PI3K/AKT signaling alters glucose metabolism in uterine microenvironment of women with idiopathic recurrent spontaneous miscarriage.

BACKGROUND: This study aims to identify metabolomic signatures in uterine fluid of women with idiopathic recurrent spontaneous miscarriage (IRSM) during window of implantation (WOI). Also, glucose transporters GLUT3 and GLUT4 and proteins of PI3K-Akt signaling pathway in endometrial tissue are assessed. METHODS: Paired uterine fluid and endometrial biopsies were collected during WOI from women with IRSM (n = 24) and healthy women with azoospermic male partners as controls (n = 15). NMR metabolomics was used to identify the dysregulated metabolites in uterine fluid of IRSM women. Additionally, proteins and glucose transporters were investigated in the endometrial tissue using immunohistochemistry (IHC) and western blotting. RESULTS: Uterine fluid metabolomics indicated eleven metabolites to be significantly downregulated in IRSM. While expression levels of PI3K (p85), PI3K (p110), p-Akt (Thr308), p-Akt (Ser473), GLUT3 and GLUT4 were significantly downregulated in endometrial tissue of these women, p-IKK α/ß (Ser176/180) and p-NFkBp65 (Ser536) were significantly increased. CONCLUSION: Our findings suggest that dysregulation of PI3K/Akt pathway in the uterine microenvironment could be a likely cause of endometrial dysfunction, thereby affecting implantation. Further studies on the downstream effects of the Akt signaling pathway in-vitro for improved understanding of the Akt-mediated cellular responses in IRSM is, therefore, warranted.

Fabrication of a Label-Free Immunosensor Using Surface-Engineered AuPt@GQD Core-Shell Nanocomposite for the Selective Detection of Trace Levels of Escherichia coli from Contaminated Food Samples.

Fabrication of label-free immunosensors is highly necessitated due to their simplicity, cost-effectiveness, and robustness. Herein, we report the facile development of a label-free, direct, rapid, capacitive immunosensor for ultrasensitive and rapid recognition of trace levels of Escherichia coli from contaminated food samples. This was achieved using gold platinum core-shell nanoparticles loaded with graphene quantum dots (AuPt@GQDs) that were utilized as electrode modifiers. The incorporation of GQDs to the surface of AuPt core-shell nanoparticles was performed using the "greener" probe-sonication method. The electrochemical properties of AuPt@GQDs, determined using cyclic voltammetry and electrochemical impedance spectroscopy, suggested the optimized loading concentration of AuPt to be 0.05% in the core-shell nanocomposite to exhibit the highest current response. Furthermore, immobilization of anti-E. coli monoclonal antibodies (anti-E. coli mAb) onto the surface of modified electrodes was performed using amine coupling. The high specific binding of E. coli cells onto the surface of the immuno-electrode was measured as a direct function of change in transient capacitance with time that was measured at low and high frequencies. The resultant immunosensor (bovine serum albumin/anti-E. coli mAb/AuPt0.05@GQDs/FTO) demonstrated a detection range (5 to 4.5 × 103 cells/mL), with the detection limit as low as 1.5 × 102 cells/mL, and an excellent sensitivity ∼171,281.40 µF-1 mL cells-1 cm-2 without the use of any labels (R2-0.99). These findings were further verified using real sample analysis wherein the immuno-electrode demonstrated outstanding sensitivity, the highest noticed so far. More interestingly, the high resuability ∼48 weeks (RSD-5.92%) and excellent reproducibility in detection results (RSD ∼ 9.5%) testify its potential use in a clinical setting. The results reveal the usefulness of the surface-engineered AuPt@GQDs core-shell nanocomposite as an electrode modifier that can be used for the development of newer on-site monitoring devices to estimate trace levels of pathogens present as contaminants in food samples.

Injectable biocompatible RAFT mediated nitroxide nanogels: A robust ROS-reduction antioxidant approach.

This work introduces novel nitroxide-based nanogels (NGs) crafted through controlled RAFT (Reversible Addition Fragmentation chain Transfer) polymerization, showcasing over 85% improved shelf-life compared to native superoxide dismutase (SOD) enzymes. These 30-40 nm NGs hold great promise for injectable delivery, effectively reducing foam cell formation and displaying potent antioxidant behavior against various reactive oxygen species (ROS), revolutionizing antioxidant therapy. Featuring a meticulously designed core-shell structure via precise RAFT polymerization, these NGs mimic SOD enzymatic activity with nitroxide-based antioxidants, providing unprecedented defense against ROS. Combining methacrylated 2,2,6,6-Tetramethyl-4-piperidyl methacrylate (PMA) and Glycidyl methacrylate (GMA) monomers with precisely synthesized nitroxyl radicals results in exceptional properties. Validated through comprehensive analytical methods, these NGs exhibit remarkable stability, halting foam cell formation even at high concentrations, and demonstrate notable biocompatibility. Their ability to protect low density lipoprotein (LDL) from oxidation for up to a month positions them at the forefront of combating cardiovascular diseases, especially atherosclerosis. This study pioneers injectable antioxidant therapy, offering an innovative approach to cardiovascular ailments. Targeting narrow plaques signifies a promising intervention, reshaping cardiovascular disease treatments. It highlights the potential of advanced drug delivery in biomedicine, promising more effective cardiovascular disease treatments.

Correction: Evaluating adherence to government recommendations for post-exposure rabies vaccine among animal-bite victims: A hospital-based study in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgph.0002506.].

Evaluating adherence to government recommendations for post-exposure rabies vaccine among animal-bite victims: A hospital-based study in Bangladesh.

Rabies is a fatal but preventable zoonotic disease with an approximately 100% case fatality rate. The most common way to contract rabies is through the bite of a rabid animal. Post-exposure prophylaxis (PEP) by vaccination and/or immunoglobulin therapy is the most effective measure for rabies prevention. The effectiveness of vaccination depends on the level of completion of vaccination. In Bangladesh, no previous studies were conducted to evaluate adherence to government recommendations for post-exposure rabies vaccine among animal-bite cases. We conducted a cross-sectional study to collect information about adherence to government recommendations for post-exposure rabies vaccine. A total of 457 animal bite victims were selected to collect data and follow up after one month of enrollment. The majority of participants (58%, n = 265, 95% CI: 53-63%) had a history of animal bites. Most of the participants (77%) were advised to receive three doses of vaccine and 100% of them completed 3-dose of vaccine. Among the 4-dose recommended group of participants (n = 105), 78% completed full vaccination. Of the 457 participants, 20% received post-exposure vaccine on the day of bite/scratch and the majority of the participants (66%, n = 303, 95% CI: 62-71%) received post-exposure vaccine on the day between the first and third day of bite or scratch. Increasing awareness of the importance of timely vaccination is the key to reducing the time gap between animal bites and intake of the first dose post-exposure vaccine.

Coal waste-derived synthesis of yellow oxidized graphene quantum dots with highly specific superoxide dismutase activity: characterization, kinetics, and biological studies.

The disintegration of coal-based precursors for the scalable production of nanozymes relies on the fate of solvothermal pyrolysis. Herein, we report a novel economic and scalable strategy to fabricate yellow luminescent graphene quantum dots (YGQDs) by remediating unburnt coal waste (CW). The YGQDs (size: 7-8 nm; M.W: 3157.9 Da) were produced using in situ "anion-radical" assisted bond cleavage in water (within 8 h; at 121 °C) with yields of ∼87%. The presence of exposed surface and edge groups, such as COOH, C-O-C, and O-H, as structural defects accounted for its high fluorescence with εmax ∼530 nm at pH 7. Besides, these defects also acted as radical stabilizers, demonstrating prominent anti-oxidative activity of ∼4.5-fold higher than standard ascorbic acid (AA). In addition, the YGQDs showed high biocompatibility towards mammalian cells, with 500 µM of treatment dose showing <15% cell death. The YGQDs demonstrated specific superoxide dismutase (SOD) activity wherein 15 µM YGQDs equalled the activity of 1-unit biological SOD (bSOD), measured using the pyrogallol assay. The Km for YGQDs was ∼10-fold higher than that for bSOD. However, the YGQDs retained their SOD activity in harsh conditions like high temperatures or denaturing reactions, where the activity of bSOD is completely lost. The binding affinity of YGQDs for superoxide ions, measured from isothermal calorimetry (ITC) studies, was only 10-fold lower than that of bSOD (Kd of 586 nM vs. 57.3 nM). Further, the pre-treatment of YGQDs (∼10-25 µM) increased the cell survivability to >75-90% in three cell lines during ROS-mediated cell death, with the highest survivability being shown for C6-cells. Next, the ROS-induced apoptosis in C6-cells (model for neurodegenerative diseases study), wherein YGQDs uptake was confirmed by confocal microscopy, showed ∼5-fold apoptosis alleviation with only 5 µM pretreatment. The YGQDs also restored the expression of pro-inflammatory Th1 cytokines (TNF-α, IFN-γ, IL-6) and anti-inflammatory Th2 cytokines (IL-10) to their basal levels, with a net >3-fold change observed. This further explains the molecular mechanism for the antioxidant property of YGQDs. The high specific SOD activity associated with YGQDs may provide the cheapest alternative source for producing large-scale SOD-based nanozymes that can treat various oxidative stress-linked disorders/diseases.

Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke.

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit-/- MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes.

Catalytic polymer nanocomposites for environmental remediation of wastewater.

The removal of harmful chemicals and species from water, soil, and air is a major challenge in environmental remediation, and a wide range of materials have been studied in this regard. To identify the optimal material for particular applications, research is still ongoing. Polymer nanocomposites (PNCs), which combine the benefits of nanoparticles with polymers, an alternative to conventional materials, may open up new possibilities to overcome this difficulty. They have remarkable mechanical capabilities and compatibility due to their polymer matrix with a very high surface area to volume ratio brought about by their special physical and chemical properties, and the extremely reactive surfaces of the nanofillers. Composites also provide a viable answer to the separation and reuse problems that hinder nanoparticles in routine use. Understanding these PNCs materials in depth and using them in practical environmental applications is still in the early stages of development. The review article demonstrates a crisp introduction to the PNCs with their advantageous properties as a catalyst in environmental remediation. It also provides a comprehensive explanation of the design procedure and synthesis methods for fabricating PNCs and examines in depth the design methods, principles, and design techniques that guide proper design. Current developments in the use of polymer nanocomposites for the pollutant treatment using three commonly used catalytic processes (catalytic and redox degradation, electrocatalytic degradation, and biocatalytic degradation) are demonstrated in detail. Additionally, significant advances in research on the aforementioned catalytic process and the mechanism by which contaminants are degraded are also amply illustrated. Finally, there is a summary of the research challenges and future prospects of catalytic PNCs in environmental remediation.

Revolutionizing Food Safety with Quantum Dot-Polymer Nanocomposites: From Monitoring to Sensing Applications.

The present review article investigates the prospective utilisation of quantum dot-polymer nanocomposites in the context of ensuring food safety. The text pertains to the advancement of nanocomposites, encompassing their distinctive optical and electrical characteristics, and their prospective to transform the detection and perception of food safety risks. The article explores diverse methodologies for producing nanocomposites and underscores their potential utility in identifying impurities, microorganisms, and harmful substances in food. The article provides an overview of the challenges and limitations associated with the utilisation of nanocomposites in food safety applications, encompassing concerns regarding toxicity and the necessity for standardised protocols. The review article presents a comprehensive examination of the present research status in this area and underscores the potential of quantum dots-polymer nanocomposites in transforming food safety monitoring and sensing.

Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer's disease progression.

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability and break the blood-brain barrier which may trigger AD pathogenesis via redox signaling, neuronal, immune, and metabolic pathways. Dysbiosis increases the oxidative stress. Oxidants affect the innate immune system through recognizing microbial-derived pathogens by Toll-like receptors and initiating the inflammatory process. Most of the gut microbiome research work highlights the relationship between the gut microbiota and AD, but the contributory connection between precise bacteria and brain dysfunction in AD pathology cannot be fully demonstrated. Here, we summarize the current information of the fundamental connections between oxidative stress, inflammation, and gut dysbiosis in AD. This review emphasizes on the involvement of gut microbiota in the regulation of oxidative stress, inflammation, immune responses including central and peripheral cross-talk. It provides insights for novel preventative and therapeutic approaches in AD.

Common Signaling Pathways Involved in Alzheimer's Disease and Stroke: Two Faces of the Same Coin.

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-ß aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are the disruption of neuronal circuitry at different levels of cellular signaling, leading to the death of neurons and glial cells in the brain. Therefore, it is necessary to find out the common molecular mechanisms of these two diseases to understand their etiological connections. Here, we summarized the most common signaling cascades including autotoxicity, ApoE4, insulin signaling, inflammation, mTOR-autophagy, notch signaling, and microbiota-gut-brain axis, present in both AD and IS. These targeted signaling pathways reveal a better understanding of AD and IS and could provide a distinguished platform to develop improved therapeutics for these diseases.

Bismuth sulfoiodide (BiSI) nanorods: synthesis, characterization, and photodetector application.

The nanorods of bismuth sulfoiodide (BiSI) were synthesized at relatively low temperature (393 K) through a wet chemical method. The crystalline one-dimensional (1D) structure of the BiSI nanorods was confirmed using high resolution transmission microscopy (HRTEM). The morphology and chemical composition of the material were examined by applying scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. The average diameter of 126(3) nm and length of 1.9(1) µm of the BiSI nanorods were determined. X-ray diffraction (XRD) revealed that prepared material consists of a major orthorhombic BiSI phase (87%) and a minor amount of hexagonal Bi13S18I2 phase (13%) with no presence of other residual phases. The direct energy band gap of 1.67(1)  eV was determined for BiSI film using diffuse reflectance spectroscopy (DRS). Two types of photodetectors were constructed from BiSI nanorods. The first one was traditional photoconductive device based on BiSI film on stiff glass substrate equipped with Au electrodes. An influence of light intensity on photocurrent response to monochromatic light (λ = 488 nm) illumination was studied at a constant bias voltage. The novel flexible photo-chargeable device was the second type of prepared photodetectors. It consisted of BiSI film and gel electrolyte layer sandwiched between polyethylene terephthalate (PET) substrates coated with indium tin oxide (ITO) electrodes. The flexible self-powered BiSI photodetector exhibited open-circuit photovoltage of 68 mV and short-circuit photocurrent density of 0.11 nA/cm2 under light illumination with intensity of 0.127 W/cm2. These results confirmed high potential of BiSI nanorods for use in self-powered photodetectors and photo-chargeable capacitors.

SbI3·3S8: A Novel Promising Inorganic Adducts Crystal for Second Harmonic Generation.

In the past twenty years, the basic investigation of innovative Non-Linear Optical (NLO) crystals has received significant attention, which has built the crucial heritage for the use of NLO materials. Fundamental research is essential given the scarcity of materials for NLO compounds, especially in the deep ultraviolet (DUV) and middle- and far-infrared (MFIR) regions. In the present work, we synthesized high-quality MFIR SbI3·3S8 NLO crystals having a length in the range of 1-5 mm through rapid facile liquid phase ultrasonic reaction followed by the assistance of instantaneous natural evaporation phenomenon of the solvent at room temperature. X-ray diffraction (XRD) results ratify the hexagonal R3m structure of SbI3·3S8 crystal, and energy-dispersive X-ray spectroscopy (EDX) demonstrates that the elemental composition of SbI3·3S8 crystal is similar to that of its theoretical composition. The direct and indirect forbidden energy gaps of SbI3·3S8 were measured from the optical transmittance spectra and they were shown to be 2.893 eV and 1.986 eV, respectively. The green sparkling signal has been observed from the crystal during the second harmonic generation (SHG) experiment. Therefore, as inorganic adducts are often explored as NLO crystals, this work on the MFIR SbI3·3S8 NLO crystal can bring about additional investigations on this hot topic in the near future.

A Simplified Approach for the Aqueous Synthesis of Luminescent CdSe/ZnS Core/Shell Quantum Dots and Their Applications in Ultrasensitive Determination of the Biomarker 3-Nitro-l-tyrosine.

In contrast to the hot-injection organometallic routes, synthesizing stable and highly luminescent core/shell nanocrystals with encapsulation of biocompatible groups through an aqueous route is a long-standing challenge. In recent years, relatively high quantum efficiency and unique properties of core/shell nanostructured materials (quantum dots) have contributed toward enhancement in sensing capability. The present work reports a facile aqueous synthesis process of core/shell CdSe/ZnS quantum dots (QDs) with encapsulation of glutathione (GSH). The optimal conditions for the synthesis of the most stable particles were ascertained, and the different experimental analyses suggest that the stable core/shell QDs in question have good crystallinity with a size around 4.7 nm with a shell thickness of 0.7 nm and a photoluminescence quantum yield of about 35%. Further, it is demonstrated that the as-synthesized material has great potential in detecting as low as 0.28 nM 3-nitro-l-tyrosine (3-NT), an important marker for oxidative stress, the level of which in our body signals several chronically diseased conditions. The enthalpy-driven interactions of CdSe/ZnS-GSH QDs with 3-NT were characterized through steady-state and time-resolved luminescence spectroscopy and isothermal microcalorimetry. The devised method of probing 3-NT was further validated with human serum samples. Thus, the proposed strategy may provide a protocol for selective determination of 3-NT under different pathological conditions.

Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer's Disease Mice with Central Amyloid-ß Pathology.

BACKGROUND: Substantial evidence from recent research suggests an influential and underappreciated force in Alzheimer's disease (AD) pathogenesis: the pathological signals originate from outside the brain. Pathogenic bacteria produce amyloid-like proteins "curli" that form biofilms and show functional similarities to human amyloid-ß (Aß). These proteins may contribute to neurological disease progression via signaling cascade from the gut to the brain. OBJECTIVE: We propose that curli causes neuroendocrine activation from the gut to brain that promotes central Aß pathology. METHODS: PGP9.5 and TLR2 levels in response to curli in the lumen of Tg2576 AD mice were analyzed by immunohistochemical and qRT-PCR analysis. Western blot and human 3D in vitro enteroids culture systems were also used. 16S rRNA gene sequencing was used to investigate bacterial dysbiosis. RESULTS: We found significant increase in bacterial-amyloid curli with elevated TLR2 at the mRNA level in the pre- and symptomatic Tg-AD gut compared to littermate WT controls. This data associates with increased gram-positive bacterial colonization in the ileum of the symptomatic AD mice. We found fundamental evidence for vagus nerve activation in response to bacterial curli. Neuroendocrine marker PGP9.5 was significantly elevated in the gut epithelium of symptomatic AD mice, and this was colocalized with increased TLR2 expression. Enteroids, 3D-human ileal mini-gut monolayer in vitro model system also revealed increase levels of TLR2 upon stimulation with purified bacterial curli fibrils. CONCLUSION: These findings reveal the importance of pathological changes within the gut-vagus-brain signaling in response to luminal bacterial amyloid that might play a vital role in central Aß pathogenesis seen in the AD brain.

Review on the Use of Heavy Metal Deposits from Water Treatment Waste towards Catalytic Chemical Syntheses.

The toxicity and persistence of heavy metals has become a serious problem for humans. These heavy metals accumulate mainly in wastewater from various industries' discharged effluents. The recent trends in research are now focused not only on the removal efficiency of toxic metal particles, but also on their effective reuse as catalysts. This review discusses the types of heavy metals obtained from wastewater and their recovery through commonly practiced physico-chemical pathways. In addition, it covers the advantages of the new system for capturing heavy metals from wastewater, as compared to older conventional technologies. The discussion also includes the various structural aspects of trapping systems and their hypothesized mechanistic approaches to immobilization and further rejuvenation of catalysts. Finally, it concludes with the challenges and future prospects of this research to help protect the ecosystem.

Non-coding RNAs and their bioengineering applications for neurological diseases.

Engineering of cellular biomolecules is an emerging landscape presenting creative therapeutic opportunities. Recently, several strategies such as biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems have been developed to improve specific biological functions, however, have been confounded with fundamental and technical roadblocks. Rapidly emerging investigations on the bioengineering prospects of mammalian ribonucleic acid (RNA) is expected to result in significant biomedical advances. More specifically, the current trend focuses on devising non-coding (nc) RNAs as therapeutic candidates for complex neurological diseases. Given the pleiotropic and regulatory role, ncRNAs such as microRNAs and long non-coding RNAs are deemed as attractive therapeutic candidates. Currently, the list of non-coding RNAs in mammals is evolving, which presents the plethora of hidden possibilities including their scope in biomedicine. Herein, we critically review on the emerging repertoire of ncRNAs in neurological diseases such as Alzheimer's disease, Parkinson's disease, neuroinflammation and drug abuse disorders. Importantly, we present the advances in engineering of ncRNAs to improve their biocompatibility and therapeutic feasibility as well as provide key insights into the applications of bioengineered non-coding RNAs that are investigated for neurological diseases.

Coupling 6-chloro-3-methyluracil with copper: structural features, theoretical analysis, and biofunctional properties.

As nucleobases in RNA and DNA, uracil and 5-methyluracil represent a recognized class of bioactive molecules and versatile ligands for coordination compounds with various biofunctional properties. In this study, 6-chloro-3-methyluracil (Hcmu) was used as an unexplored building block for the self-assembly generation of a new bioactive copper(II) complex, [Cu(cmu)2(H2O)2]·4H2O (1). This compound was isolated as a stable crystalline solid and fully characterized in solution and solid state by a variety of spectroscopic methods (UV-vis, EPR, fluorescence spectroscopy), cyclic voltammetry, X-ray diffraction, and DFT calculations. The structural, topological, H-bonding, and Hirshfeld surface features of 1 were also analyzed in detail. The compound 1 shows a distorted octahedral {CuN2O4} coordination environment with two trans cmu- ligands adopting a bidentate N,O-coordination mode. The monocopper(II) molecular units participate in strong H-bonding interactions with water molecules of crystallization, leading to structural 0D → 3D extension into a 3D H-bonded network with a tfz-d topology. Molecular docking and ADME analysis as well as antibacterial and antioxidant activity studies were performed to assess the bioactivity of 1. In particular, this compound exhibits a prominent antibacterial effect against Gram negative (E. coli, P. aeruginosa) and positive (S. aureus, B. cereus) bacteria. The obtained copper(II) complex also represents the first structurally characterized coordination compound derived from 6-chloro-3-methyluracil, thus introducing this bioactive building block into a family of uracil metal complexes with notable biofunctional properties.

Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses.

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.

Conceptual disorganization and redistribution of resting-state cortical hubs in untreated first-episode psychosis: A 7T study.

Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs). We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs, and characterized the patterns of network connectivity in the 2 groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity. Compared to HCs, reduced centrality of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased centrality of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. This cluster was strongly correlated with CD scores but not with other symptom scores. Our observations are congruent with previous findings of reduced but not increased centrality. We observed increased centrality of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer. These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. Longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.