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Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Humans

Identification of CXCL13 as an agonist and CXCL11 as an inverse agonist for the viral G protein-coupled receptor ORF74.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infection in humans, but under conditions of immune suppression, it may reactivate and contribute to severe diseases, including Kaposi's sarcoma (KS) and B-cell malignancies. The KSHV genome encodes a single G protein-coupled receptor (GPCR), open reading frame 74 (ORF74), which shows homology to human chemokine receptors. Since its identification in 1996, ORF74 has subsequently been shown to interact with a broad range of human CXC chemokines, as well as CCL1 and the viral chemokine vCCL2. Compared with many human chemokine receptors, ORF74 displays high basal activity. These properties allow ORF74 to deregulate host cellular pathways through constitutive and chemokine-modulated signaling. In this study, we evaluated several human chemokines that, to our knowledge, had not previously been tested in ORF74-dependent cellular assays. Whereas CXCL9, CXCL14, CXCL16 and CXCL17 did not interact with ORF74, CXCL13 was identified as an additional ORF74 agonist and CXCL11 as an inverse agonist. CXCL13 dose-dependently induced ORF74-mediated Ca2+ release, β-arrestin1/2 recruitment and chemotaxis, and enhanced basal nuclear factor κB (NF-κB) activity in ORF74-expressing cells. In contrast, CXCL11 showed no detectable ORF74 agonist activity in the calcium mobilization or chemotaxis assay, but antagonized CXCL1-induced responses in both readouts. CXCL11 also elicited inverse agonist-like responses in β-arrestin1/2 recruitment assays and reduced basal NF-κB signaling. Our study thus reveals CXCL13 and CXCL11 as two additional chemokine ligands for ORF74, further expanding the pharmacological profile of this viral GPCR.

Humans

Integrated electronic nose, GC-MS, and metagenomic analyses reveal volatile flavor and microbial community differences in heap-fermented grains of Jiangxiangxing Baijiu across different fermentation degrees.

The fermentation degree of heap-fermented grains in Jiangxiangxing Baijiu production is a critical factor influencing base Baijiu quality. However, conventional assessment methods largely rely on empirical experience and therefore suffer from limited objectivity and accuracy. In this study, integrated volatile profiling and metagenomic approaches were employed to investigate volatile characteristics and microbial functional potential differentiation in fermented grains with different fermentation degrees (under-fermented, normally fermented, and over-fermented). Significant differences in physicochemical properties were observed among fermentation degrees, particularly in acidity and reducing sugar content. Electronic nose analysis revealed distinct sensor response patterns among different fermentation degrees, indicating differences in overall volatile odor fingerprint patterns. A total of 81 volatile compounds were identified by HS-SPME-GC-MS, with aldehydes, ketones, and pyrazines showing pronounced variations among fermentation degrees, and acetaldehyde exhibiting strong discriminatory potential. LEfSe analysis identified 18 microbial taxa as potential biomarkers associated with different fermentation degrees, including Pichia kudriavzevii, Lentibacillus daiqui, and Acetobacter pasteurianus. Correlation analysis revealed significant positive associations between acetaldehyde levels and Acetobacter abundance. Furthermore, KEGG, CAZy, and eggNOG analyses revealed differentiated functional potentials among fermentation degrees, providing insights into the potential metabolic basis associated with flavor differentiation. Overall, these findings highlight that fermentation degree differentiation is closely associated with coordinated changes in physicochemical conditions, microbial communities, and functional potentials, providing ecological insights into flavor differentiation and theoretical support for objective fermentation degree evaluation and quality control of Jiangxiangxing Baijiu production.

Fermentation

Elucidation of microbial community structure, small-molecule metabolic and flavor profile characteristics in Xuanwei ham under different processing techniques.

This study systematically compared the impacts of traditional (TH) and modern (MH) processing techniques on the physicochemical properties, microbial community structure, metabolome, and volatile aroma compounds of Xuanwei ham. The results showed that the TH group had higher moisture content and water activity, along with a more tender texture, whereas the MH group exhibited greater hardness and chewiness. Microbiological analysis revealed that the interior of the MH group had higher species richness of both fungi and bacteria, while the TH group maintained higher fungal diversity. Metabolomic analysis identified 112 differential metabolites, with sweet amino acids and certain lipids being more enriched in modern ham, whereas traditional ham contained higher levels of umami amino acids, polyunsaturated fatty acids, and flavor compounds such as carnosine. KEGG pathway enrichment indicated that the differences were primarily concentrated in amino acid biosynthesis and metabolism-related pathways. Volatile flavoromics analysis identified 45 odor-active compounds and screened 15 key aroma-active substances. Among them, modern processed ham was significantly enriched in fatty aldehydes such as (E)-2-nonenal, hexanal, nonanal, and octanal, whereas traditional processed ham was characterized by 1-octen-3-ol, (E,E)-2,4-decadienal, methional, acetoin, and benzeneacetaldehyde. Correlation analysis confirmed that dominant microbes in Xuanwei ham were significantly associated with differential metabolites and characteristic aroma compounds, respectively. This study provides a scientific basis for standardizing production processes, enabling precise quality control, and promoting high-quality industrial development of Xuanwei ham.

Animals

Transformation of antibiotics mediated by iron-bearing minerals: A review.

Iron-bearing minerals are ubiquitous in water, sediments and soil, where their surface chemical properties and redox activity can play an important role in degradation of trace antibiotics. This review systematically summarizes the roles of various iron-bearing minerals in chemical transformation and microbial degradation of antibiotics and reaction mechanisms involved, and refines the critical idea for iron-driven control of antibiotics with trace level in natural environment. Overall, antibiotics removal in the presence of iron-bearing minerals involves combination of adsorption, surface oxidative degradation, photo-induced degradation, Fenton-like reaction and microbial degradation. Adsorption of antibiotics by Fe(III)-minerals involves electrostatic interaction, complexation, H-bonding, π-π interaction and hydrophobic interaction. Adsorbed antibiotics form complexes with Fe(III)-minerals, undergoing electron transfer to generate radical intermediates, subsequently generating final products through hydroxylation, dealkylation, and deamination. Additionally, Fe(III)-minerals can be excited to produce electrons and holes under sunlight and to produce antibiotics-degrading hydroxyl radical through O2 reduction, H2O oxidation and ligand-to-metal charge transfer. Reduced iron minerals can activate oxygen to participate in Fenton-like degradation reactions. Finally, antibiotics are mainly removed by bio-driven Fenton reaction and direct enzyme biodegradation. The presence of iron-bearing minerals can promote antibiotics microbial degradation by providing nutrients for microorganisms or by changing microbial activity and microbial community structure. Existing problems and future research directions are identified. New insights for application of iron-bearing minerals in transformation of antibiotics are proposed. The work aims to suggest new methods and insights for pollution control and remediation of emerging contaminants including trace antibiotics in the natural environment.

Anti-Bacterial Agents

A novel urease-producing strain effectively induces cadmium biomineralization under low-temperature stress.

Microbially induced carbonate precipitation (MICP) has been widely used to immobilize Cadmium (Cd) in contaminated soils in mining-affected regions. However, its remediation efficacy under low-temperature stress, as well as the nucleation process that regulates Cd biomineralization via carbonate precipitation by psychrophilic bacteria, has yet to be investigated. Here, we isolated Pseudomonas sp. J-6, a novel urease-producing strain from tailings in high-altitude cold regions, exhibiting unparalleled cold adaptability at 5 °C and achieving 95.85 % Cd removal efficiency by MICP at 10 °C. Furthermore, the coprecipitation process of Ca1-xCdxCO3 was clarified through the continuous observation of the precipitates after the low-temperature MICP reaction. The crystal morphology transitioned from loose vaterite in the early stage to a dense square-block morphology in the middle stage. Cd2+ progressively shifted from a surface-bound state to lattice incorporation, ultimately resulting in the formation of stable Cd-substituted calcite crystals. In this process, low temperatures led to the formation of larger, highly ordered Cd-substituted calcite crystals, thereby strengthening Cd sequestration and its long-term stability. In addition, under low-temperature stress, Pseudomonas sp. J-6 induced MICP reaction decreased the bioavailable Cd in alpine slag soil by 44.85 % and enhanced physical properties. In the freeze-thaw cycles, the remediation efficiency remained stable. This study clarified the biomineralization potential in high-altitude cryogenic environments and the nucleation process of Cd biomineralization by psychrophilic bacteria-induced carbonate precipitation, filling a critical research gap in its application under extreme conditions and highlighting its promise for sustainable remediation of heavy metal pollution under low-temperature stress.

Cadmium

Dynamics of soil fungal communities restored with biochar from a quarry site.

Quarrying activities have intensified due to population expansion, leading to landscape degradation and ecological destruction. Quarry restoration is usually mandatory in Hong Kong, China. Although biochar is used for sustainable soil amendment, its effectiveness in restoring quarry soil with poor properties has rarely been investigated. A 24-month field study was conducted to evaluate the ecological feasibility of restoring a quarry site by using native species (that is, Castanopsis fissa and Cyclobalanopsis edithiae) and biochar amendment. The results revealed that after 24 months, the application of biochar increased the organic carbon, phosphorus and potassium of the vegetated soil by at least 120 %, 31 % and 12 %, respectively, due to higher cation exchange capacity and better plant growth. The relative abundance of Ascomycota and Basidiomycota increased by 24 % and 47 % with biochar application when C. fissa was planted, which was likely associated with the improved nutrient cycling and soil fertility. Even though adding biochar to bare soil was found to increase the complexity of fungal co-occurrence networks, biochar application only increased fungal diversity in vegetated quarry soil but usually reduced its fungal richness. Moreover, fungal co-occurrence networks in vegetated soil became less complex, suggesting that biochar potentially helped plants to assemble specific, beneficial fungal communities. This effect is most pronounced in the soil planted with C. edithiae, where the structure of fungal communities after 24 months was significantly different from that at other restoration times. This study identifies key fungal phyla enhanced by biochar in quarry soil and provides an effective strategy for facilitating the restoration and management of degraded lands, especially quarry sites.

Charcoal

Age-related differences in motor unit behaviours and maximal strength: A systematic review and meta-analysis.

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD =&#x202f;-0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Aging

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans

Dispositional optimism and open-label placebo responses in hair cortisol concentrations and psychological distress-A randomized controlled trial.

Open-label placebo (OLP) treatments show beneficial effects on various health-related outcomes, but studies investigating OLP effects on physiological measures remain scarce. This randomized controlled trial examined the effect of a 4-week OLP intervention on psychological distress and hair cortisol concentrations (HCC) in 202 healthy university students preparing for mandatory oral exams and whether dispositional optimism moderates the OLP effects. Participants were randomly assigned to an OLP or control group. Psychological distress was repeatedly assessed via negative affect, test anxiety, and subjective stress. HCC was measured before and within the intervention. Treatment expectations were additionally examined in interaction with optimism. Results show that OLPs significantly reduced psychological distress and HCC compared to the controls. Optimism moderated the OLP effect on HCC, with less optimistic individuals demonstrating the strongest reduction, independent of expectation. Optimism did not moderate OLP effects in psychological distress. However, the OLP effect on psychological distress depended on the three-way interaction of group, optimism, and expectation. The results suggest that OLPs alleviate the psychophysiological impact of a real-life stressor and indicate that optimism and expectation differently shape psychological and physiological OLP responses. These findings are discussed within the framework of the interactionist perspective.

Humans

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in&#xa0;vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17&#x3b2;-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in&#xa0;vivo reliance.

Humans

Biomonitoring of industrial heavy metal pollution via enzymatic and metabolic responses in desert ants (Cataglyphis savignyi) and beetles (Tentyrum sp) as bioindicators.

The current work seeks to evaluate the effectiveness of Cataglyphis saviginyi and Tentyrum sp as indicators of pollution in the city's main industrial regions by analyzing their enzymatic activity and primary metabolites. Soil samples were collected at each site under investigation to analyze soil characteristics and heavy metal content. C. saviginyi and Tentyrum sp were collected across four consecutive seasons (2023-2024) to investigate enzymatic (GPT, GOT, ALP, ACP, LDH) and metabolic (lipid, protein, carbohydrate) biomarkers. The physicochemical properties of the soil differed substantially between the industrial areas and the control site. Soil heavy metal buildup was highest at industrial sites (1 and 4) compared to the control site, with the order being Zn&#x2009;>&#x2009;Cr&#x2009;>&#x2009;Cd&#x2009;>&#x2009;Cu. Heavy metal pollution indices were determined. Increased industrial activity from metal industries, ceramics, and chemical painting companies defines this area, as seen by the high Cdeg, mCd, PI, and PLI values derived for industrial sites 1 and 4. While C. saviginyi and Tentyrum sp deconcentrated and released Cr, Cd, and Zn into the soil via the biological accumulation factor (BAF), Cu acted as a macro-concentrator. Compared with the control site, industrial environments were shown to increase levels of GPT, GOT, LDH, ACP, protein, and carbohydrates in C. saviginyi. However, lipid and ALP activity was suppressed. at industrial sites, Tentyrum sp carbohydrate content was higher than at control sites, but GPT, GOT, ALP, ACP, LDH, protein, and lipid activities were all suppressed. Consequently, enzymatic and metabolic biomarkers proved to be sensitive indicators for assessing industrial heavy metal pollution in desert ecosystems.

Animals

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8&#xa0;Da), and herbicolin B (1138&#xa0;Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5&#xa0;mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5&#xa0;mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea

An overview of the use of proteomics and peptidomics to characterize alternative protein foods.

The global protein transition is accelerating the development of alternative protein foods, mainly derived from plants, insects, algae, fungi, and cellular agriculture. Ensuring the authenticity, safety, and nutritional adequacy of these emerging protein matrices requires molecular-level characterization beyond traditional compositional analyses. Proteomics and peptidomics have emerged as transformative analytical platforms capable of decoding the molecular signatures that define protein origin, structural integrity, digestibility, functionality, and health potential. The review comprehensively examines the application of proteomics, and peptidomics for profiling alternative protein foods. Further, the source authentication strategies based on species-specific protein and peptide biomarkers, detection of adulteration in complex matrices, and allergenicity assessment is discussed. Special attention is also given to nutritional proteomics with protein digestibility, gastrointestinal peptide release, and identification of bioactive sequences. SIGNIFICANCE: The importance of this review is that proteomics and peptidomics are becoming central in the management of the fast-growing environment of alternative protein foods, such as plant-based, insect, algal, fungal, and cultured meat products. It provides an explanation of the application of mass spectrometry-based processes to decode molecular signatures defining the origin of proteins, their structural integrity, digestibility, allergenicity, and bioactive properties, and thus directly contribute to safety, nutritional analysis, and authenticity of the product. Presentation of the article includes the integration of the knowledge of traditional muscle foods with alternative systems of proteins, where validated protein and peptide biomarkers are used in authentication, fraud detection, and allergy risk assessment in a wide variety of matrices. It also indicates the role of nutritional proteomics and peptidomics in informing the formulation strategy to promote digestibility and release of health-promoting peptides. In general, this review will guide scientists, the food industry, and regulatory bodies to use modern proteomic technologies in quality assurance, and decision-making, for the advancementof sustainable protein-based foods.

Proteomics

Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate&#xae;; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28&#x2009;&#xb1;&#x2009;8&#x2009; years; BMI: 23.8&#x2009;&#xb1;&#x2009;2.9&#x2009;kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35&#xb0;C) to induce ~2% body mass loss (BML), then rehydrated over a 1&#x2009;h period in a laboratory (~21&#xb0;C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4&#x2009;h of seated rest (5&#x2009;h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2&#x2009;h after beverage consumption), and all urine produced was collected. RESULTS: During the 5&#x2009;h rehydration period, there was no effect of trial on total urine volume (FRU: 1266&#x2009;&#xb1;&#x2009;403&#x2009;mL, SPO: 1338&#x2009;&#xb1;&#x2009;361&#x2009;mL, WAT: 1394&#x2009;&#xb1;&#x2009;360&#x2009;mL; P&#x2009;=&#x2009;0.156) or water retention (FRU: 42&#x2009;&#xb1;&#x2009;12%, SPO: 37&#x2009;&#xb1;&#x2009;10%, WAT: 35&#x2009;&#xb1;&#x2009;11%; P&#x2009;=&#x2009;0.059). The blood glucose area under the curve differed by trial (P&#x2009;<&#x2009;0.001), with all beverages significantly different from each other (FRU: 10.12&#x2009;&#xb1;&#x2009;0.72 mmol/L/2h, SPO: 12.48&#x2009;&#xb1;&#x2009;1.34 mmol/L/2h, WAT: 7.90&#x2009;&#xb1;&#x2009;0.47 mmol/L/2h; P&#x2009;<&#x2009;0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1&#x2009;h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans

Frequent mutations in the BIRC3 gene promote metastatic potential of nasopharyngeal carcinoma cells through the TRAF2-NF-&#x3ba;B pathway.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637&#xa0;A&#xa0;>&#xa0;G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3c.637A>G mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-&#x3ba;B signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637&#xa0;A&#xa0;>&#xa0;G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-&#x3ba;B axis in the treatment of NPC.

Humans

Magnesium administration for vasospasm prevention in acute aneurysmal SAH: a multicenter randomized controlled trial.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality, with cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) being the primary contributors to poor outcomes. Magnesium sulfate (MgSO&#x2084;) has demonstrated neuroprotective and vasodilatory properties in preclinical models. This study aimed to evaluate the effect of targeted serum magnesium (Mg) maintenance on CV and exploratory clinical outcomes following aSAH. We conducted a prospective, multicenter, single-blind RCT across four neurocritical care units in Korea between 2019 and 2024. A total of 121 aSAH patients were randomized to receive either IV MgSO&#x2084;or placebo within six hours of admission. Mg was infused to maintain serum concentrations between 2.0 and 3.0 mg/dL for 14 days. The primary outcome was incidence of CV assessed by transcranial doppler. Secondary outcomes included DCI, ICU and hospital length of stay, modified rankin scale (mRS) at 30 days. There was no significant difference in overall CV incidence; however, the Mg group demonstrated significantly lower mean flow velocity and Lindegaard ratio on days 4-9, indicating reduced vasospasm severity. In exploratory multivariable analyses, a median serum Mg concentration&#x2009;>&#x2009;2.5 mg/dL during the first 14 hospital days was independently associated with lower risks of CV and DCI. No significant differences were found in mRS scores, ICU and hospital stay, or serious adverse events between groups. Early targeted Mg administration improved TCD-derived hemodynamic markers during the peak vasospasm window; however, it did not significantly reduce CV incidence, DCI, ICU or hospital stay, or 30-day functional outcome.

Humans