A comparison of efficacy of parenteral and perineural dexmedetomidine with 0.25% ropivacaine for post-thyroidectomy analgesia using bilateral superficial cervical plexus block.

Background and Aims: Opioids are conventionally used for post-thyroidectomy pain, regional anesthesia is becoming popular due to its feasibility and efficacy in minimizing use of opioids and hence its side effects. This study compared analgesic efficacy of bilateral superficial cervical plexus block (BSCPB) using perineural and parenteral dexmedetomidine with 0.25% ropivacaine in thyroidectomy patients. Material and Methods: In this double-blind study, 60 American Society of Anesthesiologists (ASA) physical status I and II thyroidectomy patients, aged 18-65 years were randomized into two groups. Group A (n = 30) received BSCPB with 0.25% ropivacaine, 10 mL on each side with dexmedetomidine 0.5 µg/kg IV infusion. Group B (n = 30) received 0.25% ropivacaine plus dexmedetomidine 0.5 µg/kg, ten mL on each side. Duration of analgesia by measuring pain visual analog scores (VAS), total dose of analgesic requirement, Haemodynamics parameters and adverse events were recorded for 24 h. Categorical variables were analyzed using Chi-square test and continuous variables were computed as mean with standard deviation and analyzed using independent sample t-test. Mann-Whitney U test was used for analysis of ordinal variables. Results: Time to rescue analgesia was longer in Group B (18.6 ± 3.27 h) as compared to Group A (10.2 ± 2.11 h) (P < 0.001). Total analgesic dose required was also found to be lesser in Group B (50.83 ± 20.37 mg) as compared to Group A (73.33 ± 18.27 mg) (P < 0.001). No significant hemodynamic changes or side effects were observed in both groups; (P > 0.05). Conclusion: Perineural dexmedetomidine with ropivacaine in BSCPB significantly prolonged the duration of analgesia with reduced rescue analgesic requirement.

Genome-wide miRNAs profiles of pearl millet under contrasting high vapor pressure deficit reveal their functional roles in drought stress adaptations.

Pearl millet (Pennisetum glaucum [L.] R. Br.) is an important crop capable of growing in harsh and marginal environments, with the highest degree of tolerance to drought and heat stresses among cereals. Diverse germplasm of pearl millet shows a significant phenotypic variation in response to abiotic stresses, making it a unique model to study the mechanisms responsible for stress mitigation. The present study focuses on identifying the physiological response of two pearl millet high-resolution cross (HRC) genotypes, ICMR 1122 and ICMR 1152, in response to low and high vapor pressure deficit (VPD). Under high VPD conditions, ICMR 1152 exhibited a lower transpiration rate (Tr), higher transpiration efficiency, and lower root sap exudation than ICMR 1122. Further, Pg-miRNAs expressed in the contrasting genotypes under low and high VPD conditions were identified by deep sequencing analysis. A total of 116 known and 61 novel Pg-miRNAs were identified from ICMR 1152, while 26 known and six novel Pg-miRNAs were identified from ICMR 1122 genotypes, respectively. While Pg-miR165, 168, 170, and 319 families exhibited significant differential expression under low and high VPD conditions in both genotypes, ICMR 1152 showed abundant expression of Pg-miR167, Pg-miR172, Pg-miR396 Pg-miR399, Pg-miR862, Pg-miR868, Pg-miR950, Pg-miR5054, and Pg-miR7527 indicating their direct and indirect role in root physiology and abiotic stress responses. Drought responsive Pg-miRNA targets showed upregulation in response to high VPD stress, further narrowing down the miRNAs involved in regulation of drought tolerance in pearl millet.

Functional characterization of late embryogenesis abundant genes and promoters in pearl millet (Pennisetum glaucum L.) for abiotic stress tolerance.

Late embryogenesis abundant (LEA) genes display distinct functions in response to abiotic stresses in plants. In pearl millet (Pennisetum glaucum L.), a total of 21 PgLEA genes were identified and classified into six groups including LEA1, LEA2, LEA3, LEA5, LEA7, and dehydrins (DHN). Open reading frames (ORFs) of PgLEAs range from 291 bp (PgLEA1-1) to 945 bp (PgLEA2-11) and distributed randomly among the seven chromosomes. Phylogenetic analysis revealed that all PgLEA proteins are closely related to sorghum LEA proteins. The PgLEAs were found to be expressed differentially under high progressive vapor pressure deficit (VPD), PgLEA7 was significantly expressed under high VPD and was selected for functional validation. In silico analysis of the PgLEA promoter regions revealed abiotic stress-specific cis-acting elements such as ABRE, CCAAT, MYBS, and LTRE. Based on the type of motifs, PgLEAPC promoter (758 bp), its deletion 1 (PgLpd1, 349 bp) and deletion 2 (PgLpd2, 125 bp) were cloned into the plant expression vector pMDC164 having the promoter-less uidA gene. All the three plant expression vectors were introduced into tobacco through Agrobacterium tumefaciens-mediated transformation to obtain T1 and T2 generations of transgenic plants. Based on expression of the uidA gene, tissue-specific expression was observed in mature stems, roots and seedlings of PgLEAPC and PgLpd1 carrying transgenics only. While the transgenic PgLEAPC plants displayed significantly higher uidA expression in the stem and root tissues under salt, drought, heat, and cold stresses, very low or no expression was observed in PgLpd1 and PgLpd2 transgenics under the tested stress conditions. The results of this study indicate that the complete promoter of PgLEAPC plays a role in developing abiotic stress tolerance in plants.

Comparison of Invasive and Noninvasive Blood Pressure Measurements for Assessing Signal Complexity and Surgical Risk in Cardiac Surgical Patients.

BACKGROUND: Continuous arterial blood pressure (ABP) is typically recorded by placement of an intraarterial catheter. Recently, noninvasive ABP monitors have been shown to be comparable in accuracy to invasive measurements. In a previous study, we showed that the fluctuations in beat-to-beat ABP measurements were not random variations but had a complex dynamical structure, and that ABP dynamical complexity was inversely associated with surgical risk estimated using the Society of Thoracic Surgeons (STS) index. Dynamical complexity is a mathematical construct that reflects the capacity of a physiological system to adapt to stimuli. The objectives of present study were to: (1) determine whether noninvasive beat-to-beat ABP measurements also exhibit a complex temporal structure; (2) compare the complexity of noninvasive versus invasive ABP time series; and (3) quantify the relationship between the complexity of noninvasive ABP time series and the STS risk scores. METHODS: Fifteen adult patients undergoing coronary artery bypass graft, valve, or combined coronary artery bypass graft/valve surgery were enrolled in this observational study. Preoperative ABP waveforms were simultaneously recorded for ≥15 minutes using a radial artery catheter (invasive) and a continuous noninvasive arterial pressure monitor. Beat-to-beat systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) time series were extracted from the continuous waveforms. Complexity was assessed using the multiscale entropy method. The Wilcoxon signed-rank test was used to compare the mean ranks of indices derived from invasive versus noninvasive ABP time series. Spearman correlation coefficients were used to quantify the relationship between invasive and noninvasive indices. Linear regression analysis was used to quantify the association between each of the complexity indices and the STS risk scores. RESULTS: Beat-to-beat fluctuations in noninvasive ABP measurements were not random but complex; however, their degree of complexity was lower than that of fluctuations in invasively obtained ABP signals (SBP: 7.05 vs 8.66, P < .001; DBP: 7.40 vs 8.41, P < .001; PP: 6.83 vs 8.82, P < .001; and MAP: 7.17 vs 8.68, P < .005). Invasive and noninvasive indices for MSEΣ·slope showed good correlation (rs) (0.53 for SBP, 0.79 for DBP, 0.42 for PP, 0.60 for MAP). The complexity of noninvasive ABP time series (-0.70 [-1.28 to -0.11]; P = .023 for DBP), like that of invasive time series (-0.94 [-1.52 to -0.35]; P = .004 for DBP), was inversely associated with estimated surgical risk in patients undergoing cardiovascular operations. CONCLUSIONS: Our results support the use of noninvasive ABP monitoring in computations of complexity-based indices that correlate with estimated surgical risk.

Changes in nonlinear dynamic complexity measures of blood pressure during anesthesia for cardiac surgeries using cardio pulmonary bypass.

Nonlinear complexity measures computed from beat-to-beat arterial BP dynamics have shown associations with standard cardiac surgical risk indices. They reflect the physiological adaptability of a system and has been proposed as dynamical biomarkers of overall health status. We sought to determine the impact of anesthetic induction and cardiopulmonary bypass (CPB) upon the complexity measures computed from perioperative BP time series. In this prospective, observational study, 300 adult patients undergoing cardiac surgery were included. Perioperative period was divided as: (1) Preoperative (PreOp); (2) ORIS-induction to sternotomy; (3) ORSB- sternotomy to CPB; (4) ORposB-post CPB and within 30 min before leaving OR and (5) postoperative phase (PostOp)-initial 30 min in the cardiac surgical intensive care unit. BP waveforms for systolic (SAP), diastolic (DAP), mean arterial pressure (MAP) and pulse pressure (PP) were recorded, and their corresponding complexity index (MSE∑) was calculated. Significant decrease in MSE∑ from Preop to PostOp phases was observed for all BP time series. Maximum fall was seen during post anesthetic induction (ORIS) phase. Mild recovery during the subsequent phases was observed but they never reached the baseline values. In an exploratory analysis, preoperative MSE∑ showed a significant correlation with postoperative length of ICU stay. Blood pressure complexity varies at different time points and is not fixed for a given individual. Preoperative BP Complexity decreased significantly following anesthetic induction and did not recover to baseline until 30 min after surgery. Prevention of this significant fall may offer restoration of MSE∑ throughout surgery. Furthermore, preoperative BP complexity needs to be explored as a predictor of major postoperative adverse events by itself or in addition with the current risk indices.

Isolation and functional characterization of three abiotic stress-inducible (Apx, Dhn and Hsc70) promoters from pearl millet (Pennisetum glaucum L.).

Pearl millet is a C4 cereal crop that grows in arid and semi-arid climatic conditions with the remarkable abiotic stress tolerance. It contributed to the understanding of stress tolerance not only at the physiological level but also at the genetic level. In the present study, we functionally cloned and characterized three abiotic stress-inducible promoters namely cytoplasmic Apx1 (Ascorbate peroxidase), Dhn (Dehydrin), and Hsc70 (Heat shock cognate) from pearl millet. Sequence analysis revealed that all three promoters have several cis-acting elements specific for temporal and spatial expression. PgApx pro, PgDhn pro and PgHsc70 pro were fused with uidA gene in Gateway-based plant transformation pMDC164 vector and transferred into tobacco through leaf-disc method. While PgApx pro and PgDhn pro were active in seedling stages, PgHsc70 pro was active in stem and root tissues of the T2 transgenic tobacco plants under control conditions. Higher activity was observed under high temperature and drought, and less in salt and cold stress conditions. Further, all three promoters displayed higher GUS gene expression in the stem, moderate expression in roots, and less expression in leaves under similar conditions. While RT-qPCR data showed that PgApx pro and PgDhn pro were expressed highly in high temperature, salt and drought, PgHsc70 pro was fairly expressed during high temperature stress only. Histochemical and RT-qPCR assays showed that all three promoters are inducible under abiotic stress conditions. Thus, these promoters appear to be immediate candidates for developing abiotic stress tolerant crops as these promoter-driven transgenics confer high degree of tolerance in comparison with the wild-type (WT) plants.

Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial.

Importance: Postoperative delirium is common following cardiac surgery and may be affected by choice of analgesic and sedative. Objective: To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery. Design, Setting, and Participants: Randomized, placebo-controlled, factorial clinical trial among 120 patients aged 60 years or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries at a US center. Enrollment was September 2015 to April 2018, with follow-up ending in April 2019. Interventions: Patients were randomized to 1 of 4 groups receiving postoperative analgesia with IV acetaminophen or placebo every 6 hours for 48 hours and postoperative sedation with dexmedetomidine or propofol starting at chest closure and continued for up to 6 hours (acetaminophen and dexmedetomidine: n = 29; placebo and dexmedetomidine: n = 30; acetaminophen and propofol: n = 31; placebo and propofol: n = 30). Main Outcomes and Measures: The primary outcome was incidence of postoperative in-hospital delirium by the Confusion Assessment Method. Secondary outcomes included delirium duration, cognitive decline, breakthrough analgesia within the first 48 hours, and ICU and hospital length of stay. Results: Among 121 patients randomized (median age, 69 years; 19 women [15.8%]), 120 completed the trial. Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, -18% [95% CI, -32% to -5%]; P = .01; HR, 2.8 [95% CI, 1.1-7.8]). Patients receiving dexmedetomidine vs propofol had no significant difference in delirium (17% vs 21%; difference, -4% [95% CI, -18% to 10%]; P = .54; HR, 0.8 [95% CI, 0.4-1.9]). There were significant differences favoring acetaminophen vs placebo for 3 prespecified secondary outcomes: delirium duration (median, 1 vs 2 days; difference, -1 [95% CI, -2 to 0]), ICU length of stay (median, 29.5 vs 46.7 hours; difference, -16.7 [95% CI, -20.3 to -0.8]), and breakthrough analgesia (median, 322.5 vs 405.3 µg morphine equivalents; difference, -83 [95% CI, -154 to -14]). For dexmedetomidine vs propofol, only breakthrough analgesia was significantly different (median, 328.8 vs 397.5 µg; difference, -69 [95% CI, -155 to -4]; P = .04). Fourteen patients in both the placebo-dexmedetomidine and acetaminophen-propofol groups (46% and 45%) and 7 in the acetaminophen-dexmedetomidine and placebo-propofol groups (24% and 23%) had hypotension. Conclusions and Relevance: Among older patients undergoing cardiac surgery, postoperative scheduled IV acetaminophen, combined with IV propofol or dexmedetomidine, reduced in-hospital delirium vs placebo. Additional research, including comparison of IV vs oral acetaminophen and other potentially opioid-sparing analgesics, on the incidence of postoperative delirium is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02546765.

Complexity of preoperative blood pressure dynamics: possible utility in cardiac surgical risk assessment.

Complexity measures are intended to assess the cardiovascular system's capacity to respond to stressors. We sought to determine if decreased BP complexity is associated with increased estimated risk as obtained from two standard instruments: the Society of Thoracic Surgeons' (STS) Risk of Mortality and Morbidity Index and the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE II). In this observational cohort study, preoperative systolic, diastolic, mean (MAP) and pulse pressure (PP) time series were derived in 147 patients undergoing cardiac surgery. The complexity of the fluctuations of these four variables was quantified using multiscale entropy (MSE) analysis. In addition, the traditional time series measures, mean and standard deviation (SD) were also computed. The relationships between time series measures and the risk indices (after logarithmic transformation) were then assessed using nonparametric (Spearman correlation, rs) and linear regression methods. A one standard deviation change in the complexity of systolic, diastolic and MAP time series was negatively associated (p < 0.05) with the STS and EuroSCORE indices in both unadjusted (21-34%) and models adjusted for age, gender and SD of the BP time series (15-31%). The mean and SD of BP time series were not significantly associated with the risk index except for a positive association with the SD of the diastolic BP. Lower preoperative BP complexity was associated with a higher estimated risk of adverse cardiovascular outcomes and may provide a novel approach to assessing cardiovascular risk. Future studies are needed to determine whether dynamical risk indices can improve current risk prediction tools.

A novel mitochondrial orf147 causes cytoplasmic male sterility in pigeonpea by modulating aberrant anther dehiscence.

KEY MESSAGE: A novel open reading frame (ORF) identified and cloned from the A4 cytoplasm of Cajanus cajanifolius induced partial to complete male sterility when introduced into Arabidopsis and tobacco. Pigeonpea (Cajanus cajan L. Millsp.) is the only legume known to have commercial hybrid seed technology based on cytoplasmic male sterility (CMS). We identified a novel ORF (orf147) from the A4 cytoplasm of C. cajanifolius that was created via rearrangements in the CMS line and co-transcribes with the known and unknown sequences. The bi/poly-cistronic transcripts cause gain-of-function variants in the mitochondrial genome of CMS pigeonpea lines having distinct processing mechanisms and transcription start sites. In presence of orf147, significant repression of Escherichia coli growth indicated its toxicity to the host cells and induced partial to complete male sterility in transgenic progenies of Arabidopsis thaliana and Nicotiana tabacum where phenotype co-segregated with the transgene. The male sterile plants showed aberrant floral development and reduced lignin content in the anthers. Gene expression studies in male sterile pigeonpea, Arabidopsis and tobacco plants confirmed down-regulation of several anther biogenesis genes and key genes involved in monolignol biosynthesis, indicative of regulation of retrograde signaling. Besides providing evidence for the involvement of orf147 in pigeonpea CMS, this study provides valuable insights into its function. Cytotoxicity and aberrant programmed cell death induced by orf147 could be important for mechanism underlying male sterility that offers opportunities for possible translation for these findings for exploiting hybrid vigor in other recalcitrant crops as well.

Peanuts that keep aflatoxin at bay: a threshold that matters.

Aflatoxin contamination in peanuts poses major challenges for vulnerable populations of sub-Saharan Africa and South Asia. Developing peanut varieties to combat preharvest Aspergillus flavus infection and resulting aflatoxin contamination has thus far remained a major challenge, confounded by highly complex peanut-Aspergilli pathosystem. Our study reports achieving a high level of resistance in peanut by overexpressing (OE) antifungal plant defensins MsDef1 and MtDef4.2, and through host-induced gene silencing (HIGS) of aflM and aflP genes from the aflatoxin biosynthetic pathway. While the former improves genetic resistance to A. flavus infection, the latter inhibits aflatoxin production in the event of infection providing durable resistance against different Aspergillus flavus morphotypes and negligible aflatoxin content in several peanut events/lines well. A strong positive correlation was observed between aflatoxin accumulation and decline in transcription of the aflatoxin biosynthetic pathway genes in both OE-Def and HIGS lines. Transcriptomic signatures in the resistant lines revealed key mechanisms such as regulation of aflatoxin synthesis, its packaging and export control, besides the role of reactive oxygen species-scavenging enzymes that render enhanced protection in the OE and HIGS lines. This is the first study to demonstrate highly effective biotechnological strategies for successfully generating peanuts that are near-immune to aflatoxin contamination, offering a panacea for serious food safety, health and trade issues in the semi-arid regions.

Three FLOWERING LOCUS T-like genes function as potential florigens and mediate photoperiod response in sorghum.

Sorghum is a typical short-day (SD) plant and its use in grain or biomass production in temperate regions depends on its flowering time control, but the underlying molecular mechanism of floral transition in sorghum is poorly understood. Here we characterized sorghum FLOWERING LOCUS T (SbFT) genes to establish a molecular road map for mechanistic understanding. Out of 19 PEBP genes, SbFT1, SbFT8 and SbFT10 were identified as potential candidates for encoding florigens using multiple approaches. Phylogenetic analysis revealed that SbFT1 clusters with the rice Hd3a subclade, while SbFT8 and SbFT10 cluster with the maize ZCN8 subclade. These three genes are expressed in the leaf at the floral transition initiation stage, expressed early in grain sorghum genotypes but late in sweet and forage sorghum genotypes, induced by SD treatment in photoperiod-sensitive genotypes, cooperatively repressed by the classical sorghum maturity loci, interact with sorghum 14-3-3 proteins and activate flowering in transgenic Arabidopsis plants, suggesting florigenic potential in sorghum. SD induction of these three genes in sensitive genotypes is fully reversed by 1 wk of long-day treatment, and yet, some aspects of the SD treatment may still make a small contribution to flowering in long days, indicating a complex photoperiod response mediated by SbFT genes.

DREB1A overexpression in transgenic chickpea alters key traits influencing plant water budget across water regimes.

KEY MESSAGE: We demonstrate the role of DREB1A transcription factor in better root and shoot partitioning and higher transpiration efficiency in transgenic chickpea under drought stress Chickpea (Cicer arietinum L.) is mostly exposed to terminal drought stress which adversely influences its yield. Development of cultivars for suitable drought environments can offer sustainable solutions. We genetically engineered a desi-type chickpea variety to ectopically overexpress AtDREB1A, a transcription factor known to be involved in abiotic stress response, driven by the stress-inducible Atrd29A promoter. From several transgenic events of chickpea developed by Agrobacterium-mediated genetic transformation, four single copy events (RD2, RD7, RD9 and RD10) were characterized for DREB1A gene overexpression and evaluated under water stress in a biosafety greenhouse at T6 generation. Under progressive water stress, all transgenic events showed increased DREB1A gene expression before 50 % of soil moisture was lost (50 % FTSW or fraction of transpirable soil water), with a faster DREB1A transcript accumulation in RD2 at 85 % FTSW. Compared to the untransformed control, RD2 reduced its transpiration in drier soil and higher vapor pressure deficit (VPD) range (2.0-3.4 kPa). The assessment of terminal water stress response using lysimetric system that closely mimics the soil conditions in the field, showed that transgenic events RD7 and RD10 had increased biomass partitioning into shoot, denser rooting in deeper layers of soil profile and higher transpiration efficiency than the untransformed control. Also, RD9 with deeper roots and RD10 with higher root diameter showed that the transgenic events had altered rooting pattern compared to the untransformed control. These results indicate the implicit influence of rd29A::DREB1A on mechanisms underlying water uptake, stomatal response, transpiration efficiency and rooting architecture in water-stressed plants.

Translation Research in Therapeutic Approaches from Conventional to Novel Nano-therapeutics for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis is a systemic autoimmune disorder related to joint inflammation, bone erosion, and deformity. Numerous studies indicate that the causes and consequences of RA are still being debated, and therapeutic strategies are in the translation stage. Non-steroidal anti-inflammatory drugs continue to be often used to relieve pain. Still, due to their poor efficacy, failure to halt the spread of the disease, and undesirable adverse effects, they are no longer regarded as first-line treatments. The development of biologic DMRDs designed to reduce the inflammatory response led to substantial changes to the strategy for managing this disease. Although biologic DMRDs have made significant strides in the management of Rheumatoid arthritis, certain patients' lack of response to biological approaches and therapy cessation due to systemic toxicity are unresolved problems. Therefore, to improve the in vivo effect and reduce systemic adverse effects, new approaches are needed to proactively target and transport therapeutic molecules to target sites. The intriguing method of nanotechnology enables the encapsulation of drugs to prevent their deterioration and systemic adverse effects. The next generation of Rheumatoid arthritis therapies might be based on advances in nanomaterial-based drug delivery, Trojan horse, and antibody targeting approaches. This article presents an overview of the advancements in Rheumatoid arthritis therapy, ranging from traditional methods to recent cutting-edge, ongoing pre-clinical and clinical approaches.

Deciphering the Therapeutic Applications of Nanomedicine in Ovarian Cancer Therapy: An Overview.

The majority of deadly cancers that afflict the female reproductive system occur in the ovary. Around 1,40,000 women worldwide die from ovarian cancer each year, making it the sixth most common cancer-associated deceases among females in the United States. Modern, cutting-edge treatments like chemotherapy and surgery frequently produce full remissions, but the recurrence rate is still very high. When this crippling condition is diagnosed, there are frequently few therapeutic choices available because of how quietly it manifests. Healthcare practitioners must have a fundamental grasp of the warning signs and symptoms of ovarian cancer, as well as the imaging techniques and treatment choices available, to give the patient the best care possible. The discipline of medical nanotechnology has gained a lot of momentum in recent years in resolving issues and enhancing the detection and treatment of different illnesses, including cancer. This article gives a brief summary of types, risk factors and approaches to ovarian cancer treatment. We subsequently discussed the pathophysiology of ovarian cancer with the risk factors. This review also emphasizes the various signalling pathways involved in ovarian cancer. Our comprehensive integration of recent findings in fundamental research in the nano arena reveals the strong interest in these nanomedicines in ovarian cancer treatment. However, these nanomedicines still require more research, as indicated by the comparatively small number of clinical trials ongoing. This article will provide a reference for ovarian cancer treatment.

Emerging Treatment Options of Pluronic in Designing Colloidal Nano and Microcarriers Carriers for Various Therapies.

Poloxamers, commonly known as Pluronics, are a special family of synthetic tri-block copolymers with a core structure made of hydrophobic poly (propylene oxide) chains sandwiched by two hydrophilic poly (ethylene oxide) chains. It is possible to modify the mechanical, bioactive, and microstructural characteristics of Pluronics to simulate the behavior of different types of tissues. Additionally, they are auspicious drug carriers with the capacity to increase therapeutic agent availability and to design nano-drug formulations for various ailments. The nanoformulation composed of Pluronics is more susceptible to cancer cells due to their amphiphilic nature and feature of selfassembling into micelles. Today's expanding poloxamer research is creating new hopes that increase the possibility of new remedies for a brand-new nanomedicine age treatment. This article provides a concise overview of the classification, grading, and attributes of drug delivery systems (DDSs) as well as the potential for Pluronics to create micro and nanocarriers. We subsequently discuss its utility in drug delivery for cancer, gene therapy, anti-infective therapy, antioxidants, anti-diabetic drugs, anti-HIV, Alzheimer's disease, and antimicrobial drugs. This review also highlighted several patented formulations that contain various grades of Pluronics in one or more different ways. The recent findings in fundamental research in the field properly demonstrate the strong interest in these novel pharmaceutical strategies.

Ectopic expression of pigeonpea Orf147 gene imparts partial sterility in Cicer arietinum.

Orf147, a cytotoxic peptide, has been found to cause cytoplasmic male sterility (CMS) in Cajanus cajanifolius (pigeonpea). In our study, Orf147 was introduced into self-pollinating Cicer arietinum (chickpea) using Agrobacterium-mediated transformation for induction of CMS. The stable integration and expression of the transgene has been assessed through PCR and qRT-PCR analysis. In addition, phenotypic sterility analysis has been performed, considering developmental parameters like flower development, pod formation and flower drop. Transgene inheritance analysis demonstrates that out of the five PCR positive events in the T0 generation, two events have segregated according to the Mendelian segregation ratio (3:1) in the T2 generation. Further, pollen viability test using microscopic analysis confirms the induction of partial CMS in transgenic chickpea. The study holds significant value regarding the heterosis of self-pollinating legumes like chickpea. As a part of the prospect, exploring inducible promoters of species-specific or related legumes would be the next step to developing a two-line hybrid system.

Multiplexed Host-Induced Gene Silencing of Aspergillus flavus Genes Confers Aflatoxin Resistance in Groundnut.

Aflatoxins are immunosuppressive and carcinogenic secondary metabolites, produced by the filamentous ascomycete Aspergillus flavus, that are hazardous to animal and human health. In this study, we show that multiplexed host-induced gene silencing (HIGS) of Aspergillus flavus genes essential for fungal sporulation and aflatoxin production (nsdC, veA, aflR, and aflM) confers enhanced resistance to Aspergillus infection and aflatoxin contamination in groundnut (<20 ppb). Comparative proteomic analysis of contrasting groundnut genotypes (WT and near-isogenic HIGS lines) supported a better understanding of the molecular processes underlying the induced resistance and identified several groundnut metabolites that might play a significant role in resistance to Aspergillus infection and aflatoxin contamination. Fungal differentiation and pathogenicity proteins, including calmodulin, transcriptional activator-HacA, kynurenine 3-monooxygenase 2, VeA, VelC, and several aflatoxin pathway biosynthetic enzymes, were downregulated in Aspergillus infecting the HIGS lines. Additionally, in the resistant HIGS lines, a number of host resistance proteins associated with fatty acid metabolism were strongly induced, including phosphatidylinositol phosphate kinase, lysophosphatidic acyltransferase-5, palmitoyl-monogalactosyldiacylglycerol Δ-7 desaturase, ceramide kinase-related protein, sphingolipid Δ-8 desaturase, and phospholipase-D. Combined, this knowledge can be used for groundnut pre-breeding and breeding programs to provide a safe and secure food supply.

Genetic enhancement of Trichoderma asperellum biocontrol potentials and carbendazim tolerance for chickpea dry root rot disease management.

Advances in biocontrol potentials and fungicide resistance are highly desirable for Trichoderma. Thus, it is profitable to use mutagenic agents to develop superior strains with enhanced biocontrol properties and fungicide tolerance in Trichoderma. This study investigates the N-methyl-n-nitro-N-nitrosoguanidine (NTG) (100 mg/L) induced mutants of Trichoderma asperellum. Six NTG (3 each from 1st & 2nd round) induced mutants were developed and evaluated their biocontrol activities and carbendazim tolerance. Among the mutant N2-3, N2-1, N1 and N2-2 gave the best antagonistic and volatile metabolite activities on inhibition of chickpea F. oxysporum f. sp. ciceri, B. cinerea and R. bataticola mycelium under in vitro condition. Mutant N2-2 (5626.40 µg/ml) showed the highest EC50 value against carbendazim followed by N2-3 (206.36 µg/ml) and N2-1 (16.41 µg/ml); and succeeded to sporulate even at 2000 µg/ml of carbendazim. The biocontrol activity of N2-2 and N2 with half-dose of carbendazim was evaluated on chickpea dry root rot under controlled environment. Disease reduction and progress of the dry root rot was extremely low in T7 (N2-2 + with half-dose of carbendazim) treatment. Further, carbendazim resistant mutants demonstrated mutation in tub2 gene of ß-tubulin family which was suggested through the 37 and 183 residue changes in the superimposed protein structures encoded by tub2 gene in N2 and N2-2 with WT respectively. This study conclusively implies that the enhanced carbendazim tolerance in N2-2 mutant did not affect the mycoparasitism and plant growth activity of Trichoderma. These mutants were as good as the wild-type with respect to all inherent attributes.

Innovation in cancer therapeutics and regulatory perspectives.

Cancer therapy has undergone a drastic revolution in the past few decades with the introduction of several novel therapies, like immunotherapy (active and passive), stem cell-based therapies, and nanocarrier-based therapies. These therapies have addressed the issues of conventional cancer therapy (chemotherapy or radiotherapy), like specificity and off-target effects. Further, the introduction of such treatments has improved survival and converted a terminal disease into a more manageable condition. However, many clinical, ethical, and regulatory issues are raised with such novel additions. Several effective therapies are under research but could not come to market or are delayed due to regulatory concerns for marketing approval. The scope of this review encompasses the examination of these regulatory issues and discuss their possible solutions. A practical and flexible regulatory approach, harmonized globally, could help the patients suffering from a terminal illness to lead a quality life.

CRISPR for accelerating genetic gains in under-utilized crops of the drylands: Progress and prospects.

Technologies and innovations are critical for addressing the future food system needs where genetic resources are an essential component of the change process. Advanced breeding tools like "genome editing" are vital for modernizing crop breeding to provide game-changing solutions to some of the "must needed" traits in agriculture. CRISPR/Cas-based tools have been rapidly repurposed for editing applications based on their improved efficiency, specificity and reduced off-target effects. Additionally, precise gene-editing tools such as base editing, prime editing, and multiplexing provide precision in stacking of multiple traits in an elite variety, and facilitating specific and targeted crop improvement. This has helped in advancing research and delivery of products in a short time span, thereby enhancing the rate of genetic gains. A special focus has been on food security in the drylands through crops including millets, teff, fonio, quinoa, Bambara groundnut, pigeonpea and cassava. While these crops contribute significantly to the agricultural economy and resilience of the dryland, improvement of several traits including increased stress tolerance, nutritional value, and yields are urgently required. Although CRISPR has potential to deliver disruptive innovations, prioritization of traits should consider breeding product profiles and market segments for designing and accelerating delivery of locally adapted and preferred crop varieties for the drylands. In this context, the scope of regulatory environment has been stated, implying the dire impacts of unreasonable scrutiny of genome-edited plants on the evolution and progress of much-needed technological advances.