bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent applications of dioxinone derivatives for macrocyclic natural product and terpenoid synthesis
Authors: Wei Kai , Zheng Xinhua , Zhang Hongbin
Published: December 2022

Dioxinone derivatives, a class of acetoacetate derivatives, have attracted widespread attention because of their multiple reactive sites, high reactivity, unique chemical properties, and potential synthetic applications. The dioxinone group is also stable under a wide range of reaction conditions, including strong acids, as well as a variety of transition-metal-catalysed processes, such as olefin metathesis and Pd-mediated cross-coupling. The inherent reactivity and diverse applications of dioxinones make them valuable reactive intermediates in organic synthesis. The conversion of dioxinones to acylketenes and their subsequent nucleophilic capture is also an excellent strategy for synthesising β-keto acid derivatives, which can be applied even in complex molecular synthesis. This review focuses on the recent advances in the application of dioxinones in synthetic method research and the total synthesis of natural products, highlighting the exceptional utility of these synthetic methodologies in the construction of macrocyclic cores and terpenoid skeletons. In particular, successful transformations of dioxinone fragments are discussed.
Preparation of biomass-based hydrogels and their efficient heavy metal removal from aqueous solution
Authors: Zhang Mingyue , Zhou Yaru , Wang Fangling , Chen Zeshao , Zhao Xu , Duan Weidong , Yin Guangting , Yang Xinling , Li Junfeng , Yin Quanyu , Zhao Mingqin
Published: December 2022

In this work, a porous tobacco straw-based polyacrylic acid hydrogel STS-PAA with high adsorption performance was prepared by polymerizing pretreated waste tobacco straw (TS) with acrylic acid/potassium acrylate by UV radiation initiation. The adsorption performance of metal ions was investigated. The effects of different temperatures (25°C, 35°C, and 45°C), adsorption times (1–420 min), pH values (2.0–6.0) and initial concentrations (0.25–4.0 mmol L−1) of metal ions on the adsorption amount of heavy metal ions were investigated. The results showed that the hydrogel had a high removal rate of Pb2+, Cd2+ and Hg2+ in aqueous solution. The adsorption of Pb2+ was particularly effective. When C0 = 4.0 mmol L−1, pH = 6, the equilibrium adsorption amount of Pb2+, Cd2+ and Hg2+ reached 1.49 mmol g−1, 1.02 mmol L−1 and 0.94 mmol g−1, respectively. The chemical structure and morphology of the hydrogels were characterized by FT-IR, EDS, SEM and XPS. The Langmuir model fits well with the adsorption system. The kinetic data suggest the adsorption of Pb2+, Cd2+ and Hg2+ follow the pseudo-first-order model. This indicates that STS-PAA adsorption of three heavy metal ions is monolayer physical adsorption. Thermodynamic analysis shows that the adsorption of Pb2+, Cd2+ and Hg2+ by STS-PAA is an endothermic (ΔH>0) entropy increase (ΔS>0) non-spontaneous reaction.
Extracellular vesicles participate in the pathogenesis of sepsis
Authors: Tian Chang , Wang Ke , Zhao Min , Cong Shan , Di Xin , Li Ranwei
Published: December 2022

Sepsis is one of the leading causes of mortality worldwide and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The early diagnosis and effective treatment of sepsis still face challenges due to its rapid progression, dynamic changes, and strong heterogeneity among different individuals. To develop novel strategies to control sepsis, a better understanding of the complex mechanisms of sepsis is vital. Extracellular vesicles (EVs) are membrane vesicles released from cells through different mechanisms. In the disease state, the number of EVs produced by activated or apoptotic cells and the cargoes they carry were altered. They regulated the function of local or distant host cells in autocrine or paracrine ways. Current studies have found that EVs are involved in the occurrence and development of sepsis through multiple pathways. In this review, we focus on changes in the cargoes of EVs in sepsis, the regulatory roles of EVs derived from host cells and bacteria, and how EVs are involved in multiple pathological processes and organ dysfunction in sepsis. Overall, EVs have great application prospects in sepsis, such as early diagnosis of sepsis, dynamic monitoring of disease, precise therapeutic targets, and prevention of sepsis as a vaccine platform.
Dental calculus: A repository of bioinformation indicating diseases and human evolution
Authors: Li Qinyang , Luo Kaihua , Su Zhifei , Huang Fangting , Wu Yajie , Zhou Fangjie , Li Yuqing , Peng Xian , Li Jiyao , Ren Biao
Published: December 2022

Dental calculus has long been considered as a vital contributing factor of periodontal diseases. Our review focuses on the role of dental calculus as a repository and discusses the bioinformation recently reported to be concealed in dental calculus from three perspectives: time-varying oral condition, systemic diseases, and anthropology at various times. Molecular information representing an individual’s contemporary oral health status could be detected in dental calculus. Additionally, pathogenic factors of systemic diseases were found in dental calculus, including bacteria, viruses and toxic heavy metals. Thus, dental calculus has been proposed to play a role as biological data storage for detection of molecular markers of latent health concerns. Through the study of environmental debris in dental calculus, an overview of an individual’s historical dietary habits and information about the environment, individual behaviors and social culture changes can be unveiled. This review summarizes a new role of dental calculus as a repository of bioinformation, with potential use in the prediction of oral diseases, systemic diseases, and even anthropology.
Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosis via gut in rats
Authors: Xu Meng-Yang , Guo Can-Can , Li Meng-Ying , Lou Yu-Han , Chen Zhuo-Ran , Liu Bo-Wei , Lan Ling
Published: December 2022

Background

The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut.

Methods

Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa β (NF-κβ), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed.

Results

The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κβ, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated.

Conclusion

Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.
In silico high-throughput screening system for AKT1 activators with therapeutic applications in sepsis acute lung injury
Authors: Wang Ziyi , Wang Xuesong , Guo Zhe , Liao Haiyan , Chai Yan , Wang Ziwen , Wang Zhong
Published: December 2022

Purpose

AKT1 is an important target in sepsis acute lung injury (SALI). The current study was aim to construct a high-throughput screening (HTS) system based on the ChemDiv database (https://www.chemdiv.com/complete-list/) and use the system to screen for AKT1 activation agents, which may provide clues for the research and development of new drugs to treat SALI.

Methods

Based on the existing X-ray structure of AKT1 and known AKT activators, a large-scale virtual HTS was performed on the ChemDiv database of small molecules by the cascade docking method and demonstrated both accuracy and screening efficiency. Molecular docking and molecular dynamics simulations were used to assess the stability and binding characteristics of the identified small-molecule compounds. The protective effect of the new highly selective compound on SALI were verified both in vitro and in vivo experiments.

Results

The small-molecule compound 7460-0250 was screened out as a specific activator of AKT1. Molecular validation experiments confirmed that compound 7460-0250 specifically promoted the phosphorylation of AKT1 and down-regulated the LPS-induced apoptosis of human umbilical vein endothelial cells (HUVECs) by activating the AKT-mTOR pathway. Up-regulated mTOR was detected to directly interact with Bax to reduce apoptosis. In vivo, compound 7460-0250 could improved survival rate and alleviated lung injury of sepsis mice induced by cecum ligation and puncture (CLP), parallel with the activation of the AKT-mTOR pathway.

Conclusion

Small-molecule compound 7460-0250 was successfully screened and confirmed as a highly selective AKT1 activator, which is a critical target in the development of new therapeutics for SALI.
Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment
Authors: Osorio Robert C. , Oh Jun Y. , Choudhary Nikita , Lad Meeki , Savastano Luis , Aghi Manish K.
Published: December 2022

Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to be caused by elevated growth hormone (GH) levels and Cushing disease’s elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.
Response of vegetation dynamic change to multi-scale drought stress in the high-latitude Nenjiang River basin in China
Authors: Zhu Guanglei , Zhao Chunzi , Tong Shouzheng , Zhu Weihong
Published: December 2022

Vegetation is an integral part of terrestrial ecosystem and plays an important role in responding to climate change, with its dynamic characteristics reflecting the ecological environmental quality. Recently, the continually increasing frequency and intensity of droughts has greatly changed how vegetation growth and development respond to drought. In this study, using normalized difference vegetation index and standardized precipitation evapotranspiration index (SPEI), we studied the response characteristics of vegetation dynamics to multi-scale drought stress (SPEI-1, SPEI-3, and SPEI-12) in the Nenjiang River basin (NRB) via Pearson correlation analysis, along with further exploration of the vegetation stability under drought. The results showed that the same period effect of drought on vegetation growth in NRB mainly occurs during the early and middle stages of vegetation growth. Furthermore, the proportion of significant positive correlation between them is 15.3%–43.3%, mainly in the central and southern parts of the basin. The lagged period effect of drought on vegetation growth mainly occurred during autumn in the southeast and middle of the basin, with a significant positive correlation of 20.8%. Under drought stress, the forest vegetation stability in NRB was the highest, with the resilience of wetland and grassland vegetation being the best and worst, respectively. Our study results will not only deepen our understanding of the dynamic vegetation changes in the high-latitude semi-arid basin under global climate change, but also provide a scientific basis for the management and water resources allocation of “agriculture-wetland-forest” complex ecosystem in the future.
Identifying the molecular mechanisms of sepsis-associated acute kidney injury and predicting potential drugs
Authors: Guo Guangfeng , Wang Yunting , Kou Wanyu , Gan Hua
Published: December 2022

Objective: To provide insights into the diagnosis and therapy of SA-AKI via ferroptosis genes.

Methods: Based on three datasets (GSE57065, GSE30718, and GSE53771), we used weighted co-expression network analysis to identify the key regulators of SA-AKI, its potential biological functions, and constructed miRNA‒mRNA complex regulatory relationships. We also performed machine learning and in vitro cell experiments to identify ferroptosis genes that are significantly related to SA-AKI in the two datasets. The CIBERSORT algorithm evaluates the degree of infiltration of 22 types of immune cell. We compared the correlation between ferroptosis and immune cells by Pearson’s correlation analysis and verified the key genes related to the immune response to reveal potential diagnostic markers. Finally, we predicted the effects of drugs and the potential therapeutic targets for septic kidney injury by pRRophetic.

Results: We found 264 coDEGs involving 1800 miRNA molecules that corresponded to 210 coDEGs. The miRNA‒mRNA ceRNA interaction network was constructed to obtain the top-10 hub nodes. We obtained the top-20 ferroptosis genes, 11 of which were in the intersection. We also identified a relationship between ferroptosis genes and the immune cells in the AKI dataset, which showed that neutrophils were activated and that regulatory T cells were surpassed. Finally, we identified EHT1864 and salubrinal as potential therapeutic agents.

Conclusion: This study demonstrated the roles of miR-650 and miR-296-3p genes in SA-AKI. Furthermore, we identified OLFM4, CLU, RRM2, SLC2A3, CCL5, ADAMTS1, and EPHX2 as potential biomarkers. The irregular immune response mediated by neutrophils and Treg cells is involved in the development of AKI and shows a correlation with ferroptosis genes. EHT 1864 and salubrinal have potential as drug candidates in patients with septic acute kidney injury.
Population genetic analyses unveiled genetic stratification and differential natural selection signatures across the G-gene of viral hemorrhagic septicemia virus
Authors: Nigar Kiran , Kakakhel Sehrish , Khan Asifullah , Khan Hizbullah , Zaib Komal , Wen Shaoqing
Published: December 2022

Introduction: Viral hemorrhagic septicemia virus (VHSV) is the most lethal pathogen in aquaculture, infecting more than 140 fish species in marine, estuarine, and freshwater environments. Viral hemorrhagic septicemia virus is an enveloped RNA virus that belongs to the family Rhabdoviridae and the genus Novirhabdovirus. The current study is designed to infer the worldwide Viral hemorrhagic septicemia virus isolates’ genetic diversity and evolutionary dynamics based on G-gene sequences.

Methods: The complete G-gene sequences of viral hemorrhagic septicemia virus were retrieved from the public repositories with known timing and geography details. Pairwise statistical analysis was performed using Arlequin. The Bayesian model-based approach implemented in STRUCTURE software was used to investigate the population genetic structure, and the phylogenetic tree was constructed using MEGA X and IQ-TREE. The natural selection analysis was assessed using different statistical approaches, including IFEL, MEME, and SLAC.

Results and Discussion: The global Viral hemorrhagic septicemia virus samples are stratified into five genetically distinct subpopulations. The STRUCTURE analysis unveiled spatial clustering of genotype Ia into two distinct clusters at K = 3. However, at K = 5, the genotype Ia samples, deposited from Denmark, showed temporal distribution into two groups. The analyses unveiled that the genotype Ia samples stratified into subpopulations possibly based on spatiotemporal distribution. Several viral hemorrhagic septicemia virus samples are characterized as genetically admixed or recombinant. In addition, differential or subpopulation cluster-specific natural selection signatures were identified across the G-gene codon sites among the viral hemorrhagic septicemia virus isolates. Evidence of low recombination events elucidates that genetic mutations and positive selection events have possibly driven the observed genetic stratification of viral hemorrhagic septicemia virus samples.
Inhibition of the different complement pathways has varying impacts on the serum bactericidal activity and opsonophagocytosis against Haemophilus influenzae type b
Authors: Muri Lukas , Schubart Anna , Thorburn Christine , Zamurovic Natasa , Holbro Thomas , Kammüller Michael , Pluschke Gerd , Ispasanie Emma
Published: December 2022

Defense againstHaemophilus influenzaetype b (Hib) is dependent on antibodies and complement, which mediate both serum bactericidal activity (SBA) and opsonophagocytosis. Here we evaluated the influence of capsule-specific antibodies and complement inhibitors targeting the central component C3, the alternative pathway (AP; fB, fD), the lectin pathway (LP; MASP-2) and the terminal pathway (C5) on both effector functions. Findings may be relevant for the treatment of certain diseases caused by dysregulation of the complement system, where inhibitors of complement factors C3 or C5 are used. Inhibitors against other complement components are being evaluated as potential alternative treatment options that may carry a reduced risk of infection by encapsulated bacteria. Serum and reconstituted blood of healthy adults were tested for bactericidal activity before and after vaccination with the Hib capsule-conjugate vaccine ActHIB. Most sera had bactericidal activity prior to vaccination, but vaccination significantly enhanced SBA titers. Independently of the vaccination status, both C3 and C5 inhibition abrogated SBA, whereas inhibition of the LP had no effect. AP inhibition had a major inhibitory effect on SBA of pre- vaccination serum, but vaccination mitigated this inhibition for all disease isolates tested. Despite this, SBA-mediated killing of some Hib isolates remained retarded. Even for the most serum-resistant isolate, SBA was the dominating defense mechanism in reconstituted whole blood, as addition of blood cells to the serum did not enhance bacterial killing. Limited Fc receptor-mediated opsonophagocytosis was unmasked when bacterial killing by the membrane attack complex was blocked. In the presence of C3 or C5 inhibitors, addition of post-vaccination, but not of pre-vaccination serum to the blood cells triggered opsonophagocytosis, leading to suppression of bacterial multiplication. Taken together, our data indicate that for host defense against Hib, killing by SBA is more efficient than by blood cell opsonophagocytosis. However, additional defense mechanisms, such as bacterial clearance by spleen and liver, may play an important role in preventing Hib-mediated sepsis, in particular for Hib isolates with increased serum-resistance. Results indicate potentially improved safety profile of AP inhibitors over C3 and C5 inhibitors as alternative therapeutic agents in patients with increased susceptibility to Hib infection.
Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression
Authors: Dong Shi , Li Wancheng , Li Xin , Wang Zhengfeng , Chen Zhou , Shi Huaqing , He Ru , Chen Chen , Zhou Wence
Published: December 2022

Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.
Case report: Mafb promoter activity may define the alveolar macrophage dichotomy
Authors: Vo Thao , Saini Yogesh
Published: December 2022

Cre-LoxP system has been widely used to induce recombination of floxed genes of interest. Currently available macrophage promoter-specific Cre recombinase mice strains have various limitations that warrants the testing of additional Cre strains. V-maf musculoaponeurotic fibrosarcoma oncogene family, protein b -Cre (Mafb-Cre) mice label macrophages in most organs such as spleen, small intestine, lung, bone marrow, and peritoneal cavity. However, whether Mafb-Cre recombinase targets the gene recombination in alveolar macrophage remains untested. Here, we utilized MafbCre/WTR26mTmG/WT strain that expresses mTOM protein in all the cells of mouse body except for those that express Mafb-Cre-regulated mEGFP. We performed fluorescent microscopy and flow cytometry to analyze mTOM and mEGFP expression in alveolar macrophages from MafbCre/WTR26mTmG/WT mice. Our analyses revealed that the Mafb-Cre is active in only ~40% of the alveolar macrophages in an age-independent manner. While Mafb- (mTOM+/mEGFP-) and Mafb+ (mEGFP+) alveolar macrophages exhibit comparable expression of CD11b and CD11c surface markers, the surface expression of MHCII is elevated in the Mafb+ (mEGFP+) macrophages. The bone marrow-derived macrophages from MafbCre/WTR26mTmG/WT mice are highly amenable to Cre-LoxP recombination in vitro. The bone marrow depletion and reconstitution experiment revealed that ~98% of alveolar macrophages from MafbCre/WTR26mTmG/WT → WT chimera are amenable to the Mafb-Cre-mediated recombination. Finally, the Th2 stimulation and ozone exposure to the MafbCre/WTR26mTmG/WT mice promote the Mafb-Cre-mediated recombination in alveolar macrophages. In conclusion, while the Mafb-/Mafb+ dichotomy thwarts the use of Mafb-Cre for the induction of floxed alleles in the entire alveolar macrophage population, this strain provides a unique tool to induce gene deletion in alveolar macrophages that encounter Th2 microenvironment in the lung airspaces.
Circulating monocytes in acute pancreatitis
Authors: Liu Shiyu , Szatmary Peter , Lin Jing-wen , Wang Qiqi , Sutton Robert , Chen Lu , Liu Tingting , Huang Wei , Xia Qing
Published: December 2022

Acute pancreatitis is a common gastrointestinal disease characterized by inflammation of the exocrine pancreas and manifesting itself through acute onset of abdominal pain. It is frequently associated with organ failure, pancreatic necrosis, and death. Mounting evidence describes monocytes - phagocytic, antigen presenting, and regulatory cells of the innate immune system - as key contributors and regulators of the inflammatory response and subsequent organ failure in acute pancreatitis. This review highlights the recent advances of dynamic change of numbers, phenotypes, and functions of circulating monocytes as well as their underling regulatory mechanisms with a special focus on the role of lipid modulation during acute pancreatitis.
Structure and status of the Italian red coral forests: What can a large-scale study tell?
Authors: Toma Margherita , Bo Marzia , Giudice Daniele , Canese Simonepietro , Cau Alessandro , Andaloro Franco , Angiolillo Michela , Greco Silvestro , Bavestrello Giorgio
Published: December 2022

The precious coral Corallium rubrum (Linnaeus, 1758) is a charismatic Mediterranean species. A recent large-scale investigation along the Italian coast highlighted its widespread occurrence at mesophotic and upper bathyal depths, especially on coralligenous and bathyal vertical hardgrounds. The lack of morphometric data limited the considerations on the structure and health status of the populations, fundamental to identify the most vulnerable sites and the correct management actions. For this reason, a ROV dataset, consisting of 624 dives carried out between 40 m and 1825 m in the Ligurian Sea, Tyrrhenian Sea, and Sicily Channel, was analysed to extrapolate quantitative data to describe the populations. Ten random frames were obtained from each of the 170 sites hosting red coral. Density, height, and entanglement were evaluated for about 15700 colonies counted in the frames. The densest populations were mainly found between 40 m and 80 m, with a clear latitudinal density decrease. The mesophotic populations were characterized by both scattered and densely aggregated colonies, while the bathyal ones were dominated by sparse colonies. This study identified 17 major coral areas based on the geographic proximity of the sites hosting red coral and their topographic and oceanographic affinity. The size-frequency distribution of the heights was skewed towards the smaller classes in almost all populations, with a modal class between 2 cm and 4 cm. This study depicted a stress situation of the populations throughout the entire study area, which could be correlated also to the long-term harvesting pressure carried out in the basins. Two additional sources of direct mortality were pointed out in this study. Entanglement to artisanal and recreational fishing gear interested about 18% of the recorded colonies, mainly at mesophotic depths. Almost all populations suffered from mechanical entanglement, with the highest percentages in the Ligurian Sea and Sicilian areas. This study also highlighted a massive occurrence of recent deep mortality events, mainly along the eastern and southern coast of Sardinia and in the Campanian Archipelago. Thirty sites with extensive patches of dead colonies still in place were reported from 70 m to around 200 m, but their formation remains unclear.
Yinchen Linggui Zhugan decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease by modulation of SIRT1/Nrf2 signaling pathway and gut microbiota
Authors: Jiang Hui , Mao Tangyou , Sun Zhongmei , Shi Lei , Han Xiao , Zhang Yang , Zhang Xiaosi , Wang Jiali , Hu Juncong , Zhang Liming , Li Junxiang , Han Haixiao
Published: December 2022

Yinchen Linggui Zhugan decoction (YLZD) is an effective and classical traditional herbal prescription for treating the nonalcoholic fatty liver disease (NAFLD) and has been proven to be effective in the regulation of lipid metabolism disorder and attenuate inflammation for a NAFLD rat model. However, the exact underlying mechanism has not been elucidated. In the current study, a NAFLD rat model was established using a high-fat diet (HFD) for 10 weeks, followed by YLZD treatment with 1.92 g/kg/day for 4 weeks to explore the mechanisms of YLZD. Our results showed that YLZD decreased the hepatic lipid deposition, restored the liver tissue pathological lesions, inhibited the expression of oxidative stress, and decreased the inflammatory cytokines levels. Meanwhile, the genes and proteins expressions of SIRT1/Nrf2 signaling pathway together with downstream factors including HO-1 and NQO1 were elevated in the YLZD treated NAFLD rats. For further elaborating the upstream mechanism, short-chain fatty acids (SCFAs) in serum and feces were measured by liquid chromatograph mass spectrometer and gas chromatograph mass spectrometer, and the differences in gut microbiota of rats in each group were analyzed through high-throughput sequencing of 16S rRNA. The results demonstrated that the contents of butyric acid (BA) and total SCFAs in YLZD-treated NAFLD rats were significantly increased in serum and feces. 16S rRNA sequencing analysis illustrated that YLZD intervention led to a modification of the gut microbiota composition, with a decrease of Oribacterium, Lactobacillus and the ratio of Firmicutes/Bacteroides, as well as the increase in SCFAs-producing bacteria such as Christensenellaceae, Clostridia, Muribaculaceae, and Prevotellaceae. Spearman rank correlation analysis indicated that BA and total SCFAs were negatively co-related with oxidative stress-related factors and inflammatory cytokines, while they were positively co-related with SIRT1/Nrf2 pathway related genes and proteins. Furthermore, in vitro study confirmed that BA effectively reduced oxidative stress by activating SIRT1/Nrf2 signaling pathway in L02 cells. Together, the present data revealed YLZD could ameliorate HFD-induced NAFLD in rats by the modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.
Limited nucleotide changes of HIV-1 subtype B Rev response element in China affect overall Rev-RRE activity and viral replication
Authors: Shi Yuting , Han Jingwan , Zhu Bo , Liu Zhi , Liang Qingmiao , Lan Chunlin , Li Zhengyang , Li Hanping , Liu Yongjian , Jia Lei , Li Tianyi , Wang Xiaolin , Li Jingyun , Zhang Bohan , Jiang Junjun , Li Lin
Published: December 2022

The HIV-1 Rev response element (RRE) is a cis-acting RNA element that facilitates the nuclear export of mRNA-containing introns by binding specifically to the Rev protein, enabling a critical step in the viral replication cycle. This study aims to determine the subtype-specific loci of HIV-1 subtype B RRE circulating in China and to analyze their effects on Rev-RRE function and HIV-1 replication. We amplified 71 HIV-1 subtype B RRE full-length sequences from the HIV patients’ blood samples collected in China, analyzed the subtype-specific loci on them by comparing them with subtype B in the United States, and predicted their RNA secondary structures. Rev-RRE activity assay was used to test the binding activity of Rev and different RREs. Infectious clones were mutated to test the effect of the subtype-specific loci on replication capacity. In this study, two sites were determined to be the subtype-specific loci of HIV-1 subtype B RRE circulating in China. Both site 186 and site 56-57insAAC can significantly increase the viral mRNA transcription and Rev-RRE activity, but only the site 186 can significantly improve viral replication ability. Collectively, the subtype-specific loci of subtype B RRE circulating in China have a significant effect on the Rev-RRE activity and viral replication. This study investigates the subtype-specific loci of RRE, which are unique to retroviruses and essential for viral replication, and will help to explore the reasons why subtype B circulating in China is more widespread and persistent than American subtype B in China at the genetic level, and will provide theoretical support for the development of more inclusive detection and treatment methods for subtype B circulating in China. At the same time, it will also provide insight into the impact of different subtype HIV-1 genetic characteristics on viral replication.
Addressing the implementation gap in advanced therapeutics for spinal muscular atrophy in the era of newborn screening programs
Authors: Leon-Astudillo Carmen , Byrne Barry J. , Salloum Ramzi G.
Published: December 2022

Spinal muscular atrophy (SMA) is a rare genetic disease that results in progressive neuromuscular weakness. Without therapy, the most common form of the disease, type 1, typically results in death or chronic respiratory failure in the first 2 years of life. Thanks to the recent introduction of newborn screening programs and the discovery of three disease-modifying therapies in the last decade, the outcomes of children with SMA have dramatically improved. Patients are able to achieve many, if not all, of the typical neuromotor milestones, such as sitting, standing and walking, as well as safe oral intake. As the natural history of treated patients is continuously evolving, children with SMA continue to require complex and multidisciplinary care, posing implementation and sustainability challenges. Accordingly, there is a significant need for the application and evaluation of implementation science to address the steps involved in the diagnosis and treatment of patients with SMA, ensuring that all pertinent stakeholders and systems are working effectively to deliver timely and appropriate care. In this manuscript, we discuss the current challenges and gaps in the care for children with SMA, as well as how implementation science can advance this field. In addition, we provide an adapted implementation science framework that includes the main domains and subdomains involved in the care of patients with SMA.
Preference-based versus randomized controlled trial in prostate cancer survivors: Comparison of recruitment, adherence, attrition, and clinical outcomes
Authors: Alibhai Shabbir M. H. , Papadopoulos Efthymios , Durbano Sara , Tomlinson George , Mina Daniel Santa , Ritvo Paul , Sabiston Catherine M. , Matthew Andrew G. , Chiarotto James , Sidani Souraya , Culos-Reed S. Nicole
Published: December 2022

Introduction

Patients’ unwillingness to be randomized to a mode of exercise may partly explain their poor recruitment, adherence, and attrition in randomized controlled trials (RCTs) of exercise in oncology. It is unknown whether a preference-based trial can improve recruitment, adherence, retention, and clinical outcomes compared to a RCT of the same exercise interventions.

Objective

We assessed the effects of a 2-arm exercise preference trial on adherence and clinical outcomes compared to a similar 2-arm RCT in men with prostate cancer (PC).

Methods

This was a two-arm preference-based trial of group-based training (GROUP) or home-based training (HOME). PC survivors on androgen deprivation therapy (ADT) who declined randomization to the RCT but chose to participate in a preference trial were recruited in four Canadian centers. All study participants engaged in aerobic and resistance training, 4-5 days weekly for 6 months, aiming for 150 minutes/week of moderate-to-vigorous physical activity. The primary outcomes were changes from baseline to 6 months in fatigue and functional endurance. Secondary outcomes were quality of life, physical fitness, body composition, blood markers, and adherence. Linear mixed models were used to assess the effects of HOME versus GROUP on primary outcomes. In pooled preference and RCT data, the selection effect (i.e., difference between those who were and were not willing to be randomized) and treatment effect (i.e., difference between GROUP and HOME) were estimated using linear regression.

Results and conclusion

Fifty-four participants (mean [SD] age, 70.2 [8.6] years) were enrolled (GROUP n=17; HOME n=37). Comparable effects on primary and secondary outcomes were observed following GROUP or HOME in the preference-based trial. Adherence was similar between preference and RCT participants. However, attrition was higher in the RCT (50.0% vs. 27.8%, p= 0.04). Compared to GROUP, HOME was more effective in ameliorating fatigue (mean difference: +5.2, 95%CI=1.3 to 9.3 p=0.01) in pooled preference and RCT data. A preference-based trial results in comparable observed effects on clinical outcomes and adherence and lower attrition compared with a RCT of the same exercise interventions in PC survivors on ADT. Given the appeals of preference-based trials to study participants, additional studies are warranted.

Clinical trial registration

clinicaltrials.gov, identifier (NCT03335631).
Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
Authors: Bollino Dominique , Claiborne J. Preston , Hameed Kanwal , Ma Xinrong , Tighe Kayla M. , Carter-Cooper Brandon , Lapidus Rena G. , Strovel Erin T. , Emadi Ashkan
Published: December 2022

The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino acid panel measurements in healthy immunodeficient/immunocompetent mice as well as in preclinical mouse models of acute myeloid leukemia (AML) and pancreatic ductal adenocarcinoma (PDAC) using long-acting crisantaspase, and in an AML clinical study (NCT02283190) using short-acting crisantaspase. In addition to the expected decrease of plasma glutamine and asparagine, we observed a significant increase in plasma serine and glycine post-crisantaspase. In PDAC tumors, crisantaspase treatment significantly increased expression of serine biosynthesis enzymes. We then systematically reviewed clinical studies using asparaginase products to determine the extent of plasma amino acid reporting and found that only plasma levels of glutamine/glutamate and asparagine/aspartate were reported, without measuring other amino acid changes post-asparaginase. To the best of our knowledge, we are the first to report comprehensive plasma amino acid changes in mice and humans treated with asparaginase. As dysregulated serine metabolism has been implicated in tumor development, our findings offer insights into how leukemia/cancer cells may potentially overcome glutamine/asparagine restriction, which can be used to design future synergistic therapeutic approaches.
Determination of a cost-effectiveness threshold for cancer interventions in Iran
Authors: Safari Hossein , Poder Thomas G. , Afshari Somayeh , Nahvijou Azin , Arab-Zozani Morteza , Moradi Nasrin , Ameri Hosein
Published: December 2022

Background and objectives

The estimation of a cost- Effectiveness (CE) threshold from the perspective of those who have experienced a life-threatening disease can provide empirical evidence for health policy makers to make the best allocation decisions on limited resources. The aim of the current study was to empirically determine the CE threshold for cancer interventions from the perspective of cancer patients in Iran.

Methods

A composite time trade-off (cTTO) task for deriving quality adjusted life-year (QALY) and a double-bounded dichotomous choice (DBDC) approach followed by open-ended question for examining patients’ willingness-to-pay were performed. A nationally representative sample of 580 cancer patients was recruited from the largest governmental cancer centers in Iran between June 2021 and January 2022, and data were gathered using face-to-face interviews. The CE threshold was calculated using the nonparametric Turnbull model and parametric interval-censored Weibull regression model. Furthermore, the factors that affect the CE threshold were determined using the parametric model.

Results

The estimated CE threshold using the nonparametric Turnbull model and parametric interval-censored Weibull regression model was IRR 440,410,000 (USD 10,485.95) and IRR 595,280,000 (USD 14,173.33) per QALY, respectively. Gender, age, education, income, type of cancer, and current treatment status were significantly associated with the estimated CE threshold.

Conclusions

The value of parametric model-based threshold in this study was 1.98 times the Iranian GDP per capita, which was lower than the CE threshold value recommended by the WHO (i.e., 3 times the GDP per capita) for low-and middle-income countries.
Respiratory support strategies in the prevention of bronchopulmonary dysplasia: A single center quality improvement initiative
Authors: White Heather , Merritt Kamaris , Martin Kirsti , Lauer Emily , Rhein Lawrence
Published: December 2022

Background and objectives

Bronchopulmonary dysplasia (BPD) continues to be a significant morbidity affecting very preterm infants, despite multiple advancements in therapies to treat respiratory distress syndrome and prevent BPD. Local quality improvement (QI) efforts have shown promise in reducing unit or system-wide rates of BPD. In preterm infants born between 23- and 32-weeks' gestation, our aim was to decrease the rate of BPD at 36 weeks corrected gestational age from 43% to 28% by January 2019.

Methods

Directed by a multidisciplinary respiratory QI team, we gradually implemented the following interventions to reach our aim: (1) early initiation of non-invasive ventilation in the delivery room, (2) initiation of caffeine prior to 24 h of life, (3) administration of early selective surfactant per a well-defined guideline, (4) continuation of non-invasive ventilation until 32 and 0/7 weeks corrected gestational age (CGA), and (5) a revision of the early selective surfactant guideline. Outcome measures included rates of BPD, and process measures included compliance with the above interventions.

Results

A total of 509 infants with an average gestational age of 29 1/7 weeks and birth weight of 1,254 (SD±401) grams were included. The rate of BPD in our unit decreased from a baseline of 43% to 19% from the start of the project in October 2016 until the first quarter of 2022 (p < 0.00001). The greatest reductions in BPD rates were seen after the initiation of the guideline to extend non-invasive ventilation until 32 0/7 weeks CGA. The rate of severe BPD decreased from 22% to 9%.

Conclusions

In preterm infants born between 23- and 32-weeks' gestation, our local QI interventions to reduce rates of BPD were associated with a reduction in rates by 56%. Increased use of antenatal steroids and higher birth weights post- vs. pre-intervention may have contributed to this successes.
PHD-finger family genes in wheat (Triticum aestivum L.): Evolutionary conservatism, functional diversification, and active expression in abiotic stress
Authors: Pang Fei , Niu Junqi , Solanki Manoj Kumar , Nosheen Shaista , Liu Zhaoliang , Wang Zhen
Published: December 2022

Plant homeodomain (PHD) transcription factors (TFs) are a class of proteins with conserved Cys4-His-Cys3 domains that play important roles in plant growth and development and in response to abiotic stresses. Although characterization of PHDs has been performed in plants, little is known about their function in wheat (Triticum aestivum L.), especially under stress conditions. In the present study, 244 TaPHDs were identified in wheat using comparative genomics. We renamed them TaPHD1-244 based on their chromosomal distribution, and almost all PHD proteins were predicted to be located in the nucleus. According to the unrooted neighbor-joining phylogenetic tree, gene structure, and motif analyses, PHD genes were divided into four clades. A total of 149 TaPHD genes were assigned to arise from duplication events. Furthermore, 230 gene pairs came from wheat itself, and 119, 186, 168, 7, 2, and 6 gene pairs came from six other species (Hordeum vulgareto, Zea mays, Oryza sativa, Arabidopsis thaliana, Brassica rapa, and Gossypium raimondii, respectively). A total of 548 interacting protein branches were identified to be involved in the protein interaction network. Tissue-specific expression pattern analysis showed that TaPHDs were highly expressed in the stigma and ovary during flowering, suggesting that the TaPHD gene plays an active role in the reproductive growth of wheat. In addition, the qRT-PCR results further confirmed that these TaPHD genes are involved in the abiotic stress response of wheat. In conclusion, our study provides a theoretical basis for deciphering the molecular functions of TaPHDs, particularly in response to abiotic stress.
Direct and indirect effects of banker plants on population establishment of Harmonia axyridis and aphid control on pepper crop
Authors: Wang Jie , Yang Yajie , Li Yuanxi , Jin Zhenyu , Desneux Nicolas , Han Peng , Wang Su , Li Shu
Published: December 2022

Banker plant systems increase biological pest control by supporting populations of natural enemies, i.e., using non-pest arthropod species as alternative prey. However, the presence of alternative prey does not always result in improved control of the target pest species owing to the complexity of biotic interactions. To increase the effectiveness of banker plants in IPM programs, a fine understanding of the indirect interactions between target aphid and alternative prey mediated by biocontrol agents is necessary. In this study, we first established a banker plant system, banker plant (Vicia faba)–alternative prey (Megoura japonica)–predator (Harmonia axyridis), to control the target pest (Myzus persicae) on pepper. We found that M. japonica strongly preferred faba bean as a host plant and posed no risk to Solanaceous crops. Harmonia axyridis adults had no significant predation preference for the alternative prey. In the short term, the interaction direction of the two aphid species depended on the relative initial density and the timescale. Harmonia axyridis showed a stronger negative effect on M. persicae than that on M. japonica. In the long term, the presence of alternative prey, M. japonica, enhanced the control effect of H. axyridis to M. persicae with initial density of 100–500 aphids per plant. The presence of the alternative prey could proliferate the population of H. axyridis, with from 0.2- to 2.1-fold increase of H. axyridis eggs. Overall, we put forward a strategy for setting the initial density of alternative prey of the banker plant system to target the high and low density of aphids, which highlighted the importance of indirect interactions in designing a proper banker plant system.