD16+ NK cells were mature circulating NK cells with functional capacities. Upon expansion, CD56neg CD16+ NK cells from AML patients showed altered proteomic phenotype, with increased frequency of terminally mature CD56neg CD16+ NK cells expressing TIGIT along with decreased frequency of Siglec-7+ CD56neg CD16+ NK cells.

Discussion

Taken together, our results suggest that we could harness CD56neg CD16+ NK cells cytotoxic potential in vitro to restore NK cell anti-tumor response in AML patients with CD56neg CD16+ NK cells expansion and improve patients’ prognosis. To conclude, CD56neg CD16+ NK cells represent a relevant target for future NK-cell-based immunotherapies in AML.
Pan-cancer analysis of Arp2/3 complex subunits: focusing on ARPC1A’s role and validating the ARPC1A/c-Myc axis in non-small cell lung cancer
Authors: Zhou Chenkang , Chen Yuxin , Chen Shuhui , Hu Lijuan , Wang Junjun , Wang Yumin
Published: January 2025

Background

The Arp2/3 complex is a key regulator of tumor metastasis, and targeting its subunits offers potential for anti-metastatic therapy. However, the expression profiles, prognostic relevance, and diagnostic value of its subunits across cancers remain poorly understood. This study aims to investigate the clinical relevance of Arp2/3 complex subunits, particularly ARPC1A, in pan-cancer, and to further analyze the potential biological mechanisms of ARPC1A, as well as its association with immune infiltration and chemotherapy drug sensitivity.

Methods

To explore the differential expression of Arp2/3 complex subunits and their clinical relevance across cancers, we analyzed data from TCGA and GTEx databases. The relationship between ARPC1A and immune infiltration, as well as its interactions with functional proteins, was examined using the TCPA and TIMER2.0 databases. Gene Set Enrichment Analysis (GSEA) was performed to identify ARPC1A-associated signaling pathways. Chemotherapy drug sensitivity correlated with ARPC1A expression was assessed using CellMiner, GDSC, and CTRP databases. The effect of ARPC1A on c-Myc expression was validated by quantitative PCR (qPCR) and Western blot. Finally, the biological role of ARPC1A in non-small cell lung cancer (NSCLC) cells was further validated using CCK-8, EdU incorporation, colony formation, and Transwell assays.

Results

The Arp2/3 complex subunits, particularly ARPC1A, are frequently overexpressed in a majority of cancers, correlating with poor prognostic outcomes and demonstrating significant diagnostic utility. Copy number variations may play a role in the dysregulation of Arp2/3 complex subunit expression. The small molecule X4.5.dianilinophthalimide has shown promise as a targeted therapeutic agent in a pan-cancer context. Functional predictions indicate that ARPC1A is implicated in oxidative phosphorylation pathways and cell proliferation-related signaling pathways, including those mediated by MYC, with ASNS potentially acting as an upstream regulator. Furthermore, ARPC1A has been implicated in the resistance to chemotherapy drugs, including gefitinib. In vitro experiments corroborate that ARPC1A may enhance malignant phenotypes in non-small cell lung cancer (NSCLC) cells through the regulation of c-Myc expression.

Conclusion

Our study offers novel insights into targeting Arp2/3 complex subunits as an anti-cancer strategy and underscores the potential of ARPC1A as a novel biomarker for tumor diagnosis, prognosis, and the prediction of immune therapy responses.
Association between complete blood cell count-derived inflammatory biomarkers and gallstones prevalence in American adults under 60 years of age
Authors: Fu Chang , Chen Junhong , Wang Yongxin , Yang Yibo , Li Xiaocong , Liu Kai
Published: January 2025

Background

The trend of gallstones occurring in younger populations has become a noteworthy public health issue. This study aims to investigate the association between complete blood cell count (CBC)-derived inflammatory indicators and gallstones in adults under 60 years of age in the United States.

Methods

This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Associations between CBC-derived inflammatory biomarkers and gallstones were assessed using multivariable logistic regression models, with results presented as odds ratio (OR) and 95% confidence interval (CI). Restricted cubic splines (RCS) were employed to examine potential non-linear relationships. Subgroup analyses were also conducted to explore differences across population subgroups.

Results

This study comprised 4,977 participants, among whom 398 were diagnosed with gallstones. After adjusting for confounding variables, the highest quartile of systemic inflammation response index (SIRI) [OR (95%CI): 1.65(1.12,2.43)], systemic immune-inflammation index (SII) [OR (95%CI): 1.53(1.05,2.25)], monocyte-to-lymphocyte ratio (MLR) [OR (95%CI): 1.66(1.16,2.37)], and pan immune inflammatory value (PIV) [OR (95%CI): 1.82(1.23,2.71)] were associated with a significantly increased risk of gallstones compared to the lowest quartiles. RCS plots indicated a nonlinear relationship between several inflammatory biomarkers and gallstones.

Conclusion

Our study found that SIRI, SII, MLR, and PIV can serve as clinical indicators for predicting the risk of gallstones in adults under 60 years of age in the United States.
Higher monomeric C-reactive protein levels are associated with premature coronary artery disease
Authors: Melnikov Ivan , Kozlov Sergey , Okhota Sergey , Saburova Olga , Avtaeva Yuliya , Kuznetsova Tatiana , Guria Konstantin , Prokofieva Lyudmila , Riazantseva Tatiana , Ji Shang-Rong , Wu Yi , Gabbasov Zufar
Published: January 2025

Introduction

Chronic inflammation is a major risk factor for coronary artery disease (CAD). Currently, the inflammatory cardiovascular risk is assessed via C-reactive protein (CRP) levels measured using a high-sensitivity assay (hsCRP). Monomeric CRP (mCRP) is a locally produced form of CRP that has emerged as a potential biomarker of inflammation.

Aim

This study investigated whether mCRP levels are associated with premature CAD.

Materials and methods

This study comprised 103 participants of both sexes, including 50 patients 56 ± 7 years old with premature CAD and 53 patients 51 ± 10 years old without CAD. CAD was verified using coronary angiography, hsCRP levels were measured using a standard assay, and mCRP levels were measured using fluorescent cytometric beads conjugated with an anti-mCRP antibody.

Results

The levels of hsCRP were 0.99 (0.59; 3.10) mg/L vs. 0.63 (0.35; 1.85) mg/L (p = 0.067), and mCRP 6.84 (4.20; 13.78) µg/L vs. 2.57 (0.32; 5.66) µg/L (p <0.001) in patients with CAD vs. patients without CAD, respectively. There was a weak positive correlation between the mCRP and hsCRP levels (ρ = 0.214; p = 0.030). hsCRP levels were below 2.0 mg/L (i.e., residual inflammatory cardiovascular risk should have been excluded) in 70% of patients with CAD and 79% of patients without CAD (p = 0.365). mCRP levels differed between the groups of patients with hsCRP levels below 2.0 mg/L: 5.14 (4.07; 10.68) µg/L vs. 2.77 (0.53; 5.00) µg/L in patients with or without CAD, respectively (p <0.001). Logistic regression analysis demonstrated that mCRP levels were independently associated with premature CAD. The adjusted odds ratio was 1.18 (95% CI 1.06-1.33, p = 0.004) per each µg/L increase in mCRP levels.

Conclusion

Higher mCRP levels were associated with premature CAD, independent of hsCRP levels and traditional risk factors.
Massive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells
Authors: Laguía Fernando , Chojnacki Jakub , Erkizia Itziar , Geli María Isabel , Enrich Carlos , Martinez-Picado Javier , Resa-Infante Patricia
Published: January 2025

Introduction

HIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol–dependent and involves transient disruption of cortical actin. Here, we investigate the potential involvement of massive endocytosis (MEND) in this process.

Methods

We used live cell confocal imaging to measure the dimensions and dynamics of the compartment. We assessed the role of actin and cholesterol in fixed and live cells using confocal microscopy and evaluated the effect of PI3K and protein palmytoilation inhibitors during viral uptake.

Results

Our data demonstrate extensive plasma membrane invagination based on sac-like compartment dimensions (2.9 μm in diameter and 20 μm3 in volume). We showed that the cholesterol concentration doubles within the regions of viral uptake, suggesting lipid-phase separation, and that development of the sac-like compartment is accompanied by transient depolarization of cortical actin. Moreover, we observed that protein palmitoylation and PI3K inhibition reduce the sac-like compartment formation rate from 70% to 20% and 40%, respectively.

Conclusions

Our results indicate the involvement of MEND mechanisms during sac-like compartment formation.
Identification of hub genes and immune-related pathways in acute myeloid leukemia: insights from bioinformatics and experimental validation
Authors: Shan Mingliang , Xu Li , Yang Wenzhe , Liu Shiguo , Cui Zhaoqing
Published: January 2025

Background

This study aims to identify the hub genes and immune-related pathways in acute myeloid leukemia (AML) to provide new theories for immunotherapy.

Methods

We use bioinformatics methods to find and verify the hub gene. At the same time, we use the results of GSEA enrichment analysis to find immune-related mediators. Through Mendelian randomization(MR) analysis, on the one hand, we look for related immune cells, and on the other hand, we use it to determine the causal relationship among immune cells, immune mediators, and AML. Finally, in vitro experiments are conducted to further verify and improve the reliability and physiological functions of the hub gene and its immune-related pathways.

Results

Complement Factor D(CFD) gene is identified as the highly expressed hub gene and is positively correlated with IL-2. IL-2 is also positively correlated with CD27 on CD24+CD27+B cells, JAK/STAT, and PI3K/Akt. The latter three are positively correlated with the occurrence and development of AML.

Conclusion

We conclude that CFD gene uses IL-2 as a mediator to promote the disease progression of AML by promoting the CD27 on CD24+CD27+B cells, JAK-STAT, and PI3K-Akt pathways.
m5C methylation modification may be an accomplice in colorectal cancer escaping from anti-tumor effects of innate immunity-type I/III interferon
Authors: Sun Yiqi , Liu Yunfei , Jiang Lu , Zhong Chao
Published: January 2025

Colorectal cancer (CRC) is one of the most prevalent malignant tumors in the world, and its occurrence and development are closely related to the complex immune regulatory mechanisms. As the first barrier of the body’s defense, innate immunity plays a key role in tumor immune surveillance and anti-tumor response, in which type I/III interferon (IFN) is an important mediator with significant antiviral and anti-tumor functions. 5-methylcytosine (m5C) modification of RNA is a key epigenetic regulation that promotes the expression of CRC oncogenes and immune-related genes. It can enhance the proliferation, migration, and invasion of tumor cells by affecting mRNA stability, translation efficiency, and nuclear export. In addition, m5C modification modulates the activity of innate immune signaling pathways and inhibits interferon production and function, further helping tumor cells evade immune surveillance. However, there are insufficient elucidations on the interaction between m5C modification and innate immunity in CRC. In this study, the mechanism of interferon I/III in colorectal cancer was systematically reviewed and explored. This work focused on how m5C modification promotes tumor immune escape by affecting the interferon signaling pathway, thereby providing new diagnostic markers and therapeutic targets for clinical use, and enhancing the immunotherapy efficacy.
Lactate-induced protein lactylation in cancer: functions, biomarkers and immunotherapy strategies
Authors: Wang Wenjuan , Wang Hong , Wang Qi , Yu Xiaojing , Ouyang Liangliang
Published: January 2025

Lactate, long viewed as a byproduct of glycolysis and metabolic waste. Initially identified within the context of yogurt fermentation, lactate’s role extends beyond culinary applications to its significance in biochemical processes. Contemporary research reveals that lactate functions not merely as the terminal product of glycolysis but also as a nexus for initiating physiological and pathological responses within the body. Lysine lactylation (Kla), a novel post-translational modification (PTM) of proteins, has emerged as a pivotal mechanism by which lactate exerts its regulatory influence. This epigenetic modification has the potential to alter gene expression patterns, thereby impacting physiological and pathological processes. Increasing evidence indicates a correlation between lactylation and adverse prognosis in various malignancies. Consequently, this review article aims to encapsulate the proteins that interact with lactate, elucidate the role of lactylation in tumorigenesis and progression, and explore the potential therapeutic targets afforded by the modulation of lactylation. The objective of this review is to clarify the oncogenic significance of lactylation and to provide a strategic framework for future research directions in this burgeoning field.