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Abstract Constructed wetlands (CWs) are engineered environments designed to utilise natural processes to treat urban or industrial wastewater, with the core driver of the bioremediation process provided by the microorganisms present within. This study isolated 32 bacterial strains from sediment across the Sardar Bherry CW to find candidates with remediation properties and to understand how the physiochemical gradient from wastewater input influences the functional properties of the bacteria present. Bacterial isolates recovered closer to the wastewater effluence were more likely to be pathogenic, with increased haemolytic activity, causing high rates of fish mortality. In contrast, isolates recovered further from the wastewater source were observed to be non-pathogenic and have increased inhibitory effect against pathogenic strains. Extracellular proteins extracted from non-pathogenic isolates also appeared to be effective at inhibiting the growth of pathogenic bacteria, including multidrug resistant strains. Non-pathogenic isolates recovered across all sampling sites displayed the ability to reduce high levels of ammonia in solution during laboratory testing. Antibiogram assays of the recovered isolates showed a relatively high rate of multidrug resistant or marginally resistant bacteria across all sampling sites, highlighting a potential limitation within the CW bioremediation process in mitigating antibiotic resistant strains. This isolate based study provided an avenue to understand the influence of spatial succession from wastewater effluence on bacterial characteristics, as well as obtain candidates that can be further investigated for optimisation in bioremediation efforts. The cultured isolates can supplement future environmental sequencing studies by providing wet lab specimens to compare (meta)genomic information discovered within the CW ecosystem.

We report on a new experimental method based on initial-state radiation (ISR) in e–p scattering, which exploits the radiative tail of the elastic peak to study the properties of electromagnetic processes and to extract the proton charge form factor (GEp) at extremely small Q2. The ISR technique was implemented in an experiment at the three-spectrometer facility of the Mainz Microtron (MAMI). This led to a precise validation of radiative corrections far away from elastic line and provided first measurements of GEp for 0.001≤Q2≤0.004(GeV/c)2. Keywords: Initial state radiation, Proton, Form factor, Radiative corrections

Aim Orthodontic treatment relies heavily on the mechanical properties and surface characteristics of archwire materials to achieve optimal outcomes. This study aimed to comprehensively evaluate the mechanical properties, including tensile strength, yield strength, and modulus of elasticity, as well as the surface characteristics, such as surface roughness and frictional properties, of different archwire materials. Methods Four types of archwire materials, stainless steel, nickel-titanium (NiTi), beta-titanium, and esthetic archwires, were subjected to mechanical testing and surface analysis, with 31 in each group. Tensile testing was conducted to determine the maximum tensile strength, yield strength, and elastic modulus of each material. Surface roughness analysis was performed using profilometry techniques, and frictional properties were evaluated using an orthodontic friction testing apparatus. Results Stainless steel exhibited the highest tensile strength (900 N), followed by beta-titanium (850 N), NiTi (800 N), and esthetic archwire (750 N). Stainless steel also demonstrated the highest yield strength (780 N), followed by beta-titanium (740 N), NiTi (710 N), and esthetic archwire (650 N). The modulus of elasticity was the highest for stainless steel (200 GPa), followed by beta-titanium (170 GPa), NiTi (150 GPa), and esthetic archwires (120 GPa). Surface roughness was lowest in stainless steel archwires (mean Ra value of 0.25 µm), leading to reduced frictional resistance, whereas esthetic archwires exhibited the highest surface roughness (mean Ra value of 0.40 µm) and frictional forces. Significant differences in the mechanical properties and surface characteristics were observed among the materials (p < 0.05). Conclusions The choice of archwire material significantly influences orthodontic treatment outcomes by affecting the efficiency and effectiveness of tooth movement. Stainless steel and beta-titanium wires are ideal for high-stress applications, providing the robust mechanical strength necessary for complex movements. In contrast, NiTi wires, with their superelasticity, offer consistent and gentle forces, enhancing patient comfort and accelerating the alignment phase. Esthetic archwires, while visually appealing, often compromise mechanical performance, potentially prolonging treatment duration., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, V S et al.)

Cavity-electromechanical systems are extensively used for sensing and controlling the vibrations of mechanical resonators down to their quantum limit. The nonlinear radiation-pressure interaction in these systems could result in an unstable response of the mechanical resonator showing features such as frequency-combs, period-doubling bifurcations and chaos. However, due to weak light-matter interaction, typically these effects appear at very high driving strengths. By using polariton modes formed by a strongly coupled flux-tunable transmon and a microwave cavity, here we demonstrate an electromechanical device and achieve a single-photon coupling rate g 0 / 2 π of 160 kHz, which is nearly 4% of the mechanical frequency ω m . Due to large g 0 /ω m ratio, the device shows an unstable mechanical response resulting in frequency combs in sub-single photon limit. We systematically investigate the boundary of the unstable response and identify two important regimes governed by the optomechanical backaction and the nonlinearity of the electromagnetic mode. Such an improvement in the single-photon coupling rate and the observations of microwave frequency combs at single-photon levels may have applications in the quantum control of the motional states and critical parametric sensing. Our experiments strongly suggest the requirement of newer approaches to understand instabilities., (© 2024. The Author(s).)

In recent years biochar (BC) has gained importance for its huge carbon (C) sequestration potential and positive effects on various soil functions. However, there is a paucity of information on the long-term impact of BC on the priming effect and nutrient availability in soil with different properties. This study investigates the effects of BC prepared from rice husk (RBC4, RBC6), sugarcane bagasse (SBC4, SBC6) and mustard stalk (MBC4, MBC6) at 400 and 600 °C on soil C priming and nitrogen (N), phosphorus (P), and potassium (K) availability in an Alfisol, Inceptisol, and Mollisol. BC properties were analyzed, and its decomposition in three soil orders was studied for 290 days in an incubation experiment. Post-incubation, available N, P, and K in soil were estimated. CO 2 evolution from BC and soil alone was also studied to determine the direction of priming effect on native soil C. Increasing pyrolysis temperature enhanced pH and EC of most of the BC. The pyrolysis temperature did not show clear trend with respect to priming effect and nutrient availability across feedstock and soil type. MBC6 increased C mineralization in all the soil orders while RBC6 in Alfisol and SBC6 in both Inceptisol and Mollisol demonstrated high negative priming, making them potential amendments for preserving native soil C. Most of the BC showed negative priming of native SOC in long run (290 days) but all these BC enhanced the available N, P, and K in soil. SBC4 enhanced N availability in Alfisol and Inceptisol, RBC4 improved N and P availability in Mollisol and P in Alfisol and MBC6 increased K availability in all the soils. Thus, based on management goals, tailored BC or blending different BC can efficiently improve C sequestration and boost soil fertility., (© 2024. The Author(s).)

Objectives: Cervical cancer is increasing worldwide and is becoming resistant to the existing drugs in clinical practice. Here, ethanolic extract of fruit body of Pleurotus florida was evaluated as antioxidant, anticancer agent against HeLa cell lines and anti-tumor against cervical cancer in mice model., Methods: Fruit bodies of P. florida in 90% ethanol, and the P. florida ethanolic extract (PFEE) was subsequently investigated for its antioxidant content and activity, anticancer properties against the cervical cancer cell line, HeLa, and antitumor activity against HeLa implanted mice., Results: The antioxidant activity bioassay showed that the IC 50 of PFEE was 41.17 ± 1.42a μg/ml. The cytotoxicity assay revealed that PFEE caused inhibition of cell proliferation. At the highest dose (1,250 μg/ml) after 24 h, 48 h, or 72 h of treatment, the percentages of cell growth inhibition were 75.22%, 77.77%, and 84.65%, respectively. It revealed that PFEE-treated cells became rounded and the nuclei became fragmented. PFEE induced intracellular generation of reactive oxygen species and reduced the mitochondrial membrane potential. PFEE also led to an up regulation of the apoptotic genes for caspases-3, -9, and Bax, whereas Bcl-2 gene was down regulated, and it also promoted the expression of p53. Cell cycle analysis revealed that cell cycle was arrested at the G 0 /G 1 checkpoint. PFEE suppressed metastasis and colonization. At a dosage of PFEE of 50 mg/kg of body weight, a 66.72% reduction in the size of tumors and an 87.44% reduction in the tumor weight were observed in mice., Conclusions: It has demonstrated that PFEE is a highly potent anti-cervical cancer agent in vitro and in vivo ., (Copyright: © International Journal of Health Sciences.)

Studies to date have not resolved how diverse transcriptional programs contribute to the intratumoral heterogeneity of small cell lung carcinoma (SCLC), an aggressive tumor associated with a dismal prognosis. Here, we identify distinct and commutable transcriptional states that confer discrete functional attributes in individual SCLC tumors. We combine an integrative approach comprising the transcriptomes of 52,975 single cells, high-resolution measurement of cell state dynamics at the single-cell level, and functional and correlative studies using treatment naïve xenografts with associated clinical outcomes. We show that individual SCLC tumors contain distinctive proportions of stable cellular states that are governed by bidirectional cell state transitions. Using drugs that target the epigenome, we reconfigure tumor state composition in part by altering individual state transition rates. Our results reveal new insights into how single-cell transition behaviors promote cell state equilibrium in SCLC and suggest that facile plasticity underlies its resistance to therapy and lethality.

Food samples are routinely screened for food-contaminating beetles (i.e., pantry beetles) due to their adverse impact on the economy, environment, public health and safety. If found, their remains are subsequently analyzed to identify the species responsible for the contamination; each species poses different levels of risk, requiring different regulatory and management steps. At present, this identification is done through manual microscopic examination since each species of beetle has a unique pattern on its elytra (hardened forewing). Our study sought to automate the pattern recognition process through machine learning. Such automation will enable more efficient identification of pantry beetle species and could potentially be scaled up and implemented across various analysis centers in a consistent manner. In our earlier studies, we demonstrated that automated species identification of pantry beetles is feasible through elytral pattern recognition. Due to poor image quality, however, we failed to achieve prediction accuracies of more than 80%. Subsequently, we modified the traditional imaging technique, allowing us to acquire high-quality elytral images. In this study, we explored whether high-quality elytral images can truly achieve near-perfect prediction accuracies for 27 different species of pantry beetles. To test this hypothesis, we developed a convolutional neural network (CNN) model and compared performance between two different image sets for various pantry beetles. Our study indicates improved image quality indeed leads to better prediction accuracy; however, it was not the only requirement for achieving good accuracy. Also required are many high-quality images, especially for species with a high number of variations in their elytral patterns. The current study provided a direction toward achieving our ultimate goal of automated species identification through elytral pattern recognition., Competing Interests: Author CF was employed by company HK3 Lab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bisgin, Bera, Wu, Ding, Bisgin, Liu, Pava-Ripoll, Barnes, Campbell, Vyas, Furlanello, Tong and Xu.)

Probiotics with antimicrobial activity are gaining interest as a topic in the research field. Urinary tract infections (UTIs), acquired in the hospital or the community, are among the most prevalent infections. The emergence of multidrug resistance (MDR) uro-pathogens has made the current situation more critical in terms of global public health. To face this situation, in this study, Lactobacillus fermentum TIU19 (L. fermentum TIU19) was isolated and characterized as a new probiotic strain of the rice-based fermented beverage Haria. Subsequently, we also investigated its application as a biological agent that inhibits the growth of multidrug-resistant uro-pathogens, Escherichia coli, and Enterococcus faecalis . The results showed that, the isolated strain L . fermentum TIU19 was sensitive to all antibiotics tested except vancomycin and was devoid of virulence factors, such as haemolytic and gelatinase activities. Therefore, it may be considered safe for public health. It has many probiotic properties, such as survival in simulated gastrointestinal fluid, antioxidant activity, β-galactosidase producing ability, high cell surface hydrophobicity, adhesion ability to epithelial cells, and strong biofilm producer. The growth inhibitory and antibiofilm activities were shown against two uro-pathogens. All these results suggest that L. fermentum TIU19 can be explored as a potential probiotic with antagonistic activity against MDR uro-pathogenic E. coli and E. faecalis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that would have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The human transferrin receptor (TFR) is overexpressed in most breast cancers, including preneoplastic ductal carcinoma in situ (DCIS). HB21(Fv)-PE40 is a single-chain immunotoxin (IT) engineered by fusing the variable region of a monoclonal antibody (HB21) against a TFR with a 40 kDa fragment of Pseudomonas exotoxin (PE). In humans, the administration of other TFR-targeted immunotoxins intrathecally led to inflammation and vascular leakage. We proposed that for treatment of DCIS, intraductal (i.duc) injection of HB21(Fv)-PE40 could avoid systemic toxicity while retaining its potent antitumor effects on visible and occult tumors in the entire ductal tree. Pharmacokinetic studies in mice showed that, in contrast to intravenous injection, IT was undetectable by enzyme-linked immunosorbent assay in blood following i.duc injection of up to 3.0 μg HB21(Fv)-PE40. We demonstrated the antitumor efficacy of HB21(Fv)-PE40 in two mammary-in-duct (MIND) models, MCF7 and SUM225, grown in NOD/SCID/gamma mice. Tumors were undetectable by In Vivo Imaging System (IVIS) imaging in intraductally treated mice within 1 wk of initiation of the regimen (IT once weekly/3 wk, 1.5 μg/teat). MCF7 tumor-bearing mice remained tumor free for up to 60 d of observation with i.duc IT, whereas the HB21 antibody alone or intraperitoneal IT treatment had minimal/no antitumor effects. These and similar findings in the SUM225 MIND model were substantiated by analysis of mammary gland whole mounts, histology, and immunohistochemistry for the proteins Ki67, CD31, CD71 (TFR), and Ku80. This study provides a strong preclinical foundation for conducting feasibility and safety trials in patients with stage 0 breast cancer.

Background and Aim: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel., Methods: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles., Results: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment ( P > 0.05) and between the responder and non-responder categories ( P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences ( P = 0.001) in the neoadjuvant chemotherapy group., Conclusion: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment., Relevance for Patients: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies., Competing Interests: The authors declare no conflict of interest., (Copyright: © Whioce Publishing Pte. Ltd.)

Loss of mitosis regulation is a common feature of malignant cells that leads to aberrant cell division with inaccurate chromosome segregation. The mitotic checkpoint is responsible for faithful transmission of genetic material to the progeny. Defects in this checkpoint, such as mutations and changes in gene expression, lead to abnormal chromosome content or aneuploidy that may facilitate cancer development. Furthermore, a defective checkpoint response is indicated in the development of drug resistance to microtubule poisons that are used in treatment of various blood and solid cancers for several decades. Mitotic slippage and senescence are important cell fates that occur even with an active mitotic checkpoint and are held responsible for the resistance. However, contradictory findings in both the scenarios of carcinogenesis and drug resistance have aroused questions on whether mitotic checkpoint defects are truly responsible for these dismal outcomes. Here, we discuss the possible contribution of the faulty checkpoint signaling in cancer development and drug resistance, followed by the latest research on this pathway for better outcomes in cancer treatment.

Identifying the exact species of pantry beetle responsible for food contamination, is imperative in assessing the risks associated with contamination scenarios. Each beetle species is known to have unique patterns on their hardened forewings (known as elytra) through which they can be identified. Currently, this is done through manual microanalysis of the insect or their fragments in contaminated food samples. We envision that the use of automated pattern analysis would expedite and scale up the identification process. However, such automation would require images to be captured in a consistent manner, thereby enabling the creation of large repositories of high-quality images. Presently, there is no standard imaging technique for capturing images of beetle elytra, which consequently means, there is no standard method of beetle species identification through elytral pattern analysis. This deficiency inspired us to optimize and standardize imaging methods, especially for food-contaminating beetles. For this endeavor, we chose multiple species of beetles belonging to different families or genera that have near-identical elytral patterns, and thus are difficult to identify correctly at the species level. Our optimized imaging method provides enhanced images such that the elytral patterns between individual species could easily be distinguished from each other, through visual observation. We believe such standardization is critical in developing automated species identification of pantry beetles and/or other insects. This eventually may lead to improved taxonomical classification, allowing for better management of food contamination and ecological conservation.

Elevated levels of nitrous oxide (N 2 O) emissions are a matter of concern in agricultural soils especially when flooding (hypoxic conditions) results from over irrigation or frequent rains. This study is the first to report the use of two solid oxygen fertilizers (SOFs, calcium peroxide and magnesium peroxide) to reduce N 2 O production in mineral and organic soils amended with N fertilizer in a short-term laboratory incubation besides two biochars. In general, organic soil had greater N 2 O production than mineral soil. Soils amended with nitrogen fertilizer exhibited increased N 2 O production, by 74 times in mineral soil and 2 times in organic soil. Both solid oxygen fertilizers in mineral soil (98-99%) and calcium peroxide in organic soil (25%) successfully reduced N 2 O production than corresponding N fertilized treatments. Additionally, a greater level of available nitrate-N (52-57 and 225 mg kg -1 in mineral and organic soil, respectively) was recorded with the solid oxygen fertilizers. Corn residue biochar with N fertilizer increased N 2 O production in mineral soil but decreased in organic soil, while pine bark biochar with N did not affect the N 2 O production in either soil. Depending on soil, appropriate SOFs applied were able to reduce N 2 O production and maintain greater nitrate-N levels in flooded soil. Thus, solid oxygen fertilizers can potentially be used as an effective way to reduce N 2 O emission from hypoxic soil in agricultural production systems.

Objective: In this study, we aimed to harness some solvent extracts of one wild mushroom Hexagonia glabra and test their anti-cancer activity against cervical human cell lines, namelyHeLa, SiHa, and CaSki., Methods: It includes cell morphological study by microscope, nuclear morphology by DAPI staining under fluorescence microscopy, apoptosis assay by fluorescence technique, anti-proliferation by MTT assay and expression of apoptotic and anti-apoptotic genes by Western blotting and cell cycle analysis was done., Results: The selected cervical cancer cells were treated separately with 150 µg/mL of three extracts, namely of ethanolic (EE), ethyl acetate (EAE), and water extract (WE) and exhibited features like round, shrink and dead. All extracts caused apoptosis in cell lines and EE had the highest effect in this regard. The percentages of apoptotic cells in HeLa, SiHa and CaSki, at the same concentration of EE were 79.23, 75.42, and 76.36% respectively. Cytotoxicity assay showed that all three extracts (50 - 250 μg/mL) were potent for inhibition of cell growth of three cell lines and again EE had the highest effect. The percentages of cell growth inhibition in HeLa, SiHa, and CaSki cells treated with EE at 24 h at 50 µg/mL were 45.79±4.11, 41.66±4.03, and 36.72±2.67, while they were 74.23±7.45, 62.31±5.97, and 54.23±5.04 at 150 µg/mL concentration. At 250 µg/mL concentration, the percentages of cell growth inhibition were 94.25 ±8.11, 90.02 ±8.67, and 85.43±6.21, respectively. The expression of apoptotic gene (Caspase 3, 9) and tumor guard gene (p53), as their proteins in Western blotting increased . However, anti-apoptotic BcL2 gene of all cell lines was decreased following treatment with extracts. In addition, the cell cycle analysis (CaSki cell) showed that treatment (EE) arrested at G2/M check point cell cycle., Conclusion: All extracts of this mushroom were active in arresting growth of three cell lines and EE had the highest effect, indicating that this mushroom can be a valuable source of anticancer agents.

A new [3 + 3]- and [3 + 4]-annulation strategy involving azaoxyallyl cation and [1, m ]-amphoteric compounds ( m = 3,4) is presented. This concise method enables easy assembly of functionalized saturated N-heterocycles, comprised of six-and seven-membered rings and is of high significance in the context of drug discovery approaches. This reaction also represents a new trapping modality of the azaoxyallyl cation with amphoteric agents of different chain lengths that consist of a heteroatom nucleophilic site and a π-electrophilic site.

The beneficial role of biochar on improvement of soil quality, C sequestration, and enhancing crop yield is widely reported. As such there is not much consolidated information available linking biochar modulated soil condition improvement and soil nutrient availability on crop yields. The present review paper addresses the above issues by compilation of world literature on biochar and a new dimension is introduced in this review by performing a meta-analysis of published data by using multivariate statistical analysis. Hence this review is a new in its kind and is useful to the broad spectrum of readers. Generally, alkalinity in biochar increases with increase in pyrolysis temperature and majority of the biochar is alkaline in nature except a few which are acidic. The N content in many biochar was reported to be more than 4% as well as less than 0.5%. Poultry litter biochar is a rich source of P (3.12%) and K (7.40%), while paper mill sludge biochar is higher in Ca content (31.1%) and swine solids biochar in Zn (49810 mg kg -1 ), and Fe (74800 mg kg -1 ) contents. The effect of biochar on enhancing soil pH was higher in Alfisol, Ferrosol and Acrisol. Soil application of biochar could on an average increase (78%), decrease (16%), or show no effect on crop yields under different soil types. Biochar produced at a lower pyrolysis temperature could deliver greater soil nutrient availabilities than that prepared at higher temperature. Principal component analysis (PCA) of available data shows an inverse relationship between [pyrolysis temperature and soil pH], and [biochar application rate and soil cation exchange capacity]. The PCA also suggests that the original soil properties and application rate strongly control crop yield stimulations via biochar amendments. Finally, biochar application shows net soil C gains while also serving for increased plant biomass production that strongly recommends biochar as a useful soil amendment. Therefore, the application of biochar to soils emerges as a 'win-win strategy' for sustainable waste management, climate change mitigation and food security., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Lewis acid catalyzed ring opening reaction of Donor-Acceptor (D-A) cyclopropanes with alkyl hydroperoxides is reported to furnish various peroxycarbonyls and 1,3-haloperoxygenated compounds in good to excellent yields. This method adds another instance to scarcely reported noncyclilizing 1,3-bisfunctionalization of D-A cyclopropanes with two different functional groups and relies on the dual role of peroxide as nucleophile and oxidant through an orchestrated reaction sequence. The products obtained, including α-heterosubstituted peroxy compounds, are amenable to useful synthetic elaboration.

LMB-100 is a mesothelin-targeted recombinant immunotoxin (iTox) that carries a modified Pseuodomonas exotoxin A (PE) payload. PE kills cells by inhibiting synthesis of new proteins. We found that treatment of pancreatic cancer cells with LMB-100 for 24⁻48 h did not change total protein level despite inducing protein synthesis inhibition (PSI). Further, increased levels of ubiquitinated proteins were detected, indicating that cells may have limited ability to compensate for PSI by reducing protein degradation. Together, these data suggest that PE depletes concentrations of a minority of cellular proteins. We used reverse phase protein array and Luminex assay to characterize this subset. LMB-100 decreased the abundance of 24 of 32 cancer-related proteins (including Bcl-x, Her2, Her3 and MUC16) without compensatory increases in other analytes. Further, cancer cells failed to maintain extracellular concentrations of cancer cell secreted growth factors (CCSGFs), including Vascular Endothelial Growth Factor (VEGF) following treatment with cytostatic LMB-100 doses both in culture and in mouse tumors. Decreased VEGF concentration did not change tumor vasculature density, however, LMB-100 caused tissue-specific changes in concentrations of secreted factors made by non-cancer cells. In summary, our data indicate that PSI caused by cytostatic LMB-100 doses preferentially depletes short-lived proteins such as oncogenic signaling molecules and CCSGFs.

Insect pests, such as pantry beetles, are often associated with food contaminations and public health risks. Machine learning has the potential to provide a more accurate and efficient solution in detecting their presence in food products, which is currently done manually. In our previous research, we demonstrated such feasibility where Artificial Neural Network (ANN) based pattern recognition techniques could be implemented for species identification in the context of food safety. In this study, we present a Support Vector Machine (SVM) model which improved the average accuracy up to 85%. Contrary to this, the ANN method yielded ~80% accuracy after extensive parameter optimization. Both methods showed excellent genus level identification, but SVM showed slightly better accuracy  for most species. Highly accurate species level identification remains a challenge, especially in distinguishing between species from the same genus which may require improvements in both imaging and machine learning techniques. In summary, our work does illustrate a new SVM based technique and provides a good comparison with the ANN model in our context. We believe such insights will pave better way forward for the application of machine learning towards species identification and food safety.

This paper presents the nonlinear six degrees of freedom dynamic modeling of a fixed wing micro air vehicle. The static derivatives of the micro air vehicle are obtained through the wind tunnel testing. The propeller effects on the lift, drag, pitching moment and side force are quantified through wind tunnel testing. The dynamic derivatives are obtained through empirical relations available in the literature. The trim conditions are computed for a straight and constant altitude flight condition. The linearized longitudinal and lateral state space models are obtained about trim conditions. The variations in short period mode, phugoid mode, Dutch roll mode, roll subsidence mode and spiral mode with respect to different trim operating conditions is presented. A stabilizing static output feedback controller is designed using the obtained model. Successful closed loop flight trials are conducted with the static output feedback controller., Competing Interests: The authors declare no conflict of interest.

Background: Type I hypersensitivity is an allergic reaction characterized by the overactivity of the immune system provoked by normally harmless substances. Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of treatment for type I hypersensitivity. Even though these drugs have the anti-allergic effect, they can have several side effects in prolong use. Cedrol is the main bioactive compound of Cedrus atlantica with anti-tumor, anti-oxidative, and platelet-activating factor inhibiting properties., Methods: In this study, the preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid carriers (NLCs) were evaluated. NLCs were prepared using Compritol ® 888 ATO and triolein as lipid phase and vitamin E d-α-tocopherylpolyethyleneglycol 1000 succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers., Results: The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C 1 ) and 91.93 nm (NLC-C 2 ). The particle had negative zeta potential values of -31.9 mV (NLC-C 1 ) and -44.5 mV (NLC-C 2 ). Type I anaphylactoid reaction in the animal model is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast cell degranulation and histamine release from mast cells. Furthermore, compound 48/80-evoked Ca 2+ uptake into mast cells was reduced in a dose-dependent manner by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I anaphylactoid response in vivo in mice and compound 48/80-induced mast cell activation in vitro are greatly enhanced by the loading of cedrol into the NLCs. The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C 2 was found to be 11.5-fold greater than both prednisolone and cromolyn sodium., Conclusion: Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery of cedrol to protect anaphylactic reactions., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Cholestatic liver fibrosis is caused by obstruction of the biliary tract and is associated with early activation of portal fibroblasts (PFs) that express Thy-1, fibulin 2, and the recently identified marker mesothelin (MSLN). Here, we have demonstrated that activated PFs (aPFs) and myofibroblasts play a critical role in the pathogenesis of liver fibrosis induced by bile duct ligation (BDL). Conditional ablation of MSLN+ aPFs in BDL-injured mice attenuated liver fibrosis by approximately 50%. Similar results were observed in MSLN-deficient mice (Msln-/- mice) or mice deficient in the MSLN ligand mucin 16 (Muc16-/- mice). In vitro analysis revealed that MSLN regulates TGF-β1-inducible activation of WT PFs by disrupting the formation of an inhibitory Thy-1-TGFβRI complex. MSLN also facilitated the FGF-mediated proliferation of WT aPFs. Therapeutic administration of anti-MSLN-blocking Abs attenuated BDL-induced fibrosis in WT mice. Liver specimens from patients with cholestatic liver fibrosis had increased numbers of MSLN+ aPFs/myofibroblasts, suggesting that MSLN may be a potential target for antifibrotic therapy.

Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis)., Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer., Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE., Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Liquid crystal (LC) droplets dispersed in aqueous solution have emerged as an optical probe for sensing the adsorption and interaction of biological species at the LC/aqueous interface. In this paper, we modify the surface of 4-n-pentyl-4'-cyanobiphenyl (5CB) LC droplets by the adsorption of positively charged poly(diallyldimethylammonium chloride) (PDADMAC) and poly(ethylenimine) (PEI) with different molecular weights at the 5CB/water interface. The PDADMAC and PEI-modified 5CB droplets show a radial director configuration in aqueous solution with salt concentrations above 150 mM. The adsorption of negatively charged bovine serum albumin (BSA) on the positively charged PDADMAC and PEI-modified 5CB droplets through electrostatic interaction can induce the radial-to-bipolar configuration transition of the 5CB inside the droplets. We find that the concentration of BSA required to induce the configuration transition increases linearly with the decrease of the molecular weight of PDAMAC and PEI. Our results highlight the capability of the director configuration of LC droplets as an optical probe for sensing the interaction between proteins and polyelectrolytes at the LC/aqueous interface.

Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was isolated from Porphyra vietnamensis followed by the fact that its alkali induced safe reduction in molecular weight was achieved. Formulation was optimized using three-factor three-level (3(3)) central composite design. High concentration of POR in NPs was confirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH range. Hemolytic toxicity data suggested the safety of prepared formulation. In vivo and in vitro antifungal activity demonstrated the high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. Throughout the study TPP addition did not cause any significant changes. Therefore, these experimental oral NPs may represent an interesting carrier system for the delivery of AmB.

Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.

Gold nanoparticles (Aunp) through biogenetic processes have induced enormous interest for lower toxicity and precise applications. A rapid, one pot synthesis for uniformly sized gold nanoparticles was developed using polyphenolic compound quercetin. Reduction process was followed at low temperatures in a simple bath type sonicator. Nanoparticle plasmon response was recorded at 540 nm and the average size in TEM was observed at 15.07 nm. Detailed X-ray diffraction (XRD) observations proved fcc crystalline structure of metallic gold and the Fourier transform infrared (FTIR) analysis has confirmed nanoparticles conjugation with quercetin. Leishmaniasis, is a neglected tropical disease (NTD) classified by the World Health Organization (WHO). The leishmanial parasite multiply in host macrophages and most strains have developed drug resistance to available chemotherapeutics. Drug delivery is therefore a major problem in macrophage specific leishmanial parasite infections. New quercetin conjugated gold nanoparticles (QAunp) were successfully evaluated for the first time against leishmanial macrophage infections. Antileishmanial efficiency of QAunp was established against wild type (IC50 15±3), sodium stibogluconate resistant strain (IC50 40±8) and the paramomycin resistant (IC50 30±6) strains. Macrophage uptake of QAunp was complete within an hour as observed in TEM experiments., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Context: Performance of medical students in developing nations like India is perceived to have largely declined., Aims: We attempted to assess the reasons behind such trends., Settings and Design: Students in their third year of medical study were given a predesigned, pretested structured and validated questionnaire that they filled in anonymously. The key areas assessed were concentration, interest and understanding of the subject and other perceived causes of poor performance. Tests for descriptive statistics were applied for evaluation., Results and Conclusions: One hundred and fifty students participated in the study. Fifty-five (36.66%) students performed poorly. Male gender, inability to clear the previous professional examination at the first attempt, difficulty in understanding medium of instruction, self-assessed depression, sleep disorders and perceived parental and peer pressure and dissatisfaction with career choice were significantly linked with poor performance (P<0.05 for each factor). Socioeconomic status and regularity in class were not linked to academic performance.

Community based study on health expenditure is a rarity in India. A Rural Community based longitudinal study was undertaken in Jaulgaon village of Maharashtra, with objectives of finding out the health expenditure contributed by direct treatment, related travel and relevant loss of wages with certain pertinent associated factors. 50% of the village population was studied (N = 256) by pre-designed, pre-tested schedule following WHO guidelines. A monthly house to house interview was conducted over 12 months. During study period, 78% study subjects suffered some illness with mean illness episode 1.74/person and 6.37/family without any sex difference. The annual health expenditure of the community was Rs 1,576/family, 4,31/person and 2,42/episode, which was about 4.3% of their income. The major part of the expenditure (82%) was for direct treatment cost, followed by loss of wages (12%) and travel related cost (6%). Expenditure was seen to be significantly associated with family income (P = 0.000) and education (P = 0.006).

Stimuli-responsive organic tubes are an attractive supramolecular assembly which has potential applications as a controlled release vehicle. We synthesize a smart organic tube by the coassembly of lithocholic acid (LCA) and taurolithocholic acid (TLCA) in aqueous solution. The coassembled LCA/TLCA tubes can be longitudinally unzipped into flat sheets by capillary force after being dehydrated on substrates. Consequently, the encapsulated guest molecules are released from the unzipping tubes. After the release of guest molecules, the flat sheets can be zipped back into hollow tubes upon hydration with aqueous solution. The zipping/unzipping LCA/TLCA tubes provide a new type of delivery vehicles, which may have potential for surface decontaminations.

Liquid-crystal droplets are of great interest because of their large surface areas, rich phases, and tunable optical properties. The director configuration of liquid-crystal droplets provides a unique optical sign to detect the events occurring at the droplet surface. In this article, we report the alternating bipolar/radial configuration transitions of 4-n-pentyl-4'-cyanobiphenyl (5CB) droplets triggered by the layer-by-layer coating of negatively charged poly(styrenesulfonate sodium (PSS) and positively charged poly(diallyldimethylammonium chloride) (PDADMAC) on the droplet surface. The alternating configuration transitions are due to the interactions of the 5CB with polar versus nonpolar PDADMAC/PSS multilayer coatings. Furthermore, we find that the coating of PDADMAC/PSS multilayers makes the director configuration of the 5CB in the droplets sensitive to environmental salt concentrations., (© 2011 American Chemical Society)

Andrographolide (AG) is a diterpenoid lactone isolated from the leaves of Andrographis paniculata. AG is a potent and low-toxicity antileishmanial agent. Chemotherapy applications of AG are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. Nanoparticulation of AG was therefore envisaged as a possible solution. AG nanoparticles (AGnp) loaded in 50:50 poly(DL-lactide-co-glycolic acid) were prepared for delivery into the monocyte-macrophage cells infested with the amastigote form of leishmanial parasite for evaluation in the chemotherapy of leishmaniasis. Particle characteristics of AGnp were optimized by proportionate application of a stabilizer, polyvinyl alcohol (PVA). Physicochemical characterization of AGnp by photon correlation spectroscopy exhibited an average particle size of 173 nm and zeta potential of -34.8 mV. Atomic force microscopy visualization revealed spherical nanoparticles with a smooth surface. Antileishmanial activity was found to be significant for the nanoparticle preparation with 4% PVA (IC₅₀) 34 μM) in about one-fourth of the dosage of the pure compound AG (IC₅₀) 160 μM). AGnp therefore have significant potential to target the infested macrophage cells and prove valuable in chemotherapy of neglected tropical diseases such as leishmaniasis.

Background: Currently, a major problem in the management of visceral leishmaniasis or kala-azar, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy. Membrane bound pyrophophatase (PPases) do not exist in plasma membrane from mammals. Thus, H(+)-PPases from Leishmania plasma membrane might be potential target in rational chemotherapy of the disease caused by Leishmania parasites., Objective: To characterize the activities of inorganic pyrophophatase (PPase) in the plasma membrane of Leishmania donovani promastigote and amastigote., Methods: Culture method of promastigote and amastigote were developed. We assayed PPase activity in isolated plasma membrane of L. donovani., Results: We characterized K(+)-PPase present in the plasma membrane of Leishmania donovani and investigated its possible role in the survival of promastigote and amastigote. PPase activity was stimulated by K(+) ions and sodium orthovanadate, inhibited by pyrophosphate analogs imidodiphosphate and alendronate, KF, DCCD, thiol reagent parachloromercuribenzenesulfonate (PCMBS), N-ethylmaliemide (NEM), phenylarsineoxide, ABC superfamily transport modulator verapamil and was also by F(1)F(o)-ATPase inhibitor quercetin., Conclusion: We conclude that there are significant differences within promastigote, amastigote and mammalian host in cytosolic pH homeostasis to merit the inclusion of PPase transporter as putative targets for rational drug design.

We report here syntenic loci in humans and mice incorporating gene clusters coding for secreted proteins each comprising 10 cysteine residues. These conform to three-fingered protein/Ly-6/urokinase-type plasminogen activator receptor (uPAR) domains that shape three-fingered proteins (TFPs). The founding gene is PATE, expressed primarily in prostate and less in testis. We have identified additional human PATE-like genes (PATE-M, PATE-DJ, and PATE-B) that co-localize with the PATE locus, code for novel secreted PATE-like proteins, and show selective expression in prostate and/or testis. Anti-PATE-B-specific antibodies demonstrated the presence of PATE-B in the region of the sperm acrosome and at high levels on malignant prostatic epithelial cells. The syntenic mouse Pate-like locus encompasses 14 active genes coding for secreted proteins, which are all, except for Pate-P and Pate-Q, expressed primarily in prostate and/or testis. Pate-P and Pate-Q are expressed solely in placental tissue. Castration up-regulates prostate expression of mouse Pate-B and Pate-E, whereas testosterone ablates this induced expression. The sequence similarity between TFP/Ly-6/uPAR proteins that modulate activity of nicotinic acetylcholine receptors and the PATE (Pate)-like proteins stimulated us to see whether these proteins possess analogous activity. Pharmacological studies showed significant modulation of the nicotinic acetylcholines by the PATE-B, Pate-C, and Pate-P proteins. In concert with these findings, certain PATE (Pate)-like genes were extensively expressed in neuron-rich tissues. Taken together, our findings indicate that in addition to participation of the PATE (Pate)-like genes in functions related to fertility and reproduction, some of them likely act as important modulators of neural transmission.

Purpose: Mesothelin is a glycosyl-phosphatidylinositol-anchored glycoprotein present on the cell surface. Mesothelin is a differentiation antigen that is highly expressed on mesothelioma, ovarian cancer, and pancreatic cancer. The existence of a spontaneous humoral immune response to mesothelin in humans has not been fully studied. Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer., Experimental Design: Using an ELISA, we analyzed immunoglobulin G antibodies specific for mesothelin in sera from patients with mesothelioma and epithelial ovarian cancer. Tumor specimens were examined by immunohistochemistry for mesothelin protein expression., Results: Elevated levels of mesothelin-specific antibodies were detected in the sera of 39.1% of patients with mesothelioma (27 of 69 patients) and 41.7% with epithelial ovarian cancer (10 of 24 patients) when compared with a normal control population (44 blood donors; P < 0.01 for both mesothelioma and ovarian cancer). We also found that 53% to 56% of patients with mesothelin immunostaining-positive mesothelioma and ovarian cancer had antibodies specific for mesothelin, whereas only 0% to 8% of patients with negative mesothelin immunostaining had detectable mesothelin-specific antibodies (chi(2) test: P < 0.01 for mesothelioma and P = 0.025 for ovarian cancer)., Conclusions: Our findings indicate that mesothelin is a new tumor antigen in patients with mesothelioma and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immune-based therapies.

Mesothelin is a differentiation antigen present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield the 40-kDa protein, mesothelin, attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor. The biological function of mesothelin is not known. Mesothelin is a promising candidate for tumor-specific therapy, given its limited expression in normal tissues and high expression in several cancers. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin that is undergoing clinical evaluation in patients with mesothelin-expressing tumors. There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas.

Background & Objectives: The study was undertaken to explore the locus of interaction of clofazimine and niclosamide which showed substantial growth inhibition property in Leishmania donovani promastigotes., Methods: The uptake of final electron acceptor oxygen and 2,6-dichlorophenolindophenol (DCPIP) reduction in the electron transport chain were measured by constant volume Warburg respirometer and monitoring absorbance at 600 nm, respectively. Irreversibility of O2 uptake inhibition by clofazimine and niclosamide was determined by dilution of cell suspension followed by centrifugation., Results: Clofazimine and niclosamide showed their minimum inhibitory concentration (MIC) at 33 and 150 micrograms/ml, respectively. Oxygen uptake inhibition by clofazimine and niclosamide was not reversed by removal of the drug by centrifugation. Rotenone, a potent inhibitor of mammalian electron transport chain showed no inhibition on the electron transport chain of L. donovani promastigotes. Cyanide at 1 mM concentration showed partial inhibition in L. donovani promastigotes. Oxygen uptake and DCPIP reduction by L. donovani promastigotes were highly sensitive to sulphhydryl group inhibitors. Strong inhibition of oxygen uptake (80-100%) by L. donovani promastigotes was achieved by clofazimine, niclosamide and amphotericin B. Amphotericin B failed to inhibit DCPIP reduction by L. donovani promastigotes, whereas DCPIP reduction was inhibited by clofazimine and niclosamide, respectively., Interpretation & Conclusion: DCPIP reduction was mediated by transplasma membrane electron transport as evidenced by its inhibition with membrane impermeable quinone 1,2-naphthoquinone-4-sulphonic acid (NQSA). Transplasma membrane electron transport requires b-cytochromes and sulphhydryl groups for its function and was inhibited by clofazimine and niclosamide.