Validation of the AnticFast® Beta-Lactams & Tetracyclines Combo Test Kit for Detection of Residues of Beta-Lactams (Penicillins and Cephalosporins) and Tetracyclines in Raw Cows' Milk: AOAC Performance Tested MethodSM 032403.

BACKGROUND: AnticFast® Beta-lactams & Tetracyclines Combo Test Kit is a qualitative two-step (2 min + 5 min) rapid lateral flow assay to detect ß-lactam (penicillins and cephalosporins) and tetracycline antibiotic residues in raw commingled cows' milk. OBJECTIVE: The method performance was evaluated according to Commission Implementing Regulation 2021/808 and Community Reference Laboratories Residues Guidelines for the Validation of Screening Methods for Residues of Veterinary Medicines and submitted for AOAC Performance Tested Methods  SM certification. METHODS: The AnticFast Beta-lactams & Tetracyclines Combo Test Kit was evaluated for detection capability (CCß), selectivity, false-positive results, repeatability, robustness, suitability for various milk types and milk compositions, milks from various species, and test kit consistency and stability. Samples included milks spiked at concentrations bracketing the EU Maximum Residue Limits (MRLs) for ß-lactams and tetracyclines as well as bulk farm and tanker milks. RESULTS: The AnticFast Beta-lactams & Tetracyclines Combo Test Kit is specific for the detection of residues of ß-lactams and tetracyclines in milk and does not detect residues from other antibiotic families. Interference was seen with clavulanic acid, a ß-lactamase inhibitor, which was expected. The test can detect (minimum a 95% detection) all residues of ß-lactams (penicillins and cephalosporins) and tetracyclines (parent drugs and their 4-epimers) present on the EU-MRL list for milk at their respective MRL except for desfuroylceftiofur and cephalexin, with a 95% detection only above the MRL. No false positives were detected in 599 (305 blank farm and 301 tanker load) samples tested on both channels. Five real positives were detected and confirmed on the tetracycline channel for the blank farm milk, and two positives were detected and confirmed on the ß-lactam channel for the tanker samples. Robustness testing indicated that the detection in high protein raw cows' milk and heat-treated milk types (UHT, sterilized and reconstituted milk powder) may be slightly hampered. For substances with a detection capability well below the MRL this interference is not causing problems since detection at MRL remains guaranteed, but care should be taken for substances with a CCß at or near their MRL. Diminished sample flow was seen for high fat raw cows' milk and for all other cows' milk types other than raw milk and blank ewes' milk, so sample flow should always be verified for these milk types. CONCLUSIONS: Results of this validation show that the AnticFast Beta-lactams & Tetracyclines Combo Test Kit is a reliable test for rapid screening of raw cows' milk for residues of ß-lactam and tetracycline antibiotics. HIGHLIGHTS: The AnticFast Beta-lactams & Tetracycline Combo Test Kit is an easy, reliable, robust and highly specific test for screening of ß-lactam (penicillins and cephalosporins) and tetracycline antibiotic residues in milk with incubation at room temperature. In raw cows' milk, all tetracyclines are detected below 10 µg/kg.

Low-Temperature Photothermal Therapy Platform Based on Pd Nanozyme-Modified Hydrogenated TiO2.

In photothermal treatments (PTTs), normal tissues around cancerous tumors get injured by excessive heat, whereas damaged cancer cells are easily restored by stress-induced heat shock proteins (HSPs) at low temperatures. Therefore, to achieve a unique tumor microenvironment (TME), it is imperative to increase PTT efficiency and reduce normal tissue injury by adopting appropriate reactive oxygen species (ROS) and lipid peroxides (LPO) cross-linked with HSPs. In the present research, a potential strategy for mild photothermal treatments (mPTTs) was proposed by initiating localized catalytic chemical reactions in TME based on Pd nanozyme-modified hydrogenated TiO2 (H-TiO2@Pd). In vitro and in vivo evaluations demonstrated that H-TiO2@Pd had good peroxidase-like activities (POD), glutathione oxidase-like activities (GSHOx), and photodynamic properties and also satisfactory biocompatibility for 4T1 cells. Localized catalytic chemical reactions in H-TiO2@Pd significantly depleted GSH to downregulate the protein expression of GPX4 and promoted the accumulation of LPO and ROS, which consumed HSP70 or inhibited its function in 4T1 cells. Hence, the as-constructed low-temperature photothermal therapeutic platform based on Pd nanozyme-modified H-TiO2 can be a promising candidate to develop a safe and effective mPTT for cancer treatments.

Validation of the AnticFast® Beta-Lactams Rapid Test Kit for Detection of Beta-Lactams (Penicillins and Cephalosporins) in Raw Cow's Milk: AOAC Performance Tested MethodSM 032303.

BACKGROUND: AnticFast® Beta-Lactams Rapid Test Kit is a qualitative two-step (2 min + 5 min) rapid lateral flow assay to detect ß-lactam (penicillins and cephalosporins) antibiotic residues in raw commingled cow's milk. OBJECTIVE: The method performance was evaluated according to Commission Decision 2002/657/EC, Commission Implementing Regulation 2021/808, and Community Reference Laboratories Residues Guidelines for the Validation of Screening Methods for Residues of Veterinary Medicines. METHODS: The AnticFast Beta-Lactams Rapid Test Kit was evaluated for detection capability, selectivity, false-positive results, repeatability, robustness, suitability for various milk types and milk compositions, milks from various species, and test kit consistency and stability. Samples included milks spiked at concentrations bracketing the EU maximum residue limits (MRLs) for ß-lactams as well as bulk farm and tanker milks. RESULTS: The AnticFast Beta-Lactams Rapid Test Kit is specific for the detection of ß-lactams in milk and does not detect compounds from other antibiotic families. Interference was seen with clavulanic acid, a ß-lactamase inhibitor, which was expected. The test can detect all residues of ß-lactams (penicillins and cephalosporins) present on the EU-MRL list for milk at their respective MRL except for desfuroylceftiofur and cephalexin, which were above the MRL. No false positives were detected in the 602 (300 blank farm and 302 tanker load) samples tested. Robustness testing indicated that the detection in heat-treated milk types may be slightly hampered. For substances with a detection capability well below the MRL, this interference does not cause problems since detection at MRL remains guaranteed, but care should be taken for substances with a CCß at or near their MRL. Diminished sample flow was seen with reconstituted milk powder and blank ewes' milk, so sample flow should always be verified for these milk types. CONCLUSIONS: Results of this validation show that the AnticFast Beta-Lactams Rapid Test Kit is a reliable test for rapid screening of raw cows' milk for residues of ß-lactam antibiotics. HIGHLIGHTS: AnticFast Beta-Lactams Rapid Test Kit is an easy, realiable, robust and highly specific test for screening of raw cows' milk for residues of penicillins and cephalosporins.

A novel dose fall-off index and preliminary application in brain and lung stereotactic radiotherapy.

BACKGROUND: Stereotactic radiotherapy (SRT) has been widely used for the treatment of brain metastases and early stage non-small-cell lung cancer (NSCLC). Excellent SRT plans are characterized by steep dose fall-off, making it critical to accurately and comprehensively predict and evaluate dose fall-off. PURPOSE: A novel dose fall-off index was proposed to ensure high-quality SRT planning. METHODS: The novel gradient index (NGI) had two different modes: NGIx V for three-dimensions and NGIx r for one-dimension. NGIx V and NGIx r were defined as the ratios of the decreased percentage dose (x%) to the corresponding isodose volume and equivalent sphere radii, respectively. A total of 243 SRT plans at our institution between April 2020 and March 2022 were enrolled, including 126 brain and 117 lung SRT plans. Measurement-based verifications were performed using SRS MapCHECK. Ten plan complexity indexes were calculated. Dosimetric parameters related to radiation injuries were also extracted, including the normal brain volume exposed to 12 Gy (V12 ) and 18 Gy (V18 ) during single-fraction SRT (SF-SRT) and multi-fraction SRT (MF-SRT), respectively, and the normal lung volume exposed to 12 Gy (V12 ). The performance of NGI and other common dose fall-off indexes, gradient index (GI), R50% and D2cm were evaluated using Spearman correlation analysis to explore their correlations with the PTV size, gamma passing rate (GPR), plan complexity indexes, and dosimetric parameters. RESULTS: There were statistically significant correlations between NGI and PTV size (r = -0.98, P < 0.01 for NGI50 V and r = -0.93, P < 0.01 for NGI50 r), which were the strongest correlations compared with GI (r = 0.11, P = 0.13), R50% (r = -0.08, P = 0.19) and D2cm (r = 0.84, P < 0.01). The fitted formulas of NGI50 V = 23.86V-1.00 and NGI50 r = 113.5r-1.05 were established. The GPRs of enrolled SRT plans were 98.6 ± 1.7%, 94.2 ± 4.7% and 97.1 ± 3.1% using the criteria of 3%/2 mm, 3%/1 mm, and 2%/2 mm, respectively. NGI50 V achieved the strongest correlations with various plan complexity indexes (|r| ranged from 0.67 to 0.91, P < 0.01). NGI50 V also showed the highest r values with V12 (r = -0.93, P < 0.01) and V18 (r = -0.96, P < 0.01) of the normal brain during SF-SRT and MF-SRT, respectively, and V12 (r = -0.86, P < 0.01) of the normal lung during lung SRT. CONCLUSIONS: Compared with GI, R50% and D2cm , the proposed dose fall-off index, NGI, had the strongest correlations with the PTV size, plan complexity and V12 /V18 of the normal tissues. These correlations established on NGI are more helpful and reliable for SRT planning, quality control, and reducing the risk of radiation injuries.

Co-assembled Nanocarriers of De Novo Thiol-Activated Hydrogen Sulfide Donors with an RGDFF Pentapeptide for Targeted Therapy of Non-Small-Cell Lung Cancer.

Hydrogen sulfide releasing agents (or H2S donors) have been recognized gasotransmitters with potent cytoprotective and anticancer properties. However, the clinical application of H2S donors has been hampered by their fast H2S-release, instability, and lack of tumor targeting, despite the unclear molecular mechanism of H2S action. Here we rationally designed an amphiphilic pentapeptide (RGDFF) to coassemble with the de novo designed thiol-activated H2S donors (CL2/3) into nanocarriers for targeted therapy of non-small-cell lung cancer, which has been proved as a one-stone-three-birds strategy. The coassembly approach simply solved the solubility issue of CL2/3 by the introduction of electron-donating groups (phenyl rings) to slow down the H2S release while dramatically improving their biocompatible interface, circulation time, slow release of H2S, and tumor targeting. Experimental results confirmed that as-prepared coassembled nanocarriers can significantly induce the intrinsic apoptotic, effectively arrest cell cycle at the G2/M phase, inhibit H2S-producing enzymes, and lead to mitochondrial dysfunction by increasing intracellular ROS production in H1299 cells. The mouse tumorigenesis experiments further confirmed the in vivo anticancer effects of the coassembled nanocarriers, and such treatment made tumors more sensitive to radiotherapy then improved the prognosis of tumor-bearing mice, which holds great promise for developing a new combined approach for NSCLC.

Fabrication of strontium carbonate-based composite bioceramics as potential bone regenerative biomaterials.

Strontium carbonate (SrC) bioceramics are proposed as potential biomaterials to efficaciously repair the bone defects. However, the development of SrC bioceramics is restricted by their intrinsic low mechanical strength. In this study, SrC-based composite bioceramics (SrC-SrP) were fabricated by incorporating strontium-containing phosphate glass (SrP). The results indicated that aside from the main crystalline phase SrC, new compounds were generated in the SrC-SrP bioceramics. Incorporating 10 wt% SrP promoted densification, thus dramatically improving compressive strength of SrC-SrP bioceramics. The SrC-SrP bioceramics facilitated apatite precipitation on their surface, and sustainedly released strontium, phosphorus and sodium ions. Compared with the well-known ß-tricalcium phosphate bioceramics, the SrC-SrP bioceramics with certain amounts of SrP enhanced proliferation, alkaline phosphatase activity and osteogenesis-related gene expressions of mouse bone mesenchymal stem cells. The SrC-SrP bioceramics with appropriate constituent can serve as novel bone regenerative biomaterials.

Sensing Hypochlorite or pH variations in live cells and zebrafish with a novel dual-functional ratiometric and colorimetric chemosensor.

Both HClO and pH are essential players in multiple biological processes, which thus need to be controlled properly. Dysregulated HClO or pH correlates with many diseases. To meet these challenges, we need to develop highly competent probes for monitoring them. Over the years, despite a rich history of the development of HClO or pH probes, those that can do both jobs are still deficient. Herein, we present a novel dual-functional chemosensor, CMHN, which exhibits a blue and red shift of its fluorescence emission upon reacting with HClO or OH-, respectively. CMHN was successfully harnessed in the imaging detection of HClO or OH- in aqueous solutions, live cells, and zebrafish. Results indicated CMHN can detect HClO with high sensitivity (LOD -132 nM), a quick response time (<70 s), and high selectivity over dozens of interfering species through a colorimetric and ratiometric response. Besides, CMHN can probe pH changes sensitively and reversibly. Its working mechanism was verified by DFT calculations. These superior features make CMHN excel among the HClO or pH probes reported so far. Taken together, CMHN replenishes the deficiency in currently developed HClO or pH probes and paves the way for developing multifunctional HClO or pH probes in the future.

Correlation between the γ passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer.

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

Activity and Safety of Tegafur, Gimeracil, and Oteracil Potassium for Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

In clinical practice, tegafur, gimeracil, and oteracil potassium (S-1) therapy is commonly administered to treat nasopharyngeal carcinoma (NPC). However, its efficacy and safety remain controversial in both randomized controlled trials (RCTs) and non-RCTs. We aimed to evaluate the efficacy and safety of S-1 treatment for NPC. We searched PubMed, Ovid, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and VIP databases for RCTs of chemotherapy with or without S-1 for NPC, from 2001 to 2020. A meta-analysis was performed using RevMan5.3 and Stata15. Randomized controlled trials published in journals were included irrespective of blinding and language used. Patients were diagnosed with NPC through a clinicopathological examination; patients of all cancer stages and ages were included. Overall, 25 trials and 1858 patients were included. There were significant differences in the complete remission (OR = 2.42, 95% CI (1.88-3.10), P < 0.05) and overall response rate (OR = 2.68, 95% CI (2.08-3.45), P < 0.05) between the S-1 and non-S-1 groups. However, there was no significant difference in partial remission (OR = 1.10, 95% CI (0.87-1.39), P=0.42) and seven adverse reactions (leukopenia, thrombocytopenia, nausea and vomiting, diarrhea, dermatitis, oral mucositis, and anemia) between the S-1 and non-S-1 groups. Additionally, statistical analyses with six subgroups were performed. S-1 was found to be a satisfactory chemotherapeutic agent combined with radiotherapy, intravenous chemotherapy, or chemoradiotherapy for NPC. As an oral medicine, the adverse reactions of S-1, especially gastrointestinal reactions, can be tolerated by patients, thereby optimizing their quality of life. S-1 may be a better choice for the treatment of NPC. This trial is registered with CRD42019122041.

Trap Energy Upconversion-Like Near-Infrared to Near-Infrared Light Rejuvenateable Persistent Luminescence.

Persistent-luminescence phosphors (PLPs) have a wide variety of applications in the fields of photonics and biophotonics due to their ultralong afterglow lifetime. However, the existing PLPs are charged and recharged with short-wavelength high-energy photons or inconvenient and potentially risky X-ray beams. To date, deep tissue penetrable NIR light has mainly been used for photostimulated afterglow emission, which continues to decay and weaken after each cycle, Herein, a new paradigm of trap energy upconversion-like near-infrared (NIR) to near-infrared light rejuvenateable persistent luminescence in bismuth-doped calcium stannate phosphors and nanoparticles is reported. In contrast to the existing PLPs and persistent-luminescence nanoparticles, the materials enable the occurrence of a reversed transition of the carriers from a deep-level energy trap to a shallow-level trap upon excitation by low-energy NIR photons. Thus these new materials can be charged circularly via deep-tissue penetrable NIR photons, which is unable to be done for existing PLPs, and emit afterglow signals. This conceptual work will lay the foundation to design new categories of NIR-absorptive-NIR-emissive PLPs and nanoparticles featuring physically harmless and deep tissue penetrable NIR light renewability and sets the stage for numerous biological applications, which have been limited by current materials.

Fabrication of Biomolecule-Loaded Composite Scaffolds Carried by Extracellular Matrix Hydrogel.

Fabrication of multifunctional scaffolds with biomimicking physical and biological signals play an important role in enhancing tissue regeneration. Multifunctional features come from the composite scaffold with various bioactive molecules. However, simple, biocompatible, and controllable hybridization strategy is still lacking. In this study, we leverage naturally derived extracellular matrix (ECM) as chemically controllable hydrogel carrier to effectively load functional biomolecules. The use of ECM hydrogel takes advantage of both native functionality of ECM components and tunability of hydrogel in controlling release of loaded molecules. As a proof of concept, porous acellular bone scaffold was selected as the solid pristine scaffold to be composited with BMP-2 and VEGF, which are loaded by spinal cord-derived ECM (SC-ECM) hydrogel. Crosslinking degree of SC-ECM hydrogel is tuned by changing genipin concentration, which renders the control over release kinetics of BMP-2 and VEGF. The mechanical strength of scaffold maintained after hybridization and is not significantly decreased in wet condition. In vitro evaluations of scaffolds cocultured with osteoblasts and mesenchymal stem cells (MSCs) demonstrate the biocompatible and bioactive features resulting from the composite scaffolds. Evidenced by alkaline phosphatase test, immunofluorescence, and real-time polymerase chain reaction, differentiation of MSCs towards osteoblast lineage is significantly enhanced by composite scaffolds. Therefore, our strategy in fabricating composite scaffold enabled by biomolecule-loaded ECM hydrogel holds great promise in regenerating diverse tissue types by appropriate combinations of solid pristine scaffolds, ECM, and bioactive molecules. Impact statement We developed a bioactive molecule (e.g., growth factor, protein) loading method using extracellular matrix hydrogel as a carrier. It brings a new strategy to fabricate composite scaffolds with unique biofunctions.

Degradation of petroleum hydrocarbons by embedding immobilized crude oil degrading bacteria.

In this study, the removal effect of free and immobilized bacteria on crude oil was determined. Sodium alginate and polyvinyl alcohol were used as embedding agent, and ramie was modified as an adsorbent to immobilize free bacteria. The conditions for preparing immobilized pellets were optimized using the response surface method, and the best combination was simulated and obtained by Design-Expert 8.0. The best degradation rate of immobilized bacteria was 75.52%. The degradation by free bacteria and immobilized bacteria showed that the selected microorganisms had a good degradation effect on petroleum hydrocarbons.

Carbon Quantum Dots: In vitro and in vivo Studies on Biocompatibility and Biointeractions for Optical Imaging.

BACKGROUND: Understanding the biocompatibility and biointeractions of nano-carbon quantum dots (nano-CQDs) in vitro and in vivo is important for assessing their potential risk to human health. In the previous research, the physical properties of CQDs synthesized by the laser ablation in liquid (LAL) method were analyzed in detail; however, possible bioapplications were not considered. MATERIALS AND METHODS: CQDs were prepared by LAL and characterized by atomic force microscopy, fluorescence lifetime, absorption spectrum, Fourier-transform infrared spectroscopy, and dynamic light scattering. Their biocompatibility was evaluated in vitro using assays for cytotoxicity, apoptosis, and biodistribution and in vivo using immunotoxicity and the relative expression of genes. Cells were measured in vitro using fluorescence-lifetime imaging microscopy to analyze the biointeractions between CQDs and intracellular proteins. RESULTS: There were no significant differences in biocompatibility between the CQDs and the negative control. The intracellular interactions had no impact on the optical imaging of CQDs upon intake by cells. Optical imaging of zebrafish showed the green fluorescence was well dispersed. CONCLUSION: We have demonstrated that the CQDs have an excellent biocompatibility and can be used as efficient optical nanoprobes for cell tracking and biomedical labeling except for L929 and PC-3M cells.

In vivo immunotoxicity of Gd2 O3 :Eu3+ nanoparticles and the associated molecular mechanism.

The in vivo toxicity of Gd2 O3 :Eu3+ nanoparticles (NPs) used as dual-modal nanoprobes for molecular imaging has not been studied, and the corresponding molecular mechanism of immunotoxicity remains unknown. In this study, we investigated the cytotoxicity, in vitro apoptosis, and in vivo immunotoxicity of Gd2 O3 :Eu3+ NPs. The NPs showed little immunotoxicity to BALB/c mice. We explored the possible role of the phosphoinositide 3-kinase (PI3K) signaling pathway and found that reactive oxygen species could act as secondary messengers in cellular signaling, inhibiting PI3K expression in the liver. The immune suppression caused by PI3K inhibition helped the mice adapt to stress. The immunotoxicities caused by Gd2 O3 :Eu3+ and gadodiamide, a commonly used contrast agent, were not significantly different, and the mice were able to tolerate the immunotoxicity caused Gd2 O3 :Eu3+ NPs in vitro and in vivo experiments. The results suggest that Gd2 O3 :Eu3+ NPs are sufficiently biocompatible to be used safely in preclinical applications and show promise as bio-imaging agents. Moreover, the in vivo molecular mechanism of immunotoxicity caused by the Gd2 O3 :Eu3+ NPs provides a platform for further research on the immunotoxicity of nano-sized biomaterials.

The prognosis analysis of RFWD2 inhibiting the expression of ETV1 in colorectal cancer.

BACKGROUND: The poor prognosis is partly due to the lack of efficient methods for early diagnosis on colorectal cancer (CRC). METHODS: Bioinformatic analysis and Immunohistochemical analysis were used to evaluate E3 ubiquitin ligase Ring finger and WD domain 2 (RFWD2) and ETS variant 1 (ETV1) mRNA and protein expression levels. RESULTS: The abundance of RFWD2 and ETV1 proteins from 76 CRC patients were examined. The relationship between their expression levels and clinic pathological parameters including prognostic significances were also detected. The expression of RFWD2 and ETV1 and the relative genes functions in CRC through bioinformatics methods were further analyzed. CONCLUSIONS: In conclusion, RFWD2 functioning as a tumor suppressor by negative regulating ETV1, which might play an important role in the development and progression of CRC. RFWD2 and ETV1 have the potential to serve as a pair of molecular biomarkers for the early diagnosis of CRC.

Erratum to the prognosis analysis of RFWD2 inhibiting the expression of ETV1 in colorectal cancer.

[This corrects the article DOI: 10.21037/tcr.2019.11.35.].

Synthesis and biological evaluation of arylpiperazine derivatives as potential anti-prostate cancer agents.

A novel scaffold of arylpiperazine derivatives was discovered as potent androgen receptor (AR) antagonist through rational drug designation based on our pre-work, leading to the discovery of a series of new antiproliferative compounds. Compounds 10, 16, 27, 29 and 31 exhibited relatively strong antagonistic potency against AR and exhibited potent AR binding affinities, while compounds 5, 6, 10, 14, 16, 19, 21, 27 and 31 exhibited strong cytotoxic activities against LNCaP cells (AR-rich) as well as also displayed the higher activities than finasteride toward PC-3 (AR-deficient) and DU145 (AR-deficient). Docking study suggested that the most potent antagonist 16 mainly bind to AR ligand binding pocket (LBP) site through hydrogen bonding interactions. The structure-activity relationship (SAR) of these designed arylpiperazine derivatives was rationally explored and discussed. These results indicated that the novel scaffold compounds demonstrated a step towards the development of novel and improved AR antagonists, and promising candidates for future development were identified.

Cancer risk assessment in modern radiotherapy workflow with medical big data.

Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose-response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI.

Inorganic fullerene-like molybdenum selenide with good biocompatibility synthesized by laser ablation in liquids.

The fabrication of inorganic fullerene-like nanoparticles (IFNPs) is an attractive idea due to their unique structures and various potential applications. To date, IFNPs have been made from numerous compounds with layered two-dimensional structures, based on various synthetic methods. Here we have demonstrated for the first time that inorganic fullerene-like molybdenum selenide nanoparticles (MoSe2 IFNPs) can be synthesized by laser ablating a molybdenum selenide target in 30 vol % ethanol/water mixture at ambient temperature and pressure. The formation mechanism was proposed to elucidate the production of MoSe2 IFNPs in the process of laser ablation in liquids (LAL). The appropriate solvent facilitates the condensation of the plasma plume created by LAL to planar MoSe2. Then, laser-induced high temperature and high pressure lead to the formation of a vacancy in the planar MoSe2, causing the generation of nucleation and growth of the MoSe2 IFNPs. In addition, a CCK-8 (cell counting kit-8) assay and a cell viability assay were performed to examine the cytotoxic behavior and the effect on cell viability of MoSe2 IFNPs. The results show that MoSe2 IFNPs are reasonably nontoxic and biocompatible with the given cells, showing they have significant potential in biomedical applications.