Search Results (19,787)

Tuberculosis (TB) remains a major global cause of morbidity and mortality. Current tools for monitoring treatment response rely on sputum-based microscopy and culture, which are often insensitive, time-consuming, and impractical in extrapulmonary or pediatric TB and in individuals unable to produce sputum. Metabolomics has emerged as a promising approach for identifying host-derived biomarkers that reflect treatment-associated immunometabolic changes; however, the available evidence remains heterogeneous and has not been comprehensively synthesized. We conducted a comprehensive literature review of human studies evaluating metabolomic biomarkers in relation to TB treatment response or outcomes. PubMed, Scopus, and EMBASE were searched for human studies evaluating targeted or untargeted metabolomics (NMR, LC-MS, GC-MS, CE-MS) in relation to treatment response or outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using QUIPS and PROBAST. Findings were synthesized using a structured framework organized across treatment stages and outcomes. Of 218 records identified, 139 titles and abstracts were screened and 42 full texts assessed; 15 studies met the inclusion criteria. Recurrent treatment-associated signals involved amino acid metabolism, particularly the tryptophan–kynurenine pathway, as well as vitamin and cofactor metabolites (pyridoxate, nicotinamide, trigonelline). Plasma studies frequently reported lipid remodeling and bile acid perturbations, whereas urine studies highlighted polyamine metabolism (e.g., N¹,N¹²-diacetylspermine) and fatty acid β-oxidation markers. Common limitations included inadequate adjustment for confounders and, in prediction models, small sample sizes and limited external validation. Metabolomics reveals reproducible but heterogeneous immunometabolic changes during TB therapy. Key pathways include tryptophan–kynurenine metabolism, vitamin and cofactor metabolism, lipid remodeling, and urine polyamine pathways. Standardization and prospective multicenter validation are needed for clinical translation. Full article

Sarcopenia is an age-related skeletal muscle disorder characterized by reduced muscle mass, strength, and physical performance, as well as increased risk of disability, hospitalization, and mortality. Emerging evidence suggests that gut microbiota alterations may contribute to muscle decline via a microbiota–gut–muscle axis, acting as a context-dependent modulator rather than a primary causal driver. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut dysbiosis to sarcopenia. Preclinical studies show that microbiota modulation (e.g., antibiotics, probiotics, prebiotics, postbiotics, fecal microbiota transplantation) affects muscle mass, strength, and metabolism through pathways including inflammation, mitochondrial dysfunction, altered short-chain fatty acid production, and impaired anabolic signaling. In humans, observational studies associate lower microbial diversity and reduced short-chain fatty acid-producing taxa with poorer muscle outcomes, but findings are heterogeneous and non-causal. Interventional trials remain limited and characterized by small sample sizes, with effects more consistent for functional outcomes than muscle mass. Overall, the gut microbiota represents a modifiable contributor within the complex biology of sarcopenia. Future studies should integrate microbiome profiling and multi-omics approaches within well-designed clinical trials to identify responder phenotypes and define the role of microbiota-targeted strategies within multimodal interventions. Full article

γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter, is known for its physiological functions in alleviating anxiety and improving sleep. Currently, high-yielding GABA food products are mainly obtained through screening wild-type high-producing strains (e.g., Saccharomyces cerevisiae isolated from Sichuan pickles yielding 0.67 g/L) or employing co-culture systems (e.g., Enterococcus faecium and Lactiplantibacillus plantarum reaching 6.35 g/L). While effective, these methods often rely on natural screening strains or multi-microbial interactions. This study employed CRISPR-Cas9 technology to knockout the UGA1 gene in Saccharomyces cerevisiae, a key gene responsible for GABA degradation. Starting from the low higher alcohol Saccharomyces cerevisiae SY-LH, we successfully constructed the recombinant strain SY-LHU. Remarkably, this study discovered a significant upregulation of GAD1 gene expression following UGA1 knockout, which further enhanced GABA synthesis capacity. Under optimal fermentation conditions (inoculum size 4 × 10⁷ cells/mL, wort concentration 10 °P, sugar addition 60 g/L, 30 °C for 10 days, and mixing the malt broth every 48 h), the validation fermentation was performed and the GABA content in the wort beverage reached 280.36 mg/L, representing a 385.4% increase compared to the pre-optimization level. Furthermore, sensory evaluation by a trained panel yielded a mean score of 88, with no significant off-flavors detected, demonstrating the product’s high consumer acceptance. This pioneering work provides a novel and feasible technical pathway for developing functional alcoholic beverages with sleep-aiding properties. Full article

Background: The early detection of prostate and testicular tumors remains challenging as standard diagnostic tools often lack sensitivity and produce ambiguous results. Seminal fluid is a biologically rich medium that closely reflects the state of male reproductive tissues and has therefore emerged as a promising source of non-invasive molecular biomarkers. Objective: This study aimed to critically evaluate the evidence regarding cell-free DNA, RNA, proteins and metabolites in seminal fluid, and to assess their potential for improving the early detection of male reproductive cancers. Methods: A systematic review was performed according to PRISMA guidelines. Comprehensive searches of the PubMed and Scopus databases were conducted to identify original clinical studies analyzing molecular biomarkers in seminal fluid from patients with prostate or testicular tumors. For each study, data were extracted on biomarker types, cohort characteristics, analytical methods and diagnostic performance. Results: Forty-two eligible studies were included, covering multiple biomarker classes. Most were observational, single-center investigations classified as level 3b evidence. Across the different types of biomarkers, seminal fluid was associated with tumor-associated molecular changes. Alterations in the concentration, fragmentation and methylation patterns of cell-free DNA (e.g., GSTP1, RARβ2, LGALS3 and OCT3/4) distinguished malignant from benign conditions with sensitivities of up to 80–100%. RNA-based markers, including microRNAs, small non-coding RNAs, and tRNA fragments, showed improved performance in several studies, with multimarker models achieving areas under the curve (AUCs) of 0.85–0.93. Proteomic analyses identified high-specificity candidates such as TGM4, AMACR, PROS1 and DKK3. Metabolomic profiling further strengthened the diagnostic potential; reduced seminal citrate outperformed prostate-specific antigen (AUC 0.748 vs. 0.548), and reproducible shifts in amino acid and lipid profiles were observed in testicular tumors. However, substantial heterogeneity in study design, patient selection, and analytical platforms was observed. Risk of bias varied, and large prospective validation cohorts were lacking. Conclusions: Current evidence suggests that seminal fluid contains molecular signals associated with tumors that could be used for diagnosis. However, the available data are predominantly exploratory and methodologically heterogeneous. Before seminal fluid-based biomarkers can be considered for routine clinical implementation, robust prospective studies with standardized protocols are required. Full article

Purpose: Black soils in Northeast China are declining in fertility under intensive fertilization, motivating strategies that integrate crop residue return with microbial inoculation. We conducted a field experiment to test whether maize straw return combined with compound microbial inoculants improves soil properties, bacterial communities, and soybean performance. Methods: A field experiment compared four treatments: fertilization alone (F), fertilization + inoculants (CF), fertilization and straw (SF), and fertilization and straw with inoculants (CSF). Soil physicochemical properties, enzyme activities, 16S rDNA-based bacterial communities, and soybean agronomic yield were measured across growth stages. Results: CSF produced the highest soybean performance, and increased yield by 3.91–5.46% compared with F. CSF increased soil pH, moisture, and nutrient availability (notably available P and K) and enhanced sucrase, urease, catalase, and acid phosphatase activities compared with other treatments. Bacterial communities were dominated by Acidobacteriota and Proteobacteria. CSF increased bacterial abundance and shifted community composition, and pH and available P were key factors associated with community variation. Conclusions: Co-applying maize straw and compound microbial inoculants enhances soybean yield while improving soil biochemical functioning and reshaping bacterial communities in black soil. Full article

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca’ Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4⁺ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management. Full article

Lignocellulosic biomass represents an abundant and renewable carbon source, and its valorization through microalgal cultivation offers a sustainable route to resource-efficient bioprocessing. This study examined the effects of various carbon and nitrogen sources on the growth and lipid metabolism of Desmodesmus subspicatus, with a focus on ryegrass enzymatic hydrolysates as an alternative carbon source. Cultures were supplied with glucose, xylose, or arabinose at different concentrations, along with sodium nitrate or yeast extract, under different carbon-to-nitrogen ratios. Additionally, the impacts of alkaline- and acid-pretreated enzymatic ryegrass hydrolysates were evaluated. Growth was assessed by optical density and gravimetric analysis, and fatty acid profiles by gas chromatography. Glucose supplementation enhanced lipid accumulation, yielding fatty acid profiles dominated by C16 and C18 fatty acids, which are favorable for the quality of the produced biodiesel. Nitrogen limitation further promoted lipid accumulation; cultures supplied with sodium nitrate achieved higher total lipid content, while yeast extract favored greater proportions of PUFAs. Alkaline-pretreated ryegrass hydrolysate supported dose-dependent biomass formation reaching approximately 12 g L⁻¹ at 50%, whereas the acid-pretreated hydrolysate exhibited inhibitory effects at the same concentration. Scale-up in a 1 L photobioreactor yielded lower biomass but higher lipid content with a fatty acid profile shifted to SFA. These results support ryegrass as a viable alternative carbon source and highlight cultivation parameters that influence growth and lipid quality relevant for biofuel applications. Full article

The biochemical diversity among tea plant (Camellia sinensis) cultivars serves as the core material basis associated with tea quality and is of great significance for the innovation of tea germplasm resources and the genetic improvement of tea varieties. Here, we systematically analyzed 16 biochemical components, 7 mineral elements, and water-soluble fluoride (WSF) in 65 tea cultivars using multivariate analysis. These cultivars were grouped into high-component, high-epigallocatechin (EGC), low-component, and balanced-quality clusters. Significant variation was observed in quality-related parameters, including tea polyphenols, catechins, and amino acids and related quality indices. Mineral elements were significantly correlated with quality components, with potassium and boron showing significant correlation with the accumulation of these components. WSF content exhibited a pronounced cultivar-dependent variation, with more than 72% of cultivars containing less than 100 mg·kg⁻¹. The balanced-quality cluster exhibited broad processing adaptability, making it suitable for producing various tea types. The high-EGC cluster is ideal for developing specialty functional teas. The high-component cluster offers core parental material for breeding cultivars high in tea polyphenols and epigallocatechin gallate. This study provides a scientific basis for the screening and utilization of tea germplasm resources and the development of new, high-quality, and safe tea varieties. Full article

The gut microbiota serves as a critical interface for host immunity, making it a promising target for probiotic intervention. In this study, we investigated the immunomodulatory potential of the strain Bifidobacterium breve (B. breve) MN15965 and the underlying role of gut bacterial communities in this process. We first assessed its in vitro immunomodulatory activity by measuring nitric oxide and cytokine secretion in THP-1 macrophages. Subsequently, an immunosuppressed mouse model was established by treating BALB/c mice with cyclophosphamide (CTX), a chemotherapeutic agent known to cause immune dysfunction and mucosal damage. In this model, we performed a series of analyses, including H&E staining, measurement of hematological parameters and serum cytokines/immunoglobulins, quantification of fecal short-chain fatty acids (SCFAs) by gas chromatography, and profiling of gut microbiota composition via 16S rRNA gene amplicon sequencing. The results showed that MN15965 supernatant enhanced TNF-α, IL-1β, and GM-CSF secretion in THP-1 cells, promoting M1 macrophage activation in vitro. In the in vivo model, MN15965 administration restored spleen and thymus tissue integrity and improved physiological indices, hematological parameters, and immunoglobulin levels. Furthermore, MN15965 increased fecal SCFAs, particularly butyric and valeric acid, increased gut bacterial diversity, and enriched potentially beneficial SCFA-producing taxa, including Lachnospiraceae and Eubacterium. These findings demonstrate that B. breve MN15965 alleviated CTX-induced immunosuppression by activating immune responses, regulating gut bacterial communities, and boosting SCFA production. Full article

Luminescent organic–inorganic Cu(I) halide hybrid molecular crystals exhibit remarkable structural diversity and photophysical properties, but their application in aqueous environments is often limited by insufficient stability. Herein, we report portable and reusable photoluminescent sensors based on Cu(I)–I triethylenediamine derivatives [Cu₄I₆(pr-ted)₂] and [Cu₃I₅(bz-ted)₂] (pr-ted = 1-propyl-1,4-diazabicyclo[2.2.2]octan-1-ium; bz-ted = 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium). Their submicrometric particles exhibit intense UV-excited emissions and high photoluminescence quantum yields but limited water stability. To address this limitation, ultrasound sonication was employed to control particle size and produce stable suspensions that can be incorporated into polymeric matrices via 3D printing with photocurable resins or polylactic acid (PLA) films by drop-casting, yielding mechanically robust composites that retain their structural and optical properties. The devices used act as selective turn-off luminescent sensors for Fe³⁺ in aqueous media, with nanomolar detection limits (1.33–1.58 nM) below regulatory thresholds for drinking water. Moreover, [Cu₃I₅(bz-ted)₂] enables tetracycline detection in river water with a limit of detection of 0.038 nM. Mechanistic studies indicate that reversible photoinduced electron transfer is the primary quenching pathway, while composites maintain sensing performance over multiple reuse cycles. Full article

Currently, the main method for producing the vitamin C precursor 2-keto-l-gulonic acid (2-KLG) is a two-step fermentation process, in which secondary sterilization and fermentation processes result in higher costs and energy consumption. Consequently, the development of a one-step fermentation process is seen as a more desirable approach for 2-KLG production. In this study, we used Gluconobacter oxydans WTF0512 and Ketogulonicigenium vulgare WTF0114 as co-cultured strains for the production of 2-KLG from d-sorbitol via one-step fermentation. The fermentation behaviors of G. oxydans WTF0512 and K. vulgare WTF0114 were initially investigated. Subsequently, the fermentation process and medium were optimized, and the titer of 2-KLG reached 132.99 ± 0.52 g/L, with a molar conversion rate of 92.42%, which, to the best of our knowledge, is the highest production via one-step fermentation reported to date. These findings will provide a basis for developing a more economical large-scale one-step fermentation process for the production of 2-KLG. Full article

Olive tree (Olea europaea L.) is a major Mediterranean crop, valued for both fruit yield and high-quality oil, yet extreme summer stress, including high temperature, intense irradiance, and water limitation, can substantially reduce productivity and affect oil composition. The objective of the present study was to evaluate the mitigating efficacy of foliar applications of glycine betaine (GB), kaolin (K), and calcium carbonate (CC) under rainfed conditions across three Greek sites on “Koroneiki” (in two sites) and “Lianolia Kerkyras” (in one site) cultivars. Treatments were applied during the summer, and effects on fruit yield, oil content per fruit, oil yield per tree, and key oil quality parameters—including total phenols, flavonoids, antioxidant capacity, and fatty acid composition—were assessed. GB significantly enhanced fruit yield and oil production for “Koroneiki” at the site with the harshest environmental conditions (24.37 Kg fruits per tree and 4.69 Kg of oil per tree compared to 19.16 Kg fruits per tree and 3.48 Kg of oil per tree in control). In contrast, K proved most effective at the other two sites for both cultivars (43% and 52.8% increase in fruit yield and oil mass per tree in “Koroneiki” respectively and 30% as well as 34% increase in yield and oil mass per tree in “Lianolia Kerkyras”, respectively. CC exhibited limited impact on both productivity and quality. Under all treatments, the oils produced could be classified as extra virgin olive oils, with the products exhibiting minor effects on the functional properties of the oils. These findings indicate that the efficacy of stress-alleviating foliar treatments is strongly influenced by both environmental conditions and cultivar. Overall, K was the most effective treatment, followed by GB. Tailored application of these treatments represents a sustainable approach to maintaining olive productivity and preserving oil quality in the context of climate change. Full article

Producing single-cell protein (SCP) from syngas-derived ethanol and acetate offers a sustainable solution to global protein shortages, yet microbial utilization mechanisms for these mixtures remain underexplored. This study establishes a systematic bioconversion strategy using Cyberlindnera jadinii TU389. To mitigate acetaldehyde accumulation during ethanol metabolism, we engineered the strain TU546 to overexpress acylating acetaldehyde dehydrogenase (ADA6). TU546 achieved a maximum biomass of 46.7 g/L and a protein yield of 21.69 g/L, representing enhancements of 28.16% and 23.02% over the wild-type, respectively. Transcriptomic analysis revealed extensive metabolic reprogramming. In the C2 assimilation pathway, upregulated aldehyde dehydrogenase and acetyl-CoA Synthetase 1 accelerated acetate conversion to acetyl-CoA, while downregulated pyruvate decarboxylase and alcohol dehydrogenase minimized carbon flux loss. The upregulation of tricarboxylic acid cycle enzymes, the glyoxylate shunt, and acyl-coA oxidase improved carbon skeleton retention. Moreover, the upregulation of transaminases and N-acetylglutamate synthase, synergized with intensified cell proliferation signaling, redirected amino acid metabolism toward a synthesis-enhanced and degradation-controlled paradigm. This synergistic regulatory network drives the high-efficiency bioconversion of ethanol and acetate into SCP, establishing a molecular mechanistic foundation for the valorization of syngas-derived C2 substrates in biological macromolecule production. Full article

Microalgae and cyanobacteria are photosynthetic microorganisms capable of removing nutrients from eutrophic waters and producing biomass. Therefore, the aim of this study was to evaluate the bioremediation performance of three microalgae and one cyanobacterium native to Lake Xochimilco and to assess their potential for biofuel production (biodiesel and biogas) from biomass generated. In photobioreactors, ammonium (96.61–97.06%), nitrate (82.4–100%), and phosphate (83.95–89.71%) were effectively removed from the lake water. The specific growth rates ranged from 0.041 to 0.144 d⁻¹ and biomass productivities from 0.016 to 0.049 g L⁻¹ d⁻¹, with high biomass yield on the substrate. The estimated CO₂ fixation rates ranged from 0.024 to 0.092 g L⁻¹ d⁻¹. Chlorella sp. achieved the highest yield of fatty acid methyl esters (FAMEs) with 91.24% of the extracted lipids. Overall, saturated FAMEs were predominant in the biodiesel; however, the presence of monounsaturated FAMEs such as methyl palmitoleate and methyl oleate enhances their fluidity and oxidative stability. Synechocystis sp. and Chlorella sp. produced the most biogas using biomass after lipid extraction, at 429.5 L kg⁻¹ VS and 404.9 L kg⁻¹ VS, respectively, with over 60% biomethane. These strains represent a sustainable and promising possibility for water bioremediation and generating biofuels. Full article

Yogurt represents a traditional fermented dairy product characteristic of the Balkan Peninsula and is widely consumed in the Republic of Bulgaria. The aim of the present study was to develop omega-3-enriched yogurt. Four yogurts were produced: one control sample and three experimental variants enriched with chia oil (0.63%), cod liver oil (1.55%), and algal oil (1.10%). Coriander essential oil (0.038%) was added to each oil formulation. The products were monitored on days 1 and 14 of storage. The oils were pre-encapsulated in alginate beads to limit oxidative processes and preserve sensory properties. Yogurt samples were evaluated for oxidative stability, fatty acid composition, microbiological parameters, physicochemical properties, textural and sensory characteristics. Titratable acidity, pH, water-holding capacity, antioxidant activity, and microbiological parameters were not significantly affected by the incorporation of encapsulated oils. In contrast, significant differences were observed in texture and sensory attributes among the enriched variants. The chia oil sample exhibited the highest oxidative stability, followed by the algal oil yogurt, whereas the lowest stability was observed in the cod liver oil variant; however, all products remained within acceptable oxidation limits up to day 14. Approximately 350 g, 260 g, and 120 g of yogurt enriched with chia, cod liver, and algal oil, respectively, were required to meet the recommended daily omega-3 intake. The developed products demonstrated potential as dairy foods enriched with omega-3 fatty acids, with improved nutritional value. Full article