Dietary supplementation with a novel acidifier sodium diformate improves growth performance by increasing growth-related hormones levels and prevents Salmonella enterica serovar Pullorum infection in chickens.

Since the use of antibiotics as growth promoters in animal feed has been restricted or banned in several countries, finding suitable alternatives is crucial for maintaining animal health. In this study, a novel formate acidifier named sodium diformate (NaDF) was synthesized, and the effects on growth performance and the prevention effects against Salmonella enterica serovar Pullorum infections in chickens were assessed. In broilers, NaDF supplementation improved growth performance, as evidenced by increased body weights and reduced feed conversion ratios. At 38 days of age, NaDF supplementation increased the levels of growth-hormone and ghrelin in the serum, lowered pH values in the gut, improved duodenal morphology, as shown by increased villus length/crypt depth ratios. NaDF also modulated the abundance of beneficial and harmful bacteria without changing the general microbiota diversity and short-chain fatty acids levels, which would be beneficial for maintaining gut homeostasis during its use. NaDF exhibited a broad spectrum of antibacterial activity in vitro. Supplementation with NaDF effectively decreased S. Pullorum colonization in the cecum, liver and spleen in chickens, and mitigated pathological changes in the tissues. Therefore, as a novel acidifier, NaDF can improve chicken growth performance by increasing growth-related hormones levels while maintaining the diversity of gut microbiota, and also resist intestinal bacterial infection. These results provided evidences for the application of NaDF as an effective and safe animal feed in poultry farming.

Maternal and Newborn Outcomes of SARS-CoV-2/COVID-19 and Pregnancy: Parallels and Contrasts with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

Purpose of Review: Our review aims to compare and contrast Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome and SARS-CoV-2/COVID-19's impact on maternal and neonatal outcomes. We have made significant progress in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome prevention and treatment over the last few decades. Drawing on empirical evidence with past public health crises can offer valuable insights into dealing with current and future pandemics. Therefore, it is imperative to conduct a comparative analysis of the resemblances and disparities existing between Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome and SARS-CoV-2/COVID-19.This research endeavor represents a pioneering and all-encompassing examination, aiming to discern and comprehend the parallels and contrasts in the respective impacts of SARS-CoV-2 and Human Immunodeficiency Virus on pregnancy. Recent Findings: Based on the current evidence, there is no indication that pregnancy increases women's susceptibility to acquiring Human Immunodeficiency Virus or SARS-CoV-2. Nevertheless, the state of being pregnant was correlated with the worsening of diseases and their progression. Both Human Immunodeficiency Virus and SARS-CoV-2 pose increased risks of maternal mortality and several obstetric complications, including premature birth and pre-eclampsia. While the vertical transmission of Human Immunodeficiency Virus is well-established, a comprehensive understanding of the vertical transmission of SARS-CoV-2 remains elusive, emphasizing the need for further investigations. Initial data suggest low SARS-CoV-2 vertical transmission rates in the setting of proper preventative interventions and universal screening. A cesarean delivery could reduce the risk of mother-to-child transmission in Human Immunodeficiency Virus-infected women with high viral loads or poor adherence to antiretroviral therapy (ART). However, it did not offer additional protection for Human Immunodeficiency Virus-infected women who adhered to Adherence to Antiretroviral Therapy or those with COVID-19. Human Immunodeficiency Virus and SARS-CoV-2 were linked to neonatal complications such as stillbirth, low birth weight, and neonatal intensive care unit (ICU) admissions. The universal testing of both pregnant patients and neonates is an effective strategy to prevent the spread and complications of both Human Immunodeficiency Virus and SARS-CoV-2. Human Immunodeficiency Virus control largely relies on preventing vertical transmission and medications during pregnancy and postpartum, whereas safety behaviors and vaccines have proven effective in preventing SARS-CoV-2 vertical transmissions. Summary: This review aims to compare and contrast the impact of Human Immunodeficiency Virus and SARS-CoV-2 on pregnancy outcomes, vertical transmissions, delivery modalities, neonatal outcomes, and clinical management. SARS-CoV-2 and Human Immunodeficiency Virus were associated with significant obstetric-related complications, making close clinical monitoring and preparation essential. Integration of SARS-CoV-2/COVID-19 management with reproductive health services is crucial to ensuring maternal and neonatal outcomes. Our review is not only the first to establish a groundwork for the current state of knowledge and its clinical implications on this topic, but it also sheds new insights for future research directions.Comparing Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome and SARS-CoV-2 in terms of their impact on maternal and neonatal outcomes provides valuable insights despite their differences. Leveraging Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome research can help understand SARS-CoV-2 effects on pregnancy. Both infections pose risks to pregnant individuals and their fetuses, leading to increased maternal mortality and complications. Identifying common patterns and risk factors can improve clinical management for pregnant individuals with SARS-CoV-2. While a direct observational study for this comparison may not be feasible, comparing with Human Immunodeficiency Virus offers an ethical and practical approach. However, specific studies on SARS-CoV-2 are still necessary to gather detailed data on maternal and fetal outcomes.

[Acupoint massage, acupoint sticking combined with moxibustion for postpartum urinary retention: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) for postpartum urinary retention. METHODS: A total of 120 patients with postpartum urinary retention were randomly divided a triple-combination group, a double-combination group, and a massage group, with 40 patients in each group. All groups received standard postpartum care to stimulate urination. The patients in the massage group received rapid acupoint massage at the bilateral Shuidao (ST 28); the patients in the double-combination group additionally received acupoint sticking of self-made Tongquan powder at bilateral Shuidao (ST 28); the patients in the triple-combination group further received moxibustion at bilateral Shuidao (ST 28). The treatment was given once in all three groups. After 5 hours of treatment completion, bladder residual volume was measured; the time and volume of first urination as well as total urination volume after 5 hours of treatment completion were recorded; the patients' sensation of urination smoothness, satisfaction rate, length of hospital stay, and hospital costs were evaluated. RESULTS: The triple-combination group showed significantly lower residual urine volumes (P<0.05), earlier first urination time (P<0.05, P<0.001), and higher first urination volumes and total urination volumes after 5 hours of treatment completion compared to the other two groups (P<0.05, P<0.001). The sensation of urination smoothness and patient satisfaction were also significantly better in the triple-combination group (P<0.001, P<0.05). The double-combination group had higher volume of first urination and total urination volume after 5 hours of treatment completion than the massage group (P<0.05), and better sensation of urination smoothness and patient satisfaction (P<0.05). There was no significant difference in the length of hospital stay and costs among the three groups (P>0.05). The total effective rates were 100.0% (40/40) for the triple-combination group, 90.0% (36/40) for the double-combination group, and 70.0% (28/40) for the massage group, with the triple-combination group significantly outperforming the other two groups (P<0.05, P<0.001), and double-combination group outperforming the massage group (P<0.05). CONCLUSION: Acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) could effectively improve urination in patients with postpartum urinary retention, and enhance patient satisfaction.

Coordination analysis and evaluation of population, water resources, economy, and ecosystem coupling in the Tuha region of China.

The non-coordination between the socio-economic systems and ecosystems of a region is a crucial obstacle to sustainable development. To reveal the relationships between complex urban systems and achieve the goal of sustainable and coordinated urban development, we constructed a coupling coordination degree model (CCDM) and coupling angle model (CAM) and analyzed the degree of coupling coordination and evolution process among the population, water resources, economy, and ecology (PWEE) system of the Tuha region for 2005-2020. The results indicated that: (1) During 2005-2020, the comprehensive development index (CDI) of the population, water resources and economy subsystems was 0.21-0.65, with the three subsystems portraying an overall increase; the average values of the RSEI at five-year intervals were 0.29, 0.28, 0.28, and 0.26, indicating a downward trend in the environmental quality. (2) The coupling coordination effect of the PWEE system portrayed a low level; the coupling coordination degree (CCD) values were 0.28-0.58, portraying a fluctuating upward trend. The level of CCD increased from low disorder to marginal coordination. (3) The PWEE system's scissor difference reflects large evolutionary characteristics. The ecological support capacity was not observed until the late stage. We conclude that the PWEE composite system of the region is in a stage of disordered development. These findings significantly bolster the theoretical underpinnings of sustainable development studies, offering essential scientific theories and methodological frameworks for crafting sustainable development policies tailored to urban systems in the Tuha region.

[Clinical analysis and genetic diagnosis of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes].

OBJECTIVE: To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. METHODS: Two children with 17ß hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with ß-ketothiolase deficiency (BKD) diagnosed at Shanghai Children's Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools. RESULTS: The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5:1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c.347G>A (p.R116Q) variant and a c.274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c.547G>A (p.G183R) and a c.331G>C (p.A111P). Among these, the c.274G>A (p.A92T) and c.331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+PM2_supporting) and likely pathogenic (PM3+PM2_Supporting+PP3_Moderate+PP4). CONCLUSION: Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c.274G>A (p.A92T) variant and the ACAT1: c.331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai.

BACKGROUND: Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. METHODS: Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. RESULTS: 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. CONCLUSION: There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

A comprehensive review of the anticancer effects of decursin.

Cancer is a globally complex disease with a plethora of genetic, physiological, metabolic, and environmental variations. With the increasing resistance to current anticancer drugs, efforts have been made to develop effective cancer treatments. Currently, natural products are considered promising cancer therapeutic agents due to their potent anticancer activity and low intrinsic toxicity. Decursin, a coumarin analog mainly derived from the roots of the medicinal plant Angelica sinensis, has a wide range of biological activities, including anti-inflammatory, antioxidant, neuroprotective, and especially anticancer activities. Existing studies indicate that decursin affects cell proliferation, apoptosis, autophagy, angiogenesis, and metastasis. It also indirectly affects the immune microenvironment and can act as a potential anticancer agent. Decursin can exert synergistic antitumor effects when used in combination with a number of common clinical anticancer drugs, enhancing chemotherapy sensitivity and reversing drug resistance in cancer cells, suggesting that decursin is a good drug combination. Second, decursin is also a promising lead compound, and compounds modifying its structure and formulation form also have good anticancer effects. In addition, decursin is not only a key ingredient in several natural herbs and dietary supplements but is also available through a biosynthetic pathway, with anticancer properties and a high degree of safety in cells, animals, and humans. Thus, it is evident that decursin is a promising natural compound, and its great potential for cancer prevention and treatment needs to be studied and explored in greater depth to support its move from the laboratory to the clinic.

Construction and Evaluation of an Efficient Live Attenuated Salmonella Choleraesuis Vaccine and Its Ability as a Vaccine Carrier to Deliver Heterologous Antigens.

The gram-negative facultative intracellular pathogen Salmonella enterica serotype Choleraesuis, also known as S. Choleraesuis, is a major financial loss for the pig business. C500 is a vaccine strain that has been used for preventing S. Choleraesuis infection in pigs for many years in China. Although it possessed good immunogenicity and protection efficacy, it still showed severe side effects. The truncation of the key gene rpoS in C500 was believed to take the major responsibility for its attenuation. To achieve a good balance between attenuation and immunogenicity, rpoS was restored to an active state, and other essential virulent genes of crp, fur, phoP, and aroA were evaluated for their effects of deletion on safety and immunogenicity. Animal experiments demonstrated that C5001 (C500 rpoS+ Δcrp10) and C5002 (C500 rpoS+ Δfur9) showed an excellent ability to induce an immune response. To further decrease the endotoxic activity, the combination mutations of ΔpagL7 ΔpagP81::PlpplpxE ΔlpxR9 were introduced into the mutant strains to generate 1'-dephosphorylated lipid A. Animal experiments showed that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) induced higher levels of IgG and secreted IgA antibodies and provided a higher protection rate than SC1 (C500 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) and SC2 (C500 rpoS+ Δcrp10 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9). We also evaluated the ability of SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) as a vaccine carrier to deliver heterologous protein antigens and polysaccharide antigens. The results indicated that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) showed an excellent ability to deliver heterologous antigens and induce the host to produce high levels of antibodies. Together, these results indicate that we constructed a safe and efficient attenuated strain of the S. Choleraesuis vaccine, which demonstrated strong resistance to infection with wild-type S. Choleraesuis and can be employed as a universal vector for the delivery of recombinant antigens.

Comparative Transcriptomics Analysis Reveals the Differences in Transcription between Resistant and Susceptible Pepper (Capsicum annuum L.) Varieties in Response to Anthracnose.

Pepper (Capsicum annuum L.) is a herbaceous plant species in the family Solanaceae. Capsicum anthracnose is caused by the genus Colletotrichum. spp., which decreases pepper production by about 50% each year due to anthracnose. In this study, we evaluated the resistance of red ripe fruits from 17 pepper varieties against anthracnose fungus Colletotrichum capsici. We assessed the size of the lesion diameter and conducted significance analysis to identify the resistant variety of B158 and susceptible variety of B161. We selected a resistant cultivar B158 and a susceptible cultivar B161 of pepper and used a transcription to investigate the molecular mechanisms underlying the plant's resistance to C. capsici, of which little is known. The inoculated fruit from these two varieties were used for the comparative transcription analysis, which revealed the anthracnose-induced differential transcription in the resistant and susceptible pepper samples. In the environment of an anthrax infection, we found that there were more differentially expressed genes in resistant varieties compared to susceptible varieties. Moreover, the response to stimulus and stress ability was stronger in the KANG. The transcription analysis revealed the activation of plant hormone signaling pathways, phenylpropanoid synthesis, and metabolic processes in the defense response of peppers against anthracnose. In addition, ARR-B, AP2-EREBP, bHLH, WRKY, and NAC are associated with disease resistance to anthracnose. Notably, WRKY and NAC were found to have a potentially positive regulatory role in the defense response against anthracnose. These findings contribute to a more comprehensive understanding of the resistance mechanisms of red pepper fruit to anthracnose infection, providing valuable molecular insights for further research on the resistance mechanisms and genetic regulations during this developmental stage of pepper.

Optimized Pepper Target SNP-Seq Applied in Population Structure and Genetic Diversity Analysis of 496 Pepper (Capsicum spp.) Lines.

Peppers are a major vegetable crop worldwide. With the completion of additional genome assemblies, a multitude of single-nucleotide polymorphisms (SNPs) can be utilized for population structure and genetic diversity analysis. In this study, we used target SNP-sequencing as a new high-throughput sequencing technology, screening out 425 perfect SNPs for analyzing the genetic diversity and population structure among 496 pepper lines from five pepper species in China and abroad. The perfect SNP panel exhibited commendable discriminative ability, as indicated by the average values of polymorphism information content, observed heterozygosity, minor allele frequency, and genetic diversity, which were 0.346, 0.011, 0.371, and 0.449, respectively. Based on phylogenetic, population structure, and principal component analyses, 484 C. annuum lines were divided into four subpopulations according to the shape of fruit: blocky fruit, wide-horn fruit, narrow-horn fruit, and linear fruit. These subpopulations displayed clear clustering with minimal or no overlap. Moreover, F statistic (Fst) analysis revealed considerable distinctions among these subpopulations. Additionally, we established a set of 47 core SNPs that could effectively differentiate among all pepper lines. This core SNP set could precisely classify the C. annuum lines into four distinct fruit-shape groups. The blocky and narrow-horn fruit subpopulations displayed the lowest and highest genetic diversity, respectively. This study highlights the importance of fruit shape as a crucial trait in pepper breeding. Moreover, this work indicates the immense potential of optimized target SNP technology in the addition of foreground markers of important traits to improve molecular breeding efficiency, and demonstrates its broad application prospects in the genetic analysis and variety identification of peppers.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Construction and characterization of Aeromonas hydrophila crp and fur deletion mutants and evaluation of its potential as live-attenuated vaccines in crucian carp.

Aeromonas hydrophila (A. hydrophila) is a typical zoonotic pathogenic bacterium that infects humans, animals, and fish. It has been reported that the Fur, a Fe2+ regulatory protein, and the Crp, a cAMP receptor protein, play important roles in bacterial virulence in many bacteria, but no research has been investigated on A. hydrophila. In this study, the Δfur and Δcrp mutant strains were constructed by the suicide plasmid method. These two mutant strains exhibited a slightly diminished bacterial growth and also were observed some alterations in the number of outer membrane proteins, and the disappearance of hemolysis in the Δcrp strain. Animal experiments of crucian carp showed that the Δfur and Δcrp mutant strains significantly decreased virulence compared to the wild-type strain, and both mutant strains were able to induce good immune responses by two kinds of administration routes of intraperitoneal immunization (i.p) and immersion immunization, and the protection rates through intraperitoneal injection of Δfur and Δcrp to crucian carp were as high as 83.3 % and 73.3 %, respectively, and immersion immunization route of Δfur and Δcrp to crucian carp provided protection as high as 40 % and 20 %, respectively. These two mutant strains showed abilities to induce changes in enzymatic activities of the non-specific enzymes SOD, LZM, AKP, and ACP in crucian carp. Together, these results indicated the Δfur and Δcrp mutants were safe and effective candidate vaccine strains, showing good protection against the wild-type A. hydrophila challenge.

Inhibiting Hepatocyte Uric Acid Synthesis and Reabsorption Ameliorates Acetaminophen-Induced Acute Liver Injury in Mice.

BACKGROUND & AIMS: Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. METHODS: We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. RESULTS: APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. CONCLUSIONS: APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

Lower limit characterization of segregation degree for large-size low-alloy steel.

Based on the original position statistic distribution analysis technique, the characterization method of segregation for large-size metal materials gives significant guidance to the research of material properties and production. However, random errors are inevitably brought into the calculation of segregation degree for materials characterization by the Spark Mapping Analysis for Large Sample (SMALS) technique, resulting in a misguide of the segregation degree. In this paper, we present the lower limit of segregation degree (Ds(L)) method to distinguish the random error from metal material segregation for large-size samples over the SMALS method. The random error of standard material in the 95% confidence interval was utilized as Ds(L) and the method has been applied for macro-segregation quantitative analysis. The precision correlation between Spark Atomic Emission Spectrometry (Spark-AES) and SMALS was established. Furthermore, the functional relationship between the Ds(L) and element content C can be obtained in the SMALS method. The Ds(L) method as the criterion can be used to not only characterize the minimum limit of the segregation degree but also the segregation existence for large-size samples. Applying to low-alloy steel can illustrate the effective performance of the Ds(L) method. Results on both spark mapping analysis and Spark-AES verify the substantial consistency.

Obesity alters immunopathology in cancers and inflammatory diseases.

Obesity is characterized by chronic low-grade inflammation and is strongly associated with multiple immunological diseases, including cancer and inflammatory diseases. Recent animal studies revealed that obesity-induced immunological changes worsen immune-driven diseases and cause resistance to immunotherapy. Here, we discuss the role of obesity in the immunopathology and treatment responses of cancers, respiratory and allergic diseases, and IL-17-mediated inflammatory diseases. We summarize the unique features of the inflammatory state of these diseases, which are orchestrated by obesity. In particular, obesity alters the immune landscape in cancers with a reprogrammed metabolic profile of tumor-infiltrating immune cells. Obesity exacerbates airway inflammation by dysregulating multiple immune-cell subsets. Obesity also dysregulates Th17, IL-17-producing mucosal-associated invariant T (MAIT), and γδ T cells, which contribute to IL-17-mediated inflammatory response in multiple sclerosis, inflammatory bowel disease, psoriasis, atopic dermatitis, and rheumatoid arthritis. By identifying the effects of obesity on immunological diseases, new strategies could be devised to target immune dysregulation caused by obesity.

Fine mapping of the flavonoid 3',5'-hydroxylase gene controlling anthocyanin biosynthesis in pepper anthers and stems.

Pepper (Capsicum annuum L) is one of the most important vegetables grown worldwide. Nevertheless, the key structural and regulatory genes involved in anthocyanin accumulation in pepper have not been well understood or fine mapped yet. In this study, F1, F2, BC1P1, and BC1P2 pepper populations were analyzed and these populations were derived from a cross between line 14-Z4, which has yellow anthers and green stems, and line 14-Z5, which has purple anthers and stems. The results showed that the yellow anthers and green stems were determined by a single recessive locus called to as ayw. While, using preliminary and fine mapping techniques, ayw locus was located between markers aywSNP120 and aywSNP124, with physical distance of 0.2 Mb. The CA11g18550 gene was identified as promising candidate for the ayw locus, as it co-segregated with the yellow anthers and green stems phenotypes. CA11g18550 encodes a homolog of the F3'5'H (flavonoid 3',5'-hydroxylase) anthocyanin synthesis structure gene. The missense mutation of CA11g18550 possibly resulted in a loss-of-function. The expression analysis showed that CA11g18550 was significantly expressed in the stems, leaves, anthers and petals in 14-Z5, and it's silencing caused the stems changing from purple to green. This study provides a theoretical basis for using yellow anthers and green stems in pepper breeding and helps to advance the understanding of anthocyanin synthesis.

Analysis of Ti-inclusions in high carbon chromium bearing steel by laser-induced breakdown spectroscopy.

The presence of Ti-inclusions has a significant impact on the fatigue life of bearing steel. Laser-induced breakdown spectroscopy (LIBS) is a useful tool for analyzing Ti-inclusions, despite the fact that the effective excitation area of LIBS is actually larger than the pre-set spot diameter. The area affected by the LIBS spot ranges from 150 µm to 376.6 µm. A new parameter L has been introduced for better understanding the characterization of Ti-inclusions detected in SEM-EDS and LIBS measurements, When the L threshold falls below the value of 188.3 µm, the SEM-EDS and LIBS data are obtained from the same Ti-inclusion. The study demonstrates that there is a linear relationship between LIBS intensity and Ti-inclusions area, which was tested both theoretically and practically. The analysis of six samples of rolling GCr15 bearing steel with a Cr element content of 1.5% shows that one regression line is enough for analyzing the same type of inclusion processed under the same conditions. This method can significantly reduce the workload and analysis time during the actual analysis process.

Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis.

Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.

Chaetocin exhibits anticancer effects in esophageal squamous cell carcinoma via activation of Hippo pathway.

Dysfunction of the Hippo pathway is common in esophageal squamous carcinoma (ESCC). Chaetocin, a small molecular compound isolated from the marine fungus, exhibits potent anticancer effects. However, the anticancer effects of chaetocin on ESCC and its potential relationship to Hippo pathway remain unclear. Here, we demonstrated that chaetocin dramatically inhibited the proliferation in ESCC cells by causing cycle arrest in the M phase and activating the caspase-dependent apoptosis signaling pathway in vitro, and we also found that chaetocin induced the accumulation cellular reactive oxygen species (ROS). The RNA-seq analysis indicated that the Hippo pathway is one of the most enriched pathways after chaetocin treatment. We further revealed that chaetocin triggered the activation of Hippo pathway in ESCC cells, which is characterized by elevated phosphorylation levels of almost all core proteins in Hippo pathway, such as MST1 (Thr183), MST2 (Thr180), MOB1 (Thr35), LAST1 (Thr1079 and Ser909) and YAP (Ser127), ultimately leading to decreased nuclear translocation of YAP. Moreover, the MST1/2 inhibitor XMU-MP-1 not only partially rescued the inhibitory effect chaetocin-induced proliferation, but also rescued the chaetocin-induced apoptosis in ESCC cells. Furthermore, in vivo results confirmed the antitumor effect of chaetocin and its relationship with Hippo pathway. Taken together, our study demonstrates that chaetocin exhibits anticancer effects in ESCC via activation of Hippo pathway. These results provide an important basis for further research of chaetocin as a potential candidate for ESCC treatment.