BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Role of manures and crop residue in alleviating soil fertility constraints to crop production: With special reference to the Sahelian and Sudanian zones of West Africa

In the West African semi-arid tropics (WASAT), continuous cultivation leads to drastically reduced levels of soil organic matter. Such reductions in the level of soil organic matter have resulted in decreased soil productivity. The addition of organic materials either in the form of manures or crop residue has beneficial effects on the soils' chemical and physical properties. For many of the countries in this region, the amounts of nutrients in crops and crop residue are often several orders of magnitude higher than the quantity of the same nutrients applied as fertilizers. The return of the crop residue for soil fertility improvement cannot be overstressed. It is essential that more information on the rates of organic matter decomposition as well as the many reactions between products of organic matter decomposition and the soil under WASAT conditions be made available.     

Mathematical Modeling of the Coupled Transport Phenomena and Color Development: Finish Drying of Trellis-Dried Sultanas

A mathematical model for simulation of simultaneous heat and mass transport was developed to describe the drying kinetics during finish drying of trellis-dried sultanas. In this model, the governing partial differential equations for heat and mass transfer for a solid spherical body were numerically solved using a finite difference technique. In addition, a kinetic model was coupled to the heat and mass transfer calculations to simultaneously predict the evolution of product color during the drying process. This allows predictions of moisture content, temperature, and color profiles of the product in a space–time domain during the drying process as a function of various operating conditions.

Predictions compared well with the experimental values, implying that the proposed numerical model can be used with confidence for the simulation of the important transport phenomena in optimizing the design and operation of a drying system for sultanas that maximizes the retention of the desired product color. The work has demonstrated the importance of establishing optimal and closely controlled drying conditions because significant effects of the key operational parameters on drying kinetics and the associated changes of product color were found. The modeling approach proposed here can be extended to other products and for incorporation of other product quality indices.     

Back to the suture: the distribution of intraspecific genetic diversity in and around anatolia

The effect of ice ages in speciation and diversification is well established in the literature. In Europe, the Iberian, the Italian and the Balkan peninsulas comprise the main glacial refugia, where the subsequent re-population of Europe started. Though not studied as extensively, Anatolia has also been hinted to be a potential glacial refugium for Europe, and with its proximity to the Caucasus and the Middle East at the same time, has potential to exhibit high levels of intraspecific diversity. The more ubiquitous use and cheaper availability of molecular methods globally now makes it possible to better understand molecular ecology and evolution of the fauna and flora in the genetically understudied regions of the world, such as Anatolia. In this review, the molecular genetic studies undertaken in Anatolia in the last decade, for 29 species of plants and animals, are examined to determine general phylogeographic patterns. In this regard, two major patterns are observed and defined, showing genetic breaks within Anatolia and between Anatolia and the Balkans. A third pattern is also outlined, which suggests Anatolia may be a center of diversity for the surrounding regions. The patterns observed are discussed in terms of their relevance to the location of suture zones, postglacial expansion scenarios, the effect of geographic barriers to gene flow and divergence time estimates, in order to better understand the effect of the geological history of Anatolia on the evolutionary history of the inhabitant species. In view of the current state of knowledge delineated in the review, future research directions are suggested.     

From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases

Enzymes in the transcarbamylase family catalyze the transfer of a carbamyl group from carbamyl phosphate (CP) to an amino group of a second substrate. The two best-characterized members, aspartate transcarbamylase (ATCase) and ornithine transcarbamylase (OTCase), are present in most organisms from bacteria to humans. Recently, structures of four new transcarbamylase members, N-acetyl-l-ornithine transcarbamylase (AOTCase), N-succinyl-l-ornithine transcarbamylase (SOTCase), ygeW encoded transcarbamylase (YTCase) and putrescine transcarbamylase (PTCase) have also been determined. Crystal structures of these enzymes have shown that they have a common overall fold with a trimer as their basic biological unit. The monomer structures share a common CP binding site in their N-terminal domain, but have different second substrate binding sites in their C-terminal domain. The discovery of three new transcarbamylases, l-2,3-diaminopropionate transcarbamylase (DPTCase), l-2,4-diaminobutyrate transcarbamylase (DBTCase) and ureidoglycine transcarbamylase (UGTCase), demonstrates that our knowledge and understanding of the spectrum of the transcarbamylase family is still incomplete. In this review, we summarize studies on the structures and function of transcarbamylases demonstrating how structural information helps to define biological function and how small structural differences govern enzyme specificity. Such information is important for correctly annotating transcarbamylase sequences in the genome databases and for identifying new members of the transcarbamylase family.     

Methodologies and Perspectives of Proteomics Applied to Filamentous Fungi: From Sample Preparation to Secretome Analysis

Filamentous fungi possess the extraordinary ability to digest complex biomasses and mineralize numerous xenobiotics, as consequence of their aptitude to sensing the environment and regulating their intra and extra cellular proteins, producing drastic changes in proteome and secretome composition. Recent advancement in proteomic technologies offers an exciting opportunity to reveal the fluctuations of fungal proteins and enzymes, responsible for their metabolic adaptation to a large variety of environmental conditions. Here, an overview of the most commonly used proteomic strategies will be provided; this paper will range from sample preparation to gel-free and gel-based proteomics, discussing pros and cons of each mentioned state-of-the-art technique. The main focus will be kept on filamentous fungi. Due to the biotechnological relevance of lignocellulose degrading fungi, special attention will be finally given to their extracellular proteome, or secretome. Secreted proteins and enzymes will be discussed in relation to their involvement in bio-based processes, such as biomass deconstruction and mycoremediation.     

Exposure to Environmental Toxicants and Pathogenesis of Amyotrophic Lateral Sclerosis: State of the Art and Research Perspectives

There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease, is caused by gene-environment interactions. In fact, given that only about 10% of all ALS diagnosis has a genetic basis, gene-environmental interaction may give account for the remaining percentage of cases. However, relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron degeneration leading to ALS, although exposure to chemicals—including lead and pesticides—agricultural environments, smoking, intense physical activity, trauma and electromagnetic fields have been associated with an increased risk of ALS. This review provides an overview of our current knowledge of potential toxic etiologies of ALS with emphasis on the role of cyanobacteria, heavy metals and pesticides as potential risk factors for developing ALS. We will summarize the most recent evidence from epidemiological studies and experimental findings from animal and cellular models, revealing that potential causal links between environmental toxicants and ALS pathogenesis have not been fully ascertained, thus justifying the need for further research.     

几种药剂对玉米红蜘蛛的室内和大田药效

几种杀螨剂对玉米红蜘蛛窜内药效结果显示:对玉米红蜘蛛的主要种类--截形叶螨第7天的室内防效为28%哒螨灵乳油(78.3%)>240 g/L螨危FS(76.7%)>1.8%阿维菌素乳油(72.O%)>40%炔满特乳油(65.9%)>40%氧乐果乳油(63.3%)>2.5%溴氰菊酯乳油(58.3%).大田试验结果表明:30 d后以240 g/L螨危FS 150 mL/hm2的效果最佳,防效为76.8%;氧乐果由于在当地长期使用,效果已经很不理想,防治效果只有38.7%.     

Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.     

Oxygen Toxicity to the Immature Lung—Part I: Pathomechanistic Understanding and Preclinical Perspectives

In utero, the fetus and its lungs develop in a hypoxic environment, where HIF-1α and VEGFA signaling constitute major determinants of further development. Disruption of this homeostasis after preterm delivery and extrauterine exposure to high fractions of oxygen are among the key events leading to bronchopulmonary dysplasia (BPD). Reactive oxygen species (ROS) production constitutes the initial driver of pulmonary inflammation and cell death, altered gene expression, and vasoconstriction, leading to the distortion of further lung development. From preclinical studies mainly performed on rodents over the past two decades, the deleterious effects of oxygen toxicity and the injurious insults and downstream cascades arising from ROS production are well recognized. This article provides a concise overview of disease drivers and different therapeutic approaches that have been successfully tested within experimental models. Despite current studies, clinical researchers are still faced with an unmet clinical need, and many of these strategies have not proven to be equally effective in clinical trials. In light of this challenge, adapting experimental models to the complexity of the clinical situation and pursuing new directions constitute appropriate actions to overcome this dilemma. Our review intends to stimulate research activities towards the understanding of an important issue of immature lung injury.     

印染废水回用色度测定方法探讨

文章简要介绍水样色度的三种测定方法,重点介绍稀释倍数法,结合实际对稀释倍数法的测定过程进行探讨,得出回用印染废水最佳的测定途径,并指出此方法测定的意义。     

Chiral Separations using Miniaturized Techniques: State of the Art and Perspectives

The separation and analysis of chiral compounds is an important topic of research, because these analytes are involved in various processes, e.g., biological, pharmacological, human health, etc. Their separation has also been recently obtained utilizing microfluidic techniques, such as capillary electrophoresis (CE), electrochromatography (CEC), and capillary/nano-liquid chromatography (CLC/nano-LC). Enantiomeric separation is mainly obtained by applying the direct resolution method, where a chiral selector (CS) is present in the separation system, either added to the mobile phase (MP) or bonded to the stationary phase or to the capillary wall. Among the several CSs used in microfluidic techniques, cyclodextrins, proteins, peptides, glycopeptide antibiotics, and modified polysaccharides are the most employed. Microfluidic techniques can offer several advantages over conventional analytical tools, e.g., high efficiency, high mass sensitivity, and reduced volumes of MP and sample. Optimized methods have been applied in different fields, such as biomedical, food chemistry, environment, pharmaceutical, etc. Excellent results have been achieved in CE and nano-LC. Although CEC can offer higher efficiency due to the use of a strong electroosmotic flow, its use is less popular than the other. This limitation can be explained with the limited number of the stationary phases (SPs) commercially available.     

Application of the DNDC model to tile-drained Illinois agroecosystems: model comparison of conventional and diversified rotations

Using the DeNitrification–DeComposition (DNDC) model we compare conventional, fertilizer-driven corn–soybean rotations to alternative management scenarios which include the management of cereal rye cover crops and corn–soybean–wheat–red clover rotations. We conduct our analysis for tile-drained, silty clay loam soils of Illinois. DNDC simulations suggest that, relative to conventional rotations, a nitrate leaching reduction of 30–50% under corn and of 15–50% under soybean crops can be achieved with diversified rotations, an outcome which corroborates results from a quantitative literature review we previously conducted using a meta-analysis framework. Additionally, over a 10-year simulation, legume-fertilized systems are predicted to result in 52% lower N₂O gas flux relative to fertilizer-driven systems. We identify soil organic carbon storage, legume N-fixation rate, and cereal rye cover crop growth as areas requiring further development to accurately apply DNDC to diversified cropping systems. Overall, DNDC simulation suggests diversified rotations that alternate winter and summer annuals have the potential to dramatically increase N retention in agroecosystems.     

Challenges of the Immunotherapy: Perspectives and Limitations of the Immune Checkpoint Inhibitor Treatment

Immunotherapy is a quickly developing type of treatment and the future of therapy in oncology. This paper is a review of recent findings in the field of immunotherapy with an emphasis on immune checkpoint inhibitors. The challenges that immunotherapy might face in near future, such as primary and acquired resistance and the irAEs, are described in this article, as well as the perspectives such as identification of environmental modifiers of immunity and development of anti-cancer vaccines and combined therapies. There are multiple factors that may be responsible for immunoresistance, such as genomic factors, factors related to the immune system cells or to the cancer microenvironment, factors emerging from the host cells, as well as other factors such as advanced age, biological sex, diet, many hormones, existing comorbidities, and the gut microbiome.     

Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back

Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice.     

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation,through Visible and Near-Infrared Light: From the Origins to Modern Therapies

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.     

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.     

Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research

Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.