Search Results (31)

The development of simple and yet accurate formulations of frequency–amplitude relationships for non-conservative nonlinear oscillators is an important issue. The present paper is concerned with integral-type frequency–amplitude formulas in the dimensionless time domain and time domain to accurately determine vibrational frequencies of nonlinear oscillators. The novel formulation is a balance of kinetic energy and the work during motion of the nonlinear oscillator within one period; its generalized formulation permits a weight function to appear in the integral formula. The exact values of frequencies can be obtained when exact solutions are inserted into the formulas. In general, the exact solution is not available; hence, low-order periodic functions as trial solutions are inserted into the formulas to obtain approximate values of true frequencies. For conservative nonlinear oscillators, a powerful technique is developed in terms of a weighted integral formula in the spatial domain, which is directly derived from the governing ordinary differential equation (ODE) multiplied by a weight function, and integrating the resulting equation after inserting a general trial ODE to acquire accurate frequency. The free parameter is involved in the frequency–amplitude formula, whose optimal value is achieved by minimizing the absolute error to fulfill the periodicity conditions. Several examples involving two typical non-conservative nonlinear oscillators are explored to display the effectiveness and accuracy of the proposed integral-type formulations. Full article

The human exposome, including dietary exposures such as pesticides, additives, and environmental contaminants, plays a critical role in shaping the gut microbiota (GM) and long-term health outcomes. While the Mediterranean Diet is known for its health-promoting effects, the role of food quality, specifically organic vs. conventional products, in modulating GM within this dietary pattern remains underexplored. The aim of this study was to evaluate (1) whether an Italian Mediterranean Organic Diet (IMOD) confers additional benefits compared to an Italian Mediterranean non-Organic Diet (IMnOD), and (2) the impact of IMOD and IMnOD versus a free diet (No Diet) on GM and anthropometric parameters. A randomized, controlled trial was conducted on 39 healthy subjects. Eligible subjects were divided into the following groups: (1) 4 weeks No Diet, (2) 4 weeks IMOD, and (3) 4 weeks IMnOD. Microbiota profiling (16S rRNA sequencing), body composition (BIA), and dietary adherence (MEDAS, FFQ) were evaluated. Distinct microbial shifts following both IMOD and IMnOD compared to No Diet were revealed. Several taxa previously associated with short-chain fatty acid (SCFA) biosynthesis (i.e., Anaerobutyricum hallii, Anaerostipes hadrus, and Dorea longicatena) were increased after both Mediterranean Diet interventions, while Parabacteroides distasonis showed a specific increase in the IMOD group. No significant changes in body weight or composition were observed. These findings suggest that adherence to a Mediterranean Diet, regardless of food source, reshapes the gut microbiota, while organic food intake may influence specific microbial trajectories. Our results support the relevance of food quality in dietary interventions. Full article

Photosynthetic bacteria exhibit significant bioremediation potential and resource recycling characteristics, rendering them valuable candidates for sustainable wastewater treatment applications. Sea cucumber boiling broth (SCBB) contains high concentrations of organic compounds and nutrient salts, whose indiscriminate discharge poses serious environmental risks. This study aimed to evaluate a photosynthetic bacterium capable of effectively treating SCBB, which was isolated from the intertidal sediment samples. The bacterial strain was identified using 16S rDNA sequencing, and optimal growth conditions, including light, pH, and temperature, were determined. Finally, a small-scale trial was conducted in a fed-batch fermenter. The results showed that 16S rDNA analysis placed this strain in the Chromatiaceae family, forming a distinct lineage from the closest related species Marichromatium purpuratum and M. gracile, and was tentatively named Marichromatium sp. DYYC01. The strain exhibited optimal growth under anaerobic conditions at 30 °C, light intensity of 100 μmol photons/m²/s, and pH 7.0. Batch culture experiments demonstrated maximum biomass accumulation (OD₆₆₀ = 0.831) in SCBB medium with an initial COD loading of 3913 mg L⁻¹, concomitant with significant nutrient removal efficiencies: 76.45% COD, 55.82% total nitrogen (TN), and 56.67% total phosphorus (TP). Scaling up to fed-batch fermentation enhanced bioremediation performance, achieving removal rates of 83.13% COD, 72.17% TN, and 73.07% TP with enhanced growth (OD₆₆₀ = 1.2). This study reveals Marichromatium sp. DYYC01’s exceptional halotolerance in high-salinity organic wastewater treatment. The strain’s capacity for simultaneous biomass production and efficient nutrient recovery from hypersaline processing effluent positions it as a promising candidate for developing circular bioeconomy strategies. Full article

Biological research traditionally relies on experimental methods, which can be inefficient and hinder knowledge transfer due to redundant trial-and-error processes and difficulties in standardizing results. The complexity of biological systems, combined with large volumes of data, necessitates precise mathematical models like ordinary differential equations (ODEs) to describe interactions within these systems. However, the practical use of ODE-based models is limited by the need for curated data, making them less accessible for routine research. To overcome these challenges, we introduce LazyNet, a novel machine learning model that integrates logarithmic and exponential functions within a Residual Network (ResNet) to approximate ODEs. LazyNet reduces the complexity of mathematical operations, enabling faster model training with fewer data and lower computational costs. We evaluate LazyNet across several biological applications, including HIV dynamics, gene regulatory networks, and mass spectrometry analysis of small molecules. Our findings show that LazyNet effectively predicts complex biological phenomena, accelerating model development while reducing the need for extensive experimental data. This approach offers a promising advancement in computational biology, enhancing the efficiency and accuracy of biological research. Full article

In this study, we collected soybean inter-root soil (clay soil) from the cold region of Heilongjiang Province, China, screening for cold-tolerant phosphorus- and potassium-solubilizing bacteria by the gradient-cooling-directed screening and design of mixed bacterial agents. This study screened cold-tolerant phosphorus-solubilizing and potassium-solubilizing bacteria by gradient-cooling-directed screening and constructed mixed bacterial agents. We analyzed the strain’s phosphorus/potassium solubilizing capacity, as well as its organic acid secretion ability, to reveal its mechanism of detoxification of phosphorus and potassium. Clay soil from the cold region of Heilongjiang, China, was collected for soybean potting trials. The soybean pot experiment was used to investigate the growth-promoting effects of cold-tolerant strains applied to soybeans and to analyze the effects of changes in soil bacterial activity on soybean growth. A dominant phosphorus-solubilizing bacteria strain P-5 (Pantoea ananatis) was screened, and the amount of phosphorus-solubilizing bacteria was 34.94 mg/L with a PSI (Phosphorus Solubilization Index) of 1.80 for 7 days of incubation at 15 °C. The OD₆₀₀ value (optical density of 600 nm) on the 10th day was 0.61. The dominant potassium-solubilizing bacteria, K-1 (Rahnella aquatilis), solubilized 23.02 mg/L of potassium under the same culture conditions, with a KSI (Potassium Solubilization) of 1.51 and an OD₆₀₀ value of 0.59 on day 10. The dominant mixed bacterial agents H-5 (25% P-5 and 75% K-1), designed with the above two, detoxified phosphorus at 62.58 mg/L and potassium at 37.59 mg/L under the same culture conditions. It was shown that P-2 secretes gluconic acid and P-5 secretes lactic acid to degrade insoluble phosphorus at low temperatures and that K-1 secretes citric acid to degrade insoluble potassium. The soybean pot experiment study showed that the application of phosphorus-solubilizing bacteria (PSB), potassium-solubilizing bacteria (KSB), and mixed bacterial agents (MSB) alone could enhance the relative abundance of Pseudomonas, Rhizobium, and other bacterial genera in the soybean planting soil, compared with the control treatment without bacterial agents (BLK). Indirectly, they can enhance the accumulation of phosphorus and potassium in various organs of soybean, promote the development of soybean leaves and stems, and achieve the effect of promoting production and increasing income. This study has important theoretical value for the replacement of chemical fertilizer application by microbial agents in the cold region of China, and it has important practical and strategic significance for the promotion of income green safety in China’s main grain-producing areas. Full article

Background/Objectives: Transanal irrigation (TAI) has been recognized as a safe and effective treatment for neurological bowel dysfunction, chronic constipation or fecal incontinence and has also been proposed for patients with low anterior resection syndrome (LARS). The aim of the present systematic review was to evaluate the feasibility and effectiveness of TAI in patients with significant LARS symptoms. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines in addition to the Cochrane Handbook for Systematic Reviews of Interventions. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023436839). The risk of bias was assessed using a modified version of the Downs and Black checklist. The main outcome was improvement in low anterior resection syndrome after TAI assessed by change in LARS score. Results: After an initial screening of 3703 studies, 9 were included and underwent qualitative synthesis (among them, 3 were randomized clinical trials). All studies recorded an improvement in LARS score following TAI procedure and almost all studies showed an improvement in other bowel function outcomes (Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI, ), Cleveland Clinic Incontinence Score (CCIS), visual analog scale (VAS), Cleveland Clinic Florida Fecal Incontinence Score (CCFFIS), fecal incontinence score (FI score), Obstructed Defecation Syndrome (ODS) score) and quality of life (QoL) scores. The discontinuation rate ranged from 0% to 41%. The rate of adverse events was high (from 0 to 93%); moreover, no uniformity was found in the various protocols used among the different studies. Conclusions: The results of this review show that TAI is effective in the treatment of LARS, improving the LARS score, the other bowel function outcomes and the QoL scores. The absence of a treatment protocol validated by the scientific community is reflected in the high disparity in terms of adverse events and discontinuation of therapy, in addition to representing an intrinsic limitation to the study itself. Full article

Obesity is an emerging public health problem. Chronic low-grade inflammation is considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, and several cancer entities. Most preliminary studies on obesity-induced immune responses have been conducted in male rodents. Sex-specific differences between men and women in obesity-induced immune dysregulation have not yet been fully outlined but are highly relevant to optimizing prevention strategies for overweight-associated complications. In this study, we fed C57BL/6 female vs. male mice with either standard chow or an obesity-inducing diet (OD). Blood and spleen immune cells were isolated and analyzed by flow cytometry. Lean control mice showed no sex bias in systemic and splenic immune cell composition, whereas the immune responses to obesity were significantly distinct between female and male mice. While immune cell alterations in male OD mice were characterized by a significant reduction in T cells and an increase in myeloid-derived suppressor cells (MDSC), female OD mice displayed preserved T cell numbers. The sex-dependent differences in obesity-induced T cell dysregulation were associated with varying susceptibility to body weight gain and fatty liver disease: Male mice showed significantly more hepatic inflammation and histopathological stigmata of fatty liver in comparison to female OD mice. Our findings indicate that sex impacts susceptibility to obesity-induced T cell dysregulation, which might explain sex-dependent different incidences in the development of obesity-associated secondary diseases. These results provide novel insights into the understanding of obesity-induced chronic inflammation from a sex-specific perspective. Given that most nutrition, exercise, and therapeutic recommendations for the prevention of obesity-associated comorbidities do not differentiate between men and women, the data of this study are clinically relevant and should be taken into consideration in future trials and treatment strategies. Full article

Postbiotics possess various functional activities, closely linked to their source bacterial strains and preparation methods. Therefore, the functional activities of postbiotics need to be evaluated through in vitro and in vivo methods. This study aims to prepare a postbiotic and explore its antihemolytic, anti-inflammatory, antioxidant, and antibacterial activities. Specifically, a postbiotic preparation named PostbioP-6 was prepared by intercepting 1–5 kDa of Lacticaseibacillus paracasei Postbiotic-P6 fermentation broth. The results demonstrate that PostbioP-6 exhibited notable biological activities across multiple assays. It showed significant antihemolytic activity, with a 4.9–48.1% inhibition rate at 10–50% concentrations. Anti-inflammatory effects were observed both in vitro, where 8–40% PostbioP-6 was comparable to 259.1–645.4 μg/mL diclofenac sodium, and in vivo, where 3.5 and 4.0 μL/mL PostbioP-6 significantly reduced neutrophil counts in inflamed zebrafish (p < 0.05). Antioxidant properties were evident through increased reducing power (OD₇₀₀ increased from 0.279 to 2.322 at 1.25–12.5% concentrations), DPPH radical scavenging activity (38.9–92.4% scavenging rate at 2.5–50% concentrations), and hydroxyl radical scavenging activity (4.66–10.38% scavenging rate at 0.5–4% concentrations). Additionally, PostbioP-6 demonstrated antimicrobial activity against two Gram-positive bacteria, eight Gram-negative bacteria, and one fungus. Furthermore, PostbioP-6 significantly inhibited the increase in peroxide value and malondialdehyde content in cookies, highlighting its potential application in food preservation. In conclusion, we prepared a novel postbiotic, termed PostbioP-6, which proved to have prominent anti-hemolytic, anti-inflammatory, antioxidant, and broad-spectrum antimicrobial activities. The multifunctional properties of PostbioP-6 position it as a potentially effective functional food supplement or preservative. In the future, further research is necessary to elucidate the precise mechanisms of action, identify the active components, and validate its biological activities in animal models or clinical trials. Full article

Streptococcosis caused by Streptococcus agalactiae (S. agalactiae) is a major bacterial disease affecting the production of Nile tilapia (Oreochromis niloticus L.), causing significant economic losses due to mortality in the growing phase. Vaccination is the most effective method for preventing streptococcosis on Nile tilapia farms. In Brazil, the major tilapia-producing regions have long production cycles (6–10 months) and harvest tilapias weighing over 900 g for fillet production. Thus, data on the duration of the humoral immune response and protection in farmed tilapia have not been reported or are poorly described. Furthermore, the efficiency of serological testing for the long-term monitoring of immune responses induced by vaccination against S. agalactiae has never been addressed. This study evaluated the duration of protection and humoral immune response induced in Nile tilapia vaccinated against S. agalactiae until 300 days post-vaccination (dpv). The immunization trial was composed of two groups: vaccinated (Vac), vaccinated intraperitoneally with a commercial vaccine, and unvaccinated (NonVac) group, injected fish with sterile saline solution. At 15, 30, 150, 180, 210, and 300 dpv, blood sampling was conducted to detect anti-S. agalactiae IgM antibodies using indirect Enzyme-Linked Immunosorbent Assay (ELISA), and the fish were challenged with pathogenic S. agalactiae to determine the duration of vaccine protection through relative percentage survival (RPS). Spearman’s rank correlation was performed between the ELISA optical density (OD) of vaccinated tilapia and the duration of vaccine protection (RPS). The mean cumulative mortality in NonVac and Vac groups ranged from 65 to 90% and less than 35%, respectively. The average RPS was 71, 93, 94, 70, 86, and 67% at 15, 30, 150, 180, 210, and 300 dpv, respectively. RPS revealed that the vaccine provided protection from 15 to 300 dpv. The specific anti-S. agalactiae IgM antibody levels were significantly higher in the Vac group than that non-Vac group up to 180 dpv. The vaccinated fish exhibited significant protection for up to 10 months after vaccination. There was a positive correlation between the antibody response and RPS. This study revealed that a single dose of commercial vaccine administered to Nile tilapia can confer long-term protection against S. agalactiae and that indirect ELISA can monitor the duration of the humoral immune response for up to six months following vaccination. Finally, vaccine protection over six months can be associated with other components of the fish immune system beyond the humoral immune response by IgM antibodies. Full article

We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate and germline targeting priming immunogen. Production was carried out via transient expression in the human embryonic kidney 293 (HEK293) cell line followed by a combination of purification techniques. A large-scale cGMP (200 L) production run yielded 354 mg of the purified eOD-GT8 60mer drug product material, which was formulated at 1 mg/mL in 10% sucrose in phosphate-buffered saline (PBS) at pH 7.2. The clinical trial material was comprehensively characterized for purity, antigenicity, glycan composition, amino acid sequence, and aggregation and by several safety-related tests during cGMP lot release. A comparison of the purified products produced at the 1 L scale and 200 L cGMP scale demonstrated the consistency and robustness of the transient transfection upstream process and the downstream purification strategies. The cGMP clinical trial material was tested in a Phase 1 clinical trial (NCT03547245), is currently being stored at −80 °C, and is on a stability testing program as per regulatory guidelines. The methods described here illustrate the utility of transient transfection for cGMP production of complex products such as glycosylated self-assembling nanoparticles. Full article

Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual’s quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort. Full article

Maize is a globally important cereal and fodder crop. Accurate monitoring of maize planting densities is vital for informed decision-making by agricultural managers. Compared to traditional manual methods for collecting crop trait parameters, approaches using unmanned aerial vehicle (UAV) remote sensing can enhance the efficiency, minimize personnel costs and biases, and, more importantly, rapidly provide density maps of maize fields. This study involved the following steps: (1) Two UAV remote sensing-based methods were developed for monitoring maize planting densities. These methods are based on (a) ultrahigh-definition imagery combined with object detection (UHDI-OD) and (b) multispectral remote sensing combined with machine learning (Multi-ML) for the monitoring of maize planting densities. (2) The maize planting density measurements, UAV ultrahigh-definition imagery, and multispectral imagery collection were implemented at a maize breeding trial site. Experimental testing and validation were conducted using the proposed maize planting density monitoring methods. (3) An in-depth analysis of the applicability and limitations of both methods was conducted to explore the advantages and disadvantages of the two estimation models. The study revealed the following findings: (1) UHDI-OD can provide highly accurate estimation results for maize densities (R² = 0.99, RMSE = 0.09 plants/m²). (2) Multi-ML provides accurate maize density estimation results by combining remote sensing vegetation indices (VIs) and gray-level co-occurrence matrix (GLCM) texture features (R² = 0.76, RMSE = 0.67 plants/m²). (3) UHDI-OD exhibits a high sensitivity to image resolution, making it unsuitable for use with UAV remote sensing images with pixel sizes greater than 2 cm. In contrast, Multi-ML is insensitive to image resolution and the model accuracy gradually decreases as the resolution decreases. Full article

Ripretinib, a novel tyrosine kinase inhibitor used in advanced gastrointestinal stromal tumors (GIST) resistant to standard therapies, was assessed in the United Kingdom (UK) within an Expanded Access Program (EAP). A retrospective review of patients treated between January 2020 and October 2021 within the ripretinib EAP in our Institution was conducted. Clinician-documented and mRECIST 1.1 assessments were collected. The primary endpoints were progression-free survival (PFS) and time to treatment discontinuation (TTD). Treatment beyond progression (TBP), overall survival (OS), objective response rates and safety data were also analyzed. Survival curves were constructed using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were performed. All analyses were performed with R software. Overall, forty-five patients were included. After a median follow-up of 24.2 (95% CI 19.7–29.7) months, the median PFS of the group receiving 150 mg ripretinib once daily (OD) was 7.9 (95% CI 5.6–19.3) months. In the cohort of 22 patients with dose escalation upon tumor progression to 150 mg ripretinib twice daily (BD), the median PFS from BD was 5.4 (95% CI 2.8–9.3) months. Overall, median PFS and OS values for patients on ripretinib were 9.7 (95% CI 8.3–18.1) and 14.0 (95% CI 9.9–NA) months, respectively. TTD was similar to PFS. TBP was observed in about one third of all patients. Objective responses to ripretinib OD and BD treatments were observed in 16.7% and 10.0% of the patients, respectively. No new safety signals were identified. In conclusion, patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials. Full article

Background: With promising outcomes, platelet-rich plasma (PRP) has recently been suggested as a treatment for olfactory dysfunction (OD). Methods: Clinical studies utilizing PRP in OD caused by COVID-19, trauma, anesthetic exposure, viral infection, and chronic rhinosinusitis were included in a systematic review. Results: Ten clinical studies were qualitatively analyzed. Six of these studies used the PRP for OD caused by COVID-19, one on OD after functional endoscopic sinus surgery, and three on post-infectious or post-trauma OD. The population included 531 patients, ranging in age from 15 to 63. Conclusion: The use of PRP may be a risk-free and efficient therapeutic option with very encouraging outcomes. Indeed, it enhances olfactory perception in patients who not only exhibit COVID-19 infection aftereffects, but also in those who have lost their sense of smell due to trauma, rhinosinusitis, rhinitis, or even surgery. To evaluate the PRP’s therapeutic benefits in OD patients and to compare the efficacy of different therapeutic protocols with regard to treatment schedules, there is an urgent need for focused controlled trials. Full article

The impact of yttrium 90 radioembolization (Y90-RE) in combination with immune checkpoint inhibitors (ICIs) has recently gained attention. However, it is unclear how sequencing and dosage affect therapeutic efficacy. The purpose of this study was to develop a mathematical model to simulate the synergistic effects of Y90-RE and ICI combination therapy and find the optimal treatment sequences and dosages. We generated a hypothetical patient cohort and conducted simulations to apply different treatments to the same patient. The compartment of models is described with ordinary differential equations (ODEs), which represent targeted tumors, non-targeted tumors, and lymphocytes. We considered Y90-RE as a local treatment and ICIs as a systemic treatment. The model simulations show that Y90-RE and ICIs administered simultaneously yield greater benefits than subsequent sequential therapy. In addition, applying Y90-RE before ICIs has more benefits than applying ICIs before Y90-RE. Moreover, we also observed that the median PFS increased up to 31~36 months, and the DM rates at 3 years decreased up to 36~48% as the dosage of the two drugs increased (p < 0.05). The proposed model predicts a significant benefit of Y90-RE with ICIs from the results of the reduced irradiated tumor burden and the associated immune activation and suppression. Our model is expected to help optimize complex strategies and predict the efficacy of clinical trials for HCC patients. Full article