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In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu-Fang Huang reports was provided by National Science and Technology Council, Taiwan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

A new library of non-nitrocatechol compounds (HetCAMs) was developed and their efficacy was compared to tolcapone, a standard COMT inhibitor for PD. Compound 9 emerged as the most potent inhibitor, showing selective inhibition of brain (IC 50 = 24 nM) and liver (IC 50 = 81 nM) MB-COMT over liver S-COMT (IC 50 = 620 nM) isoforms. Although compound 9 presented higher IC 50 values than tolcapone, it was more selective for brain MB-COMT than liver S-COMT. Unlike tolcapone, compound 9 is not a tight-binding inhibitor and is less cytotoxic to HepG2 and SK-N-SH cells. Additionally, compound 9 is predicted to cross the blood-brain barrier (BBB) by passive diffusion and chelate divalent metals like Fe(II) and Cu(II). The results demonstrate the potential of this rational drug design strategy for developing new CNS-active drug candidates, offering symptom relief via COMT inhibition that can provide a long-term, disease-modifying outcome (chelation of divalent metals) in PD.

Photodynamic therapy (PDT) plays a crucial role in treating cancer and major infectious diseases. However, the hypoxic microenvironment and deep-seated tumors often compromise the effectiveness of photosensitizers (PSs). PSs primarily generate type-II reactive oxygen species (ROS), which are limited under hypoxic conditions. Pyridinium salts frequently exhibit critical dark toxicity in vitro . Moreover, PDT alone often fails to achieve optimal anti-tumor effects compared to its combined application with photothermal therapy (PTT). To address these issues, we replaced pyridinium with quinolinium, significantly reducing dark toxicity. Additionally, the incorporation of benzophenone enhanced ROS generation, achieving a synergistic effect of type-I and type-II PDT. Fine-tuning the conjugated structure enhanced the donor-acceptor (D-A) intensity, while the stretching vibrations of carbon-carbon double bonds and carbon-nitrogen triple bonds red-shifted the excitation wavelength to the near-infrared (NIR) region and improved the photothermal conversion efficiency (PCE). This strategy provides a molecular design approach for achieving synergy between PDT and PTT. The synthesized four NIR-emitting aggregation-induced emission quinolinium salts exhibited mitochondrial targeting ability and low dark toxicity. Among them, FCN-TPAQ-BP showed excellent ROS generation capability, a PCE of 39.2%, good biocompatibility, and low dark toxicity, making it an ideal candidate for enhancing PDT's antitumor efficacy.

Novel benzophenone-thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an ex vivo human whole-blood assay. All hybrids (3c and 5a-h) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone-thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising ex vivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors., (© 2024 John Wiley & Sons Ltd.)

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFβ, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1β). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Today, it would be difficult for us to live a full life without polymers, especially in medicine, where its applicability is constantly expanding, giving satisfactory results without any harm effects on health. This study focused on the formation of hexagonal domains doped with AgNPs using a KrF excimer laser (λ=248 nm) on the polyetheretherketone (PEEK) surface that acts as an unfailing source of the antibacterial agent - silver. The hexagonal structure was formed with a grid placed in front of the incident laser beam. Surfaces with immobilized silver nanoparticles (AgNPs) were observed by AFM and SEM. Changes in surface chemistry were studied by XPS. To determine the concentration of released Ag + ions, ICP-MS analysis was used. The antibacterial tests proved the antibacterial efficacy of Ag-doped PEEK composites against Escherichia coli and Staphylococcus aureus as the most common pathogens. Because AgNPs are also known for their strong toxicity, we also included cytotoxicity tests in this study. The findings presented here contribute to the advancement of materials design in the biomedical field, offering a novel starting point for combating bacterial infections through the innovative integration of AgNPs into inert synthetic polymers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The synthesis of benzimidazole compounds containing benzophenone group in accordance with the literature and the investigation of DNA binding properties of these compounds by using UV-vis and photoluminescence spectroscopy methods constitute the basis of this research. The structures of the compounds were determined by methods such as FT-IR, 1 H, 13 C NMR, UV- vis , Photoluminescence spectroscopy, and X-ray crystallography. By using methods such as UV- vis , Photoluminescence spectroscopy, and viscosity tests, information were collected about the binding types, binding mode, and binding energies of the compounds with DNA. In addition, the binding interactions of the compounds with DNA were investigated using the molecular docking technique. Using this information, calibration equations, correlation coefficients ( r 2 ), and DNA binding constants ( K b ) were calculated for their compounds. The binding constants ( K b ) calculated for substances A , B , and C were found to be 3.0 × 10 4 , 7.0 × 10 4 , and 3.0 × 10 4  M -1 , respectively. UV- vis , EB competitive binding, and viscosity tests showed that the compounds tended to bind to the DNA structure via the groove binding mode. At the end of molecular docking studies, it was determined that compound B showed the best DNA binding activity in in vitro studies. Compared with the studies in the literature, it is thought that the synthesized compounds can take place in cancer drug research as DNA binding agents.Communicated by Ramaswamy H. Sarma.

Bisphenols and benzophenones are two typical kinds of endocrine-disrupting compounds (EDCs) that have been extensively detected in water environments, posing unanticipated risks to aquatic organisms and humans. It is urgent to develop efficient sample pretreatment methods for precise measurement of such EDCs. In this study, a magnetic and multi-shelled metal-organic framework derivative material has been prepared to extract and enrich trace bisphenols and benzophenones from water. Via a solvothermal reaction induced by sodium citrate followed by a carbonization treatment, a ZIF-67@ZIF-8 derived CoZn-magnetic hierarchical carbon (CoZn-MHC) material has been synthesized as a high-performance magnetic solid-phase extraction (MSPE) adsorbent. This adsorbent exhibited a good specific surface area (213.80 m 2 ⋅g -1 ) and a saturation magnetization of 63.2 emu·g -1 . After the optimization of several parameters (including adsorbent dosage, extraction time, pH, ionic strength, desorption solvent, and solvent volume), an efficient MSPE method for several EDCs (comprising bisphenols and benzophenones) was developed with a good linear range (R 2  ≥ 0.990), a high sensitivity range (LODs: 0.793-5.37 ng⋅L -1 ), and good reusability (RSD ≤4.67 % in five consecutive tests). Furthermore, the material exhibited commendable resistance to matrix interference in natural water samples with the recovery rates of target compounds ranging from 74.8 % to 107 %. We envision that the preparation strategy of this functional metal-organic framework (MOF)-based adsorbent for EDCs may provide insights for relevant research in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, the demand for clinical bone grafting has increased. As a new solution for orthopedic implants, polyether ether ketone (PEEK, crystalline PAEK) has excellent comprehensive performance and is practically applied in the clinic. In this research, a noteworthy elevated scheme to enhance the performance of PEEK scaffolds is presented. The amorphous aggregated poly (aryl ether ketone) (PAEK) resin is prepared as the matrix material, which maintains high mechanical strength and can be processed through the solution. So, the tissue engineering scaffolds with multilevel pores can be printed by low-temperature deposited manufacturing (LDM) to improve biologically inert scaffolds with smooth surfaces. Also, the feature of PAEK's solution processing is profitable to uniformly add the functional components for bone repair. Ultimately, A system of orthopedic implantable PAEK material based on intermolecular interactions, surface topology, and surface modification is established. The specific steps include synthesizing PAEK that contain polar carboxyl structures, preparing bioinks and fabricating scaffolds by LDM, preparation of scaffolds with strontium-doped mineralized coatings, evaluation of their osteogenic properties in vitro and in vivo, and investigation on the effect and mechanism of scaffolds in promoting osteogenic differentiation. This work provides an upgraded system of PAEK implantable materials for clinical application., (© 2024 Wiley‐VCH GmbH.)

Protein phosphorylation is catalyzed by kinases to regulate cellular events and disease states. Identifying kinase-substrate relationships represents a powerful strategy to understand cell biology and disease yet remains challenging due to the rapid dynamics of phosphorylation. Over the last decade, several γ-phosphoryl modified ATP analogs containing crosslinkers were developed to covalently conjugate kinases, their substrates, and their associated proteins for subsequent characterization. Here, kinetics and crosslinking experiments demonstrated that the UV-activated analogs, ATP-aryl azide and ATP-benzophenone, offered the most robust crosslinking, whereas electrophilic ATP-aryl fluorosulfate promoted the most effective proximity-enabled crosslinking. The data will guide future applications of kinase-catalyzed crosslinking to study normal and disease biology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phytochemical investigations on the aerial parts of Hypericum cerastioides led to the isolation and identification of a novel normonoterpene (1) and a previously undescribed benzophenone glycoside (3) along with eleven known secondary metabolites (2, 4-13). Their structures were deduced based on extensive 1D and 2D NMR analyses as well as HRESIMS. Compound 1 is a rare type of normonoterpene derivative with eight carbon atoms. The chemotaxonomic significance of the isolates was also discussed. Compounds were evaluated for their in vitro cytotoxic activities against SW480, A375, DU145 and MCF7 cancer cell lines using doxorubicin as a reference drug. Compounds 1 and 7 demonstrated weak cytotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The repair of large bone defects poses a significant challenge in orthopedics. Polyetheretherketone (PEEK) is a promising bone substitute, while it suffers a lack of bioactivity. Although several studies have been performed to further improve the bioactivities of PEEK by various surface modifications, PEEK offering long-term, multifaceted biofunctionalities remains still desired. In this study, we introduced metal-organic frameworks (MOFs), specifically ZIF-8 loaded with celecoxib (ZIF-8(CEL)), onto the PEEK surface through dopamine adhesion. The resulting PEEK@ZIF-8(CEL) aims to achieve long-term stable release of Zn ions and CEL for enhanced bone integration. Material characterization and biological experiments confirmed the successful integration of ZIF-8(CEL) onto PEEK and its positive biomedical effects, including creating a positive bone immunological environment and promoting bone growth. This study demonstrates the potential of PEEK@ZIF-8(CEL) as a novel repair material for large bone defects, offering a promising alternative in orthopedic applications.

With the increasing demand for trace sample analysis, injecting trace samples into liquid chromatography-mass spectrometry (LC-MS) systems with minimal loss has become a major challenge. Herein, we describe an in situ LC-MS analytical probe, the Falcon probe, which integrates multiple functions of high-pressure sample injection without sample loss, high-efficiency LC separation, and electrospray. The main body of the Falcon probe is made of stainless steel and fabricated by the computer numerical control (CNC) technique, which has ultrahigh mechanical strength. By coupling a nanoliter-scale droplet reactor made of polyether ether ketone (PEEK) material, the Falcon probe-based LC-MS system was capable of operating at mobile-phase pressures up to 800 bar, which is comparable to those of conventional ultraperformance liquid chromatography (UPLC) systems. Using the probe pressing microamount in situ (PPMI) injection approach, the Falcon probe-based LC-MS system showed high separation efficiency and good repeatability with relative standard deviations (RSDs) of retention time and peak area of 1.8% and 9.9%, respectively, in peptide mixture analysis ( n = 6). We applied this system to the analysis of a trace amount of 200 pg of HeLa protein digest and successfully identified an average of 766 protein groups ( n = 5). By combining in situ sample pretreatment at the nanoliter range, we further applied the present system in single-cell proteomic analysis, and 241 protein groups were identified in single 293 cells, which preliminarily demonstrated its potential in the analysis of trace amounts of samples with complex compositions.

Photochemical transformation is an important attenuation process for the non-steroidal anti-inflammatory drug naproxen (NPX) in both engineered and natural waters. Herein, we investigated the photolysis of NPX in aqueous solution exposed to both ultraviolet (UV, 254 nm) and natural sunlight irradiation. Results show that N 2 purging significantly promoted NPX photolysis under UV irradiation, suggesting the formation of excited triplet state ( 3 NPX*) as a critical transient. This inference was supported by benzophenone photosensitization and transient absorption spectra. Sunlight quantum yield of NPX was only one fourteenth of that under UV irradiation, suggesting the wavelength-dependence of NPX photochemistry. 3 NPX* formed upon irradiation of NPX underwent photodecarboxylation leading to the formation of 2-(1-hydroxyethyl)-6-methoxynaphthalene (2HE6MN), 2-(1-hydroperoxyethyl)-6-methoxynaphthalene (2HPE6MN), and 2-acetyl-6-methoxynaphthalene (2A6MN). Notably, the conjugation and spin-orbit coupling effects of carbonyl make 2A6MN a potent triplet sensitizer, therefore promoting the photodegradation of the parent NPX. In hospital wastewater, the photolysis of NPX was influenced because the photoproduct 2A6MN and wastewater components could competitively absorb photons. Bioluminescence inhibition assay demonstrated that photoproducts of NPX exhibited higher toxicity than the parent compound. Results of this study provide new insights into the photochemical behaviors of NPX during UV treatment and in sunlit surface waters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 μm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED 50 s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The adenylation (A) domain of non-ribosomal peptide synthetases (NRPSs) catalyzes the adenylation reaction with substrate amino acids and ATP. Leveraging the distinct substrate specificity of A-domains, we previously developed photoaffinity probes for A-domains based on derivatization with a 5'-O-N-(aminoacyl)sulfamoyl adenosine (aminoacyl-AMS)-appended clickable benzophenone. Although our photoaffinity probes with different amino acid warheads enabled selective detection, visualization, and enrichment of target A-domains in proteomic environments, the effects of photoaffinity linkers have not been investigated. To explore the optimal benzophenone-based linker scaffold, we designed seven photoaffinity probes for the A-domains with different lengths, positions, and molecular shapes. Using probes 2-8 for the phenylalanine-activating A-domain of gramicidin S synthetase A (GrsA), we systematically investigated the binding affinity and labeling efficiency of the endogenous enzyme in a live producer cell. Our results indicated that the labeling efficiencies of probes 2-8 tended to depend on their binding affinities rather than on the linker length, flexibility, or position of the photoaffinity group. We also identified that probe 2 with a 4,4'-diaminobenzophenone linker exhibits the highest labeling efficiency for GrsA with fewer non-target labeling properties in live cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A challenge remains in the development of anti-infectious coatings for the inert surfaces of biomedical devices that are prone to bacterial colonization and biofilm formation. Here, a facile photocuring method to construct functionalized polymeric coatings on inert polydimethylsiloxane (PDMS) surfaces, is developed. Using atom transfer radical polymerization (ATRP) initiator bearing thymol group, hydrophilic DMAEMA and benzophenone (BP)-containing monomers are copolymerized to form polymers with end functional groups. An end-functionalized biocidal coating is then constructed on the inert PDMS surface in one step using a photocuring reaction. The functionalized PDMS surfaces show excellent antibacterial and antifouling properties, are capable of completely eradiating MRSA within ≈6 h, and effectively inhibit the growth of biofilms. In addition, they have good stability and long-lasting antibacterial activity in body fluid environments such as 0.9% saline and urine. According to bladder model experiments, the catheter's lifespan can be extended from ≈7 to 35 days by inhibiting the growth and migration of bacteria along its inner surface. The photocuring technique is therefore very promising in terms of surface functionalization of inert biomedical devices in order to minimize the spread of infection., (© 2024 Wiley‐VCH GmbH.)

Implant-associated infections and excessive immune responses are two major postsurgical issues for successful implantation. However, conventional strategies including antibiotic treatment and inflammatory regulation are always compromised due to the comodification of various biochemical agents and instances of functional interference. It is imperative to provide implant surfaces with satisfactory antibacterial and anti-inflammatory properties. Here, a dual-effect nanostructured polyetheretherketone (PEEK) surface (NP@PDA/Zn) with bionic mechano-bactericidal nanopillars and immobilized immunomodulatory Zn 2+ is designed. The constructed hybrid nanopillars display remarkable antibacterial performance against Gram-negative and Gram-positive strains through the synergy of physical and chemical bactericidal effects imposed by nanopillars and Zn 2+ . Meanwhile, the immunoregulatory property is evaluated through the investigation of macrophage polarization both in vitro and in vivo, and the results reveal that NP@PDA/Zn could downregulate the expression of M1-related cytokines and decrease the M1 macrophage recruitment to lower the inflammatory response. Notably, the surface exhibited exceptional biocompatibility with discerning biocidal activity between bacterial and mammalian cells and antioxidant performance that effectively scavenges ROS, minimizing potential cytotoxicity. Taken together, NP@PDA/Zn presents a convenient and promising strategy of combining synergistic bactericidal activity and inflammatory regulation without any mutual interference, which can support the development of multifunctional implant-associated materials.

Effective removal of organic UV filters from aquatic environmental compartments and swimming waters is very important because these substances are hazardous to humans and wildlife at low concentrations and act as endocrine disruptors. Therefore, the aim of the present article is to determine the extraction efficiencies of hydrophobic deep eutectic solvents (HDES) for the selected UV filters based on benzophenone structure (benzophenone, 2,4-dihydroxybenzophenone, 2,2´,4,4´-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2´-dihydroxy-4-methoxybenzophenone, 4-methacryloxy-2-hydroxybenzophenone) from aqueous matrices. For this purpose, six HDESs based on dl-menthol in combination with caprylic, decanoic and lauric acid are prepared and compared with referent terpene solvents such as terpineol and linalool. The effect of various parameters such as HDES composition, volume ratio, frequency and shaking time are studied. The highest extraction efficiency is shown by HDES of menthol:caprylic acid (1:1) composition at the aqueous:organic phase volume ratio of 1:1, shaking frequency of 1500 rpm and shaking time of 15 min. The achieved extraction efficiencies are higher than 99.6 % for all benzophenones studied in the purification of stagnant pond water, swimming pool water and river water samples. After a simple and fast sample treatment, the residual levels of benzophenones in the waters are controlled by a newly developed sensitive HPLC-MS/MS method with LOQs in the range of 0.7 - 5.0 ng/mL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Benzophenone chemicals (BPs) have been developed to prevent the adverse effects of UV radiation and they are widely contaminated. 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyze the conversion of inactive glucocorticoid to active glucocorticoid, playing critical role in many physiological function. However, the direct effect of BPs on human, pig, rat, and mouse 11β-HSD1 remains unclear. In this study, we screened the inhibitory strength of 12 BPs on 4 species, and performed the structure-activity relationship (SAR) and in silico docking analysis. The inhibitory potency of BPs was: for human 11β-HSD1, BP6 (IC 50  = 18.76 μM) > BP8 (40.84 μM) > BP (88.89 μM) > other BPs; for pig 11β-HSD1, BP8 (45.57 μM) > BP6 (59.44 μM) > BP2 (65.12 μM) > BP (135.56 μM) > other BPs; for rat 11β-HSD1, BP7 (67.17 μM) > BP (68.83 μM) > BP8 (133.04 μM) > other BPs; and for mouse 11β-HSD1, BP8 (41.41 μM) > BP (50.61 μM) > other BPs. These BP chemicals were mixed/competitive inhibitors of these 11β-HSD1 enzymes. The 2,2'-dihydroxy substitutions in two benzene rings play a key role in enhancing the effectiveness of inhibiting 11β-HSD1, possibly via increasing hydrogen bond interactions. Docking analysis shows that these BPs bind to NADPH/glucocorticoid binding sites and forms hydrogen bonds with catalytic residues Ser and/or Tyr. In conclusion, this study demonstrates that BP chemicals can inhibit 11β-HSD1 from 4 species, and there are subtle species-dependent difference in the inhibitory strength and structural variations of BPs., Competing Interests: Declaration of competing interest We have no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Two new benzophenone derivatives ( 1 and 2 ), named Pogonatone C and pogonatone D , were isolated from the moss Pogonatum spinulosum . Their structures were elucidated by spectroscopic data analyses. The cytotoxicity of compounds for HepG2, HCT-116, A-549 and PANC-1 cells line was also evaluated by using the MTT method. Pogonatone C ( 1 ) displays high cytotoxicity on PANC-1 cell with IC 50 value of 9.2 μM.

Natural and synthetic polymeric materials, particularly soft and hard tissue replacements, are paramount in medicine. We prepared calcium-incorporated sulfonated polyether-ether ketone (SPEEK) polymer membranes for bone applications. The bioactivity was higher after 21 days of immersion in simulated body fluid (SBF) due to calcium concentration in the membrane. We present a new biomaterial healing system composed of calcium and sulfonated polyether ether ketone (Ca-SPEEK) that can function as a successful biomaterial without causing inflammation when tested on bone marrow cells. The Ca-SPEEK exhibited 13 ± 0.5% clot with low fibrin mesh formation compared to 21 ± 0.5% in SPEEK. In addition, the Ca-SPEEK showed higher protein adsorption than SPEEK membranes. As an inflammatory response, IL-1 and TNF-α in the case of Ca-SPEEK were lower than those for SPEEK. We found an early regulation of IL-10 in the case of Ca-SPEEK at 6 h, which may be attributed to the down-regulation of the inflammatory markers IL-1 and TNF-α. These results evidence the innovative bioactivity of Ca-SPEEK with low inflammatory response, opening venues for bone applications., (© 2024 The Author(s).)

Polyetheretherketone (PEEK), particularly its sulfonated form (SPEEK), has emerged as a promising synthetic biomaterial for artificial bone implants, providing an alternative to conventional titanium metal. However, postoperative infections pose a critical challenge, driven by diverse and antibiotic-resistant bacteria. To address this issue, we propose the modification of the SPEEK surface using a thin graphene oxide (GO) film containing silver (Ag) ions. The resulting coating exhibits substantial antibacterial effects against various pathogens, including Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Candida albicans . Experimental assessments elucidate the coating's impact on bacterial adhesion, biofilm formation, and morphology. The results suggest that hindered bacterial growth stems from reduced biofilm production and the controlled release of Ag ions facilitated by the GO coating. The Ag/GO-SPEEK material holds promise as a bioactive implant, addressing the challenges associated with bacterial targeting in bone tissue engineering applications.

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum , and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso -guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold ( iso -guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study presents new insights into the potential role of polyelectrolyte interfaces in regulating low friction and interstitial fluid pressurization of cartilage. Polymer brushes composed of hydrophilic 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a PEEK substrate (SPMK- g -PEEK) are a compelling biomimetic solution for interfacing with cartilage, inspired by the natural lubricating biopolyelectrolyte constituents of synovial fluid. These SPMK- g -PEEK surfaces exhibit a hydrated compliant layer approximately 5 μm thick, demonstrating the ability to maintain low friction coefficients (μ ∼ 0.01) across a wide speed range (0.1-200 mm/s) under physiological loads (0.75-1.2 MPa). A novel polyelectrolyte-enhanced tribological rehydration mechanism is elucidated, capable of recovering up to ∼12% cartilage strain and subsequently facilitating cartilage interstitial fluid recovery, under loads ranging from 0.25 to 2.21 MPa. This is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behavior of polymer brushes. Contrary to conventional theories that emphasize interstitial fluid pressurization in regulating cartilage lubrication, this work demonstrates that SPMK- g -PEEK's frictional behavior with cartilage is independent of these factors and provides unabating aqueous lubrication. Polyelectrolyte-enhanced tribological rehydration can occur within a static contact area and operates independently of known mechanisms of cartilage interstitial fluid recovery established for converging or migrating cartilage contacts. These findings challenge existing paradigms, proposing a novel polyelectrolyte-cartilage tribological mechanism not exclusively reliant on interstitial fluid pressurization or cartilage contact geometry. The implications of this research extend to a broader understanding of synovial joint lubrication, offering insights into the development of joint replacement materials that more accurately replicate the natural functionality of cartilage.

Polyetheretherketone (PEEK), as a high-performance polymer, is widely used for bone defect repair due to its homogeneous modulus of elasticity of human bone, good biocompatibility, excellent chemical stability and projectability. However, the highly hydrophobic surface of PEEK is biologically inert, which makes it difficult for cells and proteins to attach, and is accompanied by the development of infections that ultimately lead to failure of PEEK implants. In order to further enhance the potential of PEEK as an orthopedic implant, researchers have explored modification methods such as surface modification by physical and chemical means and the addition of bioactive substances to PEEK-based materials to enhance the mechanical properties, osteogenic activity and antimicrobial properties of PEEK. However, these current modification methods still have obvious shortcomings in terms of cost, maneuverability, stability and cytotoxicity, which still need to be explored by researchers. This paper reviews some of the modification methods that have been used to improve the performance of PEEK over the last three years in anticipation of the need for researchers to design PEEK orthopedic implants that better meet clinical needs.

Benzophenone-4 (BP-4) is one of the UV filters widely used in personal care products (PCPs). BP-4 has been identified as an emergent contaminant detected in influent and effluent of wastewater treatment plants (WWTPs) at high concentrations showing that conventional treatment is unable to remove it, subsequently, the presence of BP-4 in surface water is inevitable. In this study, we focus on the degradation of this compound by chlorine, and we report the efficiency of its removal from water by applying two advanced oxidation processes UV/TiO 2 and UV/H 2 O 2 aiming to achieve a superior mineralization result. The study was performed in purified water (pH = 6.5, temperature = 25 °C) with an initial concentration of BP-4 similar to that detected in WWTPs (10 mg/L). The results showed that 76% of BP-4 was degraded after 80 min of reaction with chlorine leading to the formation of one by-product persistent in the solution. The oxidation by UV/TiO 2 and UV/H 2 O 2 led to a total removal of BP-4 and their generated by-products after 50 and 10 min of reactions, respectively. The kinetic study showed that BP-4 degradation by UV/H 2 O 2 and UV/TiO 2 followed pseudo-first-order reaction kinetics and the apparent rate constants (k app ) were determined to be 0.48 min -1 and 0.08 min -1 , respectively. The degradation of BP-4 by chlorine followed first-order reaction kinetics with k app = 0.02 min -1 . The identification of by-product structures was performed using liquid chromatography with electrospray ionization and tandem mass spectrometry (MS/MS. The fragmentation of BP-4 and by-product ions at different collision energies allowed to propose the pathways of degradation and to predict the toxicity using a silico toxicity program which confirmed a higher toxicity of all generated by-products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives., Objectives: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages., Material and Methods: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1 H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics., Results: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 μg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 μg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 μg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids., Conclusion: To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed., (© 2023 The Authors. Phytochemical Analysis published by John Wiley & Sons Ltd.)

The fate of selected UV filters (UVFs) was investigated in two soil aquifer treatment (SAT) systems, one supplemented with a reactive barrier containing clay and vegetable compost and the other as a traditional SAT reference system. We monitored benzophenone-3 (BP-3) and its transformation products (TPs), including benzophenone-1 (BP-1), 4,4'-dihydroxybenzophenone (4DHB), 4-hydroxybenzophenone (4HB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), along with benzophenone-4 (BP-4) and avobenzone (AVO) in all involved compartments (water, aquifer sediments, and biofilm). The reactive barrier, which enhances biochemical activity and biofilm development, improved the removal of all detected UVFs in water samples. Among monitored UVFs, only 4HB, BP-4, and AVO were detected in sediment and biofilm samples. But the overall retained amounts were several orders of magnitude larger than those dissolved. These amounts were quantitatively reproduced with a specifically developed simple analytical model that consists of a mobile compartment and an immobile compartment. Retention and degradation are restricted to the immobile water compartment, where biofilm absorption was simulated with well-known compound-specific K ow values. The fact that the model reproduced observations, including metabolites detected in the biofilm but not in the (mobile) water samples, supports its validity. The results imply that accumulation ensures significant biodegradation even if the degradation rates are very low and suggest that our experimental findings for UVFs and TPs can be extended to other hydrophobic compounds. Biofilms act as accumulators and biodegraders of hydrophobic compounds.

Pesticide deposits post-treatment and before diffusing inside the plants are exposed to sunlight. Many of them degrade into a variety of photoproducts that may be harmful to living beings through accidental ingestion. The addition of ultraviolet light absorbers to the pesticide formulations is an attractive strategy to prevent photodegradation of the pesticides. Water-soluble quaternary ammonium ultraviolet light absorbers (QAUVAs) were synthesized from 2,4-dihydroxy benzophenones (BP-1) and their structures were confirmed by 1 H NMR, 13 C NMR, UV, and FTIR. A cost-saving approach for the photoprotection of disulfoton insecticide using these QAUVAs is presented. All the four QAUVAs exhibit excellent UV screening effect. The insecticide disulfoton was recovered in much higher amounts (22.27 ~ 25.64% higher than control) when it was irradiated in the presence of QAUVAs in comparison with the amount of recovery of pesticide exposed in absence of them., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The chemistry of Costa Rican propolis from Apis mellifera remains underexplored despite its potential applications. This study identified its chemical composition, linking chemotypes to antioxidant potential., Methods: Proton nuclear magnetic resonance ( 1 H NMR) spectra were obtained for 119 propolis extracts and analyzed using multivariate analyses. In parallel, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was used to assess antioxidant activity. A generalized linear regression model (GLM) correlated this with its chemical profiles and geographical origin. Chromatographic methods were used to isolate active and inactive compounds, which were identified using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS)., Results: Principal component analysis (PCA) revealed three chemical profile groups for the 119 propolis extracts, explaining 73% of the total variance with two components. Radical scavenging activity was found to correlate with chemical composition. Isolation yielded n -coniferyl benzoate in type I (EC 50 = 190 µg/mL, ORAC = 0.60 µmol TE/µmol) and nemorosone in type II (EC 50 = 300 µg/mL, ORAC = 0.7 µmol TE/µmol). Type III was represented in terpene-like components, which exhibited lower antioxidant activity., Conclusions: This study categorizes Costa Rican propolis into three chemical types and identifies two key components linked to antioxidant activity. Notably, nemorosone, a valuable natural product, was found to be highly concentrated in a particular region of Costa Rica.

To carry out risk assessments of benzophenone-type UV filters (BPs), fast and accurate analytical methods are crucial to determine and monitor levels in the environment. This study presents an LC-MS/MS method that requires minimal sample preparation and yet can identify 10 different BPs in environmental samples such as surface or wastewater resulting in a LOQ range from 2 to 1060 ng/L. The method suitability was tested through environmental monitoring, which showed that, BP-4 is the most abundant derivative found in the surface waters of Germany, India, South Africa and Vietnam. BP-4 levels correlate with the WWTP effluent fraction of the respective river for selected samples in Germany. Peak values of 171 ng/L for 4-hydroxybenzophenone (4-OH-BP), as measured in Vietnamese surface water, already exceed the PNEC value of 80 ng/L, elevating 4-OH-BP to the status of a new pollutant that needs more frequent monitoring. Moreover, this study reveals that during biodegradation of benzophenone in river water, the transformation product 4-OH-BP is formed which contain structural alerts for estrogenic activity. By using yeast-based reporter gene assays, this study provides bio-equivalents of 9 BPs, 4-OH-BP, 2,3,4-tri-OH-BP, 4-cresol and benzoate and complements the existing structure-activities relationships of BPs and their degradation products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop "greener" PIs with high efficiency, low migration, and low toxicity.

Ten undescribed benzophenones, schomburginones A-J, together with 14 known analogs were isolated from the leaves of Garcinia schomburgkiana, an edible plant native to the Indochina region. The structures of the undescribed compounds were elucidated by NMR combined with HRMS spectroscopy, while their absolute configurations were determined using ECD and single-crystal X-ray diffraction analysis. The isolated metabolites represent benzophenone derivatives containing a modified monoterpene unit, including tri- and tetracyclic skeletons, which are rarely found in genus Garcinia. The cytotoxic evaluation on three cancerous cell lines demonstrated that schomburginone G, schomburginone H, and 3-geranyl-2,4,6-trihydroxybenzophenone were active against HeLa cells with IC 50 values in the range of 12.2-15.7 μM, respectively, and selective compared to the non-cancerous L929 cells (SI > 3.5). In addition, the three cytotoxic compounds together with clusiacyclol A showed significant NO inhibitory activity in RAW 264.7 macrophage cells over 85% inhibition without obvious cytotoxicity at a final concentration of 100 μM. The promising activities of these compounds in cytotoxic and anti-inflammatory assays make them attractive for further study in the development of anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Here, we report the detailed mechanisms of benzophenone (BZP) photosensitized thymine damage and repair by Paternò-Büchi (PB) cycloaddition. It was found that the head-to-head and head-to-tail PB cycloadditions lead to the formation of the C-O bonds in the 3 (nπ*) state and the 3 (ππ*) state, respectively. The conical intersection occurs before the head-to-tail C-O bonding. Then, the C-C bonds are formed via intersystem crossing (ISC). The C-O bonding is the rate-determining step of PB cycloaddition. For the cycloreversion reactions, the ring-opening processes completely occur in the singlet excited states of oxetanes. The head-to-head oxetane goes through a conical intersection before cycloreversion with a little energy barrier of 1.8 kcal mol -1 . The head-to-tail oxetane splits without a barrier. Then, the ISC processes take place to restore thymine. Throughout the ring-closing and ring-opening processes, ISC plays an important role. These findings are in good agreement with the available experimental findings. We hope that this comprehensive work can provide a deeper understanding of photosensitive DNA damage and repair.

Nemorosone is a bicyclic polyprenylated acylphloroglucinol derivative originally isolated from Clusia spp. and it can be obtained through chemical synthesis employing different synthetic strategies. Since its discovery, it has attracted great attention both from a biological and chemical viewpoint. In the present article, we attempted to review various chemical and biological topics around nemorosone, with an emphasis on its antiproliferative activities. For this purpose, relevant data was collected from different scientific databases including Google Scholar, PubMed, Scopus and ISI Web of Knowledge. This natural compound has shown activity against several types of malignancies such as leukemia, human colorectal, pancreatic, and breast cancer because it modulates multiple molecular pathways. Nemorosone has both cytostatic and cytotoxic activity and it also seems to induce apoptosis and ferroptosis. Additionally, it has antimicrobial capabilities against Gram-positive bacteria and parasites belonging to genus Leishmania. Its promising antiproliferative pre-clinical effects deserve further attention for anticancer and anti-parasitic drug development and translation to the clinic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.

Benzophenone-type UV filters (BPs) are common in natural aquatic environments. They can cause endocrine disruption or other adverse effects once they enter the human body via the food chain or drinking water. The primary cause of BPs accumulation and toxicity is the transport of BPs into the human body. Functional group substitutions can have a significant impact on the interactions of BPs and transporters, resulting in a variety of impact effects. Therefore, we explored the interaction between human serum albumin (HSA, a typical transporter) and ten typical BPs [benzophenone (BP1), 2-hydroxybenzophenone (BP2), 4-hydroxybenzophenone (BP3), 2,2'-dihydroxybenzophenone (BP4), 2,4-dihydroxybenzophenone (BP5), 4,4'-dihydroxybenzophenone (BP6), 2,4,4'-trihydroxybenzophenone (BP7), 2,2',4,4'-tetrahydroxybenzophenone (BP8), 2-hydroxy-4-methoxybenzophenone (BP9), and 2,2'-dihydroxy-4-methoxybenzophenone (BP10)] to study the role of functional group substitutions in binding. The results showed that BPs could bind to HSA at site 2, with binding constants ranging from 2.01 × 10 3 to 4.57 × 10 5  L/mol. Compared to BP1, hydroxyl and methoxy substitutions enhanced the BPs-HSA binding. The combined effect of the number and site of hydroxyl substitution at BPs determined the binding strength between BPs and HSA. It was more accessible to bind HSA when BPs were substituted with para-hydroxyl (4-hydroxyl) groups than with ortho-hydroxyl (2-hydroxyl) groups. Moreover, the additional para-methoxy (4-methoxy) group increased the BP-HSA binding strength by approximately 47 times under the same hydroxyl substitution conditions. Theoretical calculations revealed that functional group substitutions increased the intermolecular binding force by increasing the negative electrostatic potential surface area of BPs, which significantly increased the electrostatic and dispersion forces between the BPs and HSA. This BPs-HSA binding decreased the α-helix of HSA and influenced the ratio of other secondary structures, including β-sheet, β-turn, and random coil of HSA. This study provides a theoretical and experimental foundation for understanding the human health risks associated with BPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure-activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21' induce apoptosis was studied. Cambogin and 21' were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21' might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ten common benzophenone-based UV filters (BPs), sharing the same basic structure and differing only in their substituents, were investigated with respect to their primary and ultimate biodegradability. This study was carried out in order to gain deeper insights into the relationship between structure and biodegradability. The primary biodegradation of the selected BPs was studied in river water at environmentally relevant concentrations (1 µg/L) while varying specific, crucial environmental conditions (aerobic, suboxic, supplementation of nutrients). For this purpose, both batch and column degradation tests were performed, which allowed a systematic study of the effects. Subsequently, the ultimate biodegradation, i.e. the potential to achieve full mineralization of BPs, was examined according to OECD guideline 301 F. The results indicate that mineralization is limited to derivatives in which both aromatic rings contain substituents. This hypothesis was supported by docking simulations showing systematic differences in the orientation of BPs within the active site of the cytochrome P450 enzyme. These differences in orientation correspond to the substitution pattern of the BPs. This study provides valuable insights for assessing the environmental hazards of this class of trace organic compounds., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate the mechanical properties of porous polyetherketoneketone (PEKK) meshes with different thicknesses, pore sizes, and porosities through finite element analysis to provide an optimal PEKK design for alveolar bone augmentation in the posterior mandibular region., Methods: A three-dimensional evaluation model of severe alveolar bone defects in the mandibular posterior was constructed based on cone beam computerized tomography (CBCT) data. Then, PEKK meshes with different structural designs were obtained. Two key parameters were set with different values: five levels of thickness (0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, and 0.6 mm) and three levels of pore size (1 mm, 2 mm, and 3 mm) with a corresponding porosity of 19.18%-42.67%. A 100 N physiological force was simultaneously loaded by finite element analysis (FEA), and the deformation and stress data were outputted for further analysis., Results: The deformation and stress of the PEKK meshes are negatively correlated with the changes in thickness and positively correlated with the changes in pore size. The FEA results show that the maximum deformation, equivalent stress, and maximum principal stress of the PEKK meshes are 0.168 mm-0.478 mm, 49.243 MPa-124.890 MPa, and 31.549 MPa-104.200 MPa, respectively. The PEKK mesh group with a thickness of 0.2 mm, pore size of 3 mm, and porosity of 42.67% is in danger of plastic deformation or even fracture during use., Conclusion: According to the FEA results, the PEKK meshes with larger thicknesses and smaller pore sizes and porosities behave better. In consideration of reducing soft tissue stimulation and promoting bone regeneration, an ultrathin porous PEKK mesh with a pore size of no more than 3 mm, porosity of no more than 42.67%, and thickness of 0.2 mm can be used clinically to meet the mechanical performance requirements of the guided bone regeneration (GBR) structure., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Xiaowen Hao et al.)

The ubiquitous presence of emerging contaminants in the environment is an issue of great concern. Notably, for some of them, no established regulation exists. Benzophenones are listed as emerging contaminants, which have been identified in the environment as well as in human fluids, such as urine, placenta, and breast milk. Their accumulation and stability in the environment, combined with the revealed adverse effects on ecosystems including endocrine, reproductive, and other disorders, have triggered significant interest for research. Benzophenones should be extracted from environmental samples and determined for environmental-monitoring purposes to assess their presence and possible dangers. Numerous sample preparation methods for benzophenones in environmental matrices and industrial effluents have been proposed and their detection in more complex matrices, such as fish and sludges, has also been reported. These methods range from classical to more state-of-the-art methods, such as solid-phase extraction, dispersive SPE, LLE, SBSE, etc., and the analysis is mostly completed with liquid chromatography, using several detection modes. This review critically outlines sample preparation methods that have been proposed to date, for the extraction of benzophenones from simple and complex environmental matrices and for cleaning up sample extracts to eliminate potential interfering components that coexist therein. Moreover, it provides a brief overview of their occurrence, fate, and toxicity.

Oxybenzone, a common ultraviolet (UV) filter, is a growing environmental concern due to its ecotoxicological effects. However, the responses of Symbiodiniaceae and their bacterial communities to oxybenzone are largely unknown. In this study, the effects of oxybenzone on Effrenium voratum and Cladocopium goreaui were investigated. The results revealed that sensitivity of Symbiodiniaceae to oxybenzone was species-dependent. 50 μg L -1 of oxybenzone significantly impacted the cell density of C. goreaui, causing a 36.73% decrease. When oxybenzone concentration increased to 500 μg L -1 and 5000 μg L -1 , cell division was completely suppressed; meanwhile, chl-a content declined to zero. Compared to C. goreaui, E. voratum had higher resistance to oxybenzone. There was no significant difference in cell density between 50 μg L -1 group and control group. At higher dosage of oxybenzone (500 μg L -1 and 5000 μg L -1 ), the cell density declined 32.02% and 45.45% compared to the control group, respectively. Additionally, we revealed that the diversity and structure of bacterial community were affected by oxybenzone. Briefly, 500 μg L -1 and 5000 μg L -1 of oxybenzone altered the diversity of bacterial community in C. goreau. Furthermore, the relative abundances of Costertonia, Roseitalea, Rhodopirellula, and Roseobacter were negatively affected by oxybenzone ranging 50 μg L -1 to 5000 μg L -1 . Compare to C. goreaui, the bacterial community composition associated with E. voratum was more stable. As revealed by KEGG pathway analysis, oxybenzone affected energy metabolism and inhibited the metabolism of cofactors and vitamins in C. goreaui, while 5000 μg L -1 of oxybenzone significantly altered the carbohydrate metabolism, membrane transport and amino acid metabolism in E. voratum. The changes of bacterial composition may contribute to the variation in algal growth. These results indicated that oxybenzone pollution could injury Symbiodiniaceae, even threaten coral reef ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Two new polyisoprenylated benzophenones, planchoniones A ( 1 ) and B ( 2 ), together with two known benzophenones ( 3, 4 ) and six known xanthones ( 5-10 ), were isolated from an ethyl acetate extract of the pericarp of Garcinia planchonii Pierre. Their structures were established using spectroscopic methods, mainly 1D and 2D NMR. The four benzophenones were evaluated for their cytotoxicity against MCF-7 human breast cancer cells, and showed almost no activity. Meanwhile, compounds 5 - 10 were investigated for their inhibitory effects towards α-glucosidase, and γ-mangostin (5) exhibited the most remarkable effect with IC 50 value of 15.3 ± 0.9 µM (compared with acarbose, IC 50 = 224.9 ± 3.6 µM).

Two new benzophenone glycosides, hypersens A and B, along with four known compounds, ( S )-(+)-5,7-dihydroxy-2-(1-methylpropyl) chromone ( 3 ), 5,7-dihydroxy-2-isopropylchromone ( 4 ), urachromone B ( 5 ), and 3-8'' bisapigenin ( 6 ), were isolated from Hypericum seniawinii . The structures of new compounds ( 1 and 2 ) were elucidated according to comprehensive spectroscopic data analyses. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. All isolated compounds were evaluated for their neuroprotective effect using corticosterone-induced PC12 cell injury. In addition, compounds 1 - 6 were evaluated for their anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 cells. Compound 6 was a biflavonoid and significantly inhibited the production of nitric oxide with an IC 50 value of 11.48 ± 1.23 μM.

Data from globocan statistic in 2020 indicate that breast cancer has become highest incidence rate of cancer. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are known immunohistochemistry (IHC) markers that mediate cell growth and survival signaling. Furthermore, regulator proteins, receptors, and their downstream signaling pathways have emerged as critical components in breast cancer formation and proliferation, and have become well-established therapeutic targets and the core focus of breast cancer therapy research. Garcinia is a big genus in the Clusiaceae family that contains a wide spectrum of biologically active metabolites for the chemical composition of their isolated fruits, stem barks, seeds, leaves, and roots, have resulted including polyisoprenylated benzophenones, polyphenols, bioflavonoids, xanthones, lactones, and triterpenes. This review article aimed to analyze the potential of Garcinia phytochemicals as a molecular therapy of breast cancer. The results showed that phytochemicals of Garcinia (i.e., α-mangostin, Cambogin, Gambogic Acid [GA], Garcinol, Griffipavixanthone, Friedolanostane triterpenoid, Hexane, Neobractatin, 7-Epiclusianone, xanthochymol - guttiferone E, and isoxanthochymol - cycloxanthochymol) have anticancer properties, including apoptosis, inhibition of proliferation, and metastasis. This review is important to provide information regarding phytochemicals of Garcinia as an alternative treatment for breast cancer patients. This article selected 28 article researches based on inclusion criteria with the keyword "Garcinia" and "Breast cancer", in English, and available in full text and abstract searching on PubMed., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Triyasa et al.)

The hydrogen atom transfer reaction (HAT) between selected benzophenones (benzophenone BP, 3-carboxybenzophenone 3CB, and 4-carboxybenzophenone 4CB) and 2-propanol was reinvestigated focusing on stable product analysis. As expected, the primary species of these HAT's are the respective diphenyl and dimethyl ketyl radicals that eventually undergo several radical coupling reactions leading to stable photoproducts. However, the mechanisms of these free radical reactions remain unclear and open to question. In this report, we focus on the detailed analysis of the stable photoproducts of these reactions using liquid chromatography coupled with high-resolution mass spectrometry (LC-ESI-QTOF-MS/MS). Products of photopinacolization (benzpinacol and two diastereoisomers of 4CB and 3CB dimers) and isomeric radical cross-coupling adducts of respective diphenyl and dimethyl ketyl radicals were separated chromatographically, and their structures were determined by high-resolution MS/MS, and the mechanisms of the reactions are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Plants of the genus Hypericum contain various types of secondary metabolites that exhibited extensive biological activities. In the ongoing efforts to discover natural neuroinflammatory inhibitors with the potential to develop into therapeutic agents for neurodegenerative diseases, two new benzophenone glycosides, hyperewalones A and B ( 1 and 2 ), along with eight known compounds ( 3-10 ), were isolated from the aerial parts of Hypericum przewalskii . Their structures were elucidated by comprehensive analysis of IR, HRESIMS, 1D and 2D NMR spectra, and chemical derivatization. The anti-neuroinflammatory activity of compounds 1 - 10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Compounds 2 , 4 , 6 - 8 exhibited significant anti-neuroinflammatory activity with IC 50 values of 0.61-4.90 μM. These findings suggest that the benzophenone, ionone, and flavonoid glycosides isolated from H. przewalskii are promising anti-neuroinflammatory compounds worthy of further investigations.

As a class of possible carcinogens, benzophenone-type UV filters (BPs) widely exist in natural environments and organisms. The crucial step of the carcinogenic process induced by cancerous toxins is binding with DNA to form adducts. Here, the binding of 10 typical BPs, i.e., benzophenone (BP1), 2-hydroxyl benzophenone (BP2), 4-hydroxyl benzophenone (BP3), 2,2'-dihydroxyl benzophenone (BP4), 2,4-dihydroxyl benzophenone (BP5), 4,4'-dihydroxyl benzophenone (BP6), 2,4,4'-trihydroxyl benzophenone (BP7), 2,2',4,4'-tetrahydroxyl benzophenone (BP8), 2-hydroxyl-4-methoxyl benzophenone (BP9), and 2,2'-dihydroxyl-4-methoxyl benzophenone (BP10), with DNA was tested via fluorescence quenching experiments. Only hydroxyl group-substituted BPs could bind to DNA by groove binding mode, and the quenching constants were 0.93 × 10 3 -5.89 × 10 3  L/mol. Substituted BPs were preferentially bound to thymine. Circular dichroism analysis confirmed that BPs could affect DNA base stacking but could not transform its B-form. Based on molecular electrostatic surface potential analyses, molecular dynamics simulations, and energy decomposition calculations, it could be found that the site and number of hydroxyl substitution changed the molecular polarity of BPs, thereby affecting the number and strength of hydrogen bonds between BPs and DNA. The hydroxyl substitution at site 2 was more conducive to binding than at site 4. This study is beneficial in comprehending the carcinogenic mechanisms of BPs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)