Table1_New progress in the role of microRNAs in the diagnosis and prognosis of triple negative breast cancer.DOCX

Triple negative breast cancer is distinguished by its high malignancy, aggressive invasion, rapid progression, easy recurrence, and distant metastases. Additionally, it has a poor prognosis, a high mortality, and is unresponsive to conventional endocrine and targeted therapy, making it a challenging problem for breast cancer treatment and a hotspot for scientific research. Recent research has revealed that certain miRNA can directly or indirectly affect the occurrence, progress and recurrence of TNBC. Their expression levels have a significant impact on TNBC diagnosis, treatment and prognosis. Some miRNAs can serve as biomarkers for TNBC diagnosis and prognosis. This article summarizes the progress of miRNA research in TNBC, discusses their roles in the occurrence, invasion, metastasis, prognosis, and chemotherapy of TNBC, and proposes a treatment strategy for TNBC by interfering with miRNA expression levels.</p

Total Synthesis of (−)-Picrinine, (−)-Scholarisine C, and (+)-5-β-Methoxyaspidophylline

The first asymmetric total synthesis of three picrinine-type akuammiline alkaloids, (−)-picrinine, (−)-scholarisine C, and (+)-5-β-methoxyaspidophylline, has been accomplished. The synthesis features an efficient acid-promoted oxo-bridge ring-opening and further carbonyl O-cyclization to assemble the furoindoline scaffold, an unusual Dauben–Michno oxidation to construct the requisite α,β-unsaturated aldehyde functionality, and a nickel-mediated reductive Heck reaction to forge the [3.3.1]-azabicyclic core

Total Synthesis of (−)-Picrinine, (−)-Scholarisine C, and (+)-5-β-Methoxyaspidophylline

The first asymmetric total synthesis of three picrinine-type akuammiline alkaloids, (−)-picrinine, (−)-scholarisine C, and (+)-5-β-methoxyaspidophylline, has been accomplished. The synthesis features an efficient acid-promoted oxo-bridge ring-opening and further carbonyl O-cyclization to assemble the furoindoline scaffold, an unusual Dauben–Michno oxidation to construct the requisite α,β-unsaturated aldehyde functionality, and a nickel-mediated reductive Heck reaction to forge the [3.3.1]-azabicyclic core

Image_2_Analysis of serum antioxidant capacity and gut microbiota in calves at different growth stages in Tibet.png

IntroductionThe hypoxic environment at high altitudes poses a major physiological challenge to animals, especially young animals, as it disturbs the redox state and induces intestinal dysbiosis. Information about its effects on Holstein calves is limited.MethodsHere, serum biochemical indices and next-generation sequencing were used to explore serum antioxidant capacity, fecal fermentation performance, and fecal microbiota in Holstein calves aged 1, 2, 3, 4, 5, and 6 months in Tibet.Results and DiscussionSerum antioxidant capacity changed with age, with the catalase and malondialdehyde levels significantly decreasing (p  0.05) in total volatile fatty acid levels were noted between the groups. In all groups, Firmicutes, Bacteroidetes, and Actinobacteria were the three most dominant phyla in the gut. Gut microbial alpha diversity significantly increased (p < 0.05) with age. Principal coordinate analysis plot based on Bray–Curtis dissimilarity revealed significant differences (p = 0.001) among the groups. Furthermore, the relative abundance of various genera changed dynamically with age, and the serum antioxidant capacity was associated with certain gut bacteria. The study provides novel insights for feeding Holstein calves in high-altitude regions.</p

Image_1_Effect of Limit-Fed Diets With Different Forage to Concentrate Ratios on Fecal Bacterial and Archaeal Community Composition in Holstein Heifers.TIF

Limit-feeding of a high concentrate diet has been proposed as an effective method for improving feed efficiency and reducing total manure output of dairy heifers; meanwhile the effects of this method on hindgut microbiota are still unclear. This study investigated the effects of a wide range of dietary forage:concentrate ratios (F:C) on the fecal composition of bacteria and archaea in heifers using next-generation sequencing. Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to 24 Holstein heifers, and the fecal fermentation parameters and bacterial and archaeal communities were investigated. With increasing dietary concentrate levels, the fecal dry matter output, neutral detergent fiber (NDF) content, and proportion of acetate decreased linearly (P < 0.01), while the fecal starch content and proportions of propionate, butyrate, and total branched-chain volatile fatty acids (TBCVFAs) were increased (P ≤ 0.05). An increased concentrate level linearly increased (P = 0.02) the relative abundance of Proteobacteria, and linearly decreased (P = 0.02) the relative abundance of Bacteroidetes in feces. At the genus level, the relative abundance of unclassified Ruminococcaceae and Paludibacter which may have the potential to degrade forage decreased linearly (q ≤ 0.02) with increasing dietary concentrate levels, while the relative abundance of Roseburia and Succinivibrio which may be non-fibrous carbohydrate degrading bacteria increased linearly (q ≤ 0.05). Some core microbiota operational taxonomic units (OTUs) also showed significant association with fecal VFAs, NDF, and/or acid detergent fiber (ADF) content. Meanwhile, the relative abundance of most detected taxa in archaea were similar across different F:C, and only Methanosphaera showed a linear decrease (P = 0.01) in high concentrate diets. Our study provides a better understanding of fecal fermentation parameters and microbiota under a wide range of dietary F:C. These findings support the potential for microbial manipulation by diet, which could enhance feed digestibility and relieve environmental problems associated with heifer rearing.</p

Data_Sheet_1_Effect of Limit-Fed Diets With Different Forage to Concentrate Ratios on Fecal Bacterial and Archaeal Community Composition in Holstein Heifers.docx

<p>Limit-feeding of a high concentrate diet has been proposed as an effective method for improving feed efficiency and reducing total manure output of dairy heifers; meanwhile the effects of this method on hindgut microbiota are still unclear. This study investigated the effects of a wide range of dietary forage:concentrate ratios (F:C) on the fecal composition of bacteria and archaea in heifers using next-generation sequencing. Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to 24 Holstein heifers, and the fecal fermentation parameters and bacterial and archaeal communities were investigated. With increasing dietary concentrate levels, the fecal dry matter output, neutral detergent fiber (NDF) content, and proportion of acetate decreased linearly (P < 0.01), while the fecal starch content and proportions of propionate, butyrate, and total branched-chain volatile fatty acids (TBCVFAs) were increased (P ≤ 0.05). An increased concentrate level linearly increased (P = 0.02) the relative abundance of Proteobacteria, and linearly decreased (P = 0.02) the relative abundance of Bacteroidetes in feces. At the genus level, the relative abundance of unclassified Ruminococcaceae and Paludibacter which may have the potential to degrade forage decreased linearly (q ≤ 0.02) with increasing dietary concentrate levels, while the relative abundance of Roseburia and Succinivibrio which may be non-fibrous carbohydrate degrading bacteria increased linearly (q ≤ 0.05). Some core microbiota operational taxonomic units (OTUs) also showed significant association with fecal VFAs, NDF, and/or acid detergent fiber (ADF) content. Meanwhile, the relative abundance of most detected taxa in archaea were similar across different F:C, and only Methanosphaera showed a linear decrease (P = 0.01) in high concentrate diets. Our study provides a better understanding of fecal fermentation parameters and microbiota under a wide range of dietary F:C. These findings support the potential for microbial manipulation by diet, which could enhance feed digestibility and relieve environmental problems associated with heifer rearing.</p

Data_Sheet_1_Effects of altitude on the gut microbiome and metabolomics of Sanhe heifers.docx

IntroductionExtreme environments at high altitudes pose a significant physiological challenge to animals. We evaluated the gut microbiome and fecal metabolism in Sanhe heifers from different altitudes.MethodsTwenty Sanhe heifers (body weight: 334.82 ± 13.22 kg, 15-month-old) selected from two regions of China: the Xiertala Cattle Breeding Farm in Hulunbeier, Inner Mongolia [119°57′ E, 47°17′ N; approximately 700 m altitude, low altitude (LA)] and Zhizhao Dairy Cow Farm in Lhasa, Tibet [91°06′ E, 29°36′ N; approximately 3,650 m altitude, high altitude (HA)], were used in this study. Fecal samples were collected and differences in the gut microbiota and metabolomics of Sanhe heifers were determined using 16S rRNA gene sequencing and metabolome analysis.Results and discussionThe results showed that altitude did not significantly affect the concentrations of fecal volatile fatty acids, including acetate, propionate, butyrate, and total volatile fatty acids (p > 0.05). However, 16S rRNA gene sequencing showed that altitude significantly affected gut microbial composition. Principal coordinate analysis based on Bray–Curtis dissimilarity analysis revealed a significant difference between the two groups (p = 0.001). At the family level, the relative abundances of Peptostreptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Family_XIII were significantly lower (p < 0.05) in LA heifers than in HA heifers. In addition, the relative abundances of Lachnospiraceae, Domibacillus, Bacteroidales_S24-7_group, Bacteroidales_RF16_group, Porphyromonadaceae, and Spirochaetaceae were significantly higher in HA heifers than in LA heifers (p < 0.05). Metabolomic analysis revealed the enrichment of 10 metabolic pathways, including organismal systems, metabolism, environmental information processing, genetic information processing, and disease induction. The genera Romboutsia, Paeniclostridium, and g_unclassified_f_Lachnospiraceae were strongly associated with the 28 differential metabolites. This study is the first to analyze the differences in the gut microbiome and metabolome of Sanhe heifers reared at different altitudes and provides insights into the adaptation mechanism of Sanhe heifers to high-altitude areas.</p

Palladium-Catalyzed Arylation of C(sp²)–H Bonds with 2‑(1-Methylhydrazinyl)pyridine as the Bidentate Directing Group

Palladium-catalyzed C­(sp2)–H arylation of ortho C–H bonds involving 2-(1-methylhydrazinyl)­pyridine (MHP) as the directing group has been investigated. The reaction proceeds smoothly under an air atmosphere to generate biaryl derivatives in an environmentally friendly manner while tolerating a wide range of functional groups. Notably, the directing group present in the product could be easily removed under mild reductive conditions

Image_1_Analysis of serum antioxidant capacity and gut microbiota in calves at different growth stages in Tibet.pdf

IntroductionThe hypoxic environment at high altitudes poses a major physiological challenge to animals, especially young animals, as it disturbs the redox state and induces intestinal dysbiosis. Information about its effects on Holstein calves is limited.MethodsHere, serum biochemical indices and next-generation sequencing were used to explore serum antioxidant capacity, fecal fermentation performance, and fecal microbiota in Holstein calves aged 1, 2, 3, 4, 5, and 6 months in Tibet.Results and DiscussionSerum antioxidant capacity changed with age, with the catalase and malondialdehyde levels significantly decreasing (p  0.05) in total volatile fatty acid levels were noted between the groups. In all groups, Firmicutes, Bacteroidetes, and Actinobacteria were the three most dominant phyla in the gut. Gut microbial alpha diversity significantly increased (p < 0.05) with age. Principal coordinate analysis plot based on Bray–Curtis dissimilarity revealed significant differences (p = 0.001) among the groups. Furthermore, the relative abundance of various genera changed dynamically with age, and the serum antioxidant capacity was associated with certain gut bacteria. The study provides novel insights for feeding Holstein calves in high-altitude regions.</p

Data_Sheet_2_Effect of Limit-Fed Diets With Different Forage to Concentrate Ratios on Fecal Bacterial and Archaeal Community Composition in Holstein Heifers.xlsx

<p>Limit-feeding of a high concentrate diet has been proposed as an effective method for improving feed efficiency and reducing total manure output of dairy heifers; meanwhile the effects of this method on hindgut microbiota are still unclear. This study investigated the effects of a wide range of dietary forage:concentrate ratios (F:C) on the fecal composition of bacteria and archaea in heifers using next-generation sequencing. Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to 24 Holstein heifers, and the fecal fermentation parameters and bacterial and archaeal communities were investigated. With increasing dietary concentrate levels, the fecal dry matter output, neutral detergent fiber (NDF) content, and proportion of acetate decreased linearly (P < 0.01), while the fecal starch content and proportions of propionate, butyrate, and total branched-chain volatile fatty acids (TBCVFAs) were increased (P ≤ 0.05). An increased concentrate level linearly increased (P = 0.02) the relative abundance of Proteobacteria, and linearly decreased (P = 0.02) the relative abundance of Bacteroidetes in feces. At the genus level, the relative abundance of unclassified Ruminococcaceae and Paludibacter which may have the potential to degrade forage decreased linearly (q ≤ 0.02) with increasing dietary concentrate levels, while the relative abundance of Roseburia and Succinivibrio which may be non-fibrous carbohydrate degrading bacteria increased linearly (q ≤ 0.05). Some core microbiota operational taxonomic units (OTUs) also showed significant association with fecal VFAs, NDF, and/or acid detergent fiber (ADF) content. Meanwhile, the relative abundance of most detected taxa in archaea were similar across different F:C, and only Methanosphaera showed a linear decrease (P = 0.01) in high concentrate diets. Our study provides a better understanding of fecal fermentation parameters and microbiota under a wide range of dietary F:C. These findings support the potential for microbial manipulation by diet, which could enhance feed digestibility and relieve environmental problems associated with heifer rearing.</p