A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy.

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Metabolomics-driven investigation of plant defense response against pest and pathogen attack.

The advancement of metabolomics has assisted in the identification of various bewildering characteristics of the biological system. Metabolomics is a standard approach, facilitating crucial aspects of system biology with absolute quantification of metabolites using minimum samples, based on liquid/gas chromatography, mass spectrometry and nuclear magnetic resonance. The metabolome profiling has narrowed the wide gaps of missing information and has enhanced the understanding of a wide spectrum of plant-environment interactions by highlighting the complex pathways regulating biochemical reactions and cellular physiology under a particular set of conditions. This high throughput technique also plays a prominent role in combined analyses of plant metabolomics and other omics datasets. Plant metabolomics has opened a wide paradigm of opportunities for developing stress-tolerant plants, ensuring better food quality and quantity. However, despite advantageous methods and databases, the technique has a few limitations, such as ineffective 3D capturing of metabolites, low comprehensiveness, and lack of cell-based sampling. In the future, an expansion of plant-pathogen and plant-pest response towards the metabolite architecture is necessary to understand the intricacies of plant defence against invaders, elucidation of metabolic pathway operational during defence and developing a direct correlation between metabolites and biotic stresses. Our aim is to provide an overview of metabolomics and its utilities for the identification of biomarkers or key metabolites associated with biotic stress, devising improved diagnostic methods to efficiently assess pest and pathogen attack and generating improved crop varieties with the help of combined application of analytical and molecular tools.

Effect of CYP2C19 polymorphism on response to bortezomib-based therapy in multiple myeloma patients.

BACKGROUND: Bortezomib, a commonly used anti-myeloma drug, is metabolized by liver microsomal enzymes which may be polymorphic and responsible for lack of response in 30% patients. Hence, the association of CYP2C19 polymorphism with treatment response was explored in this study. METHODS: Treatment naive multiple myeloma (MM) patients, eligible for bortezomib-based induction treatment, were recruited as per the inclusion - exclusion criteria. The genotyping of CYP2C19 was done using polymerase chain reaction-restriction fragment length polymorphism for *2, *3 and *17 alleles. The incidence and severity of peripheral neuropathy were noted at follow-up visits and graded as per CTCAE criteria ver 5.0. RESULTS: Total 220 patients were recruited from August 2016 till May 2021; with a mean age of 55.6 (9.5) years and 65.9% males. Bortezomib+cyclophosphamide+dexamethasone (41.8%) and bortezomib+lenalidomide+dexamethasone (38.2%) were the most prescribed regimens. The CYP2C19 was polymorphic in 38.6%, 2.3% and 23.7% patients for *2, *3 and *17 allele respectively. There were 195 treatment responders and 25 non-responders, and CYP2C19*2 allele was different between responders and non-responders (p = 0.02). All extensive metabolisers (n = 54) were noted to be treatment responders. Peripheral neuropathy was reported by 23.2% patients. The frequency of peripheral neuropathy was somewhat lower in patients having either *2/*2 or *3/*3 allele pattern for CYP2C19 (p = 0.44). CONCLUSIONS: Polymorphism in CYP2C19 enzyme is likely to have an impact on bortezomib treatment response and peripheral neuropathy. The study suggests the role of pharmacogenetics in personalised treatment of MM.

Biochemical and Molecular Basis of Chemically Induced Defense Activation in Maize against Banded Leaf and Sheath Blight Disease.

Maize is the third most vital global cereal, playing a key role in the world economy and plant genetics research. Despite its leadership in production, maize faces a severe threat from banded leaf and sheath blight, necessitating the urgent development of eco-friendly management strategies. This study aimed to understand the resistance mechanisms against banded leaf and sheath blight (BLSB) in maize hybrid "Vivek QPM-9". Seven fungicides at recommended doses (1000 and 500 ppm) and two plant defense inducers, salicylic acid (SA) and jasmonic acid (JA) at concentrations of 50 and 100 ppm, were applied. Fungicides, notably Azoxystrobin and Trifloxystrobin + Tebuconazole, demonstrated superior efficacy against BLSB, while Pencycuron showed limited effectiveness. Field-sprayed Azoxystrobin exhibited the lowest BLSB infection, correlating with heightened antioxidant enzyme activity (SOD, CAT, POX, ß-1,3-glucanase, PPO, PAL), similar to the Validamycin-treated plants. The expression of defense-related genes after seed priming with SA and JA was assessed via qRT-PCR. Lower SA concentrations down-regulated SOD, PPO, and APX genes but up-regulated CAT and ß-1,3-glucanase genes. JA at lower doses up-regulated CAT and APX genes, while higher doses up-regulated PPO and ß-1,3-glucanase genes; SOD gene expression was suppressed at both JA doses. This investigation elucidates the effectiveness of certain fungicides and plant defense inducers in mitigating BLSB in maize hybrids and sheds light on the intricate gene expression mechanisms governing defense responses against this pathogen.

Metabolic engineering for enhanced terpenoid production: Leveraging new horizons with an old technique.

Terpenoids are a vast class of plant specialized metabolites (PSMs) manufactured by plants and are involved in their interactions with environment. In addition, they add health benefits to human nutrition and are widely used as pharmaceutically active compounds. However, native plants produce a limited amount of terpenes restricting metabolite yield of terpene-related metabolites. Exponential growth in the plant metabolome data and the requirement of alternative approaches for producing the desired amount of terpenoids, has redirected plant biotechnology research to plant metabolic engineering, which requires in-depth knowledge and precise expertise about dynamic plant metabolic pathways and cellular physiology. Metabolic engineering is an assuring tool for enhancing the concentration of terpenes by adopting specific strategies such as overexpression of the key genes associated with the biosynthesis of targeted metabolites, controlling the modulation of transcription factors, downregulation of competitive pathways (RNAi), co-expression of the biosynthetic pathway genes in heterologous system and other combinatorial approaches. Microorganisms, fast-growing host plants (such as Nicotiana benthamiana), and cell suspension/callus cultures have provided better means for producing valuable terpenoids. Manipulation in the biosynthetic pathways responsible for synthesis of terpenoids can provide opportunities to enhance the content of desired terpenoids and open up new avenues to enhance their production. This review deliberates the worth of metabolic engineering in medicinal plants to resolve issues associated with terpenoid production at a commercial scale. However, to bring the revolution through metabolic engineering, further implementation of genome editing, elucidation of metabolic pathways using omics approaches, system biology approaches, and synthetic biology tactics are essentially needed.

Emerging trends in research and development on earth abundant materials for ammonia degradation coupled with H2 generation.

Ammonia, as an essential and economical fuel, is a key intermediate for the production of innumerable nitrogen-based compounds. Such compounds have found vast applications in the agricultural world, biological world (amino acids, proteins, and DNA), and various other chemical transformations. However, unlike other compounds, the decomposition of ammonia is widely recognized as an important step towards a safe and sustainable environment. Ammonia has been popularly recommended as a viable candidate for chemical storage because of its high hydrogen content. Although ruthenium (Ru) is considered an excellent catalyst for ammonia oxidation; however, its high cost and low abundance demand the utilization of cheaper, robust, and earth abundant catalyst. The present review article underlines the various ammonia decomposition methods with emphasis on the use of non-noble metals, such as iron, nickel, cobalt, molybdenum, and several other carbides as well as nitride species. In this review, we have highlighted various advances in ammonia decomposition catalysts. The major challenges that persist in designing such catalysts and the future developments in the production of efficient materials for ammonia decomposition are also discussed.

In this dynamic area, ammonia degradation to hydrogen fuel provides a valuable contribution in the carbon neutral economy. Ammonia has been used extensively in several industries and is considered an ideal candidate for hydrogen generation and storage due to its high hydrogen content. Consequently, the ammonia decomposition to yield green hydrogen has become a hot topic in research. Although numerous studies on ammonia decomposition have been conducted over the last few decades, still very few review articles on the most recent advances in this field of catalysis have been published. Through this review, systematic information on the types of decomposition catalysts including both noble (Ru) and non-noble earth abundant metals such as iron, nickel, cobalt, molybdenum, their carbides and nitrides, catalytic routes, as well as the reactivity and mechanism can be comprehended. The literature on newly discovered catalysts, specifically from the last five years, is well documented and explained in this review article. Furthermore, the effect of catalyst supports, their reaction kinetics and mechanistic insights have also been discussed. The challenges and opportunities associated with the decomposition catalysts are comprehensively explicated in the end.

Ammonia decomposition reaction (ADR) is a viable method for hydrogen storage in the form of chemical bonds.Catalysts composed of noble, non-noble metals, amides, imides, carbides, nitrides, and their combinations have been widely explored towards the ADR.Challenges and opportunities in the ammonia oxidation are pointed out.

Toe brachial index and not ankle brachial index is appropriate in initial evaluation of peripheral arterial disease in type 2 diabetes.

BACKGROUND: Non-invasive clinic-based tools for assessing PAD are not without limitations. Therefore, costly tests like Doppler study, CT angiography and MR angiography are often required to make a diagnosis. Ankle brachial index (ABI), commonly used for assessment of PAD, has high false positivity rates in sclerosed, calcified arteries which render them non-compressible. Toe brachial index (TBI) can be an alternative, as digital arteries are relatively unaffected by these changes. AIM: To compare the reliability of ABI and TBI in diagnosing PAD in type 2 diabetes using CT angiography (CTA) as the reference. METHODS: 175 adults with T2D were selected. ABI &TBI were measured with an automated vascular Doppler XT 6 ports bilaterally for all subjects. For any subject, the limb with lower ABI and TBI was included for analysis. ABI < 0.9 & TBI < 0.6 were taken as evidence of PAD. CTA showing > 50% narrowing was taken as evidence of PAD. RESULTS: 24% of our study subjects had CTA confirmed PAD. ABI has low sensitivity of 35.29% (95% CI 0.21-0.52) compared to TBI being 82.35% (95% CI 0.66-0.92). The specificity however was similar. ABI < 0.9 was able to detect CTA confirmed PAD, but ABI > 0.9, including the so-called normal ABI (0.9-1.3) was unable to detect PAD. ROC showed ABI at 1.005 has sensitivity 64.71% (95% CI 0.48- 0.79) and specificity 61.7% (95% CI 0.53-0.69) and TBI at 0.6 has sensitivity 82.35% (95% CI 0.66-0.92) & specificity 92% (95% CI 0.87-0.96). Utilizing Cohen's Kappa, the reliability of ABI with respect to CTA showed fair agreement (K = 0.225, p = 0.001), whereas the reliability of TBI with respect to CTA showed substantial agreement (K = 0.759, p < 0.0001). CONCLUSION: ABI < 0.9 detects PAD reliably, but presence of PAD in patients with ABI > 9.0 including the normal of ABI (0.9-1.3) can be confirmed with TBI, which correlated strongly with CTA. TBI is also non-inferior for PAD detection, when ABI < 0.9. TBI and not ABI can be utilized for initial assessment of PAD in subjects with T2D.

The frequency and clinical outcome of mono-hit and multi-hit TP53 aberrations in newly diagnosed multiple myeloma.

We investigated the frequency and outcome of mono-hit and multi-hit TP53 aberrations [biallelic or ≥1 TP53 mutations (TP53mut) or TP53mut with variant allele frequency (VAF) ≥55%] in an Indian cohort of newly diagnosed multiple myeloma (NDMM) patients. We employed fluorescence insitu hybridisation (FISH; n=457) and targeted next-generation sequencing (NGS; n=244) on plasma cell-enriched samples. We also studied the impact of TP53mut in cases with and without TP53 deletions (TP53del). In our cohort with a median age of 60 years, TP53del and TP53mut were seen in 12.9% (n=59/457; 14-95% cells) and 10.2% (n=25/244; 30 variants; VAF 3.4-98.2%; median 38.2%) respectively. Mono-hit and multi-hit-TP53 aberrations were observed in 10.2% and 7.8%, respectively. Compared to TP53-wild-type (TP53wt), mono-hit and multi-hit TP53 aberrations were associated with significantly poorer progression-free survival (PFS) (22.6 vs 12.1 vs 9.5 months; p=0.004) and overall survival (OS) [not reached (NR) vs 13.1 vs 15.6 months respectively; p=0.024]. However, multi-hit TP53 did not significantly differ in OS/PFS compared to mono-hit cases. Compared to TP53wt, PFS and OS were significantly poorer in patients with TP53mut only (9.5 vs 22.6 months and 12.1 months vs NR, respectively; p=0.020/0.004). TP53mut retained its significance even in the presence of any Revised International Staging System (HR 2.1; 95% CI 1.1-3.8; p=0.015) for OS. The detection of additional cases with TP53 aberrations, as well as poor survival associated with the presence of mutation alone, supports TP53mut testing in NDMM at least in patients without TP53del and other high-risk cytogenetic abnormalities.

A novel method for detecting conformation-dependent ß-glucans-single, double, and triple-helical from Shiitake mushroom.

This pioneering study explores the structural intricacies of therapeutic ß-glucan in Shiitake (Lentinula edodes), i.e. Lentinan (LNT). Lentinan, a neutral polysaccharide [ß-(1,3; 1,6) glucan], exists in three forms; single, double, and triple-helical, but conformation-dependent bioactivity studies are lacking. In this context, we meticulously assessed indigenous Shiitake accessions from Northeast India, unveiling the conformational spectrum of LNT through an innovative pipeline. The experiment approached the simultaneous estimation of total glucan (TG), triple helical glucan (THG), and single-double helical glucan (SDG). Profiling revealed the exceptional LNT content in DMRO-623 (TG: 46.74%, SDG: 9.34%, THG: 37.39%) which emerged as the highest documented to date. Beyond the culinary delight, this research and the novel approach to LNT quantification will create a pivotal platform for advanced mushroom research, offering prospects for novel discoveries, innovative applications, and therapeutic potential.

Prevalence and determinants of anemia due to micronutrient deficiencies among children aged 12-59 months in India-Evidence from Comprehensive National Nutrition Survey, 2016-18.

The present study aimed to estimate the prevalence of anemia, and anemia with micronutrient deficiencies (iron/ vitamin B12/ folic acid) and their determinants among children aged 12-59 months in India. Comprehensive National Nutritional Survey (2016-2018) is Asia's largest nutrition survey conducted among 0-19 years aged children in India. We used generalised linear model (modified Poisson) with adjusted prevalence ratio (aPR) to assess the socio-economic and biochemical factors associated with anemia and anemia with micronutrient deficiencies amongst children aged 12 to 59 months. Out of the total of 11,237 children included in the study, 40.5% (95%CI:38·6-42·6) were anemic, 30.0% (95%CI:27·8-32·4) had anemia with micronutrient deficiencies and 60.9% (95%CI:58·2-63·5) had micronutrient deficiencies with or without anemia. Younger age (aPR(95%CI) for one year old: 1.9(1.5-2.4), two year old: 1.8(1.5-2.2), three year old: 1.4(1.2-1.7) compared to four year old children) and lower educational status of the mother (mothers without formal schooling aPR(95%CI):1.4(1.1-1.8); 1-9 standards: 1.4(1.2-1.7)) vs mother educated with high school and above, consumption of less than 100 iron-folic acid tablets during pregnancy (aPR(95%CI):1.3(1.0-1.7) vs consumption of ≥ 180 tablets, any self-reported illness among children within two weeks preceding the interview (aPR(95%CI):1.2(1.1-1.4) vs no-illnesses, iron deficiency (aPR(95%CI):2.2(2.0-2.6)) and zinc deficiency (aPR(95%CI):1.3(1.1-1.4)) were associated with anemia in children. Among anemic, the children from scheduled tribe (aPR(95%CI):1.4(1.1-1.8)) vs other caste categories, and those following unsafe child faeces disposal practices (aPR(95%CI):1.2(1.0-1.4)) vs those who follow safe faeces disposal practices had higher chance of having micronutrient deficiency. One third of children aged 12-59 months had anemia with micronutrient deficiency (iron/ folic acid/ vitamin B12). More than half of children had micronutrient deficiencies irrespective of anemia. Micronutrient deficiencies, antenatal IFA intake, safe hygiene practices need to be strengthened to leave no stone unturned in control of anemia among under-five children in India.

Hyperglycemia modulates M1/M2 macrophage polarization in chronic diabetic patients with pulmonary tuberculosis infection.

Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1ß) and CD206. Furthermore, we observed a positive correlation of IL-1ß and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1ß and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection.

Targeting neuroblastoma by small-molecule inhibitors of human ALYREF protein: mechanistic insights using molecular dynamics simulations.

Neuroblastoma is a tumour of the sympathetic nervous system mainly prevalent in children. Many strategies have been employed to target several drug-targetable proteins for the clinical management of neuroblastoma. However, the heterogeneous nature of neuroblastoma presents serious challenges in drug development for its treatment. Albeit numerous medications have been developed to target various signalling pathways in neuroblastoma, the redundant nature of the tumour pathways makes its suppression unsuccessful. Recently, the quest for neuroblastoma therapy resulted in the identification of human ALYREF, a nuclear protein that plays an essential role in tumour growth and progression. Therefore, this study used the structure-based drug discovery method to identify the putative inhibitors targeting ALYREF for the Neuroblastoma treatment. Herein, a library of 119 blood-brain barrier crossing small molecules from the ChEMBL database was downloaded and docked against the predicted binding pocket of the human ALYREF protein. Based on docking scores, the top four compounds were considered for intermolecular interactions and molecular dynamics simulation analysis, which revealed CHEMBL3752986 and CHEMBL3753744 with substantial affinity and stability with the ALYREF. These results were further supported by binding free energies and essential dynamics analysis of the respective complexes. Hence, this study advocates the sorted compounds targeting ALYREF for further in vitro and in vivo assessment to develop a drug against neuroblastoma.Communicated by Ramaswamy H. Sarma.

Exploring the role of neutrophils in infectious and noninfectious pulmonary disorders.

With the change in global environment, respiratory disorders are becoming more threatening to the health of people all over the world. These diseases are closely linked to performance of immune system. Within the innate arm of immune system, Neutrophils are an important moiety to serve as an immune defense barrier. They are one of the first cells recruited to the site of infection and plays a critical role in pathogenesis of various pulmonary diseases. It is established that the migration and activation of neutrophils can lead to inflammation either directly or indirectly and this inflammation caused is very crucial for the clearance of pathogens and resolution of infection. However, the immunopathological mechanisms involved to carry out the same is very complex and not well understood. Despite there being studies concentrating on the role of neutrophils in multiple respiratory diseases, there is still a long way to go in order to completely understand the complexity of the participation of neutrophils and mechanisms involved in the development of these respiratory diseases. In the present article, we have reviewed the literature to comprehensively provide an insight in the current development and advancements about the role of neutrophils in infectious respiratory disorders including viral respiratory disorders such as Coronavirus disease (COVID-19) and bacterial pulmonary disorders with a focused review on pulmonary tuberculosis as well as in noninfectious disorders like Chronic obstructive pulmonary disease (COPD) and asthma. Also, future directions into research and therapeutic targets have been discussed for further exploration.

Respiratory illnesses are becoming more prevalent and a substantial source of sickness and mortality worldwide as a result of the changes in the global environment. Although diagnostic and therapeutic approaches for respiratory disorders have improved over the years, a thorough and in-depth approach is still required to understand the underlying immuno-pathophysiological mechanisms. Neutrophils are a crucial part of innate immune system which functions as a first line defense against various pulmonary infections. They are known to be involved in resistance against invading pulmonary pathogens and also play an important role in repairing of damaged lung tissue by removing debris. However, emerging evidences suggest that neutrophils may also be involved in promoting and aggravating the unabating inflammation in several pulmonary disorders by release of various proteases, forming neutrophil extracellular traps or by attracting and activating other immune cells at the site of inflammation. In this article, we have discussed diverse roles and responses of neutrophils and their use in potential future research and therapeutic approaches in infectious pulmonary disorders like Tuberculosis and COVID-19 and noninfectious pulmonary disorders like Chronic obstructive pulmonary disease (COPD) and asthma.

A novel micronutrients and methyl jasmonate cocktail of elicitors via seed priming improves drought tolerance by mitigating oxidative stress in rice (Oryza sativa L.).

Drought is a major limiting factor for rice (Oryza sativa L.) production globally, and a cost-effective seed priming technique using bio-elicitors has been found to have stress mitigating effects. Till date, mostly phytohormones have been preferred as bio-elicitors, but the present study is a novel attempt to demonstrate the favorable role of micronutrients-phytohormone cocktail, i.e., iron (Fe), zinc (Zn), and methyl jasmonate (MJ) via seed priming method in mitigating the deleterious impacts of drought stress through physio-biochemical and molecular manifestations. The effect of cocktail/priming was studied on the relative water content, chlorophyll a/b and carotenoid contents, proline content, abscisic acid (ABA) content, and on the activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), NADPH oxidase (Nox), and catalase (CAT). The expressions of drought-responsive genes OsZn-SOD, OsFe-SOD, and Nox1 were found to be modulated under drought stress in contrasting rice genotypes -N-22 (Nagina-22, drought-tolerant) and PS-5 (Pusa Sugandh-5, drought-sensitive). A progressive rise in carotenoids (10-19%), ABA (18-50%), proline (60-80%), activities of SOD (27-62%), APX (46-61%), CAT (50-80%), Nox (16-30%), and upregulated (0.9-1.6-fold) expressions of OsZn-SOD, OsFe-SOD, and Nox1 genes were found in the primed plants under drought condition. This cocktail would serve as a potential supplement in modern agricultural practices utilizing seed priming technique to mitigate drought stress-induced oxidative burst in food crops.

Lingual Artery as the Recipient Vessel of Choice in Patients Requiring a Second or Third Free Flap in Recurrent Oral Cancers and Vessel-Depleted Neck: A 5-Year Experience in a Single Institute.

Introduction Reconstruction with free flaps becomes a challenge in recurrent cases having previously treated necks, in patients who have received prior radiation therapy or chemotherapy or both, and where the patient has already undergone free flap reconstruction in a prior surgery. Depleted cervical recipient vessels can increase the complexity of reconstruction in achieving successful free flap prefusion and thereby increasing flap thrombosis and eventually failure. Materials and Methods Over a period of 5 years from January 2018 to February 2023, we encountered a total of 22 cases of recurrent or second primary oral cancer with bilateral necks operated, postadjuvant chemo-radiotherapy, and requiring a second or third free flap reconstruction. In most of the cases we resorted to the lingual artery as the recipient artery of choice. Results No flap loss was reported. No cases were reexplored either for hematoma or for congestion. All patients recovered uneventfully. Conclusion To the best of our knowledge, there has been no paper yet that focuses on the lingual artery to be the recipient vessel of choice in recurrent oral cancers. We find the lingual artery to be a reliable and safe option and advocate its usage as recipient vessel of choice in recurrent oral cancers requiring more than one free flap reconstruction.

Prospective Study to Compare Efficacy of Conventional Chemoradiotherapy with Hypofractionated Chemoradiotherapy in Locally Advanced Carcinoma of Oropharynx.

AIMS: Chemoradiotherapy is the standard treatment for advanced Oropharyngeal squamous cell carcinoma (OPSCC). Upcoming hypofractionation has led to better compliance and non-inferior results in various sites such as breast and prostate cancer etc.  This study prospectively compared a dose-intensified schedule in advanced OPSCC with standard hypofractionation. MATERIALS AND METHODS: Patients with advanced stage III and IV OPSCC suitable for radical chemoradiotherapy were eligible. Patients were alternatively allocated to both the treatment arms. Arm A planned to receive 64 Gy in 25 fractions (#) with concurrent cisplatin and Arm B received standard fractionation 70 Gy in 35 # with concurrent cisplatin. All patients completed a median follow up of 6 to 18 months.  The primary end point was acute toxicity (less than 3 months) and late toxicity at 1 year. Secondary end point was disease free survival and overall survival at 1 year. RESULTS: 44 patients in arm A and 49  patients in arm B were recruited over 18 months. 34 patients completed full-dose radiotherapy in both arms. Maximum acute toxicity in arm A in terms of skin reaction was Grade II in 47.05% cases and mucositis grade II in 67.6% cases. In arm B grade II skin toxicity was seen in 47.1% and mucositis grade II was seen in 79.4 % cases. Ryle's tube dependency was seen in 38.2 % cases in arm A and 50% in arm B.  Complete response rate at 3 months was equivalent in both arms in Arm A (100%), and in Arm B (96.7%). Disease free survival (DFS), Overall survival (OS) at 3 month, 6 months, and 12 months was comparable. CONCLUSIONS: 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with equivalent results and better compliance. Shorter fractionation schedule is more acceptable and we look forward for more randomized control trials.

Comprehensive and evolutionary analysis of Spodoptera litura-inducible Cytochrome P450 monooxygenase gene family in Glycine max elucidate their role in defense.

Plants being sessile organisms and lacking both circulating phagocytic cells and somatic adaptive immune response, have thrived on various defense mechanisms to fend off insect pests and invasion of pathogens. CYP450s are the versatile enzymes, which thwart plants against insect pests by ubiquitous biosynthesis of phytohormones, antioxidants, and secondary metabolites, utilizing them as feeding deterrents and direct toxins. Therefore, a comprehensive analysis of biotic stress-responsive CYPs from Glycine max was performed to ascertain their function against S. litura-infestation. Phylogenetic analysis and evolutionary studies on conserved domains and motifs disclosed the evolutionary correspondence of these GmCYPs with already characterized members of the CYP450 superfamily and close relatedness to Medicago truncatula. These GmCYPs were mapped on 13 chromosomes; they possess 1-8 exons; they have evolved due to duplication and are localized in endoplasmic reticulumn. Further, identification of methyl-jasmonate, salicylic acid, defense responsive and flavonoid biosynthesis regulating cis-acting elements, their interaction with biotic stress regulating proteins and their differential expression in diverse types of tissues, and during herbivory, depicted their responsiveness to biotic stress. Three-dimensional homology modelling of GmCYPs, docking with heme cofactor required for their catalytic activity and enzyme-substrate interactions were performed to understand the functional mechanism of their action. Moreover, to gain insight into their involvement in plant defense, gene expression analysis was evaluated, which revealed differential expression of 11 GmCYPs upon S. litura-infestation, 12 GmCYPs on wounding while foliar spray of ethylene, methyl-jasmonate and salicylic acid differentially regulated 11 GmCYPs, 6 GmCYPs, and 10 GmCYPs respectively. Our study comprehensively analysed the underlying mechanism of GmCYPs function during S. litura-infestation, which can be further utilized for functional characterization to develop new strategies for enhancing soybean resistance to insect pests.