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This study was conducted to determine the total endogenous Ca output and to determine the effects of dietary Ca concentrations on endogenous Ca outputs, the true total tract digestibility (TTTD), and balance of Ca, P, and N in growing pigs. Thirty-six growing barrows (initial BW: 42.2 ± 2.0 kg) were placed in metabolism crates and allotted to a randomized complete block design with 6 diets and 6 pigs per diet. Diets were based on cornstarch and casein, and were formulated to provide the following levels of total Ca: 0.13,0.31,0.50,0.68, 0.87, and 1.05%, and the analyzed ratio of total Ca to total P was between 1.16:1 and 1.23:1. Calcitic limestone and mono-sodium phosphate provided the majority of the Ca and P in the diets. Feces and urine samples were collected from d 8 to d 12. Total endogenous Ca and P outputs and values for TTTD of Ca and P were determined using the regression procedure. Results indicate that the estimated total endogenous Ca and P outputs were 0.508 and 0.428 g/kg DMI, respectively. The TTTD of Ca in calcitic limestone was estimated at 76.8% and the TTTD of P in monosodium phosphate was estimated at 88.8%. It is concluded that the dietary concentration of Ca affects the retention of P significantly (P < 0.01), but does not affect the retention of Ca or N. [ABSTRACT FROM AUTHOR]

This study assessed the effects of proteinate complex zinc (Zn) on oxidative stress, trace elements concentrations and immune functions in weaned piglets. Three hundred newly weaned barrows (Duroc x Landrace x Yorkshire), 28 d of age, were randomly allotted to 3 dietary groups of 5 replicate pens per group for 4 wk of feeding. Experimental diets were: (1) zinc deficient diet (ZnD, 24 mg/kg Zn supplementation fromZnSO4), (2) inorganic Zndiet supplemented by 120 mg/ kg of Zn from Zn sulfate (ZnSO4), and (3) organic Zn diet supplemented by 120 mg/kg of Zn from proteinate complex Zn (PC-Zn). The Zn, Cu, Fe and Mn concentrations in the spleen and liver were measured using inductively coupled plasma-mass spectrometry (ICP-MS) technology. The activities of serous alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) were measured with a biochemical autoanalyzer. The concentration of malondialdehyde (MDA) was determined according to the thiobarbituric acid reactive substances (TBARS) assay and the activity of Mn and Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the spleen and liver were analyzed according to the xanthine oxidase and ammonium molybdate chromogenic methods, respectively. The hepatic MT content was examined by the Cd/hemoglobin affinity assay The levels of splenic interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-γ were determined by IL-2, IL-4, IL-10 and IFN-γ enzyme linked immunosorbent assay (ELISA) kits, respectively. The proportions of CD3+, CD4+ and CD8+ T lymphocyte were analyzed with ELISA methods. The results showed that the accumulation of Zn in the spleen, levels of SOD, GSH-Px, IL-4, IL-10, the proportions of CD3+ and CD4+ T lymphocyte, and the ratio of CD47CD8+ T lymphocyte were increased by organic Zn supplementation, while the levels of MDA, IFN-γ and proportion of CD8+T lymphocyte were lowered. These findings indicate that Zn can improve the antioxidant potential and immune functions related to T lymphocyte production in the spleen of weaned piglets. [ABSTRACT FROM AUTHOR]

Abstract Background Toxoplasma gondii is an intracellular parasite with a significant impact on human health. Inside the mammalian and avian hosts, the parasite can undergo rapid development or remain inactive in the cysts. The mechanism that regulates parasite proliferation has not been fully understood. Small noncoding RNAs (sncRNA) such as microRNAs (miRNAs) are endogenous regulatory factors that can modulate cell differentiation and development. It is anticipated that hundreds of miRNAs regulate the expression of thousands of genes in a single organism. SncRNAs have been identified in T. gondii, however the profiles of sncRNAs expression and their potential regulatory function in parasites of distinct genotypes has largely been unknown. Methods The transcription profiles of miRNAs in the two genetically distinct strains, RH and ME49, of T. gondii were investigated and compared by a high-through-put RNA sequencing technique and systematic bioinformatics analysis. The expression of some of the miRNAs was confirmed by Northern blot analysis. Results 1,083,320 unique sequences were obtained. Of which, 17 conserved miRNAs related to 2 metazoan miRNA families and 339 novel miRNAs were identified. A total of 175 miRNAs showed strain-specific expression, of which 155 miRNAs were up-regulated in RH strain and 20 miRNAs were up-regulated in ME49 strain. Strain-specific expression of miRNAs in T. gondii could be due to activation of specific genes at different genomic loci or due to arm-switching of the same pre-miRNA duplex. Conclusions Evidence for the differential expression of miRNAs in the two genetically distinct strains of T. gondii has been identified and defined. MiRNAs of T. gondii are more species-specific as compared to other organisms, which can be developed as diagnostic biomarkers for toxoplasmosis. The data also provide a framework for future studies on RNAi-dependent regulatory mechanisms in the zoonotic parasite.

Abstract Background In folklore, some people take the decoction of Calyx seu Fructus Physalis (CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material. Methods CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the in vivo and in vitro models of hyperlipidemia were utilized. The structure of active component was determined by 13 C-NMR and 1H-NMR. Results The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid in vivo and in vitro experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain. Conclusion Our results demonstrated that the 75% ethanol extract of CSFP could improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids.

Abstract A total of 2,121 growing-finishing pigs (Duroc × Landrace × Large White) were utilized in six experiments conducted to determine the effects of different ratios of standardized ileal digestible lysine (SID-Lys) to metabolizable energy (ME) on the performance and carcass characteristics of growing-finishing pigs. Exps. 1 (30 to 50 kg), 2 (52 to 70 kg) and 3 (81 to 104 kg) were conducted to find an optimum ME level and then this level was used in Exps. 4 (29 to 47 kg), 5 (54 to 76 kg) and 6 (84 to 109 kg) to test the response of pigs to different ratios of SID-Lys:ME. In Exps.1 to 3, four treatments were used consisting of diets with a formulated ME content of 3.1, 3.2, 3.3 or 3.4 in Exps. 1 and 2 while Exp. 3 used 3.05, 3.15, 3.25 or 3.35 Mcal/kg. A constant SID-Lys:ME ratio of 2.6, 2.3 or 2.0 g/Mcal was used in Exps. 1, 2 and 3, respectively. Weight gain was significantly increased with increasing energy level in Exp.1 while weight gain was unaltered in Exps. 2 and 3. For all three experiments, feed intake was decreased (P < 0.05) and feed efficiency was improved (P < 0.05) with increasing energy level. Tenth rib back fat thickness linearly increased (P < 0.05) with increasing energy level. In Exps. 4 to 6, five treatments were used consisting of diets with a SID-Lys:ME ratio of 2.4, 2.6, 2.8, 3.0 or 3.2 in Exp. 1, 2.1, 2.3, 2.5, 2.7, 2.9 or 3.2 in Exp. 2 and 1.8, 2.0, 2.2, 2.4, or 2.6 in Exp. 3. A constant ME level 3.2, 3.2 and 3.05 Mcal/kg was used in Exps. 1, 2 and 3, respectively (selected based on the results of weight gain). For all three experiments, weight gain increased (P < 0.05) and feed efficiency improved linearly (P < 0.05) as the SID-Lys:ME ratio increased. Tenth rib back fat thickness linearly decreased (P < 0.05) as the SID-Lys:ME ratio increased. Based on a straight broken-line model, the estimated SID-Lys:ME ratio to maximize weight gain was 3.0, 2.43 and 2.2 for 29 to 47, 54 to76 and 84 to 109 kg of pigs, respectively.

Abstract A total of 335 lactating sows (Landrace × Large White) were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine (SID-Lys) to metabolizable energy (ME) for mixed parity sows during lactation. In Exp. 1, 185 sows (weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3) were allocated to one of six experimental diets in a completely randomized block design within parity groups (1, 2, and 3+). The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level (0.86%). As a result, the diets provided a SID-Lys:ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly (P < 0.01) affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3+ sows and the entire cohort of sows respectively (quadratic; P < 0.01). In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys:ME ratio. Litter weight gain was affected by dietary treatment for parity 3+ sows and the entire cohort (P < 0.01). Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3+ (quadratic; P < 0.01) and the entire cohort (quadratic; P < 0.01). Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID-Lys:ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows (weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4) were allocated to one of five treatments in a completely randomized block design within parity (1, 2, and 3+). The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys:ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment (parity 3+ sows, P = 0.02; entire cohort, P < 0.01) and by sow parity (P < 0.01). Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3+ sows and the entire cohort (P < 0.01) as well as by sow parity (P < 0.01). Plasma urea nitrogen (P < 0.01), creatinine (P < 0.01) and non-esterifide fatty acids (P = 0.04) were decreased as the SID-Lys:ME ratio of the diet increased. Insulin-like growth factor-1 (P = 0.02), estradiol (P < 0.01) and luteinizing hormone (P = 0.02) were increased as the SID-Lys:ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys:ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.

Forsythia suspensa extract (FSE) has been demonstrated to attenuate physiological stress induced by high temperature or high stocking density. This experiment was conducted with 144 male Arbor Acre broilers (1-d-old, weighing 42.7 ± 1.7 g) to determine the effects of FSE on performance, nutrient digestibility, antioxidant activities, serum metabolites, and immune parameters for birds treated with corticosterone (CS). The birds were randomly allotted to 1 of 4 treatments in a 2 × 2 factorial arrangement that included FSE supplementation (0 or 100 mg/kg) and CS administration (0 or 20 mg/kg of diet for 7 consecutive days starting on d 14). The feeding program consisted of a starter diet from d 1 to 21 and a finisher diet from d 22 to 42. Corticosterone administration decreased (P < 0.01) ADG and impaired (P < 0.01) feed conversion ratio in both phases and overall, which were alleviated (P < 0.01) by dietary FSE supplementation in the finisher phase and overall. At d 21, CS administration caused decreases (P < 0.05) in the apparent digestibility of energy, relative weight of bursa and thymus, total antioxidant capacity, superoxide dismutase (SOD) activity, and antibody titers to Newcastle disease virus (NDV); however, serum malondialdehyde and uric acid were increased. All of these changes were attenuated (P < 0.05) by dietary FSE supplementation. At d 42, FSE supplementation improved (P < 0.05) the apparent digestibility of DM and CP, relative weights of bursa, SOD activity, and antibody titers to NDV, which were impaired by CS administration. Interactions (P < 0.05) were noted between CS and FSE for ADG and feed conversion ratio in the finisher phase and overall, as well as total antioxidant capacity, SOD activity, uric acid, and antibody titers to NDV at d 21, as well as relative weights of thymus at d 42. In conclusion, dietary FSE supplementation enhanced nutrient digestibility and performance of broiler possibly by reducing oxidative stress and immune depression challenged by CS. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY: Soybeans are known to stimulate food allergies; however, current therapies are lacking in alleviating hypersensitivity. The present study investigated whether Forsythia suspensa extract could attenuate purified soybean ß-conglycinin-induced anaphylactic reactions in weaned piglets. MATERIALS AND METHODS: Eighteen 14-day-old piglets were sensitized and boosted by oral administration of purified ß-conglycinin. Forsythia suspensa extract was supplemented in the diet after the initial sensitization and continued for the remainder of the experiment. Piglets were challenged on day 28, and anaphylactic symptoms, passive cutaneous anaphylaxis, plasma histamine and intestinal microbial flora were analyzed. T-cell proliferative responses and cytokine production were also determined. RESULTS: Forsythia suspensa extract alleviated ß-conglycinin-induced anaphylactic symptoms by markedly reducing anaphylactic antibodies, mast cell degranulation, and histamine release while improving intestinal microbial flora. Furthermore, Forsythia suspensa extract significantly suppressed ß-conglycinin-induced T lymphocyte proliferation and IL-4 synthesis. CONCLUSION: Forsythia suspensa extract protected ß-conglycinin-sensitized piglets from anaphylactic reactions. Forsythia suspensa extract may provide a novel effective therapy for soybean allergy. [ABSTRACT FROM AUTHOR]

This experiment was conducted to evaluate the effects of wheat bran (WB) and antibiotics on growth performance, intestinal immunity, barrier function, and microbial composition in broiler chickens. A total of 168 one-day-old male Arbor Acre chicks were allocated to 3 treatments consisting of 7 replicates with 8 birds per replicate. The 3 treatments were: an antibiotic-free control diet (control, CON), CON 1 75 mg/kg chlortetracycline as an antibiotic growth promoter (AGP), and CON 1 3% WB. Birds fed AGP and WB had greater (P, 0.05) ADG during days 1 to 21 and lower (P, 0.05) feed-to-gain ratio during each phase than those fed CON. The WB supplementation reduced (P, 0.05) serum concentrations of tumor necrosis factor-a and diamine oxidase activity compared with CON on both day 21 and 42. The AGP and WB supplementation decreased (P, 0.05) interleukin- 1b concentration in jejunal mucosa on day 21 and increased (P, 0.05) secretory immunoglobulin A concentration in jejunal mucosa on day 21 and 42. The relative expression of occludin in jejunal mucosa was upregulated (P, 0.05) in WB than in CON on day 21. Moreover, both AGP and WB supplementation upregulated (P, 0.05) the relative expression of zonula occludens-1 in jejunal mucosa on day 21 and 42. The WB supplementation enhanced the a-diversity of cecal microbiota, as evidenced by the increased Shannon index (P, 0.05). At the phylum level, the phylum Firmicutes was enriched (P, 0.05) in WB. At the genus level, the WB supplementation enriched (P, 0.05) Lachnoclostridium and Butyricicoccus. The WB supplementation increased (P, 0.05) cecal total short chain fatty acids concentrations on day 21 and 42, and butyric acid concentrations on day 42 compared with CON. Collectively, supplementation of 3% WB could promote growth by improving intestinal immunity, barrier function, and microbial composition in broilers. Thus, WB may have a role in replacing antibiotics for improved growth performance and intestinal health in broilers. [ABSTRACT FROM AUTHOR]

Broilers were used to determine the protective effects of Forsythia suspensa extract (FSE) against breast muscle oxidative injury induced by corticosterone (CS) mimicking pre-slaughter acute stress. A total of 144 male Arbor Acre broilers was randomly allotted to one of 4 treatments in a 2 × 2 factorial arrangement that included FSE supplementation (0 or 100 mg/kg) and subcutaneous injection of CS (0 or 4 mg/kg) at 3 h before slaughter. Corticosterone increased live BW loss, and the adverse effect was attenuated by FSE in broilers subjected to CS (P < 0.05). Serum levels of CS, uric acid, and glucose were increased, and postmortem breast muscle pH values at 45 min and 24 h were decreased for CS-challenged broilers (P < 0.05). Corticosterone increased lightness and yellowness values and decreased redness of breast muscle (P < 0.05), and FSE decreased yellowness and increased redness of breast muscle (P < 0.05). Drip loss was increased by CS for birds supplemented without FSE (P < 0.05) and decreased by FSE for birds under CS challenge (P < 0.05). Corticosterone increased monounsaturated fatty acid (FA) and decreased polyunsaturated FA in breast muscle (P < 0.05), and saturated FA was decreased and polyunsaturated FA was increased by FSE (P < 0.05). Malondialdehyde and carbonyl contents in breast muscle were increased by CS and decreased by FSE (P < 0.05). Inhibition of 1,1-diphenyl-2-picryl-hydrazyl was decreased by CS and increased by FSE (P < 0.05). The activities of total-antioxidant capacity, glutathione peroxidase, and superoxide dismutase in breast muscle were lower in birds subjected to CS (P < 0.05) and were greater in birds supplemented with FSE (P < 0.05). Collectively, live BW loss and breast muscle oxidative injury were increased by CS in broilers, and these stress-related adverse effects could be attenuated by FSE supplementation via enhanced scavenging ability of free radicals and antioxidant capacity. Therefore, FSE could protect broilers against breast muscle oxidative injury when acute stress happens. [ABSTRACT FROM AUTHOR]

This experiment was conducted with 126 as-hatched male Arbor Acres chicks (1-d-old, weighing 45.3 ± 0.72 g) to determine the effects of microalgae [MA, containing 29% docosahexaenoic acid (DHA)] on performance, serum composition, carcass trait, antioxidant status, and fatty acid deposition of birds. The birds were allocated randomly to 1 of 3 treatments with 7 replicate pens per treatment (6 birds per pen). The dietary treatments included a control diet [corn-soybean basal diet supplemented with 3% soybean oil (SO), CON], 1% MA diet (basal diet supplemented with 1% MA and 2% SO, 1MA), and 2% MA diet (basal diet supplemented with 2% MA and 1% SO, 2MA). All birds were raised in wirefloored cages. The trial consists of a starter phase from d 1 to 21 and a grower phase from d 22 to 42. Compared with CON, birds supplemented with MA (1MA or 2MA) had greater (P < 0.05) average daily gain, liver percentage (liver weight/body weight), and serum glucose, as well as lower (P < 0.05) feed conversation ratio, abdominal fat percentage (abdominal fat weight/body weight), and total serum cholesterol. Moreover, due to the high concentration of DHA in MA, birds fed MA showed increased (P < 0.05) concentration of eicosapentaenoic acid, DHA, superoxide dismutase, and total antioxidant capacity, as well as decreased (P < 0.05) n-6/n-3 polyunsaturated fatty acid ratio, polyunsaturated fatty acid/saturated fatty acid ratio, and malondialdehyde in the breast and thigh muscle compared with CON. In conclusion, dietary supplementation with 1% or 2% DHA-rich microalgae had positive effects on performance, serum composition, carcass trait, antioxidant status, and fatty acid deposition in birds. [ABSTRACT FROM AUTHOR]

This experiment was conducted with 144 male Arbor Acre broilers (one d old, weighing 45.6 ± 1.3 g) to determine protective effects of Forsythia suspensa extract (FSE) against breast muscle oxidative injury induced by transport stress (TS). The birds were randomly allotted to one of 4 treatments in a 2 × 2 factorial arrangement. The treatments consisted of broilers fed diets supplemented without or with FSE (100 mg/kg) and challenged without or with TS for 3 h before slaughter. Transport stress increased live BW loss of broilers (P  < 0.05), and the adverse effect was attenuated by FSE (P  < 0.05). Serum levels of corticoserone and lactate were increased for broilers after transportation (P  < 0.05), whereas these parameters were not affected by FSE. After slaughter, neither breast muscle pH value at 45 min and 24 h postmortem nor 24 h drip loss value was influenced by TS or FSE, whereas TS increased the value of pH decline within 24 h postmortem (P  < 0.05). Transportation decreased redness and increased yellowness value of breast muscle in broilers (P  < 0.05), and FSE tended to have (P = 0.06) or had the converse changes (P  < 0.05). Comparing with non-transported birds, the birds subjected to transportation had greater malondialdehyde (MDA) content and avUCP mRNA expression (P  < 0.05) and lower 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity (P  < 0.05) in breast muscle, whereas the birds supplemented with FSE had lower MDA content (P  < 0.05) and greater DPPH radical scavenging activity (P  < 0.05). Transport caused decreases (P  < 0.05) in total antioxidant capacity and glutathione peroxidase activity, and the decreases were improved by FSE (P  < 0.05). Collectively, live BW loss and breast muscle oxidative injury were increased by TS in broilers and could be attenuated by FSE via directly scavenging free radicals and increased antioxidant capacity. Therefore, FSE could protect broilers against breast muscle oxidative injury induced by TS. [ABSTRACT FROM AUTHOR]

GABAergic neurons are an essential cellular component of neural circuits. Their abundance and diversity have enlarged significantly in the human brain, contributing to the expanded cognitive capacity of humans. However, the developmental mechanism of the extended production of GABAergic neurons in the human brain remains elusive. Here, we use single-cell transcriptomics, bioinformatics, and histological analyses to uncover microglial regulation of the sustained proliferation of GABAergic progenitors and neuroblasts in the human medial ganglionic eminence (hMGE). We show that insulin-like growth factor 1 (IGF1) and its receptor IGR1R as the top ligand-receptor pair underlying microglia-progenitor communication in the prenatal human brain. Using our newly developed neuroimmune hMGE organoids, which mimics hMGE cytoarchitecture and developmental trajectory, we demonstrate that microglia-derived IGF1 promotes progenitor proliferation and the production of GABAergic neurons. Conversely, IGF1-neutralizing antibodies and IGF1 knockout human embryonic stem cells (hESC)-induced microglia (iMG) completely abolished iMG-mediated progenitor proliferation. Together, these findings reveal a previously unappreciated role of microglia-derived IGF1 in promoting proliferation of neural progenitors and the development of GABAergic neurons.

Germline genetic architecture of Alzheimer's disease (AD) indicates microglial mechanisms of disease susceptibility and outcomes. However, the mechanisms that enable microglia to mediate protective responses to AD pathology remain elusive. Adgrg1 is specifically expressed in yolk-sac-derived microglia. This study reveals the role of yolk-sac-derived microglia in AD pathology, highlighting the function of ADGRG1 in modulating microglial protective responses to amyloid deposition. Utilizing both constitutive and inducible microglial Adgrg1 knockout 5xFAD models, we demonstrate that Adgrg1 deficiency leads to increased amyloid deposition, exacerbated neuropathology, and accelerated cognitive impairment. Transcriptomic analyses reveal a distinct microglial state characterized by downregulated genes associated with homeostasis, phagocytosis, and lysosomal functions. Functional assays in mouse models and human embryonic stem cells-derived microglia support that microglial ADGRG1 is required for efficient Aβ phagocytosis. Together, these results uncover a GPCR-dependent microglial response to Aβ, pointing towards potential therapeutic strategies to alleviate disease progression by enhancing microglial functional competence.

The integration of artificial intelligence (AI) technology in e-commerce has currently stimulated scholarly attention, however studies on AI and e-commerce generally relatively few. The current study aims to evaluate how artificial intelligence (AI) chatbots persuade users to consider chatbot recommendations in a web-based buying situation. Employing the theory of elaboration likelihood, the current study presents an analytical framework for identifying factors and internal mechanisms of consumers' readiness to adopt AI chatbot recommendations. The authors evaluated the model employing questionnaire responses from 411 Chinese AI chatbot consumers. The findings of present study indicated that chatbot recommendation reliability and accuracy is positively related to AI technology trust and have negative effect on perceived self-threat. In addition, AI technology trust is positively related to intention to adopt chatbot decision whereas perceived self-threat negatively related to intention to adopt chatbot decision. The perceived dialogue strengthens the significant relationship between AI-tech trust and intention to adopt chatbot decision and weakens the negative relationship between perceived self-threat and intention to adopt AI chatbot decisions., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier B.V.)

Adhesion G-protein-coupled receptors (AGPCRs), containing large N-terminal ligand-binding domains for environmental mechano-sensing, have been increasingly recognized to play important roles in numerous physiologic and pathologic processes. However, their impact on the heart, which undergoes dynamic mechanical alterations in healthy and failing states, remains understudied. ADGRG1 (formerly known as GPR56) is widely expressed, including in skeletal muscle where it was previously shown to mediate mechanical overload-induced muscle hypertrophy; thus, we hypothesized that it could impact the development of cardiac dysfunction and remodeling in response to pressure overload. In this study, we generated a cardiomyocyte (CM)-specific ADGRG1 knockout mouse model, which, although not initially displaying features of cardiac dysfunction, does develop increased systolic and diastolic LV volumes and internal diameters over time. Notably, when challenged with chronic pressure overload, CM-specific ADGRG1 deletion accelerates cardiac dysfunction, concurrent with blunted CM hypertrophy, enhanced cardiac inflammation and increased mortality, suggesting that ADGRG1 plays an important role in the early adaptation to chronic cardiac stress. Altogether, the present study provides an important proof-of-concept that targeting CM-expressed AGPCRs may offer a new avenue for regulating the development of heart failure., (© 2024 The Author(s).)

Depression is a widespread disease, with high mortality and recurrence rates. Recent studies have shown that elevated cytokine levels are implicated in the molecular mechanisms of depression. Oxidative stress contributes to the stimulation of cytokine production. Growing evidence suggests that ginsenoside Re (Gs-Re) exerts a neuroprotective effect on the hippocampus by suppressing oxidative stress and inflammation. However, the effect and mechanism of Gs-Re in the treatment of depression remain understudied. This study aimed to evaluate the neuroprotective and antidepressant-like effects of Gs-Re and the possible underlying mechanisms. In this article, the antidepressant-like effect of the Gs-Re was studied both in vitro (H 2 O 2 -induced oxidative stress in HT-22 cells) and in vivo (reserpine-induced depressive model mice). Our results indicated that, at the cellular level, Gs-Re effectively enhanced cell survival following H 2 O 2 stimulation, inhibited the mass production of oxidative stress markers (MDA and ROS), and prevented the occurrence of apoptosis. Moreover, Gs-Re significantly reduced the levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α and restored the abnormal mitochondrial membrane potential. Subsequently, Gs-Re treatment reversed reserpine-induced neuroinflammation and depressive-like behaviors in vivo and inhibited microglia overactivation. Furthermore, the alterations in the BDNF/TrkB/ERK/CREB signaling pathway induced by H 2 O 2 or reserpine in HT-22 cells or in the mouse hippocampus were significantly reversed by Gs-Re. K252a blocked the improvement of Gs-Re on depression-like behavior and eliminated the inhibition of oxidative stress and neuroinflammation in vivo. This study suggested that Gs-Re produces neuroprotective and depressive effects by inhibiting oxidative stress and inflammation and activating the BDNF/TrkB/ERK/CREB pathway.

Kruppel-like factor 4 (Klf4) is a transcription factor that is involved in neuronal regeneration and the development of glutamatergic systems. However, it is unknown whether Klf4 is involved in acute seizure. To investigate the potential role of Klf4 in pentylenetetrazol (PTZ)-induced seizure, western blotting, immunofluorescence, behaviour test and electrophysiology were conducted in this study. We found that Klf4 protein and mRNA expression were increased in both the hippocampus (HP) and prefrontal cortex (PFC) after PTZ-induced seizure in mice. HP-specific knockout (KO) of Klf4 in mice decreased protein expression of Klf4 and the down-stream Klf4 target tumour protein 53 (TP53/P53). These molecular changes are accompanied by increased seizure latency, reduced immobility time in the forced swimming test and tail suspension test. Reduced hippocampal protein levels for synaptic proteins, including glutamate receptor 1 (GRIA1/GLUA1) and postsynaptic density protein 95 (DLG4/PSD95), were also observed after Klf4-KO, while increased mRNA levels of complement proteins were observed for complement component 1q subcomponent A (C1qa), complement component 1q subcomponent B (C1qb), complement component 1q subcomponent C (C1qc), complement component 3 (C3), complement component 4A (C4a) and complement component 4B (C4b). Moreover, c-Fos expression induced by PTZ was reduced by hippocampal conditional KO of Klf4. Electrophysiology showed that PTZ-induced action potential frequency was decreased by overexpression of Klf4. In conclusion, these findings suggest that Klf4 plays an important role in regulating PTZ-induced seizures and therefore constitutes a new molecular target that should be explored for the development of antiepileptic drugs., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) can regulate osteogenesis and osteoclastogenesis. This study aimed to further explore the effects of EZH2 modification on ferroptosis and the osteoblast-osteoclast balance in rheumatoid arthritis (RA) in vitro and in vivo., Methods: Bone marrow mesenchymal stromal cells were transfected with EZH2 overexpression (oeEZH2) and EZH2 shRNA (shEZH2) plasmids with or without ferrostatin-1 (Fer-1) treatment and subjected to an osteoblast differentiation assay. The cells were then cocultured with bone marrow-derived macrophages and subjected to an osteoclast differentiation assay. Collagen-induced arthritis (CIA) mice were generated and injected with shEZH2 adeno-associated virus (AAV)., Results: OeEZH2 repressed osteoblast differentiation, as reflected by decreased ALP and Alizarin Red S staining and increased OPN, RUNX2, OPG and RANKL; however, shEZH2 had the opposite effects. Besides, oeEZH2 promoted osteoblast ferroptosis, as suggested by increased MDA, Fe 2+ , ROS, and PTGS2 but decreased GPX4 and SLC7A11; these effects could be attenuated by Fer-1 treatment. In contrast, shEZH2 ameliorated osteoblast ferroptosis. OeEZH2 subsequently increased osteoclast differentiation, as indicated by increased TRAP + multinucleated cells, NFATC1, CTSK, and c-FOS; however, shEZH2 had the opposite effect, except that it did not regulate CTSK. In CIA mice, shEZH2 AAV decreased the clinical symptom score, histological score of cartilage, and systemic inflammation (TNF-α and IL-6) and repressed bone ferroptosis and restored the osteoblast-osteoclast balance to some extent, as reflected by immunohistochemical staining of related markers., Conclusion: Targeting EZH2 attenuates the ferroptosis-mediated osteoblast-osteoclast imbalance in RA, revealing its potential as a treatment target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and non-pharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.)

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus -based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus -based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 10 8 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 10 9 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased ( p < 0.05) average daily gain (ADG) in phase 2 and tended ( p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended ( p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased ( p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased ( p < 0.01) villus height at the jejunum, decreased ( p < 0.05) crypt depth at the ileum compared with other treatments, and tended ( p = 0.09) to have an increased villus-crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased ( p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated ( p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

Recently, our group developed a synergistic brain drug delivery method to achieve simultaneous transcranial hyperthermia and localized blood-brain barrier opening via MR-guided focused ultrasound (MRgFUS). In a rodent model, we demonstrated that the ultrasound power required for transcranial MRgFUS hyperthermia was significantly reduced by injecting microbubbles (MBs). However, the specific mechanisms underlying the power reduction caused by MBs remain unclear. The present study aims to elucidate the mechanisms of MB-enhanced transcranial MRgFUS hyperthermia through numerical studies using the finite element method. The microbubble acoustic emission (MAE) and the viscous dissipation (VD) were hypothesized to be the specific mechanisms. Acoustic wave propagation was used to model the FUS propagation in the brain tissue, and a bubble dynamics equation for describing the dynamics of MBs with small shell thickness was used to model the MB oscillation under FUS exposures. A modified bioheat transfer equation was used to model the temperature in the rodent brain with different heat sources. A theoretical model was used to estimate the bubble shell's surface tension, elasticity, and viscosity losses. The simulation reveals that MAE and VD caused a 40.5% and 52.3% additional temperature rise, respectively. Compared with FUS only, MBs caused a 64.0% temperature increase, which is consistent with our previous animal experiments. Our investigation showed that MAE and VD are the main mechanisms of MB-enhanced transcranial MRgFUS hyperthermia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The development of messenger RNA (mRNA) vaccines and therapeutics necessitates the production of high-quality in vitro -transcribed mRNA drug substance with specific critical quality attributes (CQAs), which are closely tied to the uniformity of linear DNA template. The supercoiled plasmid DNA is the precursor to the linear DNA template, and the supercoiled DNA percentage is commonly regarded as a key in-process control (IPC) during the manufacturing of linear DNA template. In this study, we investigate the influence of supercoiled DNA percentage on key mRNA CQAs, including purity, capping efficiency, double-stranded RNA (dsRNA), and distribution of poly(A) tail. Our findings reveal a significant impact of supercoiled DNA percentage on mRNA purity and in vitro transcription yield. Notably, we observe that the impact on mRNA purity can be mitigated through oligo-dT chromatography, alleviating the tight range of DNA supercoiled percentage to some extent. Overall, this study provides valuable insights into IPC strategies for DNA template chemistry, manufacturing, and controls (CMC) and process development for mRNA drug substance., Competing Interests: All authors are employees of CATUG Biotechnology and may be shareholders of CATUG Biotechnology., (© 2024 The Author(s).)

Narrowband afterglow materials display interesting functions in high-quality anti-counterfeiting and multiplexed bioimaging. However, there is still a limited exploration of these afterglow materials, especially for those with a full width at half maxima (FWHM) around 30 nm. Here, we report the fabrication of narrowband organic/inorganic hybrid afterglow materials via energy transfer technology. Coronene (Cor) with a long phosphorescence feature and broad phosphorescence band is selected as the donor for energy transfer, and inorganic quantum dots (QDs) of CdSe/ZnS with a narrowband emission are used as acceptors. Upon doping into the organic matrix, the resultant three-component materials exhibit a narrowband afterglow with an afterglow lifetime of approximately 3.4 s and an FWHM of 31 nm. The afterglow wavelength of the afterglow materials can be controlled by the QDs. This work based on organic/inorganic hybrids provides a facile approach for developing multicolor and narrowband afterglow materials, as well as opens a new way for expanding the features of organic afterglow for multifunctional applications. It is expected to rely on narrowband afterglow emitters to solve the "spectrum congestion" problem of high-density information storage in optical anti-counterfeiting and information encryption.

Panax quinquefolius L. is an important medicinal plant, and flavonoids are among its main secondary metabolites. The R2R3-MYB transcription factor plays an irreplaceable role in plant growth, development, and secondary metabolism. In our study, we identified 159 R2R3-MYBs and analyzed their physical and chemical properties in P. quinquefolius . The protein length of 159 PqMYB s varied from 107 to 1050 amino acids. The molecular weight ranged from 12.21 to 116.44 kDa. The isoelectric point was between 4.57 and 10.34. We constructed a phylogenetic tree of P. quinquefolius and Arabidopsis thaliana R2R3-MYB family members, and PqMYB members were divided into 33 subgroups. Transcriptome data analysis showed that the expression patterns of PqMYB s in root, leaf, and flower were significantly different. Following the MeJA treatment of seedlings, five candidate PqMYB genes demonstrated a response. A correlation analysis of PqMYB s and candidate flavonoid pathway genes showed that PqMYB2 , PqMYB46 , and PqMYB72 had correlation coefficients that were higher than 0.8 with PqCHS , PqANS4 , and PqCCoAMT10 , respectively. Furthermore, a transient expression assay confirmed that the three PqMYBs were localized in the nucleus. We speculated that these three PqMYB s were related to flavonoid biosynthesis in P. quinquefolius . These results provided a theoretical basis and a new perspective for further understanding the R2R3-MYB gene family and the biosynthesis mechanism of secondary metabolites in P. quinquefolius .

Blue afterglow constitutes of one of the primary afterglow colors and can convert into other afterglow colors through energy transfer. The reported studies show the fabrication of blue afterglow emitters, but most of them are formed by room-temperature phosphorescence mechanism and require UVB lights as excitation source (these high-energy lights may damage organic systems). Here we report visible-light-excitable blue thermally activated delayed fluorescence type (TADF-type) afterglow materials via delicate control of excited states in difluoroboron β-diketonate (BF 2 bdk) systems. Tiny change of the substituents in BF 2 bdk system has been found to pose significant influence on excited state energy levels and consequently narrow the singlet-triplet splitting energy of the system. As a result, both forward and reverse intersystem crossing have been accelerated, leading to the emergence of BF 2 bdk's TADF-type organic afterglow in rigid crystalline matrices. The resultant TADF-type afterglow materials exhibit emission lifetimes of several hundred milliseconds, photoluminescence quantum yield (PLQY) of 24.7 % and display temperature responsive property., (© 2024 Wiley‐VCH GmbH.)

This study sought to determine the effects of rosemary leaf powder (RP) on laying performance, egg quality, serum indices, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens. A total of 84 "Jing Tint 6" laying hens at 65-week old were randomly divided into 2 groups and fed either a basal diet (CON) or a basal diet supplemented with 0.3% RP. Our study revealed that RP improved the Haugh unit and decreased yolk n-6/n-3 polyunsaturated fatty acid (PUFA) ratio of laying hens, increased serum superoxide dismutase (SOD), jejunal activities of SOD and catalase (CAT), and jejunal zonula occludens-1 ( ZO-1 ) expression, as well as decreased serum tumor necrosis factor-α (TNF-α) level and jejunal TNF-α mRNA expression. Rosemary leaf powder markedly enhanced ( P  < 0.05) cecal abundances of Rikenellaceae, Rikenellaceae &#95;RC9&#95;gut&#95;group , and Turicibacter , tended to promote ( P  = 0.076) butyrate concentration, and reduced ( P  < 0.05) cecal abundances of Erysipelatoclostridiaceae, Sutterellaceae, Fusobacteriaceae, Campylobacteraceae, Sutterella , Campylobacter , and Fusobacterium , which were closely linked with Haugh unit, yolk n-6/n-3 PUFA ratio, serum SOD and TNF-α. In addition, RP altered the metabolic functions of cecal microbiota and enhanced the abundances of butyrate-synthesizing enzymes, including lysine 2,3-aminomutase, β-lysine 5,6-aminomutase, and 3-oxoacid CoA-transferase. Together, 0.3% RP has the potential to enhance egg quality by partially modulating serum antioxidant status, jejunal barrier function, and cecal microbiota structure and metabolites, indicating that RP could be considered a promising feed additive to promote the production performance of late-phase laying hens., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Programmable photonic circuits (PPCs) have garnered substantial interest for their potential in facilitating deep learning accelerations and universal quantum computations. Although photonic computation using PPCs offers ultrafast operation, energy-efficient matrix calculations, and room-temperature quantum states, its poor scalability hinders integration. This challenge arises from the temporally one-shot operation of propagating light in conventional PPCs, resulting in a light-speed increase in device footprints. Here we propose the concept of programmable photonic time circuits, utilizing time-cycle-based computations analogous to gate cycling in the von Neumann architecture and quantum computation. Our building block is a reconfigurable SU(2) time gate, consisting of two resonators with tunable resonances, and coupled via time-coded dual-channel gauge fields. We demonstrate universal U(N) operations with high fidelity using an assembly of the SU(2) time gates, substantially improving scalability from O(N^{2}) to O(N) in terms of both the footprint and the number of gates. This result paves the way for PPC implementation in very large-scale integration.

Objectives: The number of surgeries performed in the United States has increased over the past two decades, with a shift to the ambulatory setting. Perioperative complications and mortality pose significant health care burdens. Inadequate preoperative assessment and documentation contribute to communication failure and poor patient outcomes. The aim of this quality improvement project was to design and implement a preoperative evaluation documentation template that not only improved communication during the perioperative pathway but also enhanced the overall user experience., Methods: We implemented a revamped evidence-based documentation template in the electronic medical records of a health care organization across three internal medicine clinics on the downtown campus and seven satellite family medicine clinics. A pre- and postintervention design was used to assess the template utilization rate and clinician satisfaction., Results: The preoperative template utilization rate increased from 51.2% at baseline to 66.5% after the revamped template "went live" ( p  < 0.001). Clinician satisfaction with the preoperative documentation template also significantly increased (30.6 vs. 80.0%, p  < 0.001)., Conclusion: Adopting a user-friendly, evidence-based documentation template can enhance the standardization of preoperative evaluation documentation and reduce the documentation burden., Competing Interests: None declared., (Thieme. All rights reserved.)

This paper investigates the attack estimation and state reconstruction problem for linear cyber-physical systems with state delay and simultaneous sensor and actuator attacks. Reduced-order observer is designed for the augmented system to simultaneously estimate the actuator attack, sensor attack and the state of system. By adopting the double integral term into the Lyapunov-Krasovskii functional and decomposing the cross term, the delay-dependent results are obtained. The method proposed in this paper can accurately estimate the state, actuator and sensor attacks simultaneously without additional design. Compared with the previous method, the time delay information is fully utilized and the conservation is greatly reduced. Finally, the correctness of the results is verified by simulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction: The BAHD (benzylalcohol O-acetyl transferase, anthocyanin O-hydroxycinnamoyl transferase, N-hydroxycinnamoyl anthranilate benzoyl transferase and deacetylvindoline 4-O-acetyltransferase), has various biological functions in plants, including catalyzing the biosynthesis of terpenes, phenolics and esters, participating in plant stress response, affecting cell stability, and regulating fruit quality., Methods: Bioinformatics methods, real-time fluorescence quantitative PCR technology, and ultra-high-performance liquid chromatography combined with an Orbitrap mass spectrometer were used to explore the relationship between the BAHD gene family and malonyl ginsenosides in Panax ginseng ., Results: In this study, 103 BAHD genes were identified in P. ginseng , mainly distributed in three major clades. Most PgBAHDs contain cis-acting elements associated with abiotic stress response and plant hormone response. Among the 103 genes, 68 PgBAHDs are WGD (whole-genome duplication) genes. The significance of malonylation in biosynthesis has garnered considerable attention in the study of malonyltransferases. The phylogenetic tree results showed 34 PgBAHDs were clustered with genes that have malonyl characterization. Among them, seven PgBAHDs ( PgBAHD4 , 45 , 65 , 74 , 90 , 97 , and 99 ) showed correlations > 0.9 with crucial enzyme genes involved in ginsenoside biosynthesis and > 0.8 with malonyl ginsenosides. These seven genes were considered potential candidates involved in the biosynthesis of malonyl ginsenosides., Discussion: These results help elucidate the structure, evolution, and functions of the P. ginseng BAHD gene family, and establish the foundation for further research on the mechanism of BAHD genes in ginsenoside biosynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Yan, Yan, Piao, Wang, Lei, Yang, Zhang, Li, Di and Yang.)

The present study was to explore the Ile requirement of piglets fed 18% crude protein (CP) diets. Two hundred and fifty 28-day-old Duroc × Landrace × Yorkshire piglets (8.37 ± 1.92 kg) were randomly divided into 5 dietary treatments (10 piglets per replicate, 5 barrows and 5 gilts per replicate) with 45%, 50%, 55%, 60%, 65% standardized ileal digestible (SID) Ile-to-Lys ratios, and the SID Lys was formulated to 1.19%. The experimental design consisted of two phases (d 1 to 14 and d 15 to 28). Results showed that average daily gain (ADG) had a tendency to quadratically increase as the SID Ile-to-Lys ratio increased ( P  = 0.09), and the optimum SID Ile-to-Lys ratios required to maximize ADG were 48.33% and 54.63% for broken-line linear model and quadratic polynomial model, respectively. Different SID Ile-to-Lys ratios had no significant effects on average daily feed intake and gain-to-feed ratio. Dry matter ( P  < 0.01), CP ( P  = 0.01), ether extract ( P  = 0.04), gross energy ( P  < 0.01) and organic matter ( P  < 0.01) digestibility increased quadratically. Serum total cholesterol levels decreased linearly ( P  = 0.01) and quadratically ( P  < 0.01); aspartate aminotransferase ( P  < 0.01), interleukin-1β ( P  = 0.01), and tumor necrosis factor-α ( P  < 0.01) levels decreased quadratically; immunoglobulin G ( P  = 0.03) and immunoglobulin M ( P  = 0.01) concentrations increased quadratically. Serum Ser levels decreased linearly ( P  < 0.01) and quadratically ( P  = 0.01); Glu ( P  = 0.02), Arg ( P  = 0.05), and Thr ( P  = 0.03) levels decreased quadratically; Gly ( P  < 0.01) and Leu ( P  = 0.01) levels decreased linearly; Ile ( P  < 0.01) concentration increased linearly. Duodenal villus height ( P  < 0.01) and villus height to crypt depth ratio ( P  < 0.01) increased quadratically. The deficiency or excess of Ile decreased short chain fatty acid-producing bacteria abundance and increased pathogenic bacteria abundance. Overall, taking ADG as the effect index, the optimum SID Ile-to-Lys ratios of piglets offered 18% CP diets were 48.33% and 54.63% based on two different statistical models, respectively, and the deficiency or excess of lle negatively affected piglet growth rates and health status., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Objective: To characterize the biochemical and demographic profiles of pregnant people with maternal immune activation (MIA) and identify the prenatal characteristics associated with neurologic morbidity in offspring., Study Design: This was a retrospective cohort study of 602 mother-infant dyads with births between 2009 and 2010 in California. Multivariable logistic regression was used to build a MIA vulnerability profile including mid-pregnancy biochemical markers and maternal demographic characteristics, and its relationship with infant neurologic morbidity was examined., Results: Of the 602 mother-infant dyads, 80 mothers and 61 infants had diagnoses suggestive of MIA and neurologic morbidity, respectively. Our model, including two demographic and seven biochemical characteristics, identified mothers with MIA with good performance (AUC:0.814; 95% CI:0.7-0.8). Three demographic and five inflammatory markers together identified 80% of infants with neurological morbidity (AUC:0.802, 95% CI:0.7-0.8)., Conclusion: Inflammatory environment in mothers with pre-existing risk factors like obesity, poverty, and prematurity renders offspring more susceptible to neurologic morbidities., (© 2023. The Author(s).)

Noncoding RNAs have recently emerged as versatile regulators of endothelial dysfunction in atherosclerosis, a chronic inflammatory disease characterized by the formation of plaques within the arterial walls. Through their ability to modulate gene expression, noncoding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, play crucial roles in various cellular processes involved in endothelial dysfunction (ECD), such as inflammation, pyroptosis, migration, proliferation, apoptosis, oxidative stress, and angiogenesis. This review provides an overview of the current understanding of the regulatory roles of noncoding RNAs in endothelial dysfunction during atherosclerosis. It highlights the specific noncoding RNAs that have been implicated in the pathogenesis of ECD, their target genes, and the mechanisms by which they contribute to ECD. Furthermore, we have reviewed the current therapeutics in atherosclerosis and explore their interaction with noncoding RNAs. Understanding the intricate regulatory network of noncoding RNAs in ECD may open up new opportunities for the development of novel therapeutic strategies to combat ECD., Competing Interests: Declaration of competing interest The authors declare that they have not any competing interest., (Copyright © 2023. Published by Elsevier Inc.)

Auxin-responsive factors (ARFs) are an important class of transcription factors and are an important component of auxin signaling. This study conducted a genome-wide analysis of the ARF gene family in ginseng and presented its findings. Fifty-three ARF genes specific to ginseng ( PgARF ) were discovered after studying the ginseng genome. The coding sequence (CDS) has a length of 1092-4098 base pairs and codes for a protein sequence of 363-1565 amino acids. Among them, PgARF32 has the least number of exons (2), and PgARF16 has the most exons (18). These genes were then distributed into six subgroups based on the results obtained from phylogenetic analysis. In each subgroup, the majority of the PgARF genes displayed comparable intron/exon structures. PgARF genes are unevenly distributed on 20 chromosomes. Most PgARFs have B3 DNA binding, Auxin&#95;resp, and PB1 domains. The PgARF promoter region contains various functional domains such as plant hormones, light signals, and developmental functions. Segmental duplications contribute to the expansion of the ARF gene family in ginseng, and the genes have undergone purifying selection during evolution. Transcriptomic results showed that some PgARFs had different expression patterns in different parts of ginseng; most PgARFs were affected by exogenous hormones, and a few PgARFs responded to environmental stress. It is suggested that PgARF is involved in the development of ginseng by regulating hormone-mediated genes. PgARF14 , PgARF42 , and PgARF53 are all situated in the nucleus, and both PgARR14 and PgARF53 noticeably enhance the growth length of roots in Arabidopsis. Our findings offer a theoretical and practical foundation for exploring PgARFs ' role in the growth of ginseng roots.

Background: A protective intra-operative lung ventilation strategy has been widely recommended for laparoscopic surgery. However, there is no consensus regarding the optimal level of positive end-expiratory pressure (PEEP) and its effects during pneumoperitoneum. Electrical impedance tomography (EIT) has recently been introduced as a bedside tool to monitor lung ventilation in real-time., Objective: We hypothesised that individually titrated EIT-PEEP adjusted to the surgical intervention would improve respiratory mechanics during and after surgery., Design: Randomised controlled trial., Setting: First Medical Centre of Chinese PLA General Hospital, Beijing., Patients: Seventy-five patients undergoing robotic-assisted laparoscopic hepatobiliary and pancreatic surgery under general anaesthesia., Interventions: Patients were randomly assigned 2 : 1 to individualised EIT-titrated PEEP (PEEPEIT; n = 50) or traditional PEEP 5 cmH2O (PEEP5 cmH2O; n = 25). The PEEPEIT group received individually titrated EIT-PEEP during pneumoperitoneum. The PEEP5 cmH2O group received PEEP of 5 cmH2O during pneumoperitoneum., Main Outcome Measures: The primary outcome was respiratory system compliance during laparoscopic surgery. Secondary outcomes were individualised PEEP levels, oxygenation, respiratory and haemodynamic status, and occurrence of postoperative pulmonary complications (PPCs) within 7 days., Results: Compared with PEEP5 cmH2O, patients who received PEEPEIT had higher respiratory system compliance (mean values during surgery of 44.3 ± 11.3 vs. 31.9 ± 6.6, ml cmH2O-1; P < 0.001), lower driving pressure (11.5 ± 2.1 vs. 14.0 ± 2.4 cmH2O; P < 0.001), better oxygenation (mean PaO2/FiO2 427.5 ± 28.6 vs. 366.8 ± 36.4; P = 0.003), and less postoperative atelectasis (19.4 ± 1.6 vs. 46.3 ± 14.8 g of lung tissue mass; P = 0.003). Haemodynamic values did not differ significantly between the groups. No adverse effects were observed during surgery., Conclusion: Individualised PEEP by EIT may improve intra-operative pulmonary mechanics and oxygenation without impairing haemodynamic stability, and decrease postoperative atelectasis., Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn) identifier: ChiCTR2100045166., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: The COVID-19 pandemic has affected a significant number of pregnant women worldwide, but studies on immune responses have presented conflicting results. This study aims to systematically review cytokine profiles in pregnant women with SARS-CoV-2 infection and their infants to evaluate immune responses and potential transplacental transfer of cytokines., Materials and Methods: A comprehensive search of 4 databases was conducted to identify relevant studies. Inclusion criteria included studies measuring individual cytokines in pregnant women and/or their neonates. Studies were evaluated for quality, and data were extracted for analysis. Meta-analyses were performed using the random-effects model., Results: Seventeen studies met the inclusion criteria, including data from 748 pregnant women and 287 infants. More than three of these studies evaluated data of 20 cytokines in maternal serum, and data of 10 cytokines was available from cord blood samples. Only the serum level of CXCL10 was significantly up-regulated in SARS-CoV-2 positive pregnant women ( n  = 339) compared to SARS-CoV-2 negative pregnant women ( n  = 409). Subset analysis of maternal samples ( n  = 183) collected during the acute phase of COVID-19 infection showed elevated CXCL10 and IFN-γ. No significant differences in cytokine levels were found between cord blood samples collected from infants born to mothers with ( n  = 97) and without ( n  = 190) COVID-19 during gestation. Subset analysis of cord blood samples collected during the acute phase of maternal infection was limited by insufficient data. The heterogeneity among the studies was substantial., Conclusion: The findings suggest that maternal cytokines responses to SARS-CoV-2 infection during pregnancy are not significantly dysregulated, except for CXCL10 and IFN-γ during the acute phase of illness. No evidence of increased cytokine levels in cord blood samples was observed, although this could be impacted by the time period between initial maternal infection and cord blood collection. These results provide some reassurance to parents and healthcare providers but should be interpreted cautiously due to study variations and limitations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Jain, Allen, Song and Piao.)

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood 1,2 . Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell-type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Rosemary extract (RE) has been reported to exert antioxidant property. However, the application of RE in late-phase laying hens on egg quality, intestinal barrier and microbiota, and oviductal function has not been systematically studied. This study was investigated to detect the potential effects of RE on performance, egg quality, serum parameters, intestinal heath, cecal microbiota and metabolism, and oviductal gene expressions in late-phase laying hens. A total of 210 65-week-old "Jing Tint 6" laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet (CON) or basal diet supplemented with chlortetracycline at 50 mg/kg (CTC) or RE at 50 mg/kg (RE50), 100 mg/kg (RE100), and 200 mg/kg (RE200)., Results: Our results showed that RE200 improved (P < 0.05) Haugh unit and n-6/n-3 of egg yolk, serum superoxide dismutase (SOD) compared with CON. No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC, RE50, RE100 and RE200 groups. Compared with CTC and RE50 groups, RE200 increased serum SOD activity on d 28 and 56. Compared with CON, RE supplementation decreased (P < 0.05) total cholesterol (TC) level. CTC, RE100 and RE200 decreased (P < 0.05) serum interleukin-6 (IL-6) content compared with CON. CTC and RE200 increased jejunal mRNA expression of ZO-1 and Occludin compared with CON. The biomarkers of cecal microbiota and metabolite induced by RE 200, including Firmicutes, Eisenbergiella, Paraprevotella, Papillibacter, and butyrate, were closely associated with Haugh unit, n-6/n-3, SOD, IL-6, and TC. PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes, including 3-oxoacid CoA-transferase and butyrate-acetoacetate CoA-transferase. Moreover, transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum., Conclusions: Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier, cecal microbiota and metabolism, and oviductal function. Overall, RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production., (© 2023. Chinese Association of Animal Science and Veterinary Medicine.)