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Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, by developing mIDH1-driven genetically engineered mouse models, we show that mIDH1 supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of CD8+ T-cell activity and tumor cell–autonomous inactivation of TET2 DNA demethylase. Pharmacologic mIDH1 inhibition stimulates CD8+ T-cell recruitment and interferon γ (IFNγ) expression and promotes TET2-dependent induction of IFNγ response genes in tumor cells. CD8+ T-cell depletion or tumor cell–specific ablation of TET2 or IFNγ receptor 1 causes treatment resistance. Whereas immune-checkpoint activation limits mIDH1 inhibitor efficacy, CTLA4 blockade overcomes immunosuppression, providing therapeutic synergy. The findings in this mouse model of cholangiocarcinoma demonstrate that immune function and the IFNγ–TET2 axis are essential for response to mIDH1 inhibition and suggest a novel strategy for potentiating efficacy. Significance: Mutant IDH1 inhibition stimulates cytotoxic T-cell function and derepression of the DNA demethylating enzyme TET2, which is required for tumor cells to respond to IFNγ. The discovery of mechanisms of treatment efficacy and the identification of synergy by combined CTLA4 blockade provide the foundation for new therapeutic strategies. See related commentary by Zhu and Kwong, p. 604. This article is highlighted in the In This Issue feature, p. 587

Toxicity and physiological alterations were determined in Pseudococcus viburni nymphs treated with Artemisia annua methanolic extract. The leaf dipping bioassay showed LC50 values of 0.287% and 0.194% 24 and 48 hours post-exposure. Activities of general esterases were significantly higher in the control nymphs than in those which had been treated except for the 48 h time interval using α-naphtyl acetate. The activity of glutathione S-transferase using CDNB (1-chloro-2,4-dinitrobenzene) in the control nymphs, was significantly higher than in the control at both time intervals while no significant difference was observed after 24 h in addition to the higher enzymatic activity in the treated nymphs after 48 h. All three aminotransferases were significantly more active in the control nymphs except for time intervals of 24 h for γ-glutamyl transferase and 48 h for alanine aminotransferase. Higher activities of lactate dehydrogenase, acid- and alkaline phosphatase were found in the control nymphs than in treated nymphs for all time intervals. Activities of the enzymes involved in the antioxidant system including catalase, peroxidase, superoxide dismutase, ascorbate peroxidase and glucose-6-phosphate dehydrogenase was increased in the treated nymphs compared to the control. Results of the current study demonstrated toxic effects of A. annua methanolic extract on P. viburni nymphs causing mortality and physiological turbulences.

Background and Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease. Approach and Results: We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 (FCHSD1), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C-to-T substitution at position 547, corresponding to FCHSD1R183W, may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR-associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein. Conclusions: Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.

We examined the residues of 13 elements in soil, plant parts, nectar, bee heads, thorax, and abdomens, feces from bee guts, and bee products sampled from two Polish cities (Lublin and Poznań). Our findings indicated that bees have an extraordinary ability to remove metals from nectar when converting nectar into honey. Compared to nectar, honey contained 40-fold lower Fe, 26-fold lower Zn, and eightfold lower Cu and Cd levels, indicating removal of these elements via nectar processing, during which water is evaporated and complex sugars are decomposed into simple ones. The amount of Pb remained unchanged; however, it can also be regarded as a fourfold decrease due to water evaporation from honey, compared to nectar. Some portion of the ingested Fe, Cu, and Zn was used by bees, and the excess amounts were excreted in feces. All analyzed elements were present as biocomplexes transported from the alimentary tract through the abdomen to the thorax and head. Elements transferred in the alimentary tract were partially immobilized/metabolized in the bee fat body, and their residues were excreted with feces from the gut. We postulate that honey is not a good indicator of environmental pollution, as a high amount of elements is removed by bees from their bodies.

BACKGROUND Brucella are small, nonmotile, intracellular, and aerobic gram-negative bacteria. Of the 10 species that currently form the genus Brucella, 5 were shown to be pathogenic in humans. REVIEW SUMMARY The epidemiology, clinical manifestations, diagnosis and imaging, and treatment of neurobrucellosis will be reviewed.Brucellosis's transmission to humans occurs by direct contact with contaminated animals. Older patients are at increased risk of nervous system involvement in brucellosis. Brucella spp. can lead to central nervous system involvement through direct damage via invasion of neural tissue or indirect damage caused by endotoxins or immune inflammatory reactions elicited by the presence of the bacteria in the body. Patients can have general nonspecific symptoms in addition to neurological and psychiatric symptoms. There are 4 diagnostic criteria for the diagnosis of neurobrucellosis, which include signs and symptoms suggestive of neurobrucellosis, a positive finding of Brucella spp. in the cerebrospinal fluid (CSF), and/or a positive titer of antibodies targeting brucella in the CSF, lymphocytosis with high protein levels and low glucose levels in CSF, and imaging findings (either cranial magnetic resonance imaging or computed tomography) peculiar to neurobrucellosis. For the treatment, a combined therapy is favored over monotherapy for the eradication of Brucella. Moreover, a multirouted therapy has been associated with increased treatment efficacy. The prognosis of neurobrucellosis is dependent on patients' clinical presentation: brucellar meningitis is associated with a good prognosis, whereas diffuse central nervous system involvement is associated with the development of long-term sequelae. CONCLUSIONS Neurobrucellosis affects patients globally and in endemic areas. Neurologists should familiarize themselves with its clinical presentation, diagnosis, and treatment to provide optimal care for their patients.

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries and is threatening worldwide tomato production. Various strategies have been developed and implemented to manage this pest. Here, we present a timely review on the up-to-date development and practical implementation of integrated pest management (IPM) programs for tomato crops across different world regions infested by T. absoluta. While insecticide resistance is a growing concern, biological control via releasing or conserving arthropod natural enemies and sex pheromone-based biotechnical control are the most successful management practices. Agronomic control-related research is an emerging area where the soil fertilization and/or irrigation, as well as breeding of resistant cultivars, has the potential to enhance IPM effectiveness. Grower survey responses in the native areas (i.e., South America), early-invaded areas (i.e., first report between 2006 and 2012) and newly invaded areas (i.e., first report after 2012) showed that the control programs evolved along with the areas and time since invasion. Growers in the early-invaded areas shifted more rapidly from chemical control to biological control compared to those from the native area. In all concerned regions, the pest control failure risk following chemical insecticide applications and the high cost associated with either biological or biotechnical control methods have been the greatest concerns for growers. The information gathered from the native and/or early-invaded areas may help achieve a more effective management in newly invaded areas. Lastly, researchers are expected to break the bottlenecks of some key issues that would enable lowering application cost of novel biorational alternative management options.

Thymol and carvacrol found in Origanum syriacum “Za’atar” plant leaves have triggered interest among researchers for their natural antimicrobial and antifungal properties. However, their applications in modern pharmaceutical and cosmetic industries as natural preservatives remain challenging. In this research, extraction of thymol and carvacrol from Za’atar leaves has been investigated using the ultrasonic-assisted method and the use of sesame oil as the primary extraction solvent compared with other vegetable oils including sunflower and olive oils. In addition, a high-performance liquid chromatography (HPLC) analytical method was developed by using a C8 column and 0.05% trifluoroacetic acid as a buffering agent. The method was validated for specificity, linearity, repeatability, accuracy, and robustness for the analysis of the content of the two terpenes thymol and carvacrol in different Za’atar extracts. Using the validated analytical method, thymol and carvacrol content results revealed the best vegetable oil for extraction. Results showed that sesame oil had the highest content of thymol and carvacrol, followed by sunflower oil, and the least amount obtained by using olive oil. A consistent extraction result opens an opportunity for application in the pharmaceutical and cosmetic industries. For this reason, the essential extraction key parameters that influence the final content of thymol and carvacrol were evaluated. The highest impact originated from the quality and volume of sesame oil. Cold-pressed sesame oil resulted in a 23% higher content of thymol and decreased amount of carvacrol. It was found that wetting the Za’atar leaves powder with sesame oil was enough for extraction; any additional sesame oil volume dilutes the extracted sample. The second impact was the Za’atar cultivation conditions; less than 10% difference of thymol and carvacrol content was observed within Za’atar of Hebron origin. Finally, the origin of sesame seeds used for sesame oil production had the least impact.

This study aimed to compare the identification frequency and composition of bacteria isolated from catheter and urine in urologic patients. Methods: Ninety patients with urethral catheters were involved in the study. Urinary and catheter cultures were taken simultaneously from each patient and cultured on MacConkey's agar. Urine culture and sensitivity were performed for all samples in pre- and postoperative periods. Swab culture and sensitivity from the surface of intraluminal urethral catheters were performed for all cases in the post-operative period. Results: The median indwelling period of the catheters was 8 days (range 3 to 21). The overall positive rate of catheter culture was significantly greater than that of urine culture, even in subjects without a recent antibacterial agent history. Urine cultures and catheter cultures did not match each other completely. The percentage of patients who had the same bacterial species isolated from both specimens increased in a time-dependent manner. Conclusions: Not all species of bacteria colonizing the intraluminal surface of the urethral catheter were detected as urinary bacteria. Bacterial colonization on the intraluminal catheter surface could precede the emergence of bacteriuria.

The toxicity of a tea saponin (TS) was investigated on mortality, digestive system, detoxifying and antioxidant enzymes of Ephestia kuehniella Zeller. The larvae were fed on a diet containing diffe...

Dengue hemorrhagic fever (DHF) is a dengue virus infection transmitted by Aedes spp. Climate has a profound influence on mosquito breeding. Palembang has the highest rate of DHF in South Sumatra. This study aimed to investigate the relationship between the components of climate factors and the incidence of DHF in Palembang. This study was cross-sectional, with an observational analytic approach. The Palembang City Health Office compiled data on DHF incidence rates from 2016 to 2020. Climatic factor data (rainfall, number of rainy days, temperature, humidity, wind speed, sun irradiance) were collected from the Climatology Station Class I Palembang - BMKG Station and Task Force that same year. The Spearman test was used to conduct the correlation test. Between 2016 and 2020, there were 3,398 DHF patients. From January to May, DHF increased. There was a significant correlation between rainfall (r = 0.320; p = 0.005), number of rainy days (r = 0.295; p = 0.020), temperature (r = 0.371; p = 0.040), and humidity (r = 0.221; p = 0.024), wind speed (r= 0.76; p = 0.492), and sunlight (r = 0.008; p = 0.865). Rainfall, the number of rainy days, and temperature were three climatic factors determining the increase in dengue incidence in Palembang.

OBJECTIVES HLA-E is located on the nonclassical major histocompatibility complex class I and acts as the ligand for natural killer cells. Consequently, it has a main role in the regulation of innate immune responses by involving cell identification by natural killer cells. Differences in expression levels among HLA-E alleles have been suggested to affect transplant outcomes. In this study, we evaluated the effects of different HLA-E genotypes on allogeneic hematopoietic stem cell transplant in southern Iran. MATERIALS AND METHODS We investigated 200 patients (donors and recipients) who underwent allogeneic hematopoietic stem-cell transplant and 100 normal participants (control group) in a case-control study. Detection of HLA-E polymorphisms was performed using a sequence-specific primer polymerase chain reaction method. RESULTS Statistical analyses indicated that genotypes in the transplant group were not distributed in accordance with Hardy-Weinberg equilibrium (χ²=76.56; P < .001), whereas genotypes in the control group were distributed in accordance with Hardy-Weinberg equilibrium (χ²=0.39; P = .53). No significant differences were observed in cumulative incidence of acute (P = .76; hazard ratio = 0.80; 95% confidence interval, 0.19-3.31) and chronic (P = .75, hazard ratio = 0.048; 95% confidence interval, 0.00) graft-versus-host disease in recipients harboring HLA-E∗0103 allele compared with those homozygous for the HLA-E∗0101 allele. The HLA-E∗0103 allele showed a trend toward lower cumulative incidence of relapse compared with the homozygous HLA-E∗0101 genotype (8% vs 21.5%; P = .37; hazard ratio = 2.50; 95% confidence interval, 0.32-19.20). CONCLUSIONS Genotypes of the HLA-E molecule did not correlate with acute and chronic graft-versus-host disease in hematopoietic stem cell transplant recipients except for the HLA-E∗0101∗∕∗0103 genotype, which was protective in survival of our study patients.

The present study was done to assess the effects of dietary oak (Quercus aegilops L.) acorn powder (OAP) on the growth performance, somatic indices, and hemato-biochemical responses of common carp,...

Background: Soil-transmitted helminth infection (STH) is a parasite infection that involves humans being infected with roundworms by route of soil contamination. One billion individuals are infected with worms, including 568 million school-age children. Helminthiasis in elementary school-aged children was not documented in Musi Rawas Regency. This study's goal was to identify if not wearing footwear increases the incidence of parasitic infection.Methods: The research was a cross-sectional survey, followed by statistical analysis. The study involved elementary school-aged students in Tuah Negeri District, Musi Rawas Regency, in 2021 and at least 200 participants. This study sample consisted of 108 with a purposive sampling method. This study utilized questionnaires and stool examinations using the Kato Katz method. Chi-square and multivariate logistic regression were used for statistical analysis.Results: Positive helminth infections amounted to 37,1% of the total (n=108). STH was comprised of 17.6% Ascaris lumbricoides, 9.3% Trichuris trichiura, and 25.9% hookworms. The finding of this research demonstrated a substantial (p = 0.000) relationship between the use of footwear and the advent of parasites. The logistic regression analysis results revealed that the most critical variable influencing the incidence of helminthiasis was not wearing any footwear.Conclusions: The study's findings suggest a correlation between footwear use and the risk of worm infection; as a result, it was recommended that children be thoroughly educated on personal hygiene, specifically footwear use, when using the bathroom.

AIM The current study aims to address the patient's dental anxiety (DA) And dental fear (DF) under the treatment of a general practitioner (GP) among different parameters. MATERIALS AND METHODS The cross-sectional study included 500 patients recruited from different clinics in Jazan, Saudi Arabia. Data were collected through a questionnaire-based form consisting of three parts; the first part was personal and demographic questions whereas the second and third parts were a modified dental anxiety scale (MDAS) and a dental fear survey (DFS) to measure DA and DF among patients. Spearman's correlation was used to measure the relation between DA and DF as well as Chi-square tests and logistic regression analyses for analyzing the effect of each variable on DA and DF. RESULTS All patients fulfilled their eligibility criteria. A high percentage was found in moderate anxiety (36.8%) as well as in moderate fear (46.2%) among different anxiety and fear scales. The association between DA and DF was positively significant (p

C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. Two X-ray crystallographic studies are presented of the antibody RoAb13, which binds to the peptide PIYDIN, which is part of the N-terminal domain of CCR5. The results may provide the basis for active immunization vaccines to stimulate an antibody response to native CCR5 that will block HIV infection., C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. This led to the hypothesis that stimulating an antibody response would block HIV with minimal toxicity. Here, X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides were undertaken: one peptide is a 31-residue peptide containing the PIYDIN sequence and the other is the PIDYIN peptide alone, where PIYDIN is part of the N-terminal region of CCR5 previously shown to be important for HIV entry. In the presence of the longer peptide (the complete N-terminal domain), difference electron density was observed at a site within a hypervariable CDR3 binding region. In the presence of the shorter core peptide PIYDIN, difference electron density is again observed at this CDR3 site, confirming consistent binding for both peptides. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 in order to block HIV infection.

The aim of the present study was to evaluate the behaviour of Meriz goats using environmental enrichment technique. Sixteen goats aged two-four years, were divided into two equal groups, one group was placed in a stall without any enrichment (control), while the other group placed in another stall with enrichment. The enriched stall had six objects including canopy, grooming brush, suspended tire, trunk of tree, and plastic PET bottle suspended and freely move on the floor. The goats’ behaviours were observed for eighty minutes in the morning and eighty minutes in the evening for fifteen consecutive days. Focal-animal sampling methods were used to record the behaviours, in which each animal was observed for ten-minutes period each day. Results revealed that the animals of enriched environment group displayed lower frequency of stereotypic and abnormal behaviour than control group. The mean frequencies of the groups were significantly different (P

Introduction: TNF-α/NF-kB signaling pathway plays an important role in promoting the inflammatory process and growth of breast cancer. Accordingly, the aim of the present study was to investigate the synergistic combination effect of endurance exercise with curcumin on breast cancer progression through TNF-α/NF-kB signaling axes in female BALB/c mice with breast cancer. Methods: The design of the present study was experimental. After transplanting 4T1 breast cancer into the right flank of 40 BALB/c mice, all mice were randomly divided into four groups, including endurance training (E), endurance training-curcumin (EC), curcumin (CC), and control (C). Then, E and EC groups (5 days per week) were performed for 5 weeks. Curcumin (6 times per week) was given by gavage to EC and CC groups for five weeks. The intratumoral expression of TNF-α and NF-kβ were measured using the qRT-PCR method. One-way analysis of variance and LSD post hoc test with SPSS version 16 were used for statistical analysis. P< 0.05 was considered statistically significant. Results: A significant decline in cancer growth and the gene expression of NF-kβ and TNF-α was observed in E, CC, and EC compared to the C group (P =0.001). Furthermore, a significant decline in expression of both genes was observed in EC compared with E. Conclusion: Endurance training combined with curcumin supplementation has a more effective role in reducing TNF-α and NF-κβ, and slowing the growth of breast cancer cells when compared with either of other interventions alone.

Introduction: The roots of E. longifolia jack (E.L.) or Tongkat Ali have been used in traditional medicine as well as supplements and food additives. Many chemical compounds have been detected in extracts of its roots which are believed to be responsible for its medicinal properties. In this study, our objectives were to study the effects of EL root extracts on the growth of Streptococcus Mutans, Lactobacillus and Candida Albicans isolated from saliva of adult patients with high caries risk. Materials and Methods: The ethanolic extract of the root of this plant was tested against saliva isolated Streptococcus Mutans, Lactobacillus and Candida Albicans via disc diffusion assay at a concentration of 200mg/mL. The minimum inhibitory concentration was carried out by the standard broth microdilution method. Cell viability of test microorganisms against different concentration of the extract and inhibition zones were calculated. Results: Disk diffusion assay showed positive zones of inhibition for all test microorganisms with S. mutans, Lactobacillus and C. albicans exhibiting zones of inhibition of 8.3 ± 0.7mm, 12.4 ± 2.4mm and 21.4 ± 2.7mm respectively. For minimum inhibitory concentration, the test microorganisms were tested at concentration of 250mg/ mL, 125mg/mL, 62.5mg/mL, 31.3mg/mL and 0mg/mL. The minimum inhibitory concentration showed that MIC of S. mutans was at 62.5mg/mL, Lactobacillus at 125mg/mL and C. albicans at 31.3mg/mL. Lastly, the cell viability results supported the MIC determined prior. Conclusion: Ethanol-based E. longifolia Jack root extract has an antimicrobial effect on the following microorganisms isolated from the saliva of high-risk caries adult patients: S. mutans, Lactobacillus and C. albicans.

Plodia interpunctella and Oryzaephilus surinamensis are found in food storehouses including dates and palm storages. The current study aimed to determine competition and overlap potentials of the two pests of date fruits. Time series models were used to study two species populations and logistic growth model to estimate the effect of density of the species. The results revealed the environmental capacities of O. surinamensis and P. interpunctella were 433 and 1610 (maximum number per 20 g), respectively, and the population growth rates (r) were 1.2 and 1.3, respectively. Ecological balances of the two species were close to each other from the first to the third week. The population of O. surinamensis decreased in the fourth week of the competition. The highest population balance of the two species was in the 14th week. The potential of exploitable ecological niches (eij) and the amount of non-exploited ecological niches by any species (zij) for O. surinamensis was higher than for P. interpunctella from the 8th week untill the end of sampling period. The overlap of ecological niches in the two species (D) ranged from 0.94 to 1, indicating a complete overlap of temporal activity in the two populations on date palm. The current results of this study can be used by integrated pest management specialists. Information over the effects of species competition on population dynamics and their coexistence can be used to predict population status and to adopt simple pest control methods.

Thrips (Thysanoptera: Thripidae) have been considered serious pests infesting a wide range of host plants around the world, which has also been the case for citrus trees in Tunisia, a South Mediterranean country. The present study was performed to refine our knowledge about density and damage of the most common, emerging thrips species on Navel oranges in northern Tunisia, and to evaluate the effectiveness of three insecticides in decreasing density of thrips and their induced damage. Populations of the three thrips species, Pezothrips kellyanus, Thrips major and Frankliniella occidentalis, on citrus flowers increased from March to June with F. occidentalis being the most common species found as larval and adult stages on either orange flowers or fruits. Two types of thrips blemishes on Navel orange were observed: ring-shaped silvery scaring, and marbling damage for which a positive and significant correlation was revealed with western flower thrips F. occidentalis. All tested insecticides (spinosad, acrinathrin and terpenoid) were effective in decreasing F. occidentalis population density on Navel orange trees, with both biopesticides spinosad and terpenoid being the most effective one day after treatment, while the chemical insecticide acrinathrin proved to be the most effective 7, 17 and 21 days after treatment. Furthermore, spinosad and terpenoid applications resulted in the lowest marbling damage percentage (4% and 6%, respectively) compared to acrinathrin (26%). The implications of the obtained findings for improving integrated pest management of thrips in Tunisian citrus orchards are highlighted and discussed herein.

In this study, the phytochemical, phenolic, flavonoid and bioactive compounds were successfully screened from crude extract of Sargassum wightii by LC-MS analysis after NIST interpretation. Bacterial growth inhibition study result was shown with 24 mm zone inhibition at 200 µg/mL concentration against P. aeruginosa. The increased phenolic content was much closed to gallic acid and the range was observed at 250 μg/mL concentration. In addition, flavonoid contents of the algae extract was indicated more significant with rutin at 200 μg/mL. In result, both the phenolic and flavonoid contents of the extract were more correlated with gallic acid and rutin. Further, the total anti-oxidant and DPPH radical scavenging activities were shown increased activity at 200 μg/mL concentrations. Furthermore, the excellent anti-bacterial alteration result was observed at 200 μg/mL concentration by minimum inhibition concentration. Therefore, the result was revealed that the marine algae Sargassum wightii has excellent phytochemical and anti-oxidant activities, and it has improved anti-bacterial activity against P. aeruginosa.

Superoxide produced by mitochondria has been implicated in numerous physiologies and pathologies. Eleven different mitochondrial sites that can produce superoxide and/or hydrogen peroxide (O2.-/H2O2) have been identified in vitro, but little is known about their contributions in vivo. We introduce novel variants of S1QELs and S3QELs (small molecules that suppress O2.-/H2O2 production specifically from mitochondrial sites IQ and IIIQo, respectively, without compromising bioenergetics), that are suitable for use in vivo. When administered by intraperitoneal injection, they achieve total tissue concentrations exceeding those that are effective in vitro. We use them to study the engagement of sites IQ and IIIQo in mice lacking functional manganese-superoxide dismutase (SOD2). Lack of SOD2 is expected to elevate superoxide levels in the mitochondrial matrix, and leads to severe pathologies and death about 8 days after birth. Compared to littermate wild-type mice, 6-day-old Sod2-/- mice had significantly lower body weight, lower heart succinate dehydrogenase activity, and greater hepatic lipid accumulation. These pathologies were ameliorated by treatment with a SOD/catalase mimetic, EUK189, confirming previous observations. A 3-day treatment with S1QEL352 decreased the inactivation of cardiac succinate dehydrogenase and hepatic steatosis in Sod2-/- mice. S1QEL712, which has a distinct chemical structure, also decreased hepatic steatosis, confirming that O2.- derived specifically from mitochondrial site IQ is a significant driver of hepatic steatosis in Sod2-/- mice. These findings also demonstrate the ability of these new S1QELs to suppress O2.- production in the mitochondrial matrix in vivo. In contrast, suppressing site IIIQo using S3QEL941 did not protect, suggesting that site IIIQo does not contribute significantly to mitochondrial O2.- production in the hearts or livers of Sod2-/- mice. We conclude that the novel S1QELs are effective in vivo, and that site IQ runs in vivo and is a significant driver of pathology in Sod2-/- mice.

Trichogramma egg parasitoids are successfully used for biological control of a wide range of lepidopteran pests worldwide. However, the field success depends upon their performance that could be in...

The first dendroclimatic reconstruction of May 1 snow water equivalent (SWE) was developed from a Sequoiadendron giganteum regional tree-ring chronology network of 23 sites in central California for the period 90–2012 CE. The reconstruction is based on a significant relationship between May 1 SWE and tree-ring growth and shows climate variability from interannual to intercentennial time scales. A regression-based reconstruction equation explains up to 55% of the variance of SWE for 1940–2012. Split-sample validation supports our use of a reconstruction model based on the full period of reliable observational data (1940–2012). Thresholds for May 1 SWE low (15 percentile) and high (80 percentile) years were selected based on the exploratory scatterplots relationship between observed and reconstructed data for the period 1940–2012. The longest period of consecutive low-SWE years in the reconstruction is 2 years and the frequency of the lowest SWE years is highest during the period 710–809 CE. The longest high-SWE period, defined by consecutive wet years, is 3 years (558–560 CE). SWE and its reconstruction positively correlate with northeastern Pacific sea surface temperatures, the low-frequency variability of which may provide some predictive ability. Ultimately, the instrumental record and reconstruction suggest that unlike other sites in the region, twentieth century SWE variability in these Sequoia groves has remained within historical boundaries and relatively buffered from extremes and severe declines, though this is likely to change in coming decades with potentially negative effects on water availability for these trees.

Queen mating frequency is an important reproductive trait of the western honeybee Apis mellifera. Yet, it demands more attention when investigated under extreme or confined ecosystems. Queen mating frequency of the Yemeni Honeybee A. m. jemenetica was estimated under Saudi Arabia desert conditions, Riyadh (24°71′36″N, 46°67′53″E). Mating of queens took place after 8–13 days from emergence. Duration of mating flight ranged between 26 and 39 min. Subsequently, six microsatellite loci were used to genotype queen's progeny (n = 30 workers/queen). The average number of drone alleles using workers genotypes ranged between 5.83 ± 0.31 and 6.33 ± 1.09. However, effective paternal allele number was extremely low and ranged between 3.35 ± 0.34 and 3.60 ± 0.40. This relatively low mating frequency of the Yemeni honeybee, A. m. jemenetica, might have striking effect on the overall colony survival. Providentially, this relatively low mating frequency does not impact colonial heterozygosity, shown in this study (0.66 ± 0.07–70 ± 0.04), adversely. These results may affect hive survivability and entails distinctive management practices under such conditions.

Background Israel has a regulated system with clearly defined indications for treatment with medical cannabis. Study question The main question was whether family physicians in southern Israel face barriers/knowledge gaps in prescribing cannabis for medical indications. The secondary question was whether there was a difference between residents and specialists in family medicine. Study design A questionnaire-based cross-sectional study. Measures and outcomes Attitudes of the participating physicians on the use of medical cannabis; comparison of attitudes of specialists in family medicine and residents on the use of medical cannabis. Results One hundred and fifty-two family physicians participated in the study including 48 residents. More than 78% supported the use of medical cannabis and about 63% supported it's legalization. About 84% of the physicians believed that medical cannabis helped cancer patients and 82% believed it helped in the chronic pain. Only 28.3% believed that family physicians should recommend the use of medical cannabis. The physicians were well aware of the psychiatric (82%) and the neurological (78%) adverse effects of medical cannabis. Most (68%) were not willing to prescribe medical cannabis. No socio-demographic characteristic was associated with willingness to prescribe cannabis. About 95% of the physicians believed that the main barrier to recommending treatment was its potential for abuse, 66% percent-the danger that it would leak to the general public. About 60% of the specialists were not prepared to undergoing training in the prescription of medical cannabis compared with 31% of the residents (P = 0.004). Conclusions Family physicians are concerned about recommending medical cannabis. It is encouraging that residents are motivated to undergo training to prescribe medical cannabis. There remain medical indications and adverse effects that family physicians are less aware of. Further studies should focus on effective ways to improve the level of physicians' knowledge on the issue.

The novel coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a public health emergency of international concern. The first confirmed COVID-19 case in Indonesia was announced on 2 March 2020, and later on, 11,192 confirmed cases were reported as of 3 May. The World Health Organization has stated that performing a real-time reverse transcription–polymerase chain reaction (RT-PCR) specific for SARS-CoV-2 on specimens from the upper and the lower respiratory tracts, especially nasopharyngeal and oropharyngeal swabs, is the standard diagnostic procedure for COVID-19. In Indonesia, we also use other diagnostic tests, such as rapid antibody tests specific for SARS-CoV-2. Herein, we report an atypical case of COVID-19 and describe the diagnostic process, the clinical course, with progression to severe pneumonia on Week 3 of illness and the case management. We also try to highlight the possibility of false-negative RT-PCR tests.

This experiment was carried out to evaluate the effects of dietary addition of probiotics (Protexin) and prebiotics (active MOS, mannan oligosaccharides) on growth performance, carcasses, and antibody titer in broilers. A total number of 360-day-old Ross broiler chicks were randomly divided into 9 groups in a 3 × 3 factorial arrangement. Nine broiler starter (0–21 d) and finisher (21–35 d) diets were formulated by using 3 levels of probiotics (0, 1, and 2 g/kg of feed) and 3 levels of MOS (0, 1, and 1.5 g/kg of feed) and were randomly allotted to 9 groups. Feed intake was not affected by interaction of treatments during all phases (P > 0.05). Feed intake was improved due to the main effect of probiotic (P = 0.0001) or MOS (P = 0.005). No interaction (P > 0.05) was observed for weight gain in the starter, finisher, and overall phases. While, during the starter and finisher phases, weight gain was increased by probiotics (P = 0.028 or 0.04, respectively). Dietary supplementation of MOS improved weight gain (P = 0.01) and feed conversion ratio (FCR) (P = 0.03) during the overall period, but during starter and finisher periods, weight gain and FCR were not affected by prebiotics. Apart from dressing percentage, no interaction or individual effect of probiotics and prebiotics was observed for carcass, breast, thigh, heart, liver, and gizzard weight. Antibody titer for infectious bursal disease (IBD) was improved (P = 0.026) by the interaction effect between probiotics and prebiotics, when compared with the control group. Antibody titer against Newcastle disease (ND) was not affected by probiotics or prebiotics or their interactions (P > 0.05). It could be concluded that supplementation of prebiotics or probiotics can improve the growth performance of broilers. It may also be helpful in improving the antibody titer against IBD in broilers fed antibiotic-free diets.

The Caulerpa taxifolia is excellent marine green algae, which produced enormous bioactive compounds with more biological activities. Also, it is an excellent source for synthesis of Ag NPs with increased bioactivity against various infections. In our study, the marine algae marine algae Caulerpa taxifolia mediated Ag NPs was synthesized effectively. The synthesized Ag NPs was characterized well using UV-spectrometer and X-ray powder diffraction (XRD) and confirmed as synthesized particle was Ag NPs. The available structure of the Ag NPs was morphologically identified by scanning electron microscope (SEM), and exact minimum size, polydispersive spherical shape of the entire Ag NPs structure was confirmed by Transmission electron microscope (TEM). Further, the anti-cancer efficiency of biosynthesized Ag NPs against A549 lung cancer cells was found at 40 µg/mL concentration by cytotoxicity experiment. In addition, the phase contrast images of the result were supported the Ag NPs, which damaged the A549 morphologically clearly. Finally, florescence microscopic images were effectively proved the anti-cancerous effect against A549 lung cancer cells due to the condensed morphology of increased death cells. All the confirmed in-vitro results were clearly stated that the Caulerpa taxifolia mediated Ag NPs has superior anti-cancer agent against A549 lung cancer cells.

Histone lysine demethylases (KDMs) are enzymes that remove the methylation marks on lysines in nucleosomes' histone tails. These changes in methylation marks regulate gene transcription during both development and malignant transformation. Depending on which lysine residue is targeted, the effect of a given KDM on gene transcription can be either activating or repressing, and KDMs can regulate the expression of both oncogenes and tumour suppressors. Thus, the functions of KDMs can be regarded as both oncogenic and tumour suppressive, contingent on cell context and the enzyme isoform. Finally, KDMs also demethylate nonhistone proteins and have a variety of demethylase-independent functions. These epigenetic and other mechanisms that KDMs control make them important regulators of malignant tumours. Here, we present an overview of eight KDM subfamilies, their most-studied lysine targets and selected recent data on their roles in cancer stem cells, tumour aggressiveness and drug tolerance.

Several methods have been conducted for embryo sex preselection, which includes X- and Y- sperm separation, changing the pH of the female reproductive tract, time of mating before or after ovulation, and feeding formula, such as altering the presence of minerals in diet content before breeding may affect the embryo sex preselection ratio. In this study, three food formulas to feed female sheep were created with the cooperation of the Arabian Agricultural Services Company (Arasco). Ewes were fed with modified food formulas for one month before mating with males. The first group (A) (30 ewes), modified for male embryo gender preselection, were fed a diet with an increased percentage of the minerals Na+, K+, and P-. The second group (B) (30 ewes), modified for female sex preselection, were fed a diet with an increased percentage of the minerals Ca++ and Mg++. The third (control) group (C) (30 ewes) were fed the regular (Wafi) food formula. Our results showed no significant differences were in mean body weights between the three groups at the end of the feeding period. The results of different feeding formulas on mineral serum blood samples of ewes showed an increase in Na+, K+, and Cl- ions in the serum of group (A) compared to the other groups (B and C). The concentration of Na+ in the serum of group (A) was significantly (P < 0.05) higher than group (C). The concentration of Cl- ions in serum samples of ewes in group (A) was significantly higher than group (C) and group (B) (P < 0.05). The role of maternal feeding on embryo sex preselection shows that the pregnancy rate of animals in group (A) was 73.33%. Group (A) birthed 17 males and 5 females (77.27% and 22.72%, respectively). The pregnancy rate in group (B) was 70%. Group (B) birthed 6 males (27.27%) and 16 females (72.72%). Finally, the control group (C) had a pregnancy rate of 76.66%. They birthed 13 males (54.41%) and 11 females (44.83%). The results of our study confirm that altering the percentage of minerals in the maternal diet plays a role in sex preselection in sheep, which agree with other mammalian studies in rats and mice. Thus, the result of this study can help farmers to manage their breeding. We recommend that more studies on the relationship between minerals in the diet should be conducted for other spices and human sex preselection.

The gastrointestinal tract is colonized with trillions of bacteria that are specialized of numerous physiological and immunological functions. The gut microbiata have been shown to impact nutrients processing and energy extraction. Accordingly, a link between obesity and the diversity and size of gut microbiata has been established. This review discussed the possible biochemical mechanisms through which gut micobiota might impact obesity and fat storage regulations and processing.

Studies of the association between palatal rugae (PR) and malocclusion are scarce. While unstable following treatment such as rapid maxillary expansion, we hypothesized that PR differ among malocclusions because of genetic determination but also different environmental conditions during development. Our goal was to assess the possible association between PR morphometric measurements and both sagittal and vertical characteristics of malocclusion. Maxillary pretreatment dental casts of 243 nongrowing individuals (115 males, 128 females, age 25.5 ± 7.5 years) were laser scanned (Perceptron ScanWorks® V5, Hallam VIC, Australia); angular and linear measurements of the first three PR were recorded in transverse and anteroposterior directions. Cephalometric measurements were obtained from corresponding digitized lateral cephalograms. Statistics included analyses of variance to compare PR measurements among sagittal (class I, class II divisions 1 and 2, class III) and vertical (hypodivergent, normodivergent, hyperdivergent) malocclusion groups and the Pearson correlations among PR dimensions and cephalometric measurements. PR measurements were statistically different between malocclusions, especially with respect to vertical patterns. A majority of transverse and anteroposterior rugae measurements were greatest in class II division 2 subjects. PR were more anteriorly directed in hypodivergent than hyperdivergent groups; the transverse separation between opposing rugae points was smaller. Correlations were generally low. The findings suggest the possibility for PR to adapt to environmental effects in developing malocclusions, mostly in the class II division 2 phenotype. This premise reinforces the need to explore in longitudinal studies the long-term environmental influences on rugae superimposed on their genetically determined morphological pattern.

Hepatitis B virus (HBV) is a leading cause of liver disease and a possible worldwide source of severe morbidity and mortality. The current standard therapy using interferons or antiviral agents is not successful in all cases and is associated with severe side effects. Consequently, the development of new medicines for the treatment of HBV is still relevant. This experimental study was therefore performed to assess the anti-hepatitis B virus (HBV) potential of 10 endemic medicinal plants from Socotra Island which represents a distinctive region of Yemen. Socotra Island is renowned for its biodiversity with significant flora with globally important plants. The methanolic extracts of the selected plants were first assessed for cytotoxicity on HepG2.2.15 cells and cytotoxicity concentration (CC50) values were resolved. The methanolic extracts of the plants were additionally examined on HepG2.2.15 cells for anti-HBV potential by examining the inhibition of HBsAg and HBeAg production in the culture supernatants, and calculating their half-maximum inhibitory concentration (IC50) and therapeutic index (TI) values. Out of ten plants only five plants exhibit inhibition of HBsAg production in a dose and time dependent manner. These five plants are Acacia pennivenia, Boswellia discorea, B. socotrana, Hypoestes pubescens and Dracaena cinnabari with IC50 values of 21.15, 24.51, 118.94, 17.65, 20.93 μg/mL, respectively. Moreover, the presence of terpenoids, tannins, alkaloids and flavonoids that could contribute to antiviral efficacy was validated with a qualitative phytochemical study of active extracts. Key words: Antiviral, Hepatitis B, medicinal plants; Socotra, Yemen.

Cancer and microbial infectious diseases are considered a global threat. Plants have been investigated across the world to exploit their potential anticancer and antimicrobial effective agents. In this study, two medicinal plant species native to Saudi Arabia, namely; Artemisia judaica and Artemisia sieberi were screened to assess their antioxidant, anticancer and antimicrobial potential activities as well as phytochemical compositions. The collected aerial parts were extracted by maceration with methanol. Cytotoxic and antimicrobial activities were investigated using the MTT and MIC assays, respectively. Free radical scavenging and antioxidant potential were assessed respectively by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The total flavonoid and phenolic contents of the crude methanolic extract were quantified using standard methods. Artemisia judaica displayed a strong cytotoxicity compared to A. sieberi while both species showed approximately similar bacterial and fungal growth inhibition. In contrast, A. sieberi displayed the highest phenol and flavonoid contents between the two species which was consistent with the higher antioxidant activity found in A. sieberi. It is concluded that both Artemisia species could be a promising source of antioxidant, anticancer and antimicrobial agents. Key words: Artemisia judaica, Artemisia sieberi, anticancer, antimicrobial.

Killer-cell immunoglobulin-like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south-western Iran. KIR genes and KIR2DS4 variants were typed by polymerase chain reaction-sequence-specific primer (PCR-SSP) in 167 patients with AML and 169 healthy controls. Our results showed 10% of patients-mostly females-were classified as M3. Flt3 mutations were detected in 26% of patients, most of whom had internal tandem duplication (ITD). The frequency of activating KIRs (aKIRs)-mainly KIR3DS1-was higher in patients, whereas inhibitory KIRs (iKIRs)-particularly KIR3DL1 and KIR2DL1-were more common among controls. The incidence of the KIR2DS4fl allele was higher among patients with non-M3 AML than controls. We also found a higher frequency of 4 or more iKIR genes in the controls and a higher frequency of 4 or more aKIR genes in the patients. Individuals with more iKIR than aKIR belonged predominantly to the control group. Individuals with the telomeric AA genotype who had inherited the KIR2DS4fl allele were more frequent in the patient group. According to our results, increased frequency of aKIRs in patients with AML may lead to the hyperactivation of NK cells against malignant cells with reduced or lack of HLA class I molecules followed by NK cell exhaustion which allow malignant cells to progress.

The purpose of the work is to develop a nutrient medium for differentiation of bacillus from soil aerobic bacilli. In order to achieve the set goal, we used the method of introduction into the environment of cultivation of microorganisms separated from animals and objects of external environment (water, soil, feed, air, scrapes from different surfaces suspected of contamination by their bacillus ) of nutrient substrate sucrose, used by bacteria of Bacillus genus for synthesis of product of their metabolism, a sign absent in bacillus . This feature is essential for identification and differentiation of bacillus from closely related saprophytes. To identify and differentiate the bacillus , the microbes isolated from the external environment were cultivated in a nutrient medium consisting of agar (MPA) and () synthesis of sucrose in the amount of 10% to 100 ml of melted agar. The proposed nutrient media was prepared as follows. agar (500 ml) was melted at 1000C, 10 g of sucrose was added per 100 ml of medium and after the complete dissolution of sucrose, the nutrient medium was poured into dishes and used for sowing the studied material for identification and differentiation of grown crops. The efficiency of the method has been tested in production experiments with positive evaluation. For this purpose, soil samples taken from the territory of old cattle cemeteries were fractionally sown on MPA and for 16-18 hours at 370C and examined crops for the presence of matte and rough (R-form) colonies.

Natural products play a pivotal role in innovative drug discovery by providing structural leads for the development of new therapeutic agents against various diseases.The present study aims to focus on the in silico assessment of the therapeutic potential of antidiabetic phytoconstituents which were identified and isolated from the extracts of Bauhinia rufescens Lam, a medicinal plant traditionally used for various pharmacotherapeutic purposes. The physicochemical and pharmacokinetic parameters of the previously isolated thirty eight compounds were predicted using SwissADME web tool whereas OSIRIS Property Explorer was used for toxicity risk assessment and drug- likeliness. Twelve compounds were selected for docking on human α-glucosidase and α-amylaseenzymes using Autodock 4.0 software. Furthermore, the active extract was in vivo tested for the antidiabetic activity and then identified usingTLC bioautographic method. Eriodictyol was found to have the highest potential as an inhibitor against α-amylase with binding energy of −9.92 kcal/mol. Rutin was the most potent against α-glucosidase with binding energy of-9.15 kcal/mol. A considerable number of hydrogen bonds and hydrophobic interactions were computed between the compounds and the enzymes thereby making them energetically favorable and suggesting inhibition of these two enzymes as a plausible molecular mechanism for their antidiabetic effect. These two flavonoids could therefore be used as potential leads for structure- based design of new effective hypoglycemic agents.

The Saw-toothed grain beetle, Oryzaephilus surinamensis L. is a stored product pest that 7 imposes significant damages on the dried and semi-dried date fruits. The current study aimed to the 8 inve...

An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level Schistosoma infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with Schistosoma mansoni and Schistosoma haematobium gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.

Background To investigate the age-dependent changes in circulating anti-Müllerian hormone (AMH) levels in healthy Arabic-speaking Lebanese women, and to correlate changes in serum AMH levels with serum FSH and LH values, and LH/FSH ratio. Methods Cross-sectional study, involving 1190 healthy females, age 17–54 years, with regular menses and both ovaries. Serum AMH levels (ng/ml) were measured by ELISA. Results There was an inverse proportion of AMH and subject’s age, which declined from median 6.71 (2.91) ng/ml in young subjects, to 0.68 (0.45) ng/ml in subjects older than 50 years. Average yearly decrease in median AMH levels was 0.27 ng/ml/year through age 35, but then diminished to 0.12 ng/ml/year afterwards. Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of age as determinant of AMH levels. In contrast to AMH, FSH levels increased progressively from 5.89 (0.11–62.10) ng/ml in young subjects, to 38.43 (3.99–88.30) ng/ml in subjects older than 50 years. On the other hand, age-dependent changes in LH/FSH ratio paralleled those of AMH. Linear regression modeling testing the independent effect of AMH on FSH and LH, adjusted for age, showed that AMH was significant predictor of FSH and LH/FSH ratio, but not LH. This did not contribute significantly to baseline LH and FSH prediction. Conclusions Circulating AMH levels are inversely related to age as also shown elsewhere, and are predictors of LH/FSH ratio and FSH but not LH levels in eumenorrheic females.

With respect to given contradictory data in radiobiology, that according to some authors, irradiation of cells of plant and animal origin initiates DNA changes and according to others, repeated irradiation of cells in small doses has a stimulating effect on metabolism without increasing the purity of mutations, we conducted the present study, with the aim to study the stability of the genome of MDBK cell line against a background of single and double (fractional) irradiation. The object of the study was a continuous MDBK cell line (Madin-Darby Bovire Kidney Cell, cattle, kidney), which was grown in medium 199, manufactured by Federal State Budget Institution FCTRB-ARRVI (Kazan) with 10% bovine serum and the addition of antibiotics (benzylpenicillin sodium salt, kanamycin at 100 units/ml) (streptomycin sulfate at 100 μg/ml) according to standard procedure. A monolayer culture of MDBK cells in the logarithmic growth phase (3-4 days after culture) served as contacting cells. As a result, a radio-modified cell line, called MDBK-2, was obtained. Moreover, in an unirradiated MDBK cell culture, the level of chromosomal breakdowns was in the range of 1.03-3.1% with respect to the total number of studied anaphases. Based on the obtained data, it can be concluded, that during prolonged cultivation of MDBK cells, irradiated in a small (adaptive) dose and re-irradiated in 3-minute higher dose (5.95 Gy), there is a significant decrease in the yield of aberrant cells, induced by a test dose of γ-rays.

Thrips are major economic insect pests of citrus worldwide. During the few last years these insects have become serious pests of citrus in Tunisia. The objective of this study was to determine the species of thrips’ natural enemies occurring in citrus orchards and assess the effects of manure application on the abundance of soil predatory mites. Sampling of thrips and their natural enemies was performed in citrus orchards in northern Tunisia from 2015 to 2017. Results revealed that (i) the most abundant predatory species found on plant leaves was Chrysoperla carnea representing 40.38% of the total number of natural enemies collected, followed by Coccinella septempunctata (13.57%) and that (ii) the most abundant soil predatory mite was Parasitus americanus representing 43.44% of the total number of predatory mites collected, followed by Stratiolaelaps scimitus, Pachylaelaps imitans and Odontoscirus sp. (9.43%, 6.45% and 5.41%, respectively). Higher population densities of P. americanus and S. scimitus in the soil were directly correlated with decreased thrips’ abundance and reduced plant damage. Our findings suggest that manure application significantly affects the abundance of both predatory mites and thrips in the soil. Here we provide first knowledge on natural enemies’ action against thrips and their potential use as biocontrol agents in Tunisian citrus orchards. The implications of the obtained results for developing and implementing the most eco-friendly and sustainable pest management options for citrus pest thrips are stated and discussed herein.

Psoriasis is characterized by hyperproliferation and defective differentiation of keratinocytes (KCs). Patients with psoriasis are at a high risk of developing diabetes and cardiovascular diseases. The debate on the genetic origin of psoriasis pathogenesis remains unresolved due to lack of suitable in vitro human models mimicking the disease phenotypes. In this study, we provide the first human induced pluripotent stem cell (iPSC) model for psoriasis carrying the genetic signature of the patients. iPSCs were generated from patients with psoriasis (PsO-iPSCs) and healthy donors (Ctr-iPSCs) and were efficiently differentiated into mature KCs. RNA sequencing of KCs derived from Ctr-iPSCs and PsO-iPSCs identified 361 commonly upregulated and 412 commonly downregulated genes. KCs derived from PsO-iPSCs showed dysregulated transcripts associated with psoriasis and KC differentiation, such as HLA-C, KLF4, chemokines, type I interferon-inducible genes, solute carrier family, IVL, DSG1, and HLA-DQA1, as well as transcripts associated with insulin resistance, such as IRS2, GDF15, GLUT10, and GLUT14. Our data suggest that the KC abnormalities are the main driver triggering psoriasis pathology and highlights the substantial contribution of genetic predisposition in the development of psoriasis and insulin resistance.

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.