Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.     

Hippocampal Expression of Cytochrome P450 1B1 in Penetrating Traumatic Brain Injury

Hippocampal dysfunction contributes to multiple traumatic brain injury sequala. Female rodents’ outcome is superior to male which has been ascribed the neuroprotective sex hormones 17β-estradiol and progesterone. Cytochrome P450 1B1 (CYP1B1) is an oxidative enzyme influencing the neuroinflammatory response by creating inflammatory mediators and metabolizing neuroprotective 17β-estradiol and progesterone. In this study, we aimed to describe hippocampal CYP1B1 mRNA expression, protein presence of CYP1B1 and its key redox partner Cytochrome P450 reductase (CPR) in both sexes, as well as the effect of penetrating traumatic brain injury (pTBI). A total 64 adult Sprague Dawley rats divided by sex received pTBI or sham-surgery and were assigned survival times of 1-, 3-, 5- or 7 days. CYP1B1 mRNA was quantified using in-situ hybridization and immunohistochemistry performed to verify protein colocalization. CYP1B1 mRNA expression was present in all subregions but greatest in CA2 irrespective of sex, survival time or intervention. At 3-, 5- and 7 days post-injury, expression in CA2 was reduced in male rats subjected to pTBI compared to sham-surgery. Females subjected to pTBI instead exhibited increased expression in all CA subregions 3 days post-injury, the only time point expression in CA2 was greater in females than in males. Immunohistochemical analysis confirmed neuronal CYP1B1 protein in all hippocampal subregions, while CPR was limited to CA1 and CA2. CYP1B1 mRNA is constitutively expressed in both sexes. In response to pTBI, females displayed a more urgent but brief regulatory response than males. This indicates there may be sex-dependent differences in CYP1B1 activity, possibly influencing inflammation and neuroprotection in pTBI.     

无线、智能、安全是智能家居的关键词

1 智能家居的应用 最近,我们看到了家庭自动化和安全解决方案的广泛采用,其中包括照明、温度控制、安防、娱乐以及无处不在的传感器.短期内我们将看到的一大趋势是远距离应用,其将延伸到家庭之外的范围,例 如 Z-Wave Long?Range和Sidewalk,它们将开启一系列新的应用场景.     

Development and validation of a new LC–MS/MS method for the simultaneous determination of six major ergot alkaloids and their corresponding epimers. Application to some food and feed commodities

A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of six major ergot alkaloids, ergometrine, ergosine, ergotamine, ergocornine, ergokryptine and ergocristine, as well as their corresponding epimers in food and feed samples. The method involves extraction under alkaline conditions and subsequent clean-up by applying a simple and rapid liquid–liquid partitioning procedure prior to LC–MS/MS analysis. Evaluation of the method revealed good linearity, accuracy and precision. The limits of quantification varied from 0.1 to 1 μg/kg depending on the analyte and matrix. The average extraction and clean-up recoveries in different matrices were between 45 (only for ergometrine in biscuit) and 90%. The uncertainty associated with the analytical method was not higher than 51% and 30%, at concentration levels of 2.5 and 150 μg/kg respectively. Analyte epimerization proved to be minimal during the analytical procedure. The method has been successfully applied to the determination of ergot alkaloids in some Belgian food and feed commodities. Ergot alkaloids were found in 104 out of 122 samples investigated. Ergosine was the most frequently occurring alkaloid, while the highest levels were observed for ergotamine, ergocristine or ergosine, depending on the product type. The total alkaloid content in positive samples varied from 1 to 1145 μg/kg.     

Multi-level Modeling of Silica–Template Interactions During Initial Stages of Zeolite Synthesis

Zeolite synthesis is driven by structure-directing agents, such as tetrapropyl ammonium ions (TPA⁺) for Silicalite-1 and ZSM-5. However, the guiding role of these organic templates in the complex assembly to highly ordered frameworks remains unclear, limiting the prospects for advanced material synthesis. In this work, both static ab initio and dynamic classical modeling techniques are employed to provide insight into the interactions between TPA⁺ and Silicalite-1 precursors. We find that as soon as the typical straight 10-ring channel of Silicalite-1 or ZSM-5 is formed from smaller oligomers, the TPA⁺ template is partially squeezed out of the resulting cavity. Partial retention of the template in the cavity is, however, indispensable to prevent collapse of the channel and subsequent hydrolysis.

Model selection, identification and validation in anaerobic digestion: a review

Anaerobic digestion enables waste (water) treatment and energy production in the form of biogas. The successful implementation of this process has lead to an increasing interest worldwide. However, anaerobic digestion is a complex biological process, where hundreds of microbial populations are involved, and whose start-up and operation are delicate issues. In order to better understand the process dynamics and to optimize the operating conditions, the availability of dynamic models is of paramount importance. Such models have to be inferred from prior knowledge and experimental data collected from real plants. Modeling and parameter identification are vast subjects, offering a realm of approaches and methods, which can be difficult to fully understand by scientists and engineers dedicated to the plant operation and improvements. This review article discusses existing modeling frameworks and methodologies for parameter estimation and model validation in the field of anaerobic digestion processes. The point of view is pragmatic, intentionally focusing on simple but efficient methods.     

Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies

The 5-year relative survival for patients with head and neck cancer, the seventh most common form of cancer worldwide, was reported as 67% in developed countries in the second decade of the new millennium. Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Recently, liquid biopsy monitoring of the molecular fingerprint of head and neck squamous cell carcinoma has been proposed and investigated as a strategy for longitudinal patient care. These innovative methods offer rapid, safe, and highly informative genetic analysis that can identify small tumors not yet visible by advanced imaging techniques, thus potentially shortening the time to treatment and improving survival outcomes. In this review, we provide insights into the available evidence that the molecular tumor fingerprint can be used in the surveillance of head and neck squamous cell carcinoma. Challenges to overcome, prior to clinical implementation, are also discussed.     

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice (KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7 heterozygotes mice that underwent renal ischemia/reperfusion (IR) exhibited the characteristic hallmarks of AKI: renal dysfunction, tubular damage, albuminuria, increased oxidative stress, and renal inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI, exhibiting lesser albuminuria and reduction in urinary biomarkers of tubular damage, despite similar renal dysfunction. The renoprotection in the Sirt7-KO+IR group was associated with reduced kidney weight, minor expression of inflammatory cytokines and less renal infiltration of inflammatory cells. This anti-inflammatory effect was related to diminished p65 expression and in its active phosphorylation, as well as by a reduction in p65 nuclear translocation. Sirt7 deficient mice are protected from AKI, suggesting that this histone deacetylase promotes tubular damage and renal inflammation. Therefore, our findings indicate that Sirt7 inhibitors may be an attractive therapeutic target to reduce NFκB signaling.     

SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by Streptococcus pneumoniae and Staphylococcus aureus

The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike–biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.