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In the past decades, the production of biopharmaceuticals has gained high interest due to its great sensitivity, specificity, and lower risk of negative effects to patients. Biopharmaceuticals are mostly therapeutic recombinant proteins produced through biotechnological processes. In this context, L-asparaginase (L-asparagine amidohydrolase, L-ASNase (E.C. 3.5.1.1)) is a therapeutic enzyme that has been abundantly studied by researchers due to its antineoplastic properties. As a biopharmaceutical, L-ASNase has been used in the treatment of acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), and other lymphoid malignancies, in combination with other drugs. Besides its application as a biopharmaceutical, this enzyme is widely used in food processing industries as an acrylamide mitigation agent and as a biosensor for the detection of L-asparagine in physiological fluids at nano-levels. The great demand for L-ASNase is supplied by recombinant enzymes from Escherichia coli and Erwinia chrysanthemi. However, production processes are associated to low yields and proteins associated to immunogenicity problems, which leads to the search for a better enzyme source. Considering the L-ASNase pharmacological and food importance, this review provides an overview of the current biotechnological developments in L-ASNase production and biochemical characterization aiming to improve the knowledge about its production.Key points• Microbial enzyme applications as biopharmaceutical and in food industry• Biosynthesis process: from the microorganism to bioreactor technology• Enzyme activity and kinetic properties: crucial for the final application

Oxygen reduction reaction (ORR) is an important electrochemical process for renewable energy conversion and storage applications such as fuel cells and metal‐air batteries. ORR is sluggish in kinetics and requires a large amount of platinum group metal (PGM)‐based catalysts to facilitate its slow reaction rate. Application of precious metals raises the cost and decreases the competitivity of these devices in the market. To address this challenge, PGM‐free ORR catalysts have been intensively investigated as an alternative to replace the PGM‐based catalysts and to promote the deployment of ORR‐related applications. In particular, the biomass holds promising potential to be used as the precursor material for PGM‐free ORR catalysts. This pathway has gained more and more attention in recent years. In this review, recent advances regarding biomass‐derived ORR catalysts are summarized with a focus on the rational design of both active sites and porous structures which are the two key factors in determining ORR performance of catalysts. At the end, the perspectives of development of biomass‐derived catalysts is discussed. The renewable and sustainable biomass‐derived catalysts are promising to facilitate the oxygen reduction reaction (ORR), which is the cornerstone reaction for renewable energy conversion and storage applications. The rational engineering of active sites and porous structure of the biomass‐derived ORR catalysts are reviewed in this paper.

l-asparaginase (ASNase, EC 3.5.1.1) is an aminohydrolase enzyme with important uses in the therapeutic/pharmaceutical and food industries. Its main applications are as an anticancer drug, mostly for acute lymphoblastic leukaemia (ALL) treatment, and in acrylamide reduction when starch-rich foods are cooked at temperatures above 100 °C. Its use as a biosensor for asparagine in both industries has also been reported. However, there are certain challenges associated with ASNase applications. Depending on the ASNase source, the major challenges of its pharmaceutical application are the hypersensitivity reactions that it causes in ALL patients and its short half-life and fast plasma clearance in the blood system by native proteases. In addition, ASNase is generally unstable and it is a thermolabile enzyme, which also hinders its application in the food sector. These drawbacks have been overcome by the ASNase confinement in different (nano)materials through distinct techniques, such as physical adsorption, covalent attachment and entrapment. Overall, this review describes the most recent strategies reported for ASNase confinement in numerous (nano)materials, highlighting its improved properties, especially specificity, half-life enhancement and thermal and operational stability improvement, allowing its reuse, increased proteolysis resistance and immunogenicity elimination. The most recent applications of confined ASNase in nanomaterials are reviewed for the first time, simultaneously providing prospects in the described fields of application.

Provides the research insights from the international business field on entrepreneurship in the global firm. This collection offers a comprehensive perspective on the wide variety of conceptual and managerial issues that arise as a result of entrepreneurial action in firms operating in the global economy.

Much of the recent excitement in the cancer immunotherapy approach has been generated by the recognition that immune checkpoint proteins, like the receptor PD-1, can be blocked by antibody-based drugs with profound effects. Promising clinical data have already been released pointing to the efficiency of the drug pembrolizumab to block the PD-1 pathway, triggering the T-lymphocytes to destroy the cancer cells. Thus, a deep understanding of this drug/receptor complex is essential for the improvement of new drugs targeting the protein PD-1. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT), we investigate in silico the binding energy features of the receptor PD-1 in complex with its drug inhibitor. Our computational results give a better understanding of the binding mechanisms, being also an efficient alternative towards the development of antibody-based drugs, pointing to new treatments for cancer therapy.

International human migration has been rapidly growing. Migrants coming from low and middle income countries continue to be considerably vulnerable and at higher risk for infectious diseases, namely HIV (Human Immunodeficiency Virus) and tuberculosis (TB). In Europe, the number of patients with HIV-TB co-infection has been increasing and migration could be one of the potential driving forces. This systematic review aims to improve the understanding on the burden of HIV-TB co-infection among migrants in Europe and to assess whether these populations are particularly vulnerable to this co-infection compared to nationals. MEDLINE®, Web of Science® and Scopus® databases were searched from March to April 2016 using combinations of keywords. Titles and abstracts were screened and studies meeting the inclusion criteria proceeded for full-text revision. These articles were then selected for data extraction on the prevalence, incidence and mortality. The majority of HIV-TB prevalence data reported in the analysed studies, including extrapulmonary/disseminated TB forms, was higher among migrant vs. nationals, some of the studies even showing increasing trends over time. Additionally, while HIV-TB incidence rates have decreased among migrants and nationals, migrants are still at a higher risk for this co-infection. Migrants with HIV-TB co-infection were also more prone to unsuccessful treatment outcomes, death and drug resistant TB. However, contradicting results also showed lower mortality compared to nationals. Overall, a disproportionate vulnerability of migrants to acquire the HIV-TB co-infection was observed across studies. Such vulnerability has been associated to low socioeconomic status, poor living conditions and limited access to healthcare. Adequate social support, early detection, appropriate treatment, and adequate access to healthcare are key improvements to tackle HIV-TB co-infection among these populations.

This work presents a cost-effective, label-free in point-of-care (POC) biosensor for the sensitive detection of 8-hydroxy-2′-deoxyguanosine (8-OHdG), the most abundant oxidative product of DNA, that may allow a premature assessment of cancer disease, thereby improving diagnosis, prognostics and survival rates. The device targets the direct detection of 8-OHdG by using for the first time a carbon-ink 3-electrode on a paper substrate coupled to Differential Pulse Voltammetry readings. This design was optimized by adding nanostructured carbon materials to the ink and the conducting polymer PEDOT, enhancing the electrocatalytic properties of the sensor towards 8-OHdG detection. Meanwhile, the ability of this oxidative stress biomarker to undertake an oxidation reaction enabled the development of the sensing electrochemical device without the need of chemical probes and long incubation periods. This paper-modified sensor presented high electrochemical performance on the oxidation of 8-OHdG with a wide linear range (50–1000 ng/ml) and a low detection limit (14.4 ng/ml). Thus, our results showed the development of a direct and facile sensor with good reproducibility, stability, sensitivity and more importantly, selectivity. The proposed carbon-based electrochemical sensor is a potential candidate to be miniaturized to small portable size, which make it applicable for in-situ 8-OHdG sensing in real biological samples.

l- asparaginase (ASNase, EC 3.5.1.1) is an enzyme that catalyzes the l- asparagine hydrolysis into l- aspartic acid and ammonia, being mainly applied in pharmaceutical and food industries. However, some disadvantages are associated with its free form, such as the ASNase short half-life, which may be overcome by enzyme immobilization. In this work, the immobilization of ASNase by adsorption over pristine and modified multi-walled carbon nanotubes (MWCNTs) was investigated, the latter corresponding to functionalized MWCNTs through a hydrothermal oxidation treatment. Different operating conditions, including pH, contact time and ASNase/MWCNT mass ratio, as well as the operational stability of the immobilized ASNase, were evaluated. For comparison purposes, data regarding the ASNase immobilization with pristine MWCNT was detailed. The characterization of the ASNase-MWCNT bioconjugate was addressed using different techniques, namely Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA) and Raman spectroscopy. Functionalized MWCNTs showed promising results, with an immobilization yield and a relative recovered activity of commercial ASNase above 95% under the optimized adsorption conditions (pH 8, 60 min of contact and 1.5 × 10 –3  g mL −1 of ASNase). The ASNase-MWCNT bioconjugate also showed improved enzyme operational stability (6 consecutive reaction cycles without activity loss), paving the way for its use in industrial processes.

The integration of graphene materials into electrochemical biosensing platforms has gained significant interest in recent years. Bulk quantities of graphene can be synthesized by oxidation of graphite to graphite oxide and subsequent exfoliation to graphene oxide (GO). However, the size of the resultant GO sheets changes from the parent graphite yielding a polydispersed solution of sizes ranging from a few nanometers to tens of micrometers. Here, we investigate the direct effect of GO sheets sizes on biosensor performance. We separated different GO sheets sizes, and we characterized them via atomic force, scanning electron, Raman and X-ray photoelectron spectroscopies and solid state nuclear magnetic resonance (NMR). As proof of concept, the sensing performance of these GO samples was probed using a well-known ssDNA aptasensor against microcystin-LR toxin and an immunosensor against β-lactoglobulin. The resulting aptasensors and immunosensors are fabricated by using covalent attachment and physical adsorption. We found that the aptasensors fabricated using physical adsorption, the binding signal variation was dramatically increased with increasing the GO sheet size. In contrast, for the aptasensor fabricated using covalent immobilization, the binding signal variation decreased with increasing GO sheet size. However, for the β-lactoglobulin immunosensors, the optimum signals were observed at intermediate GO sheet size. GO sheet size could enhance or inhibit the sensitivity of the graphene-based electrochemical sensors. Our results demonstrate that controlling the size of GO sheets may have a profound impact in specific biosensing applications.

Biosensors harness biological materials as receptors linked to transducers, enabling the capture and transformation of primary biorecognition signals into measurable outputs. This study presents a novel carboxylation method for synthesizing carboxylated graphene (CG) under acidic conditions, enhancing biosensing capabilities. The characterization of the CG was performed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, thermogravimetric analysis (TGA), and X-ray diffraction (XRD). We modified screen-printed carbon electrodes (SPCEs) with CG to immobilize the SARS-CoV-2 N-protein, facilitating targeted detection of IgA antibodies (IgA-SARS-CoV-2). The analytical performance was assessed via electrochemical techniques such as cyclic voltammetry and electrochemical impedance spectroscopy, confirming CG synthesis effectiveness and biosensor functionality. The developed biosensor efficiently detects IgA-SARS-CoV-2 across a dilution range of 1:1000 to 1:200 v/v in a phosphate-buffered saline (PBS) solution, with a limit of detection calculated at 1:1601 v/v. This device shows considerable potential because of its fast response time, miniaturized design facilitated by SPCEs, reduced sample volume requirements, high sensitivity and specificity, low detection limits, and signal enhancement achieved through nanomaterial integration.