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Abstract Estimating the state of health (SOH) of batteries powering electronic devices in real-time while in use is a necessity. The applicability of most of the existing methods is limited to the datasets that are used to train the models. In this work, we propose a generic method for SOH estimation with much wider applicability. The key problem is the identification of the right feature set which is derived from measurable voltage signals. In this work, relative rise in voltage drop across cell resistance with aging has been used as the feature. A base artificial neural network (ANN) model has been used to map the generic relation between voltage and SOH. The base ANN model has been trained using limited battery data. Blind testing has been done on long cycle in-house data and publicly available datasets. In-house data included both laboratory and on-device data generated using various charge profiles. Transfer learning has been used for public datasets as those batteries have different physical dimensions and cell chemistry. The mean absolute error in SOH estimation is well within 2% for all test cases. The model is robust across scenarios such as cell variability, charge profile difference, and limited variation in temperature.

The Vietnamese indica landrace 'Tetep' is known worldwide for its durable and broad spectrum-resistance to blast. We performed genetic and molecular analyses of leaf blast resistance in a Tetep derived recombinant inbred line 'RIL4' which is resistant to both leaf and neck blast. Phenotypic analysis of segregating F2 progenies suggested that leaf blast resistance in RIL4 was controlled by a dominant gene tentatively designated as Pi-l(t). The gene was mapped to a 2.4 cm region close to the centromere of chromosome 12. The search for the gene content in the equivalent genomic region of reference cv. Nipponbare revealed the presence of five NBS-LRR genes, two of which corresponded to the alleles of Pita and Pi67 genes previously identified from Tetep. The two other genes, LOC_Os12g17090, and LOC_Os12g17490 represented the homologs of stripe rust resistance gene Yr10. The allelic tests with Pita2 and Pi67 lines suggested that the leaf blast resistance gene in RIL4 is either allelic or tightly linked to these genes. The genomic position of the leaf blast resistance gene in RIL4 perfectly coincided with the genomic position of a neck blast resistance gene Pb2 previously identified from this line suggesting that the same gene confers resistance to leaf and neck blast. The present results were discussed in juxtaposition with past studies on the genes of Pita/Pita2 resistance gene complex. [ABSTRACT FROM AUTHOR]

Abstract Patient-reported outcome measures for quality of life (QoL) like the Oswestry-Disability-Index (ODI) are useful for a quick, comprehensive and comparable evaluation of spondylodiscitis treatment. While it is known that even after successful surgical treatment, the QoL of spondylodiscitis patients remains below that of the general population, risk factors for a poor outcome have not been described so far. We did a retrospective post-hoc analysis of 130 surgically treated spondylodiscitis patients from 2008 to 2022. Biographical, clinical und QoL data were prospectively collected before (T0) and one year (T1) after surgery. The primary outcome was QoL at T1. Patients were grouped according to their ODI score at T1 (Group 1: ODI

Abstract Histolocalization and quantification of secondary metabolites established the occurrence of alkaloids, phenols and acetogenins in various plant organs of A. muricata at different stages of plant growth. Annona muricata L. possesses broad assemblage of ethno-pharmaceutical and therapeutic upsides ascribed to biosynthesis of secondary metabolites. Currently, the bioactivity is characterized by the production of acetogenins (ACGs), and also by the biosynthesis of alkaloids, primarily benzylisoquinolines derived from tyrosine and phenolic compounds. As a result of high variability of metabolite production in A. muricata, the present study evaluated the histochemical analysis of various plant parts at different developmental stages of growth. Presences of phytometabolites were determined using in-situ histochemical localization of alkaloids, phenolic compounds and acetogenins, while its estimation employing spectroscopic quantification techniques to understand structure, development, time-course deposition, content and distribution of secondary phytoconstituents. Study revealed distinct presence of secondary metabolites in cells and tissues of all plant organs in various intensities and patterns. Alkaloids and acetogenins occurred mostly in secretory cavities or idioblast cells while sparsely associated with other cells or tissues. Phenolic compounds emerged widely, with no confined distribution patterns occurring in storage cells and tissues. Quantitative analysis revealed highest accumulation of alkaloids, phenols and acetogenins in mature root-barks, mature unripe fruit rind and mature leaf respectively. Secondary metabolites generally occurred in young stages at low concentrations as compared to matured growth stages of plant parts. Such in-situ histochemical and biochemical approach will help in identifying the cells and tissues responsible for synthesis, storage and biological effects of potential secondary metabolites which could be further used for culturing and enhancing its production with biotechnological aids.

Abstract There is an ongoing debate whether a surgical drainage is beneficial to prevent local accumulation of hematoma and to reduce the rate of wound infections, and neurological deficits. Data from the German Spine Society (DWG) registry were filtered for surgically treated spine tumor cases between 2017 and 2021. Cases were categorized into with (Group I) and without (Group II) placement of a surgical drainage. Subgroups were compared for demographic data, type of surgery, experience of the surgeon and postoperative surgical complications. 10,029 cases were included into final analysis (Group I: 3007; Group II: 7022). There was no significant difference between both groups regarding age or gender distribution. Average morbidity of patients was significantly elevated in Group I (p

Abstract Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

Diseases and diagnoses are predominant in the human population. Early diagnosis of etiological agents plays a vital role in the treatment of bacterial infections. Existing standard diagnostic platforms are laborious, time-consuming, and require trained personnel and cost-effective procedure, though they are producing promising results. These shortcomings have led to a thirst for rapid diagnostic procedures. Fluorescence-based diagnosis is one of the efficient rapid diagnostic methods that rely on specific and sensitive bacterial detection. Emerging bio-sensing studies on conducting polymers (CPs) are gaining popularity in medical diagnostics due to their promising properties of high fluorescence efficiency, good light stability, and low cytotoxicity. Poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), is the first identified soluble polymer and model material for understanding the fundamental photophysics of conventional CPs. In this present study, MEH-PPV is used as a fluorescent dye for direct pathogen detection applications by interacting with the microbial cell surface. An optimized concentration of MEH-PPV solution used to confirm the presence of selective bacterial structures. The present study endeavours towards bacterial detection based on the emission from bacteria due to interfacial interaction between polymer and bacterial surface., (© 2024. The Author(s).)

The probabilistic hesitant elements (PHFEs) are a beneficial augmentation to the hesitant fuzzy element (HFE), which is intended to give decision-makers more flexibility in expressing their biases while using hesitant fuzzy information. To extrapolate a more accurate interpretation of the decision documentation, it is sufficient to standardize the organization of the elements in PHFEs without introducing fictional elements. Several processes for unifying and arranging components in PHFEs have been proposed so far, but most of them result in various disadvantages that are critically explored in this paper. The primary objective of this research is to recommend a PHFE unification procedure that avoids the deficiencies of operational practices while maintaining the inherent properties of PHFE probabilities. The prevailing study advances the hypothesis of permutation on PHFEs by suggesting a new sort of PHFS division and subtraction compared with the existing unification procedure. Eventually, the proposed PHFE-unification process will be used in this study, an innovative PHFEs based on the Weighted Aggregated Sum Product Assessment Method-Analytic Hierarchy Process (WASPAS-AHP) perspective for selecting flexible packaging bags after the prohibition on single-use plastics. As a result, we have included the PHFEs-WASPAS in our selection of the most effective fuzzy environment for bio-plastic bags. The ranking results for the suggested PHFEs-MCDM techniques surpassed the existing AHP methods in the research study by providing the best solution. Our solutions offer the best bio-plastic bag alternative strategy for mitigating environmental impacts., (© 2023. The Author(s).)

Recent clinical trials show docetaxel (DTX), given in conjunction with radiation therapy (RT) and androgen suppression, improves survival in high-risk prostate cancer. Addition of gold nanoparticles (GNPs) to this current DTX/RT protocol is expected to further improve therapeutic benefits remarkably. However, the foundation for the triple combination of RT, DTX, and GNPs must be elucidated to ensure quicker facilitation to the clinic. In this study, we explored the use of low concentrations of DTX combined with GNPs in two prostate cancer cell lines in a two-dimensional monolayer, a three-dimensional spheroid, and a mouse xenograft model. When used together, DTX and GNPs induced a nearly identical relative increase in uptake of gold in both the spheroid model and the mouse xenograft, which saw a 130% and 126% increase respectively after 24 h, showcasing the benefit of using spheroids as an in vitro model to better optimize in vivo experiments. Further, the benefits of using low concentrations of DTX combined with GNPs extended for over 72 h, allowing for less frequency in dosing when translating to the clinic. Overall, these results highlight the benefits of using DTX combined with GNPs and lays the groundwork for the translation of the triple combination of RT, GNPs, and DTX to the clinic., (© 2022. The Author(s).)

Immune checkpoint inhibitors (ICI) with anti-PD-1/PD-L1 agents have improved the survival of patients with metastatic non-small cell lung cancer (mNSCLC). Tumor PD-L1 expression is an imperfect biomarker as it does not capture the complex interactions between constituents of the tumor microenvironment (TME). Using multiplex fluorescent immunohistochemistry (mfIHC), we modeled the TME to study the influence of cellular distribution and engagement on response to ICI in mNSCLC. We performed mfIHC on pretreatment tissue from patients with mNSCLC who received ICI. We used primary antibodies against CD3, CD8, CD163, PD-L1, pancytokeratin, and FOXP3; simple and complex phenotyping as well as spatial analyses was performed. We analyzed 68 distinct samples from 52 patients with mNSCLC. Patients were 39-79 years old (median 67); 44% were male and 75% had adenocarcinoma histology. The most used ICI was atezolizumab (48%). The percentage of PD-L1 positive epithelial tumor cells (EC), degree of cytotoxic T lymphocyte (CTL) engagement with EC, and degree of CTL engagement with helper T lymphocytes (HTL) were significantly lower in non-responders versus responders (p = 0.0163, p = 0.0026 and p = 0.0006, respectively). The combination of these 3 characteristics generated the best sensitivity and specificity to predict non-response to ICI and was also associated with shortened overall survival (p = 0.0271). The combination of low CTL engagement with EC and HTL along with low expression of EC PD-L1 represents a state of impaired endogenous immune reactivity. Together, they more precisely identified non-responders to ICI compared to PD-L1 alone and illustrate the importance of cellular interactions in the TME., (© 2022. The Author(s).)

Herein, we report various physico-chemical approaches to probe the nature of the interface between few layers graphene (FLG) and carboxylated nitrile rubber (XNBR) nanocomposites prepared through efficient blending of XNBR latex with an aqueous dispersion of FLG. The extent of physical interaction between FLG and XNBR was investigated using Lorentz-Park and Cunneen-Russell models. The chemical interface between FLG and sulfur crosslinked XNBR was studied using model reactions between sulfur and graphene in presence of zinc 2-mercaptobenzothiazole (ZMBT). We propose that an edge sulfurated FLG is formed, which could chemically bond with XNBR during the vulcanization process. Density Functional Theory (DFT) was employed to unravel the mechanistic insights, which support this hypothesis and suggest a kinetically favorable sulfuration of both XNBR and FLG. The formation of a chemical bond between edge-FLG and XNBR through the proposed intermediacy of sulfurated FLG leads to the observed improvement in mechanical properties of the nanocomposites., (© 2022. The Author(s).)

Sepsis is a life-threatening condition and understanding the disease pathophysiology through the use of host immune response biomarkers is critical for patient stratification. Lack of accurate sepsis endotyping impedes clinicians from making timely decisions alongside insufficiencies in appropriate sepsis management. This work aims to demonstrate the potential feasibility of a data-driven validation model for supporting clinical decisions to predict sepsis host-immune response. Herein, we used a machine learning approach to determine the predictive potential of identifying sepsis host immune response for patient stratification by combining multiple biomarker measurements from a single plasma sample. Results were obtained using the following cytokines and chemokines IL-6, IL-8, IL-10, IP-10 and TRAIL where the test dataset was 70%. Supervised machine learning algorithm naïve Bayes and decision tree algorithm showed good accuracy of 96.64% and 94.64%. These promising findings indicate the proposed AI approach could be a valuable testing resource for promoting clinical decision making., (© 2021. The Author(s).)

Blue emission giving nanoscale molecular clusters of Oleylamine-Acetone system was formed by an aging assisted hydrogen bond formation between the interacting molecular systems, at room temperature. The as-formed nanoscale molecular clusters were found to be self-assembled into flower-like aggregates and shifted the emission wavelength to red colour depicting an exciton delocalization in the aggregate system. Interestingly aging process has also produced imine type binding between Oleylamine and Acetone due to the condensation reaction. The experimental conditions and formation mechanism of hydrogen bond assisted Oleylamine-Acetone molecular aggregates and imine bond assisted Oleylamine-Acetone is elaborated in this paper in a systematic experimental approach with suitable theory. Finally we have introduced this Acetone assisted aging process in In 2 S 3 QD system prepared with Oleylamine as functional molecules. It was found that the aging process has detached Oleylamine from QD surface and as a consequence In 2 S 3 QD embedded Oleylamine-Acetone aggregates was obtained. When this In 2 S 3 QD embedded molecular cluster system was used as an active layer in a photo conductor device then a maximum photo current value of the order of milli Ampere was obtained. The surfactant molecules normally inhibit the charge transport between QD systems and as a result it is always problematic to have the functional molecules in the QD based transport devices. Our approach has a solution to this problem and the present paper discusses the outcome of the results in detail.

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14 + cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14 + cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14 + cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14 + monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14 + monocytes, which may affect ubiquitination, histone methylation and autophagy.

5-Fluorouracil (5-FU) is a standard treatment option for colorectal cancer (CRC) but its rapid metabolism and systemic instability (short half-life) has hindered its therapeutic efficacy. The objective of this study was to develop a novel drug delivery system, solid lipid nanoparticle (SLN), capable of delivering high payload of 5-FU to treat CRC. The rational was to improve 5FU-nanocarrier compatibility and therapeutic efficacy. The SLN-loaded 5-FU was developed by utilizing a Strategic and unique Method to Advance and Refine the Treatment (SMART) of CRC through hot and cold homogenization approach. The SLN was made of unique PEGylated lipids and combination of the surfactants. Cytotoxicity studies, clonogenic assay, flow cytometry and confocal imaging were conducted to evaluate the effectiveness and cellular uptake of 5FU-SLN 4 in HCT-116 cancer cells. Pharmacokinetic (PK) parameters and receptor expressions were determined while tumor efficacy studies were conducted on mouse bearing subcutaneous HCT-116 cancer. Among the all the formulations, 5FU-SLN 4 was the most effective with particle size of was 263 ± 3 nm, zeta potential was 0.1 ± 0.02 and entrapment efficiency of 81 ± 10%. The IC 50 value of 5FU-SLN 4 (7.4 ± 0.02 µM) was 2.3 fold low compared with 5-FU (17.7 ± 0.03 µM). For tumor efficacy studies, 5FU-SLN 4 significantly inhibited tumor growth in comparison to 5-FU while area-under plasma concentration-time curve (AUC) of 5FU-SLN 4 was 3.6 fold high compared with 5-FU. HER2 receptors expression were markedly reduced in 5-FU-SLN 4 treated mice compared with 5FU and liver and kidney tissues showed no toxicity at dose of 20 mg/kg. 5FU-SLN 4 was highly cytotoxic against HCT-116 cells and significantly inhibited subcutaneous tumor growth in mice compared with 5-FU. This emphasizes the significance of developing a smart nano-delivery system to optimize the delivery efficiency of anticancer drugs to tumors.

Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.

This paper aims to examine the effect of cellulose nanocrystals (CNCs) derived from oil palm empty fruit bunch fiber (EFB) incorporating cement mortar on its structural performances. Cellulose nanocrystals (CNCs) were extracted from α-cellulose extracted from EFB using an acid hydrolysis process with a concentration of acid used was 64% w/v under the temperature of 45 °C for 60 minutes. The Cellulose nanocrystals (CNCs) were mixed into the cement mortar ranging from 0 to 0.8% w/w and its mechanical properties were determined. The developed CNCs mortar was characterized for their compressive and flexural properties as well as microstructure. The influence of CNCs concentration, curing method, dispersion of CNCs on mortar's mechanical performance was thoroughly examined to find out the optimum condition. Overall results revealed that an addition of 0.4% cellulose nanocrystals has shown to increase the compressive and flexural strength to 46% and 20%, respectively cured under the wrapping method. The hydration of cementitious composites also improved significantly with the addition of CNCs by the formation of highly crystalline of portlandite observed under the XRD test. This present work demonstrates the importance of palm oil empty fruit bunch waste as a sustainable resource of cellulose nanocrystals admixture to achieve structural strength of cement mortar and promotes green technologies in construction.

External cephalic version (ECV) is associated with a moderate degree of pain. Virtual reality (VR) is a technology that has shown promise in offering procedural analgesia. We undertook a clinical pilot to assess the viability of VR to reduce pain during ECV. In an open randomised controlled trial (RCT), we randomised 50 women to either VR or standard care each (25 per group). Women receiving VR were administered VR content (Skylights) via a headset. Pre- and post-procedural measures of pain, anxiety, device experience and vital signs were measured. There were no significant differences between groups (VR/no VR) in pain scores (60.68 vs 49.76; p = 0.2), ECV success rates (80% vs 76%; p = 0.7) or anxiety levels. The women receiving VR had a significantly higher anticipation of pain pre-procedurally (70.0 vs 50.0; p = 0.03). 20 (80%) of the VR women indicated that they would use VR again and 22 (88%) indicated they would recommend it to a friend having ECV. There were no significant differences between groups for side effects encountered or changes in vital signs. We have shown that using VR during ECV is feasible and appears safe. Our results inform the design of future RCTs.

In this study, the new material Fe 3 O 4 @BTCA has been synthesized by immobilization of 1,2,4,5-Benzenetetracarboxylic acid (BTCA) on the surface of Fe 3 O 4 NPs, obtained by co-precipitation of FeCl 3 .6H 2 O and FeCl 2 .4H 2 O in the basic conditions. Characterization by P-XRD, FE-SEM, and TEM confirm Fe 3 O 4 has a spherical crystalline structure with an average diameter of 15 nm, which after functionalization with BTCA, increases to 20 nm. Functionalization also enhances the surface area and surface charge of the material, confirmed by BET and zeta potential analyses, respectively. The dye adsorption capacity of Fe 3 O 4 @BTCA has been investigated for three common dyes; Congo red (C.R), Methylene blue (M.B), and Crystal violet (C.V). The adsorption studies show that the material rapidly and selectively adsorbs C.R dye with very high adsorption capacity (630 mg/g), which is attributed to strong H-bonding ability of BTCA with C.R dye as indicated by adsorption mechanism study. The material also shows excellent recyclability without any considerable loss of adsorption capacity. Adsorption isotherm and kinetic studies suggest that the adsorption occurs by the Langmuir adsorption model following pseudo-second-order adsorption kinetics.

The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known. Here, we used immunohistochemical (IHC) staining and 7-color multiplex staining to evaluate CD8 (cluster of differentiation 8), CD68, PD-L1 (programmed death-ligand 1), CD34, FAP (fibroblast activation protein), and cytokeratin in 220 tissue cores from 26 high-grade serous ovarian cancer samples. Comparisons were drawn between a larger tumor specimen and smaller core biopsies based on number and location (central tumor vs. peripheral tumor) of biopsies. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies. Moreover, this correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. These findings could have a substantial impact on longitudinal assessment for detection of biomarkers in clinical trials.

Recent reports have shown that very high dose rate radiation (35-100 Gy/second) referred to as FLASH tends to spare the normal tissues while retaining the therapeutic effect on tumor. We undertook a series of experiments to assess if ultra-high dose rate of 35 Gy/second can spare the immune system in models of radiation induced lymphopenia. We compared the tumoricidal potency of ultra-high dose rate and conventional dose rate radiation using a classical clonogenic assay in murine pancreatic cancer cell lines. We also assessed the lymphocyte sparing potential in cardiac and splenic irradiation models of lymphopenia and assessed the severity of radiation-induced gastrointestinal toxicity triggered by the two dose rate regimes in vivo. Ultra-high dose rate irradiation more potently induces clonogenic cell death than conventional dose rate irradiation with a dose enhancement factor at 10% survival (DEF 10 ) of 1.310 and 1.365 for KPC and Panc02 cell lines, respectively. Ultra-high dose rate was equally potent in depleting CD3, CD4, CD8, and CD19 lymphocyte populations in both cardiac and splenic irradiation models of lymphopenia. Radiation-induced gastrointestinal toxicity was more pronounced and mouse survival (7 days vs. 15 days, p = 0.0001) was inferior in the ultra-high dose rate arm compared to conventional dose rate arm. These results suggest that, contrary to published data in other models of radiation-induced acute and chronic toxicity, dose rates of 35 Gy/s do not protect mice from the detrimental side effects of irradiation in our models of cardiac and splenic radiation-induced lymphopenia or gastrointestinal mucosal injury.

Metal nanoparticles have significant interaction cross-sections with electromagnetic waves due to their large surface area-to-volume ratio, which can be exploited in cancer radiotherapy to locally enhance the radiation dose deposition in tumors. We developed a new type of silver nanoparticle composite, PEGylated graphene quantum dot (GQD)-decorated Silver Nanoprisms (pGAgNPs), that show excellent in vitro intracellular uptake and radiosensitization in radiation-sensitive HCT116 and relatively radiation-resistant HT29 colorectal cancer cells. Furthermore, following biodistribution analysis of intravenously injected nanoparticles in nude mice bearing HCT116 tumors radiosensitization was evaluated. Treatment with nanoparticles and a single radiation dose of 10 Gy significantly reduces the growth of colorectal tumors and increases the survival time as compared to treatment with radiation only. Our findings suggest that these novel nanoparticles offer a promising paradigm for enhancing colorectal cancer radiation therapy efficacy.

The absence of proper nanoscale experimental techniques to investigate the dose-enhancing properties of gold nanoparticles (GNPs) interacting with radiation has prompted the development of various Monte Carlo (MC)-based nanodosimetry techniques that generally require considerable computational knowledge, time and specific tools/platforms. Thus, this study investigated a hybrid computational framework, based on the electron dose point kernel (DPK) method, by combining Geant4 MC simulations with an analytical approach. This hybrid framework was applied to estimate the dose distributions around GNPs due to the secondary electrons emitted from GNPs irradiated by various photon sources. Specifically, the equivalent path length approximation was used to rescale the homogeneous DPKs for heterogeneous GNPs embedded in water/tissue. Compared with Geant4 simulations, the hybrid framework halved calculation time while utilizing fewer computer resources, and also resulted in mean discrepancies less than 20 and 5% for Yb-169 and 6 MV photon irradiation, respectively. Its appropriateness and computational efficiency in handling more complex cases were also demonstrated using an example derived from a transmission electron microscopy image of a cancer cell containing internalized GNPs. Overall, the currently proposed hybrid computational framework can be a practical alternative to full-fledged MC simulations, benefiting a wide range of GNP- and radiation-related applications.

Superantigens (SAgs) play a major role in the pathogenesis of Staphylococcus aureus and are associated with several diseases, including food poisoning, bacterial arthritis, and toxic shock syndrome. Monoclonal antibodies to these SAgs, primarily TSST-1, SEB and SEA have been shown to provide protection in animal studies and to reduce clinical severity in bacteremic patients. Here we quantify the pre-existing antibodies against SAgs in many human plasma and IVIG samples and demonstrate that in a major portion of the population these antibody titers are suboptimal and IVIG therapy only incrementally elevates the anti-SAg titers. Our in vitro neutralization studies show that a combination of antibodies against SEA, SEB,and TSST-1 can provide broad neutralization of staphylococcal SAgs. We report a single fusion protein (TBA 225 ) consisting of the toxoid versions of TSST-1, SEB and SEA and demonstrate its immunogenicity and protective efficacy in a mouse model of toxic shock. Antibodies raised against this fusion vaccine provide broad neutralization of purified SAgs and culture supernatants of multiple clinically relevant S. aureus strains. Our data strongly supports the use of this fusion protein as a component of an anti-virulence based multivalent toxoid vaccine against S. aureus disease.

Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method's dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM's low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries.

Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.

The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL's immunomodulatory function. HDL were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) (n = 13), and diabetic hemodialysis (HD) patients (n = 24). Concentrations of HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycovariations of ApoC-III, A1AT, and A2HSG were measured. Secretion of interleukin 6 (IL-6) in lipopolysaccharide-stimulated monocytes was used as a prototypical assay of HDL's immunomodulatory capacity. HDL from HD patients were enriched in SAA, LBP, ApoC-III, di-sialylated ApoC-III (ApoC-III 2 ) and desialylated A2HSG. HDL that increased IL-6 secretion were enriched in ApoC-III, di-sialylated glycans at multiple A1AT glycosylation sites and desialylated A2HSG, and depleted in mono-sialylated ApoC-III (ApoC-III 1 ). Subgroup analysis on HD patients who experienced an infectious hospitalization event within 60 days (HD+) (n = 12), vs. those with no event (HD-) (n = 12) showed that HDL from HD+ patients were enriched in SAA but had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including the site-specific glycosylation, differentiate between clinical groups, correlate with HDL's immunomodulatory capacity, and may be predictive of HDL's ability to protect from infection.

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mother's HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3'-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.

Leaf elongation rate (LER) is an important factor controlling plant growth and productivity. The objective of this study was to determine whether genetic variation in LER for a fast-growing ('K-31'), and a dwarf cultivar ('Bonsai') of tall fescue (Festuca arundinacea) and gibberellic acid (GA) regulation of LER were associated with differential expression of cell-expansion genes. Plants were treated with GA3, trinexapac-ethyl (TE) (GA inhibitor), or water (untreated control) in a hydroponic system. LER of 'K-31' was 63% greater than that of 'Bonsai', which corresponded with 32% higher endogenous GA4 content in leaf and greater cell elongation and production rates under the untreated control condition. Exogenous application of GA3 significantly enhanced LER while TE treatment inhibited leaf elongation due to GA3-stimulation or TE-inhibition of cell elongation and production rate in leaves for both cultivars. Real-time quantitative polymerase chain reaction analysis revealed that three α-expansins, one β-expansin, and three xyloglucan endotransglycosylase (XET) genes were associated with GA-stimulation of leaf elongation, of which, the differential expression of EXPA4 and EXPA7 was related to the genotypic variation in LER of two cultivars. Those differentially-expressed expansin and XET genes could play major roles in genetic variation and GA-regulated leaf elongation in tall fescue.

X-ray fluorescence computed tomography (XFCT) is a technique that can identify, quantify, and locate elements within objects by detecting x-ray fluorescence (characteristic x-rays) stimulated by an excitation source, typically derived from a synchrotron. However, the use of a synchrotron limits practicality and accessibility of XFCT for routine biomedical imaging applications. Therefore, we have developed the ability to perform XFCT on a benchtop setting with ordinary polychromatic x-ray sources. Here, we report our postmortem study that demonstrates the use of benchtop XFCT to accurately image the distribution of gold nanoparticles (GNPs) injected into a tumor-bearing mouse. The distribution of GNPs as determined by benchtop XFCT was validated using inductively coupled plasma mass spectrometry. This investigation shows drastically enhanced sensitivity and specificity of GNP detection and quantification with benchtop XFCT, up to two orders of magnitude better than conventional x-ray CT. The results also reaffirm the unique capabilities of benchtop XFCT for simultaneous determination of the spatial distribution and concentration of nonradioactive metallic probes, such as GNPs, within the context of small animal imaging. Overall, this investigation identifies a clear path toward in vivo molecular imaging using benchtop XFCT techniques in conjunction with GNPs and other metallic probes.

Serotonergic neurons have been implicated in a broad range of processes, but the principles underlying their effects remain a puzzle. Here, we ask how these neurons influence the tendency of larval zebrafish to swim in the light and avoid regions of darkness. Pharmacological inhibition of serotonin synthesis reduces dark avoidance, indicating an involvement of this neuromodulator. Calcium imaging of tph2-expressing cells demonstrates that a rostral subset of dorsal raphe serotonergic neurons fire continuously while the animal is in darkness, but are inhibited in the light. Optogenetic manipulation of tph2 neurons by channelrhodopsin or halorhodopsin expression modifies preference, confirming a role for these neurons. In particular, these results suggest that fish prefer swimming in conditions that elicits lower activity in tph2 serotonergic neurons in the rostral raphe.

Nanomaterial-based photoluminescence (PL) diagnostic devices offer fast and highly sensitive detection of pesticides, DNA, and toxic agents. Here we report a label-free PL genosensor for sensitive detection of Vibrio cholerae that is based on a DNA hybridization strategy utilizing nanostructured magnesium oxide (nMgO; size >30 nm) particles. The morphology and size of the synthesized nMgO were determined by transmission electron microscopic (TEM) studies. The probe DNA (pDNA) was conjugated with nMgO and characterized by X-ray photoelectron and Fourier transform infrared spectroscopic techniques. The target complementary genomic DNA (cDNA) isolated from clinical samples of V. cholerae was subjected to DNA hybridization studies using the pDNA-nMgO complex and detection of the cDNA was accomplished by measuring changes in PL intensity. The PL peak intensity measured at 700 nm (red emission) increases with the increase in cDNA concentration. A linear range of response in the developed PL genosensor was observed from 100 to 500 ng/μL with a sensitivity of 1.306 emi/ng, detection limit of 3.133 ng/μL and a regression coefficient (R(2)) of 0.987. These results show that this ultrasensitive PL genosensor has the potential for applications in the clinical diagnosis of cholera.