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Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury (mTBI). Using a rat model of in utero and post-natal oxycodone (IUO) exposure and a low force weight drop model of mTBI, we show that not only neonatal opioid exposure significantly affects neuroinflammation, brain metabolites, synaptic proteome, mitochondrial function, and altered behavior in juvenile rats, but also, in conjunction with mTBI these aberrations are further exacerbated. Specifically, we observed long term metabolic dysregulation, neuroinflammation, alterations in synaptic mitochondria, and impaired behavior were impacted severely by mTBI. Our research highlights the specific vulnerability caused by IUO exposure to a secondary stressor such as later life brain injury. In summary, we present a comprehensive study to highlight the damaging effects of prenatal opioid abuse in conjunction with mild brain injury on the developing brain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human-based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human-based FXS model via differentiation of astrocytes from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca 2+ signaling, impaired sterol biosynthesis, and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Oxygenic photogranules have received increasing interest due to their ability to treat wastewater without aeration and recover wastewater's chemical energy and solar energy. It has been reported that these photogranules can be produced under both hydrostatic and hydrodynamic conditions, and enrichment of filamentous cyanobacteria is required for this photogranulation to occur. Despite the critical role extracellular polymeric substances (EPS) play in granulation, EPS in photogranulation is yet virtually unknown. Here, we present the fate and dynamics of different fractions of EPS in sludge-based photogranulation under hydrostatic conditions. The study shows that during the transformation of activated sludge into a photogranular biomass, sludge's base-extractable proteins selectively degrade. Strong correlations between base-extracted proteins and the growth of chlorophyll a and chlorophyll a/ b ratio suggest that the bioavailability of this organic nitrogen is linked with selection and enrichment of filamentous cyanobacteria under hydrostatic conditions. The results of soluble and sonication-extractable EPS and microscopy also show that the growth of filamentous cyanobacteria required large amounts of polysaccharide-based EPS for their motility and maintenance. With findings on the progression of photogranulation, the fate and dynamics of EPS, and microscopy on microstructures associated with EPS, we discuss potential mechanisms of photogranulation occurring under hydrostatic conditions.

Microorganisms often respond to their environment by growing as densely packed communities in biofilms, flocs or granules. One major advantage of life in these aggregates is the retention of its community in an ecosystem despite flowing water. We describe here a novel type of granule dominated by filamentous and motile cyanobacteria of the order Oscillatoriales. These bacteria form a mat-like photoactive outer layer around an otherwise unconsolidated core. The spatial organization of the phototrophic layer resembles microbial mats growing on sediments but is spherical. We describe the production of these oxygenic photogranules under static batch conditions, as well as in turbulently mixed bioreactors. Photogranulation defies typically postulated requirements for granulation in biotechnology, i.e., the need for hydrodynamic shear and selective washout. Photogranulation as described here is a robust phenomenon with respect to inoculum characteristics and environmental parameters like carbon sources. A bioprocess using oxygenic photogranules is an attractive candidate for energy-positive wastewater treatment as it biologically couples CO 2 and O 2 fluxes. As a result, the external supply of oxygen may become obsolete and otherwise released CO 2 is fixed by photosynthesis for the production of an organic-rich biofeedstock as a renewable energy source.

Recently, the use of phototrophs for wastewater treatment has been revisited because of new approaches to separate them from effluent streams. One manifestation uses oxygenic photogranules (OPGs) which are dense, easily-settleable granular biofilms of cyanobacteria, which surrounding populations of heterotrophs, autotrophs, and microalgae. OPGs can remove COD and nitrogenous compounds without external aeration. To better grow and maintain biomass in the proposed wastewater process, this study seeks to understand the factors that contribute to successful granulation. Availability of initial inorganic nitrogen, particularly ammonium, was associated with successful cultivation of OPGs. In the first days of granulation, a decrease in ammonium coupled with an increase in a cyanobacterial-specific 16S rRNA gene, may suggest that ammonium was assimilated in cyanobacteria offering a competitive environment for growth. Though both successful and unsuccessful OPG formation demonstrated a shift from non-phototrophic bacterial dominated communities on day 0 to cyanobacterial dominated communities on day 42, the successful community had a greater relative abundance (46%) of OTUs associated with genera Oscillatoria and Geitlernema than the unsuccessful community (27%), supporting that filamentous cyanobacteria are essential for successful OPG formation. A greater concentration of chlorophyll b in the unsuccessful OPG formation suggested a greater abundance of algal species. This study offers indicators of granulation success, notably availability of inorganic nitrogen and chlorophyll a and b concentrations for monitoring the health and growth of biomass for a potential OPG process.

Background: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies., Patients and Methods: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up., Results: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ≥ 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were hand-foot skin reaction (20%), diarrhea (17%), and rash (8%)., Conclusion: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)