Resilience to diabetic retinopathy.

Chronic elevation of blood glucose at first causes relatively minor changes to the neural and vascular components of the retina. As the duration of hyperglycemia persists, the nature and extent of damage increases and becomes readily detectable. While this second, overt manifestation of diabetic retinopathy (DR) has been studied extensively, what prevents maximal damage from the very start of hyperglycemia remains largely unexplored. Recent studies indicate that diabetes (DM) engages mitochondria-based defense during the retinopathy-resistant phase, and thereby enables the retina to remain healthy in the face of hyperglycemia. Such resilience is transient, and its deterioration results in progressive accumulation of retinal damage. The concepts that co-emerge with these discoveries set the stage for novel intellectual and therapeutic opportunities within the DR field. Identification of biomarkers and mediators of protection from DM-mediated damage will enable development of resilience-based therapies that will indefinitely delay the onset of DR.

Biomarkers of heart failure: advances in omics studies.

Heart failure is a complex syndrome characterized by progressive circulatory dysfunction, manifesting clinically as pulmonary and systemic venous congestion, alongside inadequate tissue perfusion. The early identification of HF, particularly at the mild and moderate stages (stages B and C), presents a clinical challenge due to the overlap of signs, symptoms, and natriuretic peptide levels with other cardiorespiratory pathologies. Nonetheless, early detection coupled with timely pharmacological intervention is imperative for enhancing patient outcomes. Advances in high-throughput omics technologies have enabled researchers to analyze patient-derived biofluids and tissues, discovering biomarkers that are sensitive and specific for HF diagnosis. Due to the diversity of HF etiology, it is insufficient to study the diagnostic data of early HF using a single omics technology. This study reviewed the latest progress in genomics, transcriptomics, proteomics, and metabolomics for the identification of HF biomarkers, offering novel insights into the early clinical diagnosis of HF. However, the validity of biomarkers depends on the disease status, intervention time, genetic diversity and comorbidities of the subjects. Moreover, biomarkers lack generalizability in different clinical settings. Hence, it is imperative to conduct multi-center, large-scale and standardized clinical trials to enhance the diagnostic accuracy and utility of HF biomarkers.

An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice.

Diabetic retinopathy (DR) is a complex and progressive ocular disease characterized by two distinct phases in its pathogenesis. The first phase involves the loss of protection from diabetes-induced damage to the retina, while the second phase centers on the accumulation of this damage. Traditional assays primarily focus on evaluating capillary degeneration, which is indicative of the severity of damage, essentially addressing the second phase of DR. However, they only indirectly provide insights into whether the protective mechanisms of the retinal vasculature have been compromised. To address this limitation, a novel approach was developed to directly assess the retina's protective mechanisms - specifically, its resilience against diabetes-induced insults like oxidative stress and cytokines. This protection assay, although initially designed for diabetic retinopathy, holds the potential for broader applications in both physiological and pathological contexts. In summary, understanding the pathogenesis of diabetic retinopathy involves recognizing the dual phases of protection loss and damage accumulation, with this innovative protection assay offering a valuable tool for research and potentially extending to other medical conditions.

Multidimensional sleep health and diabetic retinopathy: Systematic review and meta-analysis.

Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for diabetes and poor glycemic control. Recent studies have suggested associations between poor sleep health/OSA and DR. Furthermore, there have been suggestions of melatonin dysregulation in the context of DR. We conducted a systematic review and meta-analysis exploring the associations between multidimensional sleep health (duration, satisfaction, efficiency, timing/regularity and alertness), OSA and melatonin with DR. Forty-two studies were included. Long, but not short sleep, was significantly associated with DR, OR 1.41 (95%CI 1.21, 1.64). Poor sleep satisfaction was also significantly associated with DR, OR 2.04 (1.41, 2.94). Sleep efficiency and alertness were not associated with DR, while the evidence on timing/regularity was scant. Having OSA was significantly associated with having DR, OR 1.34 (1.07, 1.69). Further, those with DR had significantly lower melatonin/melatonin metabolite levels than those without DR, standardized mean difference -0.94 (-1.44, -0.44). We explored whether treating OSA with continuous positive airway pressure (CPAP) led to improvement in DR (five studies). The results were mixed among studies, but potential benefits were observed in some. This review highlights the association between poor multidimensional sleep health and DR.

Transarterial chemoembolization combined donafenib with/without PD-1 for unresectable HCC in a multicenter retrospective study.

Background & aims: This multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC). Methods: The clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.2 g) twice daily until intolerable toxicity or disease progression. Patients in the TACE+D group received the same dose of donafenib for 3-5 days after TACE. Overall survival (OS) and progression-free survival (PFS)were analyzed by Kaplan-Meier method and log-rank test. The tumor response was compared between the two groups according to modified RECIST criteria. Adverse events were also analyzed between the two groups. Results: The TACE+D group included 157 patients and the TACE+DP group included 166 patients. Patients in the TACE+DP group had a longer median OS (18.1 vs. 13.2 months, P<0.001) and longer median PFS (10.6 vs. 7.9 months, P<0.001) than those in the TACE+D group. Patients in the TACE+DP group achieved a greater objective response rate (ORR; 50.6% vs. 41.4%, P=0.019) and greater disease control rate (DCR) (89.2% vs. 82.8%, P=0.010) than those in the TACE+D group. No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). Conclusion: With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.

Photodynamic therapy with hematoporphyrin derivative for recurrent plantar cutaneous squamous cell carcinoma: A case report.

Cutaneous squamous cell carcinoma (cSCC) is a prevalent malignant tumor typically treated through surgical removal. However, when the lesion is situated in specific areas like the hands, feet, or lips, particularly if it's sizable, surgical interventions can adversely impact appearance and function. In such cases, non-surgical treatments are preferable to preserve both aesthetics and functionality. We present a case of recurrent cSCC on the plantar region post-surgery. Given the extensive lesion area, deep infiltration, and the patient's reliance on foot function, hematoporphyrin derivative-photodynamic therapy (HpD-PDT) was chosen over traditional surgery. The lesion was successfully treated, and while a minor recurrence was observed after 20 months, it was localized and amenable to non-surgical intervention. We posit that HpD-PDT is a viable treatment for cSCC, especially in unique locations, with extensive lesions, and postoperative recurrence.

Case report: Hematoporphyrin injection (HpD) photodynamic therapy for the treatment of groin extramammary Paget's disease in an elderly male patient.

Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) is a modality for cancer treatment, particularly suitable for challenging sites or elderly patients who can benefit from its minimally invasive and selective nature. We report a case of groin extramammary Paget's disease (EMPD) in a male patient with a lesion located in the right mons pubis. The patient was deemed unsuitable for surgical treatment due to his advanced age, underlying health conditions, extensive rash area, and the specific location of the groin lesion. He opted for hematoporphyrin photodynamic therapy instead of traditional wide local excision. The tumors were successfully treated, with no recurrence observed during the follow-up period. We suggest that hematoporphyrin photodynamic therapy may be an effective alternative to conventional surgery for the treatment of extramammary Paget's disease.

Tripartite motif containing 59 mediates protective anti-oxidative effects in intestinal injury through Nrf2 signaling.

Elevated evidence has reported the important role of oxidative stress injury and inflammatory response in the progression of colitis. Tumor Suppressor TSBF1, TRIM59, is a ubiquitin E3 ligase and mediates immune response. However, the underlying molecular function of TRIM59 on regulation of colitis is still not understood. In the current study, we identify the TRIM59 as a critical and novel endogenous suppressor of kelch-like ECH-associated protein 1 (KEAP1), and we also determine that TRIM59 is a KEAP1-interacting partner protein that catalyses its ubiquitination and degradation in intestinal epithelial cells (IEC). Moreover, IEC-specific loss of the Trim59 disrupts colon metabolic homeostasis, accompanied by intestinal oxidative stress injury, elevated endogenous reactive oxygen species (ROS) production and pro-inflammatory cytokines release, significantly promotes acute or chronic colitis progression. Conversely, transgenic mice with Trim59 overexpression by adeno-associated virus (AAV)-induced Trim59 gene therapeutics mitigates colitis in acute or chronic colitis rodent models and in vitro experiments. Mechanistically, in response to onset of colitis, TRIM59 directly interacts with KEAP1 and promotes ubiquitin-proteasome degradation, thus results in NRF2 activation and its downstream cascade anti-oxidative stress-related pathway activation, which facilitates anti-oxidant defense and reduces tissue damage. All the findings elucidated the potential role of TRIM59 in colitis progression by mediating KEAP1 deactivation and degradation, and could be considered as a therapeutic target for the treatment of such disease.

The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant defense genes was increased soon after the onset of DM. In addition, ischemia/oxidative stress caused less death in the retinal vasculature of DM versus non-DM mice. Further investigation with T1D mice revealed that protection was transient; it waned as the duration of DM was prolonged. Finally, a loss of protection was associated with the manifestation of both neural and vascular abnormalities that are diagnostic of DR in mice. These observations demonstrate that DM can transiently activate protection from oxidative stress, which is a plausible explanation for the delay in the development of DR from the onset of DM.

Characterizing legacy nitrogen-induced time lags in riverine nitrogen reduction for the Songhuajiang River Basin: Source analysis, spatio-seasonal patterns, and impacts on future water quality improvement.

Legacy nitrogen (N) originating from net N inputs (NNI) may pose ongoing threats to riverine water quality worldwide and even cause serious time-lags between water quality restoration and NNI declines. A better understanding of legacy N effects on riverine N pollutions in different seasons is essential to improve riverine water quality. Here, we investigated contributions of legacy N on riverine dissolved inorganic N (DIN) changes in different seasons and quantified spatio-seasonal time-lags in the Songhuajiang River basin (SRB), a hotspot of NNI with four distinct seasons, by exploring long-term (1978-2020) NNI-DIN relationships. Results firstly showed a significant seasonal difference in NNI, with the highest value observed in spring (average, 2184.1 kg/km2), 1.2, 5.0, and 4.6 times higher than that in summer, autumn, and winter, respectively. Cumulative legacy N had dominated riverine DIN changes, with a relative contribution of approximately 64% in 2011-2020, causing time-lags of 11-29 years across the SRB. The longest seasonal lags existed in spring (average, 23 years) owing to greater impacts of legacy N to riverine DIN changes in this season. Mulch film application, soil organic matter accumulation, N inputs, and snow cover were identified as the key factors that strengthened seasonal time-lags by collaboratively enhancing legacy N retentions in soils. Furthermore, a machine learning-based model system suggested that timescales for water quality improvement (DIN, ≤1.5 mg/L) varied considerably (from 0 to >29 years, Improved N Management-Combined scenario) across the SRB, with greater lag effects contributing to slower recovery. These findings can provide a more comprehensive insight into sustainable basin N management in the future.

Efficacy of hematoporphyrin injection (HpD) photodynamic therapy in the treatment of widespread extramammary Paget's disease.

Photodynamic therapy (PDT) utilizing Hematoporphyrin Derivative (HpD) injection has been demonstrated as an efficacious treatment for various conditions, including Bowen's disease, subtypes of basal cell carcinomas, and actinic keratosis. While surgical resection is considered the primary treatment option for extramammary Paget's disease (EMPD), some patients may not be suitable candidates for surgical intervention. ALA-PDT may have some benefits in treating EMPD in select patients, while Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) has demonstrated promising potential as a cancer treatment. We present one case of vulvar extramammary Paget's disease (EMPD), that is a female patient with lesions in the vulva and involving the urethra. Due to advanced age, underlying diseases, the extensive affected area, and the specific location of the vulvar lesion, the patients were unable to undergo surgical treatment. Therefore, the patient declined traditional wide local excision and instead opted for hematoporphyrin photodynamic therapy. Treatment eliminated the tumor, but it recurred locally after 1.5 years of follow-up. Localized small-scale recurrence at the affected site can be treated with surgical resection or photodynamic therapy to achieve complete clearance of the lesion. However, the patient refuses further examination and treatment. EMPD has a high recurrence rate, but we propose that hematoporphyrin photodynamic therapy is an effective alternative to conventional surgery for treating this condition, even in case of recurrence.

Fabrication and characterizations of Zn-doped SnO2-Ti4O7 anode for electrochemical degradation of hexafluoropropylene oxide dimer acid and its homologues.

Hexafluoropropylene oxide dimer acid (HFPO-DA) and its homologues, as perfluorinated ether alkyl substances with strong antioxidant properties, have rarely been reported by electrooxidation processes to achieve good results. Herein, we report the use of an oxygen defect stacking strategy to construct Zn-doped SnO2-Ti4O7 for the first time and enhance the electrochemical activity of Ti4O7. Compared with the original Ti4O7, the Zn-doped SnO2-Ti4O7 showed a 64.4% reduction in interfacial charge transfer resistance, a 17.5% increase in the cumulative rate of •OH generation, and an enhanced oxygen vacancy concentration. The Zn-doped SnO2-Ti4O7 anode exhibited high catalytic efficiency of 96.4% for HFPO-DA within 3.5 h at 40 mA/cm2. Hexafluoropropylene oxide trimer and tetramer acid exhibit more difficult degradation due to the protective effect of the -CF3 branched chain and the addition of the ether oxygen atom leading to a significant increase in the C-F bond dissociation energy. The degradation rates of 10 cyclic degradation experiments and the leaching concentrations of Zn and Sn after 22 electrolysis experiments demonstrated the good stability of the electrodes. In addition, the aqueous toxicity of HFPO-DA and its degradation products was evaluated. This study analyzed the electrooxidation process of HFPO-DA and its homologues for the first time, and provided some new insights.

Transcatheter arterial chemoembolization plus apatinib with or without camrelizumab for unresectable hepatocellular carcinoma: a multicenter retrospective cohort study.

BACKGROUND: The evidence of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitor and immune checkpoint inhibitor in unresectable hepatocellular carcinoma (HCC) was limited. This study aimed to evaluate the role of TACE plus apatinib (TACE + A) and TACE combined with apatinib plus camrelizumab (TACE + AC) in patients with unresectable HCC. METHODS: This study retrospectively reviewed patients with unresectable HCC who received TACE + A or TACE + AC in 20 centers of China from January 1, 2019 to June 31, 2021. Propensity score matching (PSM) at 1:1 was performed to reduce bias. Treatment-related adverse events (TRAEs), overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were collected. RESULTS: A total of 960 eligible patients with HCC were included in the final analysis. After PSM, there were 449 patients in each group, and the baseline characteristics were balanced between two groups. At data cutoff, the median follow-up time was 16.3 (range: 11.9-21.4) months. After PSM, the TACE + AC group showed longer median OS (24.5 vs 18.0 months, p < 0.001) and PFS (10.8 vs 7.7 months, p < 0.001) than the TACE + A group; the ORR (49.9% vs 42.5%, p = 0.002) and DCR (88.4% vs 84.0%, p = 0.003) of the TACE + AC group were also higher than those in the TACE + A group. Fever, pain, hypertension and hand-foot syndrome were the more common TRAEs in two groups. CONCLUSIONS: Both TACE plus apatinib and TACE combined with apatinib plus camrelizumab were feasible in patients with unresectable HCC, with manageable safety profiles. Moreover, TACE combined with apatinib plus camrelizumab showed additional benefit.

Toxic effects of cadmium on the physiological and biochemical attributes of plants, and phytoremediation strategies: A review.

Anthropogenic activities pose a more significant threat to the environment than natural phenomena by contaminating the environment with heavy metals. Cadmium (Cd), a highly poisonous heavy metal, has a protracted biological half-life and threatens food safety. Plant roots absorb Cd due to its high bioavailability through apoplastic and symplastic pathways and translocate it to shoots through the xylem with the help of transporters and then to the edible parts via the phloem. The uptake and accumulation of Cd in plants pose deleterious effects on plant physiological and biochemical processes, which alter the morphology of vegetative and reproductive parts. In vegetative parts, Cd stunts root and shoot growth, photosynthetic activities, stomatal conductance, and overall plant biomass. Plants' male reproductive parts are more prone to Cd toxicity than female reproductive parts, ultimately affecting their grain/fruit production and survival. To alleviate/avoid/tolerate Cd toxicity, plants activate several defense mechanisms, including enzymatic and non-enzymatic antioxidants, Cd-tolerant gene up-regulations, and phytohormonal secretion. Additionally, plants tolerate Cd through chelating and sequestering as part of the intracellular defensive mechanism with the help of phytochelatins and metallothionein proteins, which help mitigate the harmful effects of Cd. The knowledge on the impact of Cd on plant vegetative and reproductive parts and the plants' physiological and biochemical responses can help selection of the most effective Cd-mitigating/avoiding/tolerating strategy to manage Cd toxicity in plants.

Tripartite motif-containing protein 31 confers protection against nonalcoholic steatohepatitis by deactivating mitogen-activated protein kinase kinase kinase 7.

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.

Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.

lncRNA TRPM2-AS Promotes Colorectal Cancer Progression by Regulating miR-22-3p and FSTL1.

Background: In recent years, long noncoding RNAs (lncRNAs) relate to many biological processes, which affect the progression of tumors. Transient receptor potential melastatin 2 antisense RNA (TRPM2-AS) is reported to play an oncogene-like role in tumors. TRPM2-AS is highly expressed in colorectal cancer (CRC), but the mechanism of TRPM2-AS is still unclear. The regulatory mechanism of TRPM2-AS in the occurrence of CRC was explored, so as to find new markers and therapeutic targets for CRC. Methods: TRPM2-AS and miR-22-3p expression in CRC cells were measured through reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Then, TRPM2-AS knockdown cell lines were constructed, and cell counting kit-8 (CCK-8), clone formation, wound healing, and invasion assays were used to detect cell malignant behavior. Follistatin-like 1 (FSTL1) protein was detected by western blotting. The interaction between miR-22-3p and TRPM2-AS or FSTL1 was verified by the luciferase reporter and RNA immunoprecipitation (RIP) assay. Subcutaneous xenografts were performed using animal experiments. Results: TRPM2-AS expression in CRC cells was increased, and miR-22-3p expression was decreased in CRC cells. TRPM2-AS inhibition inhibited cell malignant behavior. miR-22-3p has a targeting relationship with TRPM2-AS and FSTL1. In cells, downregulation of TRPM2-AS expression promoted miR-22-3p and inhibited FSTL1 expression, while mimics inhibited FSTL1 expression. miR-22-3p inhibition or FSTL1 overexpression could offset the inhibition of TRPM2-AS downregulation on CRC cells. Conclusions: The TRPM2-AS/miR-22-3p/FSTL1 regulation axis could regulate CRC cell malignant behavior, which may provide a new perspective for interpreting the mechanism of CRC development.

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway.

The MYH9 (Myosin heavy chain 9), an architecture component of the actomyosin cytoskeleton, has been reported to be dysregulated in several types of cancers. However, how this molecule contributes to cancer development is still obscure. This study deciphered the molecular function of MYH9 in head and neck cancer (HNC). Cellular methods included clonogenic survival, wound-healing migration, and Matrigel invasion assays. Molecular techniques included RT-qPCR, western blot, luciferase reporter assays, and flow cytometry. Clinical association studies were undertaken by TCGA data mining, Spearman correlation, and Kaplan-Meier survival analysis. We found that MYH9 was overexpressed in tumors and associated with poor prognosis in HNC patients. MYH9 promoted cell motility along with the modulation of the extracellular matrix (fibronectin, ITGA6, fascin, vimentin, MMPs). Also, MYH9 contributed to radioresistance and was related to the expression of anti-apoptotic and DNA repairing molecules (XIAP, MCL1, BCL2L1, ATM, RAD50, and NBN). Mechanically, MYH9 suppressed cellular ROS levels, which were achieved by activating the pan-MAPK signaling molecules (Erk, p38, and JNK), the induction of Nrf2 transcriptional activity, and the up-regulation of antioxidant enzymes (GCLC, GCLM, GPX2). The antioxidant enzyme GCLC was further demonstrated to facilitate cell invasion and radioresistance in HNC cells. Thus, MYH9 exerts malignant functions in HNC by regulating cellular ROS levels via activating the MAPK-Nrf2-GCLC signaling pathway. As MYH9 contributes to radioresistance and metastasis, this molecule may serve as a prognostic biomarker for clinical application. Furthermore, an in vivo study is emergent to support the therapeutic potential of targeting MYH9 to better manage refractory cancers.

State-of-the-art OMICS strategies against toxic effects of heavy metals in plants: A review.

Environmental pollution of heavy metals (HMs), mainly due to anthropogenic activities, has received growing attention in recent decades. HMs, especially the non-essential carcinogenic ones, including chromium (Cr), cadmium (Cd), mercury (Hg), aluminum (Al), lead (Pb), and arsenic (As), have appeared as the most significant air, water, and soil pollutants, which adversely affect the quantity, quality, and security of plant-based food all over the world. Plants exposed to HMs could experience significant decline in growth and yield. To avoid or tolerate the toxic effects of HMs, plants have developed complicated defense mechanisms, including absorption and accumulation of HMs in cell organelles, immobilization by forming complexes with organic chelates, extraction by using numerous transporters, ion channels, signalling cascades, and transcription elements, among others. OMICS strategies have developed significantly to understand the mechanisms of plant transcriptomics, genomics, proteomics, metabolomics, and ionomics to counter HM-mediated stress stimuli. These strategies have been considered to be reliable and feasible for investigating the roles of genomics (genomes), transcriptomic (coding), mRNA transcripts (non-coding), metabolomics (metabolites), and ionomics (metal ions) to enhance stress resistance or tolerance in plants. The recent developments in the mechanistic understandings of the HMs-plant interaction in terms of their absorption, translocation, and toxicity invasions at the molecular and cellular levels, as well as plants' response and adaptation strategies against these stressors, are summarized in the present review. Transcriptomics, genomics, metabolomics, proteomics, and ionomics for plants against HMs toxicities are reviewed, while challenges and future recommendations are also discussed.