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Variables responsible for the differential COVID-19 pandemic severity among countries remain undefined. Zinc, a micronutrient required for immunocompetence, is found deficient in populations. We hypothesized the differential COVID-19 severity observed among European countries could be associated with the Zn-deficiency prevalence. The COVID-19 data from different stages of pandemic, i.e., 8 April, 12 and 26 May 2020, were analyzed for covariation with the estimated Zn-deficiency. A significant, relatively stable, but negative correlation of Zn-deficiency with cases per million for the time period [r(20): -0.4930 to -0.5335, p-value: 0.02720 to 0.0154] and a steady improvement of covariation with deaths per million [r(20): -0.4056; p-value: 0.0760 on 26 May 2020] was observed. Considering, Zinc’s key immunomodulatory role, widespread deficiency along with the self- and prescribed intervention in different target groups, e.g. children, women, elderly, carefully planned dedicated exploratory studies to understand the basis of the observed association are advisable.

Various studies are underway to identify protective variables for the COVID-19 pandemic. We hypothesized that if indeed the Vitamin D levels would be protective in the European population, as recently proposed, the correlation would become more robust when the countries had passed the infection peak as on May 12, 2020, compared to April 8, 2020, when the majority had not. Comparative analysis of data from the mentioned stages indicated a significant increase in negative correlation of vitamin D levels with COVID-19 cases per million population in later stage (r(20): -0.5504; R2=0.3029; p-value: 0.0119 vs r(20): -0.4435; R2=0.1967; p-value: 0.0501) whereas the correlation with deaths per million population became insignificant (r(20): -0.3935; R2=0.1549; p-value: 0.0860 vs r(20): -0.4378; R2=0.1917; p-value: 0.0535). Considering divergence of vitamin D levels from the mean in subgroups, e.g. children, women, aged, dedicated exploratory studies with carefully chosen matched target groups is advisable.

Proteases have been implicated in the tumorigenesis and aggressiveness of a variety of cancer types. In fact, proteases have proven to be very clinically useful as tumor biomarkers in the blood of patients. Proteases are typically involved in complex systems of substrates, activators, and inhibitors, thus making our ability to establish their exact function in cancer more difficult. Trypsin, perhaps the most famous of proteases, has been shown to play a role in cancer progression, but its functional role in ovarian cancer has not been much studied. PAR2, a transmembrane receptor that is known to be activated by trypsin, has been reported to be associated with ovarian cancer. Here, we found that stimulation of ovarian cancer cell lines with trypsin or PAR2 activating peptide markedly increased MAPK signaling and cell proliferation. Additionally, HE4, a WAP-family glycoprotein and ovarian cancer biomarker, was found to inhibit trypsin degradation, thereby retaining its activity. Patient data seemed to support this phenomenon, as the serum of ovarian cancer patients with high HE4 expression, revealed significantly elevated trypsin levels. These data support the hypothesis that trypsin plays a tumorigenic role in ovarian cancer, which can be mediated by its receptor PAR2, and potentiated by HE4.

Background: Parkinson’s Disease (PD) is characterized by both motor and non-motor symptoms. The presynaptic neuronal protein, α-Synuclein, plays a pivotal role in PD pathogenesis and is associated with both genetic and sporadic origin of the disease. Ursolic Acid (UA) is a well-known bioactive compound found in various medicinal plants, widely studied for its anti-inflammatory and antioxidant activities. Objective: In this research article, the neuroprotective potential of UA has been further explored in the Rotenone-induced mouse model of PD. Methods: To investigate our hypothesis, we have divided mice into 4 different groups, control, drug only control, Rotenone-intoxicated group, and Rotenone-intoxicated mice treated with UA. After the completion of dosing, behavioral parameters were estimated. Then mice from each group were sacrificed and the brains were isolated. Further, the biochemical tests were assayed to check the balance between the oxidative stress and endogenous anti-oxidants; and TH (Tyrosine Hydroxylase), α-Synuclein, Akt (Serine-threonine protein kinase), ERK (Extracellular signal-regulated kinase) and inflammatory parameters like Nuclear Factor-κB (NF-κB) and Tumor Necrosis Factor- α (TNF-α) were assessed using Immunohistochemistry (IHC). Western blotting was also done to check the expressions of TH and α-Synuclein. Moreover, the expression levels of PD related genes like α-Synuclein, β-Synuclein, Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were assessed by using Real-time PCR. Results: The results obtained in our study suggested that UA significantly reduced the overexpression of α-Synuclein and regulated the phosphorylation of survival-related kinases (Akt and ERK) apart from alleviating the behavioral abnormalities and protecting the dopaminergic neurons from oxidative stress and neuroinflammation. Conclusion: Thus, our study shows the neuroprotective potential of UA, which can further be explored for possible clinical intervention.

While high-load resistance training increases muscle hypertrophy, the intramuscular protein responses to this form of training remains largely unknown. In the current study, recreationally resistance-trained college-aged males (N = 15; mean ± SD: 23 ± 3 years old, 6 ± 5 years training) performed full-body, low-volume, high-load [68–90% of one repetition maximum (1RM)] resistance training over 10 weeks. Back squat strength testing, body composition testing, and a vastus lateralis biopsy were performed before (PRE) and 72 h after the 10-week training program (POST). Fiber type-specific cross-sectional area (fCSA), myofibrillar protein concentrations, sarcoplasmic protein concentrations, myosin heavy chain and actin protein abundances, and muscle tissue percent fluid were analyzed. The abundances of individual sarcoplasmic proteins in 10 of the 15 participants were also assessed using proteomics. Significant increases (p < 0.05) in type II fCSA and back squat strength occurred with training, although whole-body fat-free mass paradoxically decreased (p = 0.026). No changes in sarcoplasmic protein concentrations or muscle tissue percent fluid were observed. Myosin heavy chain protein abundance trended downward (−2.9 ± 5.8%, p = 0.069) and actin protein abundance decreased (−3.2 ± 5.3%, p = 0.034) with training. Proteomics indicated only 13 sarcoplasmic proteins were altered with training (12 up-regulated, 1 down-regulated, p < 0.05). Bioinformatics indicated no signaling pathways were affected, and proteins involved with metabolism (e.g., ATP-PCr, glycolysis, TCA cycle, or beta-oxidation) were not affected. These data comprehensively describe intramuscular protein adaptations that occur following 10 weeks of high-load resistance training. Although previous data from our laboratory suggests high-volume resistance training enhances the ATP-PCr and glycolytic pathways, we observed different changes in metabolism-related proteins in the current study with high-load training.

Coronary allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation (HT) in children. Variation in CAV screening practices may impact detection rates and patient outcomes.Among 50 Pediatric Heart Transplant Society (PHTS) sites from 2001 to 2016, coronary evaluations were classified as angiography or non-invasive testing, and angiograms were designated as routine or symptom based. CAV detection rates stratified by routine vs symptom-based angiograms were calculated. Freedom from CAV and mortality after CAV diagnosis, stratified by study indication, were calculated.A total of 3,442 children had 13,768 coronary evaluations; of these, 97% (n = 13,012) were for routine surveillance, and only 3% (n = 333) were for cause. Over the study period, CAV was detected in 472 patients (14%). Whereas 58% (n = 29) of PHTS sites evaluate by angiography alone, 42% reported supplementing with a non-invasive test, although only 423 non-invasive studies were reported. Angiographic detection of CAV was higher for symptom-based testing than for routine testing (29% vs 4%, p0.0001), although routine testing identified a majority of cases (88%; n = 414). The 10-year freedom from CAV was 77% overall. Once CAV is detected, 5-year graft survival was 58%, with lower survival for patients diagnosed after symptoms angiogram than after routine angiogram (30% vs 62%; p0.0001).Development of a robust model for CAV risk should allow low-risk patients to undergo less frequent invasive angiography without adverse impact on CAV detection rates or outcomes.

Septin expressions are altered in cancer cells and exhibit poor prognoses in malignancies. As the first approach to develop a septin filament targeting agent, we optimized the structure of Forchlorfenuron (FCF), a known plant cytokinin to generate UR214-9, which contrary to FCF, causes septin-2/9 filamental structural catastrophe in cancer cells without altering cellular septin protein levels.In-silicodocking using septin-2/septin-2 dimer complex showed that UR214-9 displaced the guanine carbonyl oxygen from the GDP binding domain and showed increased binding energy than FCF(−8.59vs-7.21). UR214-9 reduced cancer cell growth, downregulated HER2/STAT-3 axis and controlled growth of HER2+ pancreatic, breast and ovarian cancer xenografts in NSG mice and enhanced response of Herceptin against HER2+breast cancer xenograft. Transcriptome analysis of UR214-9 exposed cells demonstrated significant perturbation of 1200 genes in JIMT-1 breast cancer cells indicating target specificity and non-transcriptional functions of UR214-9. In summary, disrupting septins via UR214-9 is a new approach to control the growth of HER2+ malignancies.

Protein–protein interactions are crucial for all biological processes. Compiling this network provides many new insights into protein function and gives directions for the development of new drugs targeted to the pathogen. Mycobacterium tuberculosis Nucleoside diphosphate kinase (Mtb Ndk) has been reported to promote survival of mycobacterium within the macrophage and contribute significantly to mycobacterium virulence. Hence, the present study was aimed to identify and characterize the interacting partner for Ndk. The in vitro experiments, pull down and far western blotting have demonstrated that Mtb Ndk interacts with Rv1273c, a probable drug ABC transporter ATP-binding protein annotated to export drugs across the membrane. This observation was further confirmed by molecular docking and dynamic simulations studies. The homology model of Rv1273c was constructed and docked with Mtb Ndk for protein–protein interaction analysis. The critical residues involved at interface of Rv1273c–Ndk interaction were identified. MDS and Principal Component analysis carried out for conformational feasibility and stability concluded that the complex between the two proteins is more stable as compared to apo proteins. Our findings would be expected to improve the dissection of protein–protein interaction network and significantly advance our understanding of tuberculosis infection. Communicated by Ramaswamy H. Sarma

There has been a growing burden of anxiety among Nepalese adolescents. Social anxiety in particular is one of the commonly reported symptoms indicating mental health problem among adolescents. The purpose of this study was to assess social anxiety, and identify how social support, emotion regulation and mindfulness uniquely contribute to social anxiety among adolescents in Birgunj, Nepal. The study was conducted by using a self-administered questionnaire among 384 adolescents (65.4% boys; M = 16.05 years, SD = 1.39) studying at secondary schools of Birgunj. Results show that there was a positive correlation between social anxiety symptoms and age, and girls reported more symptoms. Traits such as non-acceptance of emotions, lack of clarity and lack of awareness of emotions were related to increased social anxiety; while acting with awareness, non-reactivity, and better ability to describe emotions was related to decreased social anxiety. Finally, more social support from close friends was related to lower social anxiety. These results suggest that improving emotion regulation, dispositional mindfulness, and social support may be helpful for adolescents who are at risk of, or are suffering from, social anxiety.

Background: Typhoid is mainly a disease of developing country, and inappropriately treated most of time due to lack of highly skilled diagnostic tools specially at primary level. So to validate most easy and rapid investigation Typhidot EIA with nested PCR may prove quite necessary due to low yield of culture reports. Aims: The objective was to evaluate the clinical profile and immediate diagnostic tool typhidot considering nested PCR as gold standard due to it’s high sensitivity and specificity rates. Material and Methods: Clinical profile of 100 case of provisional enteric fever recorded along with amplification of The DNA fragment of flagellin (H1-d) and stkG gene for salmonella typhi and salmonella paratyphi A respectively by nested PCR done in blood clot,unine and stool sample, along with blood clot culture,urine and stool culture done. Further validation of ELISA card test i.e. typhidot EIA done considering nested PCR as gold standard, for validation of test control group consisted of 40 health subjects. Results: Nested PCR which showed overall 84% positivity. Total Culture positivity was 60 among all samples and among that Clot culture 35(35%),urine culture 3(3%)and stool culture yield was 22(22%) respectively .Validation of Typhipoint EIA IgM showed 92.8% sensitivity and 68.7% specificity. Conclusion: It may be advised that 2-3 specific antigens of S. Typhi are spotted on the membrane and ELISA based detection should be carried out to reach the satisfactory level of diagnosis of enteric fever in field condition for more accuracy in rapid test to avoid inappropriate antimicrobial therapy and costly investigations. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: The study was conducted as a part of dissertation in collaboration with department of general medicine and department of microbiology at I.M.S , B.H.U Varanasi. The well informed consent was taken from each of the participants and the study plan was approved by the Institute Ethics Committee.

Neutrophils are the first responders to inflammation, infection, and injury. As one of the most abundant leukocytes in the immune system, neutrophils play an essential role in cancer progression, through multiple mechanisms, including promoting angiogenesis, immunosuppression, and cancer metastasis. Recent studies demonstrating elevated neutrophil to lymphocyte ratios suggest neutrophil as a potential therapeutic target and biomarker for disease status in cancer. This chapter will discuss the phenotypic and functional changes in the neutrophil in the tumor microenvironment, the underlying mechanism(s) of neutrophil facilitated cancer metastasis, and clinical potential of neutrophils as a prognostic/diagnostic marker and therapeutic target.

Effect of cold plasma generated using Nitrogen–Oxygen and Nitrogen as feed gases on the properties of skim milk treated for 1, 2, 3, 4 and 5 min was evaluated. Cold plasma treatment with N2–O2 plasma (0.9 mol N2 & 0.1 mol O2 per mol feed gas) significantly decreased the pH and increased the titratable acidity of milk. Furthermore, skim milk treated with N2–O2 plasma showed higher browning intensity at the end of 5 min. Also, the particle size of milk significantly increased with time in case of N2–O2 plasma treatment , indicating aggregation of proteins. SDS PAGE results showing changes in the electrophoretic bands of casein as well as whey proteins also signified denaturation and aggregation of proteins and indicated the formation of insoluble protein aggregates. Apparently, the resultant protein aggregation led to a significant decrease in the surface hydrophobicity of skim milk. FTIR spectroscopy used to study the changes in the secondary structure of milk proteins revealed an overall increase in α-helix and aggregated β-sheet. The results showed that the composition of feed gas had a significant effect on physico-chemical properties, particle characteristics and surface hydrophobicity of skim milk as well as the molecular weight of milk proteins.

Introduction Prior studies have reported that hidradenitis suppurativa (HS) is accompanied by a myriad of physical and mental conditions. However, given the small sample sizes and the limited number of pre-selected comorbidities, these studies do not provide a complete picture of the comorbidity burden of HS in the USA. Moreover, the relationship between HS severity and comorbidity burden has yet to be characterized. Using a large US claims database, we estimated the comorbidity burden associated with HS, stratified by disease severity. Methods A retrospective matched cohort design was used. Patients with HS were classified into two severity cohorts (milder and more severe) using an empirical algorithm based on treatments received. The comorbidity burden was compared between each HS cohort and their matched HS-free cohort, and between patients with milder vs. those with more severe forms of HS. Results Several physical and mental comorbidities were found to be more prevalent in both cohorts of patients with milder and more severe forms of HS than in their matched HS-free cohorts. The comorbidity burden also increased greatly as the disease progressed to more severe forms. Conclusions The results of this study highlight the complexity of the comorbidity burden of HS patients and the need for a multidisciplinary approach to optimize the management of HS and its numerous associated comorbidities. Funding AbbVie, Inc. Electronic supplementary material The online version of this article (10.1007/s13555-018-0264-z) contains supplementary material, which is available to authorized users.

Resistance training generally increases skeletal muscle hypertrophy, whereas aging is associated with a loss in muscle mass. Interestingly, select studies suggest that aging, as well as resistance training, may lead to a reduction in the abundance of skeletal muscle myofibrillar (or contractile) protein (per mg tissue). Proteomic interrogations have also demonstrated that aging, as well as weeks to months of resistance training, lead to appreciable alterations in the muscle proteome. Given this evidence, the purpose of this small pilot study was to examine total myofibrillar as well as total sarcoplasmic protein concentrations (per mg wet muscle) from the vastus lateralis muscle of males who were younger and resistance-trained (denoted as YT, n = 6, 25 &plusmn, 4 years old, 10 &plusmn, 3 self-reported years of training), younger and untrained (denoted as YU, n = 6, 21 &plusmn, 1 years old), and older and untrained (denoted as OU, n = 6, 62 &plusmn, 8 years old). The relative abundances of actin and myosin heavy chain (per mg tissue) were also examined using SDS-PAGE and Coomassie staining, and shotgun proteomics was used to interrogate the abundances of individual sarcoplasmic and myofibrillar proteins between cohorts. Whole-body fat-free mass (YT &gt, YU = OU), VL thickness (YT &gt, YU = OU), and leg extensor peak torque (YT &gt, YU = OU) differed between groups (p &lt, 0.05). Total myofibrillar protein concentrations were greater in YT versus OU (p = 0.005), but were not different between YT versus YU (p = 0.325). The abundances of actin and myosin heavy chain were greater in YT versus YU (p &lt, 0.05) and OU (p &lt, 0.001). Total sarcoplasmic protein concentrations were not different between groups. While proteomics indicated that marginal differences existed for individual myofibrillar and sarcoplasmic proteins between YT versus other groups, age-related differences were more prominent for myofibrillar proteins (YT = YU &gt, OU, p &lt, 0.05: 7 proteins, OU &gt, YT = YU, p &lt, 0.05: 11 proteins) and sarcoplasmic proteins (YT = YU &gt, 0.05: 8 proteins, YT&amp, YU, p &lt, 0.05: 29 proteins). In summary, our data suggest that modest (~9%) myofibrillar protein packing (on a per mg muscle basis) was evident in the YT group. This study also provides further evidence to suggest that notable skeletal muscle proteome differences exist between younger and older humans. However, given that our n-sizes are low, these results only provide a preliminary phenotyping of the reported protein and proteomic variables.

The lacuna in the knowledge of immunobiology, especially in visceral infections that are fatal if left untreated, are a major hurdle in getting a vaccine candidate for leishmaniasis. Till date, only a few drugs are available to combat human leishmaniasis and a vaccine candidate either prophylactic or preventive is still awaited. Therefore, identification of host and parasitic factors involved in the regulation of specific immune mechanisms are essentially needed. In this study, we observed that CD200-CD200R immune inhibitory axis regulates host macrophages effectors properties and helps antigen experienced T cells (CD4

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies. Desmoplasia and tumor-supporting inflammation are hallmarks of PDAC. The tumor microenvironment contributes significantly to tumor progression and spread. Cancer-associated fibroblasts (CAFs) facilitate therapy resistance and metastasis. Recent reports emphasized the concurrence of multiple subtypes of CAFs with diverse roles, fibrogenic, and secretory. C-X-C motif chemokine receptor 2 (CXCR2) is a chemokine receptor known for its role during inflammation and its adverse role in PDAC. Oncogenic Kras upregulates CXCR2 and its ligands and, thus, contribute to tumor proliferation and immunosuppression. CXCR2 deletion in a PDAC syngeneic mouse model produced increased fibrosis revealing a potential undescribed role of CXCR2 in CAFs. In this study, we demonstrate that the oncogenic Kras-CXCR2 axis regulates the CAFs function in PDAC and contributes to CAFs heterogeneity. We observed that oncogenic Kras and CXCR2 signaling alter CAFs, producing a secretory CAF phenotype with low fibrogenic features; and increased secretion of pro-tumor cytokines and CXCR2 ligands, utilizing the NF-κB activity. Finally, using syngeneic mouse models, we demonstrate that oncogenic Kras is associated with secretory CAFs and that CXCR2 inhibition promotes activation of fibrotic cells (myofibroblasts) and impact tumors in a mutation-dependent manner.

Low moisture foods, including seasoning spices, have been associated with a number of multi-state outbreaks of salmonellosis in the past decade. The long-term objective of this study was to develop an effective in-package pasteurization treatment for seasoning mixtures based on radio frequency (RF) heating. Seasoning spices obtained from grocery stores included red, white, and black pepper; cumin; curry powder; and garlic powder with moisture contents ranging from 3.1 to 12.3% (wet basis). The dielectric properties (DP) of the seasoning spices and their mixtures as influenced by frequency, moisture, temperature, mixing fraction and salt content were determined using a precision LCR meter and liquid test fixture at frequency ranging from 1 to 30 MHz. The RF heating rates of each spice and their mixtures were evaluated using a 27.12-MHz, 6-kW pilot scale RF system with 105 mm gap between electrodes. To evaluate the effect of mixing on heating uniformity, a sample (50 g) was placed into a polystyrene plastic cylindrical container and heated to 70 °C, and surface images were taken by an infrared camera. The results showed that the relationship among moisture content, temperature and DP of white pepper can be explained by a second-order model at 13.56 and 27.12 MHz. The DP and heating rates of spice mixtures ranged between the highest and lowest values of their respective individual spices. Increase in salt content resulted in a decrease in heating rate, which resulted a better heating uniformity with smaller uniformity index (UI). The RF heating rate of samples ranged from 2.97 to 23.61 (°C min−1). The highest heating rate in samples was in a correspondence to the worst heating uniformity, and highest average temperature on the sample surface. The most uniform heat distrubition on top surface was obtained for garlic powder as 0.012 (UI) at 70 °C. The information obtained from this study is important to develop an effective RF heating strategy for pathogen control in seasoning mixture.

Psoriasis is a risk factor for cardiovascular events.To assess the risk of major cardiovascular events and the effect of cumulative treatment exposure on cardiovascular event risk in patients with psoriasis treated with tumor necrosis factor-α inhibitors (TNFis) versus phototherapy.Adult patients with psoriasis were selected from a large US administrative claims database (from the first quarter of 2000 through the third quarter of 2014) and classified in 2 mutually exclusive cohorts based on whether they were treated with TNFis or phototherapy. Cardiovascular event risk was compared between cohorts using multivariate Cox proportional hazards models. Cumulative exposure was defined based on treatment persistence.A total of 11,410 TNFi and 12,433 phototherapy patients (psoralen plus ultraviolet A light phototherapy, n = 1117; ultraviolet B light phototherapy, n = 11,316) were included in this study. TNFi patients had a lower risk of cardiovascular events compared to phototherapy patients (adjusted hazard ratio 0.77, P .05). The risk reduction associated with 6 months of cumulative exposure was 11.2% larger for patients treated with TNFis compared to phototherapy (P .05).Information on psoriasis severity and mortality was limited/not available.Patients with psoriasis who were treated with TNFis exhibited a lower cardiovascular event risk than patients treated with phototherapy. Cumulative exposure to TNFis was associated with an incremental cardiovascular risk reduction compared to phototherapy.

To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012-2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant proportion of PsA and RA patients.

Vertebral artery dissection (VAD), a well-recognized cause of stroke in young, can be easily missed on magneto resonance angiography of the brain. Computed tomography and catheter−based angiography are often used to detect arterial dissection, but they have their limitations. Here, we discuss cases of stroke in young where the presence of the additional track sign on a gradient echo sequence provided the clue to VAD being the etiology of stroke. This sign observed on the routine magnetic resonance imaging brain might be of great help to clinicians and radiologists for the easy detection of VAD.

Six new cis-chelate complexes, [M(L)2] (L = methyl-3-hydroxy-3-(furyl)-2-propenedithioate L1, M = Ni(II) 1, Pd(II) 4; methyl-3-hydroxy-3-(thiophenyl )-2-propenedithioate L2, M = Ni(II) 2, Pd(II) 5 and methyl-3-hydroxy-3-(phenyl)-2-propenedithioate L3, M = Ni(II) 3, Pd(II) 6 have been prepared and characterized by elemental analyses, spectroscopy (IR, UV–Vis., 1H and 13C{1H} NMR). The structures of 2–6 have been revealed by X-ray crystallography. In all the crystal structures, the metal has four-coordinate slightly distorted square planar geometry with a cis-configuration of the ligands. Anti-leishmanial properties of the complexes have been studied; 2, 3 and 6 showed potential anti-promastigote and anti-amastigote activities with IC50 values of 1.70 ± 0.50, 1.62 ± 0.19, 9.20 ± 2.16 μg/mL and IC50 2.50 ± 0.10, 2.05 ± 0.40, 12.84 ± 3.46 μg/mL respectively. Cytotoxicity assays on these complexes showed toxicity on the promastigotes but less toxicity against RAW 264.7 cell lines at different concentrations. Palladium complexes 4, 5 and 6 show luminescent characteristics in CH2Cl2 solution at room temperature. Complexes 1–6 are weakly conducting (σrt = 10−4-10−6 S cm−1, Ea = 0.19–1.13 eV) but show semiconducting behavior in the solid phase.

The objective of this study was to determine the effect of micronization techniques for particle size reduction from D (v, 0.9) ≥ 800 μm to D (v, 0.9) ≤ 100 μm on the rheological and structural characteristics of tart cherry puree. Commercially frozen cherry puree was thawed and micronized using Megatron MT5000 at 15000 rpm for three cycles (M1, M2, M3; 10 min each) followed by high-pressure homogenization at 200 MPa. The particle size distribution was measured using Malvern laser particle size analyzer and total soluble and insoluble solid contents by using the AOAC official method 20.5 or 30.2. All samples were further characterized for rheology, total solids content and particle morphology. Results showed a significant reduction in apparent viscosities (2.59 Pa s to 0.0144 Pa s) with a reduction in particle size (800 μm–100 μm) and this trend was consistent in different shear rate ranges. The change in serum viscosity followed the similar trend as observed in puree viscosity with micronization. Comparative analysis of the effect of shear rate (0–1000 s−1) on viscosity showed an inverse relationship, suggesting a shear thinning behavior of the fluid. This effect on serum viscosity (0.0119 Pa s to 0.0047 Pa s) was found to be higher in the shear rate range of 0–10 s−1, as opposed to a relatively less reduction from 0.0047 Pa s to 0.0022 Pa s and 0.0015 Pa s at higher shear rates in ranges of 20–100 s−1 and 20 to 1000 s−1 respectively. The viscosity–shear rate changes were approximated by Ostwald-de Waele model (power law relation) for serum and Herschel Bulkley model for puree. The total solid content (14.20 ± 1.10 °Brix) was not significantly affected by particle size reduction. Results of this study provide useful information about the rheological properties of fruit juices/purees, which are influenced by the interactions between the dispersed phase and the serum, and are critical indicators of textural properties, mouth-feel, commercial acceptability, requirements of mixing and transport equipment.

Periodontitis is a biofilm-associated irreversible inflammation of the periodontal tissues. Reports suggest the role of Porphyromonas gingivalis specific Arg- and Lys-specific proteinases in the orchestration of the initiation and progression of periodontal diseases. These proteinases are precisely termed as gingipains R and K. Curcumin is an active polyphenol that is extracted from the rhizomes of Curcuma longa. However, the molecule curcumin owing to its high hydropathy index and poor stability has not been able to justify its role as frontline drug modality in the treatment of infectious and non-infectious diseases as claimed by several investigators. In the present study, at first, we synthesized and characterized quantum curcumin, and investigated its biocompatibility. This was subsequently followed by the evaluation of the role of quantum curcumin as an antimicrobial, anti-gingipains and antibiofilm agent against Porphyromonas gingivalis and select reference strains. We have successfully synthesized the quantum curcumin utilizing a top-down approach with the average size of 3.5 nm. Apart from its potent antimicrobial as well as antibiofilm properties, it also significantly inhibited the gingipains in a dose-dependent manner. At the minimal concentration of 17.826 μM, inhibition up to 98.7% and 89.4% was noted for gingipain R and K respectively. The data was also supported by the in silico docking experiments which revealed high exothermic enthalpies (−7.01 and −7.02 cal mol−1). Besides, the inhibition constant was found to be 7.24 μM and 7.1 μM against gingipains R and K respectively. The results suggest that quantum curcumin is a potential drug candidate which needs further clinical validation.

Current treatment options for relapsed acute myeloid leukemia (AML) are limited and ineffective for the majority of patients. In AML, primitive leukemia stem cells (LSCs) and pre-leukemic populations are able to maintain the disease and drive relapse. Thus, therapies targeting LSC populations may increase the overall survival of AML patients. In this study, we aim to identify the drivers favoring LSC expansion following treatment and relapse and develop potential therapies for AML. The transcriptome analyses of 12 pairs of functionally defined LSC fractions at diagnosis and relapse revealed significant changes of IL-1 signaling in AML patients. We demonstrated that the protein expression levels of interleukin-1 receptor type I (IL1R1) and its complex member interleukin-1 receptor accessory protein (IL1RAP) were both up-regulated in human leukemia stem and progenitor cells (LSPCs) at diagnosis or in relapse compared to normal hematopoietic stem and progenitor cells (HSPCs). Knockdown of IL1R1 and IL1RAP suppressed the clonogenicity and engraftment growth of primary human AML cells but showed low impacts on HSPCs in the normal bone marrow. Additionally, knockout of IL1R1 in leukemia MLL-AF9 mice significantly reduced the LSC frequency and prolonged the overall survival rate. To target IL-1/TLR signaling in LSCs, we performed iterative structure-activity relationship (SAR) guided medicinal chemistry, in silico modeling and leukemia cell line reporter assays to screen and identify a novel interleukin-1 receptor-associated kinase 1/4 (IRAK1/4) inhibitor (termed UR241-2). UR241-2 robustly inhibits IL-1/TLR signaling in AML cells including the activation of NF-κB following IL-1 stimulation. UR241-2 repressed LSPC function as assessed by colony-forming unit assays in primary human AML cells at diagnosis and in relapse while minimally impacting normal HSPC function. Taken together, our findings demonstrate the important role of IL-1/TLR signaling in supporting AML LSC expansion following treatment and relapse and suggest that targeting IL-1/TLR signaling using the novel IRAK1/4 inhibitor, UR241-2, can target LSC function to improve patient outcomes in AML. Disclosures No relevant conflicts of interest to declare.

Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D), Pdx1-Cre; LSL-Kras(G12D); LSL-p53(R172H) and RIP1-Tag2) to analyze SEMA5A expression during PC progression. Using human patients and different mouse models, we demonstrated that SEMA5A expression was highest in liver metastases, followed by primary pancreatic tumors, and the lowest expression was found in the normal pancreas. SEMA5A expression was localized on tumor cells with no staining in the surrounding stroma. To understand the functional significance of SEMA5A, we treated PC cell lines with recombinant SEMA5A. We observed an increase in migration, chemotaxis, and scattering of PC cells. To delineate the signaling axis of SEMA5A, we generated SEMA5A receptor-Plexin-B3 knockdown in T3M-4 and CD18/HPAF PC cell lines and observed that the effect of SEMA5A treatment was absent in the Plexin-B3 knockdown counterparts of T3M-4 and CD18/HPAF cells. SEMA5A treatment leads to phosphorylation of cMET in Plexin-B3 dependent manner. Our data demonstrate that there is an increase in SEMA5A expression during PC progression and the elevation of this expression takes place at metastatic sites especially the liver in both exocrine and endocrine tumors. SEMA5A can elicit a migratory response in cells by activating cMET through the Plexin-B3 receptor. In conclusion, SEMA5A signaling represents a potential molecule for targeting metastasis in pancreatic cancer.

Non-uniform heating is a major challenge for using radio frequency (RF) heat treatment in pasteurization of low moisture food products. The objective of this study was to evaluate the effect of different electrode gaps, moisture content (MC), bulk density and surrounding materials on RF heating uniformity and rate in corn flour. Additionally, the dielectric and thermal properties of corn flour were determined as affected by MC, temperature (°C), and frequency (MHz). Changes in MC, water activity (a w ) and color in the sample after RF heating were measured to evaluate treatment effect on food quality. A precision LCR meter and a liquid test fixture were used to study DP of the sample at RF frequency ranging from 1 to 30 MHz. The RF heating uniformity and temperature profiles of corn flour as exposed to RF heating were obtained with an infrared camera and a data logger connected to a fiber optic sensor. The DP values increased with increasing MC and temperature, but decreased with frequency. The heating rate increased from 3.5 to 6.8 °C min − 1 with increasing MC (from 10.4 to 16.7%), but decreased from 12.7 to 5.2 °C min − 1 with increasing electron gap (from 11 to 15 cm). The corner and edge heating were observed at all layers of the samples for all the distances, and the hottest and the most uniform layer were determined as the middle layer at an electrode gap of 15 cm. Glass petri dish provided better uniformity than those of polyester plastic petri dish. Covering by foam led to more uniform RF heating uniformity in corn flour, and better moisture and a w distribution. This study provided useful information to develop an effective RF process as an alternative of conventional thermal treatments for pasteurization of low-moisture products. Industrial relevance This paper describes a novel methodology based on Radio Frequency heating to pasteurize food powder while maintaining the quality. The study addresses the ever-increasing global demand from consumers for safe food products.

Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression. This receptor, in conjunction with its primary chemokine ligand CXCL12, promotes pancreatic cancer development, invasion, and metastasis through the management of the tumor microenvironment via complex crosstalk with other pathways. Thus, CXCR4 likely contributes to the poor prognoses observed in patients afflicted with this malignancy. Recent exploration of combination therapies with CXCR4 antagonists have demonstrated improved outcomes, and abolishing the contribution of this pathway may prove crucial to effectively treat pancreatic cancer at both the primary tumor and metastases.

Lipid oxidation products, like α, β-unsaturated aldehydes, can react with proteins and influence meat quality. Two such key end products are 4-hydroxy-2-nonenal (4-HNE) and 4-oxo-2-nonenal (4-ONE). These compounds are far more stable than the lipid hydroperoxides from which they form; so, they can diffuse from the site of generation and cause extensive cellular damage and oxidative pathology. Glycolytic enzymes involved in the reduction of metmyoglobin (e.g., lactate dehydrogenase) are highly reactive with 4-HNE, and subsequently become less functional. Other aldehydes, such as 4-ONE, are more reactive than 4-HNE with certain functional groups/moieties including mercapto groups and arginine residues of glycolytic enzymes. Yet, little research has considered the influence of 4-ONE on an in-vitro meat model system. Findings from this study establish that 4-ONE causes loss of lactate dehydrogenase activity compared to 4-HNE at similar effective concentrations. Myoglobin, when incubated with 4-ONE, exhibited a loss in its redox stability at pH 5.8. Both 4-HNE and 4-ONE were found to be potent covalent modifiers of myoglobin, disrupting functional and structural morphology of bovine heart mitochondria. This study reveals that 4-ONE is a novel and highly toxic chemical species, which causes damage to mitochondrial structure and impairment of myoglobin's redox stability.

Radio frequency (RF) heat treatment holds great potential for packaged food powder pasteurization by providing rapid and volumetric heating with a high penetration depth. Edge and corner overheating create high temperature differences throughout the product, which is a major drawback in its industrial applications. In this study, the effect of the surrounding media (air, DI water, and soybean oil), medium level, heating mode, electrode gap, and heating time on the heating uniformity was investigated by determining the thermal distributions, heating uniformity index, and heating rate at the top and middle layers of RF heated corn flour. The thermal images indicated that less edge and corner overheating occurred when corn flour container was immersed in soybean oil. A higher heating rate (7.77 and 9.86 °C/min at the top and middle layers, respectively) and a better heating uniformity (as indicated by lower heating uniformity indices: 0.047 and 0.037 at the top and middle layers, respectively) were obtained for the corn flour heated in soybean oil with an 11 cm electrode gap compared to those heated in air. The study proposed a method for improving the heating uniformity of RF heated food powders which can be easily implemented in industrial applications of RF treatment.

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest survival rates of cancers, with a five-year relative survival of 9%. The significant factor contributing to low survivorship is the intrinsic resistance to chemotherapy. In the present study, we elucidate a targetable pathway that facilitates resistance in these cells. One inflammatory pathway used in cancer progression is CXCR2, which binds chemokines CXCL 1-3 and 5-8. Our group and others have shown an association of CXCR2 with tumor progression, angiogenesis and metastasis in PDAC, and chemotherapy resistance in other cancers. In this study, we test the hypothesis that CXCR2 is integral in PDAC chemotherapy resistance. We generated gemcitabine resistant cell lines (GemR) from the parent cell lines of T3M4 (WT KRAS) and CD18/HPAF (Mutant KRAS) with 40- and 67-fold higher resistance in comparison to the parent cell lines, respectively. Using qRT-PCR and ELISA, we profiled chemokines' expression, CXCL1, 5, and 8, on parent- and GemR-cell lines. We observed a higher basal level expression of CXCL1, 5, and 8 ligands in GemR cells than the parent cell lines. Further treatment with gemcitabine, the parent cell lines had a higher increase in CXCL1 and 8 ligand expression in comparison with GemR cell lines. With further investigation of T3M4, we found a dose-dependent and time-dependent increase for CXCL1 and CXCL8. CXCL5 had a constant high expression with all doses of gemcitabine. With our initial observations of gemcitabine treatment enhancing CXCR2 ligands in PDAC cells, we evaluated the effects of the small molecule CXCR2 antagonist SCH 479833 (SCH 47) in combination with gemcitabine treatment on the parent and GemR cell lines. We used the relative IC50 and half the relative IC50 for both the gemcitabine and SCH 47 treatment doses. We observed that a lower concentration of gemcitabine in the presence of the SCH 47 was more effective than the higher concentration of gemcitabine without SCH 47 for the GemR-cell lines. Together, our observations show chemotherapy-resistant PDAC cell lines express higher CXCR2 ligand levels at baseline, with parent cell lines increasing expression with chemotherapy treatment. We also show an advantageous combination treatment of CXCR2 antagonist with lower gemcitabine concentration. Overall, these results show a promising future for CXCR2 antagonism in the treatment of resistant PDAC tumors. Citation Format: Caitlin Molczyk, Dipakkumar R. Prajapati, Sugandha Saxena, Paran Goel, Michelle Varney, Rakesh K. Singh. CXCR2 and its ligands modulate chemotherapy resistance in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1087.

Rifamycin B is produced by Amycolatopsis mediterranei S699 as a secondary metabolite. Its semi-synthetic derivatives have been used for curing tuberculosis caused by Mycobacterium tuberculosis. But the emergence of rifampicin-resistant strains required analogs of rifamycin B to be developed by rifamycin biosynthetic gene cluster manipulation. In 2014 genetic engineering of the rifamycin polyketide synthase gene cluster in S699 led to a mutant, A. mediterranei DCO#34, that produced 24-desmethylrifamycin B. Unfortunately, the productivity was strongly reduced to 20 mgL−1 as compared to 50 mgL−1 of rifamycin B. To understand the mechanisms leading to reduced productivity and rifamycin biosynthesis by A. mediterranei S699 during the early and late growth phase we performed a proteome study for wild type strain S699, mutant DCO#34, and the non-producer strain SCO2-2. Proteins identification and relative label-free quantification were performed by nLC-MS/MS. Data are available via ProteomeXchange with identifier PXD016416 . Also, in-silico protein-protein interaction approach was used to determine the relationship between different structural and regulatory proteins involved in rifamycin biosynthesis. Our studies revealed RifA, RifK, RifL, Rif-Orf19 as the major regulatory hubs. Relative abundance expression values revealed that genes encoding RifC-RifI and the transporter RifP, down-regulated in DCO#34 and genes encoding RifR, RifZ, other regulatory proteins up-regulated. Significance The study is designed mainly to understand the underlying mechanisms of rifamycin biosynthesis in Amycolatopsis mediterranei. This resulted in the identification of regulatory hubs which play a crucial role in regulating secondary metabolism. It elucidates the complex mechanism of secondary metabolite biosynthesis and their conversion and extracellular transportation in temporal correlation with the different growth phases. The study also elucidated the mechanisms leading to reduced production of analog, 24-desmethylrifamycin B by the genetically modified strain DCO#34, derivatives of which have been found effective against rifampicin-resistant strains of Mycobacterium tuberculosis. These results can be useful while carrying out genetic manipulations to improve the strains of Amycolatopsis to produce better analogs/drugs and promote the eradication of TB. Thus, this study is contributing significantly to the growing knowledge in the field of the crucial drug, rifamycin B biosynthesis by an economically important bacterium Amycolatopsis mediterranei.

Aflatoxins (AFs) contamination is prevalent in foods around the world. Many studies have been performed to recover foods contaminated with unacceptable levels of AFs. This review evaluated AFs detoxification technologies of ultraviolet (UV), hydrogen peroxide (H2O2), and their combination. Microscopic evidence has demonstrated that AFs are mainly distributed on or near the surface of contaminated foods, and thus a treatment applied near the surface would be sufficient for detoxification. UV is an ideal treatment due to its ability to detoxify AFs, affordable cost, and less quality impact. UV can degrade aflatoxin B1 into more than 200 times less toxic compound, aflatoxin B2a, justifying the use of this method in practice. However, the “shadow effect” and poor penetrability are concerns when applying UV on solid materials. H2O2 can oxidize AFs into less toxic compounds with negligible quality change and no residual issue after treatment. H2O2 is usually combined with heat, radiation, or alkali to promote the oxidation process. Combining UV and H2O2 (Advanced Oxidation Processes, AOPs) can photolyze H2O2 into free radicals, which can oxidize most organic compounds and has been used for pollutants decontamination in water treatment. Previous works demonstrated that AOPs could successfully detoxify AFs in contaminated food.

Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis.

The present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O2−), hydrogen peroxide (H2O2), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis. Keywords: Leishmaniasis, Renal, TLRs, Apoptosis

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine’s safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from ±33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

Agriclinics and agribusiness centres (ACABC‟s) scheme is a subsidy based credit linked scheme launched by government of India on 9th April, 2002 for the strengthen technology transfer, public extension system and employment generation in rural areas. The present study was conducted in Rajasthan state during 2011 to 2015 and based on the primary data collected through field survey by pre tested questionnaires from 150 sample agrigraduates. The objective of study was to analyse the profile of agrigraduates on the basis of socio economic characteristics. The socio-economic profile were covered under broad categories such as socioeconomic profile of the trained agripreneurs, status of agriventure taken, status of loans obtained and approached, reasons for refusal of loan application, reasons for willingness and not willingness to take up agriventures under the scheme. The appropriate statistical techniques such as frequencies, scores and percentages were used to analyse the socio economic profile of agrigraduates under agriclinics and agribusiness centres scheme. The study results and previous literature are indicated that the most important factors influencing establishment of agribusiness units are attitude towards self-employment, better livelihood opportunities, entrepreneurial ability, motivation from successful entrepreneurs and self-confidence. Gender-related variations were also significant with regard to attitude towards self-employment, decision-making ability and information seeking behaviour. Thus, there is need to change in the attitude of agrigraduates towards self-employment, develop entrepreneurial ability and enhance self-confidence of the trainees through the training programmes.

Treatment of prostate cancer with paclitaxel often fails due to the development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that codelivery of paclitaxel and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes paclitaxel-resistant prostate cancer cells, killing both cancer stem–like cells (CSC) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells. Paclitaxel and rubone combination therapy inhibited tumor cell growth, migration, and CSC population growth. We synthesized poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol; PEG-PCD) to prepare micelles. The drug-loading capacities were 9.70% ± 0.10% and 5.34% ± 0.02% for paclitaxel and rubone, respectively, controlling a drug release of 60.20% ± 2.67% and 60.62% ± 4.35% release of paclitaxel and rubone at 24 hours. Delivery of miR-34a and rubone decreased PC3-TXR cell viability with increasing paclitaxel concentration. Coincubation with a miR-34a inhibitor diminished the effect of rubone. Paclitaxel IC50 in PC3 and PC3-TXR cells was 55.6 and 2,580 nmol/L, respectively, but decreased to 49.8 and 93.2 nmol/L when treated in combination with rubone, demonstrating a reversal of paclitaxel resistance by rubone. Systemic administration of micelles carrying paclitaxel and rubone inhibited orthotopic prostate tumor growth in nude mice, compared with monotherapy, by reversing the expression of miR-34a, SIRT1, cyclin D1, and E-cadherin. In summary, our results showed how rubone acts as an efficient small-molecule modulator of miR-34a to reverse chemoresistance and further enhance the therapeutic efficacy of paclitaxel in paclitaxel-resistant prostate cancer. Cancer Res; 77(12); 3244–54. ©2017 AACR.

The main factors behind the growing popularity of infrared radiation heating in food processing include its energy efficiency, food quality retention and process speed, as well as the simplicity of equipment. Infrared radiation was employed as an alternative heat treatment to the conventional hot air method used in peanut blanching. The present study aimed to investigate the application of infrared heating for blanching peanuts and determine their blanchability and sensory quality under various processing conditions.; Results: The total blanchabilities (expressed as a percentage of total blanched) of the infrared radiation trials (radiant wall oven) at 343 °C for 1.5 min, 316 °C for 1.5 min, 288 °C for 1.5 min and 343 °C for 1 min did not differ significantly compared to the hot air control trials (impingement oven) at 100 °C for 30 and 20 min. All infrared trials had significantly lower (P < 0.05) numbers of split kernels compared to those of the conventional trials and all blanched peanuts in the experiment remained raw. A descriptive sensory shelf-life study with one control and three infrared samples demonstrated the possible initiation of oxidation for the conventionally blanched sample at 18 weeks of storage at 24 °C (room temperature), with no indication of oxidation in the infrared samples stored at the same temperature.; Conclusion: Infrared radiation peanut blanching is a viable alternative to conventional hot air blanching because of the shorter process time and longer shelf-life, as evident from the sensory storage study. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

The cardiac troponin C (TnC)-A8V mutation is associated with hypertrophic and restrictive cardiomyopathy (HCM and RCM) in human and mice. The residue affected lies in the N-helix, a region known to affect Ca 2+ -binding affinity to the N-terminal domain. Here we report on the functional effects of this mutation in skinned papillary muscle fibers from homozygous knock-in TnC-A8V mice. Muscle fibers from left ventricle were activated at 25°C under the ionic conditions of working cardiomyocytes. The pCa-tension relationship showed a 3× increase in Ca 2+ -sensitivity and a decrease (0.8×) in cooperativity ( n H ) in mutant fibers. The elementary steps of the cross-bridge (CB) cycle were investigated by sinusoidal analysis. The ATP study revealed that there is no significant change in the affinity of ATP ( K 1 ) for the myosin head. In TnC-A8V mutant fibers, the CB detachment rate ( k 2 ) and its equilibrium constant ( K 2 ) increased (1.5×). The phosphate study revealed that rate constant of the force-generation step ( k 4 ) decreased (0.5×), reversal step ( k −4 ) increased (2×), and the phosphate-release step (1/ K 5 ) increased (2×). Pro-Q Diamond staining of the skinned fibers samples revealed no significant changes in total phosphorylation of multiple sarcomeric proteins. Further investigation using liquid chromatography-tandem mass spectrometry revealed hypophosphorylation of the rod domain of myosin heavy chain in TnC-A8V mutant fibers compared to wild-type. Immunoblotting confirmed the results observed in the mass spectrometry analysis. The results suggest perturbed CB kinetics—possibly caused by changes in the α -myosin heavy chain phosphorylation profile—as a novel mechanism, to our knowledge, by which a mutation in TnC can have rippling effects in the myofilament and contribute to the pathogenesis of HCM/RCM.

New homoleptic zinc(II) dithiocarbamates, [Zn(L)2] (L = N-ferrocenyl-N-methyl dithiocarbamate (L1) 1, (N-(benzo[d][1,3]dioxol-5-ylmethyl)-N-furfuryl) dithiocarbamate (L2) 2, N-(benzo[d][1,3]dioxol-5-ylmethyl)-(N-benzyl) dithiocarbamate (L3) 3, N-(benzo[d][1,3]dioxol-5-ylmethyl)-(N-methyl) dithiocarbamate (L4) 4, N-ethylmorpholine-(N-4-methoxyphenylmethyl) dithiocarbamate (L5) 5 and N-(benzo[d][1,4]dioxol-6-ylmethyl)-(N-benzylmethyl) dithiocarbamate (L6) 6, have been synthesized and characterized by elemental analyses and spectroscopy (IR, UV-vis, 1H and 13C{1H} NMR). X-ray crystallography revealed different dimeric structures for (1 and 2) and (3, 4, and 5) adopting distorted tetrahedral and TBP/SP coordination geometries, respectively, in which the dithiocarbamate ligands are bonded to the metal centers both in terminal S,S-chelating and μ2,κ2S,S-bridging and μ2,κ2-S,S-chelating–bridging arrangements. 6 is a mononuclear complex showing a distorted tetrahedral geometry. The supramolecular frameworks in these complexes have been sustained by C–H⋯S, C–H⋯O, C–H⋯π, π⋯π, C–H⋯π (ZnCS2, chelate) and H⋯H interactions. The anti-leishmanial activities of the complexes have been screened; 4 and 6 showed potential anti-promastigote and anti-amastigote activities with IC50 values of 0.66 ± 0.22, 1.48 ± 0.10 μg mL−1 and IC50 2.98 ± 0.30, 2.51 ± 0.10 μg mL−1, respectively. Cytotoxicity assays on both complexes showed toxicity on promastigotes but lower toxicity against the RAW 264.7 cell line at different concentrations. All the complexes show luminescence characteristics in CH2Cl2 solution at room temperature arising from the metal perturbed intra-ligand charge transfer (ILCT) states. Their TG analyses show single step decomposition with formation of binary ZnS and ternary FeZn2S3 materials which have been examined by PXRD, SEM and EDAX.