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Abstract Background As we delve into the intricate world of venetoclax combination therapy in relapsed or refractory acute myeloid leukemia (AML), our exploration not only aims to contribute to the current body of knowledge but also strives to inform future research directions, clinical decision-making, and the ongoing evolution of therapeutic strategies in the relentless pursuit of improved outcomes for patients facing this formidable hematologic malignancy. Methods We systematically searched PubMed, Embase, and Cochrane databases from inception to November 2023 for English-language studies on venetoclax combination therapy in relapsed/refractory AML. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. Meta-analysis was performed using STATA 15.1. Results Out of 58 identified articles, seven were included in the meta-analysis. The pooled complete remission (CR) rate was 15.4%, and the composite complete remission (CRc) rate was 35.7%. The partial remission (PR) rate was 2.6%, while the non-remission (NR) rate was 24.4%. The minimal residual disease status in CRc patients (MRD-CRc) rate was 39.4%, and the morphologic leukemia-free state (MLFS) rate was 10.3%. Incidence of adverse events included diarrhea (10.0%), nausea (4.3%), vomiting (2.6%), hypokalemia (16.4%), hypomagnesemia (0.8%), decreased appetite (4.2%), fatigue (9.1%), febrile neutropenia (39.6%), and thrombocytopenia (28.4%). Subgroup analysis based on combined drugs revealed varying CR and CRc rates. the combination of venetoclax and azacitidine + demonstrates superior outcomes, displaying the highest rates of CR at 31.3% and CRc at 62.7%. In contrast, venetoclax and idasanutlin exhibits a moderate CR rate of 6.1% and a CRc rate of 26.5%, while venetoclax and mivebresib shows the lowest CR rate at 3.3% and a moderate CRc rate of 8.0%. Conclusion In conclusion, while venetoclax combination therapies, particularly with azacitidine + , show promise in achieving favorable treatment responses in relapsed/refractory AML patients, a comprehensive evaluation of safety profiles is essential. Nevertheless, it is essential to underscore the markedly increased incidence rates of febrile neutropenia and thrombocytopenia observed among adverse events.

Abstract Skeletal editing of single-atom insertion to basic chemicals has been demonstrated as an efficient strategy for the discovery of structurally diversified compounds. Previous endeavors in skeletal editing have successfully facilitated the insertion of boron, nitrogen, and carbon atoms. Given the prevalence of oxygen atoms in biologically active molecules, the direct oxygenation of C-C bonds through single-oxygen-atom insertion like Baeyer-Villiger reaction is of particular significance. Herein, we present an approach for the skeletal modification of styrenes using O2 via oxygen insertion, resulting in the formation of aryl ether frameworks under mild reaction conditions. The broad functional-group tolerance and the excellent chemo- and regioselectivity are demonstrated in this protocol. A preliminary mechanistic study indicates the potential involvement of 1,2-aryl radical migration in this reaction.

Abstract Ancient Platycladus orientalis holds significant ecological, landscape, historical, and cultural value. In northern China, leaf blight has significantly impacted the growth and ornamental value of ancient P. orientalis. In this study, 26 blight leaf samples of ancient P. orientalis were collected in Beijing, China. Phylogenetic analysis based on the concatenated internal transcribed spacer (ITS), β-tubulin (tub2), and RNA polymerase second largest subunit (rpb2) DNA sequence data combined with fungal morphological characteristics revealed three taxa of Nothophoma, i.e. N. platycladus, N. spiraeae, and N. juglandis. Of which, N. platycladus is a species new to science. Koch’s postulates indicated that all these three species of Nothophoma could cause leaf blight of P. orientalis.

Abstract Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp 2-Csp 3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.

Abstract Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown. Results In this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P

Abstract To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP—with the osteogenic active zone labelled by RUNX2—tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead compounds optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, “the most fruitful basis for the discovery of a new drug is to start with an old drug”1. Late-stage modification or functionalization of drugs, natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds promptly. Such modifications alter the chemical space and physiochemical properties of these compounds, ultimately influencing their potency and druggability. To enrich a toolbox of chemical modification methods for drug discovery, this review focuses on the incorporation of halogen, oxygen, and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades, and discusses the state and challenges faced in these fields. We also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized molecules. Ultimately, we hope this review would serve as a valuable resource, facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.

Abstract The photochemical properties of Electron Donor-Acceptor (EDA) complexes present exciting opportunities for synthetic chemistry. However, these strategies often require an inert atmosphere to maintain high efficiency. Herein, we develop an EDA complex photocatalytic system through rational design, which overcomes the oxygen-sensitive limitation of traditional EDA photocatalytic systems and enables aerobic oxygenation reactions through dioxygen activation. The mild oxidation system transfers electrons from the donor to the effective catalytic acceptor upon visible light irradiation, which are subsequently captured by molecular oxygen to form the superoxide radical ion, as demonstrated by the specific fluorescent probe, dihydroethidine (DHE). Furthermore, this visible-light mediated oxidative EDA protocol is successfully applied in the aerobic oxygenation of boronic acids. We believe that this photochemical dioxygen activation strategy enabled by EDA complex not only provides a practical approach to aerobic oxygenation but also promotes the design and application of EDA photocatalysis under ambient conditions.

Abstract Background Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. Methods Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. Results Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. Conclusions These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

Consumer demand for high-quality meat has increased. This study aimed to investigate the potential application of cocrystals of thymol and carvacrol in broilers for high-quality meat production. Eight hundred 1-day-old chicks were assigned to four groups fed diets supplemented with 0, 40, 60, and 80 mg/kg of Crystal EO® (CEO), containing 25% cocrystals of thymol and carvacrol in a 42-d feeding trial. The results showed that dietary CEO supplementation decreased the muscle fiber diameter and increased the muscle fiber density, glycogen content, L*45 min value, and proportion of α-linolenic acid in the breast muscle; dietary 40 and 60 mg/kg of CEO decreased the lactate content, MDA concentration, cooking loss, shear force, and thrombogenicity index and increased the proportion of lauric acid in the breast muscle; dietary 60 and 80 mg/kg of CEO increased the glucose content, total superoxide dismutase, and total antioxidant capacity levels of breast muscle. Citrate synthase activity, free radical scavenging capacity, pH24 h and a*45 min values, and the cystine content in the breast muscle were especially higher in the 60 mg/kg CEO group compared to the control group. Collectively, dietary CEO supplementation improved meat quality and nutritional values and enhanced the antioxidant capacity of broiler meat, with 60 mg/kg of CEO having the greatest effect.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

This experiment was conducted to study the protective effects of dietary Chinese gallotannins (CGT) supplementation against Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury in broilers. Four hundred and fifty healthy Arbor Acres broilers (one-day-old) were randomly divided into three groups: (1) basal diet (CON group), (2) basal diet with LPS challenge (LPS group), and (3) basal diet supplemented with 300 mg/kg CGT as well as LPS challenge (LPS+CGT group). The experiment lasted for 21 days. Intraperitoneal LPS injections were administered to broilers in the LPS group and the LPS+CGT group on days 17, 19, and 21 of the trial, whereas the CON group received an intraperitoneal injection of 0.9% physiological saline. Blood and intestinal mucosa samples were collected 3 h after the LPS challenge. The results showed that LPS administration induced intestinal inflammation and apoptosis and damaged small intestinal morphology and structure in broilers. However, dietary supplementation with CGT alleviated the deleterious effects on intestinal morphology and barrier integrity caused by the LPS challenge, while also reducing intestinal apoptosis and inflammation, enhancing intestinal antioxidant capacity, and increasing cecal microbial alpha diversity in the LPS-challenged broilers. Therefore, our findings demonstrated that a 300 mg/kg CGT addition could improve intestinal morphology and gut barrier structure, as well as maintaining bacterial homeostasis, in broilers exposed to LPS. This might partially be attributed to the reduced cell apoptosis, decreased inflammatory response, and enhanced antioxidant capacity in the small intestinal mucosa.

Abstract Cascaded H‐bridge rectifier (CHBR) is widely used in high‐power fields such as STATCOM and power electric traction transformer (PETT) due to its high efficiency and easy expandability. With the high‐reliability operation requirements of power equipment, the fault‐tolerance capability has gradually become a research hotspot nowadays. In order to improve the reliability of the power supply, cascaded H‐bridge rectifier should restore as soon as possible after a fault. However, the traditional fault‐tolerant strategies have a great effect on the grid side and a long recovery time. This paper proposed a quasi‐hot standby fault‐tolerant control strategy. Compared with the traditional strategies, the quasi‐hot standby fault‐tolerant control strategy has a faster recovery speed after the malfunction, and its transient recovery process has less impact on the power grid. Simulation and experiment results show the effectiveness and good recovery performance of the proposed fault‐tolerant control strategy.

This study sought to explore the effects and potential mechanisms of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata to alleviate lipopolysaccharide (LPS)-induced intestinal epithelium injury in broilers. A total of 486 1-day-old broilers were assigned at random to a control (CON) group, LPS group, and LPS+IA group in a 21-d study. The CON and LPS groups received a basal diet, while the LPS+IA group received a basal diet supplemented with 0.6 mg/kg IA. At 17, 19, and 21 days of age, the LPS and LPS+BP groups were injected intraperitoneally with LPS, and the CON group was intraperitoneally injected equivalent amount of saline solution. The results manifested that LPS injection caused intestinal inflammation and lipid peroxidation, disrupted intestinal barrier and function, and increased the abundance of harmful microorganisms. However, dietary IA supplementation alleviated LPS-induced adverse changes in intestinal morphology, apoptosis, mucosal barrier integrity, cecum microorganisms, and homeostasis disorder by decreasing inflammatory cytokines and enhancing antioxidant-related genes expressions; inhibited LPS-induced increases in TLR4 and NF-κB expressions and decreases in Nrf2 and GPX1 genes expressions. Our findings indicated that Macleaya cordata IA addition attenuated LPS-induced intestinal epithelium injury and disorder of intestinal homeostasis by enhancing the anti-inflammatory and antioxidant capacity of broiler chickens possibly via co-regulating TLR4/MyD88/NF-κB and Nrf2 signaling pathways.

Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed to investigate the role of glutamine (Gln) in intestinal inflammation and microbiota in BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according to 2 factors including BPA (0 vs. 0.1%) and Gln (0 vs. 1%) supplemented in basal diet for a 42-day feeding experiment. The results showed BPA exposure impaired piglet growth, induced intestinal inflammation and disturbed microbiota balance. However, dietary Gln supplementation improved the growth performance, while decreasing serum pro-inflammatory cytokine levels in BPA-challenged piglets. In addition, Gln attenuated intestinal mucosal damage and inflammation by normalizing the activation of toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Moreover, dietary Gln supplementation decreased the abundance of Actinobacteriota and Proteobacteria, and attenuated the decreased abundance of Roseburia, Prevotella, Romboutsia and Phascolarctobacterium and the content of short-chain fatty acids in cecum contents caused by BPA exposure. Moreover, there exerted potential relevance between the gut microbiota and pro-inflammatory cytokines and cecal short-chain fatty acids. In conclusion, Gln is critical nutrition for attenuating BPA-induced intestinal inflammation, which is partially mediated by regulating microbial balance and suppressing the TLR4/p38 MAPK/NF-κB signaling.

Abstract Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single‐cell transcriptomic sequencing analysis (scRNA‐seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle‐resident cell profiles and identifies novel and breed‐specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle‐resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro‐adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross‐species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection.

Subway tunnel construction often crosses existing railways, and the soil loss caused by shield construction will inevitably lead to deformation of the surrounding strata and uneven settlement of the adjacent railway tracks, but there are few studies on the existing railway deformation caused by double shield construction in soil–rock composite strata. In this paper, based on the field monitoring data, the deformation analysis of the railway under-crossed by double shield tunnel in soil–rock​ composite stratum was carried out, and the influence law of hard-layer ratio, tunnel burial depth and railway roadbed reinforcement on the railway track deformation was revealed by numerical simulation. Results show that the track settlement mainly occurred in the middle and late stages of the shield crossing the railway. The track settlement showed an obvious trend of decreasing with the increase of hard-layer ratio or tunnel buried depth. The roadbed reinforcement can significantly reduce the settlement of the railway track, the smaller the hard-layer ratio, the better the roadbed reinforcement effect.

Multiple techniques have been suggested to achieve control balance in single-phase three-level neutral-point clamped (3L-NPC) converters. Nevertheless, there is a deficiency of quantitative calculations related to the extent of balancing. Operating beyond the balancing range may result in a sequence of safety incidents. This paper presents a conceptualization of the 3L-NPC converter as two cascaded H-bridges. By employing power conservation principles, the balancing range for the NPC converter is derived, and two novel methods are investigated to broaden the balance range in accordance with the calculated balance range. A comparison is made among the balancing ranges under different balancing control methods. This study establishes a theoretical foundation to ensure the secure and stable operation of the NPC converter.

This study aimed to investigate the impacts of dietary supplementation with Galla chinensis tannins (GCT) on the growth performance, antioxidant capacity, and lipid metabolism of young broilers. Overall, a total of 216 healthy 1 day-old broilers were randomly allocated to CON group and GCT group, and provided with a basal diet or a basal diet added with 300 mg/kg microencapsulated GCT, respectively, in a 21 days trial. Our findings indicated that dietary GCT addition had no significant effects (p > 0.05) on growth performance. However, GCT supplementation led to a significant reduction in the total cholesterol (TC) concentration in the serum and liver (p

This study aims to investigate the effects of macleaya extract and glucose oxidase combination (MGO) on growth performance, antioxidant capacity, immune function, and cecal microbiota in piglets. A total of 120 healthy 28-day-old weaned piglets were randomly divided into two treatments of six replicates. Piglets were either received a basal diet or a basal diet supplemented with 250 mg/kg MGO (2 g/kg sanguinarine, 1 g/kg chelerythrine, and 1 × 106 U/kg glucose oxidase). The results showed that MGO supplementation increased average daily gain (ADG) and decreased feed:gain ratio (F/G) (p

The objective of this study was to evaluate the effect of replacing dicalcium phosphate (DCP) with mono-dicalcium phosphate (MDCP) to formulate low-phosphorus (P) diets on laying performance, egg quality, phosphorus-calcium metabolism, and bone metabolism of 69–78-week-old aged laying hens. Hy-Line Brown laying hens (n = 1,350, 69 weeks old) were randomly assigned to six treatments, each with five replicates of 45 hens. A corn–soybean meal–based diet was formulated to contain 0.12% non-phytate phosphorus (NPP), 3.81% calcium (Ca), and 1,470 FTU/kg phytase. The control group (CON) was supplemented with DCP inorganic phosphorus (Pi) at the NPP level of 0.20% (dietary NPP levels of 0.32%). Test groups (T1–T5) were supplemented with MDCP Pi at NPP levels of 0.07%, 0.11%, 0.15%, 0.18, and 0.20% (dietary NPP levels of 0.19, 0.23, 0.27, 0.30, and 0.32%, respectively). Calcium carbonate levels were adjusted to ensure all experimental diets contained the same Ca levels (3.81%). The feeding trial lasted 10 weeks, with hens increasing in age from 69 to 78 weeks. When supplemented with 1,470 FTU/kg phytase, extra DCP Pi or MDCP Pi did not affect (p > 0.05) laying performance (day laying rate, average egg weight, feed intake, feed-to-egg mass ratio, broken egg rate), egg quality (eggshell strength, albumen height, haugh units), or serum P, Ca, copper (Cu), iron (Fe), zinc (Zn), and manganese (Mn) levels. However, when laying hens were fed MDCP Pi (NPP levels of 0.07 to 0.20%), yolk color improved (p = 0.0148). The tibia breaking strength was significantly higher (p 0.05) different from those in 0.20% NPP DCP Pi hens. Hens fed 0.07% NPP MDCP Pi had higher (p 0.05). The expression of P transporters type IIa Na/Pi cotransporter (NaPi-IIa) in 0.11% and 0.15% NPP MDCP Pi hens were higher than those in 0.20% NPP MDCP Pi group and 0.20% NPP DCP Pi group (p

Bisphenol A (BPA), a kind of environmental toxin, widely impacts daily life. Cysteine (Cys) is a nutritionally important amino acid for piglets. However, it remains unclear whether Cys can alleviate BPA-induced oxidative damage in piglets. The aim of the present study was to explore the protective effects of Cys in BPA-challenged piglets. A total of twenty-four piglets were divided into four groups that were further subdivided based on the type of exposure (with or without 0.1% BPA) in a basal or Cys diet for a 28 d feeding trial. The results showed that BPA exposure decreased the piglets’ average daily weight gain by 14.9%, and decreased dry matter, crude protein and ether extract digestibility by 3.3%, 4.5% and 2.3%, respectively; these decreases were attenuated by Cys supplementation. Additionally, Cys supplementation restored BPA-induced decreases in superoxide dismutase (SOD) and glutathione (GSH), and increases in malondialdehyde (MDA) levels, in the serum and jejunum (p < 0.05). Moreover, BPA decreased the jejunal mRNA expression of antioxidant genes, which were restored by Cys supplementation (p < 0.05). Cys also restored BPA and increased serum D-lactate levels and diamine oxidase (DAO) activity, and BPA decreased jejunal disaccharidase activity (p < 0.05). Further investigations in this study showed that the protective effects of Cys were associated with restoring intestinal barrier integrity by improving the jejunal morphology and enhancing the mRNA expression of tight junction proteins (p < 0.05). Collectively, the results herein demonstrated that Cys supplementation attenuated the impact of BPA-induced oxidative damage on growth performance, nutrient digestibility and intestinal function.

The current study aimed to investigate the effects of dietary Galla Chinensis tannin (GCT) supplementation on antioxidant capacity and gut microbiota composition in broilers. Two hundred eighty-eight Arbor Acres broiler chicks were divided into the CON group and the GCT group; each treatment group contained 6 replicates with 24 broiler chicks per replicate for a period of 42 days, and were fed either a basal diet or the basal diet supplemented with 300 mg/kg GCT. Results revealed that GCT supplementation significantly increased glutathione peroxidase (GSH-Px) activity (p < 0.05) and significantly decreased malondialdehyde (MAD) concentrations in serum (p < 0.05) and significantly increased GSH-Px and catalase (CAT) (p < 0.05) and significantly decreased MDA concentrations in the small intestine. In addition, GCT significantly up-regulated (p < 0.05) the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme-oxygenase 1 (HO-1), catalase (CAT), glutathione peroxidase-1 (GPX1), and NAD(P)H quinone oxidoreductase 1(NQO1). High-throughput sequencing results showed that GCT supplementation significantly increased abundances of Faecalibacterium and Megamonas (p < 0.05). These findings will contribute to our understanding of the effects of dietary Galla Chinensis tannin supplementation on antioxidant capacity and intestinal microbiota composition in broilers.

Herein, Galla Chinensis tannin (GCT) was examined for its influence on preventing lipopolysaccharide (LPS)-induced liver damage in broiler chickens. Approximately 486 one-day-old healthy broilers were randomly allocated to 3 treatment groups (control, LPS, and LPS + GCT). The control and LPS groups were fed a basal diet and the LPS+GCT group was fed the basal diet supplemented with 300 mg/kg GCT. LPS was intraperitoneally injected (1 mg/kg body weight BW) in broilers in the LPS and LPS+GCT groups at 17, 19, and 21 days of age. The results manifested that dietary GCT addition attenuated LPS-induced deleterious effects on serum parameters and significantly increased serum immunoglobulin and complement C3 concentrations relative to the control and LPS groups. Dietary supplementation of GCT inhibited LPS-induced increase in broiler hepatic inflammatory cytokines, caspases activities, and TLR4/NF-κB pathway-related gene mRNA expression. Therefore, 300 mg/kg GCT addition to the diet improved the immune function of broilers and inhibit liver inflammation by blocking the TLR4/NF-κB pathway. Our findings provide support for the application of GCT in poultry production.

Abstract Background Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. Material/methods Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein–protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. Results We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. Conclusions Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.

During the heterotrophic cultivation of microalgae, a cooled process against temperature rise caused by the metabolism of exogenous organic carbon sources greatly increases cultivation cost. Furthermore, microalgae harvesting is also a cost-consuming process. Cell harvesting efficiency is closely related to the characteristics of the algal cells. It may be possible to change cell characteristics through controlling culture conditions to make harvesting easier. In this study, the mesophilic Chlorella pyrenoidosa was found to be a thermal-tolerant species in the heterotrophic mode. The cells could maintain their maximal specific growth rate at 40°C and reached 1.45 day−1, which is equivalent to that of cultures at 35°C but significantly higher than those cultured at lower temperatures. Interestingly, the cells cultured at 40°C were much easier to be harvested than those at lower temperatures. The harvesting efficiency of the cells cultured at 40°C reached 96.83% after sedimentation for 240 min, while the cells cultured at lower temperatures were reluctant to settle. Likely, the same circumstance occurred when cells were harvested by centrifugation or flocculation. The promotion of cell harvesting for cells cultured at high temperatures was mainly attributed to increased cell size and decreased cell surface charge. To the best of our knowledge, this is the first report that cells cultured at high temperatures can promote microalgae harvesting. This study explores a new approach to simplify the cultivation and harvesting of microalgae, which effectively reduces the microalgae production cost.

This experiment was conducted to investigate the effects of Galla Chinensis tannic acid (TA) on growth performance, immune function, and liver health status in broilers. A total of 288 1-day-old Arbor Acres broiler chickens were randomly divided into two groups in a 42-days study. The two groups were a basal diet (CON group) and a basal diet supplemented with 300 mg/kg Galla Chinensis tannic acid (TA group). The results showed that the TA group had significantly decreased feed-to-gain ratio (F/G) throughout the experiment (P < 0.05). The levels of total protein, albumin, low density lipoprotein, high density lipoprotein, urea, total cholesterol, and glucose in the TA group were significantly higher than in the CON group (P < 0.05). In addition, the serum immunoglobulin G, immunoglobulin M, and complements (C3, C4) levels in the TA group were significantly higher than those in the CON group (P < 0.05). Compared with the CON group, the hepatic interleukin-6, interleukin-18, NLRs family pyrin domain containing 3 (NLRP3), caspase-1, and caspase-3 in the TA group were significantly decreased (P < 0.05). Besides, TA group had significantly lower mRNA expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB), and NLRP3 in liver (P < 0.05). The TA group had significantly higher the mRNA expression levels of Bcl-2 than CON group in liver (P < 0.05). Moreover, TA group tended to decrease Bax/Bcl-2 ratio in liver (P < 0.10). To sum up, dietary supplemented with microencapsulated TA from Galla Chinensis had beneficial effects on growth performance, immune function, and liver health status in broilers. The protective role of TA from Galla Chinensis in liver health of broilers might be related to the inhibition of hepatic apoptosis and pyroptosis via inactivation of TLR4/MyD88/NF-κB signaling pathway.

This study aimed to investigate the effect of dietary supplementation with Bopu powder on intestinal development and bacterial community composition in broiler chickens. A total of 486 1-day-old arbor acres broilers were fed a basal diet (CON group), a basal diet supplemented with 50 mg/kg aureomycin (AB group), or a basal diet supplemented with 40 mg/kg Bopu powder (BP group). The results showed that the BP group had significantly lower serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and diamine oxidase concentrations and had significantly higher serum IL-10 concentrations than CON group (p

The aim of this study was to explore the effects of supplementing paraformic acid (PFA) to the diet of broiler chickens on intestinal development, inflammation, and microbiota. A total of 378 healthy 1-day-old Arbor Acres broilers with similar birth weight were used in this study, and randomly assigned into two treatment groups. The broiler chickens were received a basal diet or a basal diet supplemented with 1,000 mg/kg PFA. Results showed that PFA supplementation increased (P < 0.05) small intestinal villus height and villus height/crypt depth ratio, elevated intestinal mucosal factors (mucin 2, trefoil factor family, and zonula occludens-1) concentrations, and upregulated mNRA expression of y + L amino acid transporter 1. Moreover, PFA supplementation decreased (P < 0.05) the concentrations of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10), activities of caspase-3 and caspase-8, and mNRA expressions of Toll-like Receptor 4, nuclear factor-kappa B, Bax, and Bax/Bcl-2 ratio in small intestinal mucosa. Dietary PFA supplementation also increased (P < 0.05) alpha diversity of cecal microbiota and relative abundance of Alistipes. The present study demonstrated that supplementation of 1,000 mg/kg PFA showed beneficial effects in improving intestinal development, which might be attributed to the suppression of intestinal inflammation and change of gut microbiota composition in broiler chickens. These findings will aid in our knowledge of the mechanisms through which dietary PFA modulates gut development, as well as support the use of PFA in poultry industry.

This study investigated the effects of Bacillus subtilis BC02 supplementation on broiler performance, antioxidant capacity, and cecal microbes. A total of 288 one-day-old Arbor Acres broilers were randomly divided into three groups. The control group were fed a basal diet, and experimental groups were fed a basal diet supplemented with 250 and 500 mg/kg Bacillus subtilis BC02 (BS250 and BS500), respectively. The results showed that Bacillus subtilis BC02 supplementation increased the average daily feed intake but decreased the feed to gain ratio in broilers from 0 to 14, 0 to 28, and 0 to 42 days. Meanwhile, BS500 significantly decreased triglyceride and serum urea nitrogen levels compared with the control and BS250 groups (p < 0.05). Moreover, diet supplemented with 500 mg/kg Bacillus subtilis BC02 improved the antioxidant capacity by increasing the serum and jejunum levels of superoxide dismutase and glutathione, decreasing that of malondialdehyde and increasing the jejunum mRNA expression of SOD2, CAT, GPX1, and Nrf2 (p < 0.05). Dietary Bacillus subtilis BC02 supplementation increased the villus height, velvet concealed ratio, and the mRNA expressions of IL-2, IL-4, IL-10, and IL-12 (p < 0.05). In addition, the Bacteroidota, Proteobacteria, Helicobacter, and Prevotellaceae UCG-001 were significantly increased (p < 0.05) in the BS500 group. In conclusion, dietary Bacillus subtilis BC02 supplementation can improve the growth performance, antioxidant capacity, and intestinal microflora abundances in broilers.

Abstract Background There is no consensus or management algorithm for primary hyperparathyroidism (PHPT) in pregnancy. Methods This study comprises a retrospective case series. From August 2014 to December 2020, 9 cases of PHPT in pregnancy were diagnosed by a multidisciplinary team (MDT) consultation center of obstetrics in our hospital. Their clinical manifestations, treatment strategies, and maternal and infant outcomes were analyzed. Results The median onset age of the patients was 32 (25 ~ 38) years. PHPT was diagnosed in two cases before pregnancy, in six cases during pregnancy and in one case postpartum. The main clinical manifestations were nausea, vomiting, and other nonspecific symptoms, with anemia as the most common maternal complication. Hypercalcemia crisis was developed in one case. The median levels of preoperative serum calcium and parathyroid hormone (PTH) were 3.08 (2.77 ~ 4.21) mmol/L and 300.40 (108.80 ~ 2603.60) pg/ml, respectively. The parathyroid ultrasonography tests were positive in eight cases and negative in one patient who had an ectopic lesion localized by 99mTc-MIBI. Parathyroidectomy was conducted in 7 cases during the 2nd trimester, including 2 patients diagnosed before pregnancy who refused surgery, 1 patient during the 1st trimester, and 1 patient postpartum, with a significant reduction in serum concentrations of calcium and PTH. A management algorithm was developed. Conclusion This case series suggests that pregnant women with PHPT should be managed by MDT according to the algorithm. If PHPT is confirmed in fertile women before pregnancy, parathyroidectomy should be strongly suggested and performed. If PHPT is diagnosed during pregnancy, even in its mild form, surgical treatment, optimally during the 2nd trimester, is effective and safe for pregnancy and neonatal outcome.

Cao, Li, et al. sequence 13 perennial woody plant species of Lycium, and specifically provide a draft assembly of L. ruthenicum and a chromosome-level assembly of L. barbarum, the wolfberry or Goji berry. From a phylogenetic tree the authors identify an ancient hexaploidization event, and report the evolution of gene families including fruit ripening, fruit coloration, polysaccharide synthesis and self-incompatibility within Solanaceae and the general biogeography of L. barbarum.

Organohalides are widely used as synthetic precursors and target products, but for various halogenation reactions there is a need for effective catalysts to activate commercially available haleniums. Here, the authors report that TEMPO and its derivatives are active catalysts for electrophilic halogenation of olefins, alkynes and aromatics, under mild reaction conditions and with good functional group tolerance.

This study aimed to investigate the effects of dietary supplementation with Macleaya cordata extract (MCE) containing protopine and allotypotopine on the growth performance and liver health in broiler chickens. A total of 486 1-day-old male AA broiler chickens were randomly assigned to the following three groups: (1) control (CON) group, broiler chickens fed a basal diet; (2) AGP group (positive control), broiler chickens fed a basal diet supplemented with 50 mg/kg aureomycin; (3) MCE group, broiler chickens fed a basal diet supplemented with 0.6 mg/kg MCE including 0.4 mg/kg protopine and 0.2 mg/kg allotypotopine. The results showed that the MCE group had significantly higher final body weight and average daily gain from d 0 to 42 than the other groups (p < 0.05), and groups MCE and AGP both had significantly lower feed-to-gain ratio from d 0 to 42 than the CON group (p < 0.05). Serum total protein, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, glucose, immunoglobulin A, immunoglobulin M, and complements (C3, C4) concentrations in the MCE group were significantly higher than in the CON group (p < 0.05). Dietary MCE or aureomycin supplementation significantly reduced the hepatic contents of 8-hydroxy-2'-deoxyguanosine, malondialdehyde, interleukin (IL)-1β, IL-6, NLRs family pyrin domain containing 3 (NLRP3), and caspase-1 in the liver (p < 0.05). Moreover, MCE or aureomycin supplementation significantly inhibited mRNA expressions of Toll-like receptor 4, myeloid differentiation factor 88, nuclear factor-κB, and NLRP3, as well as the expression ratio of Bax to Bcl-2 mRNA (p < 0.05). Therefore, our study suggested that dietary supplementation with 0.6 mg/kg MCE containing protopine and allocryptopine improved growth performance and benefited liver health in broiler chickens possibly through inhibiting caspase-1-induced pyroptosis by inactivating TLR4/MyD88/NF-κB/NLRP3 signaling pathway, and provided support for the application of MCE containing protopine and allocryptopine as an alternative to antibiotics in the feed industry.

Oral cancer is one of the most common tumours in the world threatening human life and health. The 5-years survival rate of patients with oral cancer has not been improved significantly for many years. The existing clinical diagnostic methods rarely achieve early diagnosis due to deficiencies such as lack of sensitivity. Most of the patients have progressed to the advanced stages when oral cancer is detected. Unfortunately, the traditional treatment methods are usually ineffective at this stage. Therefore, there is an urgent need for more effective and precise techniques for early diagnosis and effective treatment of oral cancer. In recent decades, nanomedicine has been a novel diagnostic and therapeutic platform for various diseases, especially cancer. The synthesis and application of various nanoagents have emerged at the right moment. Among them, polymer nanoagents have unique advantages, such as good stability, high biosafety and high drug loading, showing great potential in the early accurate diagnosis and treatment of tumours. In this review, we focus on the application of advanced polymeric nanoagents in both the diagnosis and treatment of oral cancer. Then, the future therapy strategies and trends for polymeric nanoagents applied to oral cancer are discussed, with the hope that more advanced nanomedical technology will be applied to oral cancer research and promote the development of stomatology.

This study was conducted to evaluate the effects of phytase supplementation in low-phosphorus diets on the production performance, phosphorus–calcium metabolism, and bone metabolism in laying hens from 69 to 78 weeks of age. Hy-Line Brown laying hens (n = 1350) were assigned randomly to six treatments with five replicates of 45 birds. A corn–soybean meal-based diet with no inorganic phosphates was formulated to contain 0.12% non-phytate phosphorus (NPP) and 1470 FTU/kg phytase (Released phytate phosphorus content ≥ 0.1%). Inorganic phosphorus (dicalcium phosphate) was supplemented into the basal diet to construct five test diets (level of NPP supplementation = 0.10%, 0.15%, 0.20%, 0.25%, and 0.30%). The level of calcium carbonate was adjusted to ensure that all six experimental diets contained the same calcium percentage (3.81%). The feeding trial lasted 10 weeks (hens from 69 to 78 weeks of age). Upon supplementation with phytase (1470 FTU/kg), supplemental inorganic phosphates (dicalcium phosphate) had no significant effects (p > 0.05) on the production performance or egg quality. Significant differences in serum levels of calcium, phosphorus, copper, iron, zinc, or manganese were not detected across treatments (p > 0.05). Hens fed NPP (0.15%, 0.20%, 0.25%, and 0.30%) had higher levels (p < 0.0001) of tibial ash, calcium, and phosphorus than those not fed inorganic phosphates. The tibial breaking strength of the group without inorganic phosphates was significantly lower than that of the other groups (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of calcitonin (CT) and 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3). Hens that did not receive supplementation with inorganic phosphates had higher serum levels of parathyroid hormone (PTH), osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) compared with those in the other groups (p < 0.01). Serum levels of CTX-I and TRACP-5b were significantly lower in the NPP-supplementation groups of 0.25% and 0.30% than in the 0.10% NPP-supplementation group (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of bone-alkaline phosphatase (BAP), osteocalcin (OCN), or osteopontin (OPN). Hens not fed inorganic phosphate had the highest renal expression of phosphorus transporter type IIa Na/Pi cotransporter (NaPi-Ⅱa). Renal expression of NaPi-Ⅱa was increased significantly in NPP-supplementation groups of 0.10–0.20% compared with that in NPP-supplementation groups of 0.25% and 0.30% (p < 0.0001). The results indicated that a reduction in NPP supplementation to 0.15% (dietary NPP level = 0.27%) with phytase inclusion did not have an adverse effect on the production performance or bone health of laying hens from 69 to 78 weeks of age, which might be attributed to renal phosphorus reabsorption and bone resorption. These findings could support the application of low-phosphorus diets in the poultry industry.

Abstract Background Long non-coding RNAs (lncRNAs) are emerging key regulators involved in a variety of biological processes such as cell differentiation and development. The balance between myogenesis and adipogenesis is crucial for skeletal muscle homeostasis in humans and meat quality in farm animals. The present study aimed to reveal the global transcriptomic profiles of adipogenic (Adi-) and myogenic (Myo-) precursors derived from porcine skeletal muscle and identify lncRNAs involved in the modulation of myogenesis homeostasis in porcine skeletal muscle. Results In this study, a total of 655 novel individual lncRNAs including differentially expressed 24 lncRNAs, and 755 differentially expressed mRNAs were identified (fold change ≥2 or ≤ 0.5 and adjusted P

This study was conducted to evaluate the effects of organic trace elements (Cu, Fe, Zn, and Mn) on performance, egg quality, trace elements utilization, and intestinal function in late-phase laying hens. A total of 1,080 laying hens (Hy-line brown, 65 weeks old) were randomly assigned to four treatments with six replications of 45 layers each. The basal diet was prepared without adding exogenous trace elements. The control group was fed with a basal diet supplemented with 600 mg/kg of inorganic trace elements. The three treatment groups were fed basal diets supplemented with 300, 450, and 600 mg/kg organic trace elements (OTE300, 450, and 600), respectively. The results showed that there was no significant difference in growth performance among all treatments. However, OTE450 significantly improved the eggshell strength of laying hens (p < 0.05), but had no significant effects on haugh unit, egg yolk weight, eggshell weight, and eggshell thickness, compared with other groups. Moreover, compared with the control group, OTE450 significantly increased the contents of copper, iron, and zinc in serum (p < 0.05). Meanwhile, all of the trace elements had a lower deposition in the feces in organic trace elements groups (p < 0.05). Histological analysis showed that the addition of organic trace elements could significantly improve the villus height and villus concealment ratio (p < 0.05). In addition, the messenger RNA (mRNA) and protein expressions of divalent metal transporter 1 (DMT1), zinc transporter 1 (ZnT-1), and ferroportin 1 (FPN1) were the highest in the OTE450 group. In conclusion, OTE450 could improve egg quality, intestinal function, and trace element utilization efficiency. Thus, this study provides a theoretical basis for the application of low levels of organic trace elements in laying hens.

Line commutated converter (LCC) has been widely applied in hybrid high voltage direct current (HVDC) transmission system, where the modular multilevel converter (MMC) is applied as receiving end and may induce low order harmonics in DC-link voltage. These low order harmonics will introduce the low frequency fluctuation into the control loop of LCC and complex the harmonics analysis. The traditional method to calculate LCC harmonics is derived by the switching function and modulation theory, which only obtains characteristic harmonics. The low-frequency fluctuation superimposed on the firing angle in the control system is ignored in the traditional method. In this paper, the interharmonics, which is introduced by firing angle fluctuation, is revealed by the double Fourier method. A fitting function method is applied for depicting the varied commutation overlap caused by firing angle fluctuation. Compared to the traditional method, the proposed method can effectively analyze both characteristic harmonics and interharmonics in the condition of low-frequency fluctuation of the firing angle. The accuracy and effectiveness of the theoretical analysis are verified with a three-phase LCC rectifier built in PSCAD/EMTDC and experimental test.

AimAngiogenesis plays a vital role in airway remodeling in chronic asthma. ORMDL3 has been identified to be closely associated with the development of asthma remodeling. This study was to investigate the mechanism of ORMDL3 in angiogenesis of chronic asthma.MethodsBALB/c mice were divided into three groups, including an asthmatic group (group A), a budesonide-treated group (group B), and a normal control group (group C). Hematoxylin and eosin and Masson staining were used to evaluate the pathological changes. Angiogenesis in lung tissue was examined by CD31 staining. The changes of ORMDL3, ERK1/2, and angiogenesis-associated MMP-9 and Vascular endothelial growth factor (VEGF) expression were examined. Furthermore, ORMDL3, MMP-9, and VEGF mRNA and protein levels were examined after transfection in BEAS-2B cells with the ORMDL3-overexpressed lentiviral vector.ResultsCompared with the control group, asthmatic mice indicated more severe airway angiogenesis with increased ORMDL3, ERK1/2, MMP-9, and VEGF expression. Budesonide alleviated airway angiogenesis, and CD31 expression was positive with the levels of ORMDL3, MMP-9, and VEGF (P < 0.01). After successful transfection in BEAS-2B cells with the ORMDL3-overexpressing lentiviral vector, VEGF, and MMP-9 expression were activated in vitro (P < 0.01).ConclusionIn conclusion, our study provides novel evidence that ORMDL3 promotes angiogenesis through upregulating VEGF and MMP-9 in chronic asthma.

Fritillaria wilt is a kind of soil-borne disease that causes a large reduction in the yield of Fritillaria ussuriensis. The diversity and structure of the soil microbial community are important factors affecting the health of Fritillaria ussuriensis. The analysis of the microbial community in the diseased and healthy soils provided a theoretical basis for revealing the pathological mechanism and prevention of Fritillaria wilt disease. In the present study, we sequenced the soil microorganisms from healthy (H), pathology (P) and blank (B) soil samples by Illumina MiSeq. Determined the soil physicochemical properties respectively, analyzed the soil microbial diversity and structure, and constructed single factor co-correlation networks among microbial genera. The results showed that Ascomycota (48.36%), Mortierellomycota (23.06%), Basidiomycota (19.00%), Proteobacteria (31.74%), and Acidobacteria (20.95%) were dominant in the soil. The diversity of healthy soil was significantly greater than that of diseased soil samples (P and B) (P < 0.05). The populations of Fusarium and Humicola significantly increased in the diseased soil sample (P and B) (P < 0.05). RB41 (4.74%) and Arthrobacter (3.30%) were the most abundant genera in the healthy soil. Total nitrogen (TN), available nitrogen (AN), total potassium (TK), available potassium (AK), and inorganic salt (salt) were significantly correlated with soil microbial communities (P < 0.05). The relationship between fungi and the plant was mostly positive, whereas bacteria showed the opposite trend. In conclusion, the diversity and structure of the soil microbial community were closely related to the health level of Fritillaria ussuriensis. Fusarium and Humicola affect the severity of Fritillaria wilt disease, while RB41 and Arthrobacter are the important indicators for maintaining the health of Fritillaria ussuriensis. Moreover, environmental factors greatly affect the abundance and formation of soil microbial community. The interactions in microbial communities also influence the healthy growth of Fritillaria ussuriensis.

A total of 24,000 healthy 1-day-old Arbor Acres broilers with similar initial weights were used in this study and fed a basal diet supplemented with 0, 400 and 800 mg/kg isoleucine (Ile), denoted CON, ILE400 and ILE800, respectively. Results revealed that the final body weight, average daily weight gain, and eviscerated carcass rate, of broiler chickens in the ILE400 group were significantly higher than in other groups (p < 0.05). In addition, the ILE400 and ILE800 groups had a lower feed conversion rate and a higher survival rate and breast muscle rate (p < 0.05), while the abdominal fat rate was significantly lower than the CON group (p < 0.05). There were significantly lower serum concentrations of UREA, glucose (GLU) and total cholesterol (TCHO) in the ILE400 and ILE800 groups than in the CON group (p < 0.05); glutathione peroxidase (GSH-Px) activity was significantly higher in the ILE400 group than in the other groups, and tumor necrosis factor-alpha (TNF-α) concentration was considerably lower than in other groups (p < 0.05). Moreover, interleukin (IL)-10 concentration in the ILE800 group was significantly higher than in the other groups (p < 0.05). The ILE400 group significantly down-regulated the mRNA expressions of fatty-acid synthase (FASN) and solid alcohol regulatory element binding protein 1c (SREBP1c), and significantly up-regulated the mRNA expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and sirtuin1 (Sirt1) (p < 0.05). The ILE400 group had significantly higher intestinal villus height than the CON and ILE800 groups, while the ILE800 group had significantly lower intestinal villus height/crypt depth (p < 0.05). Furthermore, high-throughput sequencing showed that the Shannon index, and Verrucomicrobiota, Colidextribacter and Bacteroides abundances were significantly higher in the ILE400 group than in the CON group (p < 0.05). Interestingly, the ILE800 group reduced the Simpson index, phylum Firmicutes and Bacteroidota abundances (including genera Colidextribacter, Butyricicoccus, [Ruminococcus]_torques_group, Bacteroides, Alistipes, Barnesiella and Butyricimonas), and increased Proteobacteria and Cyanobacteria (including genera Dyella, Devosia, unidentified_Chloroplast and Hyphomicrobium) (p < 0.05). Overall, our study showed that adding 400 mg/kg Ile to the diet (diets total Ile levels at 1.01%, 0.90% and 0.87% during the starter, grower and finisher phases, respectively) increased production performance and improved the health status in broiler chickens.

The current study aimed to explore the effects of supplementing paraformic acid (PFA) into broilers’ diet on growth performance, inflammatory responses, and liver protection. A total of 567 healthy one-day-old broilers were used in a 42-d study, and they were randomized into three groups. Broilers were fed a basal diet (CON group) or the basal diet supplemented with either 50 mg/kg aureomycin (AB group) or 1000 mg/kg PFA (PFA group). The results showed that the PFA and AB groups had a higher feed conversion rate than the CON group from day 21 to 42 (p < 0.05). Dietary PFA or aureomycin supplementation decreased serum levels of interleukin (IL)-1β, IL-6, IL-10, alanine transaminase, diamine oxidase, and D-lactate, and significantly increased serum concentrations of immunoglobulin (Ig) A, IgM, and complement C4 (p < 0.05). Moreover, dietary PFA or aureomycin supplementation decreased hepatic levels of caspase-1, NOD-like receptor family pyrin domain containing 3 (NLRP3), tumor necrosis factor-alpha, IL-6, and IL-18, as well as NF-κB mRNA expression (p < 0.05). Above all, PFA supplementation into the broilers’ diet improved growth performance, inhibited inflammatory responses, and benefited liver protection. The protective effects of PFA on the liver might be related to inhibition of caspase-1-induced pyroptosis via inactivating the NF-κB/NLRP3 inflammasome axis in broiler chickens.

The aim of this study was to explore the effect of zearalenone (ZEA) exposure on uterine development in weaned gilts by quantitative proteome analysis with tandem mass spectrometry tags (TMT). A total of 16 healthy weaned gilts were randomly divided into control (basal diet) and ZEA3.0 treatments groups (basal diet supplemented with 3.0 mg/kg ZEA). Results showed that vulva size and uterine development index were increased (p < 0.05), whereas serum follicle stimulation hormone, luteinizing hormone and gonadotropin-releasing hormone were decreased in gilts fed the ZEA diet (p < 0.05). ZEA, α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) were detected in the uteri of gilts fed a 3.0 mg/kg ZEA diet (p < 0.05). The relative protein expression levels of creatine kinase M-type (CKM), atriopeptidase (MME) and myeloperoxidase (MPO) were up-regulated (p < 0.05), whereas aldehyde dehydrogenase 1 family member (ALDH1A2), secretogranin-1 (CHGB) and SURP and G-patch domain containing 1 (SUGP1) were down-regulated (p < 0.05) in the ZEA3.0 group by western blot, which indicated that the proteomics data were dependable. In addition, the functions of differentially expressed proteins (DEPs) mainly involved the cellular process, biological regulation and metabolic process in the biological process category. Some important signaling pathways were changed in the ZEA3.0 group, such as extracellular matrix (ECM)-receptor interaction, focal adhesion and the phosphoinositide 3-kinase–protein kinase B (PI3K-AKT) signaling pathway (p < 0.01). This study sheds new light on the molecular mechanism of ZEA in the uterine development of gilts.