Assessment of Non-Phytate Phosphorus Requirements of Chinese Jing Tint 6 Layer Chicks from Hatch to Day 42.

We aimed to estimate the non-phytate phosphorus (NPP) requirements of Chinese Jing Tint 6 layer chicks. We randomly allocated 720 birds to five treatments with six cages of 24 birds each, feeding them a corn-soybean diet containing 0.36%, 0.41%, 0.46%, 0.51%, and 0.56% NNP. The results showed that the body weight gain (BWG), tibial length, and apparent total tract digestibility coefficients (ATTDC) of P were affected (p < 0.05) by dietary NPP level. A quadratic broken-line analysis (p < 0.05) of BWG indicated that the optimal NPP for birds aged 1-14 d was 0.411%. Similarly, 0.409% of NPP met tibial growth needs. However, 0.394% of NPP was optimal for P utilization according to the ATTDC criterion. For 15-42 d birds, 0.466% NPP, as estimated by the BWG criterion, was sufficient for optimal growth without decreasing P utilization. Using the factorial method, NPP requirements were calculated as 0.367% and 0.439%, based on the maintenance factors and BWG for 1-14 and 15-42 d birds, respectively, to maintain normal growth. Combining the non-linear model with the factorial method, this study recommends dietary NPP levels of 0.367% and 0.439% for 1-14 and 15-42 d birds, respectively, to optimize P utilization without affecting performance.

Metachronous multifocal carcinoma: A case report.

BACKGROUND: The incidence of multiple primary carcinomas (MPC) varies greatly, ranging from 0.73% to 11.70% in foreign countries, with duo-duplex carcinoma being the most common, trio-duplex carcinoma and above being rare, and simultaneous multigenic carcinoma being even rarer, accounting for 18.4% to 25.3% of the incidence of MPC. However, there is no report regarding patients presenting with simultaneous dual-origin carcinoma of the liver and colon and heterochronous pancreatic cancer. CASE SUMMARY: We report a special case of multifocal carcinoma, in which one patient had a medical condition of primary liver and colon cancer and pancreatic cystadenocarcinoma 2 years after surgery. Through aggressive advanced fluorescent laparoscopic techniques, standardized immunotherapy, targeting, and chemotherapy, a better prognosis and a desirable survival period were achieved for the patient. CONCLUSION: There is a need to clarify the nature of MPC through advanced surgical means to ensure better diagnosis and treatment.

Laparoscopic left hemihepatectomy guided by indocyanine green fluorescence: A cranial-dorsal approach.

BACKGROUND: Advancements in laparoscopic technology and a deeper understanding of intrahepatic anatomy have led to the establishment of more precise laparoscopic hepatectomy (LH) techniques. The indocyanine green (ICG) fluorescence navigation technique has emerged as the most effective method for identifying hepatic regions, potentially overcoming the limitations of LH. While laparoscopic left hemihepatectomy (LLH) is a standardized procedure, there is a need for innovative strategies to enhance its outcomes. AIM: To investigate a standardized cranial-dorsal strategy for LLH, focusing on important anatomical markers, surgical skills, and ICG staining methods. METHODS: Thirty-seven patients who underwent ICG fluorescence-guided LLH at Qujing Second People's Hospital between January 2019 and February 2022 were retrospectively analyzed. The cranial-dorsal approach was performed which involves dissecting the left hepatic vein cephalad, isolating the Arantius ligament , exposing the middle hepatic vein, and dissecting the parenchyma from the dorsal to the foot in order to complete the anatomical LLH. The surgical methods, as well as intra- and post-surgical data, were recorded and analyzed. Our hospital's Medical Ethics Committee approved this study (Ethical review: 2022-019-01). RESULTS: Intraoperative blood loss during LLH was 335.68 ± 99.869 mL and the rates of transfusion and conversion to laparotomy were 13.5% and 0%, respectively. The overall incidence of complications throughout the follow-up (median of 18 months; range 1-36 months) was 21.6%. No mortality or severe complications (level IV) were reported. CONCLUSION: LLH has the potential to become a novel, standardized approach that can effectively, safely, and simply expose the middle hepatic vein and meet the requirements of precision surgery.

Ferrous-sucrose complex supplementation regulates maternal plasma metabolism and the fecal microbiota composition and improves neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows.

Pregnancy is a dynamic state involving rapid physiological changes in metabolism, affecting the health and development of the offspring. During pregnancy, the placenta constitutes a physical and immunological barrier to provide fetal nutrition through the maternal blood and prevent the exposure of the fetus to dangerous signals. Metabolic changes in the plasma, the fecal microbiota profile, and functional regulation in the placenta were studied in sows supplied with a ferrous-sucrose complex (FeSuc) from late gestation to parturition. The results revealed that maternal FeSuc supplementation enhanced arginine and proline metabolism, glutathione metabolism, with increased glutamic acid, beta-D-glucosamine, L-proline, 1-butylamine, and succinic acid and reduced sphingosine and chenodeoxycholic acid sulfate levels in the plasma. Moreover, significantly increased abundances of Christensenellaceae_R-7_group, Prevotellaceae_NK3B31_group, and Lachnospiraceae_NK4B4_group were detected in the feces of sows from the FeSuc group (P < 0.05). Spearman's correlation analysis indicated that Prevotellaceae_NK3B31_group abundances were positively correlated with glutamic acid, indoxyl sulfate, acetyl-DL-leucine, and beta-D-glucosamine, while Christensenellaceae_R-7_group was positively correlated with beta-D-glucosamine. Furthermore, maternal FeSuc supplementation significantly increased neonatal glucose (P < 0.01) and iron (P < 0.01) in the neonatal serum, significantly increased IL-10 and TGF-ß1 levels in the neonatal liver (P < 0.01) and jejunum (P < 0.05), promoted the transcription of immune molecules in the placenta, and significantly increased the protein expressions of EGF (P < 0.05), PI3K (P < 0.01), p-PI3K (P < 0.001), p-AKT (P < 0.01), and glucose transporter 1 (GLUT1) (P < 0.001) in the placenta. The current study demonstrated that FeSuc supplementation regulated maternal metabolism processes by altering the fecal microbial composition and improved neonatal immunity and placental glucose transportation by activating the EGF/PI3K/AKT signaling pathways in sows.

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging.

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions, such as developing and preserving the skeletal muscle system. However, the interplay between gut microbiota/metabolites and the regulation of satellite cell (SC) homeostasis, particularly during aging, remains elusive. We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development, regeneration, and aging process. Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice, leads to the activation of SCs or a significant reduction in the total number. Furthermore, employing multi-omics (e.g., RNA-seq, 16S rRNA gene sequencing, and metabolomics) and bioinformatic analysis, we demonstrate that the reduced butyrate levels, alongside the gut microbial dysbiosis, could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging. Meanwhile, butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota, potentially by inhibiting the proliferation and differentiation of SCs/myoblasts. The butyrate effect is likely facilitated through the monocarboxylate transporter 1 (Mct1), a lactate transporter enriched on membranes of SCs and myoblasts. As a result, butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging. Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

Dynamic changes of endophytic bacteria in the bark and leaves of medicinal plant Eucommia ulmoides in different seasons.

The bark and leaves of the Eucommia ulmoides Oliv. (E. ulmoides) have good medicinal value. Studies show endophytes play important roles in host medicinal plant secondary metabolite synthesis, with season being a key influencing factor. Therefore, we used 16 S rRNA to detect endophytic bacteria (EB) in E. ulmoides bark and leaves collected in winter, spring, summer, and autumn, and analyzed the contents of major active components respectively. The results showed that the species diversity and richness of EB of the E. ulmoides bark were higher than those of leaves in all seasons except fall. Among them, the higher species diversity and richness were found in the E. ulmoides bark in winter and spring. EB community structure differed significantly between medicinal tissues and seasons. Concurrently, the bark and leaves of E. ulmoides showed abundant characteristic EB across seasons. For active components, geniposidic acid showed a significant positive correlation with EB diversity and richness, while the opposite was true for aucubin. Additionally, some dominant EB exhibited close correlations with the accumulation of active components. Delftia, enriched in autumn, correlated significantly positively with aucubin. Notably, the impact of the same EB genera on active components differed across medicinal tissues. For example, Sphingomonas, enriched in summer, correlated significantly positively with pinoresinol diglucoside (PDG) in the bark, but with aucubin in the leaves. In summary, EB of E. ulmoides was demonstrated high seasonal dynamics and tissue specificity, with seasonal characteristic EB like Delftia and Sphingomonas correlating with the accumulation of active components in medicinal tissues.

Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma.

The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis-trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1-2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II-III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.

Gut microbiota in muscular atrophy development, progression, and treatment: New therapeutic targets and opportunities.

Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options. Muscle atrophy can have various causes, including myogenic, neurogenic, and other factors. Recent investigation has underscored a compelling link between the gut microbiota and skeletal muscle. Discerning the potential differences in the gut microbiota associated with muscle atrophy-related diseases, understanding their influence on disease development, and recognizing their potential as intervention targets are of paramount importance. This review aims to provide a comprehensive overview of the role of the gut microbiota in muscle atrophy-related diseases. We summarize clinical and pre-clinical studies that investigate the potential for gut microbiota modulation to enhance muscle performance and promote disease recovery. Furthermore, we delve into the intricate interplay between the gut microbiota and muscle atrophy-related diseases, drawing from an array of studies. Emerging evidence suggests significant differences in gut microbiota composition in individuals with muscle atrophy-related diseases compared with healthy individuals. It is conceivable that these alterations in the microbiota contribute to the pathogenesis of these disorders through bacterium-related metabolites or inflammatory signals. Additionally, interventions targeting the gut microbiota have demonstrated promising results for mitigating disease progression in animal models, underscoring the therapeutic potential of modulating the gut microbiota in these conditions. By analyzing the available literature, this review sheds light on the involvement of the gut microbiota in muscle atrophy-related diseases. The findings contribute to our understanding of the underlying mechanisms and open avenues for development of novel therapeutic strategies targeting the gut-muscle axis.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

Integration of gut microbiota and metabolomics for the hematopoiesis of Siwu paste on anemia rats.

Background: To investigate the regulation mechanism of hematopoiesis of Siwu paste (SWP) in anemia rats, which is a classic Chinese prescription used for nourishing blood or blood deficiency over 1000 years. Methods: Blood cell and biochemical analysis were used to evaluate the hematopoietic function of SWP in anemia rats. The intestinal microbial composition was analyzed with 16S rRNA gene sequencing, and the metabolites were profiled using UPLC-TripleTOF system nontargeting metabolomics. Results: SWP can improve the levels of red blood cells, hemoglobin, platelet, hematocrit value, white blood cells, lymphocyte, EPO, TPO, and GM-CSF in anemia rats, and significantly change the microbial community and its metabolites. The correlation analysis of intestinal microbiota-hematopoietic efficacy shows that 13 kinds of different intestinal flora were related to hematopoietic efficacy, in which Prevotella_1, Prevotella_9, Lactobacillus, and norank_f__Muribaculaceae were significantly positively correlated with hematopoiesis, nine kinds of intestinal flora are negatively correlated with hematopoietic effect. Compared with anemia rats, 218 potential metabolic biomarkers and 36 metabolites with significant differences were identified in the SWP treatment group, and the key metabolites were mainly amino acids and lipids. An in-depth analysis of metabolic pathways showed that SWP mainly affected 7 metabolic pathways, including aminobenzoic acid degradation and tryptophan metabolism. Conclusion: The study provides novel insights into the regulation of hematopoiesis of SWP in anemia rats that were correlated with gut microbiota and the metabolites, which through the restoration of the firmicutes/bacteroidetes ratio.

Gut microbiota bridges the iron homeostasis and host health.

The gut microbiota acts as a symbiotic microecosystem that plays an indispensable role in the regulation of a number of metabolic processes in the host by secreting secondary metabolites and impacting the physiology and pathophysiology of numerous organs and tissues through the circulatory system. This relationship, referred to as the "gut-X axis", is associated with the development and progression of disorders, including obesity, fatty liver and Parkinson's disease. Given its importance, the gut flora is a vital research area for the understanding and development of the novel therapeutic approaches for multiple disorders. Iron is a common but necessary element required by both mammals and bacteria. As a result, iron metabolism is closely intertwined with the gut microbiota. The host's iron homeostasis affects the composition of the gut microbiota and the interaction between host and gut microbiota through various mechanisms such as nutrient homeostasis, intestinal peaceability, gut immunity, and oxidative stress. Therefore, understanding the relationship between gut microbes and host iron metabolism is not only of enormous significance to host health but also may offer preventative and therapeutic approaches for a number of disorders that impact both parties. In this review, we delve into the connection between the dysregulation of iron metabolism and dysbiosis of gut microbiota, and how it contributes to the onset and progression of metabolic and chronic diseases.

Design, Synthesis, and Biological Activity of Donepezil: Aromatic Amine Hybrids as Anti-Alzheimerss Drugs.

In this study, benzylpiperidine, the active group of donepezil (DNP), was connected with the neurotransmitter phenylethylamine by square amide, in which the fat chain of phenylethylamine was reduced and the benzene rings were substituted. A series of multifunctional hybrid compounds, including DNP-aniline hybrids (1-8), DNP-benzylamine hybrids (9-14), and DNP-phenylethylamine hybrids (15-21) were obtained and their cholinesterase inhibitory activity and neuroprotection of the SH-SY5Y cell line were determined. Results showed that compound 3 exhibited excellent acetylcholinesterase inhibitory activity with an IC50 value of 4.4 µM, higher than that of positive control DNP and significant neuroprotective effects against H2O2-induced oxidative damage in SH-SY5Y cells with 80.11% viability rate at 12.5 µM, much higher than that of the model group (viability rate = 53.1%). The mechanism of action of compound 3 was elucidated by molecular docking, reactive oxygen species (ROS), and immunofluorescence analysis. The results suggest that compound 3 could be further explored as a lead compound for the treatment of Alzheimer's disease. In addition, molecular docking research indicated that the square amide group formed strong interactions with the target protein. Based on the above analysis, we believe that square amide could be an interesting construction unit in anti-AD agents.

Dietary iron regulates intestinal goblet cell function and alleviates Salmonella typhimurium invasion in mice.

Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient (2 mg kg-1 feed), iron-sufficient (35 mg kg-1 feed), or iron-enriched diet (350 mg kg-1 feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice. Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.

Characteristics of endophytic bacteria and active ingredients in the Eucommiae cortex from different origins.

Objective: This study aimed to explore the differences between Eucommiae cortex (EC) endophytic bacteria from different origins and their effects on the active ingredients of EC. Methods: A total of 10 samples of Eucommia ulmoides Oliv. (E. ulmoides) bark were collected from each of the following four regions, namely, Zunyi in Guizhou (GZ), Baokang in Hubei (HUB), Cili in Hunan (HUN), and Loyang in Shaanxi (SX). Subsequently, the contents of the main active ingredients of EC were determined by ultra-performance liquid chromatography (UPLC), and the endophytic bacteria of EC were detected by 16S rRNA sequencing. The relationship between the dominant endophytic bacteria and the active ingredients was investigated by correlation analysis. Results: A total of 4,551 different operational taxonomic units (OTUs) were delineated in the four groups of samples, of which 585, 439, 957, and 684 genera were annotated from GZ, HUB, HUN, and SX, respectively. The richness and diversity of endophytic bacteria from different origins were ranked as HUN > SX > GZ or HUB. The analysis demonstrated that there was no significant correlation between the diversity and richness of endophytic bacteria in EC and its active ingredients. Nevertheless, notable variations in the community structures of endophytic bacteria were observed across different origins, and they had a considerable impact on certain active ingredients in EC. Comamonas and Cedecea were the dominant genera. Characteristic bacteria of different origins could be clearly distinguished. Simultaneous, significant correlations had been identified between some characteristic endophytic bacteria derived from different origins and active ingredients of EC. For example, Delftia, a characteristic bacterium from GZ, showed a significant positive correlation with pinoresinol diglucoside. Paenibacillus and Klebsiella, two characteristic bacteria from HUB, exhibited significant positive correlations with geniposidic acid. Thauera, a characteristic bacterium from HUN, demonstrated a significant positive correlation with geniposide. Brevundimonas, a characteristic bacterium from SX, displayed a significant positive correlation with pinoresinol diglucoside. Conclusion: There was a complex correlation between EC endophytic bacteria and active ingredient content, while EC endophytic bacteria from different origins had significant differences at the genus level.

CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function.

Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins KCNJ4 and KCNJ12, inducing cell cycle arrest, disruption of DNA replication and base excision repair. Overexpression of KCNJ4 and KCNJ12 was involved in ZEA resistance by regulating cell cycle to neutralize toxicity, sustaining mitochondrial morphology and function via attenuating the damage from oxidative stress in the KCNJ4-mitoKATP pathway. In vivo experiments showed that AAV-KCNJ4 delivery significantly improved ZEA-induced renal impairment and increased antioxidative enzyme activity by improving mitochondrial function. Our findings suggest that increasing potassium channel levels may be a putative therapeutic target for mycotoxin-induced damage.