Biocatalytic oxidative kinetic resolution of (±)-4-(chlorophenyl)phenylmethanol by Nocardia corallina B-276

Chiral diarylmethanols are versatile building blocks for the preparation of biologically active substances, but they are difficult to obtain in enantiopure form. We used Nocardia corallina B-276 for the oxidative kinetic resolution of (±)-4-(chlorophenyl)phenylmethanol, 1. Two experimental methods were used: 1) Suspension of cells in a phosphate buffer solution and 2) Cells in the culture media, in a 3-L bioreactor. After 36 hrs using the first method, the ketone/alcohol ratio was 56/44 and the unoxidized alcohol had an enantiomeric ratio of 93/7, predominating the R-alcohol

Comparative Economic Analysis Between Endogenous and Recombinant Production of Hyaluronic Acid

Hyaluronic acid (HA) is a biopolymer with a wide range of applications, mainly in the cosmetic and pharmaceutical sectors. Typical industrial-scale production utilizes organisms that generate HA during their developmental cycle, such as Streptococcus equi sub. zooepidemicus. However, a significant disadvantage of using Streptococcus equi sub. zooepidemicus is that it is a zoonotic pathogen, which use at industrial scale can create several risks. This creates opportunities for heterologous, or recombinant, production of HA. At an industrial scale, the recovery and purification of HA follow a series of precipitation and filtration steps. Current recombinant approaches are developing promising alternatives, although their industrial implementation has yet to be adequately assessed. The present study aims to create a theoretical framework to forecast the advantages and disadvantages of endogenous and recombinant strains in production with the same downstream strategy. The analyses included a selection of the best cost-related recombinant and endogenous production strategies, followed by a sensitivity analysis of different production variables in order to identify the three most critical parameters. Then, all variables were analyzed by varying them simultaneously and employing multiple linear regression. Results indicate that, regardless of HA source, production titer, recovery yield and bioreactor scale are the parameters that affect production costs the most. Current results indicate that recombinant production needs to improve current titer at least 2-fold in order to compete with costs of endogenous production. This study serves as a platform to inform decision-making for future developments and improvements in the recombinant production of HA

Primary recovery of hyaluronic acid produced in Streptococcus equi subsp. zooepidemicus using PEG-citrate aqueous two-phase systems

Given its biocompatibility, rheological, and physiological properties, hyaluronic acid (HA) has become a biomaterial of increasing interest with multiple applications in medicine and cosmetics. In recent decades, microbial fermentations have become an important source for the industrial production of HA. However, due to its final applications, microbial HA must undergo critical and long purification processes to ensure clinical and cosmetic grade purity. Aqueous two-phase systems (ATPS) have proven to be an efficient technique for the primary recovery of high-value biomolecules. Nevertheless, their implementation in HA downstream processing has been practically unexplored. In this work, polyethylene glycol (PEG)–citrate ATPS were used for the first time for the primary recovery of HA produced with an engineered strain of Streptococcus equi subsp. zooepidemicus. The effects of PEG molecular weight (MW), tie-line length (TLL), volume ratio (VR), and sample load on HA recovery and purity were studied with a clarified fermentation broth as feed material. HA was recovered in the salt-rich bottom phase, and its recovery increased when a PEG MW of 8000 g mol−1 was used. Lower VR values (0.38) favoured HA recovery, whereas purity was enhanced by a high VR (3.50). Meanwhile, sample load had a negative impact on both recovery and purity. The ATPS with the best performance was PEG 8000 g mol−1, TLL 43% (w/w), and VR 3.50, showing 79.4% HA recovery and 74.5% purity. This study demonstrated for the first time the potential of PEG–citrate ATPS as an effective primary recovery strategy for the downstream process of microbial HA

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Speciation of Gold Nanoparticles by Ex Situ Extended X‑ray Absorption Fine Structure and X‑ray Absorption Near Edge Structure

A combined X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) methodology is here presented on a series of partially and fully reduced AuIII samples. This allows monitoring the relative fraction of AuIII and Au0 in the studied samples, displaying a consistent and ndependent outcome. The strategy followed is based, for the first time, on two structural models that can be fitted simultaneously, and it evaluates the correlation among strongly correlated parameters such as coordination number and the Debye 12Waller factor. The results of the present EXAFS and XANES approach can be extended to studies based on X-ray absorption spectroscopy experiments for the in situ monitoring of the formation of gold nanoclusters

Speciation of Gold Nanoparticles by Ex Situ Extended X‑ray Absorption Fine Structure and X‑ray Absorption Near Edge Structure

A combined X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) methodology is here presented on a series of partially and fully reduced Au^III samples. This allows monitoring the relative fraction of Au^III and Au⁰ in the studied samples, displaying a consistent and independent outcome. The strategy followed is based, for the first time, on two structural models that can be fitted simultaneously, and it evaluates the correlation among strongly correlated parameters such as coordination number and the Debye–Waller factor. The results of the present EXAFS and XANES approach can be extended to studies based on X-ray absorption spectroscopy experiments for the in situ monitoring of the formation of gold nanoclusters

Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer

Purpose: Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A > G, XRCC3 c.722C > T, RAD51 (c.-3429G > C, c.-3392G > T), and GSTP1 c.313A > G. Materials and methods: Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED). Results: Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR = 1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR = 4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G > C status were associated to higher likelihood of occurrence of acute toxicities (HR = 2.03). Conclusions: Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A > G and RAD51 c.-3429 G > C, and the development of radiation-induced toxicities in SCCHN patients. © 2011 Elsevier Ireland Ltd. All rights reserved