Harnessing molecular hybridization approach to discover novel quinoline EGFR-TK inhibitors for cancer treatment.

Aim: Using molecular hybridization approach, novel 18 quinoline derivatives (6a-11) were designed and synthesized as EGFR-TK inhibitors. Materials & methods: The antiproliferative activity was assessed against breast (MCF-7), leukemia (HL-60) and lung (A549) cancer cell lines. Moreover, the most active quinoline derivatives (6d and 8b) were further investigated for their potential as EGFR-TK inhibitors. In addition, cell cycle analysis and apoptosis induction activity were conducted. Results: A considerable cytotoxic activity was attained with IC50 values spanning from 0.06 to 1.12 µM. Besides, the quinoline derivatives 6d and 8b displayed potent inhibitory activity against EFGR with IC50 values of 0.18 and 0.08 µM, respectively. Conclusion: Accordingly, the afforded quinoline derivatives can be used as promising lead anticancer candidates for future optimization.

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Effect of Transplanted Bone Marrow on Spleen of Irradiated Pregnant Rats and Their Fetuses.

<b>Background and Objective:</b> Prenatal ionizing radiation exposure may hinder fetal and embryonic growth depending on the dose and gestational age. The current study's objective was to discover how bone marrow transplants affected the spleens of pregnant rats that had been subjected to γ (Gamma) radiation. <b>Materials and Methods:</b> Sixty rats that were pregnant were separated into five different groups, each with 6 females. The pregnant rats in the second Group were exposed to 2Gy of γ-rays. Group III; pregnant rats subjected to 2Gy of γ-rays, followed by an intraperitoneal injection of newly prepared bone marrow transplantation (BMT). The fifth Group were exposed to 2Gy γ-rays and received 1 dosage of BMT an hour later. Spleen samples from the pregnant rats as well as their fetuses were taken for histological and histochemical analyses. <b>Results:</b> Gamma rays damaged the splenic tissue of women and their fetuses on days 7 or 14 of pregnancy in a variety of histological and histochemical ways, although bone marrow transplantation significantly reduced the damage. Treated mothers with bone marrow post-radiation showed a noticeable recovery in spleen of their fetuses. Improved spleen architecture was accompanied by appearance of normal content of collagen, polysaccharides and total protein in the fetal spleen tissue especially on day 7 of gestation. <b>Conclusion:</b> Bone marrow transplantation can lessen the damage caused by gamma radiation.

Evaluating the Differential Risk of Contrast-Induced Nephropathy Among Diabetic and Non-diabetic Patients Following Percutaneous Coronary Intervention.

Background Contrast-induced nephropathy (CIN) significantly complicates percutaneous coronary intervention (PCI), with a higher prevalence in diabetic patients. This study compares the incidence of CIN in diabetic and non-diabetic patients undergoing PCI. Material and methods Conducted at Lady Reading Hospital, Peshawar, PAK, from January to December 2023, this observational study involved 450 adult patients with coronary artery disease (CAD) undergoing PCI. The cohort was categorized based on diabetes status, excluding patients with chronic kidney disease and those on renal replacement therapy. Baseline characteristics documented included age, gender, blood pressure, creatinine levels, and the presence of acute coronary syndrome (ACS). CIN was defined as a ≥25% increase in serum creatinine from baseline within 48-72 hours post-PCI. Data analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY), incorporating descriptive statistics, Chi-square tests, and independent t-tests, with a significance level of p<0.05. Results The median age of the study population was 55 years. The cohort comprised 52% male (n=234) and 48% female (n=216). Notably, 33% (n=149) had ACS. Diabetic patients exhibited a significantly higher incidence of CIN post-PCI compared to non-diabetics. The highest incidence of CIN (17%, n=77) occurred in the 70+ age group. The findings highlight the criticality of renal function monitoring and procedural adjustments for diabetic patients. Conclusion Diabetic patients demonstrate an increased risk of CIN following PCI. This necessitates the development of tailored prevention strategies for this high-risk subgroup.

Outcomes with allogeneic hematopoietic stem cell transplantation in TP53-mutated myelodysplastic syndrome: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.

Vertical alveolar bone augmentation of atrophied posterior mandibular regions with simultaneous dental implant placement using allogeneic bone rings vs autogenous bone rings: a randomized controlled clinical trial.

OBJECTIVE: Ideal implant placement in atrophied posterior mandibular regions is challenging due to surgical difficulties and anatomical limitations. This study aimed to evaluate the use of allogeneic bone rings for vertical augmentation of atrophied posterior mandibular regions with simultaneous implants compared to autogenous bone rings, while avoiding donor site morbidity. METHOD AND MATERIALS: A total of 24 vertically atrophied posterior mandibular segments (in 14 patients) were equally randomized into a study group in which mineralized freeze-dried allogeneic bone rings were used, and a control group in which autogenous bone rings with prepared implant osteotomies were harvested from the chin and used. All augmentation sites were prepared before inserting the bone rings. Implants were simultaneously inserted, fixing the bone rings into the native bone. All patients were clinically assessed after 1 week, 2 weeks, and 1 month. Crestal bone level was radiographically assessed after 1 week, 6 months, and 3 months of prosthetic loading. RESULTS: None of the 24 bone rings showed signs of implant or graft failure. There was no significant difference in the crestal bone level between the groups. CONCLUSION: Allogeneic bone rings can be a viable alternative to autogenous bone rings in augmenting the posterior aspect of the mandible, mitigating the concerns associated with donor site complications.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site.

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.

Reasons for leaving home and pattern of child abuse and substance misuse among street children in Khartoum, Sudan: a cross-sectional survey.

Street children are particularly susceptible to health-related adversities, including those resulting from substance abuse and child abuse. Information on street children is deficient in Sudan. This study provides basic data on characteristics, factors for leaving home, the pattern of child abuse and substance misuse among street children in Khartoum State, Sudan. This is a descriptive, cross-sectional, and community-based study. Data were collected through direct questioning of a sample of street children using a structured, standardized, and pretested interview-administered questionnaire. Two hundred and seventy-five (275) street children were interviewed. Most street children were males (83%). Of the interviewed children, 36.7% were illiterate, 66.1% had a single parent, and 36% did not recognize a home to return to. The commonest reported reasons for being on the streets were family conflicts and financial/economic difficulties (28.4 % and 27.5%), respectively. 89.1% of the children admitted to being substance abusers, mostly of glue (86.5%) and smoked tobacco (67.3%). Seventy-five-point three percent 75.3% of the children reported being subjected to a form of abuse, with physical and sexual abuse reported by 70.2% and 27%, respectively. Of the 74 children who reported sexual abuse, 49 were males (29% of males), and 25 were females (65% of females). The survey results are thought to guide further research and shape appropriate policymaking and coordinated interventions by concerned stakeholders, whether governmental or non-governmental.

Demaghi, a polyherbal formulation, mitigates aluminum chloride-induced neurological impairment in mice: Insights from phytochemical analysis and behavioral assessment.

Herbal products have been very popular in Pakistan for their curative significance against various disorders. Demaghi (DEMG) is a widely used herbal product claimed to own natural substances having neuroprotective potential. The current study aims to scientifically validate the chemical composition as well as its neuroprotective claims of this widely used herbal tonic. The commercially available Demaghi product was chemically characterized for its phytocomposition. The mice were treated with two doses of Demaghi (DEMG 50 mg and 100 mg/kg/day), and the effects of its prolonged exposure on animal anxiety, memory, and depression were noted through a series of behavioral tests in the AlCl3-induced memory deficient mice model. Besides that, dissected brains were biochemically analyzed for oxidative stress markers and acetylcholinesterase activity, as well as histopathological changes. The study outcomes showed that DEMG (100 mg/kg/day) has prominent anti-anxiety effects, memory-enhancing properties, and anti-depressants effects observed in the AlCl3-induced memory-deficient mice model. Biochemical assays also showed a greater decrease in oxidative stress of tested animals treated with 100 mg/kg/day of DEMG. The histopathological analysis also revealed that administration of DEMG reduced the AlCl3-induced toxicity. UPLC-MS results revealed the presence of many phytoconstituents, which showed to support cholinergic signaling in in-silico studies. The current research validates the neurological benefits of Demaghi for memory-boosting properties. The phytocompounds present in Demaghi exert neuroprotective effects, possibly by enhancing the cholinergic neurotransmission and combating the neurotoxin-induced oxidative stress.

Intraoperative Diagnosis of Gallbladder Volvulus.

Background: A gallbladder torsion typically presents as an acute abdomen presentation with nonspecific clinical signs. When not detected by a clinician preoperatively, it can lead to the delay of emergency surgery and possible misdiagnosis for other, more common causes of an acute abdomen. Case Presentation. We report the case of acute gallbladder volvulus in an 80-year-old woman complaining of constant pain in the right upper quadrant of the abdomen. Conclusions: The patient was successfully treated with cholecystectomy. The case highlights the high index of suspicion required to diagnose the condition preoperatively in this population of patients to reduce complications such as biliary peritonitis and death.

Design, synthesis and antiproliferative screening of newly synthesized coumarin-acrylamide hybrids as potential cytotoxic and apoptosis inducing agents.

On the basis of the observed biological activity of coumarin and acrylamide derivatives, a new set of coumarin-acrylamide-CA-4 hybrids was designed and synthesized. These compounds were investigated for their cytotoxic activity against cancerous human liver cell line HepG2 cells using 5-fluorouracil (5-FU) as a reference drug. Compound 6e had promising antiproliferative activity with an IC50 value of 1.88 µM against HepG2 cells compared to 5-FU (IC50 = 7.18 µM). The results of ß-tubulin polymerization inhibition indicated that coumarin-acrylamide derivative 6e was the most active, with a percentage inhibition value of 84.34% compared to podophyllotoxin (88.19% ß-tubulin inhibition). Moreover, the active coumarin-acrylamide molecule 6e exerted cell cycle cession at the G2/M phase stage of HepG2 cells. In addition, this compound produced a 15.24-fold increase in apoptotic cell induction compared to no-treatment control. These observations were supported by histopathological studies of liver sections. The conducted docking studies illustrated that 6e is perfectly positioned within the tubulin colchicine binding site, indicating a significant interaction that may underlie its potent tubulin inhibitory activity. The main objective of the study was to develop new potent anticancer compounds that might be further optimized to prevent the progression of cancer disease.

Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage.

BACKGROUND: Minimally invasive surgery (MIS) for spontaneous supratentorial intracerebral haemorrhage (ICH) is controversial but may be beneficial if end-of-treatment (EOT) haematoma volume is reduced to ≤15 mL. We explored whether MRI findings of cerebral small vessel disease (CSVD) modify the effect of MIS on long-term outcomes. METHODS: Prespecified blinded subgroup analysis of 288 subjects with qualified imaging sequences from the phase 3 Minimally Invasive Surgery Plus Alteplase for Intracerebral Haemorrhage Evacuation (MISTIE) trial. We tested for heterogeneity in the effects of MIS and MIS+EOT volume ≤15 mL on the trial's primary outcome of good versus poor function at 1 year by the presence of single CSVD features and CSVD scores using multivariable models. RESULTS: Of 499 patients enrolled in MISTIE III, 288 patients had MRI, 149 (51.7%) randomised to MIS and 139 (48.3%) to standard medical care (SMC). Median (IQR) ICH volume was 42 (30-53) mL. In the full MRI cohort, there was no statistically significant heterogeneity in the effects of MIS versus SMC on 1-year outcomes by any specific CSVD feature or by CSVD scores (all Pinteraction >0.05). In 94 MIS patients with EOT ICH volume ≤15 mL, significant reduction in odds of poor outcome was found with cerebral amyloid angiopathy score <2 (OR, 0.14 (0.05-0.42); Pinteraction=0.006), absence of lacunes (OR, 0.37 (0.18-0.80); Pinteraction=0.02) and absence of severe white matter hyperintensities (WMHs) (OR, 0.22 (0.08-0.58); Pinteraction=0.03). CONCLUSIONS: Following successful haematoma reduction by MIS, we found significantly lower odds of poor functional outcome with lower total burden of CSVD in addition to absence of lacunes and severe WMHs. CSVD features may have utility for prognostication and patient selection in clinical trials of MIS.

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues.

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 µM, as compared to CA-4 (IC50 = 1.27 ± 09 µM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against ß-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

Machine learning applications and challenges in graft-versus-host disease: a scoping review.

PURPOSE OF REVIEW: This review delves into the potential of artificial intelligence (AI), particularly machine learning (ML), in enhancing graft-versus-host disease (GVHD) risk assessment, diagnosis, and personalized treatment. RECENT FINDINGS: Recent studies have demonstrated the superiority of ML algorithms over traditional multivariate statistical models in donor selection for allogeneic hematopoietic stem cell transplantation. ML has recently enabled dynamic risk assessment by modeling time-series data, an upgrade from the static, "snapshot" assessment of patients that conventional statistical models and older ML algorithms offer. Regarding diagnosis, a deep learning model, a subset of ML, can accurately identify skin segments affected with chronic GVHD with satisfactory results. ML methods such as Q-learning and deep reinforcement learning have been utilized to develop adaptive treatment strategies (ATS) for the personalized prevention and treatment of acute and chronic GVHD. SUMMARY: To capitalize on these promising advancements, there is a need for large-scale, multicenter collaborations to develop generalizable ML models. Furthermore, addressing pertinent issues such as the implementation of stringent ethical guidelines is crucial before the widespread introduction of AI into GVHD care.

Anticancer Properties of Ru and Os Half-Sandwich Complexes of N,S Bidentate Schiff Base Ligands Derived from Phenylthiocarbamide.

The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the metal complexes. Phenylthiocarbamide-based N,S donor Schiff bases converted into RuII /OsII (cymene) complexes and characterized by spectroscopic techniques and elemental analysis. The hydrolytic stability of metal complexes to undergo metal-halide ligand exchange reaction was confirmed both by the DFT and NMR experimentation. The ONIOM (QM/MM) study confirmed the histone protein targeting nature of aqua/hydroxido complex 2 aH with an excellent binding energy of -103.19 kcal/mol. The antiproliferative activity against a panel of cancer cells A549, MCF-7, PC-3, and HepG2 revealed that ruthenium complexes 1 a-3 a were more cytotoxic than osmium complexes and their respective ligands 1-3 as well. Among these ruthenium cymene complex bearing sulfonamide moiety 2 a proved a strong cytotoxic agent and showed excellent correlation of cellular accumulation, lipophilicity, and drug-likeness to the anticancer activity. Moreover, the favorable physiochemical properties such as bioavailability and gastrointestinal absorption of ligand 2 also supported the development of Ru complex 2 a as an orally active anticancer metallodrug.

Design, synthesis, anti-inflammatory evaluation, and molecular modelling of new coumarin-based analogs combined curcumin and other heterocycles as potential TNF-α production inhibitors via upregulating Nrf2/HO-1, downregulating AKT/mTOR signalling pathways and downregulating NF-κB in LPS induced macrophages.

Persistent inflammation contributes to various inflammatory conditions. Inflammation-related diseases may be treated by inhibiting pro-inflammatory mediators and cytokines. Curcumin and coumarin derivatives can target signalling pathways and cellular factors to address immune-related and inflammatory ailments. This study involved designing and synthesising three series of coumarin-based analogs that incorporated curcumin and other heterocycles. These analogs were evaluated for their potential as anti-inflammatory agents in LPS-induced macrophages. Among the fourteen synthesised coumarin derivatives, compound 14b, which contained 3,4-dimethoxybenzylidene hydrazinyl, demonstrated the highest anti-inflammatory activity with an EC50 value of 5.32 µM. The anti-inflammatory effects of 14b were achieved by modulating signalling pathways like AKT/mTOR and Nrf2/HO-1, and downregulating NF-kß, resulting in reduced production of pro-inflammatory cytokines such as IL-6, IL-1ß, and TNF-α. The modelling studies revealed that 14b and dexamethasone bind to the same TNF-α pocket, suggesting that 14b has potential as a therapeutic agent superior to dexamethasone for TNF-α.

Three series of curcumin-based analogs, incorporating other heterocycles, were synthesised with the intention of exploring their potential as anti-inflammatory agents.Subsequently, these analogs underwent biological assessment in macrophages induced by LPS to determine their anti-inflammatory efficacy.Among the fourteen coumarin derivatives synthesised, the most potent anti-inflammatory activity was observed in the coumarin compound 14b, which featured a 3,4-dimethoxybenzylidene hydrazinyl moiety, with an EC₅₀ value of 5.32 µM.The anti-inflammatory effects of compound 14b were achieved through the modulation of signalling pathways such as AKT/mTOR and Nrf2/HO-1, as well as the downregulation of NF-kß, resulting in decreased production of pro-inflammatory cytokines including IL-6, IL-1ß, and TNF-α.Molecular modelling studies revealed that both compound 14b and dexamethasone bind to the same binding site on TNF-α, suggesting that 14b has the potential to serve as a therapeutic agent for TNF-α and other pro-inflammatory cytokines that surpasses that of dexamethasone.

Optimization of microwave-enhanced extraction parameters to recover phenolic compounds and antioxidants from Corchorus olitorius leaves.

Vegetables are industrial crops endowed with both nutritional and medicinal values. The overwhelming contributions of vegetables to human living in the form of nutrients and medicine cannot be under emphasised. Thus, this study examined the recoveries of phenolic compounds and antioxidants from Corchorus olitorius leaves using a microwave-enhanced extraction technique. Furthermore, the phenolic compounds in the leaf extract of C. olitorius were comprehensively identified using liquid chromatography-mass spectrometry quadrupole of flight (LC-QToF-MS). At the optimized conditions of microwave-enhanced extraction (extraction time of 131 s, microwave power 305 W, solvent/sample ratio of 12 mL/g, and ethanol concentration of 50%), total phenolic content (TPC) of 343.098 ± 3.05 mg GAE/10 g d.b., IC50 values of 68.89 ± 1.08 and 29.76 ± 1.00 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6'-sulfonic acid) (ABTS) assays, respectively, were achieved. Furthermore, an aggregate of fourteen phenolic compounds that include 1-galloyl-glucose, 1,3,5-O-tricaffeoylquinic acid, procyanidin C-1, 4,4',5,6-tetrahydroxystilbene, 3,4,5-O-tricaffeoylquinic acid, 5-desgalloylstachyurin, sanguiin H-4, corilagin_1, 1-O-galloylpedunculagin, laevigatin A, pedunculagin, 2,4,6-tri-O-galloyl-ß-D-glucose, 1,3,6-trigalloyl-ß-D-glucose, and 1,2,3,6-tetra-O-galloyl-ß-D-glucose was tentatively identified in the leaf extract of C. olitorius. In general, this study has established C. olitorius leaves as sources of phenolic compounds and natural antioxidants. Thus, the intake can continue to be promoted as a way forward in solving the problem of food insecurity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-023-02771-x.

Assessment of 222Rn, 226Ra, 238U, 218Po, and 214Po activity concentrations in the blood samples of workers at selected building material factories in Erbil City.

The objective of this research is to assess the impact of radon concentration on workers at certain construction material industries in Erbil, Kurdistan Region of Iraq. The CR-39 solid-state track detector was used in this experiment to monitor radon levels and their daughters. For this purpose, as a case study group, 70 workers were divided into seven subgroups (gypsum, cement plant, lightweight block, marble, red brick 1, crusher stone, and concrete block 2), and 20 healthy volunteers were selected as a control group. The findings demonstrate that the mean concentrations of radon, radium, uranium, and radon daughters deposited on the detector face (POS) and chamber walls (POW) for the case study group were 9.61 ± 1.52 Bq/m3, 0.33 ± 0.05 Bq/Kg, 5.39 ± 0.86 mBq/Kg, 4 ± 0.63, and 16.62 ± 2.64 mBq/m3, whereas for the control group, they were 3.39 ± 0.58 Bq/m3, 0.117 ± 0.03 Bq/Kg, 1.91 ± 0.32 mBq/Kg, 1.41 ± 0.24, and 5.88 ± 1 mBq/m3, respectively. The statistical analysis revealed that radon, radium, uranium, and POW and POS concentrations were statistically significant (p ≤ 0.001) in the samples for the case study groups of cement, lightweight block, red brick 1, marble, and crusher stone factories in comparison to the control group; however, the results for gypsum and concrete block 2 factories were not statistically significant in comparison to the control group. Intriguingly, the radon levels in every blood sample examined were far lower than the 200 Bq/m3 limit established by the International Atomic Energy Agency. Hence, it may be argued that the blood is devoid of contaminants. These results are crucial for determining whether or not an individual is exposed to substantial quantities of radiation and for demonstrating a link between radon, its daughter, uranium, and the prevalence of cancer among workers in the Kurdish region of Iraq.

Nickel (Ni) phytotoxicity and detoxification mechanisms: A review.

Scientists studying the environment, physiology, and biology have been particularly interested in nickel (Ni) because of its dual effects (essentiality and toxicity) on terrestrial biota. It has been reported in some studies that without an adequate supply of Ni, plants are unable to finish their life cycle. The safest Ni limit for plants is 1.5 µg g-1, while the limit for soil is between 75 and 150 µg g-1. Ni at lethal levels harms plants by interfering with a variety of physiological functions, including enzyme activity, root development, photosynthesis, and mineral uptake. This review focuses on the occurrence and phytotoxicity of Ni with respect to growth, physiological and biochemical aspects. It also delves into advanced Ni detoxification mechanisms such as cellular modifications, organic acids, and chelation of Ni by plant roots, and emphasizes the role of genes involved in Ni detoxification. The discussion has been carried out on the current state of using soil amendments and plant-microbe interactions to successfully remediate Ni from contaminated sites. This review has identified potential drawbacks and difficulties of various strategies for Ni remediation, discussed the importance of these findings for environmental authorities and decision-makers, and concluded by noting the sustainability concerns and future research needs regarding Ni remediation.

Combined Minimally Invasive Surgical and Percutaneous Catheter Ablation of Atrial Fibrillation: JACC Review Topic of the Week.

Hybrid ablation is a novel therapy in the invasive management of patients with atrial fibrillation (AF) which combines minimally invasive surgical and percutaneous catheter-based techniques. The evidence is mainly based on observational studies from experienced centers, with success rates of approximately 70% and risks that are 2.0-fold to 3.6-fold higher than catheter-based ablation. Hybrid ablation is offered typically to patients with persistent or longstanding persistent AF which, by design, requires 2 procedures (epicardial surgical and endocardial catheter-based ablation). One randomized trial demonstrated that hybrid ablation was more effective than catheter-based ablation, but with higher complication rates. The incidence of the most serious complications has decreased in contemporary studies of hybrid ablation. At present, hybrid ablation should be performed by experienced centers on selected patients with persistent or longstanding persistent AF. Additional randomized trials are needed to define the risks, benefits, and cost effectiveness of hybrid ablation to identify its most appropriate application in clinical practice.