Search Results (4,657)

Nanopore raw read accuracy has improved to over 99%, making it a potential tool for metabarcoding. For broad adoption, guidelines on quality filtering are needed to ensure reliable taxonomic unit recovery. This study aims to provide those guidelines for a fungal metabarcoding context and to apply them to a case study of ectomycorrhizae in the decaying bark of Fagus sylvatica. We introduce the eNano pipeline to test two standard metabarcoding approaches: (1) Reference-based mapping leveraging UNITE’s species hypothesis system (SH approach); (2) Constructing 98% OTUs (OTU approach). Our results demonstrate that both approaches are effective with Nanopore data. When using a reference database, we recommend strict mapping criteria rather than Phred-based filtering. Leveraging the SH-system further enhances reproducibility and facilitates cross-study communication. For the 98% OTUs, filtering reads at ≥Q25 is recommended. Our case study reveals that the decay gradient is a primary determinant of community composition and that specific mycorrhizal fungi colonize decaying bark. Complementing our metabarcoding results with root tip morphotypification, we identify Laccaria amethystina and Tomentella sublilacina as key ectomycorrhizae of saplings on decaying logs. These findings demonstrate that Nanopore sequencing can provide valuable ecological insights and support its broader use in fungal metabarcoding as read quality continues to improve. Full article

In surgically treated individuals with surgical stomas, the return to physical activity is an indicator of quality of life that reflects their well-being. With the aim of synthesizing the available evidence regarding the return to physical activity in individuals with surgical stomas, a scoping review was developed following the methodological approach of the Joanna Briggs Institute and the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews criteria. Searches were conducted in Medline (PubMed), Scopus, Web of Science, Cinahl, and Lilacs, as well as the meta-search engines TripDatabase and Epistemonikos, using MeSH terms. Included studies were written in Spanish, English, Portuguese, and German, without any limitation on the year of publication. A total of n = 15 studies was included (n = 2 qualitative; n = 2 case reports; n = 1 case series; n = 1 cohort; n = 8 cross-sectional; and n = 1 randomized clinical trial), which showed variability in the quality of the designs. The qualitative studies explored themes such as motivation, beliefs about physical activity, and other lifestyle factors. The case reports described physiological, psychological, and functional implications of returning to physical activity for specific individuals after ostomy surgery. Quantitative studies evaluated the effects of different types of physical activity on quality of life and tolerance to physical activity in these individuals, employing various measurement instruments. In conclusion, the evidence on returning to sports and physical activity after stoma surgery is limited and varied. While studies highlight the importance of social support and self-confidence, they generally lack rigor and primarily focus on adults and oncology patients. There is a need for more research to establish clear guidelines on physical activity type, frequency, and intensity to ensure safe and beneficial outcomes for individuals with stomas. Full article

Cardiovascular disease (CVD) represents the leading cause of death worldwide. For individuals at elevated risk for cardiovascular disease, early detection and monitoring of lipid status is imperative. The majority of lipid measurements conducted in hospital settings employ optical detection, which necessitates the use of relatively large-sized detection machines. It is, therefore, necessary to develop point-of-care testing (POCT) for lipoprotein in order to monitor CVD. To enhance the management and surveillance of CVD, this study sought to develop a POCT approach for apolipoprotein B (ApoB) utilizing a shear horizontal surface acoustic wave (SH-SAW) platform to assess the risk of heart disease. The platform employs a reflective SH-SAW sensor to reduce the sensor size and enhance the phase-shifted signals. In this study, the platform was utilized to monitor the impact of a weekly almond and oat milk or statins intervention on alterations in CVD risk. The SH-SAW ApoB test exhibited a linear range of 0 to 212 mg/dL, and a coefficient correlation (R) of 0.9912. Following a four-week intervention period, both the almond and oat milk intervention (−23.3%, p < 0.05) and statin treatment (−53.1%, p < 0.01) were observed to significantly reduce ApoB levels. These findings suggest that the SH-SAW POCT device may prove a valuable tool for monitoring CVD risk, particularly during routine daily or weekly follow-up visits. Full article

Objectives: This systematic review addressed the following questions: what are the most recommended diagnostic criteria for pulley injuries in finger flexors among climbers? What is the best functional or classification clinical test for these injuries based on the available evidence? Materials and Methods: Following the PRISMA Statement checklist, a systematic literature review was conducted between August and September 2023, using a search on the PubMed database with a string of keywords and MeSH terms. The PEDro scale was used to analyze bias in the individual studies examined. Conclusions: Based on the exclusion criteria and research question, 14 articles with heterogeneous study designs were selected. Studies involving diagnosis through clinical examination or instrumental tests were analyzed. The data obtained provide an overview of different diagnostic and classification criteria for the injury under consideration. Ultrasounds remain the gold standard in diagnosing finger pulley injuries. The distance between the tendon and bone is the most used diagnostic criterion, with a distance greater than 2 mm corresponding to an A2 or A4 pulley injury. The clinical sign of bowstringing coincides with a multiple pulley injury involving A2, A3, and A4. Clinical signs, ultrasounds, and grip strength should be evaluated for a comprehensive diagnosis. A grip deficit of 41.4% corresponds to a pulley injury. Full article

China’s vulnerability to fluvial floods necessitates extensive exposure studies. Previous large-scale regional analyses often relied on a limited set of assessment indicators due to challenges in data acquisition, compounded by the scarcity of corresponding large-scale flood distribution data. The integration of public datasets offers a potential solution to these challenges. In this study, we obtained four key exposure indicators—population, built-up area (BA), road length (RL), and average gross domestic product (GDP)—and conducted an innovative analysis of their correlations both overall and locally. Utilising these indicators, we developed a comprehensive exposure index employing entropy-weighting and k-means clustering methods and assessed fluvial flood exposure across multiple return periods using fluvial flood maps. The datasets used for these indicators, as well as the flood maps, are primarily derived from remote sensing products. Our findings indicate a weak correlation between the various indicators at both global and local scales, underscoring the limitations of using singular indicators for a thorough exposure assessment. Notably, we observed a significant concentration of exposure and river flooding east of the Hu Line, particularly within the eastern coastal region. As flood return periods extended from 10 to 500 years, the extent of areas with flood depths exceeding 1 m expanded markedly, encompassing 2.24% of China’s territory. This expansion heightened flood risks across 15 administrative regions with varying exposure levels, particularly in Jiangsu (JS) and Shanghai (SH). This research provides a robust framework for understanding flood risk dynamics, advocating for resource allocation towards prevention and control in high-exposure, high-flood areas. Our findings establish a solid scientific foundation for effectively mitigating river flood risks in China and promoting sustainable development. Full article

Dysregulated fatty acid metabolism is an attractive therapeutic target for colorectal cancer (CRC). We previously reported that fatty acid synthase (FASN), a key enzyme of de novo synthesis, promotes the initiation and progression of CRC. However, the mechanisms of how upregulation of FASN promotes the initiation and progression of CRC are not completely understood. Here, using Apc/VillinCre and Apc^Min mouse models, we show that upregulation of FASN is associated with an increase in activity of β-catenin and expression of multiple stem cell markers, including Notum. Genetic and pharmacological downregulation of FASN in mouse adenoma organoids decreases the activation of β-catenin and expression of Notum and significantly inhibits organoid formation and growth. Consistently, we demonstrate that NOTUM is highly expressed in human CRC and its expression positively correlates with the expression of FASN in tumor tissues. Utilizing overexpression and shRNA-mediated knockdown of FASN, we demonstrate that upregulation of FASN increases β-catenin transcriptional activity, NOTUM expression and secretion, and enhances stem-like properties of human CRC cells. Pharmacological inhibition of NOTUM decreases adenoma organoids growth and proliferation of cancer cells. In summary, upregulation of FASN enhances β-catenin signaling, increases NOTUM expression and stem-like properties of CRC cells, thus suggesting that targeting FASN upstream of the β-catenin/NOTUM axis may be an effective preventative therapeutic strategy for CRC. Full article

FER zeolites have a unique framework structure and acid distribution, and are widely studied as a catalyst for reactions such as n-butene skeletal isomerization and dimethyl ether carbonylation. The Brönsted acid site (BAS) located in the 10-member ring (10-MR) of FER zeolites serves as the active site for the isomerization reaction of skeletal n-butene to produce isobutene. This study prepared five types of FER zeolites using different methods: using pyrrolidine (PY) alone as a template; using Na-form FER as seeds (SN) or H-form FER as seeds without organic structure directing agents (OSDAs); and combining the seeds of SN or SH with PY as OSDAs. The differences in the structure and acid distribution of the five zeolites were investigated, as well as their catalytic performance for the skeletal isomerization of n-butene. Experiments and characterization results showed that under hydrothermal synthesis conditions, the FER-PY+SH zeolites synthesized by using both H-form zeolites seeds and pyridine exhibited the highest aluminum concentrations at T1 and T3 sites, along with the greatest BAS located in the 10-MR. This unique composition contributed to the highest selectivity of isobutene. The FER-PY+SH catalyst was continuously used for 720 h at 350 °C, 0.1 MPa, and an n-butene mass space velocity of 2.0 h⁻¹ for three cycles of 2160 h. During this period, the conversion of n-butene was over 39%, while the selectivity of isobutene exceeded 95%. The FER-PY+SH catalyst exhibited excellent stability and activity. Full article

Background: Long non-coding RNAs (lncRNAs) are key regulators of cellular processes that underpin cancer development and progression. DRAIC is a migration inhibitor that has been linked with lung adenocarcinoma progression; however, its mechanisms remain to be studied. Methods: Several bioinformatics tools were used to explore the role of DRAIC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Results: Our bioinformatics analysis illustrates that patients with low expression of DRAIC have poor overall survival outcomes. In addition, the mRNA of SH3 domain-binding kinase 1 (SBK1) was downregulated in this cohort of patients. Mechanistic analysis showed that SBK1 is under the DRAIC competing endogenous RNAs network, potentially through sponging of miRNA-92a. Conclusions: Consistent dysregulation of the DRAIC-SBK1 axis was linked to poor survival outcome in both LUAD and LUSC, suggesting a tumour inhibitor role and providing potential for new diagnostics and therapeutic approaches. Full article

To ensure the quality of their analyses, medical laboratories carry out internal quality control (IQC) on a daily basis. IQC involves control samples with known target values for all parameters used by a laboratory in clinical practice. The use of IQC enables the laboratory to monitor the accuracy and precision of laboratory results. The use of appropriate IQC strategies has been accepted in medical laboratories for decades, and IQC has been included in international recommendations and guidelines. The term “IQC strategy” (also termed a quality control plan) refers to the types of IQC materials to be measured, the frequency of IQC events, the number of concentration levels in each IQC event, and the IQC rules to be used. A scientifically sound IQC strategy must follow two principles, namely, (1) statistical follow-up on the IQC results generated in the laboratory by means of Levey–Jennings control charts and Westgard rules (i.e., quality control by means of statistical procedures) and (2) the determination of limits on the basis of medical considerations and the definition of analytical goals (quality control on the basis of medical relevance). In this narrative review, we describe the fundamental principles of an adequate IQC strategy for laboratorians and nonlaboratorians. Full article

Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival. In this study, we tested the effects of synthetic indole (NC009-1, -2, -3, -6) and coumarin (LM-022, -031) derivatives as chemical chaperones to assist mutant ATXN3-Q₇₅ folding, as well as autophagy inducers to clear aggregated protein. Among the tested compounds, NC009-1, -2, and -6 and LM-031 interfered with Escherichia coli-derived ATXN3-Q₇₅ aggregation in thioflavin T binding and filter trap assays. In SH-SY5Y cells expressing GFP-fused ATXN3-Q₇₅, these compounds displayed aggregation-inhibitory and neurite growth-promoting potentials compared to untreated cells. Furthermore, these compounds activated autophagy by increasing the phosphatidylethanolamine-conjugated LC3 (microtubule associated protein 1 light chain 3)-II:cytosolic LC3-I ratio in these cells. A biochemical co-immunoprecipitation assay by using a mixture of HEK 293T cell lysates containing recombinant ATXN3-Q₇₅-Venus-C-terminus (VC) or Venus-N-terminus (VN)-LC3 protein indicated that NC009-1 and -2 and LM-031 served as an autophagosome-tethering compound (ATTEC) to interact with ATXN3-Q₇₅ and LC3, and the interaction was further confirmed by bimolecular fluorescence complementation analysis in cells co-expressing both ATXN3-Q₇₅-VC and VN-LC3 proteins. The study results suggest the potential of NC009-1 and -2 and LM-031 as an ATTEC in treating SCA3 and, probably, other polyQ diseases. Full article

The TaqIA polymorphism is a marker of both the Ankyrin Repeat and Kinase Domain containing I gene (ANKK1) encoding a RIP-kinase, and the DRD2 gene for the dopamine receptor D2. Despite a large number of studies of TaqIA in addictions and other psychiatric disorders, there is difficulty in interpreting this genetic phenomenon due to the lack of knowledge about ANKK1 function. In SH-SY5Y neuroblastoma models, we show that ANKK1 interacts with the synapse protein FERM ARH/RhoGEF and Pleckstrin Domain 1 (FARP1), which is a guanine nucleotide exchange factor (GEF) of the RhoGTPases RAC1 and RhoA. ANKK1–FARP1 colocalized in F-ACTIN-rich structures for neuronal maturation and migration, and both proteins activate the Wnt/PCP pathway. ANKK1, but not FARP1, promotes neuritogenesis, and both proteins are involved in neuritic spine outgrowth. Notably, the knockdown of ANKK1 or FARP1 affects RhoGTPases expression and neural differentiation. Additionally, ANKK1 binds WGEF, another GEF of Wnt/PCP, regulating its interaction with RhoA. During neuronal differentiation, ANKK1–WGEF interaction is downregulated, while ANKK1–FARP1 interaction is increased, suggesting that ANKK1 recruits Wnt/PCP components for bidirectional control of F-ACTIN assembly. Our results suggest a brain structural basis in TaqIA-associated phenotypes. Full article

Generally, essential genes identified using shRNA and CRISPR are not always the same, raising questions about the choice between these two screening platforms. To address this, we systematically compared the performance of CRISPR and shRNA to identify essential genes across different gene expression levels in 254 cell lines. As both platforms have a notable false positive rate, to correct this confounding factor, we first developed a graph-based unsupervised machine learning model to predict common essential genes. Furthermore, to maintain the unique characteristics of individual cell lines, we intersect essential genes derived from the biological experiment with the predicted common essential genes. Finally, we employed statistical methods to compare the ability of these two screening platforms to identify essential genes that exhibit differential expression across various cell lines. Our analysis yielded several noteworthy findings: (1) shRNA outperforms CRISPR in the identification of lowly expressed essential genes; (2) both screening methodologies demonstrate strong performance in identifying highly expressed essential genes but with limited overlap, so we suggest using a combination of these two platforms for highly expressed essential genes; (3) notably, we did not observe a single gene that becomes universally essential across all cancer cell lines. Full article

Background: As our population ages, the demand for aged care services and palliative care is expected to increase. Allied health professionals have a diverse set of skills to offer in the management of older adults. This scoping review aimed to identify what evidence exists to support the best practice of allied health clinicians in palliative and aged care. Methods: Searches were conducted using broad keywords and MeSH headings with relevance to palliative, ageing and allied health care in the databases Ovid MEDLINE (R), CINAHL, EMCARE, INFORMIT, REHABDATA, PEDRO and SCOPUS, as well as the grey literature. Results: Only 15 studies met the inclusion criteria. A prominent finding was that regular exercise interventions delivered improved mobility, balance, sleep and quality of life outcomes when measured (n = 5). Broader allied health input and outcomes, such as nutrition, were not well described, other than to suggest an interprofessional approach contributed to health benefits where these were observed. Conclusions: The lack of research creates uncertainty about what excellent care looks like and how it can be measured, making it harder for allied health professionals to advocate for funded time in providing care at the end of life and leading to poorer outcomes for older adults. Full article

The effects of trehalose, an autophagy-inducing disaccharide with neuroprotective properties, on the neurotoxicity of parkinsonian mimetics 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpiridinium (MPP⁺) are poorly understood. In our study, trehalose suppressed 6-OHDA-induced caspase-3/PARP1 cleavage (detected by immunoblotting), apoptotic DNA fragmentation/phosphatidylserine externalization, oxidative stress, mitochondrial depolarization (flow cytometry), and mitochondrial damage (electron microscopy) in SH-SY5Y neuroblastoma cells. The protection was not mediated by autophagy, autophagic receptor p62, or antioxidant enzymes superoxide dismutase and catalase. Trehalose suppressed 6-OHDA-induced activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK), as revealed by immunoblotting. Pharmacological/genetic inhibition of JNK, p38 MAPK, or AMPK mimicked the trehalose-mediated cytoprotection. Trehalose did not affect the extracellular signal-regulated kinase (ERK) and mechanistic target of rapamycin complex 1 (mTORC1)/4EBP1 pathways, while it reduced the prosurvival mTORC2/AKT signaling. Finally, trehalose enhanced oxidative stress, mitochondrial damage, and apoptosis without decreasing JNK, p38 MAPK, AMPK, or AKT activation in SH-SY5Y cells exposed to MPP⁺. In conclusion, trehalose protects SH-SY5Y cells from 6-OHDA-induced oxidative stress, mitochondrial damage, and apoptosis through autophagy/p62-independent inhibition of JNK, p38 MAPK, and AMPK. The opposite effects of trehalose on the neurotoxicity of 6-OHDA and MPP+ suggest caution in its potential development as a neuroprotective agent. Full article

Neuroblastoma is a devastating disease accounting for ~15% of all childhood cancer deaths. Collagen content and fiber association within the tumor stroma influence tumor progression and metastasis. High expression levels of collagen receptor kinase, Discoidin domain receptor II (DDR2), are associated with the poor survival of neuroblastoma patients. Additionally, cancer cells generate and sustain mechanical forces within their environment as a part of their normal physiology. Despite this, evidence regarding whether collagen-activated DDR2 signaling dysregulates these migration forces is still elusive. To address these questions, a novel shRNA DDR2 knockdown neuroblastoma cell line (SH-SY5Y) was engineered to evaluate the consequence of DDR2 on cellular mechanics. Atomic force microscopy (AFM) and traction force microscopy (TFM) were utilized to unveil the biophysical altercations. DDR2 downregulation was found to significantly reduce proliferation, cell stiffness, and cellular elongation. Additionally, DDR2-downregulated cells had decreased traction forces when plated on collagen-coated elastic substrates. Together, these results highlight the important role that DDR2 has in reducing migration mechanics in neuroblastoma and suggest DDR2 may be a promising novel target for future therapies. Full article