Exploring non-cytotoxic, antioxidant, and anti-inflammatory properties of selenium nanoparticles synthesized from Gymnema sylvestre and Cinnamon cassia extracts for herbal nanomedicine.

The increasing need for pharmaceutical agents that possess attributes such as safety, cost-effectiveness, environmental sustainability, and absence of side effects has driven the advancement of nanomedicine research, which lies at the convergence of nanotechnology and medicine. AIMS AND OBJECTIVES: The study aimed to synthesize non-toxic selenium nanoparticles (SeNPs) using Gymnema sylvestre (G. sylvestre) and Cinnamon cassia (C. cassia) extracts. It also sought to develop and evaluate versatile nanomedicine formulations i.e. selenium nanoparticles of G. sylvestre and C. cassia (SeNPs), drug (lupeol) loaded SeNPs (DLSeNPs), drug-loaded and coated (PEG) SeNPs (DLCSeNPs) without side effects. METHODS: The SeNPs formulations were hydrothermally synthesized, loaded with lupeol to improve efficacy, coated with polyethylene glycol (PEG) for targeted delivery, and characterized using UV-Vis spectrophotometry, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), zeta potential analysis, size distribution analysis, and X-ray diffraction (XRD). Hemolytic cytotoxicity, 2,2-Diphenyl-1-picrylhydzayl (DPPH), total Reducing power, and total antioxidant capacity (TAC) antioxidant assays, carrageenan-induced paw edema, and histological studies were used to estimate the acute anti-inflammatory activity of the synthesized SeNPs. RESULTS: The final form of PEGylated and drug (lupeol)-loaded selenium nanoparticles (DLCSeNPs) exhibited an average particle size ranging from 100 to 500 nm as evidenced by SEM, and Zeta potential results. These nanoparticles demonstrated no cytotoxic effects and displayed remarkable antioxidant (IC50 values 19.29) and anti-inflammatory capabilities. These results were fed into Graph-pad Prism 5 software and analyzed by one-way ANOVA, followed by Tukey's post hoc test (p < 0.001). All nano-formulations exhibited significant overall antioxidant activity, with IC50 values ≤ 386 (p < 0.05) as analyzed by ANOVA. The study's results suggest that G. sylvestre outperformed C. cassia in terms of reducing 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical, potassium ferricyanide, and ammonium molybdate in respective antioxidant assays. As far as anti-inflammatory activities are concerned drug (lupeol)-loaded and PEG-coated G. sylvestre SeNPs exhibited the highest anti-inflammatory potential from all other nano-formulations including drug (lupeol)-loaded and PEG-coated C. cassia SeNPs, as exhibited to reduce the release of pro-inflammatory signals i.e. cytokines and NF-kB, making them innovative anti-inflammatory nanomedicine. CONCLUSION: The study synthesized lupeol-loaded and PEG-coated SeNPs, showcasing the potential for biocompatible, cost-effective anti-inflammatory nanomedicines. G. Sylvester's superior antioxidant and anti-inflammatory performance than Cinnamon cassia emphasizes medicinal plant versatility.

Association between CYP1A2 gene variants -163 C/A (rs762551) and -3860 G/A (rs2069514) and bladder cancer susceptibility.

BACKGROUND: Bladder cancer (BLCA) poses a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options. AIMS AND OBJECTIVES: This study aims to investigate the association between two specific polymorphisms, CYP1A2-163 C/A and CYP1A2-3860G/A, within the Cytochrome P450 1A2 (CYP1A2) gene and susceptibility to BLCA. METHODS: The study employed a case-control design, genotyping 340 individuals using Polymerase Chain Reaction-High-Resolution Melting Curve (PCR-HRM). Various genetic models were applied to evaluate allele and genotype frequencies. Genetic linkage analysis was facilitated using R packages. RESULTS: The study reveals a significant association with the - 163 C/A allele, particularly in the additive model. Odds ratio (OR) analysis links CYP1A2-163 C/A (rs762551) and CYP1A2-3860G/A(rs2069514) polymorphisms to BLCA susceptibility. The rs762551 C/A genotype is prevalent in 55% of BLCA cases and exhibits an OR of 2.21. The A/A genotype has an OR of 1.54. Regarding CYP1A2-3860G/A, the G/A genotype has an OR of 1.54, and the A/A genotype has an OR of 2.08. Haplotype analysis shows a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. This study underscores associations between CYP1A2 gene variants, particularly rs762551 (CYP1A2-163 C/A), and an increased susceptibility to BLCA. Haplotype analysis of 340 individuals reveals a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. CONCLUSION: In conclusion, the - 163 C/A allele, C/A genotype of rs762551, and G/A genotype of rs2069514 emerge as potential genetic markers associated with elevated BLCA risk.

Endophytic Fungi-Mediated Defense Signaling in Maize: Unraveling the Role of WRKY36 in Regulating Immunity against Spodoptera frugiperda.

Seed priming with beneficial endophytic fungi is an emerging sustainable strategy for enhancing plant resistance against insect pests. This study examined the effects of Beauvaria bassiana Bb20091317 and Metarhizium rileyi MrCDTLJ1 fungal colonization on maize growth, defence signalling, benzoxazinoid levels and gene expression. The colonization did not adversely affect plant growth but reduced larval weights of Spodoptera frugiperda. Maize leaves treated with M. rileyi exhibited higher levels of jasmonic acid, jasmonoyl-Isoleucine, salicylic acid, and indole acetic acid compared to control. B. bassiana and M. rileyi accelerated phytohormone increase upon S. frugiperda herbivory. Gene expression analysis revealed modulation of benzoxazinoid biosynthesis genes. We further elucidated the immune regulatory role of the transcription factor zmWRKY36 using virus-induced gene silencing (VIGS) in maize. zmWRKY36 positively regulates maize immunity against S. frugiperda, likely by interacting with defense-related proteins. Transient overexpression of zmWRKY36 in tobacco-induced cell death, while silencing in maize reduced chitin-triggered reactive oxygen species burst, confirming its immune function. Overall, B. bassiana and M. rileyi successfully colonized maize, impacting larval growth, defense signalling, and zmWRKY36-mediated resistance. This sheds light on maize-endophyte-insect interactions for sustainable plant protection.

An SNP based genotyping assay for genes associated with drought tolerance in bread wheat.

BACKGROUND: SnRK2 plays vital role in responding to adverse abiotic stimuli. The applicability of TaSnRK2.4 and TaSnRK2.9 was investigated to leverage the potential of these genes in indigenous wheat breeding programs. METHODS: Genetic diversity was assessed using pre-existing markers for TaSnRK2.4 and TaSnRK2.9. Furthermore, new markers were also developed to enhance their broader applicability. KASP markers were designed for TaSnRK2.4, while CAPS-based markers were tailored for TaSnRK2.9. RESULTS: Analysis revealed lack of polymorphism in TaSnRK2.4 among Pakistani wheat germplasm under study. To validate this finding, available gel-based markers for TaSnRK2.4 were employed, producing consistent results and offering limited potential for application in marker-assisted wheat breeding with Pakistani wheat material. For TaSnRK2.9-5A, CAPS2.9-5A-1 and CAPS2.9-5A-2 markers were designed to target SNP positions at 308 nt and 1700 nt revealing four distinct haplotypes. Association analysis highlighted the significance of Hap-5A-1 of TaSnRK2.9-5A, which exhibited association with an increased number of productive tillers (NPT), grains per spike (GPS), and reduced plant height (PH) under well-watered (WW) conditions. Moreover, it showed positive influence on NPT under WW conditions, GPS under water-limited (WL) conditions, and PH under both WW and WL conditions. High selection intensity observed for Hap-5A-1 underscores the valuable role it has played in Pakistani wheat breeding programs. Gene expression studies of TaSnRK2.9-5A revealed the involvement of this gene in response to PEG, NaCl, low temperature and ABA treatments. CONCLUSION: These findings propose that TaSnRK2.9 can be effectively employed for improving wheat through marker-assisted selection in wheat breeding efforts.

Removal of Cr(VI) from Wastewater Using Acrylonitrile Grafted Cellulose Extracted from Sugarcane Bagasse.

A highly efficient low-cost adsorbent was prepared using raw and chemically modified cellulose isolated from sugarcane bagasse for decontamination of Cr(VI) from wastewater. First, cellulose pulp was isolated from sugarcane bagasse by subjecting it to acid hydrolysis, alkaline hydrolysis and bleaching with sodium chlorate (NaClO3). Then, the bleached cellulose pulp was chemically modified with acrylonitrile monomer in the presence Fenton's reagent (Fe+2/H2O2) to carry out grafting of acrylonitrile onto cellulose by atom transfer radical polymerization. The developed adsorbent (acrylonitrile grafted cellulose) was analyzed by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Both raw cellulose and acrylonitrile grafted cellulose were used for chromium removal from wastewater. The effects of metal ion concentration, pH, adsorbent dose and time were studied, and their values were optimized. The optimum conditions for the adsorption of Cr(VI) onto raw and chemically modified cellulose were: metal ion concentration: 50 ppm, adsorbent dose: 1 g, pH: 6, and time: 60 min. The maximum efficiencies of 73% and 94% and adsorption capacities of 125.95 mg/g and 267.93 mg/g were achieved for raw and acrylonitrile grafted cellulose, respectively. High removal efficiency was achieved, owing to high surface area of 79.92 m2/g and functional active binding cites on grafted cellulose. Isotherm and kinetics studies show that the experimental data were fully fitted by the Freundlich isotherm model and pseudo first-order model. The adsorbent (acrylonitrile grafted cellulose) was regenerated using three different types of regenerating reagents and reused thirty times, and there was negligible decrease (19%) in removal efficiency after using it for 30 times. Hence, it is anticipated that acrylonitrile could be utilized as potential candidate material for commercial scale Cr(VI) removal from wastewater.

Comprehensive insights into the regulatory mechanisms of lncRNA in alkaline-salt stress tolerance in rice.

BACKGROUND: Alkaline-salt is one of the abiotic stresses that slows plant growth and developmental processes and threatens crop yield. Long non-coding RNAs (lncRNAs) are endogenous RNA found in plants that engage in a variety of cellular functions and stress responses. METHOD: lncRNAs act as competing endogenous RNAs (ceRNA) and constitute a new set of gene control. The precise regulatory mechanism by which lncRNAs function as ceRNAs in response to alkaline-salt stress remains unclear. We identified alkaline-salt responsive lncRNAs using transcriptome-wide analysis of two varieties including alkaline-salt tolerant [WD20342 (WD)] and alkaline-salt sensitive [Caidao (CD)] rice cultivar under control and alkaline-salt stress treated [WD20342 (WDT, and Caidao (CDT)] conditions. RESULTS: Investigating the competitive relationships between mRNAs and lncRNAs, we next built a ceRNA network involving lncRNAs based on the ceRNA hypothesis. Expression profiles revealed that a total of 65, 34, and 1549 differentially expressed (DE) lncRNAs, miRNAs, and mRNAs were identified in alkaline-salt tolerant WD (Control) vs. WDT (Treated). Similarly, 75 DE-lncRNAs, 34 DE-miRNAs, and 1725 DE-mRNAs (including up-regulated and down-regulated) were identified in alkaline-salt sensitive CD (Control) vs. CDT (Treated), respectively. An alkaline-salt stress ceRNA network discovered 321 lncRNA-miRNA-mRNA triplets in CD and CDT, with 32 lncRNAs, 121 miRNAs, and 111 mRNAs. Likewise, 217 lncRNA-miRNA-mRNA triplets in WD and WDT revealed the NONOSAT000455-osa_miR5809b-LOC_Os11g01210 triplet with the highest degree as a hub node with the most significant positive correlation in alkaline-salt stress response. CONCLUSION: The results of our investigation indicate that osa-miR5809b is dysregulated and plays a part in regulating the defense response of rice against alkaline-salt stress. Our study highlights the regulatory functions of lncRNAs acting as ceRNAs in the mechanisms underlying alkaline-salt resistance in rice.

Synergistic neuroprotection by phytocompounds of Bacopa monnieri in scopolamine-induced Alzheimer's disease mice model.

BACKGROUND: Millions of people around the globe are affected by Alzheimer's disease (AD). This crippling condition has no treatment despite intensive studies. Some phytocompounds have been shown to protect against Alzheimer's in recent studies. METHODS: Thus, this work aimed to examine Bacopa monnieri phytocompounds' synergistic effects on neurodegeneration, antioxidant activity, and cognition in the scopolamine-induced AD mice model. The toxicity study of two phytocompounds: quercetin and bacopaside X revealed an LD50 of more than 2000 mg/kg since no deaths occurred. RESULTS: The neuroprotection experiment consists of 6 groups i.e., control (saline), scopolamine (1 mg/kg), donepezil (5 mg/kg), Q (25 mg/kg), BX (20 mg/kg), and Q + BX (25 mg/kg + 20 mg/kg). Visual behavioral assessment using the Morris water maze showed that animals in the diseased model group (scopolamine) moved more slowly toward the platform and exhibited greater thigmotaxis behavior than the treatment and control groups. Likewise, the concentration of biochemical NO, GSH, and MDA improved in treatment groups concerning the diseased group. mRNA levels of different marker genes including ChAT, IL-1α, IL-1 ß, TNF α, tau, and ß secretase (BACE1) improved in treatment groups with respect to the disease group. CONCLUSION: Both bacopaside X and quercetin synergistically have shown promising results in neuroprotection. Therefore, it is suggested that Q and BX may work synergistically due to their antioxidant and neuroprotective property.

The comparative transcriptome analysis of two green super rice genotypes with varying tolerance to salt stress.

BACKGROUND: Salinity is one of the main abiotic factors that restrict plant growth, physiology, and crop productivity is salt stress. About 33% of the total irrigated land suffers from severe salinity because of intensive underground water extraction and irrigation with brackish water. Thus, it is important to understand the genetic mechanism and identify the novel genes involved in salt tolerance for the development of climate-resilient rice cultivars. METHODS AND RESULTS: In this study, two rice genotypes with varying tolerance to salt stress were used to investigate the differential expressed genes and molecular pathways to adapt under saline soil by comparative RNA sequencing at 42 days of the seedling stage. Salt-susceptible (S3) and -tolerant (S13) genotypes revealed 3982 and 3463 differentially expressed genes in S3 and S13 genotypes. The up-regulated genes in both genotypes were substantially enriched in different metabolic processes and binding activities. Biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and plant signal transduction mechanisms were highly enriched. Salt-susceptible and -tolerant genotypes shared the same salt adaptability mechanism with no significant quantitative differences at the transcriptome level. Moreover, bHLH, ERF, NAC, WRKY, and MYB transcription factors were substantially up-regulated under salt stress. 391 out of 1806 identified novel genes involved in signal transduction mechanisms. Expression profiling of six novel genes further validated the findings from RNA-seq data. CONCLUSION: These findings suggest that the differentially expressed genes and molecular mechanisms involved in salt stress adaptation are conserved in both salt-susceptible and salt-tolerant rice genotypes. Further molecular characterization of novel genes will help to understand the genetic mechanism underlying salt tolerance in rice.

Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation.

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the expression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of the well-known DNA protectant (ectoine) in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA epigenetic modifications-related gene analysis were performed. The results showed that extended ectoine treatment globally hypomethylated DNA in skin cells, especially in the CpG island (CGIs) element, and 5mC percentage was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation and did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3l, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Snrpn, and Mest. Overall, ectoine mildly demethylates DNA in skin cells, modulates the expression of epigenetic modification-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

Chlorophyll fluorescence and grain filling characteristic of wheat (Triticum aestivum L.) in response to nitrogen application level.

BACKGROUND: This study aims to understand the influence of chlorophyll fluorescence parameters on yield of winter wheat in some areas of China. Nitrogen (N) application is believed to improve photosynthesis in flag leaf ultimately increase final yield. METHODS AND RESULTS: To understand the response of chlorophyll fluorescence parameters of wheat, flag leaf and the effect of N fertilization was carried out at booting stage under greenhouse during year 2018-2019 using winter wheat cultivar "Yunhan-20410' 'Yunhan-618". The results showed that the maximum chlorophyll content of flag leaves occurred at booting stage. Under, Yunhan-20410 condition, maximum photochemical quantum efficiency (FV/Fm), potential activity (ΦPSII), potential activity of PSII (FV/FO), and photochemical quenching coefficient (qp) showed "high-low" variation, and the maximum values were observed between May 4 and May 12. However, Yunhan-20410 showed FV/Fm, FV/FO, and qp showed "low-high-low" curve at booting stage. Compared to Yunhan-618, Yunhan-20410 at booting stage significantly decreased FV/Fm, FV/FO, qp, and ΦPSII (P<0.05), and non-photochemical quenching (NPQ) significantly increased (P<0.05). CONCLUSION: The outcome of present investigation suggest that chlorophyll fluorescence parameters could be valuable insight to understand yield stability under stress condition. Moreover, the investigated parameters could be useful criteria for selection of genotypes under varying nitrogen application levels.

A survey of bluetongue infection in one-humped camels (Camelus Dromedarius); seroprevalence and risk factors analysis.

Bluetongue (BT) is an insect-borne, non-contagious viral disease which affects domestic ruminants including camels and is transmitted by Culicoides spp. Clinical symptoms of BT are typically seen in sheep, although subclinical BT infections are mostly seen in cattle, goats, and camelids. The goal of the present study was to evaluate the sero-prevalence of Bluetongue virus (BTV) in camels from some governorates in Egypt's southern and northern regions, as well as the infection's potential risk factors. During 2020-2021, a cross sectional study was conducted to screen presence of anti-BTV antibodies in 400 serum samples, which were collected randomly from camels, examined using competitive enzyme-linked immunosorbent assay (cELISA). The sera of 102 out of 400 camels tested positive for BTV, representing a frequency of 25.5%. Moreover, the odds of sero-positivity were higher among camels living in Aswan (OR = 5.33, 95%CI: 2.35-12.11), especially in females (OR = 2.63, 95%CI = 1.44-4.09) during summer season (OR = 2.40, 95%CI = 1.20-4.81). Furthermore, the probability of getting BTV infection increased when camels were exposed to the insect vectors (OR = 1.63, 95%CI = 0.87-3.09). The high prevalence of BTV in camels in several Egyptian regions highlights the need for more epidemiological investigations of BTV infection in other ruminant species in order to better control BT disease in these regions.

Sero-survey of bovine herpes virus-1 in dromedary camels and associated risk factors.

Infectious bovine rhinotracheitis (IBR) is a major animal health hazard in many countries throughout the world, caused by bovine herpesvirus-1 (BoHV-1). The study's goal was to evaluate the prevalence of BoHV-1 seropositivity among dromedary camels in three governorates in northern Egypt, as well as to identify risk variables related with BoHV-1 seropositivity. A total of 321 blood samples were collected randomly from dromedary camels living in the selected governorates and examined for presence of BoHV-1 antibody using ELISA test. The overall seroprevalence of BoHV-1 among examined camels was 5.92% (95%CI: 3.82-9.06). Univariable analysis confirmed that the significant association (P < 0.05) between sex, history of abortion, contact with small ruminants and herd size and BoHV-1 seropositivity. Using multiple logistic regression analysis, the following risk factors were identified to be related with the presence of BoHV-1 infection: sex (OR = 2.54, 95%CI: 0.63-10.22), history of abortion (OR = 4.16, 95%CI: 1.30-13.27), contact with small ruminants (OR = 5.61, 95%CI: 1.67-18.80) and large herd size (OR = 10.52, 95%CI: 2.46-44.91). This study estimated the disease's seroprevalence in Egyptian dromedary camels, implying that camels could act as a BoHV-1 reservoir for transmission to other species.

Prevalence, antimicrobial susceptibilities and risk factors of Methicillin resistant Staphylococcus aureus (MRSA) in dairy bovines.

Staphylococcus aureus is a common mastitis pathogen in dairy cows, and methicillin-resistant S. aureus (MRSA) has been found in dairy farms all over the world. The study carried out on bovines from three governorates in Egypt, with the goal of determining the prevalence of MRSA in positive milk samples of subclinical mastitis, performing an antibiotic susceptibility test against MRSA isolates and determining the risk factors associated with MRSA. A total of 350 quarter milk samples (n = 200 mixed breed cow; n = 150 water buffalo) were collected and examined for subclinical mastitis using the California mastitis test (CMT) before being exposed to standard microbiological procedures for S. aureus isolation. The disc diffusion method was used to phenotypically analyse the positive S. aureus isolates for MRSA, which was verified by a PCR assay targeting the mecA gene. According to the findings of the study, 41.4% (145/350) milk samples were positive based on CMT, while 35.7% (125/350) of positive samples identified as MRSA based on PCR assay. However, the obtained results revealed non-significant disparity between cattle and buffalo and all predicted risk factors were strongly associated with prevalence of subclinical mastitis. The in-vitro antibiotic susceptibility test revealed that cefoxitin was completely resistant, whereas linezolid, ciprofloxacin, and trimethoprim + sulphamethoxazole were sensitive against the MRSA isolates. The relevance of S. aureus to public health, as well as the development of resistance to antibiotics like methicillin, needs ongoing testing of antimicrobial medications against MRSA isolates.

Food sensitization in preschool Egyptian children with recurrent wheezing.

BACKGROUND: Food allergy is common in children with prevalence up to 10%. We assessed the clinico-laboratory characteristics and frequency of food sensitization to the commonly consumed food among upper Egyptian preschool children with recurrent wheezy chest. METHODS: This cross-sectional descriptive study was conducted on 100 preschool children with recurrent wheezy chest recruited from Emergency, Allergy, and Pulmonology units, Assiut University Children's Hospital, Egypt. All enrolled patients were subjected to history taking, through examination, chest X-ray, skin prick testing (SPT), and lab investigations. RESULTS: Family history of allergy was found in 66 patients, while history of other allergies was reported in 47 patients. History of food allergy was positive in 47% of the studied patients, and 28 patients had positive reaction by SPT. Sensitization to fish, milk, egg, and wheat was found in 15, 8, 5, and 4 patients, respectively. Eighteen out of the 28 patients who were sensitized by SPT gave positive history of food allergy, while ten patients had no suggestive history; also, history suggestive of food allergy was negative in 35.7% of sensitized patients versus 61.1% of non-sensitized patients. CONCLUSIONS: Food sensitization is common in preschool Egyptian children with recurrent wheezing. IMPACT: Food sensitization is common in children with prevalence up to 10%, and in atopic children up to 30%. Sensitization to fish was the most common type of sensitization observed among preschool children with recurrent wheezing, followed by milk, eggs, and wheat, respectively. SPT aided by history is a good screening tool to determine whether patients need to avoid some foods that can cause allergy in order to help in controlling their symptoms.

Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study.

Background: This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods: ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Results: Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4 months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks). Conclusion: Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile. Trial registration: ClinicalTrials.gov NCT02604342; Roche study MO29750.

Open compared with laparoscopic complete mesocolic excision with central lymphadenectomy for colon cancer: a systematic review and meta-analysis.

AIM: Several studies report improved survival in colon cancer with use of extended lymphadenectomy techniques (ELTs), such as D3 lymphadenectomy or complete mesocolic excision. The noninferiority of laparoscopic versus open techniques has already been established in D2 resections. The aim of this study was to compare the safety and efficacy of open and laparoscopic approaches for ELTs in colon cancer. METHOD: Major databases, including PubMed, Scopus and the Cochrane library, were searched using defined inclusion and exclusion criteria, and relevant data were extracted. The Cochrane and Newcastle-Ottawa tools were used for critical appraisal and quality assessment. Meta-analysis with various subgroup analyses were undertaken, and clinical and statistical heterogeneity, along with publication bias, were also assessed. RESULTS: One randomized and seven case-control trials were included. All studies were found to be of low methodological quality with some external validity issues. There was no difference in short-term mortality [OR = 2.16 (95% CI: 0.73-6.41); P = 0.16], anastomotic leakage, ileus or deep-sited infection/abscess. There was a trend for longer operative time [weighted mean difference (WMD) = -30.88 (95% CI: -62.38 to 0.61); P = 0.05] and shorter length of hospital stay [WMD = 2.29 (95% CI: -0.39 to 4.98); P = 0.09] with the laparoscopic approach. Laparoscopic right hemicolectomy had a lower wound-infection rate [OR = 2.87 (95% CI: 1.38-5.98); P = 0.005] compared with the relevant open group. No statistically significant difference was found in overall survival [hazard ratio (HR) = 0.85 (95% CI: 0.69-1.06); P = 0.15], disease-free survival, local recurrence and distant metastases. CONCLUSION: Based on the current evidence, the laparoscopic technique appears to be at least as safe as the open technique when used in performing ELTs for colonic cancer, with similar morbidity and oncological outcomes.

Application of CRISPR/Cas9 system to knock out GluB gene for developing low glutelin rice mutant.

The nutritional quality improvement is among the most integral objective for any rice molecular breeding programs. The seed storage proteins (SSPs) have greater role to determine the nutritional quality of any cereal grains. Rice contains relatively balanced amino acid composition and the SSPs are fractioned into albumins (ALB), globulins (GLO), prolamins (PRO) and glutelins (GLU) according to differences in solubility. GLUs are further divided into subfamilies: GluA, GluB, GluC, and GluD depending on resemblance in amino acid. The GLU protein accounts for 60-80% of total protein contents, encoded by 15 genes located on different chromosomes of rice genome. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system was employed to knockout Glu-B (LOC-Os02g15070) gene in non-basmati rice PK386 cultivar. The mutant displayed two base pair and three base pair mutation in the targeted regions. The homozygous mutant plant displayed reduction for both in total protein contents and GLU contents whereas, elevation in GLO, ALB and PRO. Moreover, the mutant plant also displayed reduction in physio-chemical properties e.g., total starch, amylose and gel consistency. The agronomic characteristics of both mutant and wild type displayed non-significant differences along with increase in higher percentage of chalkiness in mutant plants. The results obtained from scanning electron microscopy showed the loosely packed starch granules compared to wild type. The gene expression analysis displayed the lower expression of gene at 5 days after flowering (DAF), 10 DAF, 15 DAF and 20 DAF compared to wild type. GUS sub-cellular localization showed the staining in seed which further validated the results obtained from gene expression. Based on these findings it can be concluded Glu-B gene have significant role in controlling GLU contents and can be utilized in breeding programs to enhance the nutritional quality of rice, and may serve as healthy diet for patient allergic with high GLU contents.

Country-wide, multi-location trials of Green Super Rice lines for yield performance and stability analysis using genetic and stability parameters.

Rice (Oryza sativa L.) is an important member of the family Poaceae and more than half of world population depend for their dietary nutrition on rice. Rice cultivars with higher yield, resilience to stress and wider adaptability are essential to ensure production stability and food security. The fundamental objective of this study was to identify higher-yielding rice genotypes with stable performance and wider adaptability in a rice growing areas of Pakistan. A triplicate RCBD design experiment with 20 Green Super Rice (GSR) advanced lines was conducted at 12 rice growing ecologies in four Provinces of Pakistan. Grain yield stability performance was assessed by using different univariate and multivariate statistics. Analysis of variance revealed significant differences among genotypes, locations, and G x E interaction for mean squares (p < 0.05) of major yield contributing traits. All the studied traits except for number of tillers per plant revealed higher genotypic variance than environmental variance. Broad sense heritability was estimated in the range of 44.36% to 98.60%. Based on ASV, ASI, bi, Wi2, σ2i and WAAS statistics, the genotypes G1, G4, G5, G8, G11 and G12 revealed lowest values for parametric statistics and considered more stable genotypes based on  paddy yield. The additive main effects and multiplicative interaction (AMMI) model revealed significant variation (p < 0.05) for genotypes, non-signification for environment and highly significant for G × E interaction. The variation proportion of PC1 and PC2 from interaction revealed 67.2% variability for paddy yield. Based on 'mean verses stability analysis of GGE biplot', 'Which-won-where' GGE Biplot, 'discriminativeness vs. representativeness' pattern of stability, 'IPCA and WAASB/GY' ratio-based stability Heat-map, and ranking of genotypes, the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 were observed ideal genotypes with yield potential more than 8 tons ha-1. Discriminativeness vs. representativeness' pattern of stability identifies two environments, E5 (D.I Khan, KPK) and E6 (Usta Muhammad, Baluchistan) were best suited for evaluating genotypic yield performance. Based on these findings we have concluded that the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 could be included in the commercial varietal development process and future breeding program.