Publications by authors named "Vijay Singh"

1,043 Publications

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Pharmacokinetic and metabolomic studies with a BIO 300 Oral Powder formulation in nonhuman primates.

Sci Rep 2022 Aug 5;12(1):13475. Epub 2022 Aug 5.

Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine "America's Medical School", Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.

BIO 300, a pharmaceutical formulation of genistein, is being developed as a radiation countermeasure to treat hematopoietic acute radiation syndrome (H-ARS) and the delayed effects of acute radiation exposure (DEARE). Several studies have affirmed its safety and efficacy in alleviating the damaging effects of ionizing radiation. However, dose optimization of any drug has always been an important area of research because unnecessarily high drug doses may result in serious complications. In this study, we assessed the pharmacokinetics (PK) and metabolic profiles of two different doses of a novel solid-dosage formulation of BIO 300 (BIO 300 Oral Powder; 100 mg/kg and 200 mg/kg), when administered orally to nonhuman primates (NHPs). While the T values of both doses remained the same, the area under the curve at 48 h (AUC) was tripled by doubling the dose. Additionally, we monitored serum samples for global metabolomic/lipidomic changes using high resolution mass spectrometry followed by functional pathway analysis prior to and at various time points up to 48 h post drug administration. Interestingly, the metabolomic profiles of sera from NHPs that received the lower dose demonstrated a transient perturbation in numerous metabolites between the 4 and 12 h time points. Eventually, the metabolite abundance reverted to near-normal by 48 h. These study results are consistent with our previous studies focused on the PK and metabolomic analysis for parenteral and oral aqueous nanosuspension formulations of BIO 300. This study affirms that administration of a single dose of up to 200 mg/kg of BIO 300 Oral Powder is safe in NHPs and conferred no metabolomic-mediated safety features.
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http://dx.doi.org/10.1038/s41598-022-17807-7DOI Listing
August 2022

Physical intimate partner violence prevalence and associations among a nationally-representative sample of young men.

Authors:
Vijay Singh

Ann Fam Med 2022 04 1;20(20 Suppl 1). Epub 2022 Apr 1.

Context: Primary care providers can ask men about intimate partner violence (IPV) perpetration or victimization using validated questions, yet physicians feel unprepared to screen men for IPV. Few studies examine men's physical IPV categories of perpetration-only, both perpetration and victimization, and victimization-only, or their associations with technology-facilitated abuse (TFA).

Objective: Assess (1) prevalence of men's physical IPV and (2) associations of physical IPV with demographics, children, health services use, self-reported physical or mental health diagnoses, substance use problems, and TFA.

Study Design: Survey with survey-weighted descriptive statistics and multinomial logistic regression.

Setting: Community-based nationally representative sample of U.S. men using IPSOS KnowledgePanel August-September 2014.

Population Studied: 2,889 men age 18-35 with response rate 47% (1346/2889). Inclusion criteria "ever in a romantic relationship" yielded analysis sample 1074 men.

Outcome Measure: Physical IPV categories: perpetration-only, both perpetration and victimization, and victimization-only.

Results: Among young U.S. men, physical IPV was reported by 2.5% perpetration only, 16.7% both perpetration and victimization, and 10.0% victimization only. Multivariate analyses showed physical IPV perpetration-only associated with primary care use (AOR 0.25, 95%CI 0.09-0.70), chronic pain (AOR 6.92, 95%CI 1.74-27.55), and prescription opioid misuse (AOR 2.31, 95%CI 1.53-3.47); IPV both perpetration and victimization associated with belief that children who do not witness parental IPV are still harmed (AOR 0.59, 95%CI 0.43-0.82), primary care use (AOR 0.54, 95%CI 0.31-0.94), alcohol misuse (AOR 1.08, 95%CI 1.01-1.15), prescription opioid misuse (AOR 1.58, 95%CI 1.09-2.29), TFA delivered only (AOR 3.64, 95%CI 1.23-10.80), TFA both delivered and received (AOR 6.08, 95%CI 3.32-11.13), TFA received only (AOR 4.95, 95%CI 1.54-15.91); IPV victimization-only associated with mental healthcare visits (AOR 2.34, 95%CI 1.19-4.64), TFA both delivered and received (AOR 2.31, 95%CI 1.16-4.58), and TFA received only (AOR 5.26, 95%CI 2.24-12.38).

Conclusions: Among young U.S. men, physical IPV was reported by 1 in 40 for perpetration only, 1 in 6 for both perpetration and victimization, and 1 in 10 for victimization only. Primary care physicians can consider assessing physical IPV among male patients. Limitations include self-report and no context for IPV.
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http://dx.doi.org/10.1370/afm.20.s1.2881DOI Listing
April 2022

Long-segment fixation versus short-segment fixation with instrumentation of index vertebra for thoracolumbar fractures.

Surg Neurol Int 2022 3;13:233. Epub 2022 Jun 3.

Department of Orthopaedics, Seth GSMC and KEMH, Parel, Mumbai, Maharashtra, India.

Background: We assessed and analyzed the clinical, perioperative, functional, and radiological outcomes of long- versus short-segment (SS) fixation of thoracolumbar spine fractures that included the index vertebra.

Methods: We retrospectively evaluated 119 patients with thoracolumbar spine fractures (i.e., using AO classification system). The patient was followed up for a minimum of 1 year at which time the angles of correction were measured on lateral X-rays (i.e., using Cobb's method). Neurological grading employed the Frankel's grading system. Operative time, perioperative blood loss, and time to mobilization were also analyzed.

Results: After 1 year, the loss of kyphosis was not significantly different between the two groups. Although there were no statistical differences in terms, regarding neurological outcomes, time to mobilization, or duration of hospitalization, the operative times and perioperative blood loss were significantly reduced in patients undergoing SS fixation.

Conclusion: We determined the efficacy of SS fixation for thoracolumbar fractures including the index vertebra.
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http://dx.doi.org/10.25259/SNI_238_2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282815PMC
June 2022

Intensive care unit delirium in patients with severe COVID-19: A prospective observational cohort study.

Int J Crit Illn Inj Sci 2022 Apr-Jun;12(2):61-69. Epub 2022 Jun 24.

Department of Critical Care Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA.

Background: Delirium is common in patients with severe coronavirus disease-19 (COVID-19). The purpose of our study was to determine whether severe COVID-19 is an independent risk factor for the development of delirium in patients treated in the intensive care unit (ICU).

Methods: This prospective observational cohort study involved 162 critically ill patients admitted to a multidisciplinary ICU during 2019 and 2020. A validated screening tool was used to diagnose delirium. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. After univariate analysis, a multivariate logistic regression analysis was performed to determine independent risk factors associated with the development of delirium.

Results: In our study population, 50 (31%) patients developed delirium. A total of 39 (24.1%) tested positive for COVID-19. Initial analysis showed COVID-19 to be more prevalent in those patients that developed delirium (40% vs. 17%; = 0.003). Multivariate analysis showed opioid use (odds ratio [OR]: 24 [95% confidence intervals (CI): 16-27]; ≤ 0.001), benzodiazepine use (OR: 23 [95% CI: 16-63] = 0.001), and estimated mortality based on acute physiology and chronic health evaluation IV score (OR: 1.04 [95% CI: 1.01-1.07] = 0.002) to be independently associated with delirium development. COVID-19 (OR: 1.44 [95% CI: 0.13-10.6]; = 0.7) was not found to be associated with delirium.

Conclusion: Delirium is prevalent in critically ill patients admitted to the ICU, including those with COVID-19. However, after adjustment for important covariates, we found in this cohort that COVID-19 was not an independent risk factor for delirium.
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http://dx.doi.org/10.4103/ijciis.ijciis_93_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285129PMC
June 2022

Acute radiation syndrome drug discovery using organ-on-chip platforms.

Expert Opin Drug Discov 2022 Jul 18:1-14. Epub 2022 Jul 18.

Tech Micro Services, Bethesda, MD, USA.

Introduction: The high attrition rate during drug development remains a challenge that costs a significant amount of time and money. Improving the probabilities of success during the early stages of radiation medical countermeasure (MCM) development for approval by the United States Food and Drug Administration (US FDA) following the Animal Rule will reduce this burden.

Area Covered: This article focuses on new technologies involving various organ-on-chip platforms. Of late, there has been rapid development of these technologies, especially in terms of mimicking both normal and abnormal physiological conditions. Here, we suggest possible applications of these novel systems for the discovery and development of radiation MCMs for the acute radiation syndrome (ARS).

Expert Opinion: Each organ-on-a-chip system has its own strengths and shortcomings. As such, the system selected for MCM discovery, development, and regulatory approval should be carefully considered and optimized to the fullest extent in order to augment successful drug testing and the minimization of attrition rates of candidate agents. The recent encouraging progress with organ-on-a-chip technology will likely lead to additional radiation MCMs for ARS. The acceptance of organ-on-a-chip technology may be a promising step toward improving the success rate of pharmaceuticals in MCM development.
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http://dx.doi.org/10.1080/17460441.2022.2099833DOI Listing
July 2022

In vitro Antimicrobial Activity of Cucumis L. and Momordica L. against Human Pathogens.

Dokl Biol Sci 2022 Jun 12;504(1):85-93. Epub 2022 Jul 12.

Department of Microbiology, Mata Gujri College, Fatehgarh Sahib, Punjab, India.

Plants are the rich source of compounds having antimicrobial properties against human pathogens. The present study has been carried out to evaluate the antimicrobial potential of Cucumis melo var. agrestis (morphotype I), Cucumis melo var. agrestis (morphotype II), Cucumis melo var. momordica L., Cucumis melo L., Momordica balsamina L., Momordica charantia L., Momordica dioica L. against Staphylococcus aureus, Pseudomonas flourescens, Bacillus coagulans, and Klebsiella pneumoniae. Crude extract of Cucumis L. and Momordica L. species were prepared with methanol, acetone and water for the determination of antimicrobial properties. Maximum yield was reported in methanol extract while minimum in acetone for all plant species. The maximum zone of inhibition of about 32.3 ± 0.57 mm was found against Staphylococcus aureus in Cucumis melo L., 21.3 ± 0.57 mm for Pseudomonas flourescens in Cucumis melo var. agrestis (morphotype II), 17 ± 0 mm for Klebsiella pneumoniae in Momordica balsamina L., and 23.3 ± 0.57 mm for Bacillus coagulans in Cucumis melo var. agrestis (morphotype II) extracts, respectively. The most active antimicrobial plants species were reported to be Cucumis melo var. agrestis (morphotype I), Cucumis melo L. and Momordica charantia L. having antimicrobial activities against all tested microorganisms.
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http://dx.doi.org/10.1134/S0012496622030048DOI Listing
June 2022

Chemokines in ICU Delirium: An Exploratory Study.

Crit Care Explor 2022 Jul 5;4(7):e0729. Epub 2022 Jul 5.

Department of Critical Care Medicine, Mayo Clinic, Rochester, MN.

Objectives: The pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown.

Design: This was a prospective exploratory study.

Setting: A multidisciplinary ICU at an academic medical center in Phoenix, AZ.

Patients: Critically ill patients older than or equal to 18 years old admitted to the ICU.

Interventions: None.

Measurements And Main Results: Screening for delirium was performed using the Confusion Assessment Method for the ICU tool. The levels of C-C motif ligand 2 (CCL2), C-C motif ligand 3, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 10, and interleukin-8 were measured in serum samples obtained within 12 hours of ICU admission. Univariate and multivariate analyses were performed to assess the association of delirium with patient data pertaining to hospital course, laboratory values, vital signs, medication administration, and levels of the aforementioned chemokines. Forty-one of 119 patients (34.5%) in the study cohort developed ICU delirium. Each chemokine studied was associated with delirium on univariate analyses; however, CCL2 was the only chemokine found to be independently associated with the development of delirium on multivariable analysis. The association of increased CCL2 levels with delirium remained robust in various models controlling for age, presence of shock, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation IV score, mean arterial pressure at presentation, lowest mean arterial pressure, and total opioid, midazolam, propofol, and dexmedetomidine exposure.

Conclusions: The demonstrated relationship between CCL2 and delirium suggests this chemokine may play a role in the development of delirium and warrants further investigation.
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http://dx.doi.org/10.1097/CCE.0000000000000729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259165PMC
July 2022

Cytokine profiles in intensive care unit delirium.

Acute Crit Care 2022 Jun 20. Epub 2022 Jun 20.

Department of Critical Care Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.

Objective: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery.

Methods: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured.

Results: The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL)2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups.

Conclusion: We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.
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http://dx.doi.org/10.4266/acc.2021.01508DOI Listing
June 2022

Breastfeeding rates at discharge for very low birthweight neonates and their determinants: An observational study from a tertiary care neonatal intensive care unit in India.

J Paediatr Child Health 2022 Jul 2. Epub 2022 Jul 2.

Department of Community Medicine, King Georges' Medical University, Lucknow, India.

Background: Mother's milk is the best milk for neonates. Preterm very low birthweight (VLBW) neonates face many challenges leading to low rates of breastfeeding at discharge.

Aims: (i) To determine the proportion of <32 weeks preterm VLBW neonates who are exclusively breastfed (EB) at discharge and (ii) determinants of exclusive breastfeeding (EBF) at discharge.

Methods: An observational study was conducted for a duration of 1 year, from May 2019 to April 2020 in a tertiary care neonatal intensive care unit (NICU) in North India. Consecutive <32 weeks preterm VLBW neonates admitted within 72 h of birth and on full enteral feeds (FEF) within 10 days of birth were included in this study and followed up till discharge.

Results: Forty-four of 97 (45.4%) preterm VLBW neonates were exclusively breastfed and 31/97 (32%) received more than 80% mother's own milk (MOM) at discharge. Male sex (P = 0.03), those whose first feed had any amount of MOM (P = 0.038) or exclusive MOM in their first feed or when initiated on first FEF (P = 0.002), and neonates with longer duration of hospital stay (P = 0.035) had an increased chance of being exclusively breastfed at discharge.

Conclusion: Preterm VLBW neonates who receive any amount of MOM in their first feed or first FEF, male infants and those who stay longer in hospital are more likely to be exclusively breastfed at discharge.
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http://dx.doi.org/10.1111/jpc.16074DOI Listing
July 2022

Preoperative Lumbar Epidural Steroid Injection Increases the Risk of a Dural Tear During Minimally Invasive Lumbar Discectomy.

Int J Spine Surg 2022 Jun;16(3):505-511

Department of Orthopaedics and Spine Surgery, KEM Hospital, Mumbai, India.

Background: Preoperative lumbar epidural steroid injections (LESI) are known to be a risk factor for intraoperative dural tears in traditional spine surgery. However, whether the same holds true after minimally invasive surgery is debatable. The authors decided to investigate the incidence of complications in patients undergoing minimally invasive lumbar discectomy after a preoperative LESI.

Methods: A retrospective analysis was carried out on patients ages 21 to 65 years who underwent minimally invasive lumbar discectomy over 3 years between November 2017 and October 2020. These were classified into 2 groups based on the administration of an LESI within a year of surgery. Those receiving LESI were further subdivided on the basis of the proximity of the injection to the surgery. The complications encountered during and up to 6 months after the surgery were recorded. Various demographic variables were also noted.

Results: A total of 315 patients were included in the study, of which 129 were in the LESI group and 186 were in the non-LESI group. The overall complication rate was 13.65%, with 17.83% in the LESI group and 10.75% in the non-LESI group ( = 0.07). Patients receiving an LESI were 2.49 times more likely to suffer from intraoperative dural tears compared to the other group (95% CI: 1.00-6.20, = 0.049). This was more prevalent in those who were administered an LESI within 3 months of the surgery (OR: 3.24, 95% CI: 1.12-9.40, = 0.03). However, the rates of other complications including infections were comparable.

Conclusions: A history of LESI within 3 months of the surgery is a risk factor of intraoperative dural tears. However, other complications, including infections, are not affected by a preoperative LESI.

Clinical Relevance: A history of an LESI within 3 months of a proposed minimally invasive discectomy should make the surgeon extra-cautious of the risk of a dural tear.

Level Of Evidence: 3:
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http://dx.doi.org/10.14444/8249DOI Listing
June 2022

Sciatic Nerve Involvement in Rosai-Dorfman Disease.

Radiol Imaging Cancer 2022 06;4(4):e220046

From the Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.

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http://dx.doi.org/10.1148/rycan.220046DOI Listing
June 2022

Sciatic Nerve Involvement in Rosai-Dorfman Disease.

Radiol Imaging Cancer 2022 06;4(4):e220046

From the Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.

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http://dx.doi.org/10.1148/rycan.220046DOI Listing
June 2022

Nano-Structured Carbon: Its Synthesis from Renewable Agricultural Sources and Important Applications.

Materials (Basel) 2022 Jun 2;15(11). Epub 2022 Jun 2.

Department of Chemical Engineering, Konkuk University, Seoul 05029, Korea.

Carbon materials are versatile in nature due to their unique and modifiable surface and ease of production. Nanostructured carbon materials are gaining importance due to their high surface area for application in the energy, biotechnology, biomedical, and environmental fields. According to their structures, carbon allotropes are classified as carbon nanodots, carbon nanoparticles, graphene, oxide, carbon nanotubes, and fullerenes. They are synthesized via several methods, including pyrolysis, microwave method, hydrothermal synthesis, and chemical vapor deposition, and the use of renewable and cheaper agricultural feedstocks and reactants is increasing for reducing cost and simplifying production. This review explores the nanostructured carbon detailed investigation of sources and their relevant reports. Many of the renewable sources are covered as focused here, such as sugar cane waste, pineapple, its solid biomass, rise husk, date palm, nicotine tabacum stems, lapsi seed stone, rubber-seed shell, coconut shell, and orange peels. The main focus of this work is on the various methods used to synthesize these carbon materials from agricultural waste materials, and their important applications for energy storage devices, optoelectronics, biosensors, and polymer coatings.
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http://dx.doi.org/10.3390/ma15113969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182223PMC
June 2022

Identification of novel biomarkers for acute radiation injury using multi-omics approach and nonhuman primate model.

Int J Radiat Oncol Biol Phys 2022 Jun 5. Epub 2022 Jun 5.

Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address:

Purpose: The availability of validated biomarkers to assess radiation exposure and to assist in developing medical countermeasures remains an unmet need.

Methods And Materials: We used a cobalt-60 gamma-irradiated nonhuman primate (NHP) model to delineate a multi-omics-based serum probability index of radiation exposure. Both male and female NHPs were irradiated with different doses ranging from 6.0 to 8.5 Gy, with 0.5 Gy increments between doses. We leveraged high-resolution mass spectrometry for analysis of metabolites, lipids, and proteins at 1, 2, and 6 days post-irradiation in NHP serum.

Results: A logistic regression model was implemented to develop a 4-analyte panel to stratify irradiated NHPs from unirradiated with high accuracy that was agnostic for all doses of gamma-rays tested in the study, up to six days after exposure. This panel was comprised of Serpin Family A9, acetylcarnitine, PC (16:0/22:6), and suberylglycine, which showed 2 - 4-fold elevation in serum abundance upon irradiation in NHPs and can potentially be translated as a molecular diagnostic for human use following larger validation studies.

Conclusions: Taken together, this study, for the first time, demonstrates the utility of a combinatorial molecular characterization approach using an NHP model for developing minimally invasive assays from small volumes of blood that can be effectively used for radiation exposure assessments.
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http://dx.doi.org/10.1016/j.ijrobp.2022.05.046DOI Listing
June 2022

Silicon nanoforms in crop improvement and stress management.

Chemosphere 2022 Oct 3;305:135165. Epub 2022 Jun 3.

Crop Nanobiology and Molecular Stress Physiology Laboratory, Amity Institute of Organic Agriculture, Amity University Uttar Pradesh, Sector-125, Noida, 201313, India. Electronic address:

Although, silicon - the second most abundant element in the earth crust could not supersede carbon (C) in the competition of being the building block of life during evolution, yet its presence has been reported in some life forms. In case of the plants, silicon has been reported widely to promote the plant growth under normal as well as stressful situations. Nanoform of silicon is now being explored for its potential to improve plant productivity and its tolerance against various stresses. Silicon nanoparticles (SiNPs) in the form of nanofertilizers, nanoherbicides, nanopesticides, nanosensors and targeted delivery systems, find great utilization in the field of agriculture. However, the mechanisms underlying their uptake by plants need to be deciphered in detail. Silicon nanoformss are reported to enhance plant growth, majorly by improving photosynthesis rate, elevating nutrient uptake and mitigating reactive oxygen species (ROS)-induced oxidative stress. Various studies have reported their ability to provide tolerance against a range of stresses by upregulating plant defense responses. Moreover, they are proclaimed not to have any detrimental impacts on environment yet. This review includes the up-to-date information in context of the eminent role of silicon nanoforms in crop improvement and stress management, supplemented with suggestions for future research in this field.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135165DOI Listing
October 2022

Driven-Dissipative Criticality within the Discrete Truncated Wigner Approximation.

Phys Rev Lett 2022 May;128(20):200602

Institut für Theoretische Physik, Leibniz Universität Hannover, Appelstraße 2, 30167 Hannover, Germany.

We present an approach to the numerical simulation of open quantum many-body systems based on the semiclassical framework of the discrete truncated Wigner approximation. We establish a quantum jump formalism to integrate the quantum master equation describing the dynamics of the system, which we find to be exact in both the noninteracting limit and the limit where the system is described by classical rate equations. We apply our method to simulation of the paradigmatic dissipative Ising model, where we are able to capture the critical fluctuations of the system beyond the level of mean-field theory.
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http://dx.doi.org/10.1103/PhysRevLett.128.200602DOI Listing
May 2022

A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.

J Extracell Vesicles 2022 06;11(6):e12232

Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Centre, Washington, DC, USA.

Although cancer-derived extracellular vesicles (cEVs) are thought to play a pivotal role in promoting cancer progression events, their precise effect on neighbouring normal cells is unknown. In this study, we investigated the impact of pancreatic cancer ductal adenocarcinoma (PDAC) derived EVs on recipient non-tumourigenic pancreatic normal epithelial cells upon internalization. We demonstrate that cEVs are readily internalized and induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in treated normal pancreatic epithelial cells within 24 h. We further show that PDAC cEVs increase cell proliferation, migration, and invasion and that these changes are regulated at least in part, by the UPR mediator DDIT3. Subsequently, these cells release several inflammatory cytokines. Leveraging a layered multi-omics approach, we analysed EV cargo from a panel of six PDAC and two normal pancreas cell lines, using multiple EV isolation methods. We found that cEVs were enriched for an array of biomolecules which can induce or regulate ER stress and the UPR, including palmitic acid, sphingomyelins, metabolic regulators of tRNA charging and proteins which regulate trafficking and degradation. We further show that palmitic acid, at doses relevant to those found in cEVs, is sufficient to induce ER stress in normal pancreas cells. These results suggest that cEV cargo packaging may be designed to disseminate proliferative and invasive characteristics upon internalization by distant recipient normal cells, hitherto unreported. This study is among the first to highlight a major role for PDAC cEVs to induce stress in treated normal pancreas cells that may modulate a systemic response leading to altered phenotypes. These findings highlight the importance of EVs in mediating disease aetiology and open potential areas of investigation toward understanding the role of cEV lipids in promoting cell transformation in the surrounding microenvironment.
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http://dx.doi.org/10.1002/jev2.12232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164146PMC
June 2022

Ca sensor-mediated ROS homeostasis: defense without yield penalty.

Trends Plant Sci 2022 May 28. Epub 2022 May 28.

Crop Nanobiology and Molecular Stress Physiology Laboratory, Amity Institute of Organic Agriculture, Amity University Uttar Pradesh, Sector-125, Noida-201313, India. Electronic address:

Constitutively active immunity against pathogen infection affects the growth and yield of plants. Gao and colleagues recently demonstrated that a Ca sensor, RESISTANCE OF RICE TO DISEASES1 (ROD1), regulates an immune suppression network that consolidates reactive oxygen species (ROS) metabolism and Ca-sensing to equilibrate both defense responses and optimal growth in plants.
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http://dx.doi.org/10.1016/j.tplants.2022.05.003DOI Listing
May 2022

Mapping the National Phosphorus Recovery Potential from Centralized Wastewater and Corn Ethanol Infrastructure.

Environ Sci Technol 2022 May 26. Epub 2022 May 26.

Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, 205 N. Mathews Avenue, Urbana, Illinois 61801, United States.

Anthropogenic discharge of excess phosphorus (P) to water bodies and increasingly stringent discharge limits have fostered interest in quantifying opportunities for P recovery and reuse. To date, geospatial estimates of P recovery potential in the United States (US) have used human and livestock population data, which do not capture the engineering constraints of P removal from centralized water resource recovery facilities (WRRFs) and corn ethanol biorefineries where P is concentrated in coproduct animal feeds. Here, renewable P (rP) estimates from plant-wide process models were used to create a geospatial inventory of recovery potential for centralized WRRFs and biorefineries, revealing that individual corn ethanol biorefineries can generate on average 3 orders of magnitude more rP than WRRFs per site, and all corn ethanol biorefineries can generate nearly double the total rP of WRRFs across the US. The Midwestern states that make up the Corn Belt have the largest potential for P recovery and reuse from both corn biorefineries and WRRFs with a high degree of co-location with agricultural P consumption, indicating the untapped potential for a circular P economy in this globally significant grain-producing region.
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http://dx.doi.org/10.1021/acs.est.1c07881DOI Listing
May 2022

Hydrogen sulfide manages hexavalent chromium toxicity in wheat and rice seedlings: The role of sulfur assimilation and ascorbate-glutathione cycle.

Environ Pollut 2022 Aug 21;307:119509. Epub 2022 May 21.

Plant Physiology Laboratory, Department of Botany, C.M.P. Degree College, A Constituent Post Graduate College of University of Allahabad, Prayagraj, 211002, India.

The role of hydrogen sulfide (HS) is well known in the regulation of abiotic stress such as toxic heavy metal. However, mechanism(s) lying behind this amelioration are still poorly known. Consequently, the present study was focused on the regulation/mitigation of hexavalent chromium (Cr(VI) toxicity by the application of HS in wheat and rice seedlings. Cr(VI) induced accumulation of reactive oxygen species and caused protein oxidation which negatively affect the plant growth in both the cereal crops. We noticed that Cr(VI) toxicity reduced length of wheat and rice seedlings by 21% and 19%, respectively. These reductions in length of both the cereal crops were positively related with the down-regulation in the ascorbate-glutathione cycle, and were recovered by the application NaHS (a donor of HS). Though exposure of Cr(VI) slightly stimulated sulfur assimilation but addition of HS further caused enhancement in sulfur assimilation, suggesting its role in the HS-mediated Cr(VI) stress tolerance in studied cereal crops. Overall, the results revealed that HS renders Cr(VI) stress tolerance in wheat and rice seedlings by stimulating sulfur assimilation and ascorbate-glutathione which collectively reduce protein oxidation and thus, improved growth was observed.
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http://dx.doi.org/10.1016/j.envpol.2022.119509DOI Listing
August 2022

Drought propagation under global warming: Characteristics, approaches, processes, and controlling factors.

Sci Total Environ 2022 Sep 16;838(Pt 2):156021. Epub 2022 May 16.

College of Water Sciences, Beijing Normal University, Beijing 100875, China.

Drought is a costly natural hazard with far-reaching impacts on agriculture, ecosystem, water supply, and socio-economy. While propagating through the water cycle, drought evolves into different types and affects the natural system and human society. Despite much progress made in recent decades, a synthesis of the characteristics, approaches, processes, and controlling factors of drought propagation is still lacking. We bridge this gap by reviewing the recent progress of drought propagation and discussing challenges and future directions. We first introduce drought propagation characteristics (e.g., response time scale, lag time), followed by different approaches, including statistical analysis and hydrological modeling. The recent progress in the propagation from meteorological drought to different types of drought (agricultural drought, hydrological drought, and ecological drought) is then synthesized, including the basic process, commonly used indicators, data sources, and main findings of drought propagation characteristics. Different controlling factors of drought propagations, including climate (e.g., aridity, seasonality, and anomalies of meteorological variables), catchment properties (e.g., slope, elevation, land cover, aquifer, baseflow), and human activities (e.g., reservoir operation and water diversion, irrigation, and groundwater abstraction), are then summarized. Challenges in drought propagation include the discrepancy in drought indicators (and approaches) and difficulty in characterizing the full propagation process and isolating influencing factors. Future analysis of drought propagation should shift from single indicators to multiple indicators, from individual drivers to combined drivers, from uni-directional analysis to feedbacks, from hazards to impacts, and from stationary to nonstationary assumptions. This review is expected to be useful for drought prediction and management across different regions under global warming.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156021DOI Listing
September 2022

Spatiotemporal hysteresis distribution and decomposition of solar activities and climatic oscillation during 1900-2020.

Environ Res 2022 Sep 14;212(Pt C):113435. Epub 2022 May 14.

Department of Biological and Agricultural Engineering & Zachry Department of Civil Engineering, Texas A& M University, College Station, TX, 77843, USA.

Solar radiation is the external driving force of the Earth's climate system. In different spatial and temporal scales, meteorological elements have different responses and lag periods to solar activity (SA), climatic oscillation (CO), geographic factors (GF) and other influencing factors. However, such studies are not abundant and in-depth in the world. To further understand the "solar-climate-water resource" system, this study considers China as the study area and investigates the monthly data of temperature (T) and precipitation (P) during 1900-2020 that were obtained from 3836 grid stations. The strong interaction and lag distribution between T or P with SA and CO were studied and influence weights of SA, CO, and geographical factors (GF) of each grid station were calculated. A multivariate hysteretic decomposition model was established to simulate and quantitatively decompose the periodic lag considering the factors of the earth's revolution. It is found that the strong interaction/lag periods obtained in a long-time scale can be decomposed into several periods shorter than the SA period. The distribution of strong interaction/lag periods is nested with topography and echoes with cities. The underlying surface conditions and urbanization are also important factors affecting the T and P lag. There are two distinct dividing lines in the lag period and influencing factor pattern of T and P. The T dividing line moves through valleys where water or mountain ranges meet, where the gap facilitates monsoon movement across regions, while the P dividing line is a zone of dramatic terrain, where tall mountains block water vapor transport. In the lag trend of T, the northern region of China has the longest lag period, and the lag period of surrounding regions tends to converge to the northern region. The lag period caused by SN in southwest China is larger than that in northwest China, while the lag effect of CO is opposite in the above two regions. The lag trend of P also has the above characteristics, but the difference is that the lag period in central China is the longest.
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http://dx.doi.org/10.1016/j.envres.2022.113435DOI Listing
September 2022

Deciphering the role of the two conserved motifs of the ECF41 family σ factor in the autoregulation of its own promoter in Azospirillum brasilense Sp245.

Proteins 2022 May 17. Epub 2022 May 17.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, India.

In Azospirillum brasilense, an extra-cytoplasmic function σ factor (RpoE10) shows the characteristic 119 amino acid long C-terminal extension found in ECF41-type σ factors, which possesses three conserved motifs (WLPEP, DGGGR, and NPDKV), one in the linker region between the σ and σ , and the other two in the SnoaL_2 domain of the C-terminal extension. Here, we have described the role of the two conserved motifs in the SnoaL_2 domain of RpoE10 in the inhibition and activation of its activity, respectively. Truncation of the distal part of the C-terminal sequence of the RpoE10 (including NPDKV but excluding the DGGGR motif) results in its promoter's activation suggesting autoregulation. Further truncation of the C-terminal sequence up to its proximal part, including NPDKV and DGGGR motif, abolished promoter activation. Replacement of NPDKV motif with NAAAV in RpoE10 increased its ability to activate its promoter, whereas replacement of DGGGR motif led to reduced promoter activation. We have explored the dynamic modulation of σ -σ domains and the relevant molecular interactions mediated by the two conserved motifs of the SnoaL2 domain using molecular dynamics simulation. The analysis enabled us to explain that the NPDKV motif located distally in the C-terminus negatively impacts transcriptional activation. In contrast, the DGGGR motif found proximally of the C-terminal extension is required to activate RpoE10.
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http://dx.doi.org/10.1002/prot.26387DOI Listing
May 2022

Nitric oxide and hydrogen peroxide independently act in mitigating chromium stress in Triticum aestivum L. seedlings: Regulation of cell death, chromium uptake, antioxidant system, sulfur assimilation and proline metabolism.

Plant Physiol Biochem 2022 Jul 10;183:76-84. Epub 2022 May 10.

Plant Physiology Laboratory, Department of Botany, C.M.P. Degree College, A Constituent Post Graduate College of University of Allahabad, Prayagraj, 211002, India.

In this study, we have explored potential of a nitric oxide (NO) donor (SNP, sodium nitroprusside) and hydrogen peroxide (HO) in curtailing stress of hexavalent chromium [Cr(VI)] in wheat seedlings. Cr(VI) stress caused a significant decline in growth (30%) and photosynthesis (13%) as a result of enhanced uptake of Cr(VI) and root tips cell death. Further, Cr(VI) stress also accelerated indices of oxidative stress but differentially regulated antioxidant system. But application of either NO or HO separately significantly mitigated Cr(VI) stress by reducing cell death and Cr(VI) uptake in roots, and oxidative stress markers. The application of c-PTIO [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of NO] and N-acetyl-L-cysteine (a scavenger of ROS) reserved alleviatory effect of NO and HO, respectively and thus further increased Cr(VI) toxicity. Application of diphenylene iodonium (DPI, an inhibitor of NADPH oxidases) also further increased Cr(VI) toxicity. But SNP and HO significantly rescued negative effects of DPI and c-PTIO, respectively under Cr(VI) stress. Overall results suggested that NO and HO both independently act in mitigating Cr(VI) stress in wheat seedlings by minimizing cell death, restricting Cr(VI) uptake in roots, and increasing antioxidant system, sulfur assimilation and proline metabolism.
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http://dx.doi.org/10.1016/j.plaphy.2022.05.004DOI Listing
July 2022

Effects of Gamma-Tocotrienol on Intestinal Injury in a GI-Specific Acute Radiation Syndrome Model in Nonhuman Primate.

Int J Mol Sci 2022 Apr 22;23(9). Epub 2022 Apr 22.

Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 ( < 0.03) and 7 ( < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 ( < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury.
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http://dx.doi.org/10.3390/ijms23094643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100017PMC
April 2022

Evaluation of Performance of Detection of Immunoglobulin G and Immunoglobulin M Antibody Against Spike Protein of SARS-CoV-2 by a Rapid Kit in a Real-Life Hospital Setting.

Front Microbiol 2022 25;13:802292. Epub 2022 Apr 25.

Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.

Background: Antibody testing is often used for serosurveillance of coronavirus disease 2019 (COVID-19). Enzyme-linked immunosorbent assay and chemiluminescence-based antibody tests are quite sensitive and specific for such serological testing. Rapid antibody tests against different antigens are developed and effectively used for this purpose. However, their diagnostic efficiency, especially in real-life hospital setting, needs to be evaluated. Thus, the present study was conducted in a dedicated COVID-19 hospital in New Delhi, India, to evaluate the diagnostic efficacy of a rapid antibody kit against the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Sixty COVID-19 confirmed cases by reverse transcriptase-polymerase chain reaction (RT-PCR) were recruited and categorized as early, intermediate, and late cases based on the days passed after their first RT-PCR-positive test report, with 20 subjects in each category. Twenty samples from pre-COVID era and 20 RT-PCR-negative collected during the study period were taken as controls. immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the RBD of the spike (S) protein of SARS-CoV-2 virus were detected by rapid antibody test and compared with the total antibody against the nucleocapsid (N) antigen of SARS-CoV-2 by electrochemiluminescence-based immunoassay (ECLIA).

Results: The detection of IgM against the RBD of the spike protein by rapid kit was less sensitive and less specific for the diagnosis of SARS-CoV-2 infection. However, diagnostic efficacy of IgG by rapid kit was highly sensitive and specific when compared with the total antibody against N antigen measured by ECLIA.

Conclusion: It can be concluded that detection of IgM against the RBD of S protein by rapid kit is less effective, but IgG detection can be used as an effective diagnostic tool for SARS-CoV-2 infection in real-life hospital setting.
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http://dx.doi.org/10.3389/fmicb.2022.802292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087894PMC
April 2022

The effect of reducing per capita water and energy uses on renewable water resources in the water, food and energy nexus.

Sci Rep 2022 05 9;12(1):7582. Epub 2022 May 9.

Department of Geography, University of California, Santa Barbara, CA, 93016-4060, USA.

This study assesses the feedbacks between water, food, and energy nexus at the national level with a dynamic-system model, taking into account the qualitative and quantitative environmental water needs. Surface and groundwater resources are considered jointly in the water resources subsystem of this dynamic system. The developed model considers the effects of reducing the per capita use water and energy on its system's components. Results indicate that due to feedbacks the changes in per capita uses of water and energy have indirect and direct effects. About 40% of the total water savings achieved by the per capita change policy was related to energy savings, in other words, it is an indirect saving. Implementation of per capita use reductions compensates for 9% of the decline of Iran's groundwater reservoirs (non-renewable resources in the short term) that occur during the five-year study period. The Manageable and Exploitable Renewable Water Stress Index (MRWI) corresponding to water and energy savings equals 214.5%, which is better than its value under the current situation (which is equal to 235.1%).
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http://dx.doi.org/10.1038/s41598-022-11595-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085854PMC
May 2022

Impact of abdominal imaging on the diagnosis of acute pancreatitis in patients with painless lipase elevation.

Pancreatology 2022 Jun 29;22(5):547-552. Epub 2022 Apr 29.

Department of Internal Medicine, Mayo Clinic Arizona, USA; Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, USA. Electronic address:

Abdominal pain is considered a cardinal feature of acute pancreatitis (AP), and abdominal imaging is only required to diagnose AP when the pain is atypical, or serum enzyme elevation does not match the clinical picture. While painless lipase elevation is being increasingly associated with worse outcomes in various diseases, the diagnostic approach to such elevation is so-far unclear. We thus aimed to learn the impact of pain on the diagnosis of AP.

Methods: All patients presenting to the Mayo Clinic Arizona Hospital emergency department with a serum lipase ≥3x upper limit of normal between April 2016 and January 2020 were prospectively followed. Their charts were reviewed for the nature of pain, serum lipase levels on presentation, abdominal imaging, and whether a diagnosis of AP was made. Chronic pancreatitis was excluded.

Results: Among 320 patients, 85 (26.5%) had painless lipase elevation. These patients had abdominal imaging less often (56/85, 66%) than in those with abdominal pain (201/235, 83%; p = 0.001). The diagnosis of AP increased overall from 31/63 (49%) without imaging to 198/257 (77%) with imaging (P < 0.001). Imaging increased the diagnosis of AP in patients with painless lipase elevation from 2/29 (7%) without imaging to 16/56 (29%; p = 0.025) among those who were imaged.

Conclusions: Painless lipase elevation >3-fold the upper limit of normal is common in emergency department patients. 1/3 to 1/4 of these may have AP. Abdominal imaging increases the diagnosis of AP in patients with painless lipase elevation. Therefore, abdominal imaging in such patients may help detect AP that otherwise eludes diagnosis.
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http://dx.doi.org/10.1016/j.pan.2022.04.013DOI Listing
June 2022

Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms.

iScience 2022 May 27;25(5):104322. Epub 2022 Apr 27.

Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.

We compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia's impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.
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http://dx.doi.org/10.1016/j.isci.2022.104322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045865PMC
May 2022

Heavy metal induced regulation of plant biology: Recent insights.

Physiol Plant 2022 May;174(3):e13688

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.

The presence of different forms of heavy metals in the earth crust is very primitive and probably associated with the origin of plant life. However, since the beginning of human civilisation, heavy metal use and its contamination to all living systems on earth have significantly increased due to human anthropogenic activities. Heavy metals are nonbiodegradable, which directly or indirectly impact photosynthesis, antioxidant system, mineral nutrition status, phytohormones and amino acid-derived molecules. Due to the toxic behaviour of some heavy metals, the endogenous status of chemical messengers like phytohormones may get significantly influenced, leading to harmful impacts on plant growth, development and overall yield of the plants. It has been noticed that exogenous application of phytohormones, that is, abscisic acid, salicylic acid, auxins, brassinosteroids, cytokinins, ethylene and gibberellins can positively regulate the heavy metal toxicity in plants through the regulation of the ascorbate-glutathione cycle, nitrogen metabolism, proline metabolisms, transpiration rate, and cell division. Furthermore, it may also restrict the entry of heavy metals into the plant cells, which aids in the recovery of plant growth and productivity. Besides these, some defence molecules also assist the plant in dealing with heavy metal toxicity. Therefore, the present review aims to bridge the knowledge gap in this context and present outstanding discoveries related to plant life supportive processes during stressful conditions including phytohormones and heavy metal crosstalk along with suggestions for future research in this field.
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http://dx.doi.org/10.1111/ppl.13688DOI Listing
May 2022
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