Thiol-functionalized MOF modified 3D printed monolithic microextraction array for analysis of trace Cd and Pb in human urine.

Controlling the position, size, and shape of pores is a limitation of traditional monolithic preparation methods. The application of 3D printing technology offers high customizability, allowing the precise printing of pore positions, sizes, and shapes according to the designer's 3D model. Herein, by using Projection Microstereolithography (PµSL), we prepared a 3D-printed monolithic array with post-modification of thiol-functionalized metal-organic framework (MOF), and combined it with inductively coupled plasma mass spectrometry (ICP-MS) for the online analysis of trace Cd and Pb in human urine. To achieve array monolithic microextraction, six 3D-printed monolithic columns were modified with thiol-functionalized MOF-808 (MOF-808-SH), and were then assembled in the 3D printed extraction device incorporating gas valve and scaffold. The MOF-808-SH modified 3D-printed monolithic column exhibits excellent extraction performance to Cd2+ and Pb2+ due to rich active adsorption sites and hierarchical porous structure, and has long life span (>100 reused times). Under the optimized conditions, the limits of detection (LODs) are 3.5 and 17.6 ng L-1 for Cd2+ and Pb2+, respectively, with the relative standard deviations of 4.9 % and 8.2 % (0.1 µg L-1, n = 7), and the sample throughput is 11 h-1. To validate the accuracy of the method, the method was used to determine Cd and Pb in Certified Reference Materials of freeze-dried human urine, the determined results agree well with the certified values. This method was also successfully applied to the determination of trace Cd and Pb in real human urine samples. The developed method offers low LODs, robust anti-interference capability, high sample throughput, long reuse cycles, and automation analysis, showing great potential for the analysis of trace heavy metals in biological samples.

A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression.

Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.

Metagenomics reveals the characteristics and potential spread of microbiomes and virulence factor genes in the dairy cattle production system.

Virulence factor genes (VFGs) pose a potential threat to ecological security and animal health, and have attracted increasing attention in the livestock industry. As one of the primary livestock types, dairy cattle may be an important source of VFG transmission. However, the distribution, transmission, and evolution of VFGs in the gastrointestinal tract and surrounding environment of dairy cattle remain unclear. In the present study, a total of 263 samples were collected from cows, calves, colostrum, farm wastewater, and soil. Metagenomics was conducted to analyze changes in the microbiome and VFGs characteristics in these ecological niches. The VFGs of the cows showed distinct differences between the rumen and feces, and were influenced by the region. The dominant VFG hosts was regulated by their microbial structure. Colostrum administration of cows increased VFG abundance in their newborn calf feces sharply and Enterobacteriaceae became the primary host. While diet was the primary driving force for the temporal variation in calf VFGs. For samples of the surrounding environment, water and soil had higher VFG concentrations and were more structurally stable. Moreover, extensive interactions between the mobile genetic elements and VFGs and gene mobile analysis map based on metagenomic binning both displayed the potential horizontal transfer ability of VFGs in the cows and environment. Our study revealed the prevalence, diffusion, and regulatory factors of VFGs in dairy cattle production systems, providing novel insights into reducing livestock VFGs and limiting their spread.

Tranexamic Acid for the Treatment of Hyperpigmentation and Telangiectatic Disorders Other Than Melasma: An Update.

Tranexamic acid (TXA), a synthetic lysine analog, is a commonly used antifibrinolytic and procoagulant agent. Based on its good hemostatic efficacy, it is mainly used clinically for bleeding in trauma, various types of surgical and dental procedures and prevention of bleeding in patients with hemophilia. In recent years, studies have shown that TXA has the effects of anti-melanogenesis, anti-inflammation, anti-angiogenesis and promotes the recovery of the skin barrier, so it has been tried to be used as a treatment for hyperpigmentation and telangiectatic diseases. Oral, topical, intradermal injections and microneedling are all commonly used modes of administration. TXA for melasma is the most studied and has achieved indications in some countries, whereas it is still an off-label drug for many other dyschromia. We review the clinical use of TXA in hyperpigmentation and telangiectatic disorders other than melasma, such as post-inflammatory hyperpigmentation, Riehl's melanosis, rosacea, and post-acne erythema, to provide more evidence for the use of TXA in these disorders, and to provide safer and more cost-effective alternatives for the treatment of these diseases.

Maternal gastrointestinal microbiome shapes gut microbial function and resistome of newborns in a cow-to-calf model.

BACKGROUND: The maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring. RESULTS: The microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly. CONCLUSIONS: Our study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome. Video Abstract.

Identification of Key Volatile Compounds in Tilapia during Air Frying Process by Quantitative Gas Chromatography-Ion Mobility Spectrometry.

Air frying as a new roasting technology has potential for roasted fish production. In this study, the changes in volatile compounds (VCs) during air frying of tilapia were studied by quantitative gas chromatography-ion mobility spectrometry, followed by the identification of key VCs based on their odor activity value (OAV). There were 34 verified VCs, of which 16 VCs were identified as the key VCs with OAV ≥ 1. Most of the VCs were improved by air frying and peaked at 20 min. During the air frying, the total sulfhydryl content markedly decreased, while the protein carbonyl and MDA content significantly increased, suggesting the enhancement in the oxidation of lipids and proteins. The correlation network among the chemical properties and key VCs was constructed. The change in total sulfhydryl, protein carbonyl, and MDA showed significant correlation with most of the key VCs, especially 2-methyl butanal, ethyl acetate, and propanal. The results indicated that the oxidation of lipids and proteins contributed the most to the flavor improvement in air-fried tilapia. This study provides a crucial reference for the volatile flavor improvement and pre-cooked product development of roasted tilapia.

Occurrence and Ecological Risk Assessment of Highly Toxic Halogenated Byproducts during Chlorination Decolorization of Textile Printing and Dyeing Wastewater.

Textile printing and dyeing wastewater is a substantial source of highly toxic halogenated pollutants because of the chlorination decolorization. However, information on the occurrence and fate of the highly toxic halogenated byproducts, which are produced by chlorination decolorization of the textile printing and dyeing wastewater, is very limited. In this study, the occurrence of six categories of halogenated byproducts (haloacetic acids (HAAs), haloacetonitriles (HANs), N-nitrosamines (NAs), trihalomethanes, halogenated ketones, and halonitromethanes) was investigated along the full-scale treatment processes of textile printing and dyeing wastewater treatment plants. Furthermore, the ecological risk of the halogenated byproducts was evaluated. The results showed that the total concentration of halogenated byproducts increased significantly after chlorination. Large amounts of HAAs (average 122.1 µg/L), HANs (average 80.9 µg/L), THMs (average 48.3 µg/L), and NAs (average 2314.3 ng/L) were found in the chlorinated textile wastewater, and the results showed that the generations of HANs and NAs were positively correlated with the BIX and ß/α index, indicating that the HANs and NAs might form from the microbial metabolites. In addition, HAAs and HANs exhibited high ecological risk quotients (>1), suggesting their high potential ecological risk. The results also demonstrated that most halogenated byproducts could be effectively removed by reverse osmosis treatment processes except NAs, with a lower removal rate of 18%. This study is believed to provide an important theoretical basis for controlling and reducing the ecological risks of halogenated byproducts in textile printing and dyeing wastewater effluents.

Development of antifouling antibacterial polylactic acid (PLA) -based packaging and application for chicken meat preservation.

Microbial contamination is the leading cause of food spoilage and food-borne disease. Here, we developed a multifunctional surface based on polylactic acid (PLA) bioplastic with antifouling and antibacterial properties via a facile dual-coating approach. The surface was designed with hierarchical micro/nano-scale roughness and low surface energy. Bactericidal agent polyhexamethylene guanidine hydrochloride (PHMG) was incorporated to endow the film with bactericidal activity. The film had good superhydrophobic, antifouling and antibacterial performance, with a water contact angle of 154.3°, antibacterial efficiency against E. coli and S. aureus of 99.9 % and 99.6 %, respectively, and biofilm inhibition against E. coli and S. aureus of 63.5 % and 68.9 %, respectively. Synergistic effects of antibacterial adhesion and contact killing of bacteria contributed to the significant antibacterial performance of the film. The biobased biodegradable film was highly effective in preventing microbial growth when applied as antibacterial food packaging for poultry product, extending the shelf life of fresh chicken breast up to eight days.

Cross-modal deep learning model for predicting pathologic complete response to neoadjuvant chemotherapy in breast cancer.

Pathological complete response (pCR) serves as a critical measure of the success of neoadjuvant chemotherapy (NAC) in breast cancer, directly influencing subsequent therapeutic decisions. With the continuous advancement of artificial intelligence, methods for early and accurate prediction of pCR are being extensively explored. In this study, we propose a cross-modal multi-pathway automated prediction model that integrates temporal and spatial information. This model fuses digital pathology images from biopsy specimens and multi-temporal ultrasound (US) images to predict pCR status early in NAC. The model demonstrates exceptional predictive efficacy. Our findings lay the foundation for developing personalized treatment paradigms based on individual responses. This approach has the potential to become a critical auxiliary tool for the early prediction of NAC response in breast cancer patients.

Joint trajectory inference for single-cell genomics using deep learning with a mixture prior.

Trajectory inference methods are essential for analyzing the developmental paths of cells in single-cell sequencing datasets. It provides insights into cellular differentiation, transitions, and lineage hierarchies, helping unravel the dynamic processes underlying development and disease progression. However, many existing tools lack a coherent statistical model and reliable uncertainty quantification, limiting their utility and robustness. In this paper, we introduce VITAE (Variational Inference for Trajectory by AutoEncoder), a statistical approach that integrates a latent hierarchical mixture model with variational autoencoders to infer trajectories. The statistical hierarchical model enhances the interpretability of our framework, while the posterior approximations generated by our variational autoencoder ensure computational efficiency and provide uncertainty quantification of cell projections along trajectories. Specifically, VITAE enables simultaneous trajectory inference and data integration, improving the accuracy of learning a joint trajectory structure in the presence of biological and technical heterogeneity across datasets. We show that VITAE outperforms other state-of-the-art trajectory inference methods on both real and synthetic data under various trajectory topologies. Furthermore, we apply VITAE to jointly analyze three distinct single-cell RNA sequencing datasets of the mouse neocortex, unveiling comprehensive developmental lineages of projection neurons. VITAE effectively reduces batch effects within and across datasets and uncovers finer structures that might be overlooked in individual datasets. Additionally, we showcase VITAE's efficacy in integrative analyses of multiomic datasets with continuous cell population structures.

UV-Mediated Facile Fabrication of a Robust, Fully Renewable and Controllably Biodegradable Poly(lactic acid)-Based Covalent Adaptable Network.

A robust and fully biobased covalent adaptable network (CAN) that allows recyclability, biocompatibility, and controlled biodegradability is reported. The CAN was fabricated through a simple photo-cross-linking method, wherein low-molecular-weight poly(lactic acid) (∼3 kDa) was modified with end 1,2-dithiolane rings through a one-step Steglich esterification reaction with thioctic acid (TA). These incorporated 1,2-dithiolane rings undergo photoinduced ring-opening polymerization, thus enabling the cross-linking of poly(lactic acid) with abundant dynamic disulfide bonds. The resultant CAN demonstrates excellent transparency, effective UV-blocking capabilities below 320 nm, robust tensile strength (∼39 MPa), and superior dimensional stability at 80 °C, alongside attractive biocompatibility. Moreover, owing to the dynamic exchange and redox-responsiveness of disulfide bonds, the material can be recycled by hot-pressing and a reduction-oxidation process while also being capable of controllably biodegrading at the end of its lifecycle. Furthermore, it exhibits reconfigurable shape memory properties with fast recovery. This study elucidates a straightforward approach to fabricating multifunctional and sustainable polymer materials with potential applications in diverse fields such as packaging, coating, and biomedicine.

Identification of key physicochemical properties and volatile flavor compounds for the sensory formation of roasted tilapia.

Tilapia is suitable for industrial roasting production because of its good flavor and processing adaptability. In this study, the key physicochemical properties and volatile compounds for sensory formation of roasted tilapia were identified after roasting condition optimization. The highest sensory score was obtained at 215 °C, 45 min, and 4% oil. During roasting, the a*, b*, hardness, chewiness, and oxidation of proteins and lipids significantly increased, the moisture content decreased, and the myofibrillar protein aggregation was observed by scanning electron microscope. After identification and quantification by headspace-gas chromatography-ion mobility spectrometry, 10 compounds with odor active value ≥1 were selected as characteristic flavor compounds. The correlation network indicated that the sensory formation mainly resulted from Maillard reaction, myofibrillar protein aggregation, and improvement of pleasant volatile flavor compounds induced by oxidation of proteins and lipids and water loss. This study provides an important theoretical basis and technical support for roasted tilapia production.

Role of land-ocean interactions in stepwise Northern Hemisphere Glaciation.

The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth's surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Spray-Flame Synthesis of NASICON-Type Rhombohedral (α) Li1+xYxZr2-x(PO4)3 [x = 0-0.2] Solid Electrolytes.

Since solid electrolytes have a broad electrochemical stability window, are exceptionally electrochemically stable against Li metal, and function as a physical separator to prevent dendrite growth, they are at the forefront of alternate possibilities, further increasing the stability and energy density of Li-ion batteries. NASICON-type electrolytes are a promising candidate due to their negligible moisture sensitivity, which results in outstanding stability and a lower probability of Li2CO3 passivity under the ambient atmosphere. However, one of the most promising representatives, Li1+xYxZr2-x(PO4)3 (LYZP), has multiple stable phases with significant variation in their corresponding Li-ion conductivity. In this paper, we have successfully synthesized the highly ionically conductive rhombohedral phase of LYZP via spray-flame synthesis. Two different solvent mixtures (e.g., 2-ethyl hexanoic acid/ethanol, propanol/propanoic acid) were chosen to explore the effect of precursor composition and combustion enthalpy on the phase composition of the nanoparticle. The as-synthesized nanoparticles from spray-flame synthesis consisted of the crystalline tetragonal zirconia (t-ZrO2) phase, while lithium, yttrium, and phosphate were present on the nanoparticles' surface as amorphous phases. However, a short annealing step (1 h) was sufficient to obtain the NASICON phase. Moreover, we have shown the gradual phase conversion from orthorhombic ß phase to rhombohedral α phase as the annealing temperature increased from 700 °C to 1300 °C (complete removal of ß phase). In this context, Y3+ doping was also crucial, along with the appropriate solvent mixture and annealing temperature, for obtaining the much-desired rhombohedral α phase. Further, 0.2 at% Y3+ doping was added to the solvent mixture of 2-ethyl hexanoic acid/ethanol, and annealing at 1300 °C for 1 h resulted in a high ionic conductivity of 1.14∙10-5 S cm-1.

The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

Scale-inspired programmable robotic structures with concurrent shape morphing and stiffness variation.

Biological organisms often have remarkable multifunctionality through intricate structures, such as concurrent shape morphing and stiffness variation in the octopus. Soft robots, which are inspired by natural creatures, usually require the integration of separate modules to achieve these various functions. As a result, the whole structure is cumbersome, and the control system is complex, often involving multiple control loops to finish a required task. Here, inspired by the scales that cover creatures like pangolins and fish, we developed a robotic structure that can vary its stiffness and change shape simultaneously in a highly integrated, compact body. The scale-inspired layered structure (SAILS) was enabled by the inversely designed programmable surface patterns of the scales. After fabrication, SAILS was inherently soft and flexible. When sealed in an elastic envelope and subjected to negative confining pressure, it transitioned to its designated shape and concurrently became stiff. SAILS could be actuated at frequencies as high as 5 hertz and achieved an apparent bending modulus change of up to 53 times between its soft and stiff states. We further demonstrated both the versatility of SAILS by developing a soft robot that is amphibious and adaptive and tunable landing systems for drones with the capacity to accommodate different loads.

Characteristics of disinfection byproducts from dissolved organic matter during chlor(am)ination of source water in Tibetan Plateau, China.

The Tibetan Plateau, a typical high-altitude area, is less affected by human activities such as industrial development, and the external pollution to water sources is extremely low. Then it is also an important source of water samples for exploring the molecular characteristics of precursors in the dissolved organic matter (DOM) of disinfection byproducts (DBPs) in drinking water. Research data on DBPs in drinking water on the Tibet Plateau remains insufficient, leading to uncertainty about DBP contamination in the area. This study explores the formation potential of 35 typical DBPs, including 6 trihalomethanes (THMs), 9 haloacetic acids (HAAs), 2 halogenated ketones (HKs), 9 nitrosamines (NAs), and 9 aromatic DBPs, during chlorination and chloramination of typical source water samples in the Tibet Plateau of China. Moreover, in order to further investigate the characteristics of the generation of DBPs, the molecular composition of DOM in the collected water samples was characterized by Fourier transform ion cyclotron resonance mass spectrometry. The findings reveal that, for chlorination and chloramination, the average concentration of the five classes of DBPs was ranked as follows (chlorination, chloramination): HAAs (268.1 µg/L, 54.2 µg/L) > THMs (44.0 µg/L, 2.0 µg/L) > HKs (0.7 µg/L, 1.8 µg/L) > NAs (26.5 ng/L, 74.6 ng/L) > Aromatics (20.4 ng/L, 19.5 ng/L). The dominant compounds in THMs, HAAs, and NAs are trichloromethane, dichloroacetic acid, trichloroacetic acid, and nitrosopyrrolidine, respectively. This study highlights a significant positive correlation between DBP generation and UV254, SUV254, and the double bond equivalents of DOM in the source water. It systematically elucidates DOM molecular composition characteristics and DBP formation potential in high-altitude water sources, shedding light on key factors influencing DBP generation at the molecular level in high-altitude areas.

Identifying potential targets for preventing cancer progression through the PLA2G1B recombinant protein using bioinformatics and machine learning methods.

Lung cancer is the deadliest and most aggressive malignancy in the world. Preventing cancer is crucial. Therefore, the new molecular targets have laid the foundation for molecular diagnosis and targeted therapy of lung cancer. PLA2G1B plays a key role in lipid metabolism and inflammation. PLA2G1B has selective substrate specificity. In this paper, the recombinant protein molecular structure of PLA2G1B was studied and novel therapeutic interventions were designed to disrupt PLA2G1B activity and impede tumor growth by targeting specific regions or residues in its structure. Construct protein-protein interaction networks and core genes using R's "STRING" program. LASSO, SVM-RFE and RF algorithms identified important genes associated with lung cancer. 282 deg were identified. Enrichment analysis showed that these genes were mainly related to adhesion and neuroactive ligand-receptor interaction pathways. PLA2G1B was subsequently identified as developing a preventative feature. GSEA showed that PLA2G1B is closely related to α-linolenic acid metabolism. Through the analysis of LASSO, SVM-RFE and RF algorithms, we found that PLA2G1B gene may be a preventive gene for lung cancer.

Family participatory clown therapy in venipuncture in hospitalized children: A non-randomized controlled trial.

OBJECTIVE: To explore the effectiveness of family participatory clown therapy in venipuncture in hospitalized children. METHODS: We recruited 104 children aged 3 to 6 years for a non-randomized controlled trial from March to December 2022. All participants required peripheral venepuncture infusions for treatment. The children were assigned to either the control group (n = 52) or the experimental group (n = 52).Standard care was utilized in the control group. In the experimental group, two clown nurses and a parent provided family participatory clown therapy for 35-45 minutes per child before, during, and after venipuncture. We assessed children's pain (FLACC and W-B FPS), anxiety (VAS-A), medical fear (CFS), crying incidence, compliance, parental anxiety (S-AI), and parental satisfaction. RESULTS: At venipuncture, the FLACC score was lower in the experimental group (4.46±2.053) compared to the control group (5.96±2.441), the W-B FPS score was also lower in the experimental group (4.96±2.392) than in the control group (6.35±2.266), with a statistically significant difference (P<0.05).The children in the experimental group had lower levels of anxiety, medical fear, crying, and parental anxiety than the control group. In addition, child compliance and parent satisfaction were higher in the experimental group than in the control group, with statistically significant differences (P<0.05). CONCLUSION: Family participatory clown therapy can reduce pain, anxiety, medical fear, and crying during venipuncture in children. It can also improve venipuncture compliance, reduce parental anxiety, and increase parental satisfaction.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.