Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment.

Introduction: This study bridges traditional remedies and modern pharmacology by exploring the synergy between natural compounds and Ceritinib in treating Non-Small Cell Lung Cancer (NSCLC), aiming to enhance efficacy and reduce toxicities. Methods: Using a combined approach of computational analysis, machine learning, and experimental procedures, we identified and analyzed PD173074, Isoquercitrin, and Rhapontin as potential inhibitors of fibroblast growth factor receptor 3 (FGFR3). Machine learning algorithms guided the initial selection, followed by Quantitative Structure-Activity Relationship (QSAR) modeling and molecular dynamics simulations to evaluate the interaction dynamics and stability of Rhapontin. Physicochemical assessments further verified its drug-like properties and specificity. Results: Our experiments demonstrate that Rhapontin, when combined with Ceritinib, significantly suppresses tumor activity in NSCLC while sparing healthy cells. The molecular simulations and physicochemical evaluations confirm Rhapontin's stability and favorable interaction with FGFR3, highlighting its potential as an effective adjunct in NSCLC therapy. Discussion: The integration of natural compounds with established cancer therapies offers a promising avenue for enhancing treatment outcomes in NSCLC. By combining the ancient wisdom of natural remedies with the precision of modern science, this study contributes to evolving cancer treatment paradigms, potentially mitigating the side effects associated with current therapies.

Fruit extracts from Phyllanthus emblica accentuate cadmium tolerance and accumulation in Platycladus orientalis: A new natural chelate for phytoextraction.

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.

Health risk assessment of heavy metal pollution in a soil-rice system: a case study in the Jin-Qu Basin of China.

A regional field survey of a total of 109 pairs of soil and rice samples was conducted to evaluate the health risks posed by heavy metals in the Jin-Qu Basin, China. The studied soils are characterized by acid (pH in mean level of 5.5), carbon rich (soil organic matter in mean of 33.6 g kg-1) and mainly contaminated by Cd (42.2% samples exceeded the standard value of 0.3 mg kg-1 (GB15618-2018)). The spatial distributions of Cd, Pb and Zn exhibited similar geographic trends. 34% and 30% of the rice samples containing Cd and Pb exceeded the threshold value of 0.2 mg kg-1 (GB2762-2017), respectively. The risk estimation of dietary intake had a target hazard quotient value of Cd of 0.918 and a hazard index value for rice consumption of 2.141. Totally, Cd and Pb were found to be the main components contributing to the potential health risks posed by non-carcinogenic effects for local inhabitants.

Identification of high cadmium-accumulating oilseed sunflower (Helianthus annuus) cultivars for phytoremediation of an Oxisol and an Inceptisol.

Forty oilseed sunflower cultivars were screened in two soil types for phytoremediation of Cd coupled with maximum biomass yield and oil production. Several cultivars exhibited a significant difference in biomass and yield with enhanced uptake in shoots and low accumulation in roots from two Cd-contaminated soil types, an Oxisol and an Iceptisol. The Transfer Factor of Cd was >1 in several cultivars in both soil types, where as a significant difference in phytoextraction of Cd was observed in the Oxisol (acidic soil), greater than in the Inceptisol (alkaline soil). The results revealed that of the 40 cultivars, S9178, Huanong 667in the Oxisol and cvs. DW 667, HN 667, Huanong 667 and 668F1 in the Inceptisol showed a high biomass, better yield and enhanced accumulation of Cd in the shoots but a lesser accumulation in oil. The screened cultivar S 9178 produced the greatest amount of oil (55.6%) with 77% oleic acid, which makes it suitable for human consumption. Cultivar Huanong 667 was found to be the highest accumulating cultivar in both soil types. It is therefore suggested that some sunflower cultivars do exhibit phytoremediation potential together with agro-production potential.

Assessment of sunflower germplasm for phytoremediation of lead-polluted soil and production of seed oil and seed meal for human and animal consumption.

Phytoremediation is a valuable technology for mitigating soil contamination in agricultural lands, but phytoremediation without economic revenue is unfeasible for land owners and farmers. The use of crops with high biomass and bioenergy for phytoremediation is a unique strategy to derive supplementary benefits along with remediation activities. Sunflower (Helianthus annuus L.) is a high-biomass crop that can be used for the phytoremediation of polluted lands with additional advantages (biomass and oil). In this study, 40 germplasms of sunflower were screened in field conditions for phytoremediation with the possibility for oil and meal production. The study was carried out to the physiological maturity stage. All studied germplasms mopped up substantial concentrations of Pb, with maximum amounts in shoot > root > seed respectively. The phytoextraction efficiency of the germplasm was assessed in terms of the Transfer factor (TF), Metal removal efficiency (MRE) and Metal extraction ratio (MER). Among all assessed criteria, GP.8585 was found to be most appropriate for restoring moderately Pb-contaminated soil accompanied with providing high biomass and high yield production. The Pb content in the oil of GP.8585 was below the Food safety standard of China, with 59.5% oleic acid and 32.1% linoleic acid. Moreover, amino acid analysis in meal illustrated significant differences among essential and non-essential amino acids. Glutamic acid was found in the highest percentage (22.4%), whereas cysteine in the lowest percentage (1.3%). Therefore, its efficient phytoextraction ability and good quality edible oil and meal production makes GP.8585 the most convenient sunflower germplasm for phytoremediation of moderately Pb-contaminated soil, with fringe benefits to farmers and landowners.

Accumulation and distribution of cadmium and lead in 28 oilseed rape cultivars grown in a contaminated field.

Heavy metal pollution in soils has become an important concern for human health. Therefore, it is vital to develop suitable remediation strategies for contaminated soils. Oilseed rape tolerates high concentrations of heavy metals and is a promising candidate for the phytoextraction of cadmium (Cd) and lead (Pb) from metal-contaminated soils. A field experiment was conducted to evaluate 28 oilseed rape cultivars including Brassica napus L. and Brassica juncea L. for their ability to accumulate Cd and Pb. These cultivars were grown in a field co-contaminated with Cd (0.78 mg kg-1) and Pb (330 mg kg-1). The results showed that concentrations in shoots ranged from 1.22 to 3.01 mg kg-1 for Cd and from 10.8 to 29.5 mg kg-1 for Pb. Cadmium and Pb accumulations in shoots could reach 83.4 and 799 µg plant-1, respectively. The majority of translocation factors (TFs) for Cd (> 1.0) were higher than for Pb (≤ 1.0). However, concentrations of Cd and Pb in seeds were much lower, in the range of 0.04 to 0.21 mg kg-1 and 0.04 to 0.51 mg kg-1, respectively. The seed yields of oilseed rape varied from 1238 to 2904 kg ha-1, with a mean value of 2289 kg ha-1. Among the cultivars, three (OS-9, OS-12, and OS-15) were selected as Cd and Pb potential accumulators, with Cd accumulation in shoots being 2.74-3.70 times higher and Pb accumulation in shoots being 3.37-5.23 times higher as compared with the lowest accumulating cultivar. These selected cultivars (B. napus) have application potential for phytoextraction of Cd and Pb from polluted soils without stopping agricultural activities and accompanying food safety issues.

The surveillance of the epidemiological and serotype characteristics of hand, foot, mouth disease in Neijiang city, China, 2010-2017: A retrospective study.

Hand, foot, and mouth disease (HFMD) is well recognized as one of the major threats to children's health globally. The increasing complexity of the etiology of HFMD still challenges disease control in China. There is little surveillance of the molecular epidemiological characteristics of the enteroviruses (EVs) that cause HFMD in Neijiang city or the Sichuan Basin area in Southwest China. In this study, demographic and epidemiological information for 14,928 probable HFMD cases was extracted and analyzed to describe the epidemic features of HFMD in Neijiang city from Jan 2010 to Dec 2017. The swab samples of select probable HFMD cases from 2012 to 2017 were tested by reverse transcription (RT) real-time PCR to identify the serotype distribution of EVs, and 110 randomly selected RT-real-time PCR positive samples were then amplified and analyzed for the VP1 or VP4 regions of EVs to further analyze the phylogenetic characteristics of the circulating strains in this area. The eight-year average annual incidence was 49.82 per 100,000 in Neijiang. The incidence rates varied between 19.51 and 70.73 per 100,000, demonstrating peaks of incidence in even-number years (2012, 2014 and 2016). The median age of the probable cases was 27 months and the interquartile range (25th to 75th percentile) of ages for the probable HFMD cases was between 14 and 42 months. The male-to-female ratio of the probable HFMD cases was 1.47:1, and scattered children were the major population classification (81.7%). Two epidemic peaks were observed: one major peak between April and July and the other lesser peak between October and December. Of 6513 probable cases tested with RT-real-time PCR, 4015 (61.6%) were positive for enterovirus with the serotype distribution as follows: EV71+, 30.1% (n = 1210); CV-A16+, 28.7% (n = 1154) and a sole pan-enterovirus+, 41.1% (n = 1651). A total of 91 cases (82.7%, 91/110) were successfully amplified and underwent phylogenetic analysis: all EV71+ cases were C4a serotype (n = 23/30); all CV-A16+ cases were B2b serotype (n = 24/30); of 42 sole pan-enterovirus+ samples, 20 were CV-A6, 14 were CV-A10 and the rest within this group were CV-A4 (n = 4), CV-A8 (n = 2), CV-A9 (n = 1) and CV-B3 (n = 1). Our findings provide important evidence that aids the improvement of strategies for vaccination against HFMD and comprehensive disease control in China.

[Analysis on mutation of S gene and P gene of hepatitis B virus in two counties of Sichuan Province].

OBJECTIVE: To analyze HBV S gene/P gene mutation in 2 counties (districts) of Sichuan province. METHODS: HBV DNA were extracted from sera positive both for HBsAg and HBeAg. After PCR and nucleotide sequencing, nucleotide/amino acid mutation in S and P gene were compared and analyzed. RESULTS: Of 47 serum samples from patients with chronic HBV infection, amino acid mutation in 'a' determinant occurred in 12 samples (25.53%,12/47), correlating with T126A, I126T/S, P127T, T131N, M133L, M133T and T140I; high proportion of mutation clustered in first loop of 'a' determinant (92.86%,13/14), rtV207I mutation in C domain of reverse transcription occured in one sample. CONCLUSION: Naturally occurring mutation in 'a' determinant clustered predominantly in the first loop and usually associated with altered antigenicity, posing a potential threat to successfully vaccinated individuals; Lamivudine-resistant mutant might occur in patient even without nucleotide analogue treatment.