Supercritical Fluid-extracted Citrus aurantium L. var. amara Engl. Essential Oil Nanoemulsion: Preparation, Characterization, and Its Sleep-promoting Effect.

To overcome the defects of Citrus aurantium L. var. amara Engl. essential oil (CAEO), such as high volatility and poor stability, supercritical fluid-extracted CAEO nanoemulsion (SFE-CAEO-NE) was prepared by the microemulsification method. Emulsifiers comprising Tween 80, polyoxyethylenated castor oil (EL-40), and 1,2-hexanediol, and an oil phase containing SFE-CAEO were used for microemulsification. We examined the physicochemical properties of SFE-CAEO-NE and steam distillation-extracted CAEO nanoemulsion (SDE-CAEO-NE), which were prepared using different concentrations of the emulsifiers. The mean particle size and zeta potential were 21.52 nm and -9.82 mV, respectively, for SFE-CAEO-NE, and 30.58 nm and -6.28 mV, respectively, for SDE-CAEO-NE, at an emulsifier concentration of 15% (w/w). SFE-CAEO-NE displayed better physicochemical properties compared with SDE-CAEO-NE. Moreover, its physicochemical properties were generally stable at different temperatures (-20-60℃), pH (3-8), and ionic strengths (0-400 mM). No obvious variations in particle size, zeta potential, and Ke were observed after storing this nanoemulsion for 30 days at 4℃, 25℃, and 40℃, suggesting that it had good stability. The sleep-promoting effect of SFE-CAEO-NE was evaluated using a mouse model of insomnia. The results of behavioral tests indicated that SFE-CAEO-NE ameliorated insomnia-like behavior. Moreover, SFE-CAEO- NE administration increased the serum concentrations of neurotransmitters such as 5-hydroxytryptamine and γ-aminobutyric acid, and decreased that of noradrenaline in mice. It also exerted a reparative effect on the function of damaged neurons. Overall, SFE-CAEO-NE displayed a good sleep-promoting effect.

Single-Round Circular Aptamer Discovery Using Bioinspired Magnetosome-Like Magnetic Chain Cross-Linked Graphene Oxide.

Circular aptamers are promising candidates for analytical and therapeutic applications due to their enhanced biological and structural stability. However, the process of circular aptamer selection remains a great challenge, as it requires multiple rounds of binding-separation-amplification that involves issues with nonspecific binding and amplification bias. Here, we develop a highly practical solution for reliable selection of circular aptamers in a single round based on magnetosome-like magnetic chain cross-linked graphene oxide (separation efficiency ≈ 105). High-affinity aptamer candidates can be rapidly selected from a preenriched circular DNA library, while low-affinity candidates are effectively adsorbed and separated by magnetosome-like magnetic chain cross-linked graphene oxide. With lipopolysaccharide as a representative model, the single-round selected lipopolysaccharide circular aptamer has been identified to have a high binding affinity with a Kd value of low to nanomolar range. Using this method, circular aptamers for protein and small-molecule targets were also successfully generated. We envision that this approach will accelerate the discovery of various new circular aptamers and open up a new avenue for analytical and therapeutic studies.

A Bioinspired Single-Atom Fe Nanozyme with Excellent Laccase-Like Activity for Efficient Aflatoxin B1 Removal.

The applications of natural laccases are greatly restricted because of their drawbacks like poor biostability, high costs, and low recovery efficiency. M/NC single atom nanozymes (M/NC SAzymes) are presenting as great substitutes due to their superior enzyme-like activity, excellent selectivity and high stability. In this work, inspired by the catalytic active center of natural enzyme, a biomimetic Fe/NC SAzyme (Fe-SAzyme) with O2-Fe-N4 coordination is successfully developed, exhibiting excellent laccase-like activity. Compared with their natural counterpart, Fe-SAzyme has shown superior catalytic efficiency and excellent stability under a wide range of pH (3.0-9.0), temperature (4-80 °C) and NaCl strength (0-300 mm). Interestingly, density functional theory (DFT) calculations reveal that the high catalytic performance is attributed to the activation of O2 by O2-Fe-N4 sites, which weakened the O─O bonds in the oxygen-to-water oxidation pathway. Furthermore, Fe-SAzyme is successfully applied for efficient aflatoxin B1 removal based on its robust laccase-like catalytic activity. This work provides a strategy for the rational design of laccase-like SAzymes, and the proposed catalytic mechanism will help to understand the coordination environment effect of SAzymes on laccase-like catalytic processes.

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy.

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

Nanozyme-integrated alcogel colorimetric sensor for rapid and on-site detection of tert-butyl hydroquinone.

Tert-butyl hydroquinone (TBHQ) stand as one of the most widely used antioxidants in food and daily chemical products. Rapid and sensitive monitoring of TBHQ holds considerable importance in safeguarding human health due to its potential risks. In this study, we devised an alcogel-based colorimetric sensor enabling the portable and visual detection of TBHQ. The Ce-UiO-66 nanozyme exhibiting remarkable oxidase-like activity, was synthesized and characterized, facilitating the catalysis of TBHQ oxidation to 2-tert-butyl-1,4-benzoquinone (TBBQ). The ensuing chromogenic reaction between TBBQ and ethylenediamine produced a stable and colored product, serving as a reliable indicator for the rapid and specific detection of TBHQ. Building upon this discovery, a portable and low-cost colorimetric sensor was fashioned by integrating the nanozyme into κ-carrageenan alcogel, thereby enabling on-site TBHQ detection via a smartphone-based sensing platform. The colorimetric sensor exhibited a detection limit of 0.8 µg mL-1, demonstrating robust performance across various matrices such as edible oils, cosmetics, and surface water. Recoveries ranged from 84.9 to 95.5%, with the sensor's accuracy further validated through gas chromatography-mass spectrometry. Our study presents an effective approach to rapid and convenient monitoring of TBHQ, exhibiting good extensibility and practicability.

Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

INTRODUCTION: Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. OBJECTIVE: This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. METHOD: Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. RESULTS: We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. CONCLUSIONS: The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

Evaluation of sustained drug release performance and osteoinduction of magnetron-sputtered tantalum-coated titanium dioxide nanotubes.

Modifying the drug-release capacity of titanium implants is essential for maintaining their long-term functioning. Titanium dioxide nanotube (TNT) arrays, owing to their drug release capacity, are commonly used in the biomaterial sphere. Their unique half open structure and arrangement in rows increase the drug release capacity. However, their rapid drug release ability not only reduces drug efficiency but also produces excessive local and systemic deposition of antibiotics. In this study, we designed a tantalum-coated TNT system for drug-release optimization. A decreased nanotube size caused by the tantalum nanocoating was observed through SEM and analyzed (TNT: 110 nm, TNT-Ta1: 80 nm, TNT-Ta3: 40 nm, TNT-Ta5: 20 nm, TNT-Ta7: <5 nm). XPS analysis revealed the distribution of the chemical components, especially that of the tantalum element. In vitro experiments showed that the tantalum nanocoating enhanced cell proliferation; in particular, TNT-Ta5 possessed the best cell viability (about 1.18 of TNT groups at 7d). It also showed that the tantalum nanocoating had a positive effect on osteogenesis (especially TNT-Ta5 and TNT-Ta7). Additionally, hydrophilic/hydrophobic drug (vancomycin/raloxifene) release results indicated that the TNT-Ta5 group possessed the most desirable sustained release capacity. Moreover, in this drug release system, the hydrophobic drug showed more sustained release capacity than the hydrophilic drug (vancomycin: sustained release for more than 48 h, raloxifene: sustained release for more than 168 h). More importantly, TNT-Ta5 is proved to be an appropriate drug release system, which possesses cytocompatibility, osteogenic capacity, and sustained drug release capacity.

Fabrication and evaluation of silver modified micro/nano structured titanium implant.

In order to enhance the antibacterial property of titanium implant without inducing obvious cytotoxicity, the combination of Ag nanolayer and micro/nano surface structure was conducted by magnetron sputtering and hot-alkali treatment in this study. A series of specimens (AH-Ti, AH-Ti/Ag0.25, AH-Ti/Ag1, AH-Ti/Ag2, and AH-Ti/Ag5) were prepared with different sputtering durations (0 min, 0.25 min, 1 min, 2 min, 5 min), respectively, all realizing long-term release of Ag+. In vitro experiments indicated that AH-Ti/Ag1 group possessed good cytocompatibility, nice osteogenic ability, and excellent antibacterial efficiency as well. In addition, AH-Ti/Ag0.25 showed good biocompatibility, while the reduction of S.aureus (78.5%) was not enough compared with AH-Ti/Ag1. Although the AH-Ti/Ag2 and AH-Ti/Ag5 group showed superior antibacterial activity, their obvious cytotoxicity caused low ALP and mineralization level. Therefore, the design of suitable Ag nanolayer coating combined with micro/nano surface structure (AH-Ti/Ag1) might be a promising strategy to enhance osteogenic property and maintain excellent antibacterial ability at the same time.

Fish species mislabelling in China: evidence from a survey of frozen, dried, and surimi-based fish products marketed as cod-related species.

'Cod'-related species are among the most appreciated marine fish resources around the world, but are also prone to species mislabelling. In the present study, a total of 76 frozen, dried, and surimi-based fish products, sold as 'Cod' (59 products), 'Atlantic authentic Cod' (11 products), and 'Authentic Cod' (6 products), were collected in China. A species-specific LAMP (loop-mediated isothermal amplification) method was used to screen for the presence of Atlantic cod (Gadus morhua), Pacific cod (G. macrocephalus), Alaska pollock (G. chalcogrammus), Southern hake (Merluccius australis), which was cross-confirmed using real-time PCR and DNA sequencing methods. The results highlighted the greatest species diversity for 'Cod' products, and the identified species were from nine different families. It appears that the practice of assigning a specific type or category of species to the common name 'Cod' has not been widely advocated, and the misuse of this ambiguous common name has been a common practice for species adulteration, negatively impacting consumers' rights and marine conservation. To rebuild consumers' confidence, retail fish suppliers have differentiated their products by adding specific qualifiers in front of the common name 'Cod' on the label, such as 'Authentic cod' and 'Atlantic authentic cod'. The endeavour is highly meaningful, since Gadus morhua was identified as the species for a significant majority of 'Atlantic authentic cod' and 'Authentic cod' products (64.7%, 11/17), with the remaining six products identified as Alaskan pollock (G. chalcogrammus), Pacific cod (G. macrocephalus) and North Pacific hake (Merluccius productus). Despite the positive effort to reverse species mislabelling from retail on-line fish suppliers, a standardized fish nomenclature stipulated by the responsible authorities remains crucial for enhancing transparency and continuing to reduce species mislabelling.

BF.7: a new Omicron subvariant characterized by rapid transmission.

OBJECTIVES: BF.7 (BA.5.2.1.7) is a novel sublineage of Omicron BA.5, whose clinical characteristics are not yet established. METHODS: From 28 September 2022 to 3 October 2022, the first 421 patients with BF.7 were assessed in Hohhot China and the clinical data were extracted and analysed. The basic reproduction number (R0) was estimated using a statistical model calculation method. RESULTS: The R0 value was determined to be 13.79 (95% confidence interval: 12.44-15.24). The mean age was 33.43 ± 18.78 years. Asymptomatic, mild, moderate, severe, and critical patients accounted for 12.35% (52/421), 82.42% (347/421), 4.75% (20/421), 0.24% (1/421), and 0.24% (1/421) proportion, respectively. The main clinical symptoms were fever accounting for 41.09% (173/421), cough accounting for 41.09% (173/421), and throat dryness and soreness accounting for 30.88% (130/421). In the 3-dose vaccination subgroup, 31.22% (64) cases had a fever, which were significantly lower than 51.37% (96) cases of the 2-dose vaccination subgroup (p 0.000). The rates of abnormally increased C-reactive protein level in the 2-dose and 3-dose vaccination subgroups were 10.16% (19/187) and 4.88% (10/205), significantly lower than 66.67% (10/15) of the 1-dose vaccination subgroup (1-dose vs. 2-dose: p 0.000, 1-dose vs. 3-dose: p 0.000). Notably, the population with complete 3 doses of vaccination did not exhibit any severe or critical status. DISCUSSION: BF.7 exhibited a higher transmission than previously emerged SARS-CoV-2. The vaccine against COVID-19 was found to relieve fever, nausea, and vomiting as well as reduce the abnormal ratio of lymphocytes, eosinophils, neutrophils, and the C-reactive protein level.

Level and influencing factors of transition shock among new nurses in China: A multicenter cross-sectional study.

Background and Aims: New nurses are an important part of nursing teams. The failure of new nurses to successfully transition seriously affects personal career development and nursing work quality, and important influencing factors deserve the attention of nursing managers. At present, multicenter, large-sample investigations of transition shock among new nurses are lacking in China. This study aims to investigate the current level and influencing factors of transition shock among new nurses in China. Methods: We conducted a multicenter, cross-sectional study with 3414 new nurses from 16 provinces in 7 regions in China from October 22, 2021, to November 8, 2021. We used the snowball sampling method and an online questionnaire produced by the researchers to collect data; the questionnaire included questions on demographic information, a transition shock scale for new nurses and open-ended questions. Data were analyzed using SPSS version 24. Results: The effective response rate of this study was 97.89%, with 3342 effective participants from 189 hospitals in China, most of whom were female (94.88%). The study showed that the transition shock of new nurses in China was at a moderate level, with pre-job anxiety, unsatisfactory welfare treatment, resignation intention, adverse events, poor sleep quality, 1 or fewer exercise sessions per week, inability to balance work and life, and gluttony negatively affecting the transition shock of new nurses in China. Psychological shock was the strongest among the four dimensions of transition shock. Conclusions: The transition shock of new nurses, especially their psychological shock, deserves more attention from international society. Nursing managers should continue to take supportive measures to intervene in the factors influencing transition shock, with the aim of reducing the level of transition for new nurses, promoting their personal thriving, improving the quality of nursing work and increasing the retention rate of nurses.

Occurrence of liquid crystal monomers in indoor and outdoor air particle matters (PM10): Implications for human exposure indoors.

Liquid crystal monomers (LCMs) are potentially persistent, bioaccumulating, and toxic substances. However, limited data are available on the occurrence of LCMs in indoor and outdoor air particle matter (PM10) in residential areas. Herein, residential areas near an e-waste dismantling center (Guiyu Town, Shantou City), as well as areas away from the e-waste site (Jiedong District, Jieyang City) were selected as the sampling areas. PM10 was collected from the indoor environments of Guiyu (IGY) and Jieyang (IJY), as well as those from the outdoor environments (OGY and OJY) using the high-volume air samplers (TH-10000C). The levels of 57 LCMs in PM10 were analyzed, and the highest concentrations of LCMs were found in IGY (0.970-1080 pg/m3), followed by IJY (2.853-455 pg/m3), OGY (0.544-116 pg/m3) and OJY (0.258-35.8 pg/m3). No significant difference was observed for LCM levels in indoor PM10 between the two areas (p > 0.05), which were significantly higher than those in outdoors (p < 0.05), indicating that the release of electronic products in general indoor environments is a source of LCMs that cannot be ignored. The compositions of LCMs in outdoors were not consistent with those of indoors. The correlation analysis of individual LCMs suggested potential different sources to the LCMs in indoor and outdoor environments. The median daily intake values of Σ46LCMs via inhalation were estimated as 0.440, 1.46 × 10-2, 0.170 and 1.19 × 10-2 ng/kg BW/day for adults, and as 2.27, 2.60 × 10-2, 0.880 and 2.10 × 10-2 ng/kg BW/day for toddlers, respectively, indicating much higher exposure doses of LCMs indoors compared with the outdoors, and much higher doses for toddlers compared with adults (p < 0.05). These results reveal the potentially adverse effects of LCMs on vulnerable populations, such as toddlers, in indoor environments.

Profiles and diagnostic value of intestinal microbiota in schizophrenia patients with metabolic syndrome.

Aims/hypothesis: It is widely thought that the intestinal microbiota plays a significant role in the pathogenesis of metabolic disorders. However, the gut microbiota composition and characteristics of schizophrenia patients with metabolic syndrome (MetS) have been largely understudied. Herein, we investigated the association between the metabolic status of mainland Chinese schizophrenia patients with MetS and the intestinal microbiome. Methods: Fecal microbiota communities from 115 male schizophrenia patients (57 with MetS and 58 without MetS) were assessed by 16S ribosomal RNA gene sequencing. We assessed the variations of gut microbiome between both groups and explored potential associations between intestinal microbiota and parameters of MetS. In addition, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the KEGG database was used to predict the function of intestinal microbiota. We also conducted Decision Tree Analysis to develop a diagnostic model for the MetS in patients with schizophrenia based on the composition of intestinal microbiota. Results: The fecal microbial diversity significantly differed between groups with or without MetS (α-diversity (Shannon index and Simpson index): p=0.0155, p=0.0089; ß-diversity: p=0.001). Moreover, the microbial composition was significantly different between the two groups, involving five phyla and 38 genera (p<0.05). In addition, a significant correlation was observed between the metabolic-related parameters and abundance of altered microbiota including HDL-c (r2 = 0.203, p=0.0005), GLU (r2 = 0.286, p=0.0005) and WC (r2 = 0.061, p=0.037). Furthermore, KEGG pathway analysis showed that 16 signaling pathways were significantly enriched between the two groups (p<0.05). Importantly, our diagnostic model based on five microorganisms established by decision tree analysis could effectively distinguish between patients with and without MetS (AUC = 0.94). Conclusions/interpretation: Our study established the compositional and functional characteristics of intestinal microbiota in schizophrenia patients with MetS. These new findings provide novel insights into a better understanding of this disease and provide the theoretical basis for implementing new interventional therapies in clinical practice.

Ce(IV)-coordinated organogel-based assay for on-site monitoring of propyl gallate with turn-on fluorescence signal.

Propyl gallate (PG) is a commonly used synthetic phenolic antioxidant in foodstuffs and industrial products. Due to the potential health risk of PG, rapid and on-site detection in food and environment samples are important to guarantee human health. Herein, we demonstrated rapid monitoring of PG by a fluorescence turn-on strategy based on a specific fluorogenic reaction between PG and polyethyleneimine (PEI). Specifically, Ce4+ with oxidase-mimicking activity oxidized PG to its oxides, which then reacted with PEI through the Michael addition to generate the fluorescent compound. The proposed fluorogenic reaction had good specificity for PG, which could distinguish PG from other phenolic antioxidants and interferences. Furthermore, portable and low-cost organogel test kits were prepared using poly(ethylene glycol) diacrylate for quantitative and on-site detection of PG via a smartphone-based sensing platform. The organogel-based assay detection limit was 1.0 µg mL-1 with recoveries ranging from 80.2% to 106.2% in edible oils and surface water. Suitability of the developed assay was also validated by high-performance liquid chromatography. Our study provides an effective fluorescent approach to rapid, specific, and convenient monitoring of PG, which is useful for diminishing the risk of PG exposure.

Closed-tube visual detection of Atlantic cod (Gadus morhua) using self-quenched primer coupled with a designed loop-mediated isothermal amplification vessel.

BACKGROUND: Species adulteration has been widely revealed around the world, and the possible reasons include declining stocks in most source areas of the world, poor transparency in the global supply chain, and difficulty in distinguishing the features of processed products. The present work selected Atlantic cod (Gadus morhua) as a case study, and developed a novel loop-mediated isothermal amplification (LAMP) assay for Atlantic cod authentication, where a self-quenched primer and a newly designed reaction vessel were used to realize the endpoint visual detection of the target-specific products. RESULTS: A novel LAMP primer set was designed for Atlantic cod, and the inner primer BIP was selected to label the self-quenched fluorogenic element. The fluorophore's dequenching only occurred along with LAMP elongation for the target species. No fluorescence could be observed with both single-stranded DNA and partially complementary dsDNA of the non-target species. With the novel reaction vessel, both amplification as well as detection were operated in an enclosed device, and visual differentiation of Atlantic cod, negative control, and false positive generated from primer dimers was achieved. The novel assay has proved its specificity and applicability, and could detect as little as 1 pg of Atlantic cod DNA. Moreover, Atlantic cod adulteration as low as 10% could be detected in haddock (Melanogrammus aeglefinus), and no cross-reactivity was observed. CONCLUSION: The established assay could be a useful tool to detect mislabeling incidents involving Atlantic cod considering the advantages of speed, simplicity and accuracy. © 2023 Society of Chemical Industry.

The role of social network embeddedness and collective efficacy in encouraging farmers' participation in water environmental management.

Water environmental management (WEM) has a significant influence on the global ecological balance. As an institutional innovation, the River Chief System (RCS) in China has achieved a positive short-term impact on addressing water environmental problems. However, its effects are limited in rural China. As a type of public good, the rural WEM demands the active participation not only of government but also of farmers. Based on the social cognitive and social network theory, this study empirically investigates how rural social networks promote farmers' participation in WEM. Using the survey of 860 farmers in the Yellow and Yangtze River Basin, we employ the double-hurdle model (D-H-M) to craft the primary assessment. The results show that the social network embeddedness facilitates farmers' participation in WEM directly. Collective efficacy plays a full mediation role in the relationship between social network embeddedness and farmers' participation. Moreover, the perceived role of village leaders affects the relationship between social networks and farmers' participation. Our research enriches the application of social network theory in the rural social context and offers an innovative approach to solving farmers' participation problems in WEM.

HPMC films functionalized by zein/carboxymethyl tamarind gum stabilized Pickering emulsions: Influence of carboxymethylation degree.

Pickering emulsions are promising systems to act as carriers of active hydrophobic components, and to improve compatibility and the water vapor barrier properties of bio-based films. This study aimed to investigated the effects of cinnamon essential oil Pickering emulsions (CEOEs) using zein/carboxymethyl tamarind gum as stabilizers on the mechanical, barrier, antibacterial and antioxidant properties of Hydroxypropyl methyl cellulose (HPMC) films, and assessed the influence of carboxymethylation degree. In addition, the effect of the packaging was studied on the shelf life of cherry tomatoes. Results showed that the droplet size reduced approximately from 93.03 to 10.59 µm with the increasing degree of substitution (DS), greatly facilitating the droplet uniform distribution in film matrix. Moreover, with the addition of CEOEs, significant increase was observed with the tensile strength from 8.46 to 25.41 MPa, and the water vapor permeability decreased from 6.18 × 10-10 to 4.24 × 10-10 g·m-1·s-1·Pa-1. The films exhibited good UV barrier properties without sacrificing the transparency after adding CEO. Furthermore, the antibacterial and antioxidant activities of the prepared films have also been greatly improved. Consequently, the CEOEs was an ideal alternative for incorporation with HPMC based films for increasing the shelf life of cherry tomatoes.

Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design.

Selective CDK2 inhibitors have the potential to provide effective therapeutics for CDK2-dependent cancers and for combating drug resistance due to high cyclin E1 (CCNE1) expression intrinsically or CCNE1 amplification induced by treatment of CDK4/6 inhibitors. Generative models that take advantage of deep learning are being increasingly integrated into early drug discovery for hit identification and lead optimization. Here we report the discovery of a highly potent and selective macrocyclic CDK2 inhibitor QR-6401 (23) accelerated by the application of generative models and structure-based drug design (SBDD). QR-6401 (23) demonstrated robust antitumor efficacy in an OVCAR3 ovarian cancer xenograft model via oral administration.

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.

BACKGROUND: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers. METHODS: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. RESULTS: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%). CONCLUSIONS: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.

FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) expressing the androgen receptor (AR) respond poorly to neoadjuvant chemotherapy, although AR antagonists have shown promising clinical activity, suggesting these tumors are AR-dependent. cAMP responsive element binding protein (CREB)-binding protein (CBP) and p300 are transcriptional co-activators for the AR, a key driver of AR+ breast and prostate cancer, and may provide a novel therapeutic target in AR+ TNBC. OBJECTIVES: The aim of this study was to determine the therapeutic potential of FT-6876, a new CBP/p300 bromodomain inhibitor, in breast cancer models with a range of AR levels in vitro and in vivo. METHODS: Effects of FT-6876 on the CBP/p300 pathway were determined by combining chromatin immunoprecipitation (ChIP) with precision run-on sequencing (PRO-seq) complemented with H3K27 acetylation (Ac) and transcriptional profiling. The antiproliferative effect of FT-6876 was also measured in vitro and in vivo. RESULTS: We describe the discovery of FT-6876, a potent and selective CBP/p300 bromodomain inhibitor. The combination of ChIP and PRO-seq confirmed the reduction in H3K27Ac at specific promoter sites concurrent with a decrease in CBP/p300 on the chromatin and a reduction in nascent RNA and enhancer RNA. This was associated with a time- and concentration-dependent reduction in H3K37Ac associated with a decrease in AR and estrogen receptor (ER) target gene expression. This led to a time-dependent growth inhibition in AR+ models, correlated with AR expression. Tumor growth inhibition was also observed in AR+ tumor models of TNBC and ER+ breast cancer subtypes with consistent pharmacokinetics and pharmacodynamics. CONCLUSION: Our findings demonstrate FT-6876 as a promising new CBP/p300 bromodomain inhibitor, with efficacy in preclinical models of AR+ breast cancer.