Previous research identifies residual pulmonary vascular obstruction (RPVO) as an independent risk factor for venous thromboembolism (VTE) recurrence and a predictor of poor outcomes, yet its risk factors and prognostic impact remain unclear. This study developed predictive models combining clinical and metabolic biomarkers to identify high-risk RPVO patients, offering clinically actionable guidance for optimizing anticoagulation therapy. This retrospective study analyzed 363 acute pulmonary embolism (APE) patients (2018.1-2024.12) with ≥3-month follow-up. We developed comprehensive and simplified RPVO predictive models by identifying risk factors and assessing long-term outcomes. The models, incorporating metabolomic biomarkers from baseline blood samples, were validated in a prospective APE cohort (2024.12-2025.2). Multivariable analysis identified five independent RPVO predictors: 1) affected lobes on V/Q scan, 2) sPESI score, 3) pulmonary artery pressure, 4) recent surgery/immobilization, and 5) active cancer. Both the comprehensive and simplified predictive models showed excellent discrimination (kappa > 0.6) in training, validation, and prospective cohorts. Metabolomic analysis revealed azelaic acid and L-3-phenyl lactate as key differentiating metabolites, whose inclusion enhanced model performance. Notably, RPVO presence and extensive lung involvement (≥6 lobes) independently predicted adverse outcomes (recurrent VTE, cardiopulmonary failure, or mortality). We developed comprehensive and simplified RPVO prediction models incorporating five clinical predictors and two metabolic biomarkers (azelaic acid and L-3-phenyl lactic acid), significantly improving model performance. RPVO independently predicted adverse outcomes, highlighting the clinical value of combined clinical and molecular profiling.

The rising demand for health-promoting beverages, kombucha presents significant opportunities for scientific innovation and commercial growth. Symbiotic culture of bacteria and yeast (SCOBY), which includes acetic acid bacteria (AAB), lactic acid bacteria (LAB), and several yeast species, plays a major role in kombucha fermentation. During fermentation, kombucha produces bioactive compounds mainly catechins, theaflavins, tannins, and organic acids that enhance health efficacy and probiotic properties, supporting gut health and non-communicable disease prevention. The present study emphasizes, nutritional qualities of kombucha through different Komagataeibacter starter cultures and alternative substrates such as herbal infusions and fruit extracts. This review also highlights the role of AAB, LAB, and Yeast in the production mechanism of the kombucha beverage by the different microbial strains of microbial species and the fibril network of bacterial cellulose. This study further explains the bioactivities in the human body, especially mechanisms of action in the intestine through fundamental signaling pathways such as PIK3-AKT, MAPK, NFκB, PPARγ, and JAK-STAT. Therapeutic efficacy of kombucha, including various substrate-based antioxidants, antimicrobials, synergistic impact, delivery mechanism of anticancer, anti-diabetic insulin, and glycaemic responses, regulations of inflammatory markers (ILs) in anti-obese properties, has also been reviewed. Further, it is necessary to develop the advanced kombucha beverage qualities through metagenomics, metabolomics. Future studies should address these research gaps to ensure controlled microbial and probiotic stability, validate metabolites availability, and explore innovative applications for improved functionality and shelf-life.

Tryptanthrin is a natural indole-quinazoline alkaloid and a major component of the traditional blue dye indigo naturalis (IN). Although oral administration of IN has shown therapeutic effects in patients with ulcerative colitis and evidence supports its anti-inflammatory activity, its development as a drug has been limited. We hypothesized that ingested IN could engage in biomimetic reactions with human microbial metabolites, particularly reactive monoamines, leading to the formation of anti-inflammatory products. Under acid-promoted and elevated-temperature conditions, tryptanthrin selectively reacted with tryptamine to yield spirocyclic compound 1 rather than a typical imine. Kinetic evaluation revealed that endogenous organic acids, such as short-chain fatty acids and lactic acid, promoted this reaction at body temperature in aqueous solvent systems. Analogous transformations with other endogenous indole monoamines, including serotonin, 5-methoxytryptamine, and the xenobiotic indoleamine 5-chlorotryptamine, afforded spirocyclic adducts 2-4, respectively, and their kinetic data supported a chemically plausible reaction pathway. Compounds 1-4 retained anti-inflammatory activity by reducing IL-1β secretion associated with inflammasome activation in stimulated macrophages while maintaining favorable passive membrane permeability. Collectively, the formation of spirocyclic adducts of tryptanthrin with indole monoamines under biomimetic conditions provides chemical novelty and scaffold diversification without compromising druglike physicochemical properties.

Electrochemical biosensors are becoming increasingly prevalent across medical, food, and bioprocessing industries for monitoring complex biological processes. However, their sensitivity to contamination and exposure to potentially hazardous biological species often necessitates single-use disposal, contributing to the release of high-value, high-demand, and environmentally damaging materials into the environment. This study investigates the feasibility of a closed-loop recycling process for single-use glucose biosensors, with a focus on the recovery and reuse of noble metals silver and gold. Guided by ecodesign principles and using low-impact materials, we developed a silver screen ink, gold syringe ink, and a poly(lactic acid) (PLA) substrate. Sensors were fabricated by additive manufacturing and screen printing—enabling the scalability afforded by screen printing to produce the high-coverage silver layer while also minimising gold ink waste using additive manufacturing. A low-energy recovery method that exploited selective solvent compatibility was developed to reclaim silver and gold. Second-generation devices were then fabricated, demonstrating performance comparable to commercial equivalents while achieving an 80% reduction in material usage, cost, and environmental impact across 16 categories using a life cycle assessment (LCA).

Schisandra is a plant whose fruit possesses high biological potential and beneficial health effects. The pharmacological properties of Schisandra are attributed to its bioactive components, primarily polyphenols and polysaccharides. This study aimed to obtain Schisandra fruit extracts (SCE) from different locations in China and Poland, as well as Schisandra polysaccharides (SPO), and to compare their chemical composition and selected biological activities. The prebiotic and antibacterial effects of SCE and SPO on lactic acid bacteria (LAB), human and foodborne pathogens, and gut microbiota were investigated. The chemical composition of the three Chinese SCE was similar, whereas SCE from Poland (SCE-PL) differed. The main bioactive compounds differentiating the Chinese SCE were quercetin, isorhamnetin, and nicotiflorin, while gamma-tocopherol and mevalonic acid distinguished SCE-PL, as indicated through LC-QTOF-MS/MS metabolomic profiling. All SCE and SPO promoted the growth of LAB strains, confirming their prebiotic potential and ability to serve as effective carbon sources for LAB. Additionally, all SCE inhibited the growth of certain pathogens, with S. chinensis extract from China showing the strongest activity, whereas SPO did not exhibit such activity. Variations in chemical composition among SCE and SPO contribute to differences in their prebiotic and antimicrobial activity, highlighting the importance of species and geographical origin in determining their functional properties.

This research compared the physicochemical, rheological, microbiological, and sensory parameters of lactose and lactose-free buttermilk. They were obtained by whipping cream and converting high-fat cream. The analysis also involved fermented dairy drinks based on lactose and lactose-free buttermilk. They included starter microbiota of different compositions. The samples of buttermilk obtained by converting high-fat cream demonstrated relatively low mass fractions of protein, fat, solids, titrated acidity, and clot viscosity. The composition of the starter microflora affected the clot viscosity and moisture-retaining ability, which depended on the amount of microbial polysaccharide producers in the starter and solids in the buttermilk. The fermented buttermilk contained from 0.6 to 0.7% lactic acid. However, 70–90% lactose in the lactose buttermilk sample was not hydrolyzed and remained in its native form. Lactose-free buttermilk contained monosaccharides, and the content of glucose was by 27 ± 6% less than that of galactose. Bacterial concentrates MSTt, Bifilact-U, and Bifilact-AD provided a high level of starter culture microorganisms (108–109 CFU/cm3). The best sensory profile belonged to the fermented dairy product based on both lactose and lactose-free buttermilk with the content of probiotic microorganisms ranging between (2.7 ± 0.3) × 106 and (4.3 ± 0.6) × 106 CFU/cm3. This optimal sample was obtained with the bacterial concentrate Bifilact-AD, which both contained lactic acid and probiotics. Lactose-free buttermilk demonstrated a high potential for functional fermented dairy drinks fortified with probiotics.

Liquid-Liquid Equilibrium of Quaternary Systems: Experimental Data and NRTL Model Predictions for Water, Lactic Acid, 1-Octanol, and Salts

Perennial ginseng (Panax ginseng) has long been valued for its medicinal properties. However, ginseng sprouts are gaining prominence as a versatile food source due to the high levels of bioactive compounds in their leaves and stems. To further enhance their functional value, this study investigated the effects of fermentation using lactic acid bacteria, specifically Lactobacillus and Enterococcus strains, on the antioxidant and anti-inflammatory potential of ginseng sprout extract (GSE). Chemical analyses revealed that fermentation significantly increased total phenolic content (TPC) and ginsenoside Rb1 levels, which were associated with enhanced radical-scavenging activity and superoxide dismutase (SOD)-like activity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, fermented GSE (FGSE) exhibited significantly greater anti-inflammatory effects than non-fermented GSE. This enhancement was evidenced by marked downregulation of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 (PGE2), along with their corresponding enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Notably, the anti-inflammatory profile of FGSE was distinguished by its ability to suppress specific cytokines that were not significantly affected by GSE. Although both GSE and FGSE attenuated interleukin-1beta (IL-1β) and interleukin-6 (IL-6), only FGSE achieved statistically significant inhibition of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). These findings indicate that fermentation is a critical process for surpassing the efficacy threshold of GSE against key inflammatory signals. Overall, the enrichment of bioactive metabolites during fermentation suggests that FGSE can serve as a potent functional ingredient for modulating inflammatory responses, with considerable potential for the development of advanced functional foods.

Development and characterization of hybrid hemp and sisal fiber reinforced poly lactic acid composites for sustainable engineering applications

The acidic tumor microenvironment (TME) in solid tumors, driven by abnormal metabolism and lactic acid accumulation, suppresses chimeric antigen receptor-T (CAR-T) cell efficacy while posing safety risks from on-target, off-tumor toxicity (OTOT). This study aims to develop a novel CAR-T technology that leverages lactic acid as a tumor-specific trigger to achieve precise control of CAR activity. The objective is to enable adaptation to the acidic TME while maintaining robust anti-tumor efficacy and mitigating OTOT. We engineered a lactic acid-responsive promoter (LARP) using RNA sequencing-identified lactic acid-sensitive genes. This promoter was integrated into HER2-targeting CAR to construct LAR CAR-T cells. CAR expression dynamics under acidic vs neutral conditions were quantified via flow cytometry. Phenotypic profiling (memory markers), in vitro cytotoxicity, and cytokine secretion were assessed. In vivo OTOT was evaluated in our previously constructed humanized HER2 mice, while anti-tumor efficacy and OTOT were further tested in this mouse model bearing tumors. Our findings demonstrate that the LARP responds to lactic acid, leading to increased CAR expression in acidic conditions. The ex vivo-expanded LAR CAR-T cells exhibited an enhanced memory phenotype and superior tumor-killing capacity in vitro under acidity. In vivo, LAR CAR-T cells achieved tumor eradication comparable to conventional CAR-T cells and exhibited significantly enhanced safety profiles, characterized by the absence of acute hepatotoxicity and minimal off-target organ toxicity. Our LARP strategy exploits tumor acidity as a precise low/high switch for CAR-T cells. By restricting potent CAR expression to the acidic TME while minimizing activity in normal tissues, LAR CAR-T overcomes key barriers of efficacy and OTOT in solid tumors. This lactic acid-sensing paradigm offers a clinically translatable platform for precise immunotherapy.

Kombucha tea fermentation is driven by microbial consortia composed of yeasts, acetic acid bacteria (AAB) and lactic acid bacteria (LAB), whose metabolic interactions determine the product’s functional and sensory characteristics. This study focused on the isolation and characterization of cultivable microorganisms from kombucha tea and the reassembly of four defined communities to evaluate their contribution to the chemical composition of the beverage based on the physicochemical parameters and multivariate analysis (PCA) of sugars, organic acids and ethanol. Microbial isolates, identified in this study, belonged to yeast (Saccharomyces cerevisiae and Brettanomyces bruxellensis), AAB (Novacetimonas hansenii, Komagataeibacter europaeus, Komagataeibacter intermedius and Acetobacter pasteurianus) and LAB (Liquorilactobacillus nagelii). Selected strains were combined to reassemble simplified communities. Fermentation trials demonstrated that community composition markedly influenced metabolite production and acidification (acetic acid and ethanol concentration ranged from 0.30 ± 0.08 and 2.29 ± 0.03 g/L, and from not determined to 27.31 ± 3.41 g/L, respectively). Consortia combining yeasts, AAB and LAB most closely reproduced the chemical composition of the original Kombucha tea, whereas simpler yeast–bacteria consortia produced chemically distinct beverages. Overall, these findings enhance our understanding of the ecological roles of kombucha-associated microorganisms and demonstrate that community composition is a key factor in shaping the chemical profile of the beverage. Moreover, the reassembly of defined microbial communities represents a promising strategy for selecting and applying functional microorganisms to valorize agri-food by-products through sustainable fermentation processes. Kombucha-derived communities, due to their ability to grow under acidic conditions, tolerate osmotic stress and metabolize complex sugar mixtures, could be versatile biofactories for the development of new fermented beverages or functional ingredients from low-value agri-food residues, contributing to circular bioeconomy strategies and waste reduction.

Antioxidant and anti-inflammatory effects of bioactive peptides derived from whey protein using lactic acid bacteria

Cross-stress adaptation enhances the survival and stability of freeze-dried lactic acid bacteria

Introduction and objective: Heat-killed lactic acid bacteria with postbiotic effects have emerged as promising functional food ingredients for promoting intestinal health. SakuloraTM, which consists of heat-killed Lacticaseibacillus paracasei strain Shidare (strain Shidare) isolated from weeping cherry blossom, may exert postbiotic effects on the gut microbiota. However, its impact on the intestinal environment and intestinal mobility remains unclear. Therefore, the present study investigated the efficacy of SakuloraTM on intestinal serotonin and fecal IgA concentrations in mice and bowel function in healthy adults through a randomized, double-blind, placebo-controlled trial. Methods: In the pre-clinical phase, mice were administered heat-killed strain Shidare, and intestinal serotonin and fecal IgA concentrations were assessed. Forty-four healthy adults with mild constipation were then randomly assigned to receive either SakuloraTM (containing 50 billion cells of the heat-killed strain Shidare) or a placebo daily for 2 weeks. The frequency of bowel movements in one week was used as the primary outcome. Results: In murine models, the administration of heat-killed strain Shidare significantly increased intestinal serotonin and fecal IgA concentrations. In the clinical trial, the weekly frequency of bowel movements was significantly higher in the SakuloraTM group than in the placebo group. No significant improvements were observed in the secondary endpoints, including the gut microbiota and fecal short-chain fatty acids. No serious adverse events developed throughout the study period. Novelty of the Study: The bowel movement-improving effect of the heat-killed strain Shidare was demonstrated for the first time, and its mechanism was suggested to be an increase in intestinal serotonin and IgA levels. Conclusions: SakuloraTM containing heat-killed strain Shidare effectively improved the bowel function, supporting its potential as a safe functional food ingredient for maintaining digestive health in healthy individuals. Trial Registration: UMIN-CTR: UMIN000054746 Keywords: Lacticaseibacillus paracasei; postbiotics; bowel function; intestinal environment

SERS signal unification strategy: Preparation of AuNPs@4-MBA and its quantitative detection in mixed lactic acid bacteria.

To investigate the safety of anagliptin/metformin combination tablets by evaluation of lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment. The participants of type 2 diabetes with creatinine-based eGFR (eGFRcr) of ≥45 and <60 (mL/min/1.73 m2) (Group G3a) received anagliptin/metformin combination LD tablets (anagliptin: 100 mg, metformin hydrochloride: 250 mg/tablet) twice a day for 4 weeks. After 4 weeks, they received anagliptin/metformin combination HD tablets (anagliptin: 100 mg, metformin hydrochloride: 500 mg/tablet) twice daily until after 16 weeks. The participants (Group G3b) with baseline eGFRcr ≥30 and <45 (mL/min/1.73 m2) received anagliptin/metformin combination LD tablets twice daily for 16 weeks. The serum lactic acid levels were examined at weeks 4, 8, and 16 after receiving anagliptin/metformin combination tablets. The change in serum lactic acid levels from baseline to 16 weeks was -0.09 [-0.28, 0.10] mmol/L (mean [95% confidence intervals]), not exceeding the pre-specified non-inferiority margin (0.7 mmol/L). No significant differences occurred in the change in serum lactic acid levels during all observation periods. Serum lactic acid levels exceeded 2.5 mmol/L in four participants (10.5%) and 5.0 mmol/L in one participant (2.6%) during the observation period. No participant had a plasma metformin exceeding 2.5 μg/mL. This study demonstrates that the fixed-dose combination of anagliptin and metformin can be used safely in patients with type 2 diabetes complicated by moderate renal dysfunction. The advantage of this fixed-dose combination is also considered to be very large.

Osteoarthritis (OA) is a prevalent degenerative and inflammatory disease posing a significant financial and medical burden on patients and society. Lactic acid, the terminal metabolite of glycolysis, is recognized as a pivotal signaling molecule governing diverse physiological and pathological processes, particularly in cancer and inflammatory diseases. Emerging evidence suggests that metabolic disorders are closely associated with OA, which may provide a metabolic lens for further exploring its mechanisms. Glycolytic reprogramming is now recognized as a hallmark of OA, leading to the pronounced accumulation of lactic acid within the joint microenvironment. This review synthesizes current evidence to elucidate the role of lactic acid in OA pathogenesis. We summarize the mechanism of glycolytic reprogramming in chondrocytes and macrophages under pathological conditions. Furthermore, we demonstrate that lactic acid exacerbates cartilage degeneration while simultaneously promoting inflammation resolution. These dual roles are mediated by extracellular acidification, HCAR1, and lactylation. Given that duality, we suggest that redirecting lactate flux presents considerable potential as a therapeutic approach for the prevention and management of OA.

A supplement, OPTIADE® DE, containing specific lactic acid bacteria, Enterococcus faecium WB2000, has been shown to provide significant ameliorative effects in patients. However, the mechanism of the supplement has not been elucidated. In this study, we investigated the mechanism of the supplement on dry eye symptoms using an air stress-induced dry eye mice. Stress-induced dry eye in mice was produced by exposing the mice to an air stream. OPTIADE® DE was administered for 5 days during the daily exposure to the air stress, and then the tear volume and the expression of specific mRNA were measured. Furthermore, the effects of WB2000 and the other nutritional ingredients were also investigated, respectively. The contribution of peroxisome proliferator-activated receptor α (PPARα) to the regulation of tear secretion was investigated by an inhibitor of PPARα. Exposure of the mice to air stress displayed a remarkable decrease in the tear volume with a concomitant reduction in the PPARα expression in the lacrimal gland. OPTIADE® DE significantly inhibited the decrease in the tear volume and the expression of the PPARα. WB2000 and the other nutritional ingredients additively inhibited the decrease in the tear volume. Inhibition of PPARα completely canceled the effects of the OPTIADE® DE and WB2000 without influencing the effect of the mixture of other nutritional ingredients on the tear volume. These results suggest that both the PPARα-dependent pathway and the independent pathway contributed to the ameliorative effect of OPTIADE® DE in the dry eye mice.

Gut microbiota and metabolic adaptations in apple snails Pomacea canaliculata: Insights into cold tolerance.

Effects of storage temperature on silage nutrient composition, fermentation profile, and aerobic stability through a meta-analysis.