The Use of Ultrasonics in the Treatment of Waste Activated Sludge

1 INTRODUCTION Waste activated sludge (WAS) processes are key technologies to treat wastewater. Through their micro-bial activity, these biological processes produce how-ever huge amounts of WAS as an inevitable drawback of the WAS-process. Various techniques have been studied to further reduce the amount of excess sludge through (1) the maximum use of biological phospho-rus removal instead of chemical precipitation[1,2]; (2) the use of advanced treatment techniques such as per-oxidati…     

The Oxygen Dilemma: A Severe Challenge for the Application of Monooxygenases?

Monooxygenases are promising catalysts because they in principle enable the organic chemist to perform highly selective oxyfunctionalisation reactions that are otherwise difficult to achieve. For this, monooxygenases require reducing equivalents, to allow reductive activation of molecular oxygen at the enzymes' active sites. However, these reducing equivalents are often delivered to O₂ either directly or via a reduced intermediate (uncoupling), yielding hazardous reactive oxygen species and wasting valuable reducing equivalents. The oxygen dilemma arises from monooxygenases' dependency on O₂ and the undesired uncoupling reaction. With this contribution we hope to generate a general awareness of the oxygen dilemma and to discuss its nature and some promising solutions.     

The Treatment of Dyslipidemia—What's Left in the Pipeline?

Dyslipidemia is a pathological alteration of serum lipid levels. The most common forms are either elevations of triglycerides or low density lipoprotein cholesterol associated with a reduction of high density lipoprotein cholesterol. Most frequently both forms of lipid disorders are combined. Elevations of free fatty acid blood levels are commonly not subsumed under the term dyslipidemia. However, free fatty acids should also be considered, as they are frequently associated with dyslipidemia and represent a risk factor for cardiovascular diseases. Dyslipidemias are among the major etiologic factors for arterial occlusive diseases. Resulting in fatal implications such as stroke and coronary heart disease, dyslipidemias contribute to the most prevalent causes of death. Lowering of low density lipoprotein and raising of high density lipoprotein cholesterol levels have been shown in both epidemiologic and intervention studies to decrease mortality. Established treatments of dyslipidemias are statins and fibrates. However, recent research has established some new potential therapeutic targets which are currently investigated in clinical trials. New therapeutic approaches include subtype selective, dual, and pan-agonists of the peroxisome proliferator activated receptor, inhibitors of the cholesterol ester transfer protein, Acyl-CoA-cholesterol-acyltransferase, squalene synthase, microsomal triglycerid-transfer-protein, and cholesterol absorption. Clinical implications of new drugs under investigation are discussed in this review.     

Exosomes in the Treatment of Pancreatic Cancer: A Moonshot to PDAC Treatment?

Pancreatic Ductal Adenocarcinoma (PDAC) constitutes a leading cause of cancer death globally. Its mortality remains unaltered despite the considerable scientific progress made in the fields of diagnostics and treatment. Exosomes comprise of small extracellular vesicles secreted by nearly all cells; their cargo contains a vast array of biomolecules, such as proteins and microRNAs. It is currently established that their role as messengers is central to a plethora of both physiologic and pathologic processes. Accumulating data have shed light on their contributions to carcinogenesis, metastasis, and immunological response. Meanwhile, the advancement of personalized targeted therapies into everyday clinical practice necessitates the development of cost-efficient treatment approaches. The role of exosomes is currently being extensively investigated towards this direction. This review aims to summarize the current pre-clinical and clinical evidence regarding the effects of exosomal applications in the timely diagnosis, prognosis, and therapeutic management of pancreatic cancer.     

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

The Practical Application of Fractal Dimension in Water Treatment Practice–the Impact of Polymer Dosing

Abstract

The application of floc fractal dimension has been investigated in this work to determine if this parameter can have operational significance in water treatment. Natural organic matter suspensions were coagulated with aluminium sulphate and varying concentrations of a non‐ionic polymer. The fractal dimensions of the flocs formed were measured using light scattering and settling combined with image analysis. By using the correct methodology, optimum floc properties could be determined using the floc fractal dimension combined with the floc size and strength data.     

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca²⁺ homeostasis and is involved in transcellular Ca²⁺ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.     

“A Study in Yellow”: Investigations in the Stereoselectivity of Ene-Reductases

Ene-reductases from the Old Yellow Enzyme (OYE) superfamily are a well-known and efficient biocatalytic alternative for the asymmetric reduction of C=C bonds. Considering the broad variety of substituents that can be tolerated, and the excellent stereoselectivities achieved, it is apparent why these enzymes are so appealing for preparative and industrial applications. Different classes of C=C bonds activated by at least one electron-withdrawing group have been shown to be accepted by these versatile biocatalysts in the last decades, affording a vast range of chiral intermediates employed in the synthesis of pharmaceuticals, agrochemicals, flavours, fragrances and fine chemicals. In order to access both enantiomers of reduced products, stereodivergent pairs of OYEs are desirable, but their natural occurrence is limited. The detailed knowledge of the stereochemical course of the reaction can uncover alternative strategies to orient the selectivity via mutagenesis, evolution, and substrate engineering. An overview of the ongoing studies on OYE-mediated bioreductions will be provided, with particular focus on stereochemical investigations by deuterium labelling.     

Ag(I)-triazolylcarboxylates: The role of hydrocarbon tails in the formation of “sitting-on-layer” supramolecular bowls

Several α-amino acids, (l,d)-alanine and (l,d)-phenylalanine were utilized, as precursors for synthesis of 1,2,4-triazolyl carboxylic acids (l,d)-trala-H and (l,d)-trphe-H, which were explored as angular bifunctional building blocks for engineering Ag(I)-coordination polymers. Two complexes, [Ag(μ₄-trala)]·H₂O (1) and [Ag(μ₄-trphe)]·H₂O (2), were prepared under mild hydrothermal conditions and characterized. The organic ligands coordinate silver cations in a deprotonated form via a N₂O₂ donor set, where the tr group behaves in a [N–N] mode while the carboxylate function serves as a μ₂-η²:η⁰ bridge. Complexes 1 and 2 possess a layered structure consisting of [Ag([N–N]-tr)(COO)]_n chains which are interlinked through ligand spacers. Being oriented toward the neighboring layers, the hydrocarbon side “tails” display a peculiar role in the supramolecular organization of “sitting-on-layer” three-dimensional baskets. Each container is pleasantly suitable for binding a water molecule via an H-bonding acceptor portal of carboxylate fragments.     

The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

To Remove or Not to Remove? The Challenge of Extracting the Template to Make the Cavities Available in Molecularly Imprinted Polymers (MIPs)

Template removal is a critical step in the preparation of most molecularly imprinted polymers (MIPs). The polymer network itself and the affinity of the imprinted cavities for the template make its removal hard. If there are remaining template molecules in the MIPs, less cavities will be available for rebinding, which decreases efficiency. Furthermore, if template bleeding occurs during analytical applications, errors will arise. Despite the relevance to the MIPs performance, template removal has received scarce attention and is currently the least cost-effective step of the MIP development. Attempts to reach complete template removal may involve the use of too drastic conditions in conventional extraction techniques, resulting in the damage or the collapse of the imprinted cavities. Advances in the extraction techniques in the last decade may provide optimized tools. The aim of this review is to analyze the available data on the efficiency of diverse extraction techniques for template removal, paying attention not only to the removal yield but also to MIPs performance. Such an analysis is expected to be useful for opening a way to rational approaches for template removal (minimizing the costs of solvents and time) instead of the current trial-and-error methods.     

The Impact of Fluid Dynamic Stress in Stirred Bioreactors – The Scale of the Biological Entity: A Personal View

From the start of industrial biotechnology, there has been a perception that biological entities are damaged by stirring, so-called ‘shear damage'. Often, it was the soft option to explain a loss of performance when it was due to other factors, such as bubble ingestion with proteins or on scale-up, where tip speed increased when it was due to decreased homogeneity, especially in pH. For many years, poor control and the range of analytical tools available made a more in-depth explanation difficult; and the concepts of ‘high' and ‘low shear' impellers, now largely disproven, increased it. Here, the size of the biological entity is compared to the Kolmogorov microscale of turbulence leading to a reasonably clear picture emerging. The article starts with the author's introduction to the issue approximately 42 year ago with enzymes, conveniently also the smallest entity; and finishes with the largest, filamentous fungi.     

The measurement of the solubility of electrolytes in water—miscible organic solvent mixture by using the “solventing out” process

Twenty water—MOS-electrolyte systems were studied. An analytical expression which describes the relative solubility S/S^w as a function of the MOS amount, v, was found. Expressions for predicting the solubility constants λ and v₀/1 + v₀ from precipitation constants were found. These constants are applicable to the entire range, in most cases, and applicable for most of the range in other cases.