Conjugated Coordination Nanosheets with Molecular Rotors for Pseudocapacitors: Nanoarchitectonics and Enhanced Performance.

High-level pseudocapacitive materials require incorporations of significant redox regions into conductive and penetrable skeletons to enable the creation of devices capable of delivering high power for extended periods. Coordination nanosheets (CNs) are appealing materials for their high natural electrical conductivities, huge explicit surface regions, and semi-one-layered adjusted pore clusters. Thus, rational design of ligands and topological networks with desired electronic structure is required for the advancement in this field. Herein, we report three novel conjugated CNs (RV-10-M, M = Zn, Ni, and Co), by utilizing the full conjugation of the terpyridine-attached flexible tetraphenylethylene (TPE) units as the molecular rotors at the center. We prepare binder-free transparent nanosheets supported on Ni-foam with outstanding pseudocapacitive properties via a hydrothermal route followed by facile exfoliation. Among three CNs, the high surface area of RV-10-Co facilitates fast transport of ions and electrons and could achieve a high specific capacity of 670.8 C/g (1677 F/g) at 1 A/g current density. Besides, the corresponding flexible RV-10-Co possesses a maximum energy density of 37.26 Wh kg-1 at a power density of 171 W kg-1 and 70% capacitance retention even after 1000 cycles.

Neurological Complications After Transcatheter Aortic Valve Replacement: A Review.

Transcatheter aortic valve replacement (TAVR) has become the dominant procedural modality for aortic valve replacement in the United States. The reported rates of neurological complications in patients undergoing TAVR have changed over time and are dependent on diagnostic definitions and modalities. Most strokes after TAVR are likely embolic in origin, and the incidence of stroke has decreased over time. Studies have yielded conflicting results when comparing stroke rates between TAVR and surgical aortic valve replacement (SAVR), especially due to differences in diagnostic criteria and neurocognitive testing. In this narrative review, we summarize the available data on the incidence of stroke, delirium, and cognitive decline after TAVR and highlight potential areas in need of future research. We also discuss silent cerebral ischemic lesions (SCILs) and their association with a decline in postoperative neurocognitive status after TAVR. Finally, we describe that the risk of delirium and postoperative decline is increased when nonfemoral access routes are used, and we highlight the need for standardized imaging and valid, repeatable methodologies to assess cognitive changes after TAVR.

Structural modification of the propyl linker of cjoc42 in combination with sulfonate ester and triazole replacements for enhanced gankyrin binding and anti-proliferative activity.

Liver cancer is a complex disease that involves various oncoproteins and the inactivation of tumor suppressor proteins (TSPs). Gankyrin is one such oncoprotein, first identified in human hepatocellular carcinoma, that is known to inactivate multiple TSPs, leading to proliferation and metastasis of tumor cells. Despite this, there has been limited development of small molecule gankyrin binders for the treatment of liver cancer. In this study, we are reporting the structure-based design of gankyrin-binding small molecules which inhibit the proliferation of HuH6 and HepG2 cells while also increasing the levels of certain TSPs, such as Rb and p53. Interestingly the first molecule to exhibit inhibition by 3D structure stabilization is seen. These results suggest a possible mechanism for small-molecule inhibition of gankyrin and demonstrate that gankyrin is a viable therapeutic target for the treatment of liver cancer.

Study of defect density of copper vacancies in chalcogenide CuSbS2, CuSbSe2, CuBiS2, and CuBiSe2 heterojunction thin-film solar cells.

In the past decade, a new family of ternary chalcogenide absorber (TCA) materials MIMIIX2 (where MI = Cu, Ag, Pb; MII = Sb, Bi, In; and X = S, Se, Te) have been studied. The copper family of ternary chalcogenide CuSbS2 CuSbSe2 CuBiS2, and CuBiSe2 is an amazing absorber material for thin-film solar cells because of their suitable band gap, high absorption coefficient and inexpensive, nontoxic, environment friendly and sustainable nature. In the presented work, first time simulated defect density of copper vacancies in CuSbS2 (CAS), CuSbSe2 (CASe), CuBiS2 (CBS) and CuBiSe2 (CBSe) has based heterojunction thin-film solar cells (HJTFSCs) with buffer CdS, intrinsic i-ZnO, window ZnO: Al and back contact Mo and set the cell scheming ZnO: Al/i-ZnO/n-CdS/p-TCA/Mo using SCAPS 1D. Major focus of this paper is on the influence of copper vacancies defect density that impact on the performance of ternary chalcogenide with various parameters of solar cells, i.e. short-circuit current density (Jsc), open-circuit voltage (Voc), form factor (FF) and efficiency (η). The cell parameter set at constant temperature 300 K, thickness 2.5 µm, carrier density 5 × 1016 cm-3, front internal transmission coefficient 1 and illumination intensity 100 mW/cm2 with AM1.5 sun light. This study clarifies the potential benefits to utilizing of ternary chalcogenide compounds as absorber material for solar cell fabrication.

Early diagnosis of autoimmune diseases through electrochemical biosensing using a modified plastic chip electrode.

Detecting chronic autoimmune disorders (ADs) early reduces the risk of morbidity, disability, and mortality and offers the possibility of significant therapeutic action in a timely manner. Developing low-cost, reliable, and sensitive sensors for ADs can ensure the efficient utilization of healthcare resources at earlier stages. Here, we report on the development of an electrochemical biosensor for sensing CXCL10, a chemokine protein that serves as a biomarker for autoimmune diseases. A self-assembly strategy is used for the immobilization of biorecognition elements on a plastic chip electrode (PCE). A homemade PCE offers a versatile and cost-effective scaffold for sensing applications. Gold nanoparticles were electrochemically deposited on the electrode via the reduction of gold ions on the PCE galvanostatically. The CXCL10 antibody and recognition elements were immobilized on the gold-deposited PCE. The attachment of recognition molecules was confirmed by energy-dispersive scanning electron microscopy, atomic force microscopy, infrared spectroscopy, and electrochemical techniques. Electrochemical impedance spectroscopy (EIS) was used for the detection of CXCL10 within a concentration range spanning from pico- to micro-molar levels. The sensor exhibited remarkable linearity in both buffer and plasma solutions, with a limit of detection (LOD) of up to 0.72 pg mL-1.

Self-Assembled Conjugated Coordination Polymer Nanorings: Role of Morphology and Redox Sites for the Alkaline Electrocatalytic Oxygen Evolution Reaction.

Electrocatalytic water splitting provides a sustainable method for storing intermittent energies, such as solar energy and wind, in the form of hydrogen fuel. However, the oxygen evolution reaction (OER), constituting the other half-cell reaction, is often considered the bottleneck in overall water splitting due to its slow kinetics. Therefore, it is crucial to develop efficient, cost-effective, and robust OER catalysts to enhance the water-splitting process. Transition-metal-based coordination polymers (CPs) serve as promising electrocatalysts due to their diverse chemical architectures paired with redox-active metal centers. Despite their potential, the rational use of CPs has faced obstacles including a lack of insights into their catalytic mechanisms, low conductivity, and morphology issues. Consequently, achieving success in this field requires the rational design of ligands and topological networks with the desired electronic structure. This study delves into the design and synthesis of three novel conjugated coordination polymers (CCPs) by leveraging the full conjugation of terpyridine-attached flexible tetraphenylethylene units as electron-rich linkers with various redox-active metal centers [Co(II), Ni(II), and Zn(II)]. The self-assembly process is tuned for each CCP, resulting in two distinct morphologies: nanosheets and nanorings. The electrocatalytic OER performance efficiency is then correlated with factors such as the nanostructure morphology and redox-active metal centers in alkaline electrolytes. Notably, among the three morphologies studied, nanorings for each CCP exhibit a superior OER activity. Co(II)-integrated CCPs demonstrate a higher activity between the redox-active metal centers. Specifically, the Co(II) nanoring morphology displays exceptional catalytic activity for OER, with a lower overpotential of 347 mV at a current density of 10 mA cm-2 and small Tafel slopes of 115 mV dec-1. The long-term durability is demonstrated for at least 24 h at 1.57 V vs RHE during water splitting. This is presumably the first proof that links the importance of nanostructure morphologies to redox-active metal centers in improving the OER activity, and it may have implications for other transdisciplinary energy-related applications.

Up-regulation of extracellular-matrix and inflammation related genes in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy with late-presentation, site-specific heterogeneity, and high-propensity for recurrence/metastasis that has shown rise in mortality. Lately, research emphasize on dynamic interactions between tumor-cells and extracellular-matrix components within tumor-microenvironment that promote tissue integrity loss and carcinogenesis. Therefore, OSCC clinical-management is still challenging. DESIGN: Present study validated clinical utility of a 13 gene-panel in two chief sub-sites of OSCC: Buccal mucosa squamous cell carcinoma (BMSCC) (N = 50) and Tongue squamous cell carcinoma (TSCC) (N = 52) using qRT-PCR. Principal component analysis and binary logistic regression analysis were applied to acquire definite multi gene models. Protein expression analysis was employed using the Human Protein Atlas, UALCAN and TIMER 2.0 databases to explore potential correlation between immune cells and gene-panels. RESULTS: Significant up-regulation of CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, PLAU, SERPINE1 and SPP1 except OASL was observed in OSCC tissue in comparison of absolute normal controls. Although, this gene-panel could potentially discriminate OSCC tissues from absolute normal controls as solitarily diagnostic and/or predictive biomarkers, models generated also showed substantial discriminating efficacy. Eight-genes were found to be significantly associated with poor-prognosis on clinico-pathological association. Protein-expression confirmed overexpression of gene-panel and added advantage of being secretory-protein. Importantly, up-regulated genes in our study showed significant relation with immune-cells infiltration suggesting their contribution in immune-escape. CONCLUSION: Thus, we propose that the 13 gene-panel could pave the way to effective and personalized clinical-management of OSCC in terms of diagnostic and prognostic measures and thereby as therapeutic targets.

Neural Correlates of the p Factor in Adolescence: Cognitive Control With and Without Enhanced Positive Affective Demands.

BACKGROUND: Recent research has aimed to characterize processes underlying general liability toward psychopathology, termed the p factor. Given previous research linking the p factor with difficulties in both executive functioning and affective regulation, the present study investigated nonaffective and positive affective inhibition in the context of a sustained attention/inhibition paradigm in adolescents exhibiting mild to severe psychopathology. METHODS: Functional magnetic resonance imaging data were collected during an integrated reward conditioning and go/no-go task in 138 adolescents assigned female at birth. We modeled the p factor using hierarchical confirmatory factor analysis. Positive affective inhibition was measured by examining responses to no-go stimuli with a history of reward conditioning. We examined associations between p factor scores and neural function and behavioral performance. RESULTS: Consistent with nonaffective executive function as a primary risk factor, p factor scores were associated with worse behavioral performance and hypoactivation in the left superior frontal gyrus and middle frontal gyrus during response initiation (go trials). The p factor scores were additionally associated with increased error-related signaling in the temporal cortex during incorrect no-go trials. CONCLUSIONS: During adolescence, a period characterized by heightened risk for emergent psychopathology, we observed unique associations between p factor scores and neural and behavioral indices of response initiation, which relies primarily on sustained attention. These findings suggest that shared variation in mental disorder categories is characterized in part by sustained attention deficits. While we did not find evidence that the p factor was associated with inhibition in this study, this observation is consistent with our hypothesis that the p factor would be related to nonaffective control processes.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Melatonin: Emerging Player in the Management of Oral Cancer.

Oral cancer (OC) has emerged as a major medical and social issue in many industrialized nations due to the high death rate. It is becoming increasingly common in people under the age of 45, although the underlying causes and mechanisms of this increase remain unclear. Melatonin, as a pleiotropic hormone, plays a pivotal role in a wide variety of cellular and physiological functions. Mounting evidence supports melatonin's ability to modify/influence oral carcinogenesis, help in the reduction of the incidence of OC, and increase chemo- and radiosensitivity. Despite its potential anti-carcinogenic effects, the precise function of melatonin in the management of OC is not well understood. This review summarizes the current knowledge regarding melatonin function in anti-carcinogenesis mechanisms for OC. In addition, clinical assessment and the potential therapeutic utility of melatonin in OC are discussed. This review will provide a basis for researchers to create new melatonin-based personalized medicines for treating and preventing OC.

Plastic Chip Electrode: An Emerging Multipurpose Electrode Platform.

The properties of electrodes play a crucial role in the processes occurring on them. Therefore, a variety of materials have been tried as electrodes. Carbon composite materials are among the most admired ones. Use of composites as electrode material dates back to the mid of the last century when polymer-carbon composites were tried as general-purpose electrode platforms and epoxy impregnated graphite paste/ solid electrodes were tried in polarography. Later the composite electrodes have seen several phases of development. Plastic Chip Electrode (PCE) is a class of polymer composite electrode developed by our group. This monographic review gives a bird's eye account of polymer composite electrodes and appurtenant work, followed by elaborating on various aspects and state-of-the-art plastic chip electrodes.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses.

Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1], (Heath et al., 2021) [2], (Keech et al., 2020) [3], (Mallory et al., 2022) [4]. The most common adverse events seen after administration with NVX-CoV2373 were injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, nausea, or vomiting. In addition, immunogenicity against variants of interest (VOI) and variants of concern (VOC) was established with high titers of ACE2 receptor-inhibiting and neutralizing antibodies in these studies (EMA, 2022) [5], (FDA, 2023) [6]. Further studies on correlates of protection determined that titers of anti-Spike IgG and neutralizing antibodies correlated with efficacy against symptomatic COVID-19 established in clinical trials (p < 0.001 for recombinant protein vaccine and p = 0.005 for mRNA vaccines for IgG levels) (Fong et al., 2022) [7]. Administration of a booster dose of the recombinant protein vaccine approximately 6 months following the primary two-dose series resulted in substantial increases in humoral antibodies against both the prototype strain and all evaluated variants, similar to or higher than the antibody levels observed in phase 3 studies that were associated with high vaccine efficacy (Dunkle et al., 2022) [1], (Mallory et al., 2022) [4]. These findings, together with the well tolerated safety profile, support use of the recombinant protein vaccine as primary series and booster regimens.

Surgical Aortic Valve Replacement to Treat Prosthetic Valve Endocarditis After Valve-in-Valve Transcatheter Aortic Valve Replacement.

Prosthetic valve endocarditis (PVE) is an uncommon complication after heart valve replacement surgery that can result in increased morbidity and mortality. Current guidelines for management of PVE recommend antibiotic therapy followed by surgical valve replacement. The number of aortic valve replacements is expected to rise in the coming years with the expanded indications for use of transcatheter aortic valve replacement (TAVR) in patients with low, intermediate, and high surgical risk, as well as in patients with a failed aortic bioprosthetic valve. Current guidelines do not address the use of valve-in-valve (ViV) TAVR for management of PVE in patients who are at high risk for surgical intervention. The authors present a case of a patient with aortic valve PVE after surgical aortic valve replacement (SAVR); he was treated with valve-in-valve (ViV) TAVR due to the high surgical risk. The patient was discharged, but he returned to the hospital with PVE and valve dehiscence 14 months after ViV TAVR, after which he successfully underwent re-operative SAVR.

Association of Interactions between Metabolic 'Caretaker' Genes, p53, MDM2, and Tobacco Use with the Risk of Oral Cancer: A Multifactor Dimensionality Reduction Approach.

BACKGROUND: The present study investigated the association of interactions between gene polymorphisms in metabolic 'caretaker' genes (Phase I: CYP1A1, CYP2E1; Phase II: GSTM1, GSTT1), the cell cycle regulatory gene, p53, along with its negative controller, MDM-2, and the environment variable (tobacco). A nonparametric model, multifactor dimensionality reduction (MDR), was applied to analyse these interactions. MATERIALS AND METHODS: This case-control study was carried out on 242 subjects. Genomic DNA was extracted from peripheral blood lymphocytes.11 gene variants with an exposure variable (tobacco use) were analysed using MDR to identify the best locus model for gene-gene and gene-environment interactions. Statistical significance was evaluated using a 1000-fold permutation test using MDR permutation testing software (version 1.0 beta 2). The value of p<0.05 was considered statistically significant. RESULTS: The best three-locus model for gene-gene interaction included two of the p53 gene polymorphisms; rs17878362 (intron 3) and rs1042522 (exon 4) and rs6413432 in the Phase I gene, CYP2E1(DraI). The three-locus model to evaluate the gene-environment interaction included two intronic polymorphisms of the p53 gene, that is, rs17878362 (intron 3) and rs1625895 (intron 6), and rs4646903 in the Phase I gene CYP1A1*2C. The interaction graphs revealed independent main effects of the tobacco and p53 polymorphism, rs1042522 (exon 4), and a significant additive interaction effect between rs17878362 (intron 3) and rs1042522 (exon 4). CONCLUSIONS: The nonparametric approach highlighted the potential role of tobacco use and variations in the p53 gene as significant contributors to oral cancer risk. The findings of the present study will help implement preventive strategies in both tobacco use and screening using a molecular pathology approach.

Primary cilia, A-kinase anchoring proteins and constitutive activity at the orphan G protein-coupled receptor GPR161: A tale about a tail.

Primary cilia are non-motile antennae-like structures responsible for sensing environmental changes in most mammalian cells. Ciliary signalling is largely mediated by the Sonic Hedgehog (Shh) pathway, which acts as a master regulator of ciliary protein transit and is essential for normal embryonic development. One particularly important player in primary cilia is the orphan G protein-coupled receptor, GPR161. In this review, we introduce GPR161 in the context of Shh signalling and describe the unique features on its C-terminus such as PKA phosphorylation sites and an A-kinase anchoring protein motif, which may influence the function of the receptor, cAMP compartmentalisation and/or trafficking within primary cilia. We discuss the recent putative pairing of GPR161 and spexin-1, highlighting the additional steps needed before GPR161 could be considered 'deorphanised'. Finally, we speculate that the marked constitutive activity and unconventional regulation of GPR161 may indicate that the receptor may not require an endogenous ligand.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood.

OBJECTIVE: The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD: The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. RESULTS: Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. CONCLUSION: Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.