Biopharmaceuticals, such as antibody therapeutics, are produced by culturing mammalian cells with chemically defined media that consist of more than 50 synthesized components. The screening of medium components related to culture performance and the subsequent optimization of the composition are required in the development of new modalities, host cells, and culture methods. Screening the components to be optimized is typically labor-intensive. The easiest approach is media blending, which creates variations in the concentrations of the components with only liquid mixing. However, a workflow for systematically determining experimental conditions (i.e., how to blend media) has not been established. Therefore, we reassessed media blending from a mathematical perspective and proposed a workflow for the first time. In the workflow, we evaluated the use of a commercially available chemically defined media to maximize simplicity and applicability. From a mathematical perspective, we clarified that multicollinearity is an inevitable challenge in both experimental design and its analysis. Under the constraint, we showed that one of the most appropriate experimental conditions could be systematically calculated and selected by applying D-optimal design focusing on the principal components. We performed a case study of cell culture to screen medium components under 120 experimental conditions using 11 chemically defined media designed for Chinese Hamster ovary cells. The case study provided a reasonable set of components that explained the variance in viable cell concentrations, which range from 5.8 to 19.4 (× 106) cells/mL. Finally, our mathematical redefinition also enabled the design of a dedicated media set for media blending. KEY POINTS: • The constraints in media blending were clearly explained. • A systematic workflow from blending design to analysis was proposed. • The workflow also enabled the design of a dedicated media set for media blending.

The growing demand for sustainable and efficient water treatment solutions underscores the importance of high-quality activated carbon (AC) derived from renewable resources. In this study, AC was produced from sugarcane bagasse using sulfuric acid as an activating agent. A hybrid approach combining experimental design and advanced computational modeling was employed to optimize the production process and model the relationship between operational parameters and AC yield. A Box-Behnken design was used to systematically investigate the effects of four key variables: temperature, activation time, raw material-to-activating agent ratio, and acid concentration. The generated experimental data were used to develop and compare predictive models based on response surface methodology (RSM), support vector machine (SVM), and artificial neural networks (ANNs). All models demonstrated strong predictive capabilities, with ANN achieving R=0.989±0.003, outperforming SVM (R=0.950±0.004), while RSM showed a slightly higher overall fit (R=0.996±0.002). This study demonstrates that integrating experimental design with machine learning techniques enhances both the precision and efficiency of process optimization. The proposed approach offers a robust, scalable, and sustainable pathway for producing high-quality AC from agricultural waste, with significant potential for industrial applications in environmental remediation and water purification technologies.

Laser engraving of elements for injection molds is a technology that allows precise and durable engraving of various details on the surface of the molds. This method uses a focused laser beam to remove material from the mold surface, creating high-resolution patterns, text or codes. This study investigates the influence of various parameters on the laser engraving process, utilizing factorial experimental design to systematically analyze their effects. The parameters considered include power, speed, frequency, number of cuts, stepover, focal distance, and engraving strategy. The objective function of the study is the processing time, which is critical for optimizing efficiency in laser engraving applications. By employing a factorial approach, we aim to identify the interactions between these factors and their collective impact on processing time. The results indicate that certain parameters significantly affect the engraving efficiency, providing insights into optimal settings for enhanced performance. This research contributes to the understanding of laser engraving dynamics and offers practical guidelines for practitioners seeking to improve operational efficiency in laser-based manufacturing processes. Due to the high precision, and flexibility, laser engraving allows the creation of fine and very complex details with high efficiency and durability.

Irritable bowel syndrome (IBS) is a common gut-brain interaction disorder, prevalent in the general population. Current medication treatments often leave patients undertreated. Therefore, more and more IBS patients are choosing complementary and alternative medicines for treatment, especially Chinese medicine (CM). However, the therapeutic benefits of CM for IBS have not been well-accepted, and some scholars have attributed the effects of CM to a "placebo effect". It is generally recognized that different placebos could lead to different effects, and that the CM placebo effect is especially high. We think CM treatment responses may be obscured by high, non-specific placebo responses in clinical trials, and thus it is difficult to demonstrate successful treatment effects in a research setting. Thus, ascertaining the magnitude of the CM placebo effect will provide valuable support for accurately understanding CM therapeutic benefits. This study aims to evaluate the placebo and nocebo effects of CM (Tiao-Chang Ke-Min granules, TCKM) in diarrhea-predominant IBS (IBS-D) treatment. We plan to use a balanced experimental design embedded in a randomized controlled trial to investigate CM placebo and nocebo effects. This design involves two essential factors: participants' expectations regarding their treatment and the treatment that they actually receive. This balanced design enables the researchers to control the factor of participants' treatment expectations. We use a semi-scripted description of group assignment to elicit participants' expectations regarding IBS-D treatment. Eligible participants will be randomized into 4 groups at a ratio of 1:1:1:1, and receive either TCKM granules or placebo granules. The treatment duration will be 4 weeks. The primary outcome is the proportion of IBS Severity Scoring System responders at the end-of-treatment. The secondary outcomes include individual symptoms, adequate relief, quality of life, and anxiety and depression. This trial has been reviewed and approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2021-082-01). To our knowledge, this will be the first trial to investigate CM placebo and nocebo effects in the IBS population. Therefore, this trial may have a real impact on clinical studies and routine practice in the relevant fields. Chinese Clinical Trial Registry (ChiCTR2300067549), registered on 11 January 2023.

Background: The efficiency of vermicomposting in reducing antibiotic resistance genes (ARGs) in dairy manure may be compromised by co-pollutants like arsenic (As) and microplastics. Specifically, plasmids serving as carriers and vectors of ARGs were largely distributed in this process. However, the impact of As and microplastics on plasmids carrying ARGs during vermicomposting is largely unknown. Methods: This study utilized a controlled experimental design and applied plasmid metagenomics to investigate the individual and combined effects of As and polyethylene terephthalate (PET) microplastics on plasmid-mediated ARG dynamics during vermicomposting. Results: We found that vermicomposting alone mainly enriched non-mobilizable plasmids, while PET microplastics selectively promoted conjugative and mobilizable plasmids, whereas As significantly increased all plasmid types. Moreover, both PET or As alone and combined exposure (PET and As) increased total ARG abundance, with their combination inducing synergistic ARG enrichment despite unchanged total plasmid abundance. Furthermore, co-occurrence network analysis combined with ARGs/plasmid ratio assessments demonstrated that As influences ARGs through co-selective pressure by enriching ARGs co-localized with As resistance genes (e.g., the ars operon) on plasmids while simultaneously promoting horizontal gene transfer (HGT) via activation of oxidative stress and SOS response pathways. In contrast, PET primarily facilitates ARG dissemination through a “metabolism-resistance” coupling strategy by enriching colonizing bacteria with PET-degrading capacity. Their co-exposure formed As-enrichment hotspots on PET microplastic surfaces, functioning as a “super-mixer” that selectively screened for superbugs carrying potent resistance mechanisms (e.g., blaOXA-50 and mdtB/mdtE). Conclusions: This study provides the first plasmidome-level evidence of synergistic ARG propagation by As and PET microplastics during vermicomposting, highlighting mobile genetic elements’ critical role in co-pollutant risk assessments.

This study evaluated the effect of commercial and artisanal feed treated with the hormone 17-alpha-methyltestosterone on the sex reversal of tilapia (Oreochromis niloticus) in the Soconusco region of Chiapas, Mexico. A completely randomized experimental design was implemented with three treatments: hormone-treated artisanal feed (T1), hormone-treated commercial feed (T2), and a control group of mixed organisms without hormone treatment (T3), each with three replicates. The fry was fed for 28 days under controlled conditions, and the percentage of males was subsequently determined by direct gonadal analysis. The results showed masculinization rates of 93% in T1, 78% in T2, and 67% in T3. Statistical analysis using the chi-square test revealed significant differences between treatments (χ² = 12.47; p < 0.05), confirming the greater efficacy of the artisanal feed, possibly associated with better hormone fixation and stability during natural evaporation and refrigerated storage. The results demonstrate that artisanal feed containing 17-alpha-methyltestosterone at 60 mg/kg is a technically viable and low-cost alternative for producing monosex tilapia populations, highlighting the need to standardize preparation processes to optimize reproductive efficiency and environmental safety in tropical aquaculture systems. It is adoption can strengthen the productive efficiency and profitability of aquaculture systems, offering an accessible option for producers in the Soconusco region.

Human intracranial recordings, and single neuron recordings in particular, have provided much knowledge on the mechanisms of human cognition and its impairment by disease. Improvements in recording technology, experimental design, and computational analysis methods have permit increasingly sophisticated understandings of uniquely human brain processes, including those underlying executive function, memory, and language. Despite the routine clinical use of intracranial recordings for invasive epilepsy monitoring in the pediatric population, there remains a significant gap between the associated research conducted in adult and pediatric neuroscientific investigation. Single neuron recordings in pediatric epilepsy patients are ethical, technically feasible, and safe. These data can provide mechanistic insights into the neurophysiology of the developing human brain. Routine use of invasive electrophysiological monitoring via SEEG studies in pediatric drug-resistant epilepsy offers opportunities to extend the utility of single neuron recordings to the pediatric population and advance our knowledge of the neuronal basis of behaviors in children.

Rethinking drought memory in crops: a call for improved experimental design.

Aquaculture wastewater contains elevated levels of nutrients and organic pollutants that can accelerate eutrophication and impair aquatic ecosystems if discharged untreated. In the study, a fungal-based remediation approach was investigated for the removal of pollutants from aquaculture wastewater collected from Baltim Station ponds (31.55244° N, 31.092855° E) near Lake Burullus, Egypt. Two native fungal isolates, Aspergillus niger and Aspergillus flavus, were employed for primary mycoremediation experiments, while Ganoderma mbrekobenum was included only in the Plackett–Burman experimental design to evaluate the influence of environmental and nutritional factors on total phosphorus (TP) removal under optimized conditions. The fungal treatment significantly improved water quality, showing substantial reductions in total protein, phosphorus, nitrogen, organic matter, and chemical oxygen demand (COD) indicating a vital role of Aspergillus species in the bioremediation of nutrient-rich aquatic environments. The Plackett–Burman design (PBD) showed that fungal treatment significantly reduced pollutant concentrations with higher metabolic activity and enzymatic production as dehydrogenase and total protein from 9 to 12 days. Moreover, PBD identified KH2PO4 and MgSO₄ as the most influential variables for enhancing TP removal in the presence of G. mbrekobenum, while peptone and yeast extract exhibited the greatest effect in the non-fungal control system. The regression models demonstrated strong predictive accuracy (R2 > 0.99), confirming the validity of the optimization approach. The results highlight the effectiveness of fungal biomass as a cost-effective and eco-friendly bioremediation strategy for mitigating nutrient pollution in aquaculture effluents and protecting sensitive aquatic environments such as Lake Burullus.

This study aimed to investigate the effects of varying organic fertilizer substitution ratios on soil nutrients, organic matter, enzyme activities, and microbial communities, with the goal of optimizing fertilization strategies, enhancing soil fertility, and promoting sustainable agricultural development. Experimental Design: A three-year consecutive field experiment was conducted using an equal nitrogen application design with the following treatments: no fertilizer control (CK), conventional farmer fertilization (CF), and organic fertilizer substitutions at 10% (SF1), 20% (SF2), 30% (SF3), 40% (SF4), and 50% (SF5) of chemical fertilizer. Key soil parameters were analyzed, including available nutrients (alkali-hydrolyzable nitrogen, available phosphorus, and available potassium), organic matter content, enzyme activities (e.g., urease and phosphatase), and microbial community structure (bacterial and fungal diversity and abundance). Results: Partial substitution with organic fertilizer significantly enhanced soil available nutrient content and organic matter levels, with the 30–50% substitution treatments (SF3–SF5) demonstrating particularly pronounced effects. Moreover, organic fertilizer amendments markedly improved soil enzyme activities and altered microbial community composition, notably increasing the abundance of beneficial taxa such as Gemmatimonadota. These modifications further facilitated soil nutrient cycling and utilization efficiency. Conclusions: The findings demonstrate that appropriate organic fertilizer substitution not only improves soil fertility but also enhances microbial activity, thereby creating a healthier soil environment for crop growth. This study provides critical theoretical and practical insights for optimizing fertilization regimes, reducing chemical fertilizer reliance, and improving soil ecosystem functionality.

Objectives: The aim of this experiment was to explore how the addition of Schizochytrium powder to the feeding ration affected the production performance, egg quality, and antioxidant function of chickens. Schizochytrium powder is a unicellular spherical marine microalga that can be cultivated through heterotrophic fermentation, with characteristics including rapid cell growth, stable composition, and ease of large-scale production. Experimental design: Three hundred and twenty 33-week-old chickens with similar egg production rates and body weights were selected and randomly divided into four groups, with five replicates each and 16 hens in each replicate. The control group (Group I) was fed a corn–soybean meal basal diet, while the test groups were supplemented with 0.5% (Group II), 1.0% (Group III), and 2.0% (Group IV) Schizochytrium powder on top of this basal diet, respectively. The pretest period was 1 week, and the main test period was 8 weeks. The results revealed the following: (1) Compared with Group I, the average daily feed intake (ADFI) and laying rate (LR) were significantly lower (p < 0.05) in Group IV, and there was no significant difference (p > 0.05) in the ADFI and LR between Groups II and III. (2) Compared with Group I, the eggshell strength (ES) and docosahexaenoic acid (DHA) content of Groups II, III, and IV were significantly higher (p < 0.05). (3) Compared with Group I, serum triglyceride (TG) content was significantly decreased (p < 0.05), and serum low-density lipoprotein (LDL) content was significantly increased (p < 0.05) in Groups II, III, and IV. Serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and peroxidase (PO) activities were significantly higher (p < 0.05) and serum malondialdehyde (MDA) content was significantly lower (p < 0.05) in Groups II, III, and IV compared to Group I. In conclusion, adding Schizochytrium powder to the feeding ration could affect chickens’ production performance, increase egg DHA content, and improve the antioxidant capacity of the organism. Based on the results of this study, we recommend a ratio of 1.0% Schizochytrium powder addition.

Introduction Content moderators safeguard the ever-growing online realm by reviewing and filtering out harms, yet are themselves subject to the risk of psychological concerns. Method This study explored the psychological outcomes of content moderators (N = 311) who were offered a resilience training program called The TaskUs Method 2.0 from baseline to 18 months. Participants completed psychometric screeners for resilience, burnout, secondary traumatic stress, compassion satisfaction, and perceived stress. For the analyses, three timepoints were identified to follow participants across the study period based on their tenure–T0 (0–3 months tenure), T1 (5–10 months), and T2 (11–16 months tenure). Results Findings from the entire sample (regardless of whether participants had data for all three timepoints) revealed that secondary traumatic stress and perceived stress did not differ significantly between timepoints. However, burnout, compassion satisfaction and resilience showed small yet significant decline between T0 and T2. With a reduced sample of only those having data for all three timepoints, similar trends remained although the rate of change from T0 to T1 did not differ significantly from that of T1 to T2 for any of the variables. Discussion Results indicated that participants in the program showed no significant increases in secondary traumatic stress, the main target of the program. Across the different psychometrics, effect sizes were small suggesting that content moderators using the program were not at significant risk for increased psychological distress from content moderation during the study duration. These findings provide a valuable foundation for further refining interventions aimed at content moderators. Future studies may consider experimental and multifactorial designs to delve into therapeutic mechanisms and different types of psychological outcomes.

Investigation of structural and thermal properties of solid lipid-based nanocarriers optimized by microfluidic synthesis.

This study investigated the psychological attitude of primary school teachers towards retirement in Kaura Local Government Area of Kaduna State, Nigeria. The study specifically examined the effect of pre-retirement counselling on teachers’ psychological attitude towards retirement. A true experimental design was adopted, involving 40 primary school teachers randomly assigned to experimental and control groups. The instrument used for data collection was the Pre-Retirement Counselling and Attitude of Primary School Teachers Questionnaire (PCAPSTQ), which was validated by experts and had a reliability coefficient of 0.84 using Cronbach Alpha. The experimental group received an eight-week pre-retirement counselling intervention, while the control group was exposed to a placebo. Data collected were analyzed using mean, standard deviation, and independent sample t-test at 0.05 level of significance. Findings revealed that the experimental group recorded a higher post-test mean score (x̅ = 30.10) compared to the control group (x̅ = 18.90), with a mean difference of 11.20. The t-test result (t(38) = 5.95, p < 0.05) indicated a significant effect of pre-retirement counselling on teachers’ psychological attitude towards retirement. The study concluded that pre-retirement counselling effectively enhances teachers’ psychological readiness for retirement by reducing anxiety and fostering positive attitudes. It was recommended that Kaduna State Universal Basic Education Board (SUBEB) institutionalize pre-retirement counselling for teachers to ensure emotional preparedness, mental well-being, and successful post-retirement adjustment.

Abstract In inertial confinement fusion plasmas, the Trapped Particle Instability (TPI) significantly influences energy transfer dynamics in stimulated Raman scattering and two plasmon decay. This study introduces a relativistic theoretical framework that addresses the limitations of the classical Kruer-Dawson-Sudan model under weakly relativistic temperature conditions where trapped electron velocity is comparable to the speed of light. By integrating relativistic corrections to particle dynamics and wave interactions, the new model achieves improved accuracy in predicting TPI growth rates compared to the KDS model. The relativistic TPI dispersion relation, derived from the Vlasov-Poisson system, incorporates velocitydependent bounce frequency modifications, the Maxwell-Jüttner distribution for particle dynamics, resolving the growth rate discrepancies in δkλD and decay trends observed in non-relativistic models, where δk denotes the difference between the sideband wave number and the EPW (Electron Plasma Wave) wave number, and λD is the Debye length. Simulations confirm the framework’s accuracy by solving sideband growth rates triggered by externally driven electron plasma waves, validating TPI-induced electron trapping mechanisms. The model also correctly predicts TPI growth rate dependencies on the
amplitude and the wavenumber of EPW, establishing the necessity of relativistic physics in modeling TPI under high-energy-density conditions and offering a foundational tool for refining plasma instability theories and guiding inertial confinement fusion experimental designs.

Objective This study aims to investigate the exercise programs that are more suitable for obese college students. Methods A randomized controlled experimental design was used to randomly divide 57 obese college students into Baduanjin combined resistance training group (BRTG, n = 19), resistance training group (RTG, n = 19), and control group (CG, n = 19). Results 1) After an 8-week intervention, BMI, PBF, and VFI of BRTG and RTG significantly decreased, while MM significantly increased; Meanwhile, PBF and MM of BRTG were significantly lower than that of RTG. 2) The SDNN, RMSSD, and HFnorm of BRTG and RTG were significantly increased after intervention, and LFnorm and LF/HF of BRTG and RTG were significantly decreased; Meanwhile, LFnorm and LF/HF of BRTG were significantly lower than RTG, while HFnorm was significantly higher than RTG. 3) The TC, TG, and LDL-C of BRTG and RTG were significantly decreased, while HDL-C was significantly increased after intervention. 4) Compared with single resistance training, Baduanjin combined with resistance training intervention is more conducive to enhancing the subjective exercise experience and compliance of obese college students. Conclusion Moderate-intensity aerobic combined with resistance training is a more suitable exercise program for obese college students and has greater application potential in health promotion.

Purpose. Determination of the optimal unit operating parameters and molybdenum content in the coating. To achieve optimal performance and proper physico-mechanical properties, it was necessary to conduct a full factorial experiment. Methods. The chosen factors were: asymmetry coefficient, cathode current density within the range of 20–60 A/dm 2 , and Molybdenum disulfide concentration within the range of 0.2–3.4 kg/m 3 . The resulting function chosen was microhardness. Since preliminary research indicated that the response functions should be nonlinear, the factors had three variation levels. An orthogonal central composite second-order design was used to find the polynomial coefficients. The significance of the regression coefficients was checked using Student's t-test, and the adequacy of the obtained equations was verified using Fisher's F-test. Results. As a result of the conducted experiments and statistical data processing, a regression equation in coded form was obtained, linking the coating's microhardness with the studied parameters. Analysis of the coefficient significance showed that the MoS 2 concentration has the greatest influence on microhardness. The interaction effects of the factors were also statistically significant. The calculated value of Fisher's criterion was F = 3.87, which is lower than the tabulated value (Ftab = 19.4) at a 95 % significance level. Consequently, the obtained regression equation adequately describes the electrodeposition process within the studied region. Conclusion. The method of mathematical experiment planning was successfully applied to optimize the process of electrodeposition of coatings alloyed with Molybdenum disulfide. An adequate second-order regression equation was obtained, linking the coating's microhardness with the asymmetry coefficient, cathode current density, and MoS 2 concentration. The results of the work allow for recommending optimal coating application regimes for their use in conditions of increased wear and corrosion.

Intriguing results from “choice blindness” (CB) experiments have shown that when people make choices, but are presented with a false outcome, many seem not to notice the mismatch and even provide reasons for choices they never made. They appear to be “blind” about their intentions. Yet, this effect goes against decision-making accounts and experience, in which we regularly notice outcomes that do not match our choices (e.g., when ordering food). Here, we ask whether participants really fail to detect the manipulation, or whether CB can be accounted for by covert detection , in that participants detect changes, but do not report them. To test this, we measured pupil dilation during the experiments to quantify objective responses in addition to reports by participants. In both experiments, we consistently observed that participants failed to report detected mismatches. Moreover, we observed increased pupil dilation during all manipulated trials, irrespective of whether they were reported or not. Thus, we provide conclusive evidence of covert detection in CB. In addition, we show that CB is strongly modulated by the idiosyncrasies of the experimental design. Our results cast doubt on the general validity of CB, and with that on key conclusions of previous studies. Instead, our results suggest no failure of detection, but instead higher-level, cognitively or socially driven hesitance of reporting. Our evidence leads us to a cautious discussion of CB and provides an account that no longer violates our intuitions about human intentionality and rationality, in that participants are less introspectively blind than originally portrayed.

NAFLD is an important cause of liver disease in India. During the past century, dramatic modifications in lifestyle have radically changed the health priorities in most areas of the world, owing to a growing incidence of non-communicable disease. Fatty liver has earlier often been related with excessive alcohol consumption. During the past 20 years, the interest in fatty liver occurring in non-drinkers i.e. non-alcoholic fatty liver disease (NAFLD) has raised quickly. Methods A prospective experimental study design without control group.Patients will be collected from the In-patient and Out-patient Departments, Peripheral Centres, Rural Health Camps and Medical Camps conducted by Vinayaka Mission’s Homoeopathic Medical College and Hospital Result This study provides evidence to say that, there is significant reduction in the Non-alcoholic fatty liver disease after giving homoeopathic constitutional medicine

This study investigates the impact of exposure to thin-ideal and average-body images on social media on body image among female college students in Mainland China and Hong Kong, China, while exploring the potential moderating role of self-compassion. Employing a mixed experimental design, 191 participants were randomly distributed to one of four conditions: thin-ideal bodies, average bodies, landscapes (mood control), or eyeglasses (neutral control). Body image was assessed pre- and post-exposure using the Body Image States Scale (BISS), and self-compassion was measured via the Self- Compassion Scale (SCS). Results from repeated-measures ANOVA indicated a significant interaction between image type and time, with thin-ideal images reducing body satisfaction and average-body images enhancing it. Contrary to hypotheses, self- compassion did not significantly moderate these effects. The findings align with social comparison theory, highlighting the divergent effects of idealized versus realistic body portrayals. While self-compassion did not buffer against negative impacts, the study underscores the importance of promoting diverse body representations on social media to generate healthier body perceptions among young women. Limitations and cultural considerations are discussed, with recommendations for future research to explore longitudinal and contextual factors.