bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the biological treatment of a real contaminated groundwater through reductive dechlorination biostimulation
Authors: Yaqoubi Hafsa , Sassetto Geremia , Presutti Maria , Belfaquir Mustapha , Matturro Bruna , Rossetti Simona , Lorini Laura , Petrangeli Papini Marco , Zeppilli Marco
Published: January 2025

Chlorinated aliphatic hydrocarbons (CAHs) are common groundwater contaminants due to improper utilization in past industrial activity. Anaerobic reductive dechlorination, where bacteria use CAHs as electron acceptors, is crucial for bioremediation. Environmental conditions, such as nutrient availability and electron donors (i.e., molecular hydrogen), can influence the effectiveness of bioremediation processes. Also, bioremediation strategies like bioaugmentation (i.e., the supply of the enriched dechlorinating consortium) and bio-stimulation (i.e., the supply of electron donor) can improve CAHs removal performances. Here, a microcosm study is presented to assess the effectiveness of bioaugmentation with an enriched dechlorinating consortium for groundwater remediation. Target contaminants used were tetrachloroethane (TeCA), trichloroethylene (TCE) and sulphate ion. Various conditions, including biostimulation and bioaugmentation approaches were tested to evaluate the feasibility of biological treatment. Operating conditions, i.e., mineral medium and lactate, facilitated the dechlorination of TCE into ETH, leading to an increase in the dechlorinating population (Dehalococcoides mccartyi) to 67% of the total bacteria, with reductive dechlorination (RD) rates up to 7 µeq/Ld. Conversely, the RD performance of microcosms with real contaminated groundwater was negatively affected by the combined presence of TeCA and sulphate, indicated by a low abundance of D. mccartyi (<3%) and low RD rates (up to 0.39 µeq/Ld), suggesting that the native microbial population lacked the capacity for effective dechlorination. Moreover, the principal component analysis plot highlighted distinct groupings based on microbial community across different microcosm conditions, indeed, microbial community structures dominated by D. McCarty were associated with higher reductive dechlorination rates while non-augmented and non-stimulated microcosms reflected distinct microbial communities dominated by non-dechlorinating taxa. Additionally, RD decreased (48, 23, 22, and 14 µeq/Ld) with increasing sulphate concentrations (0, 150, 225, and 450 mgSO4 -2/L), further demonstrating the inhibitory effect of sulphate in the treated contaminated groundwater. Overall, this study highlights the complex interplay between environmental conditions, treatment strategies, and microbial communities in driving dechlorination processes. Specifically, the effectiveness of reductive dechlorination is heavily influenced by the availability of electron donors and the composition of the medium or groundwater, which can drive significant shifts in microbial community dynamics, either supporting or hindering the reductive dechlorination process.
Anti-cancer activity of synthetic gefitinib-1,2,3-triazole derivatives against Hela cells via induction of apoptosis
Authors: Hu Zhihong , Hou Xixi , Ren Yongjing , Wu Ziyuan , Yan Dong , Chen Hong , Wang Lan
Published: January 2025

Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.
Hexagonal zinc oxide nanoparticles: a novel approach to combat multidrug-resistant Enterococcus faecalis biofilms in feline urinary tract infections
Authors: Sewid Alaa H. , Sharaf Mohamed , El-Demerdash Azza S. , Ragab Sherif M. , Al-Otibi Fatimah O. , Taha Yassin Mohamed , Liu Chen-Guang
Published: January 2025

Introduction

Enterococcus faecalis, a common inhabitant of the feline gastrointestinal tract, has emerged as a significant pathogen causing urinary tract infections (UTIs) in domestic cats. The rise of multidrug-resistant E. faecalis strains and their propensity to form biofilms pose significant challenges in treatment. This study investigated the antibacterial and antibiofilm activities of hexagonal zinc oxide nanoparticles (ZnONPs) alone and in combination with streptomycin and Moringa oleifera leaf extract (MOLe) against multidrug-resistant E. faecalis isolates from feline UTIs.

Methods

Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm formation was assessed using the crystal violet assay, and biofilm-associated genes (sprE, gelE, fsrABC) were detected by PCR. ZnONPs, Str/ZnONPs (streptomycin-loaded ZnONPs), and Str/MOLe@ZnONPs (streptomycin and MOLe-loaded ZnONPs) were characterized using FTIR, DLS, TEM, and SEM. The antibacterial and antibiofilm activities of the synthesized nanoparticles were evaluated through time-kill assays, well diffusion assays, and gene expression analysis.

Results

A high prevalence of multidrug resistance was observed among the E. faecalis isolates, with significant resistance to ampicillin, vancomycin, and streptomycin. Characterization studies revealed the successful encapsulation of streptomycin and MOLe within the ZnONPs.In vitro assays demonstrated that Str/MOLe@ZnONPs exhibited potent antibacterial and antibiofilm activities against the tested E. faecalis strains, significantly reducing bacterial growth and biofilm formation.

Discussion

The emergence of multidrug-resistant E. faecalis strains necessitates the development of novel therapeutic strategies. This study demonstrates the promising potential of ZnONPs, particularly those loaded with streptomycin and MOLe, in combating biofilm-forming E. faecalis. The synergistic effects of the combined formulation may offer a novel approach to overcome antibiotic resistance and improve the treatment outcomes of E. faecalis UTIs in domestic cats.
Adapting educational practices for Generation Z: integrating metacognitive strategies and artificial intelligence
Authors: Chardonnens Sarah
Published: January 2025

The educational landscape is evolving rapidly due to the technological transformations brought by the digital age, necessitating innovative approaches to engage Generation Z learners. This study explores the specific educational needs of Generation Z, defined as individuals born between 1997 and 2012, and examines the role of metacognitive strategies and artificial intelligence (AI) in enhancing their learning experiences. A systematic literature review was conducted using academic databases such as Google Scholar, Scopus, and PsycINFO to identify 121 relevant studies published between 2000 and 2024. The review focused on research articles that addressed motivation, engagement, self-regulation, and cognitive processes in digital learning environments. The results reveal that active learning strategies such as project-based learning and formative assessment significantly enhance engagement and autonomy in Generation Z students. Furthermore, the integration of AI technologies provides personalized learning paths and real-time feedback, supporting self-regulated learning. However, over-reliance on AI poses risks to the development of critical thinking and self-regulatory skills. The study concludes by proposing a balanced approach to AI integration, suggesting that it should complement human guidance to foster holistic student development. Future research should explore the long-term effects of AI on cognitive development and the design of inclusive AI tools that cater to diverse learners.
Associations between lipid-lowering drugs and urate and gout outcomes: a Mendelian randomization study
Authors: Liu Min , Yin Na , Zhu Yuhang , Du Aili , Cai Chunyuan , Leng Pengyuan
Published: January 2025

Objective

Gout is a common inflammatory arthritis and lipid metabolism plays a crucial role in urate and gout. Potential associations between urate and gout and lipid-lowering drugs have been revealed in observational studies. However, the effects of lipid-lowering drugs on urate and gout remain controversial. The aim of this study was to investigate the genetic association between lipid-lowering drugs and urate and gout.

Methods

In this study, two genetic proxies were employed to approximate lipid-lowering drug exposure: expression quantitative trait loci (eQTL) associated with drug-target genes and genetic variations proximal to or within genes targeted by these drugs, which are linked to low-density lipoprotein cholesterol (LDL-C) levels. The study’s exposures encompassed genetic variants within drug target genes (HMGCR, PCSK9, NPC1L1), each representing distinct lipid-lowering mechanisms. Causal effects were estimated using the inverse variance weighting (IVW) method, while the Summary Data-based Mendelian Randomization (SMR) method, leveraging pooled data, was applied to compute effect estimates. These estimates were further refined through various approaches including MR-Egger, the weighted median method, simple and weighted models, and leave-one-out analyses to conduct sensitivity analyses.

Result

The analytical outcomes utilizing the IVW method indicated that inhibitors of HMGCR were correlated with an elevated risk of developing gout (IVW: OR [95%CI] = 1.25 [1.03, 1.46], p=0.0436), while PCSK9 inhibitors were linked to heightened levels of urate (IVW: OR [95%CI] = 1.06 [1.01,1.10], p=0.0167). Conversely, no significant correlation between NPC1L1 inhibitors and the levels of urate or the risk of gout was established. Furthermore, the SMR analysis failed to identify significant associations between the expression levels of the HMGCR, PCSK9, and NPC1L1 genes and the risk of gout or elevated urate levels (SMR method: all P values >0.05). Sensitivity analyses further confirmed the robustness of these results, with no significant heterogeneity or pleiotropy found.

Conclusion

This study furnishes novel causal evidence supporting the potential genetic correlation between the use of lipid-lowering drugs and the incidence of gout as well as urate levels. The findings indicate that inhibitors targeting HMGCR may elevate the risk associated with the development of gout, while inhibitors targeting PCSK9 are likely to increase urate concentrations.
Increasing prevalence of thyroid autoimmunity in childhood type 1 diabetes in the pre-COVID but not during the COVID era
Authors: Herczeg Vivien , Muzslay Eszter , Czipó Diána , Terkovics Lili , Takács Johanna , Garai Réka , Kovács Fanni , Luczay Andrea , Körner Anna , Tóth-Heyn Péter
Published: January 2025

Introduction

Studies assessing longitudinal changes in the prevalence of autoimmune thyroiditis (AIT) among the pediatric population are limited. During the COVID-19 era, several papers proposed a rise in AIT cases. Our study aimed to analyze the prevalence of thyroid autoimmunity (TA) over a 10-year period spanning pre-pandemic and pandemic years in a population who are regularly screened for thyroid disturbances.

Materials and methods

This single-center retrospective cohort study analyzed data from 1,361 children and young adults with type 1 diabetes (T1D) treated between 2013 and 2022 in Hungary’s largest pediatric endocrinology center. Results of anti-thyroid autoantibodies (anti-thyroid peroxidase/ATPO/and antithyroglobulin/ATG/), thyroid function tests (TFTs) and thyroid ultrasound examinations were obtained. Annual prevalence rates of TA and ultrasound-proven thyroiditis were calculated. Mean (± SD) follow-up period was 4.7 (± 2.8) years.

Results

The overall prevalence of TA among our T1D children was 22.8% ([20.3;25.5], 310 cases) with significantly more girls affected (p<0.001). From 2013 to 2022, TA prevalence rose from 15.9% to 20.6% (p=0.041). The increase was detected during the pre-pandemic years but not in the COVID-19 era. Ultrasound-confirmed thyroiditis was present in 80.0% of examined TA cases. Ultrasound positivity rate was stable during the study period. Among our children with TA, 28.5% exhibited clinically relevant thyroid-stimulating hormone (TSH) abnormalities (most commonly subclinical hypothyroidism) and/or were prescribed thyroid medication. Children with AIT had a significantly elevated risk of thyroid dysfunction compared to those with only thyroid autoantibody positivity (p<0.001).

Conclusion

Our results show a rise in the prevalence of thyroid autoimmunity among T1D children over the past decade, but our data do not support the assumed role of SARS-CoV-2 in the development of the disease.
Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and serum thyroid function measures: Recent Findings from NHANES 2007–2012 and Mendelian randomization
Authors: Tan Mo-Yao , Zhang Ping , Wu Shan , Zhu Si-Xuan , Gao Ming
Published: January 2025

Objective

There is limited epidemiological data regarding the association of blood lipids with thyroid hormones. Thus, the present article aims to explore whether there is an association between non-high-density to high-density lipoprotein cholesterol ratio (NHHR) and thyroid hormones.

Methods

We analyzed samples from 3,881 adults aged 20 years and above who took part in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. The study tested for thyroid hormones, including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), as well as thyroid-stimulating hormone (TSH). Survey-weighted linear regression and restricted cubic spline (RCS) models were employed to investigate the relationship between NHHR and thyroid hormones. Subsequently, subgroup analyses were conducted. In Mendelian randomization (MR), the inverse variance weighting method (IVW) is used as the primary analytical approach.

Results

This study finally comprised 3,881 adults aged 20 years and older. After extensive adjustments for covariables, the regression analysis revealed significant negative associations between NHHR and FT4 (β: -0.11, 95% confidence interval [CI]: -0.18, -0.04), FT4/FT3 (β: -0.06, 95% CI: -0.08, -0.04), and TT4/TT3 (β: -0.001, 95% CI: -0.001, 0.000). Both observational and Mendelian randomization studies suggest that high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol may not significantly influence the risk of hyperthyroidism or hypothyroidism.

Conclusions

The study indicates negative associations between NHHR and FT4, as well as the ratios of FT4/FT3 and TT4/TT3. This suggests that NHHR may reflect changes in thyroid function, highlighting its potential clinical significance in assessing thyroid function and metabolic health.
Molecular testing stratifies the risk of structural recurrence in high risk differentiated thyroid cancer: a retrospective cohort study
Authors: Liu Jie , Gao Wensi , Zheng Xiong , Wu Shuping , Shi Yi , Wang Feng , Wu Yu
Published: January 2025

Background

High-risk differentiated thyroid cancer in 2015 American Thyroid Association risk stratification system (ATA-RSS) exhibits a significantly increased probability of recurrence and poor outcomes. This study aimed to investigate the molecular profiles of high-risk differentiated thyroid cancer and to assess the role of molecular testing in enhancing prognostic risk stratification.

Methods

In a single-center study conducted at Fujian Cancer Hospital, Fujian Province, China, a consecutive cohort of differentiated thyroid cancer patients identified as high-risk under 2015 ATA-RSS criteria were retrospectively assessed, spanning from November 1, 2019, to March 31, 2022. Molecular characterize groups were conducted using an 18-gene next-generation sequencing assay. Patients harboring mutations in the TERT promoter, TP53, or PIK3CA genes were categorized as the high molecular risk group, while all others were assigned to the non-high molecular risk group.

Results

Among the 108 cases, 32 (29.6%) fell into the high molecular risk group, characterized by a significantly older mean age (57.8 vs. 42.6 years, p < 0.001), larger tumor size (3.1 cm vs. 2.0 cm, p = 0.003), a higher incidence of aggressive pathological subtypes (43.8% vs. 7.9%, p < 0.001), and an increased occurrence of distant metastasis (34.4% vs. 7.9%, p = 0.001). Over a median follow-up period of 32.5 months, this high-risk group demonstrated an elevated risk of local recurrence (32.1% vs. 9.5%, HR: 3.18, 95% CI: 1.15-8.78) and metachronous distant metastasis (38.1% vs. 2.9%, HR: 12.54, 95% CI: 2.60-60.41). Multivariate COX regression analysis confirmed that molecular characterize groups (HR: 5.77, 95% CI: 2.18-15.23, p < 0.001) and tumor size (HR: 1.32, 95% CI: 1.00-1.74, p = 0.047) independently predicted recurrence-free survival.

Conclusion

ATA-RSS high-risk differentiated thyroid cancer often presents with late-hit genetic alterations, which are strongly associated with increased likelihood of structural recurrence. Molecular testing offers a precise approach to recurrence risk stratification in high-risk cases, enabling personalized follow-up and treatment strategies tailored to the specific prognostic profile.
Evaluation of nutrient loads conveyed to the deep subalpine lakes of Northern Italy through their main tributaries
Authors: Dezuanni Paolo , Copetti Diego , Dresti Claudia , Pella Nicolò , Buzzi Fabio , Fenocchi Andrea
Published: January 2025

Nutrient pollution is a critical issue for lakes, leading to cultural eutrophication, which damages the ecosystem and prevents water uses. Proper watershed management practices must be put into action to effectively oppose eutrophication. Because of the complexities and the multiple layers of stakeholders involved in this process, the only factual way to evaluate improvements in watershed nutrient management is to directly estimate nutrient loads at watershed closing sections through available data from environmental monitoring. The Italian deep subalpine lakes (DSLs: Lake Como, Lake Garda, Lake Idro, Lake Iseo, Lake Maggiore) suffered from extensive eutrophication from the 1950s to the early 1980s. Their water quality improved in the 1980s and 1990s after national regulations were introduced to address nutrient pollution. After the turn of the century, increasingly pressing limits on nutrient disposal have been issued, yet steady if not worsening lake water quality conditions have been observed overall. To shed light on the issue, quantifying present and past external loads to these lakes based on direct measurements is essential. In this work, we focused on the main tributaries of the Italian DSLs, employing the observed time series of flowrate and nutrient concentrations to estimate the loading levels of nitrogen and phosphorus and their temporal evolution over a period ranging between 13 and 42 years according to data availability. The LOAD ESTimator (LOADEST) software was adopted to support the load quantification process. Results show that a general decrease in external nutrient loads is still occurring, albeit at a slow pace, the fastest reduction occurring for the Oglio River flowing into Lake Iseo, which has suffered from severe nutrient pollution till recently. Increasing loads have conversely been identified for the Sarca River flowing into Lake Garda. These outcomes highlight the beneficial actions carried out to reduce nutrient pollution, although a decorrelation analysis between external loads and flowrate is suggested for a clearer evaluation of its evolution across the DSLs.
CSE-8, a filamentous fungus-specific Shr3-like chaperone, facilitates endoplasmic reticulum exit of chitin synthase CHS-3 (class I) in Neurospora crassa
Authors: González-Téllez Samantha Verónica , Riquelme Meritxell
Published: January 2025

Chitin is a crucial structural polysaccharide in fungal cell walls, essential for maintaining cellular plasticity and integrity. Its synthesis is orchestrated by chitin synthases (CHS), a major family of transmembrane proteins. In Saccharomyces cerevisiae, the cargo receptor Chs7, belonging to the Shr3-like chaperone family, plays a pivotal role in the exit of Chs3 from the endoplasmic reticulum (ER) and its subsequent activity in the plasma membrane (PM). However, the auxiliary machinery responsible for CHS trafficking in filamentous fungi remains poorly understood. The Neurospora crassa genome encodes two orthologues of Chs7: chitin synthase export (CSE) proteins CSE-7 (NCU05720) and CSE-8 (NCU01814), both of which are highly conserved among filamentous fungi. In contrast, yeast forms only possess a single copy CHS export receptor. Previous research highlighted the crucial role of CSE-7 in the localization of CHS-4 at sites of cell wall synthesis, including the Spitzenkörper (SPK) and septa. In this study, CSE-8 was identified as an export protein for CHS-3 (class I). In the Δcse-8 knockout strain of N. crassa, CHS-3-GFP fluorescence was absent from the SPK or septa, indicating that CSE-8 is required for the exit of CHS-3 from the ER. Additionally, sexual development was disrupted in the Δcse-8 strain, with 20% of perithecia from homozygous crosses exhibiting two ostioles. A Δcse-7;Δcse-8 double mutant strain showed reduced N-acetylglucosamine (GlcNAc) content and decreased radial growth. Furthermore, the loss of cell polarity and the changes in subcellular distribution of CSE-8-GFP and CHS-3-GFP observed in hyphae under ER stress induced by the addition of tunicamycin and dithiothreitol reinforce the hypothesis that CSE-8 functions as an ER protein. The current evidence suggests that the biogenesis of CHS exclusive to filamentous fungi may involve pathways independent of CSE-mediated receptors.
The socio-economic impacts of the floriculture industries on the smallholders in Ethiopia: the case of Sululta District in Oromia National Regional State
Authors: Kassa Alemnesh Tsehay , Keno Gutema Imana , Makahamadze Tompson , Bekele Demissie
Published: January 2025

Floriculture industries produce non-edible agricultural products for the global market. Whereas, the smallholder farmers produce edible agricultural products for domestic consumption and they contribute to national food security. The purpose of this article is to uncover the impact of the floriculture industry on the socioeconomic sustainability of the smallholder farmers and associated conflicts in Sululta district, Oromia Regional State in Ethiopia. A qualitative research approach and grounded theory research design were used to carry out the study. Data was collected using document analysis, non-participant observation, and interviews conducted with twenty five research participants, 2 FGDs, and 3 key informants from the local elders. The major findings of the study indicated that floriculture industries have controlled lands in various forms that affect the smallholder farmers’ access to land and water resources. The study highlights the socioeconomic non-sustainability of smallholder farmers in the study area due to social insecurity, agricultural product damage, arable land and water resource access restrictions, resulting in the smallholder farmers shift to daily laborers. The article recommends that the government should balance the foreign exchange earnings from the floriculture industries with the sustainability of the smallholder farmers. The article also recommends government in Ethiopia should promote participatory resource management environmental and social impact assessments to mitigate potential negative impacts of industries on the smallholder farmers’ socioeconomic sustainability.
Clinical assessment and transcriptome analysis of host immune responses in a vaccination-challenge study using a glycoprotein G deletion mutant vaccine strain of infectious laryngotracheitis virus
Authors: Gopakumar Gayathri , Coppo Mauricio J. C. , Diaz-Méndez Andrés , Hartley Carol A. , Devlin Joanne M.
Published: January 2025

A glycoprotein-G-deleted live-attenuated vaccine strain of the infectious laryngotracheitis virus (ILTV), ΔgG-ILTV, is safe and efficacious against ILTV challenge. In the current study, the transcriptome of peripheral blood mononuclear cells (PBMCs) of the ΔgG-ILTV-vaccinated group of specific-pathogen-free chickens were compared to those of the nonvaccinated group at 7 days post-vaccination. Tracheal transcriptomes after challenge with virulent ILTV were compared between groups of the non-vaccinated-challenged and the vaccinated-challenged as well as the non-vaccinated-challenged and the uninfected chickens at 4 to 5 days post-challenge. The clinical outcomes after challenge between these groups were also evaluated. Significant differences were observed in the tracheal transcriptome of the non-vaccinated-challenged birds compared to the other two groups. Enriched gene ontologies and pathways that indicated heightened immune responses and impairments to ciliary and neuronal functions, cell junction components, and potential damages to cartilaginous and extracellular components in the trachea of the non-vaccinated-challenged birds were consistent with their severe tracheal pathology compared to the other two groups. On the contrary, the absence of any difference in the tracheal transcriptome between the vaccinated-challenged and the uninfected birds were reflected by the preservation of tracheal mucosal integrity in both groups and mild infiltration of leukocytes in the vaccinated-challenged birds. The results from this study demonstrated that vaccination with ΔgG-ILTV prevented the changes in tracheal transcriptome induced during ILTV challenge, resulting in clinical protection. Additionally, these results also provide insights into the molecular mechanisms underlying the tracheal pathology induced by ILTV infection.
Single-cell sequencing uncovers the mechanistic role of DAPK1 in glioma and its diagnostic and prognostic implications
Authors: Yu Tian-Hang , Ding Yan-Yu , Zhao Si-Guo , Zhao Jie-Hui , Gu Yu , Chen Dong-Hui , Zhang Fang , Hong Wen-Ming
Published: January 2025

Background

We conducted an investigation into the characteristics of single-cell differentiation data in gliomas, with a focus on developing DAPK1-based prognostic markers to predict patient outcomes. Dysregulated expression of DAPK1 has been associated with the invasive behavior of various malignancies, including gliomas. However, the precise role and underlying mechanisms of DAPK1 in gliomas remain inadequately understood.

Methods

We performed analyses on RNA-seq and microarray datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), in addition to single-cell RNA sequencing (scRNA-seq) data from glioma patients available in GEO. Utilizing the Seurat R package, we identified gene clusters associated with survival from the scRNA-seq data. Prognostic models were developed using LASSO and stepwise regression algorithms. Furthermore, we assessed the predictive potential of these genes within the immune microenvironment and their relevance in immunotherapy contexts.

Results

Our scRNA-seq data analysis revealed 32 distinct cell clusters corresponding to 10 cell types. Through dimensionality reduction and clustering, we identified three glial cell subpopulations based on their differentiation trajectories. DAPK1, serving as a marker gene for the terminal subpopulation, exhibited an association with poor prognosis.

Conclusions

DAPK1-based prognostic models show promise for accurately predicting outcomes in glioblastoma and glioma. An in-depth examination of DAPK1’s specific mechanisms in glioblastoma could elucidate its role in immunotherapy response. Targeting the DAPK1 gene may offer therapeutic benefits for glioma patients.
Pan-cancer and experimental analyses reveal the immunotherapeutic significance of CST2 and its association with stomach adenocarcinoma proliferation and metastasis
Authors: Huang Dan , Li Jing , He Zhijun , Liang Wenjing , Zhong Likun , Huang Jun , Wu Yinteng , Zhao Shijian
Published: January 2025

Purpose

Cystatin 2 (CST2) is a cysteine protease inhibitor, and recent research suggests its potential involvement in cancer development. However, its role in the occurrence, progression, and prognosis of pan-cancer has not been systematically investigated.

Materials and methods

This study comprehensively analyzes the differential expression of CST2 in pan-cancer. The expression distribution patterns of CST2 were examined using single-cell datasets. Furthermore, we conducted a comprehensive evaluation of the correlation between CST2 expression and various factors. These factors include prognosis, immune cell infiltration, immune-related genes, mutations, methylation, tumor mutation burden (TMB), and microsatellite instability (MSI). In addition, we analyzed the sensitivity of drugs dependent on CST2 expression. We utilized gene set enrichment analysis (GSEA) analysis to explore the biological functions of CST2 across different cancer types. Finally, in gastric cancer cell lines, we will investigate the impact of CST2 knockout on expression levels, clonal proliferation, cell apoptosis, and cell migration.

Results

CST2 exhibits abnormal overexpression in multiple tumors. Single-cell analysis reveals high expression of CST2 in fibroblasts. CST2 is closely associated with prognosis, immune cell infiltration, immune-related genes, mutations, methylation, TMB, and MSI. Enrichment analysis demonstrated a significant correlation between CST2 and immune-related pathways. In stomach adenocarcinoma (STAD), CST2-related risk models are associated with prognosis and demonstrate strong predictive capabilities, while also being closely linked to the immune microenvironment. Drug sensitivity analysis indicates the correlation between CST2 and 21 chemotherapy drugs. Finally, experimental validation revealed significantly elevated expression of CST2 in STAD, indicating its role as a driver gene in regulating malignant cell proliferation and migration.

Conclusion

CST2 serves as a potential tumor immune biomarker, playing a critical facilitating role in the proliferation and migration processes of STAD.
Thymus ad astra, or spaceflight-induced thymic involution
Authors: Muramatsu Wataru , Maryanovich Maria , Akiyama Taishin , Karagiannis George S.
Published: January 2025

Spaceflight imposes a constellation of physiological challenges—cosmic radiation, microgravity, disrupted circadian rhythms, and psychosocial stress—that critically compromise astronaut health. Among the most vulnerable organs is the thymus, a cornerstone of immune system functionality, tasked with generating naive T cells essential for adaptive immunity. The thymus is particularly sensitive to spaceflight conditions, as its role in maintaining immune homeostasis is tightly regulated by a balance of systemic and local factors easily disrupted in space. Cosmic radiation, an omnipresent hazard beyond Earth’s magnetosphere, accelerates DNA damage and cellular senescence in thymic epithelial cells, impairing thymopoiesis and increasing the risk of immune dysregulation. Microgravity and circadian rhythm disruption exacerbate this by altering immune cell migration patterns and stromal support, critical for T-cell development. Psychosocial stressors, including prolonged isolation and mission-induced anxiety, further compound thymic atrophy by elevating systemic glucocorticoid levels. Ground-based analogs simulating cosmic radiation and microgravity have been instrumental in elucidating mechanisms of thymic involution and its downstream effects on immunity. These models reveal that long-duration missions result in diminished naive T-cell output, leaving astronauts vulnerable to infections and possibly at high risk for developing neoplasia. Advances in countermeasures, such as pharmacological interventions targeting thymic regeneration and bioengineering approaches to protect thymic architecture, are emerging as vital strategies to preserve immune resilience during prolonged space exploration. Focusing on the thymus as a central hub of immune vulnerability underscores its pivotal role in spaceflight-induced health risks. Understanding these dynamics will not only enhance the safety of human space missions but also provide critical insights into thymus biology under extreme conditions.
Aging impairs CD8 T cell responses in adoptive T-cell therapy against solid tumors
Authors: Kadyrzhanova Gulfiya , Tamai Miho , Sarkar Shukla , Kalra Rajkumar Singh , Ishikawa Hiroki
Published: January 2025

Age-associated defects in T cell-mediated immunity can increase the risk of cancers, but how aging influences adoptive T-cell therapy (ACT) for cancers remains unclear. Here, using a mouse model of melanoma, we demonstrate that aging diminishes anti-tumor activity of engineered CD8 T cells expressing a tumor-specific T cell receptor (CD8 TCR-T cells) in ACT for solid tumors. Aged CD8 TCR-T cells cannot control tumor growth in either young or aged mice. Aged CD8 TCR-T cells are unable to accumulate efficiently in tumors and have higher tendency to become terminally exhausted T cells with lower expression of endothelial PAS domain-containing protein 1 (Epas1) compared to young cells. Crispr-mediated ablation of Epas1 promotes terminal exhaustion of young CD8 T cells in tumors, diminishing their anti-tumor activity in young mice. Conversely, retroviral expression of Epas1 enhances anti-tumor activity of aged CD8 TCR-T cells. These findings suggest that aging-induced reduction of Epas1 expression impairs anti-tumor activity of CD8 T cells in ACT against solid tumors, which can be therapeutically improved by expression of exogenous Epas1.
Distal muscle weakness as the main onset symptom in thymoma-associated myasthenia gravis: a case report and literature review
Authors: Wu Xuan , Xu Xiao-tian , Zhou Lin , Qiao Kai , Zhao Chong-bo , Luo Su-shan
Published: January 2025

Myasthenia gravis (MG) is an autoimmune disorder within the spectrum of neuromuscular rare diseases, characterized by fluctuating muscle weakness. This report presents a case of a middle-aged woman with a chronic onset of asymmetric upper limb weakness accompanied by difficulty in finger extension, without ptosis or fluctuation for 4 years. The patient was finally diagnosed with MG by a significant decrement of Compound Muscle Action Potential in repetitive nerve stimuli, positive anti-acetylcholine receptor antibodies as well as the presence of a mass located in the anterior mediastinum. With subsequent immunotherapies for one month, the patient exhibited marked enhancement in muscle strength, followed by an uneventful thymectomy. After two months, the patient’s symptoms were fully alleviated, as evidenced by the reduction in Quantitative MG Score from 9 to 4 points, Myasthenia Gravis Composite Score from 6 to 1 points, Myasthenia Gravis Activities of Daily Living Score from 4 to 1 points, and Myasthenia Gravis Quality of Life-15 score from 14 to 8 points respectively. This case highlights the importance of differentiating autoimmune disorders from hereditary neuromuscular diseases and initiating timely treatment.
Efficacy of low-dose rituximab versus immunosuppressants in refractory orbital inflammatory pseudotumors with intracranial extension
Authors: Li Yuyu , Sun Mingming , Xu Xintong , Chen Biyue , Chen Xiyun , Wang Yuhang , Xu Quangang , Zhou Huanfen , Wei Shihui
Published: January 2025

Objective

The aim of this study was to compare the efficacy of low-dose rituximab (RTX) and immunosuppressants in treating orbital inflammatory pseudotumor (OIP) with intracranial extension, a refractory and high-relapse disease.

Methods

Patients who had been diagnosed with refractory OIP with intracranial extension and who were refractory to systemic corticosteroids were retrospectively recruited at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital between December 2018 and September 2022. After methylprednisolone pulse therapy, we added 2 mg of tacrolimus per day, 1500 mg of mycophenolate mofetil per day, or 200 mg of rituximab at days 1 and 15, and then monitored those with CD19+ B cells of under 1% as adjuvant therapy.

Results

Eleven patients (six males and five females) were included, with a mean age of 45.5 ± 11.8 years (age range: 21–64 years). The average follow-up period was 3.8 years (range: 2–5). Eight patients (72.7%) had different levels of decreased vision at onset of the illness and four patients (36.4%) had severely impaired vision (three with no light perception, one with some light perception). Four patients (36.4%) showed clinical course worsening or lack of remission when treated with corticosteroids. Seven patients (63.6%) had a typical relapsing course, and the annual recurrence rate was higher than 7.36 ± 3.73 times. Of these seven, four (57.1%, 4/7) were able to undergo successful management with immunosuppressants. Three (42.9%, 3/7) failed with immunosuppressants but succeeded in controlling relapse with RTX.

Conclusion

OIP with intracranial extension is uncommon. More than half of patients with OIP with intracranial extension may be satisfactorily treated with corticosteroids combined with immunosuppressants. However, for patients who still experience recurrence or slow reduction of lesions after applying this combined therapy, RTX may be a better option.
Studies on the alleviating effect of Bifidobacterium lactis V9 on dextran sodium sulfate-induced colitis in mice
Authors: Duan Xiaoyan , Wu Rilige , Li Jianbo , Li Zeya , Liu Yanqi , Chen Ping , Wang Bangmao
Published: January 2025

Background

Inflammatory bowel disease (IBD) has become a global public health problem with complex pathogenesis and limited therapeutic options. We aimed to investigate the potential mechanisms by which Bifidobacterium lactis V9 (V9) alleviated colitis in a dextran sodium sulfate-induced colitis model mice.

Methods

Mice were induced to develop colitis by drinking DSS solution to induce colitis. The expression of the relevant factors in the blood supernatant of the mice was determined by ELISA. RT-qPCR and Western blotting were used to detect mRNA and protein expression of target genes. The fecal microbiota was analyzed by 16S rRNA sequencing. Intestinal metabolites were analyzed by untargeted metabolomics;

Results

V9 effectively improved the overall symptoms of the colitis model mice. H&E showed that V9 re-stored the intestinal tissue structure. ELISA showed that V9 decreased the levels of IL-6, IL-22, and TNF-α and increased IL-10, SP, VIP, and 5-HT. V9 increased the expression of AHR, CYP1A1, MUC2, Claudin-3, Occludin, and ZO-1, and decreased 5-hydroxytryptamine transporter and Claudin-2. V9 increased the abundance of gut microbiota in colitis mice to promote the growth of beneficial bacteria. V9 increased tryptophan metabolites, and short-chain fatty acids, and improved gut inflammation.

Conclusion

V9 attenuates intestinal inflammation, improves the mucosal barrier, modulates intestinal microecology and exerts a protective effect in a mouse model of DSS-induced colitis.
Isolation, characterization and liposome-loaded encapsulation of a novel virulent Salmonella phage vB-SeS-01
Authors: Luo Yuhang , Mahillon Jacques , Sun Lin , You Ziqiong , Hu Xiaomin
Published: January 2025

Introduction

Salmonella is a common foodborne pathogenic bacterium, displaying facultative intracellular parasitic behavior, which can help the escape against antibiotics treatment. Bacteriophages have the potential to control both intracellular and facultative intracellular bacteria and can be developed as antibiotic alternatives.

Methods

This study isolated and characterized vB-SeS-01, a novel Guernseyvirinae phage preying on Salmonella enterica, whose genome is closely related to those of phages SHWT1 and vB-SenS-EnJE1. Furthermore, nine phage-carrying liposome formulations were developed by film hydration method and via liposome extruder.

Results and Discussion

Phage vB-SeS-01 displays strong lysis ability against 9 out of 24 tested S. enterica strains (including the pathogenic “Sendai” and “Enteritidis” serovars), high replicability with a burst size of 111 ± 15 PFU/ cell and a titre up to 2.1 × 1011 PFU/mL, and broad pH (4.0 ~ 13.0) and temperature (4 ~ 80°C) stabilities. Among the nine vB-SeS-01 liposome-carrying formulations, the one encapsulated with PC:Chol:T80:SA = 9:1:2:0.5 without sonication displayed the optimal features. This formulation carried up to 1011 PFU/mL, with an encapsulation rate of 80%, an average size of 172.8 nm, and a polydispersity index (PDI) of 0.087. It remained stable at 4°C and 23°C for at least 21 days and at 37°C for 7 days. Both vB-SeS-01 and vB-SeS-01-loaded liposomes displayed intracellular antimicrobial effects and could reduce the transcription level of some tested intracellular inflammatory factors caused by the infected S. enterica sv. Sendai 16,226 and Enteritidis 50041CMCC.
Unveiling early-life microbial colonization profile through characterizing low-biomass maternal-infant microbiomes by 2bRAD-M
Authors: Hou Shuwen , Jiang Yuesong , Zhang Feng , Cheng Tianfan , Zhao Dan , Yao Jilong , Wen Ping , Jin Lijian , Huang Shi
Published: January 2025

Introduction

The microbial composition of human breast milk and infant meconium offers critical insights into the early microbial colonization profile, and it greatly contributes to the infant’s immune system and long-term health outcomes. However, analyzing these samples often faces technical challenges and limitations of low-resolution using conventional approaches due to their low microbial biomass.

Methods

Here, we employed the type IIB restriction enzymes site-associated DNA sequencing for microbiome (2bRAD-M) as a reduced metagenomics method to address these issues and profile species-level microbial composition. We collected breast milk samples, maternal feces, and infant meconium, comparing the results from 2bRAD-M with those from both commonly used 16S rRNA amplicon sequencing and the gold-standard whole metagenomics sequencing (WMS).

Results

The accuracy and robustness of 2bRAD-M were demonstrated through its consistently high correlation of microbial individual abundance and low whole-community-level distance with the paired WMS samples. Moreover, 2bRAD-M enabled us to identify clinical variables associated with infant microbiota variations and significant changes in microbial diversity across different lactation stages of breast milk.

Discussion

This study underscores the importance of employing 2bRAD-M in future large-scale and longitudinal studies on maternal and infant microbiomes, thereby enhancing our understanding of microbial colonization in early life stages and demonstrating further translational potential.
Brain-inspired multimodal motion and fine-grained action recognition
Authors: Li Yuening , Yang Xiuhua , Chen Changkui
Published: January 2025

Introduction

Traditional action recognition methods predominantly rely on a single modality, such as vision or motion, which presents significant limitations when dealing with fine-grained action recognition. These methods struggle particularly with video data containing complex combinations of actions and subtle motion variations.

Methods

Typically, they depend on handcrafted feature extractors or simple convolutional neural network (CNN) architectures, which makes effective multimodal fusion challenging. This study introduces a novel architecture called FGM-CLIP (Fine-Grained Motion CLIP) to enhance fine-grained action recognition. FGM-CLIP leverages the powerful capabilities of Contrastive Language-Image Pretraining (CLIP), integrating a fine-grained motion encoder and a multimodal fusion layer to achieve precise end-to-end action recognition. By jointly optimizing visual and motion features, the model captures subtle action variations, resulting in higher classification accuracy in complex video data.

Results and discussion

Experimental results demonstrate that FGM-CLIP significantly outperforms existing methods on multiple fine-grained action recognition datasets. Its multimodal fusion strategy notably improves the model's robustness and accuracy, particularly for videos with intricate action patterns.
Clinical efficacy of Tuina therapy combined with traditional Chinese exercises in the treatment of symptomatic lumbar disc herniation: a multicentre randomised controlled trial protocol
Authors: Fan Zhihong , Jia Shenghong , Zhou Xin , Li Chao , Shao Jiahao , Liu Xiaofeng , Liao Yitao , Xu Yenan , He Dandan , Wu Shixiang , Zhang Xian
Published: January 2025

Background

Low back pain and lower extremity sensory and functional abnormalities are common symptoms of lumbar disc herniation (LDH), which can easily cause walking dysfunction and significantly impair the quality of life of patients. Tuina and traditional Chinese exercises (TCEs) are effective in relieving pain and restoring dysfunction, and both are often used in China as a combination of passive therapy and active exercise to ease symptoms in patients with LDH. However, the majority of current clinical trials on the treatment of LDH with Tuina or TCEs are single-centre clinical studies, and the quality of these studies is generally low. Furthermore, clear evidence of clinical efficacy as to whether Tuina combined with TCEs is superior to single TCEs for improving dysfunction and pain in patients with LDH is lacking.

Methods/design

The design is a multicentre, assessor-blinded clinical randomised controlled trial. A total of 166 patients with LDH (aged 18–65 years) were recruited from four centres and randomly assigned at a 1:1 ratio to two groups: the TCE group and the Tuina combined with the TCE group. Each group received three treatments over the course of 1 week for a total of 4 weeks. The primary outcome indicator was the Oswestry Disability Index, whereas the secondary outcome indicators were the Short Form of Quality of Life Scale, the Short-Form McGill Pain Questionnaire Scale, and gait analysis. Assessments were made before the treatment, at the end of the treatment, and at the third and sixth months’ follow-ups. Gait analysis was only used for comparison between the two groups before and after treatment, and did not involve follow-up. Adverse events occurring during the trial were faithfully recorded.

Conclusion

The results of this study are expected to provide a more effective research protocol for symptomatic LDH and an evidence-based rationale for the efficacy and safety of Tuina combined with TCEs in the treatment of symptomatic LDH.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=209956, identifier ChiCTR2300077361.