Complete Genome Sequence Analysis of Bacillus subtilis MC4-2 Strain That against Tobacco Black Shank Disease.

The MC4-2 bacterium strain was isolated and purified from the Periplaneta americana intestine as a biocontrol agent with good antagonistic effect against the pathogens of a soil-borne disease called tobacco black shank. The MC4-2 strain was found to have good broad-spectrum inhibition by plate stand-off test. Based on 16S rRNA and gyrB genes, ANI analysis, and other comparative genomics methods, it was determined that the MC4-2 strain was Bacillus subtilis. The complete genome sequence showed that the genome size was 4,076,630 bp, the average GC content was 43.78%, and the total number of CDSs was 4,207. Genomic prediction analysis revealed that a total of 145 genes were annotated by the CAZy, containing mainly GH and CE enzymes that break down carbohydrates such as glucose, chitin, starch, and alginate, and a large number of enzymes involved in glycosylation were present. A total of ten secondary metabolite clusters were predicted, six clusters of which were annotated as surfactin, bacillaene, fengycin, bacillibactin, subtilosin A, and bacilysin. The present investigation found the biological control mechanism of B. subtilis MC4-2, which provides a strong theoretical basis for the best use of this strain in biological control methods and provides a reference for the subsequent development of agents of this bacterium.

Brevibacillus brevis HNCS-1: a biocontrol bacterium against tea plant diseases.

As a biocontrol bacteria, Brevibacillus has been the subject of extensive research for agricultural applications. Antibacterial peptides (AMPs) are the main antibacterial products of Brevibacillus. This study isolated a strain of Br. brevis HNCS-1 from tea garden soil, and the strain has an antagonistic effect against five types of pathogens of tea diseases, namely Gloeosporium theae-sinensis, Elsinoe leucospira, Phyllosticta theaefolia, Fusarium sp., and Cercospora theae. To determine the genetic characteristics implicated in the biocontrol mechanism, the genome sequence of the HNCS-1 strain was obtained and analyzed further, and the data are deposited in the GenBank repository (No. CP128411). Comparative genomics analyses revealed that the HNCS-1 strain and 17 public Br. brevis share a core genome composed of 3,742 genes. Interestingly, only one non-ribosomal peptide synthetase (NRPS) gene cluster annotated as edeine is present in the core genome. And UHPLC-MS/MS detection results showd that edeine B and edeine A were the principal antibacterial peptides in the HNCS-1 strain. This study proves that edeine is the main antibacterial peptide of Br. brevis, and provides a new strategy for the identification of antibacterial products from other biocontrol bacteria.

Emerging technologies for COVID (ET-CoV) detection and diagnosis: Recent advancements, applications, challenges, and future perspectives.

In light of the constantly changing terrain of the COVID outbreak, medical specialists have implemented proactive schemes for vaccine production. Despite the remarkable COVID-19 vaccine development, the virus has mutated into new variants, including delta and omicron. Currently, the situation is critical in many parts of the world, and precautions are being taken to stop the virus from spreading and mutating. Early identification and diagnosis of COVID-19 are the main challenges faced by emerging technologies during the outbreak. In these circumstances, emerging technologies to tackle Coronavirus have proven magnificent. Artificial intelligence (AI), big data, the internet of medical things (IoMT), robotics, blockchain technology, telemedicine, smart applications, and additive manufacturing are suspicious for detecting, classifying, monitoring, and locating COVID-19. Henceforth, this research aims to glance at these COVID-19 defeating technologies by focusing on their strengths and limitations. A CiteSpace-based bibliometric analysis of the emerging technology was established. The most impactful keywords and the ongoing research frontiers were compiled. Emerging technologies were unstable due to data inconsistency, redundant and noisy datasets, and the inability to aggregate the data due to disparate data formats. Moreover, the privacy and confidentiality of patient medical records are not guaranteed. Hence, Significant data analysis is required to develop an intelligent computational model for effective and quick clinical diagnosis of COVID-19. Remarkably, this article outlines how emerging technology has been used to counteract the virus disaster and offers ongoing research frontiers, directing readers to concentrate on the real challenges and thus facilitating additional explorations to amplify emerging technologies.

Bio-accumulation effects of heavy metals Pb, Zn and Cd on Procecidochares utilis parasitism to Eupatorium adenophorum at Suzu metal mines, Yunnan.

Procecidochares utilis is an obligatory parasitic insect to Eupatorium adenophorum. Both organisms have been spread to some metal mines areas. The objective of this study is to comprehend the trend of heavy metals transfer and the process of their bio-accumulation in the soil-E. adenophorum-P. utilis system and particularly their impact on the parasitic effect of P. utilis to E. adenophorum to reflect the impact of heavy metals on obligate parasitic insect and its host. Therefore, a detailed investigation was carried out at the Suzu Lead-Zinc Mine in Yunnan Province using the concentric circle's method. The results showed that the parasitic rate of P. utilis to a single plant and branch is positively correlated with distance. The metals content of the soil in E. adenophorum and P. utilis, decreased dramatically with an increase in distance away from the center of the mining area. From which is cleared that these metals could enter to E. adenophorum and P. utilis through the soil-E. adenophorum-P. utilis system which likely to affect its parasitic activities. In addition, the parasitic rate is impacted by per Zn content greatly, and the parasitic rate per plant is affected by Cd content enormously. This work could provide important basis of data for further understanding and clarifying the effects of bioaccumulation and heavy metals pollution on various aspects of the food chain. Simultaneously, it could clarify and simplify whether heavy metal contamination affects the parasitic behaviour of some obligatory parasitic insects.

Activation of the canonical ER stress IRE1-XBP1 pathway by insulin regulates glucose and lipid metabolism.

Knockout of the transcription factor X-box binding protein (XBP1) is known to decrease liver glucose production and lipogenesis. However, whether insulin can regulate gluconeogenesis and lipogenesis through XBP1 and how insulin activates the inositol-requiring enzyme-XBP1 ER stress pathway remains unexplored. Here, we report that in the fed state, insulin-activated kinase AKT directly phosphorylates inositol-requiring enzyme 1 at S724, which in turn mediates the splicing of XBP1u mRNA, thus favoring the generation of the spliced form, XBP1s, in the liver of mice. Subsequently, XBP1s stimulate the expression of lipogenic genes and upregulates liver lipogenesis as previously reported. Intriguingly, we find that fasting leads to an increase in XBP1u along with a drastic decrease in XBP1s in the liver of mice, and XBP1u, not XBP1s, significantly increases PKA-stimulated CRE reporter activity in cultured hepatocytes. Furthermore, we demonstrate that overexpression of XBP1u significantly increases cAMP-stimulated expression of rate-limiting gluconeogenic genes, G6pc and Pck1, and glucose production in primary hepatocytes. Reexpression of XBP1u in the liver of mice with XBP1 depletion significantly increases fasting blood glucose levels and gluconeogenic gene expression. These data support an important role of XBP1u in upregulating gluconeogenesis in the fasted state. Taken together, we reveal that insulin signaling via AKT controls the expression of XBP1 isoforms and that XBP1u and XBP1s function in different nutritional states to regulate liver gluconeogenesis and lipogenesis, respectively.

An Efficient Supervised Deep Hashing Method for Image Retrieval.

In recent years, searching and retrieving relevant images from large databases has become an emerging challenge for the researcher. Hashing methods that mapped raw data into a short binary code have attracted increasing attention from the researcher. Most existing hashing approaches map samples to a binary vector via a single linear projection, which restricts the flexibility of those methods and leads to optimization problems. We introduce a CNN-based hashing method that uses multiple nonlinear projections to produce additional short-bit binary code to tackle this issue. Further, an end-to-end hashing system is accomplished using a convolutional neural network. Also, we design a loss function that aims to maintain the similarity between images and minimize the quantization error by providing a uniform distribution of the hash bits to illustrate the proposed technique's effectiveness and significance. Extensive experiments conducted on various datasets demonstrate the superiority of the proposed method in comparison with state-of-the-art deep hashing methods.

Economic Friendly ZnO-Based UV Sensors Using Hydrothermal Growth: A Review.

Ultraviolet (UV) sensors offer significant advantages in human health protection and environmental pollution monitoring. Amongst various materials for UV sensors, the zinc oxide (ZnO) nanostructure is considered as one of the most promising candidates due to its incredible electrical, optical, biomedical, energetic and preparing properties. Compared to other fabricating techniques, hydrothermal synthesis has been proven to show special advantages such as economic cost, low-temperature process and excellent and high-yield production. Here, we summarize the latest progress in research about the hydrothermal synthesis of ZnO nanostructures for UV sensing. We particularly focus on the selective hydrothermal processes and reveal the effect of key factors/parameters on ZnO architectures, such as the laser power source, temperature, growth time, precursor, seeding solution and bases. Furthermore, ZnO hydrothermal nanostructures for UV applications as well as their mechanisms are also summarized. This review will therefore enlighten future ideas of low-temperature and low-cost ZnO-based UV sensors.

Gross morphology and ultrastructure of the salivary glands of the stink bug predator Eocanthecona furcellata (Wolff).

Eocanthecona furcellata Wolff (Hemiptera: Pentatomidae) is a native generalist predator which attacks and kills its prey by first inserting its stylet into the prey's body and then injecting saliva into it. Here, we describe the histology and ultrastructure of its salivary glands. The study showed that the salivary glands were made up of pairs of principal and tubular accessory salivary glands. The principal salivary glands were bilobed and consisted of a smaller anterior lobe and a larger elongated posterior lobe. The ducts of the principal and accessory salivary glands were located in a narrow region between the anterior and posterior lobe known as the hilum. The principal salivary gland was lined with a single-layered epithelium. The cells cytoplasm was enriched with rough endoplasmic reticulum and secretory, and the nucleus showed a higher level of uncondensed chromatin. The basal region of the cell had plasma membrane infoldings. The cytoplasm of the accessory gland was rich in rough endoplasmic reticulum and many large cavities. The ducts of the principal salivary gland were made up of a single layer of flattened cells which had a thin cuticle lining the apical portion. Variation in the lumen content of the different lobes, which made up the principal gland suggested that their chemical products also varied. These results indicate that these two salivary glands produce the proteins found in the saliva.

Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK.

Impaired mitochondrial respiratory activity contributes to the development of insulin resistance in type 2 diabetes. Metformin, a first-line antidiabetic drug, functions mainly by improving patients' hyperglycemia and insulin resistance. However, its mechanism of action is still not well understood. We show here that pharmacological metformin concentration increases mitochondrial respiration, membrane potential, and ATP levels in hepatocytes and a clinically relevant metformin dose increases liver mitochondrial density and complex 1 activity along with improved hyperglycemia in high-fat- diet (HFD)-fed mice. Metformin, functioning through 5' AMP-activated protein kinase (AMPK), promotes mitochondrial fission to improve mitochondrial respiration and restore the mitochondrial life cycle. Furthermore, HFD-fed-mice with liver-specific knockout of AMPKα1/2 subunits exhibit higher blood glucose levels when treated with metformin. Our results demonstrate that activation of AMPK by metformin improves mitochondrial respiration and hyperglycemia in obesity. We also found that supra-pharmacological metformin concentrations reduce adenine nucleotides, resulting in the halt of mitochondrial respiration. These findings suggest a mechanism for metformin's anti-tumor effects.

The Emerging Role(s) for Kisspeptin in Metabolism in Mammals.

Kisspeptin was initially identified as a metastasis suppressor. Shortly after the initial discovery, a key physiologic role for kisspeptin emerged in the regulation of fertility, with kisspeptin acting as a neurotransmitter via the kisspeptin receptor, its cognate receptor, to regulate hypothalamic GnRH neurons, thereby affecting pituitary-gonadal function. Recent work has demonstrated a more expansive role for kisspeptin signaling in a variety of organ systems. Kisspeptin has been revealed as a significant player in regulating glucose homeostasis, feeding behavior, body composition as well as cardiac function. The direct impact of kisspeptin on peripheral metabolic tissues has only recently been recognized. Here, we review the emerging endocrine role of kisspeptin in regulating metabolic function. Controversies and current limitations in the field as well as areas of future studies toward kisspeptin's diverse array of functions will be highlighted.

Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes.

Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/ß-catenin signaling, but serum sclerostin levels in humans exhibit a correlation with impairments in several metabolic parameters. These data, together with the increased production of sclerostin in mouse models of type 2 diabetes, suggest an endocrine function. To determine whether sclerostin contributes to the coordination of whole-body metabolism, we examined body composition, glucose homeostasis, and fatty acid metabolism in Sost-/- mice as well as mice that overproduce sclerostin as a result of adeno-associated virus expression from the liver. Here, we show that in addition to dramatic increases in bone volume, Sost-/- mice exhibit a reduction in adipose tissue accumulation in association with increased insulin sensitivity. Sclerostin overproduction results in the opposite metabolic phenotype due to adipocyte hypertrophy. Additionally, Sost-/- mice and those administered a sclerostin-neutralizing antibody are resistant to obesogenic diet-induced disturbances in metabolism. This effect appears to be the result of sclerostin's effects on Wnt signaling and metabolism in white adipose tissue. Since adipocytes do not produce sclerostin, these findings suggest an unexplored endocrine function for sclerostin that facilitates communication between the skeleton and adipose tissue.

Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males.

Impaired estrogens action is associated with features of the metabolic syndrome in animal models and humans. We sought to determine whether disruption of hepatic estrogens action in adult male mice could recapitulate aspects of the metabolic syndrome to understand the mechanistic basis for the phenotype. We found 17ß-estradiol (E2) inhibited hepatic gluconeogenic genes such as phosphoenolpyruvate carboxykinase 1 (Pck-1) and glucose 6-phosphatase (G6Pase) and this effect was absent in mice lacking liver estrogen receptor α (Esr1) (LERKO mice). Male LERKO mice displayed elevated hepatic gluconeogenic activity and fasting hyperglycemia. We also observed increased liver lipid deposits and triglyceride levels in male LERKO mice, resulting from increased hepatic lipogenesis as reflected by increased mRNA levels of fatty acid synthase (Fas) and acetyl-CoA carboxylase (Acc1). ChIP assay demonstrated estradiol (E2) induced ESR1 binding to Pck-1, G6Pase, Fas and Acc1 promoters. Metabolic phenotyping demonstrated both basal metabolic rate and feeding were lower for the LERKO mice as compared to Controls. Furthermore, the respiratory exchange rate was significantly lower in LERKO mice than in Controls, suggesting an increase in lipid oxidation. Our data indicate that hepatic E2/ESR1 signaling plays a key role in the maintenance of gluconeogenesis and lipid metabolism in males.

The undoing and redoing of the diabetic ß-cell.

A hallmark of type 2 diabetes (T2DM) is the reduction in functional ß-cell mass, which is considered at least in part to result from an imbalance of ß-cell renewal and apoptosis, with the latter being accelerated during metabolic stress. More recent studies, however, suggest that the loss of functional ß-cell mass is not as much due to ß-cell death but rather to de-differentiation of ß-cells when these cells are exposed to metabolic stressors, opening the possibility to re-differentiate and restore functional ß-cell mass by therapeutic intervention. In parallel, clinical observations suggest that temporary intensive insulin therapy in early diagnosed humans with T2DM, so as to "rest" endogenous ß-cells, allows these patients to regain adequate insulin secretion and to maintain euglycemia for prolonged periods free of continued pharmacotherapy. Whether observations made in (mostly rodent) models of diabetes mellitus and in clinical trials are revealing identical mechanisms and therapeutic opportunities remains a tantalizing possibility. Our intention is for this review to serve as an overview of the field and commentary of this particularly exciting field of research.

Prkar1a gene knockout in the pancreas leads to neuroendocrine tumorigenesis.

Carney complex (CNC) is a rare disease associated with multiple neoplasias, including a predisposition to pancreatic tumors; it is caused most frequently by the inactivation of the PRKAR1A gene, a regulator of the cyclic AMP (cAMP)-dependent kinase (PKA). The method used was to create null alleles of prkar1a in mouse cells expressing pdx1 (Δ-Prkar1a). We found that these mice developed endocrine or mixed endocrine/acinar cell carcinomas with 100% penetrance by the age of 4-5 months. Malignant behavior of the tumors was seen as evidenced by stromal invasion and metastasis to locoregional lymph nodes. Histologically, most tumors exhibited an organoid pattern as seen in the islet-cell tumors. Biochemically, the lesions exhibited high PKA activity, as one would expect from deleting prkar1a The primary neuroendocrine nature of these tumor cells was confirmed by immunohistochemical staining and electron microscopy, the latter revealing the characteristic granules. Although the Δ-Prkar1a mice developed hypoglycemia after overnight fasting, insulin and glucagon levels in the plasma were normal. Negative immunohistochemical staining for the most commonly produced peptides (insulin, c-peptide, glucagon, gastrin and somatostatin) suggested that these tumors were non-functioning. We hypothesize that the recently identified multipotent pdx1+/insulin- cell in adult pancreas, gives rise to endocrine or mixed endocrine/acinar pancreatic malignancies with complete prkar1a deficiency. In conclusion, this mouse model supports the role of prkar1a as a tumor suppressor gene in the pancreas and points to the PKA pathway as a possible therapeutic target for these lesions.

Inter-organ communication and regulation of beta cell function.

The physiologically predominant signal for pancreatic beta cells to secrete insulin is glucose. While circulating glucose levels and beta cell glucose metabolism regulate the amount of released insulin, additional signals emanating from other tissues and from neighbouring islet endocrine cells modulate beta cell function. To this end, each individual beta cell can be viewed as a sensor of a multitude of stimuli that are integrated to determine the extent of glucose-dependent insulin release. This review discusses recent advances in our understanding of inter-organ communications that regulate beta cell insulin release in response to elevated glucose levels.

There is Kisspeptin - And Then There is Kisspeptin.

While kisspeptin was initially found to function as a metastasis suppressor, after identification of its receptor KISS1R and their expression profiles in tissues such as the hypothalamus and adrenals, kisspeptin and KISS1R were predominantly assigned endocrine functions, including regulating puberty and fertility through their actions on hypothalamic gonadotropin releasing hormone production. More recently, an alter ego for kisspeptin has emerged, with a significant role in regulating glucose homeostasis, insulin secretion, as well as food intake and body composition, and deficient kisspeptin signaling results in reduced locomotor activity and increased adiposity. This review highlights these recent observations on the role of kisspeptin in metabolism as well as several key questions that need to be addressed in the future.

Human ß-cell proliferation and intracellular signaling: part 3.

This is the third in a series of Perspectives on intracellular signaling pathways coupled to proliferation in pancreatic ß-cells. We contrast the large knowledge base in rodent ß-cells with the more limited human database. With the increasing incidence of type 1 diabetes and the recognition that type 2 diabetes is also due in part to a deficiency of functioning ß-cells, there is great urgency to identify therapeutic approaches to expand human ß-cell numbers. Therapeutic approaches might include stem cell differentiation, transdifferentiation, or expansion of cadaver islets or residual endogenous ß-cells. In these Perspectives, we focus on ß-cell proliferation. Past Perspectives reviewed fundamental cell cycle regulation and its upstream regulation by insulin/IGF signaling via phosphatidylinositol-3 kinase/mammalian target of rapamycin signaling, glucose, glycogen synthase kinase-3 and liver kinase B1, protein kinase Cζ, calcium-calcineurin-nuclear factor of activated T cells, epidermal growth factor/platelet-derived growth factor family members, Wnt/ß-catenin, leptin, and estrogen and progesterone. Here, we emphasize Janus kinase/signal transducers and activators of transcription, Ras/Raf/extracellular signal-related kinase, cadherins and integrins, G-protein-coupled receptors, and transforming growth factor ß signaling. We hope these three Perspectives will serve to introduce these pathways to new researchers and will encourage additional investigators to focus on understanding how to harness key intracellular signaling pathways for therapeutic human ß-cell regeneration for diabetes.

System for exposing cultured cells to intermittent hypoxia utilizing gas permeable cultureware.

Tissue intermittent hypoxia (IH) occurs in obstructive sleep apnea, sickle cell anemia, physical exercise and other conditions. Poor gas solubility and slow diffusion through culture media hampers mimicking IH-induced transitions of O(2) in vitro. We aimed to develop a system enabling exposure of cultured cells to IH and to validate such exposure by real-time O(2) measurements and cellular responses. Standard 24-well culture plates and plates with bottoms made from a gas permeable film were placed in a heated cabinet. Desired cycling of O(2) levels was induced using programmable solenoids to purge mixtures of 95% N(2) + 5% CO(2) or 95% O(2) + 5% CO(2). Dissolved oxygen, gas pressure, temperature, and water evaporation were measured during cycling. IH-induced cellular effects were evaluated by hypoxia inducible factor (HIF) and NF-κB luciferase reporters in HEK296 cells and by insulin secretion in rat insulinoma cells. Oxygen cycling in the cabinet was translated into identical changes of O(2) at the well bottom in gas permeable, but not in standard cultureware. Twenty-four hours of IH exposure increased HIF (112%), NF-κB (111%) and insulin secretion (44%). Described system enables reproducible and prolonged IH exposure in cultured cells while controlling for important environmental factors.