Enhancing the Stability, Solubility, and Antioxidant Activity of Cinchonine through Pharmaceutical Cocrystallization.

PURPOSE: Cinchoninze hydrochloride solves the problem of the low solubility of cinchonine, but it is unstable and susceptible to deliquescence. In this study, we designed and prepared cinchonine cocrystal salts or cinchonine salts with better stability, solubility and antioxidant activity than cinchonine. METHOD: We successfully synthesized and characterized three cinchonine salts, namely, cinchonine-fumaric acid, cinchonine-isoferulic acid, and cinchonine-malic acid. The high humidity (92.5% RH) and high temperature (60°C) tests were conducted to determine the physical stability and hygroscopicity of cinchonine hydrochloride, cinchonine and three cinchonine salts. And the ultraviolet spectrophotometry was conducted to determine the equilibrium solubility and intrinsic dissolution rate of cinchonine and salts. Moreover, the DPPH, ABTS, and FRAP assays determined the antioxidant activity of cinchonine and salts. RESULT: Compared with cinchonine hydrochloride and cinchonine, all three cinchonine salts exhibited good physical stability over 15 days under high humidity (92.5% RH) and high temperature (60°C) conditions. While cinchonine and cinchonine hydrochloride are categorized as hygroscopic and deliquescent, respectively, three cinchonine salts are classified as slightly hygroscopic, meaning that they have a lower hygroscopicity than cinchonine and cinchonine hydrochloride. And three cinchonine salts had higher equilibrium solubility, faster intrinsic dissolution rates, and higher antioxidant activity in comparison to cinchonine. Moreover, they showed a "spring and parachute" pattern in the phosphate buffer (pH = 6.8). CONCLUSION: Cocrystallization technology is a viable option for improving cinchonine's poor physicochemical qualities.

Photodetector with a metalens packaging module for visible light communication based on RGBY illumination LED light source.

A novel, to the best of our knowledge, photodetector with a metalens packaging module used as the visible light communication (VLC) receiver is proposed and designed. An LED consisting of red, green, blue, and yellow chips (RGBY-LED) is adopted as the transmitter for intensity modulation direct detection VLC systems. A metalens array with a numerical aperture (NA) of 0.707 used as a polarization-insensitive planar lens of the VLC system receiver is designed at wavelengths of 457, 523, 592, and 623 nm corresponding to blue, green, yellow, and red for high efficiency. Compared with a traditional Fresnel lens positive-intrinsic-negative (PIN) photodetector module as the VLC receiver, the introduction of a metalens module can decrease the form factor of the VLC receiver module and, in particular, it is much thinner. The combination of the multi-color LED transmitter and photodetector metalens packaging module receiver can increase the modulation bandwidth due to four different wavelengths used for the VLC system. Finite-difference time domain (FDTD) simulations are performed to validate the performance of the photodetector with a metalens module. It is revealed that the corresponding efficiencies of 57.5%, 55.4%, 57%, and 56.3% were achieved at wavelengths of 623, 592, 523, and 457 nm, respectively, based on a metalens array with a 0.707 NA and 2.5 µm radius of the active area of the photodetector. It is a promising technology for indoor VLC systems such as those for smart phones and other Internet of Things devices due to the need for compact packaging for the receiver.

In-Silico and in vitro Studies Revealed that Rosmarinic Acid Inhibited Methanogenesis via Regulating Composition and Function of Rumen Microbiota.

Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of -9.355 kcal/mol. Furthermore, the effects of rosmarinic acid supplementation on methane production, rumen fermentation, and the microorganism's community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas, Desulfovibrio, and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium, an unclassified genus from Eggerthellaceae, an unclassified genus from Bacteroidales, and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, while that of Methanosphaera increased with the RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production.

Elucidating the role of T-cell exhaustion-related genes in colorectal cancer: a single-cell bioinformatics perspective.

Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups: regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.

Establishment and application of a TaqMan probe-based qPCR for the detection of Enterocytozoon hepatopenaei in shrimp Litopenaeus vannamei.

Enterocytozoon hepatopenaei (EHP) is a common parasite that invades the epithelial cytoplasm in the hepatopancreas of shrimp Litopenaeus vannamei and results in slow growth of the host shrimps to cause significant economic loss in shrimp aquaculture. In this study, a TaqMan probe-based qPCR for quantitative detection of EHP was established. A pair of specific primers and a TaqMan probe were designed based on the sequence of cysteine desulfurase gene (NFS1) of EHP. The standard curve between cycle threshold (Ct) and the logarithmic starting quantity (SQ) of the template was determined as Ct = - 3.231 lg (SQ) + 40.638, with a correlation coefficient (R2) of 0.998 and an amplification efficiency of 103.9%. The lower limit of quantification was 1.67 × 101 copies/µL for this TaqMan probe-based qPCR and 1.67 × 103 copies/µL for the conventional PCR. The TaqMan probe-based qPCR established in the research was 100 times more sensitive than the conventional PCR method. In addition, the results of clinical sample detection indicated that the present technique was efficient in detecting EHP in the hepatopancreas, feces, water, and pond bottom mud samples. Therefore, the established TaqMan probe-based qPCR is a suitable technique for detecting EHP in both shrimp and aquatic environment samples.

Treatment of type III dens invaginatus in bilateral immature mandibular central incisors: a case report.

BACKGROUND: Dens invaginatus (DI) is a developmental anomaly, Oehlers Type III DI is the most complex type and early diagnosis and treatment is complicated and challenging. This report presents a rare case of a type IIIb DI associated with a periapical lesion in bilateral immature permanent mandibular central incisors. CASE PRESENTATION: An eight-year-old boy referred to our clinic manifesting with pain along with swelling in the mandibular incisors for the past one month. Radiographic examination showed periapical radiolucency exhibiting a scantly defined border, as well as an invagination which had a central invaginated canal extending from the pulp chamber throughout the apical foramen in both mandibular central incisors. We performed two different treatment procedures on the basis of the condition of the main pulp of the mandibular central incisors. in which only the invagination root canal was treated in the right mandibular central incisor, while the invagination and main root canals were treated in the left mandibular central incisor. During the 18-month follow-up period, the teeth were clinically asymptomatic. Imaging examinations indicated complete healing of the periapical lesion and revealed that the wall of the root canal was thickened and the open apex was closed. CONCLUSION: For young permanent teeth with type III Dens invaginatus, it is particularly important to keep pulp vitality, which could maintain root development and allow a good long-term prognosis.

Multi-stage Internet public opinion risk grading analysis of public health emergencies: An empirical study on Microblog in COVID-19.

In the period of Corona Virus Disease 2019 (COVID-19), millions of people participate in the discussion of COVID-19 on the Internet, which can easily trigger public opinion and threaten social stability. This paper creatively proposes a multi-stage risk grading model of Internet public opinion for public health emergencies. On the basis of general public opinion risk grading analysis, the model continuously pays attention to the risk level of Internet public opinion based on the time scale of regular or major information updates. This model combines Analytic Hierarchy Process Sort II (AHPSort II) and Swing Weighting (SW) methods and proposes a new Multi-Criteria Decision Making (MCDM) method - AHPSort II-SW. Intuitionistic fuzzy number and linguistic fuzzy number are introduced into the model to evaluate the criteria that cannot be quantified. The multi-stage model is tested using more than 2,000 textual data about COVID-19 collected from Microblog, a leading social media platform in China. Seven public opinion risk assessments were conducted from January 23 to April 8, 2020. The empirical results show that in the early COVID-19 outbreak, the risk of public opinion is more serious on macroscopic view. In details, the risk of public opinion decreases slowly with time, but the emergence of important events may still increase the risk of public opinion. The analysis results are in line with the actual situation and verify the effectiveness of the method. Comparative analysis indicates the improved method is proved to be superior and effective, sensitivity analysis confirms its stability. Finally, management suggestions was provided, this study contributes to the literature on public opinion risk assessment and provides implications for practice.

Adhesive Ability of Different Oral Pathogens to Various Dental Materials: An In Vitro Study.

Introduction: In dental treatments, the reason for secondary caries and the failure of root canal treatment is the microbial infection, which concerns most dentists. The challenge of how to reduce the number of bacteria at the filling materials and the number of residual bacteria in the root canal has become a research hotspot. In this study, the bacterial adhesion properties of several common dental materials were compared to provide a theoretical basis for the selection of antibacterial properties of dental materials. Methodology. Three commonly used dental restorative materials and five sealers in root canal treatment were selected. Each material block was immersed in the corresponding supragingival (Streptococcus mutans and Actinomyces viscosus) or subgingival (Porphyromonas gingivalis and Enterococcus faecalis) bacterial solution and cultured under anaerobic conditions at 37°C for 2, 4, 6, 8, 12, 16, 20, and 24 h. The adhesion of bacteria was observed, and the number of different bacteria adhering to various material model disks was calculated at different time intervals under a scanning electron microscope. The adherent CFU load of the materials was determined by colony counting. Results: Streptococcus mutans and Actinomyces viscosus exhibited the strongest adhesion ability to the resin material blocks. Porphyromonas gingivalis and Enterococcus faecalis exhibited the highest adhesion ability to the AH-Plus sealer block. Conclusions: In dental treatments, dental materials should be selected based on the chemical, physical, and biological properties of materials. In addition, it is necessary to develop new antibacterial dental materials.

How local outbreak of COVID-19 affect the risk of internet public opinion: A Chinese social media case study.

Motivated by the realistic demand of controlling the Internet public opinion risk caused by the local outbreak of COVID-19, this paper creatively proposes a COVID-19 local outbreak Internet public opinion risk grading research framework. The SMAA-FAHPSort II method combining Analytic Hierarchy Process Sort II (AHPSort II) method with Stochastic Multicriteria Acceptability Analysis (SMAA-2) method is introduced into this framework, to evaluate the Internet public opinion risk level of social media during the local outbreak of COVID-19. In addition, this framework is applied to a case of Internet public opinion risk evaluation on Microblog platform of China. According to the number of new cases per day in mainland China, this paper divides the period from May 7, 2020 to September 3, 2021 into seven stages. A total of more than 10,000 Microblog hot topics were collected, after screening and preprocessing, 5422 related topics are remained to help complete the Internet public opinion risk evaluation. The case study analysis results show that the number of days classified as moderate risk and above has reached more than 280. This proves that the local outbreak of COVID-19 will indeed increase the risk of Internet public opinion, and correlation analysis confirms that the level of public opinion risk is positively correlated with the severity of the epidemic in the real world. Furthermore, the effectiveness and advantages of the proposed method are verified by comparative analysis and sensitivity analysis. Finally, some effective public opinion management suggestions have been put forward. This paper can provide reference for the government to formulate or improve relevant strategies, and also has great significance for reducing the risk of Internet public opinion in social media.

Multiomics analysis reveals the presence of a microbiome in the gut of fetal lambs.

OBJECTIVE: Microbial exposure is critical to neonatal and infant development, growth and immunity. However, whether a microbiome is present in the fetal gut prior to birth remains debated. In this study, lambs delivered by aseptic hysterectomy at full term were used as an animal model to investigate the presence of a microbiome in the prenatal gut using a multiomics approach. DESIGN: Lambs were euthanised immediately after aseptic caesarean section and their cecal content and umbilical cord blood samples were aseptically acquired. Cecal content samples were assessed using metagenomic and metatranscriptomic sequencing to characterise any existing microbiome. Both sample types were analysed using metabolomics in order to detect microbial metabolites. RESULTS: We detected a low-diversity and low-biomass microbiome in the prenatal fetal gut, which was mainly composed of bacteria belonging to the phyla Proteobacteria, Actinobacteria and Firmicutes. Escherichia coli was the most abundant species in the prenatal fetal gut. We also detected multiple microbial metabolites including short chain fatty acids, deoxynojirimycin, mitomycin and tobramycin, further indicating the presence of metabolically active microbiota. Additionally, bacteriophage phiX174 and Orf virus, as well as antibiotic resistance genes, were detected in the fetal gut, suggesting that bacteriophage, viruses and bacteria carrying antibiotic resistance genes can be transmitted from the mother to the fetus during the gestation period. CONCLUSIONS: This study provides strong evidence that the prenatal gut harbours a microbiome and that microbial colonisation of the fetal gut commences in utero.

[Historical evolution of Salviae Miltiorrhizae Radix et Rhizoma processing methods].

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.

Integrating RNA-sequencing and untargeted LC-MS metabolomics to evaluate the effect of lysine deficiency on hepatic functions in Holstein calves.

Lysine (Lys) is majorly metabolized in the liver. The liver functional consequences of a dietary Lys deficiency in young Holstein calves are unknown. This study aimed to investigate the effects of Lys deficiency in Holstein calf livers using RNA-sequencing and untargeted LC-MS metabolomics. Calves (n = 36; initial body weight 101.2 ± 10.8 kg; 90-day-old) were fed restricted diets, for 90 days, containing 19.2% crude protein that varied in Lys content (PC group 1.21%; PC-Lys group 0.85%; dry matter basis) for 90 days. Body weight, average daily gain, gain/feed, and Lys intake were significantly decreased in response to Lys deficiency (P < 0.05). Dry matter intake was not altered (P > 0.05). Network and pathway analyses revealed that noradrenaline, adenosine 5'-monophosphate, acetyl-CoA, and coenzyme A were significantly decreased. Regulating of lipolysis in adipocytes pathway and fatty acid degradation pathway were downregulated. We also identified eight significantly differentially expressed genes (SDEGs), among which adrenoceptor beta 2 (ADRB2), WAP four-disulfide core domain 2 (WFDC2), and claudin-4 (CLDN4) were associated with inhibition of lipolysis, and carbon catabolite repression 4-like (CCRN4L), FOS like 2 (FOSL2), and arginase 2 (ARG2) were associated with inhibiting lipid synthesis. Correlation tests showed that coenzyme A was strongly correlated with SDEGs (0.82 ≤|r|≤ 0.96). Acetyl-CoA and adenosine 5'-monophosphate were strongly correlated with CCRN4L (0.90 ≤|r|≤ 0.92), indicating a strong correlation between the changes in SDEGs and these metabolites. In conclusion, Lys deficiency caused dysplasia and affected lipid metabolism in the liver by inhibiting lipolysis and lipid synthesis in calves.

Effects of dietary rumen-protected Lys levels on rumen fermentation and bacterial community composition in Holstein heifers.

This study aimed to evaluate the effects of partial reducing rumen-protected Lys (RPLys) on rumen fermentation and microbial composition in heifers. Three ruminal fistulated Holstein Friesian bulls were used to determine the effective degradability of RPLys using an in situ method at incubation times of 0, 2, 6, 12, 16, 24, 36, and 48 h. Thereafter, 36 Holstein heifers at 90 days of age were assigned to one of two dietary treatments: a theoretically balanced amino acid diet (PC group; 1.21% Lys, 0.4% Met) or a 30% Lys-reduced diet (PCLys group, 0.85% Lys, 0.4% Met). Rumen fluid samples from five heifers in each group were extracted using esophageal tubing on day 90 to determine pH, microprotein, ammonia, volatile fatty acids, and microbial communities. Results showed that the effective ruminal degradability was 25.76%. Furthermore, differences in rumen fermentation parameters and alpha diversity of the microbiota between the two groups were not significant, but beta diversity was significant. Based upon relative abundance analysis, short-chain fatty acid-producing bacteria, including Sharpea, Syntrophococcus, [Ruminococcus]_gauvreauii_group, Acetitomaculum, and [Eubacterium]_nadotum_group belonging to Firmicutes, were significantly decreased in the PCLys group. Spearman's analysis revealed a positive correlation between the butyrate molar proportion and the relative abundance of butyrate-producing bacteria such as [Eubacterium]_nadotum_group, Coprococcus_1, Ruminococcaceae_UCG_013, Pseudoramibacter, and Lachnospiraceae_UCG_010. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis further validated that RPLys deduction influenced energy metabolism. Together, our findings highlight the role of RPLys or Lys in butyrate-producing bacteria. However, the number of bacteria affected by Lys was very limited and insufficient to alter rumen fermentation. Key Points • Reducing 30% Lys via rumen-protected Lys did not affect rumen fermentation parameters and alpha diversity of microbiota of Holstein heifers. It meant that the ruminal fermentation pattern was not changed. • Reducing 30% Lys via rumen-protected lysine significantly decreased relative abundance of short-chain fatty acid-producing bacteria belonging to Firmicutes. • Functions of microorganisms were changed by reducing 30% Lys via rumen-protected Lys, especially amino acid metabolism. It may affect the amino acid composition of microprotein.

MicroRNA26a inhibits cisplatin-induced renal tubular epithelial cells apoptosis through suppressing the expression of transient receptor potential channel 6 mediated dynamin-related protein 1.

Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase-3 were used to assess apoptosis. Western blot analyses and qRT-PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR-26a was remarkably decreased in cisplatin-induced AKI and in cisplatin co-cultured HK2 cells. Furthermore, we used a miR-26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR-26a protected against cisplatin-induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin-related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR-26a/TRPC6/DRP1 is a novel protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related renal injury. SIGNIFICANCE OF THE STUDY: Our study found that miR-26a was significantly downregulated during cisplatin-induced AKI and during cisplatin co-cultured HK2 cells. Further, in vitro we used miR-26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR-26a protected cisplatin-induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic-related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR-26a/TRPC6/DRP1 is a new protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related acute kidney injury.

In vivo Microbial Diversity Analysis on Different Surfaces of Dental Restorative Materials via 16S rDNA Sequencing.

BACKGROUND This study aimed to provide precise material selection guidance for proper clinical restoration and treatment of plaque-related oral diseases, such as dental caries and periodontal diseases. MATERIAL AND METHODS Four groups (n=24) of restorative material sheets (n=24) were prepared using 3M Z350 composite resin (ZR), zinc phosphate cement (ZPC), glass-ionomer (GI), and ICON permeable resin (IPR). Six volunteers wore a plaque-collection device equipped with the 4 restorative material sheets for 48 hours. Plaque samples were collected, and Miseq sequencing was applied to obtain template DNA fragments for microbial diversity analysis. The data were analyzed with nonparametric tests. RESULTS The microbial diversity on the ZPC surface was significantly lower than that on GI and IPR surfaces. The abundance of Firmicutes and Streptococcus on the ZPC surface was significantly higher than on the surfaces of GI and IPR. In contrast, the abundance of Porphyromonas on the surface of ZPC was significantly lower than that on GI and IPR surfaces. (P<0.05). CONCLUSIONS The results of the present study might serve as a basis for material selection under different oral microbial conditions to provide more accurate treatments and restorative procedures in the oral cavity.

Effect of hypoxia-inducible factor-prolyl hydroxylase inhibitors on anemia in patients with CKD: a meta-analysis of randomized controlled trials including 2804 patients.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of randomized controlled trials (RCTs) was designed to provide clear information on the efficacy and safety of HIF-PHIs on anemia in chronic kidney disease (CKD) patients. Searches included PubMed, Web of Science, Ovid MEDLINE, and Cochrane Library database up to October 2019. RCTs of patients with CKD comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in the treatment of anemia. The primary outcome was hemoglobin change from baseline (Hb CFB); the secondary outcomes included iron-related parameters and the occurrence of each adverse event. 26 trials in 17 articles were included, with a total of 2804 dialysis or patients with CKD. HIF-PHIs treatment produced a significant beneficial effect on Hb CFB compared with the placebo group (MD, 0.69; 95% CI, 0.36 to 1.02). However, this favored effect of HIF-PHIs treatment was not observed in subgroup analysis among trials compared with ESAs (MD, 0.06; 95% CI, -0.20 to 0.31). The significant reduction in hepcidin by HIF-PHIs was observed in all subgroups when compared with the placebo group, whereas this effect was observed only in NDD-CKD patients when compared with ESAs. HIF-PHIs increased the risk of nausea (RR, 2.20; 95% CI, 1.06 to 4.53) and diarrhea (RR, 1.75; 95% CI, 1.06 to 2.92). We conclude that orally given HIF-PHIs are at least as efficacious as ESAs treatment to correct anemia short term in patients with CKD. In addition, HIF-PHIs improved iron metabolism and utilization in patients with CKD.

Requirements of metabolizable protein by Dorper × thin-tailed Han crossbred ewe lambs.

The requirement of net protein (NP) and metabolizable protein (MP) by Dorper crossbred ewe lambs grown from 35 to 50 kg of body weight (BW) was assessed by comparative slaughter experiment. Thirty-five ewe lambs (33.5 ± 0.6 kg BW) of F1 crosses of Dorper × thin-tailed Han sheep were used: 7 lambs were slaughtered as reference animals at the start of the trial, and the remaining 28 lambs were randomly divided into 4 groups of 7 lambs each. Three of the 4 groups were fed a pelleted mixed diet (concentrate/roughage = 44:56, dry matter basis) for ad libitum intake or 65% or 45% of ad libitum intake, and they were all slaughtered when the lambs that were fed ad libitum reached 50 kg BW. The lambs from the fourth group were also fed ad libitum and slaughtered at 43 kg BW as the intermediate group. The intake of MP by the animals of these 4 groups was estimated, and their total body protein and protein retention were measured. The daily requirements of NP and MP for maintenance were 1.52 and 3.98 g/kg BW0.75 , respectively, with a partial efficiency of MP utilization for maintenance of 0.38. The MP requirement for growth ranged from 77.4 to 124.5 g/day for average daily gains from 100 to 250 g BW, and the partial efficiency of MP utilization for growth was 0.66. The Dorper crossbred ewe lambs required more MP for both maintenance and growth in comparison with the recommendations of the US nutritional system.

Effect of Broussonetia papyrifera L. silage on blood biochemical parameters, growth performance, meat amino acids and fatty acids compositions in beef cattle.

OBJECTIVE: The study was conducted to investigate the effects of Broussonetia papyrifera L.(B. papyrifera) silage on growth performance, serum biochemical parameters, meat quality, and meat amino acids and fatty acids compositions in beef cattle. METHODS: Sixty-four male Angus beef cattle were assigned to 4 groups with 4 pens in each group and 4 beef cattle in each pen, and fed with the total mixed ration supplemented with 0%, 5%, 10%, or 15% B. papyrifera silage for 100 days (control group, 5% group, 10% group and 15% group) separately. RESULTS: Beef cattle had significantly higher final body weight (BW) in 15% group, higher average daily gain (ADG) and dry matter intake (DMI) in 5% group, 10% group and 15% group, and higher feed conversion ratio (FCR) in 10% group and 15% group. Significantly higher blood superoxide dismutase (SOD) concentration was noted in 15% group, higher blood total antioxidant capacity (TAC) in 10% group and 15% group, lower 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 15% group. Meat had lower pH in 15% group, higher Commission International DeI'Eclairage (CIE) L* in 5% group, 10% group, and 15% group, and lower drip loss in 15% group. Greater concentration of meat polyunsaturated fatty acids (PUFA) was observed in 10% group and 15% group, and docosahexaenoic acid (DHA) in 15% group. CONCLUSION: Diet with 15% B. papyrifera silage could improve performance and increase final BW, ADG, DMI, and FCR, enhance the antioxidant functions by decreasing blood 8-OHdG and MDA and increasing blood SOD and TAC, improve the meat quality by lowing pH and drip loss and increasing CIE L*, increase the meat PUFA and DHA concentration. Polyphenols and flavonoids might be the main components responsible for the antioxidant activity and anti-biohydrogenation in the B. papyrifera silage. And B. papyrifera silage could be used as a new feedstuff in beef cattle nutrition.

Association between admission plasma 2-oxoglutarate levels and short-term outcomes in patients with acute heart failure: a prospective cohort study.

BACKGROUND: 2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain. METHODS: This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes. RESULTS: The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (µg/ml): low group (< 6.0, n = 205) and high group (≥6.0, n = 206). There was a relatively modest correlation between 2OG and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (r = 0.25; p < 0.001). After adjusting for age, sex, and body mass index, we found that the progression of the NYHA classification was associated with a gradual increase in plasma 2OG levels (p for trend< 0.001). After six months of follow-up, 76 (18.5%) events were identified. A high baseline 2OG level was positively associated with a short-term rehospitalization and all-cause mortality (OR: 2.2, 95% CI 1.3-3.7, p = 0.003), even after adjusting for NT-proBNP and estimated glomerular filtration rate (eGFR) (OR: 1.9, 95% CI 1.1-3.4, p = 0.032). After a similar multivariable adjustment, the OR was 1.4 (95% CI 1.1-1.7, p = 0.018) for a per-SD increase in 2OG level. CONCLUSIONS: High baseline 2OG levels are associated with adverse short-term outcomes in patients with AHF independent of NT-proBNP and eGFR. Hence plasma 2OG measurements may be helpful for risk stratification and treatment monitoring in AHF. TRIAL REGISTRATION: ChiCTR-ROC-17011240 . Registered 25 April 2017.

Feeding modes shape the acquisition and structure of the initial gut microbiota in newborn lambs.

Early gut microbial colonization is important for postnatal metabolic and immune development. However, little is known about the effects of different feeding modes (suckling versus bottle-feeding) or microbial sources on this process in farm animals. We found that suckled and bottle-fed newborn lambs had their own distinct gut microbiota. Results from 16S rRNA gene sequencing and qPCR showed that, compared with suckling, bottle feeding significantly increased the abundances of Escherichia/Shigella, Butyricicoccus, and Clostridium XlVa, while significantly decreased the abundance of Clostridium XI. The higher levels of Escherichia/Shigella in bottle-fed lambs suggest that artificial feeding may increase the number of potential pathogens and delay the establishment of the anaerobic environment and anaerobic microbes. Feeding modes also affected the direct transmission of bacteria from the mother and the environment to newborns. The SourceTracker analysis estimated that the early gut microbes of suckled lambs were mainly derived from the mother's teats (43%) and ambient air (28%); whereas those of bottle-fed lambs were dominated by bacteria from the mother's vagina (46%), ambient air (31%), and the sheep pen floor (12%). These findings advance our understanding of gut microbiota in early life and may help design techniques to improve gut microbiota and health.