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Brazzein-a low-calorie natural sweetener is an effective substitute for deleterious effects of sucrose. Uptill now, limited production of recombinant brazzein protein using heterologous expression system along with solubility and low yield challenges are reported. Foreseeing the potential of brazzein gene in therapeutics, molecular strategies are required to optimize production of recombinant brazzein using different prokaryotic and eukaryotic expression systems. Therefore, in this study brazzein gene synthesized from Bio Basic Inc. (BBI) which was provided in pUC57 cloning vector. The gene was retrieved from cloning vector by performing PCR and cloned in plant expression vector pBI121 with CaMV35S promoter region. Heat shock or calcium chloride method was optimized for transformation into E. coli (DH5-alpha) with recombinant vector pBI121. Kanamycin resistence selection, colony PCR and transformation efficiency analysis were performed to analyze the successful cloning procedure. Transformed cultures having cloned brazzein gene in pBI121 vector with CaMV35S promoter could be used to transform different plants such as, sorghum, sugarcane and turnip for sweet taste enhancement in future and may provide plateform for commercial scale production of therapeutic proteins using crop plants as bioreactor. [ABSTRACT FROM AUTHOR]

Nutrient-use-efficient genotypes are the part and parcel of environment-friendly sustainable agriculture. We exploited three cotton genotypes, differing in their potassium (K) use efficiency (NIBGE-2: highly efficient, NIAB-78: medium efficient and CIM-506: non-efficient), to evaluate their growth, yield and quality against different levels of soil applied K sulphate (0, 30, 60, 90 and 120 kg K ha-1). The study was comprised of two experiments, with pot experiment conducted in a completely randomized design and field experiment in a two-factor factorial split-plot randomized complete block design with three replications. The experimental soil was poorly fertile sandy clay loam (Typic Calciargids). Generally, K nutrition enhanced the growth and yield of cotton. However, cotton genotypes responded significantly (p<0.05) different at various K levels, due to difference in their K-use-efficiency, for growth, yield and quality traits in order of NIBGE-2 > NIAB-78 > CIM-506. The genotype NIBGE-2 performed well under K deficient condition and was best choice for low-K-input sustainable cotton production. © 2014 Friends Science Publishers [ABSTRACT FROM AUTHOR]

The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild-type aberrations. Twenty-four-week overall response rate was 50% (60% CI 39.3%-60.7%), and median duration of response was 11.6 months (IQR: 6.3-17). The median progression-free survival was 13.6 months (95% CI 3-19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune-mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD-1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Observational studies have reported associations between nutrition during pregnancy and mental wellbeing. As secondary outcomes, the NiPPeR double-blind randomized trial in women planning conception investigated whether a myo-inositol, probiotics and enriched micronutrients formulation (intervention) taken preconception and throughout pregnancy could improve mental wellbeing during pregnancy and post-delivery, compared with a standard micronutrient supplement (control). Mood and anxiety symptoms were ascertained (Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI-state)) at preconception (baseline), 7, 28 and 34 weeks gestation, 3-weeks and 6-months post-delivery. EPDS>=13 was categorised as low mood; STAI-state>=45 as high anxiety. Change in mental health functioning was assessed as difference between preconception baseline and 6-month post-delivery 12-item Short-Form Health Survey (SF-12v2) mental component scores. Adjusting for site, ethnicity and baseline scores, there were no robust differences in EPDS and STAI-state scores between intervention and control groups across pregnancy (n = 630) and post-delivery (n = 532). Compared to controls, intervention group women averaged a 1.21 (95 %CI 0.04,2.39) higher change in SF-12v2 mental component score from preconception to 6-months post-delivery. Taking a myo-inositol, micronutrient and probiotic supplement during preconception/pregnancy had no effect on mood and anxiety, but there was evidence of a modest improvement in mental health functioning from preconception to 6-months post-delivery., Competing Interests: Declaration of competing interest KG, YSC, WC and SC report grants from Société Des Produits Nestlé S.A. during the conduct of the study, and are co-inventors on patent filings by Nestlé S.A. relating to the NiPPeR intervention or its components. KG, SB, YSC, WC and SC are part of an academic consortium that has received grants from Nestlé S.A. and BenevolentAI Bio Ltd outside the submitted work. All other authors declare no competing interests, (Copyright © 2024. Published by Elsevier B.V.)

Sugars transported from leaves (source) to stems (sink) energize cell growth, elongation, and maintenance. which are regulated by a variety of genes. This review reflects progress and prospects in the regulatory mechanism for maximum sucrose accumulation, including the role of sucrose metabolizing enzymes, sugar transporters and the elucidation of post-transcriptional control of sucrose-induced regulation of translation (SIRT) in the accumulation of sucrose. The current review suggests that SIRT is emerging as a significant mechanism controlling Scbzip44 activities in response to endogenous sugar signals (via the negative feedback mechanism). Sucrose-controlled upstream open reading frame (SC-uORF) exists at the 5' leader region of Scbzip44 's main ORF, which inhibits sucrose accumulation through post-transcriptional regulatory mechanisms. Sucrose transporters ( SWEET1a/4a/4b/13c, TST, SUT1, SUT4 and SUT5 ) are crucial for sucrose translocation from source to sink. Particularly, SWEET13c was found to be a major contributor to the efflux in the transportation of stems. Tonoplast sugar transporters (TSTs), which import sucrose into the vacuole, suggest their tissue-specific role from source to sink. Sucrose cleavage has generally been linked with invertase isozymes, whereas sucrose synthase (SuSy)-catalyzed metabolism has been associated with biosynthetic processes such as UDP-Glc, cellulose, hemicellulose and other polymers. However, other two key sucrose-metabolizing enzymes, such as sucrose-6-phosphate phosphohydrolase (S6PP) and sucrose phosphate synthase (SPS) isoforms, have been linked with sucrose biosynthesis. These findings suggest that manipulation of genes, such as overexpression of SPS genes and sucrose transporter genes, silencing of the SC-uORF of Scbzip44 (removing the 5' leader region of the main ORF that is called SIRT-Insensitive) and downregulation of the invertase genes, may lead to maximum sucrose accumulation. This review provides an overview of sugarcane sucrose-regulating systems and baseline information for the development of cultivars with higher sucrose accumulation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Studying the thermal stress effect on sucrose-metabolizing enzymes in sugarcane is of great importance for understanding acclimation to thermal stress. In this study, two varieties, S2003-US-633 and SPF-238, were grown at three different temperatures ( ± 2°C): 30°C as a control, 45°C for various episodes of high temperature treatments and recovery conditions at 24, 48 and 72 hours. Data showed that reducing sugar content increased until the grand growth stage but sharply declined at the maturity stage in both cultivars. On the other hand, sucrose is enhanced only at the maturity stage. The expression of all invertase isozymes declined prominently; however, the expression of SPS was high at the maturity stage. Hence, the sucrose accumulation in mature cane was due to increased SPS activity while decreased invertase isozymes (vacuolar, cytoplasmic and cell wall) activities at maturity stage in both cultivars. Heat shock decreased the sucrose metabolizing enzymes, sucrose content and sugar recovery rate in both cultivars. In contrast, heat-shock treatments induced maximum proline, MDA, H 2 O 2 and EC in both cultivars. Notably, this is the first report of diverse invertase isozyme molecular weight proteins, such as those with 67, 134 and 160 kDa, produced under heat stress, suggesting that these enzymes have varied activities at different developmental stages. Overall, S2003-US-633 performs better than the cultivar SPF-238 under heat stress conditions at all development stages, with increased sucrose content, enzyme expression, proline and sugar recovery rate. This work will provide a new avenue regarding sugarcane molecular breeding programs with respect to thermal stress., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Mehdi, Liu, Riaz, Javed, Aman and Galani.)

Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory (R/R) pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been historically poor. Cord blood (CB) allows T-cell replete CB transplant (TRCB), enabling enhanced graft-versus-leukemia. We consecutively collected data from 367 patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for pediatric AML/MDS in the United Kingdom and Ireland between January 2014 and December 2021. Data were collected about the patient's demographics, disease, and its treatment; including previous transplant, measurable residual disease (MRD) status at transplant, human leukocyte antigen-match, relapse, death, graft versus host disease (GvHD), and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease, and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6%, and 5.1%, respectively, in the comparator group. Event free survival was 64.1% within the TRCB cohort, 50% in MRD-positive patients, and 79% in MRD-negative patients. To allow for the imbalance in baseline characteristics, a multivariable analysis was performed where the TRCB cohort had significantly improved event free survival, time to relapse, and reduced chronic GvHD, with some evidence of improved overall survival. The effect appeared similar regardless of the MRD status. CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Evidence that nutritional supplementation before and during pregnancy improves peripartum outcomes is sparse. In the Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) trial, we previously reported that a combined myo-inositol, probiotics, and micronutrient supplement started at preconception showed no difference in the primary outcome of gestational glycemia, but did reduce the risk of preterm delivery, preterm prelabor rupture of membranes, and major postpartum hemorrhage., Objective: This study aimed to examine the hypothesis that a reduction in major postpartum hemorrhage following a combined nutritional (myo-inositol, probiotics, and micronutrients) intervention is linked with promotion of labor progress and reduced operative delivery., Study Design: This double-blind randomized controlled trial recruited 1729 women from the United Kingdom, Singapore, and New Zealand, aged 18 to 38 years, and planning conception between 2015 and 2017. The effects of the nutritional intervention compared with those of a standard micronutrient supplement (control), taken at preconception and throughout pregnancy, were examined for the secondary outcomes of peripartum events using multinomial, Poisson, and linear regression adjusting for site, ethnicity, and important covariates., Results: Of the women who conceived and progressed beyond 24 weeks' gestation with a singleton pregnancy (n=589), 583 (99%) provided peripartum data. Between women in the intervention (n=293) and control (n=290) groups, there were no differences in rates of labor induction, oxytocin augmentation during labor, instrumental delivery, perineal trauma, and intrapartum cesarean delivery. Although duration of the first stage of labor was similar, the second-stage duration was 20% shorter in the intervention than in the control group (adjusted mean difference, -12.0 [95% confidence interval, -22.2 to -1.2] minutes; P=.029), accompanied by a reduction in operative delivery for delayed second-stage progress (adjusted risk ratio, 0.61 [0.48-0.95]; P=.022). Estimated blood loss was 10% lower in the intervention than in the control group (adjusted mean difference, -35.0 [-70.0 to -3.5] mL; P=.047), consistent with previous findings of reduced postpartum hemorrhage., Conclusion: Supplementation with a specific combination of myo-inositol, probiotics, and micronutrients started at preconception and continued in pregnancy reduced the duration of the second stage of labor, the risk of operative delivery for delay in the second stage, and blood loss at delivery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The antibiotic resistance has become a major threat to global health. The combinatorial use of two or more compounds to develop a new formulation may overcome the emerging cases of drug resistance. Moringa oleifera has been utilized as a strong nutritional, immunomodulator and therapeutic agent for decades. In this study, different parts of Moringa oleifera were screened for bioactive compounds that can act as a resistance modifying agent for multi-drug resistant organisms (MDROs)., Methodology: Initially, the combined effect of stem bark extracts and ampicillin was calculated by checkerboard assay. Active compounds of effective extract were assessed by High Performance Liquid Chromatography (HPLC). Minimal Inhibitory Concentration (MIC) and Fractional Inhibitory Concentration Index (FICI) were calculated to evaluate the synergistic behavior of stem bark extract with ampicillin. To study the blocking of resistance pathways of Methicillin-Resistant Staphylococcus aureus (MRSA) western blot was performed., Results: The results revealed that stem bark has significant anti-MRSA activity. The methanolic extract of stem bark in combination with ampicillin showed the highest synergistic effect (FICI value ≤ 0.237) against MRSA. Killing kinetics and membrane potential of ampicillin alone and in combination revealed an increase in the inhibitory potential of ampicillin against MRSA. Decolourization in iodometric assay confirmed the inhibition of β-lactamase, western blot results confirmed the blocking of penicillin-binding protein (PBP2a) expression with the restoration of MRSA sensitivity against β-lactams., Conclusion: It can be concluded that methanolic extract of Moringa oleifera stem bark has bioactive compounds and can be used as an adjuvant with antibiotics to modify the resistance of MDROs., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Antibiotic resistance poses a grave threat to One-Health. By replacing antibiotics with non-antibiotic additives (are alternatives to antibiotics, ATAs) like phytogenic feed additives and organic acids in poultry feed. ATAs are a potential alternative as these decline the proliferation of pathogenic bacteria and strengthen gut function in broiler chickens. In this study, we use 16S rRNA amplicon sequencing of the V3-V4 region to evaluate phytogenic feed additives and organic acids on the cecal microbial diversity of broiler chickens., Methods and Results: Two hundred & forty broiler chicks were divided into five treatments comprising: a controlled basal diet (CON), antibiotic group (AB), phytogenic feed additives (PHY), organic acids (ORG), and a combination of PHY + ORG (COM). A distinctive microbial community structure was observed amongst different treatments with increased microbial diversity in AB, ORG, and COM (p < 0.05). The synergistic effects of PHY and ORG increased bacterial population of phyla: Firmicutes, Bacteroides, and Proteobacteria in the cecum. The presence of species, Akkermansia muciniphila (involved in mucin degradation) and Bacillus safensis (a probiotic bacterium) were noticed in COM and PHY, respectively. Clustering analysis revealed a higher relative abundance of similar microbial community composition between AB and ORG groups., Conclusions: Treatments with PHY and ORG modified the relative abundance and presence/absence of specific microbiota in the chicken cecum. Hence, cecal microbiota modulation through diet is a promising strategy to reduce cross-contamination of zoonotic poultry pathogens, led to healthy and economical broiler meat., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In an epoch of escalating number of antibiotic-resistance bacteria, there is a dire need to develop efficient and novel feeding strategies for animal nutrition as alternatives to antibiotics. Here, implicating nutrigenomic approach, phytobiotics and organic acids were used to evaluate ghrelin gene expression levels, gut microflora composition, performance parameters and intestinal histomorphological changes in broiler chickens. One-day-old chicks (n = 315) were reared for 42 days and distributed randomly into five experimental groups; each with three replicates (21 birds per replicate). Experimental groups were control: basal diet only, antimicrobial growth promoter: 40 g/metric ton of basal diet (virginiamycin), organic acids: 4 kg/metric ton of basal diet, phytobiotics: 3 kg/metric ton of basal diet, combination: 7 kg/metric ton of basal diet (organic acids 4 kg and phytobiotics 3 kg metric ton of feed). Growth performance, histological and ghrelin gene expression analysis were executed on 21 and 42 days while, quantitative bacterial analysis of cecum and ileum was performed on day 42. Increased feed intake and body weight ( p < 0.05 ) were noticed in phytobiotics group. Addition of phytobiotics significantly improved ( p < 0.05 ) villus height and ratio of villus height/crypt depth in ileum, jejunum, and duodenum and down-regulated ghrelin gene expression levels. Total coliform and Escherichia coli in cecal and ileal digesta were decreased significantly ( p < 0.05 ) in organic acids group. Correlation analysis revealed Lactobacillus spp. were positively correlated to villus height/crypt depth ration in duodenum. The findings indicated the importance of gene-nutrient-microbiota interactions based on nutrigenomics approach. Hence, phytobiotics and organic acids might be suitable alternatives to antibiotics for improved performance and immunity, along with healthier meat production in poultry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The ongoing SARS-CoV-2 pandemic infecting millions of people globally has given rise to serious public health threats. The need for early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic pregnant women is compelling to detect vertical transmission timely. Here, 11 SARS-CoV-2 asymptomatic pregnant cases from Wuhan China were investigated. All the patients were initially tested negative for SARS-CoV-2 on RT-PCR, so a chest CT scan was performed. Also, serum antibody (IgM and IgG) titers were estimated. CT scan of patients revealed typical abnormalities related to SARS-CoV-2, indicating ground-glass opacity and infection lesions suggesting viral pneumonia. Elevated IgM and IgG antibodies levels ( p < 0.001 ) were also noticed in infected patients. Hence, CT imaging and serum antibody response are valuable in the early detection of SARS-CoV-2 in asymptomatic pregnant patients. These might serve as prognostic markers for healthcare professionals, in RT-PCR negative patients, to assess the effect of given treatment by chest CT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The plant kingdom is a rich source of bioactive compounds, many of which have been used since pre-history for their therapeutic properties to treat a range of illnesses. These metabolites have recently attracted attention to their antineoplastic activities to treat various cancers relying on different mechanisms. Some of these molecules are glycosides, which have proven useful as anti-cancer agents, namely podophyllotoxin (PPT) anaryltetralin lignan or alkaloids. There are three primary forms of alkaloids, such as indole alkaloids (vincristine and vinblastine from Catharanthus roseus), quinoline alkaloid (camptothecin from Camptotheca acuminata), and diterpenoid alkaloid (taxol and it's analogous from Taxus and Corylus species). This review considers various plant biotechnology approaches used to enhance the production of these anticancer molecules in different species. In this regard, many in vitro culture techniques such as stimulation of suspension culture and hairy roots are being used to investigate the effects of plant growth regulators and elicitors on various explants., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

This study explored the effects of natural growth promoters (phytogenic feed additives and organic acids) on animal performance, carcass characteristics, blood parameters, gut microflora composition, and microbe-host interactions in broiler chickens over a 42-day feeding period. Two-hundred-fifty-day-old chicks were randomly assigned to one of five treatments: (i) control diets (CON); (ii) control diets + 40 g/tons antibiotic growth promoter (AB); (iii) control diets + 3 kg/tons organic acids (ORG); (iv) control diets + 3 kg/tons phytogenic feed additives (PHY); (v) control diets + 3 kg/tons organic acids + phytogenic feed additive combination (COM). A non-significant differences ( p  >  0.05 ) were observed in broiler performance among treatments at 21 days of age; however, a gradually increasing body weight gain and reduced feed conversion ratio were observed at 42 days in treatments versus control group. Biochemical indices were non-significant ( p  >  0.05 ) except for decreased cholesterol ( p  <  0.05 ) and increased A/G ratio ( p  <  0.05 ) recorded in the treatment groups. The addition of PHY and ORG improved total counts of Enterococcus spp. and Lactobacillus spp. ( p  <  0.05 ) as well as reduced caecal and ileal Campylobacter spp. and Escherichia coli ( p  <  0.05 ). Correlation analysis elucidated beneficial bacteria ( Enterococcus spp. and Lactobacillus spp.) were positively and pathogenic bacteria ( Campylobacter spp. and E. coli ) were negatively correlated ( p  <  0.05 ) with host weight gain. The findings indicated that dietary supplementation of PHY and ORG sustained balanced gut microflora, which in turn improved body weight. This study broadens the significance of using PHY and ORG as safe alternatives to antibiotic growth promoters for achieving healthier and economical broiler production., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Newcastle disease is highly infectious viral disease causing huge economic losses worldwide. These losses can be prevented by control of viral diseases. Medicinal plants have been traditionally used for treatment of different diseases since long. In this study the effect of extracts from Glycyrrhiza glabra leaves are investigated against Newcastle disease virus (NDV) by an in-vivo assay. Seven groups of nine-day-old embryonated chicken eggs were inoculated with various treatments of different plant extracts. All the groups except uninoculated negative control group were inoculated with velogenic NDV strain; five groups received different concentrations of the three extracts. Daily observe the rate of embryo survival. Allantoic fluid from treated eggs was collected for hem agglutination test. Results showed that embryo survival rate was higher 300µg/mL treated group as all the extracts showed antiviral activity. Similarly, the plant extracts effectively control virus as no viruses were identified in the allantoic fluids of all groups treated with low doses of plant. The current results have clearly verified that all the extracts especially that of methanol 300µg/mL from leaves of Glycyrrhiza glabra have strong antiviral activity against NDV in vivo.

Studies on the functional roles of dehydrins (DHNs) in heat tolerance of plants are scarce. This study was conducted to immunohistolocalize DHNs in leaves of heat-tolerant (CP-4333) and heat-sensitive (HSF-240) sugarcane (Saccharum officinarum L.) clones at three phenological stages in order to elucidate their putative roles under heat stress. CP-4333 indicated greater amounts of heat-stable proteins than HSF-240 under heat stress. Western blotting revealed the expression of three DHNs in CP-4333 (13- and 15-kDa peptides at 48 h and an additional 18-kDa band at 72 h) and two (13 and 15 kDa at 48 h) in HSF-240 at formative stage; two DHNs in CP-4333 (20 and 25 kDa) and one in HSF-240 (20 kDa) at grand growth stage, while two DHNs in CP-4333 (20 and 22 kDa) and one in HSF-240 (20 kDa) at maturity stage. Tissue-specific immunohistolocalization showed that DHNs were expressed in stele particularly the phloem and the cells intervening bundle sheath and vascular bundles. Furthermore, DHNs were also found scattered along the epidermal and parenchymatous cells. Recovery of sugarcane from heat stress manifested a gradual disappearance of DHNs in both the clones, being quicker in sensitive clone (HSF-240). Results suggested specific implications for DHNs synthesis. Their synthesis in epidermis appears to protect the mesophyll tissues from heat injury. When associated to vascular tissue, they tend to ensure the normal photoassimilate loading into the sieve element-companion cell complex. DHNs diminution during recovery suggested that their expression was transitory. However, prolonged retention of DHNs by tolerant clone appears to be an adaptive advantage of sugarcane to withstand heat stress.