Multiphase Ozonolysis of Bisphenol A: Chemical Transformations on Surfaces in the Environment.

High global plastic production volumes have led to the widespread presence of bisphenol compounds in human living and working environments. The most common bisphenol, bisphenol A (BPA), despite being endocrine disruptive and estrogenic, is still not fully banned worldwide, leading to continued human exposure via particles in air, dust, and surfaces in both outdoor and indoor environments. While its abundance is well documented, few studies have addressed the chemical transformations of BPA, the properties of its reactive products, and their toxicity. Here, the first gas-surface multiphase ozonolysis experiment of BPA thin films, at a constant ozone mixing ratio of 100 ppb, was performed in a flow tube for periods up to 24 h. Three transformation products involving the addition of 1, 2, and 3 oxygen atoms to the molecule were identified by LC-ESI-HRMS analyses. Exposure of indoor air to thin BPA surface films and BPA-containing thermal paper over periods of days validated the flow tube experiments, demonstrating the rapid nature of this multiphase ozonolysis reaction at atmospherically relevant ozone levels. Multiple transformation pathways are proposed that are likely applicable to not only BPA but also emerging commercial bisphenol products.

Identification of Hydrocarbon Sulfonates as Previously Overlooked Transthyretin Ligands in the Environment.

Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (∼1%) of in vitro human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein Affinity Purification with Nontargeted Analysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T4 displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants (e.g., dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4'-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC50 of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.

Poleward shifts in the maximum of spring phenological responsiveness of Ginkgo biloba to temperature in China.

Global warming is advancing the timing of spring leaf-out in temperate and boreal plants, affecting biological interactions and global biogeochemical cycles. However, spatial variation in spring phenological responsiveness to climate change within species remains poorly understood. Here, we investigated variation in the responsiveness of spring phenology to temperature (RSP; days to leaf-out at a given temperature) in 2754 Ginkgo biloba twigs of trees distributed across subtropical and temperate regions in China from 24°N to 44°N. We found a nonlinear effect of mean annual temperature on spatial variation in RSP, with the highest response rate at c. 12°C and lower response rates at warmer or colder temperatures due to declines in winter chilling accumulation. We then predicted the spatial maxima in RSP under current and future climate scenarios, and found that trees are currently most responsive in central China, which corresponds to the species' main distribution area. Under a high-emission scenario, we predict a 4-degree latitude shift in the responsiveness maximum toward higher latitudes over the rest of the century. The identification of the nonlinear responsiveness of spring phenology to climate gradients and the spatial shifts in phenological responsiveness expected under climate change represent new mechanistic insights that can inform models of spring phenology and ecosystem functioning.

Functionalized Regulation of Metal Defects in ln2S3 of p-n Homojunctions.

The introduction of metal vacancies into n-type semiconductors could efficiently construct intimate contact interface p-n homojunctions to accelerate the separation of photogenerated carriers. In this work, a cationic surfactant occupancy method was developed to synthesize an indium-vacancy (VIn)-enriched p-n amorphous/crystal homojunction of indium sulfide (A/C-IS) for sodium lignosulfonate (SL) degradation. The amount of VIn in the A/C-IS could be regulated by varying the content of added cetyltrimethylammonium bromide (CTAB). Meanwhile, the steric hindrance of CTAB produced mesopores and macropores, providing transfer channels for SL. The degradation rates of A/C-IS to SL were 8.3 and 20.9 times higher than those of crystalline In2S3 and commercial photocatalyst (P25), respectively. The presence of unsaturated dangling bonds formed by VIn reduced the formation energy of superoxide radicals (•O2-). In addition, the inner electric field between the intimate contact interface p-n A/C-IS promoted the migration of electron-hole pairs. A reasonable degradation pathway of SL by A/C-IS was proposed based on the above mechanism. Moreover, the proposed method could also be applicable for the preparation of p-n homojunctions with metal vacancies from other sulfides.

Building the Environmental Chemical-Protein Interaction Network (eCPIN): An Exposome-Wide Strategy for Bioactive Chemical Contaminant Identification.

Although advancements in nontargeted analysis have made it possible to detect hundreds of chemical contaminants in a single run, the current environmental toxicology approaches lag behind, precluding the transition from analytical chemistry efforts to health risk assessment. We herein highlighted a recently developed "top-down" bioanalytical method, protein Affinity Purification with Nontargeted Analysis (APNA), to screen for bioactive chemical contaminants at the "exposome-wide" level. To achieve this, a tagged functional protein is employed as a "bait" to directly isolate bioactive chemical contaminants from environmental mixtures, which are further identified by nontargeted analysis. Advantages of this protein-guided approach, including the discovery of new bioactive ligands as well as new protein targets for known chemical contaminants, were highlighted by several case studies. Encouraged by these successful applications, we further proposed a framework, i.e., the environmental Chemical-Protein Interaction Network (eCPIN), to construct a complete map of the 7 billion binary interactions between all chemical contaminants (>350,000) and human proteins (∼20,000) via APNA. The eCPIN could be established in three stages through strategically prioritizing the ∼20,000 human proteins, such as focusing on the 48 nuclear receptors (e.g., thyroid hormone receptors) in the first stage. The eCPIN will provide an unprecedented throughput for screening bioactive chemical contaminants at the exposome-wide level and facilitate the identification of molecular initiating events at the proteome-wide level.

Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein Affinity Purification with Nontargeted Analysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with >50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 ± 32.9%) and PPARγ (66.0 ± 27.1%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes.

Mounting evidence has shown that ambient PM2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM2.5. In this study, the 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore the adipogenic potential of PM2.5. After 8 days of PM2.5 exposure, adipocyte fatty acid uptake and lipid accumulation were significantly increased, and adipogenic differentiation of 3T3-L1 cells was promoted in a concentration-dependent manner. Transcriptome and lipidome analyses revealed the systematic disruption of transcriptional and lipid profiling at 10 µg/mL PM2.5. Functional enrichment and visualized network analyses showed that the peroxisome proliferator-activated receptor (PPAR) pathway and the metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most significantly affected during adipocyte differentiation. Reporter gene assays indicated that PPARγ was activated by PM2.5, demonstrating that PM2.5 promoted adipogenesis by activating PPARγ. The increased transcriptional and protein expressions of PPARγ and downstream adipogenesis-associated markers (e.g., Fabp4 and CD36) were further cross-validated using qRT-PCR and western blot. PM2.5-induced adipogenesis, PPARγ pathway activation, and lipid remodeling were significantly attenuated by the supplementation of a PPARγ antagonist (T0070907). Overall, this study yielded mechanistic insights into PM2.5-induced adipogenesis in vitro by identifying the potential biomolecular targets for the prevention of PM2.5-induced obesity and related metabolic diseases.

Microbial diversity composition of apple tree roots and resistance of apple Valsa canker with different grafting rootstock types.

BACKGROUND: The composition and diversity of root microbial community are affected by plant genotypes and soil environment, which in turn affect plant growth and development. Grafting rootstock types of the apple tree can affect phenotypes in cultivation practice, but it is not clear whether grafting rootstock types can affect the composition and diversity of root microbial community and the resistance of apple tree to apple Valsa canker. METHODS: To explore root microbial differences and the correlation, 16S rRNA and ITS genes were sequenced using Novaseq technology. RESULTS: The results showed that the influence of grafting rootstock types on the composition of the root fungal community was greater than that of bacteria. And the bacterial community richness was higher in the healthy (OTUs: 1693) and dwarfing rootstock (OTUs: 1526) than in the disease (OTUs: 1181) and standard rootstock (OTUs: 1412), while the fungal community richness was the opposite. Moreover, the bacterial abundance of root zone, rhizosphere, and root endophytic microorganisms with the same grafting rootstock type exhibited a decreasing trend. Results of Nested PCR assay on soil and root tissue of Valsa mali showed that the content of V. mali in dwarfing rootstocks are lower than standard rootstocks. These results suggest that apple trees grafting with dwarfing rootstocks are more resistant to V. mali than standard rootstocks. CONCLUSIONS: Under different grafting types, the effect on the composition of fungal community in apple tree root was greater than that of bacteria. The bacterial community in dwarfing rootstocks is more abundant and diverse, including more beneficial microorganisms. Therefore, dwarfing rootstock is more conducive to the resistance to apple Valsa canker from biological control.

Triclosan is the Predominant Antibacterial Compound in Ontario Sewage Sludge.

Sewage treatment plants (STPs) accumulate both antibiotic and nonantibiotic antimicrobial compounds that can select for antibiotic resistant bacteria. Herein, we aimed to identify the predominant antibacterial compounds impacting E. coli from Ontario sewage sludge consisting of thousands of unknown compounds. Among the 10 extracted sludge samples, 6 extracts exerted significant growth inhibition effects in E. coli. A total of 103 compounds were tentatively detected across the 10 sludge samples by suspect screening, among which the bacterial enoyl-ACP reductase (FabI) inhibitor triclocarban was detected at the highest abundance. A hypomorphic FabI knockdown E. coli strain was highly susceptible to the sludge extracts, confirming FabI inhibitors as the primary antibacterial compounds in the sludge. Protein affinity pulldown identified triclosan as the major ligand binding to a His-tagged FabI protein from the sludge, despite the higher abundance of triclocarban in the same samples. Effect-directed analysis was used to determine the contributions of triclosan to the observed antibacterial potencies. Antibacterial effects were only detected in F17 and F18 across 20 fractions, which was consistent with the elution of triclosan and triclocarban in the same two fractions. Further, potency mass balance analysis confirmed that triclosan explained the majority (58-113%) of inhibition effects from sludge extracts. This study highlighted triclosan as the predominant antibacterial compound in sewage sludge impacting E. coli despite the co-occurrence of numerous other antibiotics and nonantibiotics.

Defining the Chemical Additives Driving In Vitro Toxicities of Plastics.

Increases in the global use of plastics have caused concerns regarding potential adverse effects on human health. Plastic products contain hundreds of potentially toxic chemical additives, yet the exact chemicals which drive toxicity currently remain unknown. In this study, we employed nontargeted analysis and in vitro bioassays to identify the toxicity drivers in plastics. A total of 56 chemical additives were tentatively identified in five commonly used plastic polymer pellets (i.e., PP, LDPE, HDPE, PET, and PVC) by employing suspect screening and nontargeted analysis. Phthalates and organophosphates were found to be dominant in PVC pellets. Triphenyl phosphate and 2-ethylhexyl diphenyl phosphate accounted for a high amount (53.6%) of the inhibition effect of PVC pellet extract on human carboxylesterase 1 (hCES1) activity. Inspired by the high abundances of chemical additives in PVC pellets, six different end-user PVC-based products including three widely used PVC water pipes were further examined. Among them, extracts of PVC pipe exerted the strongest PPARγ activity and cell viability suppression. Organotins were identified as the primary drivers to these in vitro toxicities induced by the PVC pipe extracts. This study clearly delineates specific chemical additives responsible for hCES1 inhibition, PPARγ activity, and cell viability suppression associated with plastic.

Remodeling of Arctic char (Salvelinus alpinus) lipidome under a stimulated scenario of Arctic warming.

Arctic warming associated with global climate change poses a significant threat to populations of wildlife in the Arctic. Since lipids play a vital role in adaptation of organisms to variations in temperature, high-resolution mass-spectrometry-based lipidomics can provide insights into adaptive responses of organisms to a warmer environment in the Arctic and help to illustrate potential novel roles of lipids in the process of thermal adaption. In this study, we studied an ecologically and economically important species-Arctic char (Salvelinus alpinus)-with a detailed multi-tissue analysis of the lipidome in response to chronic shifts in temperature using a validated lipidomics workflow. In addition, dynamic alterations in the hepatic lipidome during the time course of shifts in temperature were also characterized. Our results showed that early life stages of Arctic char were more susceptible to variations in temperature. One-year-old Arctic char responded to chronic increases in temperature with coordinated regulation of lipids, including headgroup-specific remodeling of acyl chains in glycerophospholipids (GP) and extensive alterations in composition of lipids in membranes, such as less lyso-GPs, and more ether-GPs and sphingomyelin. Glycerolipids (e.g., triacylglycerol, TG) also participated in adaptive responses of the lipidome of Arctic char. Eight-week-old Arctic char exhibited rapid adaptive alterations of the hepatic lipidome to stepwise decreases in temperature while showing blunted responses to gradual increases in temperature, implying an inability to adapt rapidly to warmer environments. Three common phosphatidylethanolamines (PEs) (PE 36:6|PE 16:1_20:5, PE 38:7|PE 16:1_22:6, and PE 40:7|PE 18:1_22:6) were finally identified as candidate lipid biomarkers for temperature shifts via machine learning approach. Overall, this work provides additional information to a better understanding of underlying regulatory mechanisms of the lipidome of Arctic organisms in the face of near-future warming.

Life Cycle Exposure to Environmentally Relevant Concentrations of Diphenyl Phosphate (DPhP) Inhibits Growth and Energy Metabolism of Zebrafish in a Sex-Specific Manner.

Due to commercial uses and environmental degradation of aryl phosphate esters, diphenyl phosphate (DPhP) is frequently detected in environmental matrices and is thus of growing concern worldwide. However, information on potential adverse effects of chronic exposure to DPhP at environmentally realistic concentrations was lacking. Here, we investigated the effects of life cycle exposure to DPhP on zebrafish at environmentally relevant concentrations of 0.8, 3.9, or 35.6 µg/L and employed a dual-omics approach (metabolomics and transcriptomics) to characterize potential modes of action. Exposure to DPhP at 35.6 µg/L for 120 days resulted in significant reductions in body mass and length of male zebrafish, but did not cause those same effects to females. Predominant toxicological mechanisms, including inhibition of oxidative phosphorylation, down-regulation of fatty acid oxidation, and up-regulation of phosphatidylcholine degradation, were revealed by integrated dual-omics analysis and successfully linked to adverse outcomes. Activity of succinate dehydrogenase and protein content of carnitine O-palmitoyltransferase 1 were significantly decreased in livers of male fish exposed to DPhP, which further confirmed the proposed toxicological mechanisms. This study is the first to demonstrate that chronic, low-level exposure to DPhP can retard growth via inhibiting energy output in male zebrafish.

Natural indole-containing alkaloids and their antibacterial activities.

As the growth in resistance to bacterial infection treatments poses a grave threat to global health in the 21st century, there is a constant need to explore novel antibacterial agents that have the ability to overcome drug resistance. Indole-containing alkaloids are widely distributed in nature, and a variety of indole-containing alkaloids have already been applied in clinical practice, proving that indole-containing alkaloids are fascinating and privileged scaffolds for the development of novel drugs. Moreover, indole-containing alkaloids could exert their antibacterial activity through the inhibition of efflux pumps, the biofilm, filamentous temperature-sensitive protein Z, and methicillin-resistant Staphylococcus aureus pyruvate kinase; so, indole-containing alkaloids constitute an important source of novel antibacterial agents. This review is an endeavor to highlight the advances in the development of indole-containing alkaloids with antibacterial potential, covering articles published in the recent 10 years.

Comparative pharmacokinetic study on three formulations of Astragali Radix by an LC-MS/MS method for determination of formononetin in human plasma.

Astragali Radix (AR) is a widely used traditional Chinese medicine for healing the cardiovascular, liver and immune systems. Recently, superfine pulverizing technology has been applied to developing novel formulations to improve bioavailability of the active constituents in herbs, such as ultrafine granular powder of AR. In this study, a universal and sensitive quantitative method based on LC-MS/MS was employed for determining formononetin, the main flavonoid in AR, in human plasma for comparative pharmacokinetics of three oral formulations of AR. Formononetin and IS (quercetin) were extracted by ethyl acetate from human plasma and were separated on a C18 column with a mobile phase consisting of acetonitrile and 0.1% formic acid. Positive-ion electrospray-ionization mode was applied in mass spectrometric detection. The quantitative method was validated with regards to selectivity, linearity, accuracy and precision, matrix effect, extraction recovery and stability, and was applied to comparing the pharmacokinetics of ultrafine granular powder (UGP), ultrafine powder (UP) and traditional decoction pieces (TDP) of AR after oral administration. The peak concentration and areas under the concentration-time curve of formononetin in UGP and UP were significantly higher than those of TDP. UGP and UP could significantly improve the bioavailability of AR in human compared with TDP after oral administration.

Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα).

Short-chain chlorinated paraffins (SCCPs) are frequently detected in environmental matrices and human tissues. It was hypothesized that SCCPs might interact with the peroxisome proliferator-activated receptor α (PPARα). In the present study, an in vitro, dual-luciferase reporter gene assay and in silico molecular docking analysis were employed together to study the interactions between SCCPs congeners and PPARα. Expressions of genes downstream in pathways activated by PPARα in liver of rats exposed to 1, 10, or 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) for 28 days were examined to confirm activation potencies of SCCPs toward PPARα signaling. Effects of exposure to C10-13-CPs (56.5% Cl) on fatty acid metabolism in rat liver were also explored via a pseudo-targeted metabolomics strategy. Our results showed that C10-13-CPs (56.5% Cl) caused a dose-dependent greater expression of luciferase activity of rat PPARα. Molecular docking modeling revealed that SCCPs had a strong capacity to bind with PPARα only through hydrophobic interactions and the binding affinity was dependent on the degree of chlorination in SCCPs congeners. In livers of male rats, exposure to 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) resulted in up-regulated expressions of 11 genes that are downstream in the PPARα-activated pathway and regulate catabolism of fatty acid. Consistently, accelerated fatty acid oxidation was observed mainly characterized by lesser concentrations of ∑fatty acids in livers of rats. Overall, these results demonstrated, for the first time, that SCCPs could activate rat PPARα signaling and thereby disrupt metabolism of fatty acid in livers of male rats.

A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway.

Stroke is a leading cause of disability and death in the worldwide. Therefore, prevention of stroke is critically important. Genistein, a natural phytoestrogen extracted from soybeans, has been found to be a potential neuroprotective agent for stroke prevention. However, the role of genistein and its underlying mechanism in ovariectomized rats has been rarely evaluated. In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. Seventy-two hours after reperfusion, the neurological function was evaluated by Garcia test, infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride staining; and neuronal damage and cell apoptosis were detected by Nissl and Tunel staining in the ischemic penumbra, respectively. In addition, Western blotting was used to detect the activity of PI3K-Akt-mTOR signal pathway in the ischemic penumbra in different groups. And we found that genistein treatment in ovariectomized rats significantly improved neurological outcomes, reduced infarct volumes, decreased neuronal damage and cell apoptosis, and increased the activity of PI3K-Akt-mTOR signal pathway. Our findings indicated that treatment genistein could alleviate neuronal apoptosis induced by cerebral ischemia in ovariectomized rats via promoting the activity of PI3K-Akt-mTOR signal pathway, which provides a new molecular mechanism for the neuroprotective effects of genistein against stroke.

An in vivo assay performed using multiple biomarkers related to testosterone synthesis and conversion for assessing the androgenic potency of refuse leachate.

Refuse leachate is likely an important source of androgens. However, common in vitro bioassays underestimate the potential androgenic activity of leachate, owing to non-receptor-mediated mechanisms that modify the balance of sex hormones and promote the accumulation of endogenous androgens. This study aimed to develop an in vivo assay by using multiple biomarkers related to testosterone synthesis and conversion for assessing the potential androgenic activity of refuse leachate sampled from a municipal solid waste treatment plant in Qingdao, China. The results indicated that exposure to leachate increased the levels of testosterone and luteinizing hormone, but decreased those of 17ß-estradiol in both male and female goldfish (Carassius auratus), suggesting a potential androgenic activity. Further, Leydig cell hyperplasia and decreased gonadal P450 aromatase mRNA levels were observed; these alterations might promote the biosynthesis of testosterone and hinder the conversion of testosterone to 17ß-estradiol, which in turn enhance testosterone accumulation. Exposure to leachate also resulted in reproductive impairments, including decreased gonadosomatic index and plasma vitellogenin levels of female goldfish, as well as decreased testicular enzyme activities in male goldfish. The integrated use of biochemical, molecular, and histological markers not only improved our understanding of the androgenic effects of leachate but also verified the reliability and validity of the results. Therefore, the in vivo bioassay described in this study might allow the investigation of the androgenic effects of other complex contaminant mixtures in the future.

Cr(III) removal by a microalgal isolate, Chlorella miniata: effects of nitrate, chloride and sulfate.

In the present study, nitrate, chloride and sulfate anion systems were used to investigate the presence of anions on the removal of Cr(III) by Chlorella miniata. Kinetic studies suggested that the equilibrium time of Cr(III) biosorption was not affected by the presence of different sodium salts, even at the concentration of 1.0 M, and all reached equilibrium after 24 h. Equilibrium experiments showed that the effects of different anions on Cr(III) biosorption varied, and the inhibitory order was SO4 (2-) > Cl(-) > NO3 (-). Langmuir isotherm indicated that the maximum sorption capacity of C. miniata increased with the increase of pH under different anion systems. The strongest inhibition effect of the sulfate system was attributed to the formation of Cr(OH)SO4 aq. and the decrease of Cr(OH)(2+) and Cr(3+) in solution, while the difference of inhibitory effect in the other two anion systems could be accounted by the formation of the inner-sphere surface complex in the nitrate system and the outer-sphere surface complex in the chloride system. The present study suggested that the presence of anions greatly affected the removal of Cr(III) on C. miniata and thereby their transport in the environment.

Recent developments of hydroxamic acid hybrids as potential anti-breast cancer agents.

Histone deacetylase inhibitors not only possess favorable effects on modulating tumor microenvironment and host immune cells but also can reactivate the genes silenced due to deacetylation and chromatin condensation. Hydroxamic acid hybrids as promising histone deacetylase inhibitors have the potential to address drug resistance and reduce severe side effects associated with a single drug molecule due to their capacity to simultaneously modulate multiple targets in cancer cells. Accordingly, rational design of hydroxamic acid hybrids may provide valuable therapeutic interventions for the treatment of breast cancer. This review aimed to provide insights into the in vitro and in vivo anti-breast cancer therapeutic potential of hydroxamic acid hybrids, together with their mechanisms of action and structure-activity relationships, covering articles published from 2020 to the present.

Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil-Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

Scrophularia ningpoensis Hemsl. holds a prominent place among Chinese medicinal herbs. Assessing the soil-plant system of its origin is crucial for ensuring medication safety. Although some trace elements are essential for the normal functioning of living organisms, exposure to higher concentrations is harmful to humans, so in order to assess the possible health risk of trace elements in the soil-plant system of Scrophularia ningpoensis Hemsl. origin for human assessment, we used non-carcinogenic risk (HI) and carcinogenic risk (CR) for their evaluation. In this paper, the following trace elements were studied in the soil-Scrophularia ningpoensis Hemsl. system: manganese (Mn), iron (Fe), cobalt (Co), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As) and lead (Pb). Correlation and structural equation analyses showed that the effect of soil in the root zone on the plant was much greater than the effect of soil in the non-root zone on the plant. The single-factor pollution index (Pi) showed that the soil in the production area of Scrophularia ningpoensis Hemsl. was polluted to a certain extent, notably with Pb showing the highest average Pi values of 0.94 and 0.89 in the non-root and root zones, respectively. Additionally, the Nemerow composite pollution indices (PN) for both zones indicated an alert range. Regarding health risks, exposure to soil in the non-root zone posed higher non-carcinogenic risk (HI) and carcinogenic risk (CR) compared to the root zone, although neither zone presented a significant carcinogenic risk. The potential non-carcinogenic risk (HI) and carcinogenic risk (CR) from consuming Scrophularia ningpoensis Hemsl. leaves and stems were more than ten times higher than that of roots. However, the carcinogenic risk (CR) values for both the soil and plant of interest in the soil- Scrophularia ningpoensis Hemsl. system did not exceed 10-4, and therefore no significant carcinogenic risk existed.