Daily versus fortnightly oral vitamin D3 in treatment of symptomatic vitamin D deficiency in children aged 1-10 years: An open labelled randomized controlled trial.

OBJECTIVE: Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years. DESIGN: Open labelled randomized controlled trial. PATIENTS: Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day. MEASUREMENTS: Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens. RESULTS: Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up. CONCLUSIONS: Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

Serum Uric Acid Levels as a Risk Stratification Tool in Hypertensive Disorders of Pregnancy: A Retrospective Study.

BACKGROUND: Worldwide, hypertensive disorders of pregnancy (HDP) are among the leading causes of maternal and fetal morbidity and mortality. Serum uric acid is a test that can evaluate the severity of HDP and the associated maternal and fetal morbidity and mortality. AIM: To examine the relationship between maternal serum uric acid levels and the severity of HDP and overall pregnancy outcomes. MATERIAL AND METHODS: A retrospective study was conducted on women with a gestational age > 20 weeks and BP >140/90 mmHg over three years. A total of 134 patients were included in the study. Patients with chronic hypertension, hyperuricemia without hypertension, and other major illnesses were excluded. Data were collected from medical records, including age, gravida, parity, weight, height, gestational age, blood pressure at admission, urine albumin, and serum uric acid levels. RESULTS: Of the 134 enrolled women with HDP, 76 had gestational hypertension, 41 had preeclampsia, and 17 had eclampsia. Mean uric acid levels in mg/dL were 6.06±1.651, 6.20±0.824, and 7.38±1.26 in gestational hypertension, preeclampsia, and eclampsia, respectively, which was a significant association (p=0.002). Mean uric acid in mg/dL was 5.86±1.27 in intensive care unit (ICU) patients compared to 6.45±1.39 in ward patients (p=0.015). There was a significantly increased risk of ICU admission and preterm delivery (r=-0.401, p<0.001) in patients with elevated uric acid levels. There was a significantly increased risk of low-birth-weight babies with elevated uric acid levels (r=-0.278, p=0.001). However, there was no statistically significant increased risk of newborn intensive care unit admissions (p=0.264) with elevated uric acid levels. CONCLUSION: Serum uric acid levels vary significantly in HDP and were found to be elevated in severe preeclampsia and eclampsia. It can be considered for risk stratification in HDP based on disease severity; however, its role in determining outcomes is debatable. Using serum uric acid levels in predictive models along with known biomarkers may determine its possible additional value in disease prediction and severity.

The Effectiveness of Routine Cerclage in In Vitro Fertilization (IVF) Twins.

INTRODUCTION: The incidence of twin pregnancies is on the rise worldwide due to assisted reproductive technologies. Cervical dilatation is a frequent complication and can be considered a cause of premature births in twin pregnancies. In vitro fertilization (IVF) twins are more prone to preterm delivery. Routine cervical cerclage with normal cervical length is not recommended in twins, but studies were not done on IVF twins. So, this study aims to evaluate the effectiveness of routine transvaginal cerclage in twin IVF pregnancies with normal cervical length on maternofetal outcome. MATERIALS AND METHODS: A retrospective case-control study was conducted at a maternity hospital in eastern India from January 2016 to December 2019 with over 21800 deliveries. Two groups were taken, cases were those IVF twins with normal cervical length in whom cervical cerclage was done as they have referred to our hospital from the IVF centers for cerclage and in control no-cervical cerclage as they are referred from other IVF centers where cerclage was not a routine protocol. We have excluded cerclage done for history, ultrasound indicated, uterine anomalies, and monochorionic twins. Fifteen participants were recruited in both cases and controls. RESULTS: In our study 2 (6.66%), 4 (13%), and 26 (86%) were IVF twins delivered at a gestational age of <28 weeks, 28-32 weeks, and 32-37 weeks, respectively. The mean age of participants, mean gestation age at delivery, and birth weight in cases and control were 35.27 ± 5.98 years (min: 23; max: 45), 32.40 ± 5.54 years (min: 25; max: 44); 34 weeks 2 days ± 3.28 (min: 31; max: 37), 33 weeks 5 days ± 1.66 (min: 25; max: 37); 1961.33 ± 340 gram, 1899.33 ± 437.48 gram, respectively with no statistical significant difference (p = 0.186, p = 1, p = 0.668, respectively) Conclusion: Routine transvaginal cerclage is not effective in twin IVF pregnancies with normal cervical length for preventing preterm births. IVF twin women usually present at a late age and their birth weight are also low.

Fabrication of novel glutathione-Fe3O4-loaded/activated carbon encapsulated sand bionanocomposites for enhanced removal of diethyl phthalate from aqueous environment in a vertical flow reactor.

The extensive use of plasticizers in various industries has made Diethyl phthalate (DEP), a serious threat to the environment and ecological water security, owing to its complex-structure and low-biodegradability. Thus, the present study aimed to design a sustainable sand-coated nano glutathione (GSH) -Fe3O4-loaded/activated carbon (AC) bionanocomposite (AC-GSH-Fe3O4@sand bionanocomposite) for effective removal of DEP from water. Characterization results suggested bionanocomposites' rough and irregular texture due to the uneven distribution of AC and Fe3O4 nanoparticles over the sand. The XRD spectra indicated high crystallinity of bionanocomposites, while the FTIR spectra confirmed the presence of all individual components, i.e., GSH, AC, Fe3O4, and sand. EDX-mapping, AFM, and TGA further verified its elemental composition, topographical changes and thermal stability. The influence of pH (3, 7, 9), bed height (2, 4, 6) cm, and flow rate (2.5, 3.5, 4.5) mL min-1 were studied in a dynamic system with an initial DEP concentration of 50 mg L-1 to investigate the removal behavior of the bionanocomposites. The best DEP removal efficiency (90.18 %) was achieved over 28-h at pH 9, bed-height-4 cm, and flow-rate-3.5 mL min-1, with an optimum qmax-200.25 mg g-1 as determined through Thomas-model. Breakthrough curves were predicted using various column models, and the corresponding parameters essential for column-reactor process design were calculated. The high reusability up to the 10th cycle (≥83.32%) and the effective treatment in complex matrices (tap-water: 90.11 %, river-water: 89.72 %, wastewater: 83.83%) demonstrated bionanocomposites' prominent sustainability. Additionally, the production cost at 6.64 USD per Kg, underscores its potentiality for industrial application. Phytotoxicity assessment on mung-bean revealed better root (5.02 ± 0.27 cm) and shoot (17.64 ± 0.35 cm) growth in the bionanocomposite-treated DEP samples over the untreated samples. Thus, AC-GSH-Fe3O4@sand bionanocomposites could be considered a highly-sustainable, low-cost technique for the effective removal of DEP and other phthalate-esters from contaminated matrices.

Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform.

Protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D), is a serine/threonine phosphatase that is recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses the activation of p53. Consistent with its oncogenic properties, genetic loss or pharmacologic inhibition of PPM1D impairs tumor growth and sensitizes cancer cells to cytotoxic therapies in a wide range of preclinical models. Given the therapeutic potential of targeting PPM1D specifically and the DDR and p53 pathway more generally, we sought to deepen our biological understanding of PPM1D as a drug target and determine how PPM1D inhibition differs from other therapeutic approaches to activate the DDR. We performed a high throughput screen to identify new allosteric inhibitors of PPM1D, then generated and optimized a suite of enzymatic, cell-based, and in vivo pharmacokinetic and pharmacodynamic assays to drive medicinal chemistry efforts and to further interrogate the biology of PPM1D. Importantly, this drug discovery platform can be readily adapted to broadly study the DDR and p53. We identified compounds distinct from previously reported allosteric inhibitors and showed in vivo on-target activity. Our data suggest that the biological effects of inhibiting PPM1D are distinct from inhibitors of the MDM2-p53 interaction and standard cytotoxic chemotherapies. These differences also highlight the potential therapeutic contexts in which targeting PPM1D would be most valuable. Therefore, our studies have identified a series of new PPM1D inhibitors, generated a suite of in vitro and in vivo assays that can be broadly used to interrogate the DDR, and provided important new insights into PPM1D as a drug target.

Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

GOALS AND BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. METHODS: We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. RESULTS: We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59 y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P<0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. CONCLUSIONS: Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

ACUTE VENOUS THROMBOEMBOLISM IS COMMON FOLLOWING ACUTE NECROTIZING PANCREATITIS AND IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES.

OBJECTIVES: While splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extra-splanchnic VTE (ESVT) is inadequately studied. Here, we aim to explore the incidence of VTE in acute necrotizing pancreatitis (ANP) and the associated mortality. METHODS: This is a retrospective cohort study utilizing an electronic health record database. Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate ICD-10-CM codes. The primary outcome was development of acute ESVT within one month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities. RESULTS: 17,942 (7.11%) patients were diagnosed with ANP during the study period and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTE, 61% were ESVT with or without SVT, and 63% (N = 1,799) were SVT. 90-day mortality (16.3% vs. 5.7%, risk ration, RR 2.86 [95% CI 2.29-3.56]) and 30-day rehospitalization (31% Vs 19%, RR 1.63 [95% CI 1.49-1.79]) were higher in patients with ESVT compared to non-VTE patients. 60% of patients with ESVT were on OAC and OAC use was associated with lower 90-day mortality (8.9% vs. 19.4%, RR 0.46) without increased risk of adverse events, like - acute gastrointestinal bleeding, intracranial bleeding, or need for packed red cell transfusion. CONCLUSIONS: Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay, and in the immediate ambulatory period.

Efficacy and safety of oral semaglutide in type 2 diabetes: A systematic review of real-world evidence.

BACKGROUND AND AIMS: Oral semaglutide has undergone global Phase 3 development programs named PIONEER and approved for therapeutic use in people with type 2 diabetes (T2D). We aim to systematically review the efficacy and safety of oral semaglutide in real-world settings. METHODS: We systematically searched the electronic databases of PubMed, Google Scholar, and ClinicalTrials.gov from inception until March 15, 2024, using several keywords with Boolean "AND". We retrieved all the available granular details of real-world studies (RWS). RESULTS: To date, results from four prospective and ten retrospective real-world studies of oral semaglutide in T2D are available. In prospective studies, the primary outcome of HbA1c reduction varied from -0.9 % to -1.6 %, weight loss varied from -4.7 kg to -8.2 kg and HbA1c target of <7 % was achieved in 30 %-64 % with oral semaglutide. In retrospective studies, HbA1c reduction varied from -0.4 % to -1.8 %, weight reduction varied from -1.4 to -9.0 kg, HbA1c target of <7 % was achieved in 32-64 %, and 30-41 % of people with T2D had ≥5 % weight loss with oral semaglutide. Gastrointestinal adverse events with oral semaglutide varied from 16 % to 50 % in prospective and 6 %-47 % in retrospective RWS. Overall, 0 %-18 % of patients had oral semaglutide discontinuation due to any cause. CONCLUSION: Oral semaglutide exhibited a reasonable reduction in HbA1c and weight in people with T2D, consistent with the findings from PIONEER trials. While no new safety issues emerged, the inherent limitations of RWS underscore the necessity of long-term investigations to comprehensively assess safety.

Real-world differences in dosing and clinical utilization of OnabotulinumtoxinA and AbobotulinumtoxinA in the treatment of upper limb spasticity.

According to prescribing information, potency units are not interchangeable between botulinum toxin A products. This exploratory study compared real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA in adults with upper limb spasticity. In this retrospective study, 101 clinicians provided chart data via online surveys for 215 US post-stroke patients treated for upper limb spasticity with ≥3 onabotulinumtoxinA or abobotulinumtoxinA doses (phase 1: 9/18/2020-12/10/2020; phase 2: 9/30/2021-12/7/2021). Most participating clinicians were physicians (70.3%) specializing in neurology (71.3%) or physiatry (20.8%). In the onabotulinumtoxinA (n = 107) and abobotulinumtoxinA (n = 108) groups, ∼75% of patients had moderate-to-severe spasticity. A range of onabotulinumtoxinA:abobotulinumtoxinA dose ratios (1:2.2 [95% CI: 1.8, 2.6] to 1:4.1 [95% CI: 3.0, 6.0]) was observed across muscles. For the most recent dose, mean number of muscles injected was greater for onabotulinumtoxinA (4.3) versus abobotulinumtoxinA (3.1; P = 0.0003). For onabotulinumtoxinA versus abobotulinumtoxinA, the proportion of injections was 81.3% versus 63.9% (P = 0.0067) in forearm muscles and 23.4% versus 3.7% (P = 0.0001) in hand muscles. Mean injection intervals were similar (onabotulinumtoxinA: 102.0 days; abobotulinumtoxinA: 99.1 days). Differences in real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA for upper limb spasticity were observed. There was no standard dose-conversion ratio, consistent with each product's prescribing information.

Assessment of Trachyspermum ammi essential oil against Aspergillus flavus, aflatoxin B1 contamination, and post-harvest quality of Sorghum bicolor.

The present investigation explored the antifungal effectiveness of Trachyspermum ammi essential oil (TAEO) against Aspergillus flavus, aflatoxin B1 (AFB1) contamination, and its mechanism of action using biochemical and computational approaches. The GC-MS result revealed the chemical diversity of TAEO with the highest percentage of γ-terpinene (39 %). The TAEO exhibited minimum inhibitory concentration against A. flavus growth (0.5 µL/mL) and AFB1 (0.4 µL/mL) with radical scavenging activity (IC50 = 2.13 µL/mL). The mechanism of action of TAEO was associated with the alteration in plasma membrane functioning, antioxidative defense, and carbon source catabolism. The molecular dynamic result shows the multi-regime binding of γ-terpinene with the target proteins (Nor1, Omt1, and Vbs) of AFB1 biosynthesis. Furthermore, TAEO exhibited remarkable in-situ protection of Sorghum bicolor seed samples against A. flavus and AFB1 contamination and protected the nutritional deterioration. Hence, the study recommends TAEO as a natural antifungal agent for food protection against A. flavus mediated biodeterioration.

Endoscopic Ultrasound-Guided vs Endoscopic Retrograde Cholangiopancreatography-Guided Biliary Drainage as Primary Approach to Malignant Distal Biliary Obstruction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage in malignant distal biliary obstruction (MDBO). This meta-analysis of randomized controlled trials (RCTs) aims to compare the outcomes of these 2 approaches. METHODS: Electronic databases from January 2005 through December 2023 were searched for RCTs comparing outcomes of EUS-BD and ERCP for treating MDBO. Pooled proportions, risk ratio (RR), and odds ratio were calculated using random-effects models. RESULTS: Five RCTs comprising 519 patients were included in the final analysis. The pooled RR for overall technical success with EUS-BD compared with ERCP was 1.05 (95% confidence interval [CI] = 0.96-1.16, P = 0.246, I2 = 61%) and for clinical success was 0.99 (95% CI = 0.95-1.04, P = 0.850, I2 = 0%). The pooled rate of procedure-related pancreatitis was 7.20% (95% CI = 3.60-13.80, I2 = 34%) in the ERCP group compared with zero in the EUS-BD group. The pooled RR for stent dysfunction with EUS-BD compared with ERCP was 0.48 (95% CI = 0.28-0.83, P = 0.008, I2 = 7%). The weighted mean procedure time was 13.43 (SD = 10.12) minutes for EUS-BD compared with 21.06 (SD = 6.64) minutes for ERCP. The mean stent patency was 194.11 (SD = 52.12) days in the EUS-BD group and 187 (SD = 60.70) days in the ERCP group. DISCUSSION: EUS-BD is an efficient and safe alternative to ERCP in MDBO. An almost nonexistent risk of procedure-related pancreatitis, lower procedure time, and ease of use make this an attractive primary approach to biliary decompression in centers with expertise.

Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study.

Background: Traumatic brain injury (TBI) is a major cause of mortality among young individuals, accounting for 65% of deaths in road traffic accidents. Paroxysmal sympathetic hyperactivity (PSH) is a common syndrome associated with TBI. This study represents the first prospective investigation aimed at assessing the impact of gabapentin on TBI patients, focusing on the prevention of secondary brain injury and brain edema while enhancing the Glasgow Coma Scale (GCS). Materials and methods: The study was conducted from September 2019 to July 2021 after receiving ethical committee approval. It included adult ICU patients (≥18 years) with moderate and severe GCS. Patients below 18 years, death within 48 hours, non-consenting, pregnant females, and individuals allergic to gabapentin were excluded from the study. Patients were randomly allocated in two groups: study group received 300 mg of gabapentin orally twice daily and control group received multivitamin tablets twice daily. The treatment period spanned 2 weeks. Follow-up occurred in the ICU and continued for up to 3 months post-discharge, including telephonic conversations. Results: About 60 patients were involved for analysis. Significant differences were found in GCS change from admission to discharge, Glasgow Outcome Scale (GOS) at 30 and 90 days, PSH episodes, and sedation bolus per day. Glasgow Coma Scale change was 53% in the study group compared with 25% in the control group (p = 0.009). Mortality was significantly lower in the study group. Glasgow Outcome Scale change between 30 and 90 days showed a 25% improvement in cases and no change in controls (p = 0.001). Conclusion: This pioneering study underscores the potential of gabapentin in managing traumatic brain injuries. How to cite this article: Singh R, Ambasta S, Bais PS, Azim A, Kumar S, Upreti B, et al. Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study. Indian J Crit Care Med 2024;28(2):120-125.

Genetic and molecular landscapes of the generalist phytopathogen Botrytis cinerea.

Botrytis cinerea Pers. Fr. (teleomorph: Botryotinia fuckeliana) is a necrotrophic fungal pathogen that attacks a wide range of plants. This updated pathogen profile explores the extensive genetic diversity of B. cinerea, highlights the progress in genome sequencing, and provides current knowledge of genetic and molecular mechanisms employed by the fungus to attack its hosts. In addition, we also discuss recent innovative strategies to combat B. cinerea. TAXONOMY: Kingdom: Fungi, phylum: Ascomycota, subphylum: Pezizomycotina, class: Leotiomycetes, order: Helotiales, family: Sclerotiniaceae, genus: Botrytis, species: cinerea. HOST RANGE: B. cinerea infects almost all of the plant groups (angiosperms, gymnosperms, pteridophytes, and bryophytes). To date, 1606 plant species have been identified as hosts of B. cinerea. GENETIC DIVERSITY: This polyphagous necrotroph has extensive genetic diversity at all population levels shaped by climate, geography, and plant host variation. PATHOGENICITY: Genetic architecture of virulence and host specificity is polygenic using multiple weapons to target hosts, including secretory proteins, complex signal transduction pathways, metabolites, and mobile small RNA. DISEASE CONTROL STRATEGIES: Efforts to control B. cinerea, being a high-diversity generalist pathogen, are complicated. However, integrated disease management strategies that combine cultural practices, chemical and biological controls, and the use of appropriate crop varieties will lessen yield losses. Recently, studies conducted worldwide have explored the potential of small RNA as an efficient and environmentally friendly approach for combating grey mould. However, additional research is necessary, especially on risk assessment and regulatory frameworks, to fully harness the potential of this technology.

Review on interactions between nanomaterials and phytohormones: Novel perspectives and opportunities for mitigating environmental challenges.

Nanotechnology offers the potential to provide innovative solutions for sustainable crop production as plants are exposed to a combination of climate change factors (CO2, temperature, UV radiation, ozone), abiotic (heavy metals, salinity, drought), and biotic (virus, bacteria, fungi, nematode, and insects) stresses. The application of particular sizes, shapes, and concentration of nanomaterials (NMs) potentially mitigate the negative impacts in plants by modulation of photosynthetic rate, redox homeostasis, hormonal balance, and nutrient assimilation through upregulation of anti-stress metabolites, antioxidant defense pathways, and genes and genes network. The present review inculcates recent advances in uptake, translocation, and accumulation mechanisms of NMs in plants. The critical theme of this review provides detailed insights into different physiological, biochemical, molecular, and stress tolerance mechanism(s) of NMs action and their cross-talk with different phytohormones. The role of NMs as a double-edged sword for climate change factors, abiotic, and biotic stresses for nutrients uptake, hormones synthesis, cytotoxic, and genotoxic effects including chromosomal aberration, and micronuclei synthesis have been extensively studied. Importantly, this review aims to provide an in-depth understanding of the hormesis effect at low and toxicity at higher doses of NMs under different stressors to develop innovative approaches and design smart NMs for sustainable crop production.