SenNet recommendations for detecting senescent cells in different tissues.

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung.

BACKGROUND: Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance. METHODS: Five-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively. RESULTS: Exposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN. CONCLUSION: Exposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.

Unique Cell Subpopulations and Disease Progression Markers in Canines with Atopic Dermatitis.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with unclear molecular and cellular contributions behind the complex etiology. To unravel these differences between healthy control and AD skin we employed single-cell transcriptomics, utilizing the canine AD model for its resemblance to human clinical and molecular phenotypes. In this study, we show that there are overall increases in keratinocytes and T cells and decreases in fibroblast populations in AD dogs. Within immune cell types, we identified an enriched γδ T cell population in AD, which may contribute to cutaneous inflammation. A prominent IL26-positive fibroblast subpopulation in AD was detected, which may activate neighboring cells in the dermal-epidermal niche. Lastly, by comparing dogs with different disease severities, we found genes that follow disease progression and may serve as potential biomarkers. In this study, we characterized key AD cell types and cellular processes that can be further leveraged in diagnosis and treatment.

A Zn/Cd/Ni Metal-Organic Framework-Based Solid and Flexible Fluoroprobes for Highly Selective Detection of 4-Nitroaniline in Real Water Samples.

The combination of diazabicyclic compound i.e. 1,4-diazabicyclo[2.2.2]octane (DABCO) and dicarboxylate linker 1,4-dicarboxylic acid are employed to self-assemble with three divalent metal ions such as Zn2+, Cd2+, Ni2+ led to the formation of highly stable pillar layered luminescent metal-organic frameworks. The emissive response of as-synthesized MOFs was studied in organic solvents with different functionalities resulting in the development of fluoroprobes having excellent recognition ability for 4-nitroaniline with detection limit upto micromolar. All the MOFs display a good linear relation between the fluorescence intensity and concentration of 4-NA in the range of 10-90 µmol L-1. The values of Ksv for Zn-MOF, Cd-MOF, and Ni-MOF are found to be 1.75 × 104 mol-1L, 1.25 × 104 mol-1L, and 28.0 × 104 mol-1L, respectively. The calculated detection limit values are 19.7 µmol L-1, 27.6 µmol L-1, and 1.19 µmol L-1 respectively. Moreover, the study was further extended to fabricate the solid membrane-based fluoroprobe using a linear chitosan polysaccharide and act as an efficient solid fluoroprobe for the detection of 4-NA. This proposed synthesis of polymeric membrane facilitates the MOF@chitosan fluorophore to transfer its fluorescence-emissive nature to a solid state.

PDE4D and miR-203 are promising biomarkers for canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses. METHODS AND RESULTS: We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls. CONCLUSIONS: We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.

Insights into the baicalein-induced destabilization of LS-shaped Aß42 protofibrils using computer simulations.

Amyloid-ß (Aß) peptides aggregate spontaneously into various aggregating species comprising oligomers, protofibrils, and mature fibrils in Alzheimer's disease (AD). Disrupting ß-sheet rich neurotoxic smaller soluble Aß42 oligomers formed at early stages is considered a potent strategy to interfere with AD pathology. Previous experiments have demonstrated the inhibition of the early stages of Aß aggregation by baicalein; however, the molecular mechanism behind inhibition remains largely unknown. Thus, in this work, molecular dynamics (MD) simulations have been employed to illuminate the molecular mechanism of baicalein-induced destabilization of preformed Aß42 protofibrils. Baicalein binds to chain A of the Aß42 protofibril through hydrogen bonds, π-π interactions, and hydrophobic contacts with the central hydrophobic core (CHC) residues of the Aß42 protofibril. The binding of baicalein to the CHC region of the Aß42 protofibril resulted in the elongation of the kink angle and disruption of K28-A42 salt bridges, which resulted in the distortion of the protofibril structure. Importantly, the ß-sheet content was notably reduced in Aß42 protofibrils upon incorporation of baicalein with a concomitant increase in the coil content, which is consistent with ThT fluorescence and AFM images depicting disaggregation of pre-existing Aß42 fibrils on the incorporation of baicalein. Remarkably, the interchain binding affinity in Aß42 protofibrils was notably reduced in the presence of baicalein leading to distortion in the overall structure, which agrees with the structural stability analyses and conformational snapshots. This work sheds light on the molecular mechanism of baicalein in disrupting the Aß42 protofibril structure, which will be beneficial to the design of therapeutic candidates against disrupting ß-sheet rich neurotoxic Aß42 oligomers in AD.

Assessing bias in the causal role of HPV in oral cancer: A systematic review and meta-analysis.

OBJECTIVE: High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from 0% to 100%. HPV DNA detection or evidence of exposure alone is insufficient to conclude causality. This systematic review assesses the extent of bias in studies of HPV detection in cancers of the oral cavity. METHODS: PubMed, Ovid MEDLINE, EMBASE, and PsycInfo databases were searched for observational studies reporting the effect of HPV in oral cavity specific cancers. RESULTS: All 15 included studies presented HPV DNA detection or serum HPV-antibodies, none included mRNA E6/E7 analysis. Cases with oral cancer had 5.36 times (95% CI 3.29-8.72) higher odds of having HPV detected compared to controls. The odds of HPV detection were higher in cell-based (OR 6.93; 95% CI 0.82-58.55) and tissue samples (OR 5.28; 95% CI 3.41-8.18) than blood-based samples (OR 3.36; 95% CI 1.53-7.40). CONCLUSION: When cancer site is clearly differentiated between oropharynx and oral cavity, 12 studies showed strong association between HPV and oral cancer, but the available estimates lack internal validity due to inconsistent measurements, high confounding, and lack of gold standard testing. There is not high-quality evidence to conclude a causal relationship of HPV with oral cancer.

Therapeutic targeting of angiopoietins in tumor angiogenesis and cancer development.

The formation and progression of tumors in humans are linked to the abnormal development of new blood vessels known as neo-angiogenesis. Angiogenesis is a broad word that encompasses endothelial cell migration, proliferation, tube formation, and intussusception, as well as peri-EC recruitment and extracellular matrix formation. Tumor angiogenesis is regulated by angiogenic factors, out of which some of the most potent angiogenic factors such as vascular endothelial growth factor and Angiopoietins (ANGs) in the body are produced by macrophages and other immune cells within the tumor microenvironment. ANGs have a distinct function in tumor angiogenesis and behavior. ANG1, ANG 2, ANG 3, and ANG 4 are the family members of ANG out of which ANG2 has been extensively investigated owing to its unique role in modifying angiogenesis and its tight association with tumor progression, growth, and invasion/metastasis, which makes it an excellent candidate for therapeutic intervention in human malignancies. ANG modulators have demonstrated encouraging outcomes in the treatment of tumor development, either alone or in conjunction with VEGF inhibitors. Future development of more ANG modulators targeting other ANGs is needed. The implication of ANG1, ANG3, and ANG4 as probable therapeutic targets for anti-angiogenesis treatment in tumor development should be also evaluated. The article has described the role of ANG in tumor angiogenesis as well as tumor growth and the treatment strategies modulating ANGs in tumor angiogenesis as demonstrated in clinical studies. The pharmacological modulation of ANGs and ANG-regulated pathways that are responsible for tumor angiogenesis and cancer development should be evaluated for the development of future molecular therapies.

MHC Class I Enables MSCs to Evade NK-Cell-Mediated Cytotoxicity and Exert Immunosuppressive Activity.

Allogeneic mesenchymal stem/stromal cells (MSCs) are frequently used in clinical trials due to their low expression of major histocompatibility complex (MHC) class I and lack of MHC class II. However, the levels of MHC classes I and II in MSCs are increased by inflammatory stimuli, raising concerns over potential adverse effects associated with allogeneic cell therapy. Also, it is unclear how the host immune response to MHC-mismatched MSCs affects the therapeutic efficacy of the cells. Herein, using strategies to manipulate MHC genes in human bone marrow-derived MSCs via the CRISPR-Cas9 system, plasmids, or siRNAs, we found that inhibition of MHC class I-not MHC class II-in MSCs lowered the survival rate of MSCs and their immunosuppressive potency in mice with experimental autoimmune uveoretinitis, specifically by increasing MSC vulnerability to natural killer (NK)-cell-mediated cytotoxicity. A subsequent survey of MSC batches derived from 6 human donors confirmed a significant correlation between MSC survival rate and susceptibility to NK cells with the potency of MSCs to increase MHC class I level upon stimulation. Our overall results demonstrate that MHC class I enables MSCs to evade NK-cell-mediated cytotoxicity and exert immunosuppressive activity.

Design of Silica@Au Hybrid Nanostars for Enhanced SERS and Photothermal Effect.

Core-shell nanostructures of silicon oxide@noble metal have drawn a lot of interest due to their distinctive characteristics and minimal toxicity with remarkable biocompatibility. Due to the unique property of localized surface plasmon resonance (LSPR), plasmonic nanoparticles are being used as surface-enhanced Raman scattering (SERS) based detection of pollutants and photothermal (PT) agents in cancer therapy. Herein, we demonstrate the synthesis of multifunctional silica core - Au nanostars shell (SiO2 @Au NSs) nanostructures using surfactant free aqueous phase method. The SERS performance of the as-synthesized anisotropic core-shell NSs was examined using Rhodamine B (RhB) dye as a Raman probe and resulted in strong enhancement factor of 1.37×106 . Furthermore, SiO2 @Au NSs were also employed for PT killing of breast cancer cells and they exhibited a concentration-dependent increase in the photothermal effect. The SiO2 @Au NSs show remarkable photothermal conversion efficiency of up to 72 % which is unprecedented. As an outcome, our synthesized NIR active SiO2 @Au NSs are of pivotal importance to have their dual applications in SERS enhancement and PT effect.

Association of blood donor characteristics and in vitro haemolysis of packed red blood cell concentrates during storage.

BACKGROUND AND OBJECTIVES: Blood donor variability can affect the storage properties of packed red blood cells (PRBCs). This study aimed to determine the association of donor characteristics with in vitro storage haemolysis of PRBCs. MATERIALS AND METHODS: In the prospective observational study, a total of 109 whole blood donors were enrolled using the purposive sampling method. A pre-donation sample was collected for haemoglobin (Hb) and serum uric acid (UA) levels. PRBC aliquots were tested for potassium, lactate dehydrogenase (LDH), Hb, haematocrit, plasma Hb and haemolysis on days 1, 21 and 35 of storage. The association of these parameters with donor age, sex, donation status, dietary pattern and body mass index was determined. RESULTS: Mean haemolysis was significantly higher in PRBCs from donors with UA levels ≤6 mg/dL than donors with UA levels >6 mg/dL on day 35 of storage (0.22 ± 0.11 vs. 0.18 ± 0.07, p = 0.03). Median plasma Hb (mg/L) was significantly higher in PRBCs from first-time donors on day 21 (586 vs. 509, p = 0.05) and day 35 (1507 vs. 1358, p = 0.02) of storage in comparison to frequent donors. Significantly higher mean potassium (p = 0.04 day 1; p = 0.02 day 21) and median LDH values (p = 0.02 day 1, p = 0.05 day 21) were observed in PRBCs from male donors. A statistically significant positive association was observed between donor UA and LDH levels of PRBCs on day 35 of storage (ß coefficient: 715.52, p-value: 0.003) on multiple regression analysis. CONCLUSION: In vitro haemolysis of PRBCs is affected by blood donor characteristics.

Physiological and psychological stress response of blood donors during the blood donation process.

BACKGROUND AND OBJECTIVES: Blood donation can be a potentially stressful event, leading to the activation of an acute stress response. Knowing and identifying potential stressors could help in optimizing the donation experience. The present study aimed to measure the physiological and psychological stress changes before, during and after blood donation. MATERIALS AND METHODS: Physiological and psychological stress response was assessed in 70 blood donors. To evaluate physiological stress response, pulse rate, respiratory rate, blood pressure (BP), beat-to-beat BP and lead II electrocardiogram were recorded. Baroreflex sensitivity was calculated using the available software. Psychological stress response was assessed using the State-Trait Anxiety Inventory scale. RESULTS: A significant increase in systolic blood pressure, diastolic blood pressure and mean arterial pressure was observed in the pre-donation period (p < 0.001). Among the time-domain parameters, SDSD (standard deviation of differences between adjacent respiratory rate intervals) and RMSSD (root mean square of the successive differences) were significantly lower during the post-donation period (p < 0.005, p < 0.007, respectively). Among the frequency-domain parameters, LF nu (relative power of the low-frequency band in normalized units), HF nu (relative power of the high-frequency band in normalized units) and LF% (relative power of the low-frequency band in percentage) were significantly lower before donation compared to during donation (p < 0.001, p < 0.001 and p < 0.012, respectively). LF nu, LF% and LF/HF ratio were also significantly lower during donation compared to after donation (p < 0.05, p < 0.016 and p < 0.042, respectively). Baroreflex sensitivity was also statistically higher during the pre-donation period. State score was significantly higher among the blood donors during the pre-donation period. CONCLUSION: Physiological and psychological stress is experienced by blood donors during the pre-donation period. A pre-donation informative conversation should be carried out with each blood donor and potential stressors should be identified in each.

Evaluation of chemiluminescence immunoassay as a screening test for syphilis on blood donor samples.

BACKGROUND AND OBJECTIVE: Global re-emergence of syphilis among blood donors necessitates novel diagnostic and prevention approaches that encourage timely intervention. Thus, the present study was planned to evaluate the efficiency of Chemiluminescence immunoassay (CLIA) as a screening test for syphilis. MATERIAL AND METHODS: This prospective cross-sectional observational study was conducted from October 2021 to September 2022. A total of 344 donors were enrolled by purposive sampling method, including additional 16 donors who were reactive by the Rapid plasma reagin test (RPR) during the study period. Data from three screening tests - RPR test, Treponema pallidum haemagglutination assay (TPHA) and CLIA for 360 blood donors were analysed. TPHA was considered the gold standard test. RESULTS: Of the total 360 samples tested, 21 (5.8 %) were reactive by the RPR test. Of these 21 RPR reactive samples, 19 (90.5 %) were reactive by both TPHA and CLIA, while 2 (9.5 %) RPR reactive samples were non-reactive by both TPHA and CLIA. Of the remaining 339 RPR non-reactive samples, 1 (0.3 %) sample was reactive by both TPHA and CLIA, and 1 (0.3 %) was reactive by CLIA alone. CLIA was found to have sensitivity and specificity of 100 % and 99.7 % and positive predictive value (PPV) and negative predictive values (NPV) of 95.2 % and 100 % respectively, while it was 95 %, 99.4 %, 90 %, and 99.7 %, respectively, with the RPR test. CONCLUSION: CLIA was found to have a higher sensitivity, specificity, PPV and NPV than the RPR test. Thus, CLIA can be an acceptable alternative for syphilis screening in blood donors.

Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD. METHODS: A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD. RESULTS: The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies). CONCLUSIONS: This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality.

Utility of reticulocyte haemoglobin content and immature reticulocyte fraction in early diagnosis of latent iron deficiency in whole blood donors.

BACKGROUND AND OBJECTIVES: The present study was planned to assess the clinical utility of reticulocyte haemoglobin content (CHr) and immature reticulocyte fraction (IRF) in the early detection of latent iron deficiency in blood donors. MATERIALS AND METHODS: The prospective longitudinal observational study was conducted using the purposive sampling method. Written informed consent was obtained and donors were allocated into the first-time (FTD) and regular donor (RD) group. The enrolled blood donors (n = 205 in each group) were followed up for two subsequent whole blood donations. Haemoglobin (Hb), CHr, IRF and serum ferritin values were recorded at enrolment and two follow-ups. RESULTS: The sensitivity of CHr in detecting iron-deficient erythropoiesis (serum ferritin values ≤ 26 µg/dl) was 45% and 56.7%, specificity 96.7%, positive predictive value (PPV) 85.6% and 90.8% and negative predictive value (NPV) 80.1% and 78.7%, respectively in FTD and RD cohorts. The sensitivity of IRF was 45.1% and 44.8%, specificity 93.4% and 97.1%, PPV 74.8% and 90.4% and NPV 79.6% and 74.5%, respectively in both the cohorts. The sensitivity of CHr in detecting absent iron stores (serum ferritin values ≤ 15 µg/dl) was 66.2% and 74.4%, specificity 92% and 90.6%, PPV 56.7% and 68.7% and NPV 94.5% and 92.8% among FTD and RD cohort, respectively. The sensitivity of IRF was 72.7% and 65.3%, specificity 90.3% and 94.3%, PPV 54.4% and 76% and NPV 95.4% and 90.8%, respectively in both the cohorts. CONCLUSION: Reticulocyte hemoglobin content and IRF can be used along with complete blood count for early detection of iron deficiency in blood donors using the same blood sample at no extra cost.

Assessment of serum iron stores in regular plateletpheresis donors.

BACKGROUND: Iron deficiency anaemia is the most common nutritional deficiency disorder in the world. Iron deficiency is a potential complication in repeated apheresis donation. The present study was aimed to evaluate serum iron stores in regular plateletpheresis donors. MATERIALS AND METHODS: A total of 60 donors were included in this study, which included 30 regular plateletpheresis donors as cases and controls were 30 first time donors. The donor samples were collected before donation for complete hemogram, transfusion transmissible infections screening and serum iron, total iron binding capacity, percentage saturation of transferrin and serum ferritin. RESULTS: Out of 60 donors, more than half of the donors (56.6 %) had serum ferritin less than 30 ng/mL. Out of these 34 donors, 25 were from the case group and 9 donors in the control group. The median serum ferritin level in cases and controls was 11.86 ng/mL (Interquartile range 4.18-17.34 ng/mL) and 37.92 ng/mL (Interquartile range 27.87-86.20 ng/mL) respectively (p < 0.001). The mean serum iron in cases and controls was 71.23 ± 31.32 µg/dL and 93.53 ± 33.53 µg/dL respectively (p = 0.016). The mean percentage saturation in cases and controls was 20.09 ± 9.31 % and 26.26 ± 9.03 % respectively (p = 0.012). A significant decline in mean serum ferritin with increase in number of annual donations and decrease in donation interval was observed. DISCUSSION: Regular plateletpheresis donation may lead to depletion of iron stores and subclinical iron deficiency. Donors with high platelet count are more likely to exhibit iron deficiency. Periodic serum ferritin estimation in donors participating in regular plateletpheresis donation is warranted.

Impact of multidisciplinary radiologic-pathologic correlation conference for benign image-guided breast biopsies on discordance rates and patient outcomes in a community teaching hospital.

As the assessment for radiologic-pathologic concordance, particularly for benign image-guided breast biopsies, is crucial in the management of patients with imaging abnormalities, many health institutions now conduct multidisciplinary conferences to assess the imaging and pathology findings in patients who had image-guided needle biopsy. We aimed to identify the radiologic-pathologic discordance rates and changes in patient outcomes resulting from the implementation of radiologic-pathologic correlation conferences in a community teaching hospital. Twenty-two (5.6%) out of 393 cases presented were deemed discordant given that the imaging characteristics of the lesions were far too suspicious radiologically to correlate with the benign pathology. Six cases were recommended for further imaging (four had stable lesion on follow- up, one was lost to follow-up and one case eventually had surgical excision which showed atypia); 14 cases for repeat core needle/excisional biopsy (seven had surgical excision with benign histology, five did not have surgery but showed stable lesion on imaging, two were lost to follow-up); one case for close imaging follow-up (lesion ultimately disappeared); the remaining case for second opinion (no follow-up data). The rad-path correlation conference led to a higher level of patient care with significant change in practice across our hospital network.

DNA-Origami-Based Assembly of Au@Ag Nanostar Dimer Nanoantennas for Label-Free Sensing of Pyocyanin.

Early-stage detection of diseases caused by pathogens is a prerequisite for expedient patient care. Due to the limited signal-to-noise ratio, molecular diagnostics needs molecular signal amplification after recognition of the target molecule. In this present study, we demonstrate the design of plasmonically coupled bimetallic Ag coated Au nanostar dimers with controlled nanogap using rectangular DNA origami. We further report the utility of the designed nanostar dimer structures as efficient SERS substrate for the ultrasensitive and label-free detection of the pyocyanin molecule, which is a biomarker of the opportunistic pathogenic bacteria, Pseudomonas aeruginosa. The experimental results showed that the detection limit of pyocyanin with such nanoantenna based biosensor was 335 pM, which is much lower than the clinical range of detection. Thus, fast, sensitive and label-free detection of pyocyanin at ultralow concentration in an infected human body can pave a facile route for early stage warning for severe bacterial infections.

Interfacial Engineering of CuCo2S4/g-C3N4 Hybrid Nanorods for Efficient Oxygen Evolution Reaction.

Altering the morphology of electrochemically active nanostructured materials could fundamentally influence their subsequent catalytic as well as oxygen evolution reaction (OER) performance. Enhanced OER activity for mixed-metal spinel-type sulfide (CuCo2S4) nanorods is generally done by blending the material that has high conductive supports together with those having a high surface volume ratio, for example, graphitic carbon nitrides (g-C3N4). Here, we report a noble-metal-free CuCo2S4 nanorod-based electrocatalyst appropriate for basic OER and neutral media, through a simple one-step thermal decomposition approach from its molecular precursors pyrrolidine dithiocarbamate-copper(II), Cu[PDTC]2, and pyrrolidine dithiocarbamate-cobalt(II), Co[PDTC]2 complexes. Transmission electron microscopy (TEM) images as well as X-ray diffraction (XRD) patterns suggest that as-synthesized CuCo2S4 nanorods are highly crystalline in nature and are connected on the g-C3N4 support. Attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy studies affirm the successful formation of bonds that bridge (Co-N/S-C) at the interface of CuCo2S4 nanorods and g-C3N4. The kinetics of the reaction are expedited, as these bridging bonds function as an electron transport chain, empowering OER electrocatalytically under a low overpotential (242 mV) of a current density at 10 mA cm-2 under basic conditions, resulting in very high durability. Moreover, CuCo2S4/g-C3N4 composite nanorods exhibit a high catalytic activity of OER under a neutral medium at an overpotential of 406 mV and a current density of 10 mA cm-2.

In vitro study of the role of FOXO transcription factors in regulating cigarette smoke extract-induced autophagy.

Cigarette smoking is the chief etiological factor for chronic obstructive pulmonary disease (COPD). Oxidative stress induced by cigarette smoke (CS) causes protein degradation, DNA damage, and cell death, thereby resulting in acute lung injury (ALI). In this regard, autophagy plays a critical role in regulating inflammatory responses by maintaining protein and organelle homeostasis and cellular viability. Expression of autophagy-related proteins (ARPs) is regulated by the fork head box class O (FOXO) transcription factors. In the current study, we examined the role of FOXO family proteins-FOXO1 and FOXO3a-in regulating CS extract (CSE)-induced autophagy. Using human lung adenocarcinoma cells with type II alveolar epithelial characteristics (A549), we observed CSE-mediated downregulation of FOXO3a. In contrast, there was a pronounced increase in the expression of FOXO1 at both the transcriptional and translational levels in the CSE-challenged cells compared with controls. Interestingly, knockdown of FOXO3a heightened the CSE-mediated increase in expression of cytokines/chemokines (IL-6, IL-8, and MCP-1), ARPs, and the FOXO1 transcription factor. Moreover, FOXO1 knockdown rescued CSE-mediated upregulation of ARPs in A549 cells. In addition, using the ROS inhibitor N-acetyl-L-cysteine (NAC), we observed abrogated mRNA expression of several ARPs and production of inflammatory cytokines/chemokines (IL-6, IL-8, MCP-1, and CCL-5) in the CSE-challenged cells suggesting an important role of ROS in regulating CSE-induced autophagy. Chromatin immunoprecipitation of FOXO1 and FOXO3a demonstrated increased binding of the former to promoter regions of autophagy genes- BECLIN1, ATG5, ATG12, ATG16, and LC3 in CSE challenged cells. These findings suggest the role of FOXO1 in regulating the expression of these genes during CSE exposure. Overall, our findings provide evidence for FOXO3a-dependent FOXO1-mediated regulation of autophagy in the CSE-challenged cells. Graphical abstract.