A Retrospective Observational Study of the Microbial Etiology and Antimicrobial Susceptibility Patterns of Blood Cultures From ICU Patients at a Healthcare Facility in North India.

Introduction Bloodstream infections (BSI) are a leading source of fatalities and morbidity in hospitals. However, the clinical spectrum and antimicrobial resistance differ globally. Identifying the pathogenic spectrum and variations in antibiotic resistance is crucial for controlling BSI and preventing inappropriate antibiotic use. Material and methods This retrospective observational study was conducted at the Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, UP, India, for one year between June 2022 and June 2023. A total of 669 adult patients' blood cultures were obtained from ICUs. Blood culture was done using a BacT/Alert 3D (BioMérieux SA, Marcy-l'Étoile, France) automated system. Identification of the bacterial as well as fungal isolates was done using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and the antimicrobial susceptibility profile was analyzed using the VITEK 2 Compact system (BioMérieux SA). Results Of the 669 blood culture samples, 213 (31.8%) showed bacterial or fungal growth. Of these 213 isolates, the most common isolate was coagulase-negative Staphylococci (21.6%), followed by Klebsiella pneumoniae (19.3%) and Acinetobacter spp. (17.8%). The majority of gram-negative bacteria were resistant to most drugs, and vancomycin and linezolid were both effective against the majority of gram-positive bacteria. Conclusion The current study found that septicemia was more frequently caused by gram-negative bacteria than by gram-positive bacteria. Blood cultures are always necessary in cases of suspected septicemia, and once the antimicrobial susceptibility profile of the pathogen causing septicemia has been determined, suitable antimicrobials should be prescribed and used to lower the antimicrobial resistance burden.

The Association Between Oxidative Stress and the Progression of Heart Failure: A Systematic Review.

Chronic heart failure (CHF) is a progressive multifactorial condition where the role of oxidative stress may have implications in the pathogenesis of the disease. Despite growing interest among researchers and clinicians, the limited, unorganized, and divergent findings regarding the association between oxidative stress and the progression of heart failure (HF) have prompted us to conduct this study. Drawing upon the evolving nature of this research domain, this study is one of the first of its kind to present a systematic and comprehensive overview of the existing evidence regarding the role of oxidative stress production in the progression of HF. This study systematically reviews peer-reviewed empirical studies published in English, particularly focusing on the association between oxidative stress and the progression of HF. Parameters, such as publication year, study design, population demographics (size, age, and gender), types of HF, and characterization of markers in the existing studies, were reviewed. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure, a thorough search was conducted on PubMed, Cochrane, Embase, and Sage databases, without any restrictions on the publication dates of articles, which yielded a total of 1,808 records on the association of oxidative stress production with clinical outcomes in HF patients. The analysis of the content of 17 articles offered a robust observation of this phenomenon, providing insights into the levels of oxidative stress, antioxidant markers, and the enzymes involved in the production of reactive oxygen species (ROS), and their association with the progression and severity of HF. The findings highlighted various knowledge gaps and future research priorities are recommended in the areas of interest and unexplored areas.

Identification and targeting of metastatic biomarkers for hepatocellular carcinoma therapeutics using small molecules library of curcumin analogues.

The understanding of the molecular basis of complex diseases like hepatocellular carcinoma (HCC) needs large datasets of multiple genes and proteins involved in different phenomenon of its development. This study focuses on the molecular basis of HCC and the development of therapeutic strategies. We analyzed a dataset of 5475 genes (Homo sapiens) involved in HCC hallmarks, involving comprehensive data on multiple genes and frequently mutated genes. As HCC is characterized by metastasis, angiogenesis, and oxidative stress, exploration of genes associated with them has been targeted. Through gene ontology, functional characterization, and pathway enrichment analysis, we identified target proteins such as Lysyl oxidase, Survivin, Cofilin, and Cathepsin B. A library of curcumin analogs was used to target these proteins. Tetrahrydrocurcumin showed promising binding affinities for all four proteins, suggesting its potential as an inhibitor against these proteins for HCC therapy.

Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EVISF ) reveals sex-dependent changes in microglial EV proteome in response to Aß pathology.

Brain-derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making EVs attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease-vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF ) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40-150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g., APPswe, PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with Aß deposition. Genotype, age, and Aß deposition modulated proteostasis- and immunometabolic-related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust- and diverse- EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.

Comparative evaluation of divergent concoction of NGF, BDNF, EGF, and FGF growth factor's role in enhancing neuronal differentiation of adipose-derived mesenchymal stem cells.

MSCs (Mesenchymal Stem Cells) can differentiate into various lineages, including neurons and glial cells. In the past few decades, MSCs have been well explored in the context of neuronal differentiation and have been reported to have the immense potential to form distinct kinds of neurons. The distinguishing features of MSCs make them among the most desired cell sources for stem cell therapy. This study involved the trans-differentiation of Adipose-derived human Mesenchymal Stem Cells (ADMSCs) into neurons. The protocol employs a cocktail of chemical inducers in different combinations, including Brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), and Nerve growth factor (NGF) Fibroblastic growth factor (FGF), in induction media. Both types have been successfully differentiated into neurons, confirmed by morphological aspects and the presence of neural-specific markers through RT-PCR (Reverse transcription polymerase chain reaction) studies and immunocytochemistry assay. They have shown excellent morphology with long neurites, synaptic connections, and essential neural markers to validate their identity. The results may significantly contribute to cell replacement therapy for neurological disorders.

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension.

BACKGROUND: Extracellular vesicles (EVs) have emerged as a promising liquid biopsy for various diseases. For the first time, using plasma and urinary EVs, we assessed the activity of renin-angiotensin system (RAS), a central regulator of renal, cardiac, and vascular physiology, in patients with control (Group I) or uncontrolled (Group II) primary hypertension. METHODS: EVs were isolated from 34 patients with history of hypertension, and characterized for size and concentration by nanoparticle tracking analyses, exosomal biomarkers by immunogold labeling coupled with transmission electron microscopy, flow cytometry and immunoblotting. EVs were analyzed for the hydrolytic activity of chymase, angiotensin converting enzyme (ACE), ACE2, and neprilysin (NEP) by HPLC. RESULTS: Plasma and urinary EVs were enriched for small EVs and expressed exosomal markers (CD63, CD9, and CD81). The size of urinary EVs (but not plasma EVs) was significantly larger in Group II compared to Group I. Differential activity of RAS enzymes was observed, with significantly higher chymase activity compared to ACE, ACE2, and NEP in plasma EVs. Similarly, urinary EVs exhibited higher chymase and NEP activity compared to ACE and ACE2 activity. Importantly, compared to Group I, significantly higher chymase activity was observed in urinary EVs (p = 0.03) from Group II, while no significant difference in activity was observed for other RAS enzymes. CONCLUSIONS: Bioactive RAS enzymes are present in plasma and urinary EVs. Detecting chymase in plasma and urinary EVs uncovers a novel mechanism of angiotensin II-forming enzyme and could also mediate cell-cell communication and modulate signaling pathways in recipient cells.

Inhibition of LINGO1 as a therapeutic target to promote axonal regeneration and repair for neurological disorders.

The Central nervous system is blemished by the high incidence of neurodegenerative diseases, which is known to cause disfiguration of regeneration and repair of axonal growth. Recognition of proteins that act as agents of repressing such repair has become the norm to tackle these abominable conditions. One such protein is LINGO1 that act as a repressor for axonal growth. Being one of the critical causative agents of several neurodegenerative pathways. Consequently, its inhibition may tend to help the outcomes of regenerative technologies aiming to outweigh the symptoms of neurodegenerative diseases. For this objective, LINGO1 was targeted with pharmacophore analogs of Fasudil and Ibuprofen, as they are known to have a deterring effect against the concerned protein. 1-Tosyl-2-(chloromethyl)-2,3-dihydro-1H-indole was found showing the least binding score of - 6.8, with verified ADMET admissibility. The pharmacological activity of the said ligand was estimated with QSAR tool showing favourable electro-steric model. All this was finally collaborated with a molecular dynamics simulation study which exhibited a stable structure compatibility of the ligand with LINGO-1. Further, the efficacy of the compound can be evaluated through experimental studies for inferring its future potential and utilization as an effective means to tackle neuronal regeneration and remyleination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03789-4.

Validating the Nutraceutical Significance of Minor Millets by Employing Nutritional-Antinutritional Profiling.

Millets are group of underutilized cereal crops with higher nutritional values. The present investigation used different classes of minor millets, including barnyard (sava), little (kutki), finger (ragi), kodo and foxtail millets, for evaluation of their nutritional parameters, i.e., the content of proteins, total amino acids, total sugars, insoluble fibers, soluble fibers, total dietary fibers, iron (Fe) and zinc (Zn), along with antinutritional and antioxidant parameters, viz., tannic acid, phytic acid, phenol, flavonoid, proline and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Alpha amylase and alpha glucosidase activity were also thought to elevate millets as a viable staple meal. Foxtail millet showed the maximum inhibition, with an IC50 value of 20.46 ± 1.80 µg mL-1 with respect to α-amylase. The coefficient of correlation between nutritional and antinutritional compositions showed that the starch content was significantly and positively correlated with insoluble fiber (r = 0.465) and dietary fiber (r = 0.487). Moreover, sugar was positively correlated with the phytic acid (r = 0.707), Fe and Zn (r = 0.681) contents. To determine the peptides responsible for anticancer activity, the foxtail protein was subjected to ultrafiltration; it was found that the 3 kDa fraction retained the greatest anticancer activity. Selected millet germplasm line(s) that have the best nutraceutical properties could be used in millet improvement programs.

Delineation of novel genomic loci and putative candidate genes associated with seed iron and zinc content in lentil (Lens culinaris Medik.).

The use of molecular breeding approaches for development of lentil genotypes biofortified with essential micro-nutrients such as iron and zinc, could serve as a promising solution to address the problem of global malnutrition. Thus, genome-wide association study (GWAS) strategy was adopted in this study to identify the genomic regions associated with seed iron and zinc content in lentil. A panel of 95 diverse lentil genotypes, grown across three different geographical locations and evaluated for seed iron and zinc content, exhibited a wide range of variation. Genotyping-by-sequencing (GBS) analysis of the panel identified 33,745 significant single nucleotide polymorphisms (SNPs) that were distributed across all the 7 lentil chromosomes. Association mapping revealed 23 SNPs associated with seed iron content that were distributed across all the chromosomes except chromosome 3. Similarly, 14 SNPs associated with seed zinc content were also identified that were distributed across chromosomes 1, 2, 4, 5 and 6. Further, 80 genes were identified in the proximity of iron associated markers and 36 genes were identified in the proximity of zinc associated markers. Functional annotation of these genes revealed their putative involvement in iron and zinc metabolism. For seed iron content, two highly significant SNPs were found to be located within two putative candidate genes namely iron-sulfur cluster assembly (ISCA) and flavin binding monooxygenase (FMO) respectively. For zinc content, a highly significant SNP was detected in a gene encoding UPF0678 fatty acid-binding protein. Expression analysis of these genes and their putative interacting partners suggests their involvement in iron and zinc metabolism in lentil. Overall, in this study we have identified markers, putative candidate genes and predicted putative interacting protein partners significantly associated with iron and zinc metabolism that could be utilized in future breeding studies of lentil for nutrient biofortification.

Nitrogen-doped zinc oxide nanoribbons for potential resonant tunneling diode applications.

Armchair ZnONRs doped with nitrogen are investigated in the current manuscript for possible applications based on negative differential resistance (NDR). To conduct the theoretical research, we use density functional theory (DFT) in conjunction with the non-equilibrium Green's function (NEGF) formalism to carry out first principles computations. Pristine ZnONR (P-ZnONRs) is a semiconductor with a wide energy bandgap (Eg) of 2.53 eV. However, one edge N-doped ZnONRs (SN-ZnO) and both edge N-doped ZnONRs (DN-ZnO) are metallic. Partial density of states (PDOS) reveals that the metallicity is caused by the doped nitrogen atom. The transport characteristics analysis revealed the negative differential resistance (NDR) characteristics in the N-doped ZnONRs. The peak-to-valley current ratios (PVCR) are computed and measured to be 4.58 × 1021 and 1.83 × 1022 for SN-ZnO and DN-ZnO, respectively. The obtained findings suggest the significant potential of armchair ZnONRs for NDR-based applications such as switches, rectifiers, oscillators, memory devices, etc.

Analysis of Changes in Electrolytes Level in Serum After Death and Its Correlation With Postmortem Interval.

Background Apropos estimation of postmortem interval is an important and difficult task for forensic pathologists. In routine practice, postmortem interval is deduced by conventional or physical methods such as early and late postmortem changes, which are subjective methods and prone to errors. Estimating time since death by thanatochemistry is a more objective method as compared to routine conventional or physical methods. The present study is an attempt to analyze the changes in electrolytes level in serum after death and its correlation with postmortem interval. Materials and methods Blood samples were taken from the deceased who were brought for a medicolegal autopsy. The concentration of electrolytes, mainly sodium, potassium, calcium, and phosphate, was evaluated in the serum. The deceased were grouped on the basis of time since death. Log-transferred regression analysis was done to establish the correlation of the concentration of electrolytes with time since death and regression formulas were derived for each parameter. Results Sodium concentration in serum showed a negative correlation with time since death. Potassium, calcium, and phosphate showed a positive correlation with time since death. No statistically significant difference exists in the concentration of electrolytes between males and females. No significant difference was observed in the electrolytes concentration between the age groups. Conclusion Considering the findings of this study, we infer that the concentration of electrolytes, primarily sodium, potassium, and phosphates, in the blood can be used to approximate the amount of time that has passed since death. Nonetheless, until 48 hours after death, electrolyte levels in the blood can be considered for the calculation of the postmortem interval.

High resolution mapping of QTLs for fruit color and firmness in Amrapali/Sensation mango hybrids.

Introduction: Mango (Mangifera indica L.), acclaimed as the 'king of fruits' in the tropical world, has historical, religious, and economic values. It is grown commercially in more than 100 countries, and fresh mango world trade accounts for ~3,200 million US dollars for the year 2020. Mango is widely cultivated in sub-tropical and tropical regions of the world, with India, China, and Thailand being the top three producers. Mango fruit is adored for its taste, color, flavor, and aroma. Fruit color and firmness are important fruit quality traits for consumer acceptance, but their genetics is poorly understood. Methods: For mapping of fruit color and firmness, mango varieties Amrapali and Sensation, having contrasting fruit quality traits, were crossed for the development of a mapping population. Ninety-two bi-parental progenies obtained from this cross were used for the construction of a high-density linkage map and identification of QTLs. Genotyping was carried out using an 80K SNP chip array. Results and discussion: Initially, we constructed two high-density linkage maps based on the segregation of female and male parents. A female map with 3,213 SNPs and male map with 1,781 SNPs were distributed on 20 linkages groups covering map lengths of 2,844.39 and 2,684.22cM, respectively. Finally, the integrated map was constructed comprised of 4,361 SNP markers distributed on 20 linkage groups, which consisted of the chromosome haploid number in Mangifera indica (n =20). The integrated genetic map covered the entire genome of Mangifera indica cv. Dashehari, with a total genetic distance of 2,982.75 cM and an average distance between markers of 0.68 cM. The length of LGs varied from 85.78 to 218.28 cM, with a mean size of 149.14 cM. Phenotyping for fruit color and firmness traits was done for two consecutive seasons. We identified important consistent QTLs for 12 out of 20 traits, with integrated genetic linkages having significant LOD scores in at least one season. Important consistent QTLs for fruit peel color are located at Chr 3 and 18, and firmness on Chr 11 and 20. The QTLs mapped in this study would be useful in the marker-assisted breeding of mango for improved efficiency.

Armchair silicon carbide nanoribbon for potential anode material in lithium-ion batteries (LIBs).

In this work, we have investigated the electrochemical characteristics of armchair silicon carbide nanoribbon (ASiCNR) for its potential deployment as 2D lithium-ion battery anode material. Density functional theory approach is used to calculate the adsorption energy, storage capacity, and open circuit voltage of ASiCNR for LIB. Adsorption of Li atoms introduces the new energy bands which cross the Fermi level; this results in semiconductor to metallic transition of ASiCNR. It indicates the strong interaction of Li atoms towards the ASiCNR. When adsorption of Li atoms increases one by one, the adsorption energy (E[Formula: see text]) per Li atoms increases gradually. When all favourable sites are adsorbed by Li atoms E[Formula: see text] reached its maximum value and it results in maximum storage capacity of 818 mAhg[Formula: see text] and open circuit voltage of 1.15 V. Diffusion barrier of Li atoms for the substrate is 0.42 eV. Our computational results suggest that ASiCNR can be used as an anode material for Li-ion batteries, and it provides the theoretical background for the future study on ASiCNR and other Li storage structures.

A Liquid Biopsy-Based Approach to Isolate and Characterize Adipose Tissue-Derived Extracellular Vesicles from Blood.

Obesity is a major risk factor for multiple chronic diseases. Anthropometric and imaging approaches are primarily used to assess adiposity, and there is a dearth of techniques to determine the changes in adipose tissue (AT) at the molecular level. Extracellular vesicles (EVs) have emerged as a novel and less invasive source of biomarkers for various pathologies. Furthermore, the possibility of enriching cell or tissue-specific EVs from the biofluids based on their unique surface markers has led to classifying these vesicles as "liquid biopsies", offering valuable molecular information on hard-to-access tissues. Here, we isolated small EVs from AT (sEVAT) of lean and diet-induced obese (DIO) mice, identified unique surface proteins on sEVAT by surface shaving followed by mass spectrometry, and developed a signature of five unique proteins. Using this signature, we pulled out sEVAT from the blood of mice and validated the specificity of isolated sEVAT by measuring the expression of adiponectin, 38 adipokines on an array, and several adipose tissue-related miRNAs. Furthermore, we provided evidence of sEV applicability in disease prediction by characterizing sEVAT from the blood of lean and DIO mice. Interestingly, sEVAT-DIO cargo showed a stronger pro-inflammatory effect on THP1 monocytes compared to sEVAT-Lean and a significant increase in obesity-associated miRNA expression. Equally important, sEVAT cargo revealed an obesity-associated aberrant amino acid metabolism that was subsequently validated in the corresponding AT. Lastly, we show a significant increase in inflammation-related molecules in sEVAT isolated from the blood of nondiabetic obese (>30 kg/m2) individuals. Overall, the present study offers a less-invasive approach to characterize AT.

MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease.

INTRODUCTION: Brain cell-derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment. METHODS: Total sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI-AD; n = 6), and AD dementia (n = 11). Various brain cell-derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs. RESULTS: miRNAs in sEV subtypes differentially expressed in MCI, MCI-AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI). DISCUSSION: miRNA analyses in specific sEVs could serve as a novel blood-based molecular biomarker for AD. HIGHLIGHTS: Multiple brain cell-derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEVCD31 and sEVPDGFRß suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.

Recent advancement in quantum dot-based materials for energy storage applications: a review.

The need for energy storage and conversion is growing as a result of the worsening consequences of climate change and the depletion of fossil fuels. Energy conversion and storage requirements are rising as a result of environmental problems including global warming and the depletion of fossil fuels. The key to resolving the energy crisis is anticipated to be the quick growth of sustainable energy sources including solar energy, wind energy, and hydrogen energy. In this review, we have focused on discussing various quantum dots (QDs) and polymers or nanocomposites used for SCs and have provided examples of each type's performance. Effective QD use has really led to increased performance efficiency in SCs. The use of quantum dots in energy storage devices, batteries, and various quantum dots synthesis have all been emphasized in a number of great literature articles. In this review, we have homed in on the electrode materials based on quantum dots and their composites for storage and quantum dot based flexible devices that have been published up to this point.

Ultra Sensitive Breast Cancer Cell Lines Detection Using Dual Nanocavities Engraved Junctionless FET.

This article reports breast cancer cell lines (Hs578T, MDA-MB-231, MCF-7, and T47D) and healthy breast cells (MCF-10A) detection based on the modulation of its electrical properties by deploying dual nanocavity engraved junctionless FET. The device has a dual gate to enhance gate control and has two nanocavities etched under both gates for breast cancer cell lines immobilization. As the cancer cells are immobilized in the engraved nanocavities, which were earlier filled with air, the dielectric constant of the nanocavities changes. This results in the modulation of the device's electrical parameters. This electrical parameters modulation is then calibrated to detect the breast cancer cell lines. The reported device demonstrates a higher sensitivity toward the detection of breast cancer cells. The JLFET device optimization is done for improving the performance by optimizing the nanocavity thickness and the SiO2 oxide length. The variation in the dielectric property of cell lines plays a key role in the detection technique of the reported biosensor. The sensitivity of the JLFET biosensor is analyzed in terms of ∆VTH, ∆ION, ∆gm , and ∆SS . The reported biosensor shows the maximum sensitivity for T47D ( κ = 32 ) breast cancer cell line with ∆VTH = 0.800 V, ∆ION = 0.165 mA/µm, ∆gm = 0.296 mA/V-µm , and ∆SS = 5.41 mV/decade. Moreover, the effect of variation in the occupancy of the cavity by the immobilized cell lines has also been studied and analyzed. With increased cavity occupancy the variation in the device performance parameter enhances Further, the sensitivity of the proposed biosensor is compared with the existing biosensors and it is reported to be highly sensitive as compared to the existing biosensors. Hence, the device can be utilized for array based screening of cell lines of breast cancer and diagnosis with the benefit of easier fabrication and cost effectiveness of the device.

Hydrogenated cove-edge aluminum nitride nanoribbons for ultrascaled resonant tunneling diode applications: a computational DFT study.

While synthesizing quasi-one-dimensional nanoribbons, there is a finite probability that edges have cove-edge defects. This paper focuses on the structural, electronic, and transport properties of cove-edge aluminum nitride nanoribbons (AlNNR) using density functional theory and the non-equilibrium Green's function (NEGF) method. The cove-edge AlNNRs are thermodynamically stable and exhibit metallic behavior. Interestingly, the calculated current-voltage characteristics of the cove-edge AlNNR-based nanodevices show negative differential resistance (NDR). The H-AlN-Cove nanodevice exhibits high peak-to-valley current ratio (PVCR) of the order of 107. The calculated PVCR of the H-AlN-Cove nanodevice is 106times higher than that of the silicene nanoribbon (SiNR) and graphene nanoribbon (GNR), and 104times higher than that of the phosphorene nanoribbon (PNR) and arsenene nanoribbons (ANR)-based devices respectively. The NDR feature with high PVCR provides a prospect for the cove-edge AlNNR in nanodevice applications.

Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EV-ISF) reveals sex-dependent changes in microglial EV proteome in response to Aß pathology.

Brain-derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. Circulating EVs are protected from degradation, making them attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease-vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labeling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40-150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g. APPswe,PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with A deposition. Genotype, age, and Aß deposition modulated proteostasis- and immunometabolic-related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust- and diverse- EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.

Envelope coronally advanced flap with site-specific bilaminar acellular dermal matrix or connective tissue graft for management of multiple marginal tissue recessions: A retrospective analysis of cases.

BACKGROUND: A proper case selection and decision making is essential for management of multiple marginal tissue recessions (MTR) using a conventional or bilaminar approach. Coronally advanced flap (CAF) is one of the commonly used methods for management of MTR. CAF has been advocated in combination with soft tissue grafts as bilaminar technique, which had showed significant success in terms of root coverage. METHODS AND RESULTS: Aim of this case series was to retrospectively evaluate Zucchelli's modification of envelope CAF (eCAF) and site-specific bilaminar methods using Acellular Dermal Matrix (ADM) and Connective Tissue Graft (CTG) for management of MTR. A total of 15 subjects (five subjects/25 sites per technique, total number of sites = 75) who were managed by three different techniques with 12 months postoperative records were retrospectively evaluated. All patients showed significant clinical improvement in root coverage outcomes when compared to baseline. Mean root coverage achieved at 3 months (90%), 6 months (95%) and 12 months (95%) postoperatively did not reveal significant difference between three methods. Complete root coverage was observed in 86.6% of eCAF cases and in 86.6% and 95% of ADM/CTG with eCAF, respectively. There was an increase in width of keratinised tissue, both individually and collectively across all of the groups. CONCLUSION: Clinical outcomes suggested that bilaminar techniques should be used only in specific cases. Predictable results can be obtained without the use of a soft tissue graft or substitute if a careful treatment plan for technique selection is developed on an individual case-by-case basis. KEY POINTS: Why is this case new information? Comparison of site-specific bilaminar modalities with modified coronally advanced flap alone What are the keys to successful management of such cases? Flap advancement and mobilisation Flap passivity What are the primary limitations to success in such cases? Case selection Flap tension Soft tissue phenotype Thickness of graft Operator skills.