Step In Synthesis Research Articles

Medical therapy of pituitary adenomas

The physiologic experiments of the 1950s and 1960s that established the hypothalamic regulation of pituitary function led to the biochemical characterization of the various release and inhibiting hormones and their receptors over the next two decades and ultimately to the development of medical therapies for the various pituitary adenoma types. The paradigm of medical therapy is the extremely successful use of dopamine agonists (DA) for the treatment of prolactinomas, which built upon the basic knowledge that dopamine is the physiologic prolactin (PRL) inhibitor factor. The discovery of somatostatin and its receptors led to the development of somatostatin receptor ligands (SRLs) for the treatment of acromegaly and thyrotropin (TSH)-secreting adenomas, Knowledge of how growth hormone (GH) interacts with its receptor led to the development of pegvisomant, which blocks the binding of GH to its receptor. Early clinical observations of patients with acromegaly have led to the use of estrogens and selective estrogen receptor modulators to aid in its treatment. DAs and SRLs have only modest activity in Cushing's disease and most therapies involve enzymatic blockade of the various steps in cortisol synthesis, the two most recent being osilodrostat and levoketoconazole. Blockade of the cortisol receptor by mifepristone was found accidentally but then was established as a good treatment for Cushing's syndrome. The finding that clinically nonfunctioning adenomas had dopamine receptors led to the use of DA in these patients as well. Finally, an understanding of some of the abnormal molecular pathways underlying the rare aggressiveness of some adenomas and carcinomas has led to the use of temozolomide and now other chemotherapies and immunotherapies in such patients.

Concise Three Step Synthesis of the Bioactive Alkaloid Huajiaosimuline via a Zn(OTf)2 -Promoted Meinwald Rearrangement.

The synthesis of the biologically active alkaloid huajiaosimulne, isolated from the roots of Zanthoxylum simulans, is reported. The natural product was assembled from simple commercial reagents via initial domino Knoevenagel/oxa-6π-electrocyclization followed by epoxidation and an epoxide/ketone rearrangement promoted by Zn(OTf)2. In vitro cytotoxicity assays identified natural products huajiaosimuline and simulansine as moderate antiproliferative agents against murine colon cancer CT26 cells.

One−Step Synthesis Strategy for a Platinum−Based Alloy Catalyst Designed via Crystal−Structure Prediction

One−Step Synthesis Strategy for a Platinum−Based Alloy Catalyst Designed via Crystal−Structure Prediction

Role of the initiation factor 3 in the fidelity of initiator tRNA selection on ribosome.

Initiation factors play critical roles in fine-tuning translation initiation, which is the first and the rate-limiting step in protein synthesis. In bacteria, initiation factors, IF1, IF2 and IF3 work in concert to accurately position the initiator tRNA (i-tRNA) in its formyl-aminoacyl form, and the mRNA start codon at the ribosomal P-site, setting the stage for accommodation of the aminoacyl-tRNA in response to the second codon, and formation of the first peptide bond. Among these, IF3 is particularly crucial in ensuring the fidelity of translation initiation as it is involved in the accuracy of the selection of i-tRNA and the start codon. The two-domains (N- and C-terminal) dumbbell shaped structure and dynamics of IF3 significantly influence its fidelity function. This review explores how the N- and C-terminal domains of IF3 communicate with each other and how their interaction with i-tRNA helps to maintain the fidelity of translation initiation.

High Strength Anhydrite Cement Based on Lime Mud From Water Treatment Process: One Step Synthesis in Water Environment, Characterization and Technological Parameters

ABSTRACTIn the process of water treatment from surface water sources, lime mud as waste is formed. This waste contains CaO, Ca(OH)2, and CaCO3. The article proposes a comprehensive method for processing lime mud into high‐strength anhydrite cement. The method involves the interaction of lime mud with waste sulfuric acid from the production of polymer fibers using a structure‐controlled method in the (CaO·Ca(OH)2·CaCO3)—H2SO4—H2O system at a temperature of 40°C. X‐ray diffraction analysis showed the presence of CaSO4 and CaSO4·0.62H2O phases with a purity of 99.8%. The structure‐controlled method makes it possible to control the formation and growth of calcium sulfate crystals of the required shape and size, due to which it is possible to obtain anhydrite cement with desired properties. Combined grinding of synthetic anhydrite with activator additives makes it possible to obtain anhydrite cement with a strength of up to 28.5 MPa.

Evaluation of the application value of mRNA vaccine of monkeypox virus

Abstract. With the advancement of technology in the global business environment, modern medicine has achieved significant milestones in vaccine development, particularly in combating various viral infections. In recent years, the global spread of the monkeypox virus has become a critical issue that the medical community urgently needs to address. This article assesses the potential value of mRNA vaccines in the application against monkeypox virus and provides a comprehensive comparison with traditional vaccines. Compared to traditional vaccines, mRNA vaccines exhibit high potential, safety, and efficacy; the paper thoroughly discusses the mechanism of action of mRNA vaccines, including their steps in the immune response, vaccine preparation, and the mechanism by which mRNA vaccines complete the immune response within infected individuals. Additionally, the article provides a detailed introduction to the synthesis steps and delivery systems of mRNA vaccines. Although the development of mRNA vaccines is still in the early stages and not yet commercially available, their application prospects in cell biology research and disease model construction are broad, and they are expected to become a powerful tool for future cell capture and analysis.

2D Nano-Photosensitizer Facilitates Proximity Labeling for Living Cells Surfaceome Deciphering.

Photocatalytic proximity labeling has shown great promise for mapping the spatiotemporal dynamics of surfaceome. Although cell-surface targeting photosensitizers relying on antibodies, lipid molecules, and metabolic labeling have gained effects, the development of simpler and stable methods that avoid complex chemical synthesis and biosynthesis steps is still a huge challenge. Here, the study has introduced 2D nanomaterials with the ability of cell surface engineering to perform the in situ anchoring of photosensitizer on living cell surface. Photosensitizer can be stabilized on nanomaterials by coordination after one-step mixing, resulting in the nano-photosensitizer combining cell surface targeting ability and photosensitivity that allowing surface-specific proximity labeling. Nano-photosensitizer can be dispersed stably in aqueous solution, avoiding the defects of poor water solubility and aggregation of traditional organic photosensitizers. Singlet oxygen is generated locally under light irradiation, enabling spatiotemporally-resolved activating and labeling of cell surface proteome. Further application in the brain metastatic lung cancer has been found effective with numerous quantified differential cell surfaces proteins highly correlated with cancer metastasis and three potential players have been validated via immunoblotting and immunofluorescence, providing important insights for metastasis supported molecular mechanism.

A Novel method of controlling the molecular weight of PAN-lignin copolymer—Synthesis and characterization

Polyacrylonitrile-lignin copolymer (PLC) has been successfully prepared via solution polymerization technique by a three step synthesis procedure. The main aim of this research is to control the molecular weight of the PLC by varying the initiator, monomer or solvent concentration in the reaction. The loading of lignin was kept constant which is 20 wt % in the PLC. The Polyacrylonitrile (PAN) homopolymer synthesized in the first step and the final copolymer PLC were characterized by various techniques such as FTIR, NMR, DSC, UV etc. The chemical bonding of lignin with the PAN backbone has been ascertained by these characterisation methods. This study explores a promising way to control the molecular weight of PLC copolymer which can be further used in the production of precursor fibre for carbon fibre.

Efficient Formylation of Alcohols Using a Core-Shell Magnetic Nanocomposite via Vilsmeier-Haack Complex Formation

Introduction: The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis. Methods: In this study, we investigated the O-formylation of alcohols using dimethylfor-mamide (DMF) in a mixture with a new magnetic nanocomposite Fe3O4@Chitosan/POCl2-x. Results: The results demonstrate that this core-shell heterogeneous nanocomposite facili-tates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite ex-hibits remarkable selectivity, favoring the formylation of less hindered benzylic and ali-phatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly. Conclusion: This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceu-tical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stabil-ity, and significant advantages over conventional methodologies.

The role of the essential GTPase ObgE in regulating lipopolysaccharide synthesis in Escherichia coli

During growth, cells need to synthesize and expand their envelope, a process that requires careful regulation. Here, we show that the GTPase ObgE of E. coli contributes to the regulation of lipopolysaccharide (LPS) synthesis, an essential component of the Gram-negative outer membrane. Using a dominant-negative mutant (named ‘ObgE*’), we show a direct interaction between ObgE and LpxA, which catalyzes the first step in LPS synthesis. This interaction is enhanced by the mutation in ObgE* which, when bound to GTP, leads to inhibition of LpxA, decreased LPS synthesis, and cell death. Although wild-type ObgE does not exert the same strong effects as ObgE* on LpxA or LPS synthesis, our data indicate that ObgE participates in the regulation of cell envelope synthesis in E. coli. Because ObgE also influences other cellular functions (i.e., ribosome assembly, DNA replication, etc.), it seems increasingly plausible that this GTPase coordinates several processes to finetune cell growth.

Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity.

We recently identified the herbicide oxyfluorfen as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), a key step in thyroid hormone synthesis, using in vitro assays. We also observed a suppression of serum T4 and T3 in juvenile rats exposed orally to oxyfluorfen for 4-8 days. The purpose of the present study was to further evaluate effects of an extended 31-day oral exposure using a male pubertal rat study (15 to 500 mg/kg). Oxyfluorfen delayed puberty at all doses (1.3 -3.5 days) suppressing ventral prostate at 62.5 mg/kg and above and seminal vesicle weights at 31.25 mg/kg and above with no effect on testosterone or luteinizing hormone. Serum T4 and T3 were suppressed by all doses up to 80%, with a linear increase in serum TSH. Based on delayed puberty without changes in testosterone, we hypothesized that oxyfluorfen interferes with androgen receptor (AR) function. Results from our Hershberger study, with oxyfluorfen (62.5 and 125 mg/kg) co-treated with testosterone proprionate (TP , 1 mg/kg) for 10 days showed 3 of 5 of the androgenic tissue weights were suppressed compared to TP alone indicating AR antagonism. We next confirmed this effect in an in vitro AR transcriptional activation reporter assay (0-20 μM) with 125 pM 5αDH-11-ketotestosterone and found concentration-dependent inhibition of AR luminescence activity (EC50 1.75 µM) without cytotoxicity. Here, we confirmed the endocrine disrupting effects of oxyfluorfen using both in vitro and in vivo evaluations of the thyroid hormone and AR pathways. This abstract doesn't necessarily reflect U.S. EPA policy.

Two step synthesis of fluorescent zirconia oxide amorphous nanosheets for highly sensitive detection of a cancer marker

This study has reported the first-ever fluorescent 2D amorphous zirconia nanosheets (ZrO2 NS) synthesis approach and their utilization for the detection of tyrosine. We have reported a novel yet simple approach to the synthesis approach by dissolving ZrCl4 in ethanol followed by the reduction with the use of sodium hydroxide. It is suggested that NaOH partially reduces Zr4+ and for Zr–OH conjugates finally forming ZrO2 sheet structure by Cl− templating due to the high affinity of reduced Zr towards oxygen. The as-synthesized 2D amorphous zirconia nanosheet suspension in ethanol resulted in a blue color fluorescence with an emission maximum of 430 nm. This nanosheet system shows a unique quenching property by tyrosine in both PBS buffer and human blood serum. This system was utilized to develop a fluorometric sensing platform for a cancer biomarker, tyrosine. The system showed firm results in 1–100 nM range with a LOD of 14.9 nM in human blood serum and 8.4 nM in PBS. This study has opened a new insight into utilizing 2D amorphous zirconia nanostructures in a novel way and also it creates a platform for using the 2D amorphous NS as a biosensor to detect cancer markers in the medical and biomedicine fields too.

Ex Situ Electro‐Organic Synthesis – A Method for Unrestricted Reaction Control and New Options for Paired Electrolysis

AbstractClassic in situ electro‐organic synthesis with substrates in an electrolyzer must compromise process conditions to balance electro‐ and thermochemical steps at both electrodes. This often restricts efficiency and product selectivity, since requirements may deviate for electrochemical (catalyst activation) and chemical (organic synthesis) steps, as well as for paired anode‐ and cathode reactions. Breaking this barrier, we report ex situ electro‐organic synthesis as a versatile method that enables unique product selectivity and unusual product pairs. We exemplify the concept for pairing H2 evolution (HER) with anodic alcohol oxidation. The two‐step method accomplishes this by separating cathode reactions from organic substrate oxidation, and anodic electrocatalyst activation from chemical conversion of organic substrates in time and space. First, the electro‐oxidation of Ni(OH)2 anodes to NiOOH is paired with H2 production by alkaline water electrolysis. Then, “charged” NiOOH electrodes are removed from the electrolyzer and used in external vessels to oxidize model substrate benzyl alcohol under regeneration of Ni(OH)2. Free choice of reaction media outside the electrolyzer allows to selectively obtain benzoic acid (in water) or benzaldehyde (in n‐hexane), whereas classic in situ electrosynthesis only produces the acid together with H2. Perspectively, the method enables electrosynthesis of previously inaccessible products paired to H2 generation.

Using Machine Learning for Systematic Literature Review Case in Point: Agile Software Development

ABSTRACTSystematic literature reviews (SLRs) are essential for researchers to keep up with past and recent research in their domains. However, the rapid growth in knowledge creation and the rising number of publications have made this task increasingly complex and challenging. Moreover, most systematic literature reviews are performed manually, which requires significant effort and creates potential bias. The risk of bias is particularly relevant in the data synthesis task, where researchers interpret each study's evidence and summarize the results. This study uses an experimental approach to explore using machine learning (ML) techniques in the SLR process. Specifically, this study replicates a study that manually performed sentiment analysis for the data synthesis step to determine the polarity (negative or positive) of evidence extracted from studies in the field of agile methodology. This study employs a lexicon‐based approach to sentiment analysis and achieves an accuracy rate of approximately 86.5% in identifying study evidence polarity.

GD2 in Breast Cancer: A Potential Biomarker and Therapeutic Target.

Expression of disialoganglioside GD2 in normal tissues is primarily limited to the central nervous system, peripheral sensory nerve fibers, dermal melanocytes, lymphocytes, and mesenchymal stem cells. Its widespread overexpression in various cancer types allows it to be classified as a tumor-associated antigen with potential diagnostic and therapeutic implications. This article reviews the synthesis pathways of GD2 and its role in cancer cell adhesion, proliferation, and metastasis with a focus on breast cancer. GD2 appears to be overexpressed on the outer membrane of most breast cancer cells and breast cancer stem cells (BCSCs) and is closely linked to epithelial-mesenchymal transition (EMT). GD3 synthase (GD3S) is considered to be the rate-determining step in GD2 synthesis. Clinical studies indicate that GD2 expression is increased in 35-70% of breast cancer samples, with higher levels in triple-negative breast cancer (TNBC). This overexpression correlates with more aggressive tumor features and worse prognosis. Therapeutic targeting of GD2 with monoclonal antibodies (moABs) like dinutuximab and naxitamab has demonstrated anti-cancer activity in preclinical cancer models and human clinical trials against high-risk neuroblastoma reducing tumor growth and enhancing survival. GD2-specific chimeric antigen receptor (CAR) T-cell therapy and GD3S inhibition present other promising therapeutic strategies to improve clinical outcomes. Furthermore, GD2-targeted vaccines are currently being investigated in cancer therapy. This narrative review article underscores the critical role of GD2 in breast cancer pathogenesis and highlights the promising therapeutic opportunities it offers. It advocates for the initiation of clinical trials to further explore the potential of GD2-targeted treatment in combination with standard breast cancer therapies.

The burden of lung cancer attributable to ambient PM2.5 exposure: a systematic literature review

Abstract Background Lung cancer is recognized as one of the most common causes of cancer morbidity and mortality worldwide and is the second cause of death with highest years of life lost in highly developed regions. Ambient exposure to particulate matter (PM2.5) is the leading global environmental risk factor. Long-term exposure to PM2.5 is associated with several health outcomes, including lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease. Aim To review and estimate the impact attributable to PM2.5 exposure due to lung cancer. Methods A systematic review and a meta-analysis were conducted to determine whether long-term exposure to PM2.5 increases the risk of lung cancer and to derive exposure-response relationships between PM2.5 and lung cancer. The literature search was performed in databases (i.e., Pubmed/Scopus) and studies published from January 1, 2010 onwards were considered. Studies describing the association between long-term exposure to the pollutant under research and the incidence, prevalence, and mortality of lung cancer, considering a relative measure of association were included, with no restriction in geographical area. Results In the literature review, 2215 articles were considered for the first step of data synthesis, all articles were screened, considering the screening of titles (first step), abstracts (second step) and full-text (third step) considering the inclusion criteria. In a second step the data was extracted from the included articles (n = 129) and considering the variables related to the characteristics of the study and the study population, exposure, and outcome measurement, and details of risk of bias assessment. Conclusions These findings provide data to synthesize effect size estimates using a Meta-Regression - Bayesian, Ensemble, Regularized, Trimmed (MR-BRT) model, important to provide evidence data on the impact of air pollution on human health, which is crucial for decision-making. Key messages • Long-term exposure to PM2.5 increases lung cancer risk so the estimating of the impact of the exposure is an urgent need to provide evidence-based data for air quality improvement. • Meta-analysis aims to establish a relation between PM2.5 exposure and the burden of lung cancer.

Gene isolation and expression analysis of galactinol synthase from proso millet (Panicum miliaceum L.)

Abstract Drought is the major devastating stress affecting plant growth and development. The plant develops some physiological and biochemical changes to withstand drought. The raffinose family of oligosaccharides (RFOs) are sugars that have a significant role in abiotic stress tolerance. Galactinol synthase (EC 2.4.1.123; GolS) initiates the primary step of the RFOs synthesis. Their accumulation implies a role for RFOs in abiotic stress adaptation. The galactinol synthase gene from proso millet was isolated and characterized. Full length proso millet galactinol synthase gene of size ~1,200 bp having 3 exons with 2 introns was isolated and predicted using bioinformatics tools. A high sequence similarity was observed at 97.2, 95.6, 91.8 and 85.4% with Panicum hallii, Panicum virgatum, Setaria italica and Zea mays mRNA, respectively. PmGolS gene expression pattern with respect to drought stress was evaluated in proso millet. PmGolS gene was highly expressed, 40.3 and 23.7-fold in vegetative and reproductive stages of drought-stressed plants respectively compared to control. It suggested that PmGolS gene has an active role in drought stress tolerance.

Bortezomib (BOR)‐Pegylated‐Gold Nanovector: Synthesis, Spectroscopic Evaluation and Diagnostic Tool as Galectin‐1 Biomarker

ABSTRACTIn this paper, we applied an original chemical methodology in which gold salt (HAuCl4) interacts with the chemotherapeutic drug (bortezomib; i.e., BOR) by chelation and then stacked with dicarboxylic acid‐terminated polyethylene‐glycol (PEG‐diacide) as a biocompatible surfactant. The suggested chemical protocol is rapid (“one‐pot”) and reproducible, providing the formation of a hybrid‐nanovector named BOR IN PEG‐AuNPs. In order to prove a therapeutic approach, our hybrid‐nanovector (BOR IN PEG‐AuNPs) interacts with Galectin‐1 (Gal‐1) protein biomarker under specific concentrations. The efficient concentration range of this nanovector is obviously profiled by tumor microenvironment (TME) heterogeneity, optimizing cells access to the interaction region. Considering several influential factors related to spatial mapping and physical profile in all extracellular matrix (ECM), drive a change in neighborhood electrical potential configuration, leading the nanovector response with biomarkers transcriptions, hence, patterning TME leads to promote antitumor immunity in favor of tumor suppression. Each step of chemical synthesis and detection was monitored by spectroscopic techniques (Raman; UV‐Vis spectroscopies) and transmission electron microscopy (TEM). Our study demonstrated that hybrid‐nanoparticle system represents a key to further synergic chemotherapeutic and diagnostic tools for the treatment of cancer.

Process Control of Multistep Surface Functionalization on Hydroxyethyl Starch Nanocapsules Determines the Reproducibility of the Biological Efficacy.

Nanocarrier synthesis is highly process-dependent, leading to potential batch-to-batch variability if it is not controlled at each step. This variability affects the reproducibility of subsequent biomodification, resulting in unpredictable biological effects, particularly for bioactive molecules such as interleukin-2 (IL-2). Inconsistent conjugation can lead to variable treatment outcomes and severe side effects. Therefore, precise control of each synthesis step is critical for ensuring a consistent quality and biological performance. Our study demonstrates that dividing nanocarrier synthesis into smaller, controlled steps improves reproducibility. Using this method, we achieved highly reproducible, concentration-dependent growth of CTLL-2 cells with hydroxyethyl starch (HES) nanocapsules functionalized with defined amounts of IL-2. We believe that such detailed, stepwise control in nanocarrier synthesis enhances batch consistency, improving the clinical applicability of the drug delivery systems.

Biosensor Based on the Immobilization of Laccase on β-Cyclodextrin Membrane for the Evaluation of Antioxidant Capacity in Real Samples.

The optimization of a new amperometric biosensor for evaluating antioxidant capacity in real samples is reported. The biosensor is based on the immobilization of Laccase from Trametes versicolor on an electropolymerized β-cyclodextrin polymeric membrane on a glassy carbon electrode. The process of electropolymerization, which was successful even in the presence of the enzyme, was a key step in biosensor synthesis. Variables such as pH, temperature, and enzyme concentration were optimized using a factorial design with two levels for each factor. Different electrodes were constructed and tested using caffeic acid as a standard. The best biosensor is synthesized at pH 3.0 with 6 mg/mL of enzyme and 30 °C. The biosensor presented a response time of ≤30 seconds and good stability in its amperometric response. The biosensor was used to evaluate the antioxidant capacity of real samples. Infusions of green, black, red, and white tea were assessed. The biosensor showed excellent stability and good performance regarding response time, stability, and easy fabrication. The proposed biosensor is a good option for evaluating antioxidant capacity in real samples without sample pretreatment. It combines a simple fabrication methodology and a minimal extraction process for rapid and reliable phenolic content determination in real samples.