Search Results (26)

Background/Objectives: We aimed to provide an updated synthesis of the efficacy and ocular safety of subretinal adeno-associated viral (AAV) RPGR gene therapy for retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (RPGR-XLRP) and to assess the certainty of the available evidence. Methods: We performed a PROSPERO-registered (CRD420251163589), PRISMA 2020 systematic review and meta-analysis using database and trial-registry searches. The primary microperimetry synthesis was restricted to mesopic Macular Integrity Assessment (MAIA) 68-loci acquisitions; continuous-outcome syntheses were conducted at the cohort level, using observed paired-eye contrasts when available; dose levels were interpreted within clinical programs; and above-maximum-tolerated-dose and peripheral-injection cohorts were reported separately. Random-effects analyses used DerSimonian–Laird models with Hartung–Knapp–Sidik–Jonkman small-sample correction. Risk of bias and certainty were assessed with design-matched tools and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: The quantitative synthesis included four trials reported in five publications (128 participants; AAV8, AAV5, and AAV2tYF platforms). Mesopic retinal sensitivity numerically favored treatment, but the pooled differences were not statistically significant at six months (mean difference [MD] +1.11 dB; 95% confidence interval [CI], −0.88 to +3.09) or twelve months (MD +0.97 dB; 95% CI, −3.99 to +5.94). Best-corrected visual acuity showed no statistically significant pooled difference (MD +0.94 letters; 95% CI, −4.97 to +6.85). The six-month ≥10-letter low-luminance responder estimate favored treatment, but was nonsignificant and attenuated by twelve months; no primary pooled efficacy outcome reached significance under small-sample-adjusted inference. Certainty was very low for functional outcomes and low for safety outcomes. Uncontrolled treated-eye proportions were 80.8% for intraocular inflammation, 17.0% for ocular serious adverse events, and 4.3% for central-injection retinal detachment. Conclusions: Current evidence does not establish a clinically actionable functional benefit, although a modest true effect cannot be excluded. Clinically relevant ocular safety signals were observed, but the estimates were uncontrolled and program dependent. Adequately powered randomized trials with standardized functional endpoints, optimized subretinal delivery strategies, and careful within-program dose selection are needed. Full article

Defective seed filling, which manifests as seed wrinkling, severely impairs the yield and commercial quality of soybean crops. Soybean varieties independently developed in Heilongjiang Province exhibit distinct phenotypic variations in seed wrinkling across diverse ecological planting regions, whereas the molecular and physiological mechanisms driving such differences remain largely uncharacterized. In this study, two soybean genotypes with divergent heat resistance, namely, the heat-sensitive cultivar HH43 and the heat-tolerant cultivar HN76, were planted in three distinct ecological sites for comparative analysis. Statistical results indicated that ecological conditions serve as the predominant factor regulating seed-wrinkling variation, with high temperatures occurring during the seed-filling stage identified as the key abiotic stress trigger. Excessively high ambient temperatures triggered abnormal sucrose accumulation in the pod husks of heat-vulnerable HH43, disrupting the coupling relationship between sucrose metabolism and energy supply and thereby restricting starch biosynthesis in developing seeds. Transcriptome profiling combined with weighted gene co-expression network analysis (WGCNA) further demonstrated that heat stress significantly suppressed the expression of energy transport-related genes and induced the dysregulated expression of starch synthesis-associated genes in susceptible soybean plants, and these transcriptional alterations were further verified via qRT-PCR assays. Collectively, short-term extreme high temperatures interrupt the carbon transport and allocation process from pod husks to seeds in heat-sensitive soybean cultivars. By contrast, heat-tolerant genotypes can sustain a stable physiological metabolism and molecular regulatory networks to effectively cope with high-temperature stress during the seed-filling period. Full article

Wheat (Triticum aestivum L.), a key grain food crop worldwide, faces increasing threats from combined abiotic stresses exacerbated by climate change. However, the comprehensive effects of drought, salinity, and high-temperature pressure on wheat seedlings remain poorly understood. Using the cultivar “Yannong 1212”, we conducted hydroponic experiments to investigate the physiological, morphological, antioxidant, osmoregulatory, membrane lipid peroxidation, and molecular responses of wheat seedlings to single and combined stresses, and then conducted multivariate statistical analyses. The results showed that drought or salt stress inhibited seed germination in a concentration-dependent manner. However, the combined stresses significantly inhibited germination and seedling growth, leading to leaf chlorosis, chlorophyll degradation, stomatal closure, and chloroplast damage. Physiologically, the combined effect of multiple stresses induced excessive ROS and MDA accumulation, promoted proline and soluble sugar synthesis, and triggered the dynamic responses of antioxidant enzymes. Drought stress increased SOD, POD, and CAT activities, whereas salt stress had the opposite effect, and combined stresses further increased SOD and POD activities, but reduced CAT activity. Additionally, stress-responsive genes were rapidly upregulated. Multivariate analyses confirmed that the combined stress of drought and heat was the most damaging. These findings explain the synergistic damage mechanisms of combined stresses, providing a theoretical basis for genetic improvement of wheat’s stress tolerance. Full article

Soil salinization poses a persistent threat to irrigated agroecosystems, yet remote sensing-based salinity assessment remains predominantly calibrated against bulk electrical conductivity without fully integrating crop physiological variability. This review examines the evolution of remote sensing approaches for soil salinity mapping (1994–2024), with particular emphasis on the role of crop salt tolerance in shaping spectral interpretation and mapping accuracy. A systematic synthesis of 58 peer-reviewed studies retrieved from the Scopus database was conducted using bibliometric analysis and structured full-text thematic classification to evaluate methodological trends and conceptual integration across soil, crops, and spectral domains. The results reveal substantial technological advancement, including multispectral and hyperspectral sensing, machine learning frameworks, and multi-source data integration. However, most approaches remain surface-oriented and statistically calibrated, with limited operationalization of crop-specific tolerance thresholds, root-zone salinity dynamics, and hydrochemical variability. The findings indicate that crop salt tolerance functions as a mediating factor within the soil–plant–spectral continuum, influencing the stability and transferability of spectral–salinity relationships. Integrating physiological tolerance parameters and subsurface processes into modeling frameworks is essential for improving agronomic interpretability and supporting more reliable salinity management in irrigated systems. Full article

Weed interference and herbicide-induced phytotoxicity, particularly from HPPD inhibitors such as tembotrione, represent significant limitations to yield stability in grain sorghum. Developing strategies to enhance crop tolerance without compromising weed control is of high practical interest. This study tested the hypothesis that a commercial Ascophyllum nodosum-based biostimulant can mitigate tembotrione-induced oxidative stress and phytotoxicity in sorghum without compromising the weed-control activity of the herbicide. Sorghum plants at the V4 phenological stage (four fully expanded leaves) were subjected to five treatments: (1) untreated control; (2) biostimulant application alone; (3) tembotrione application alone; (4) simultaneous application of tembotrione and biostimulant; and (5) tembotrione followed by biostimulant application after six days of application (6 DAT). After 10 days of treatment, photosynthetic pigment synthesis, primary photochemistry, gas exchange, antioxidant metabolism, phytotoxicity levels, growth parameters, and yield indices were evaluated. The results support the hypothesis that A. nodosum-based biostimulants can act as effective mitigating agents. The biostimulant sustained carotenoid levels and preserved the stability of the photosynthetic apparatus (PSII), counteracting HPPD enzyme inhibition caused by the herbicide. Isolated biostimulant application upregulated net photosynthesis by 60%, while simultaneous co-application with tembotrione preserved membrane integrity and the leaf area index. Furthermore, the efficacy of the mitigation strategy was highly time-dependent, as simultaneous co-application proved superior to the delayed (6 DAT) intervention. From an agronomic perspective, the biostimulant reduced visual injury and restored the grain number per plant to control levels under simultaneous co-application, although the final yield of combined treatments did not differ statistically from either the untreated control or the treatment of tembotrione alone. This study shows that the integration of A. nodosum extracts into the chemical management of sensitive crops represents a viable biotechnological strategy to enhance herbicide selectivity and yield stability. Full article

Laser acupuncture (LA) integrates principles of traditional acupuncture with photobiomodulation (PBM) and has gained increasing attention as a non-invasive modality for pain management. PBM-based integrative LA in medicine refers to the application of low-level laser irradiation to acupuncture points, combining contemporary biomedical mechanisms with holistic, system-oriented therapeutic principles. This narrative review aimed to critically assess the scientific evidence on the efficacy of LA for pain management within the framework of the Principles of Clinical Integration of Photobiomodulation (PCIPBM) in LA, summarizing frequently used laser parameters and clinical indications. LA involves special protocols in standardized acupoints, using defined parameters of wavelength, irradiation, and energy density, consistent with PBM dosing principles. Therapeutic effects are mediated through point-specific neuromodulation and photobiological mechanisms, including modulation of peripheral and central nociceptive processing, reduction in pro-inflammatory mediators, improvement of microcirculation, and mitochondrial activation via cytochrome c oxidase-dependent adenosine triphosphate (ATP) synthesis. Clinical studies report statistically and clinically significant analgesic effects, particularly in chronic musculoskeletal pain, osteoarthritis, low back and neck pain, temporomandibular disorders, neuropathic pain, and selected postoperative pain conditions, when appropriate laser parameters are applied. Reported adverse effects are minimal, and tolerability is high. LA represents a safe, non-invasive therapeutic option and patient-friendly approach with clinically relevant efficacy in pain management. When applied according to PCIPBM, including evidence-based PBM parameters, it may serve as an effective adjunct or alternative to conventional pharmacologic and interventional approaches. Further standardization and high-quality randomized controlled trials are still required. Full article

Background and Objectives: The purpose of this systematic review and meta-analysis is to assess the patient’s quality of life, as well as the safety and effectiveness of different probiotic strains in treating IBS symptoms such as IBS-C, IBS-D, IBS-M, and IBS-U. Additionally, we contrast the side effects of probiotics that are single-strain and multi-strain. Materials and Methods: PRISMA criteria were followed in the conduct and reporting of this study. The protocol for this review (CRD420251120965) was entered into PROSPERO. RCTs comparing probiotic usage to placebo or usual therapy in adult IBS patients were found using four online databases: PubMed, Google Scholar, Ovid Medline, and the Cochrane Library. Review Manager was used for data synthesis and statistical analysis. Results: After screening 660 records, 16 randomized, double-blind, placebo-controlled trials with 2823 IBS patients were included. Probiotics significantly reduced intestinal discomfort overall (MD: −93.9; 95% CI −133.1 to −54.7; p < 0.00001) and the IBS-Severity Scoring System. Probiotics showed a clinically significant overall improvement (OR 1.71; 95% CI 1.26–2.33; p = 0.0006) when compared to a placebo. They were also well tolerated and did not increase adverse events. Conclusions: According to 16 RCTs, probiotics greatly lessen overall IBS symptoms, which enhances the quality of life and has global therapeutic implications. The findings support the use of probiotics as an effective and safe supplemental treatment for IBS patients. Full article

Gamma-aminobutyric acid (GABA) is a bioactive amino acid with anti-inflammatory and neurotransmitter properties, yet limited information exists regarding its production by Lactiplantibacillus paraplantarum. We evaluated factors that influence GABA synthesis by L. paraplantarum HK-1 and assessed its production in vitro and under simulated gastrointestinal conditions. GABA production was analyzed using HPLC with pre-column derivatization, gene expression was assessed through RT-qPCR, and probiotic characteristics were evaluated using standard microbiological methods. L. paraplantarum HK-1 demonstrated dose-dependent GABA production with monosodium glutamate (MSG) supplementation, achieving maximum levels at 500 mM MSG (161.1 µg/mL), which was significantly higher than those in other treatments (p < 0.01). A strong positive correlation was observed between MSG concentration and GABA production (r = 0.908, p = 0.002). Gene expression analysis revealed a 61.6-fold higher gadB expression at 500 mM MSG compared to 250 mM, though statistical significance with GABA production was not achieved (r = 0.741, p = 0.259). The strain exhibited appropriate probiotic characteristics including γ-hemolytic activity, bile salt tolerance, and acid resistance. Under simulated gastrointestinal conditions, maximum GABA production occurred in the distal colon (148.3 ± 19.0 µg/mL with probiotic vs. 7.2 ± 6.2 µg/mL control), with overall production significantly higher in probiotic-treated groups (p < 0.001). Overall, L. paraplantarum HK-1 produced GABA throughout gastrointestinal phases and showed traits consistent with probiotic use. These results position HK-1 as a promising GABA-producing candidate for functional food applications, pending in vivo validation. Full article

This work presents the results of a research study focused on the development and evaluation of an algorithmic optimal control framework for energy-efficient operation of screw compressors in smart power systems. The proposed approach is based on the Pontryagin maximum principle (PMP), which enables the synthesis of a mathematically grounded regulator that minimizes the total energy consumption of a nonlinear electromechanical system composed of a screw compressor and a variable-frequency induction motor. Unlike conventional PID controllers, the developed algorithm explicitly incorporates system constraints, nonlinear dynamics, and performance trade-offs into the control law, allowing for improved adaptability and energy-aware operation. Simulation results obtained using MATLAB/Simulink confirm that the PMP-based regulator outperforms classical PID solutions in both transient and steady-state regimes. Experimental tests conducted in accordance with standard energy consumption evaluation methods showed that the proposed PMP-based controller provides a reduction in specific energy consumption of up to 18% under dynamic load conditions compared to a well-tuned basic PID controller, while maintaining high control accuracy, faster settling, and complete suppression of overshoot under external disturbances. The control system demonstrates robustness to parametric uncertainty and load variability, maintaining a statistical pressure error below 0.2%. The regulator’s structure is compatible with real-time execution on industrial programmable logic controllers (PLCs), supporting integration into intelligent automation systems and smart grid infrastructures. The discrete-time PLC implementation of the regulator requires only 10³ arithmetic operations per cycle and less than 10² kB of RAM for state, buffers, and logging, making it suitable for mid-range industrial controllers under 2–10 ms task cycles. Fault-tolerance is ensured via range and rate-of-change checks, residual-based plausibility tests, and safe fallbacks (baseline PID or torque-limited speed hold) in case of sensor faults. Furthermore, the proposed approach lays the groundwork for hybrid extensions combining model-based control with AI-driven optimization and learning mechanisms, including reinforcement learning, surrogate modeling, and digital twins. These enhancements open pathways toward predictive, self-adaptive compressor control with embedded energy optimization. The research outcomes contribute to the broader field of algorithmic control in power electronics, offering a scalable and analytically justified alternative to heuristic and empirical tuning approaches commonly used in industry. The results highlight the potential of advanced control algorithms to enhance the efficiency, stability, and intelligence of energy-intensive components within the context of Industry 4.0 and sustainable energy systems. Full article

Salinity and heavy metal stress significantly reduce agricultural productivity in arable lands, particularly affecting crops like rice (Oryza sativa L.). This study aimed to evaluate the efficacy of heavy metal-tolerant plant growth-promoting rhizobacteria (HMT-PGPR) in mitigating the harmful effects of salt (NaCl), chromium (Cr), and combined NaCl + Cr stress on rice plants. Two pre-isolated and well-characterized heavy metal-tolerant epiphytic (Ochrobactrum pseudogrignonense strain P14) and endophytic (Arthrobacter woluwensis strain M1R2) PGPR were tested. The LSD test (p ≤ 0.05) was used to assess the statistical significance between treatment means. Stresses caused by NaCl, Cr, and their combination were found to impair plant growth and biomass accumulation through mechanisms, including osmotic stress, oxidative damage, ionic imbalance, reduced photosynthetic pigment, lowered relative water content, and compromised antioxidant defense systems. Conversely, inoculation with HMT-PGPR alleviated these adverse effects by reducing oxidative stress indicators, including malondialdehyde (MDA), hydrogen peroxide (H₂O₂) content and electrolyte leakage (EL) and enhancing plant growth, osmolyte synthesis, and enzymatic antioxidant activity under single- and dual-stress conditions. The application of HMT-PGPR notably restricted Na⁺ and Cr⁶⁺ uptake, with an endophytic A. woluwensis M1R2 demonstrating superior performance in reducing Cr⁶⁺ translocation (38%) and bioaccumulation (42%) in rice under dual stress. The findings suggest that A. woluwensis effectively mitigates combined salinity and chromium stress by maintaining ion homeostasis and improving the plant’s antioxidant defenses. Full article

Torreya grandis is a widely cultivated fruit species in China that is valued for its significant economic and agricultural importance. The molecular mechanisms underlying pigment formation and photosynthetic performance in Torreya leaf color mutants remain to be fully elucidated. In this study, we performed transcriptome sequencing and measured photosynthetic performance indicators to compare mutant and normal green leaves. The research results indicate that the identified Torreya mutant differs from previously reported mutants, exhibiting a weakened photoprotection mechanism and a significant reduction in carotenoid content of approximately 33%. Photosynthetic indicators, including the potential maximum photosynthetic capacity (F_v/F_m) and electron transport efficiency (Ψ_o, φ_Eo), decreased significantly by 32%, 52%, and 49%, respectively. While the quantum yield for energy dissipation (φ_Do) increased by 31%, this increase was not statistically significant, which may further reduce PSII activity. A transcriptome analysis revealed that the up-regulation of chlorophyll degradation-related genes—HCAR and NOL—accelerates chlorophyll breakdown in the Torreya mutant. The down-regulation of carotenoid biosynthesis genes, such as LCY1 and ZEP, is strongly associated with compromised photoprotective mechanisms and the reduced stability of Photosystem II. Additionally, the reduced expression of the photoprotective gene psbS weakened the mutant’s tolerance to photoinhibition, increasing its susceptibility to photodamage. These changes in gene expression accelerate chlorophyll degradation and reduce carotenoid synthesis, which may be the primary cause of the yellowing in Torreya. Meanwhile, the weakening of photoprotective mechanisms further impairs photosynthetic efficiency, limiting the growth and adaptability of the mutants. This study emphasizes the crucial roles of photosynthetic pigments and photosystem structures in regulating the yellowing phenotype and the environmental adaptability of Torreya. It also provides important insights into the genetic regulation of leaf color in relation to photosynthesis and breeding. Full article

Introduction: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. Methods: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I² statistic and Cochran Qtest. Forest plots were generated for each endpoint. Results: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6–81) and 63 lesions (range: 6–126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1–10 fractions (20–70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3–91.9%). LC2 was 77.9% (95% CI: 66.4–86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0–51.4%) and PFS2 of 23.9% (95% CI: 17.8–31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2–85.0%) and OS2 of 60.7% (95% CI: 51.3–69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. Conclusions: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted. Full article

Background: Pain can have a serious impact on a patient’s physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans. Methods: Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots. Results: Sixteen eligible articles, including k = 5 studies of pain tolerance (n = 210), k = 5 studies of pain threshold (n = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges’ g = 0.28, 95% CI = 0–0.55, Z = 1.99, p = 0.05) and pain tolerance (Hedges’ g = 0.32, 95% CI = 0.05–0.59, Z = 2.30, p = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of −0.37 (95% CI = −0.77 to 0.03, Z = −1.80) but with no statistical significance (p = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges’ g = 0.37, 95% CI = 0.29–0.64, Z = 5.33, p < 0.01). Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine. Full article

Heavy metal stress, including lead, adversely affects the growth and yield of several economically important crops, leading to food challenges and significant economic losses. Ameliorating plant responses to various environmental stresses is one of the promising areas of research for sustainable agriculture. In this study, we evaluated the effect of aspartic acid-functionalized copper nanoparticles on the photosynthetic efficiency and antioxidation system of maize plants under Pb toxicity. The ion reduction method was employed for the synthesis of CuNPs, using ascorbic acid as the reducing agent and aspartic acid as the surface functionalizing agent. Isolated experiments under laboratory and field conditions were performed using a randomized complete block design (RCBD). Seeds primed in water, 1.0, 5.0, and 10 µg/mL of Asp-CuNPs were sown under 0, 500, and 1000 mg/L Pb stress in laboratory conditions, while primed seeds along with foliar-applied Asp-CuNP plants were grown in a field under applied Pb stress, and the obtained data were statistically analyzed using TWANOVA. The laboratory experiment shows that Asp-CuNPs act both as a plant growth regulator (PGR) and plant growth inhibitor (PGI), depending upon their concentration, whereby Asp-CuNPs act as a PGR at a concentration of 1 µg/mL ≤ X ≤10 µg/mL. The field experiment confirms that seed priming and foliar spraying with Asp-CuNPs activate embryos and enhance plant growth in a dose-dependent manner. In addition, Asp-CuNPs (10 µg/mL) significantly increase chlorophyll content to 0.87 mg/g from 0.53 mg/g (untreated) when plants were exposed to Pb toxicity at 1000 mg/kg of soil. It is noteworthy that Asp-CuNPs induce resilience to Pb toxicity (1000 mg/kg of soil) in plants by reducing its root absorption from 3.68 mg/kg (0 µg/mL Asp-CuNPs) to 1.72 mg/kg with the application of 10 µg/mL Asp-CuNPs. Additionally, histochemical analyses with NBT and hydrogen peroxide revealed that ROS accretion in plants treated with Asp-CuNPs declined because of the augmentation of antioxidant enzyme (POD, SOD, APOX, etc.) activities under Pb toxicity. Our findings suggest that amino acid-functionalized copper nanoparticles regulate plant defensive mechanisms related to lead tolerance, which is a promising approach for the induction of resistivity to heavy metal stress. Full article

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain. Full article