In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

Factors influencing civil servants' willingness to implement cardiopulmonary resuscitation in Chongqing, China: Based on the theory of planned behavior.

Background: Timely bystander cardiopulmonary resuscitation is the key to improving the survival rate of out-of-hospital cardiac arrest. Civil servants are potential bystander CPR providers. This study aimed to explore civil servants' willingness to implement CPR in Chongqing, identify the influencing factors and mechanisms affecting civil servants' willingness to perform CPR, and then seek countermeasures to improve civil servants' willingness to implement CPR. Methods: We introduced the theory of perceived risk into the theory of planned behavior, developed a 7-point Likert scale based on the extended theory of planned behavior, and conducted a questionnaire survey on civil servants in Chongqing, China. Descriptive statistical analysis and one-way ANOVA were employed to explore respondents' willingness and differences. Structural equation modeling was used to analyze the relationship between attitude, subjective norm, perceived behavioral control and perceived risk and respondents' willingness to implement CPR. Results: A total of 1235 valid questionnaires were included for analysis. 50.1 % of respondents were willing to implement CPR. Male, over 40 years old, living with the elderly, having previous experience performing CPR on another person, and having higher CPR knowledge scores were associated with a more positive willingness to perform CPR. Attitude, subjective norm and perceived behavioral control had significant positive effects on willingness, and the standardized regression coefficients were 0.164, 0.326 and 0.313, respectively. The perceived risk has a significant negative effect on willingness, and the standardized regression coefficient was -0.109. The four latent variables accounted for 44.2 % of the variance in the willingness of civil servants to implement CPR. Conclusions: The willingness of civil servants in Chongqing to implement CPR needs to be improved, and the countermeasures to enhance the subjective norm and perceived behavioral control of civil servants should be emphasized, such as developing a social support network for rescuing conduct, establishing regular training mechanisms and improving the practical applicability and popularization of the Chinese-style "Good Samaritan Law" etc., to improve the willingness of civil servants in Chongqing to implement CPR.

Radix Rehmanniae Praeparata promoted zebrafish fin regeneration through aryl hydrocarbon receptor-dependent autophagy.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), a staple in traditional Chinese medicine, is derived from Rehmannia glutinosa Libosch and is renowned for its wound-healing properties. Despite its clinical prevalence, the molecular mechanisms underlying RRP's wound-healing effects have not been fully elucidated. AIM OF THE STUDY: This research endeavored to delineate the molecular and cellular mechanisms underlying the beneficial effects of RRP on wound healing, utilizing a zebrafish model. MATERIALS AND METHODS: Zebrafish larvae at 3 days post-fertilization were amputated at the fin and subsequently treated with RRP. The pro-wound healing and regenerative effects of RRP were evaluated through morphological analysis, assessment of cell proliferation and apoptosis, Additionally, mechanistic insights were gained through a comprehensive approach encompassing network pharmacology analysis, cell tracing, RNA-sequencing, CRISPR/Cas9 gene editing, and pharmacological inhibition. RESULTS: Our findings demonstrate that RRP significantly accelerates caudal fin regeneration in zebrafish following injury by suppressing cell apoptosis, promoting cell proliferation, and upregulating the expression of regenerative-related genes. Furthermore, RRP triggers autophagy signals during the regenerative process, which is attenuated by the autophagy inhibitor chloroquine (CQ). Notably, the administration of RRP enhances the expression of ahr1 and ahr2 in the regenerating fin. Genetic knockout of ahr1a, ahr1b, or ahr2 using CRISPR/Cas9, or pharmacological blockade of AHR signals with the antagonist CH-223191, diminishes the regenerative potential of RRP. Remarkably, zebrafish lacking ahr2 completely lose their fin regeneration ability. Additionally, inhibition of AHR signaling suppresses autophagy signaling during fin regeneration. CONCLUSIONS: This study uncovers that RRP stimulates fin regeneration in zebrafish by inducing AHR signals and, at least partially, activating the autophagy process. These findings provide novel insights into the molecular mechanisms underlying the wound-healing effects of RRP and may pave the way for the development of novel therapeutic strategies.

Silver nanoparticles facilitate phage-borne resistance gene transfer in planktonic and microplastic-attached bacteria.

The spread of bacteriophage-borne antibiotic resistance genes (ARGs) poses a realistic threat to human health. Nanomaterials, as important emerging pollutants, have potential impacts on ARGs dissemination in aquatic environments. However, little is known about its role in transductive transfer of ARGs mediated by bacteriophage in the presence of microplastics. Therefore, this study comprehensively investigated the influence of silver nanoparticles (AgNPs) on the transfer of bacteriophage-encoded ARGs in planktonic Escherichia coli and microplastic-attached biofilm. AgNPs exposure facilitated the phage transduction in planktonic and microplastic-attached bacteria at ambient concentration of 0.1 mg/L. Biological binding mediated by phage-specific recognition, rather than physical aggregation conducted by hydrophilicity and ζ-potential, dominated the bacterial adhesion of AgNPs. The aggregated AgNPs in turn resulted in elevated oxidative stress and membrane destabilization, which promoted the bacteriophage infection to planktonic bacteria. AgNPs exposure could disrupt colanic acid biosynthesis and then reduce the thickness of biofilm on microplastics, contributing to the transfer of phage-encoded ARGs. Moreover, the roughness of microplastics also affected the performance of AgNPs on the transductive transfer of ARGs in biofilms. This study reveals the compound risks of nanomaterials and microplastics in phage-borne ARGs dissemination and highlights the complexity in various environmental scenarios.

Development and Validation of a Predictive Model for Intraoperative Hypothermia in Elderly Patients Undergoing Craniocerebral Tumor Resection: A Retrospective Cohort Study.

OBJECTIVE: Timely identification of elderly patients who are at risk of developing intraoperative hypothermia (IH) is imperative to enable appropriate interventions. This study aimed to develop a nomogram for predicting the risk of IH in elderly patients undergoing resection of craniocerebral tumor, and to validate its effectiveness. METHODS: Elderly patients who underwent craniocerebral tumor resection at a large tertiary hospital in eastern China between January 2019 and December 2022 were included (n = 988). The study population was divided into a training set and a validation set by time period. Risk factors identified through the Least Absolute Shrinkage and Selection Operator method and logistic regression analysis were used to establish the nomogram. The model was validated internally by Bootstrap method and externally by validation set through receiver operating characteristic curve analysis, Hosmer-Lemeshow test, and decision curve analysis. RESULTS: A total of 273 (27.6%) patients developed IH. Duration of anesthesia (P < 0.001), blood loss (P < 0.001), preoperative temperature (P < 0.001), tumor location (P < 0.001), age (P < 0.05), and mean arterial pressure (P < 0.05) were identified as independent risk factors for IH. A nomogram integrating these 6 factors was constructed. The area under the curve was 0.773 (95% confidence interval: 0.735-0.811) (70.5% specificity and 75.0% sensitivity), indicating good predictive performance. The decision curve analysis demonstrated the clinical benefit of using the nomogram. CONCLUSIONS: Our model showed good performance in identifying elderly patients who are at high risk of developing IH during craniocerebral tumor resection. The nomogram can help inform timely preventive interventions.

Real-time reconfigurable metasurfaces enabling agile terahertz wave front manipulation.

Real-time controlled programmable metasurfaces, having an array-of-subarrays architecture under the control of one-bit digital coding sequence, are demonstrated for rapid and precise multifunctional Terahertz wave front engineering.

Metabolic profiling of the flower of Citrus aurantium L. var. amara Engl. in rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry with data mining strategy.

RATIONALE: The flower of Citrus aurantium L. var. amara Engl. (FCAVA), an edible tea and herbal medicine with anti-obesity effect, has attracted great attention in China. The structural elucidation of chemical components in FCAVA has been realized in our previous work. It is well known that metabolic profiling provided a structural basis to discover potential anti-obesity ingredients in FCAVA. Nevertheless, there are no reports about in vivo metabolic profiles of FCAVA. Therefore, it is necessary to comprehensively identify in vivo substances of FCAVA. METHODS: The identification of in vivo substances of FCAVA remains a challenge due to the strong interference of complex chemical components, biological matrices and metabolite isomers. In this work, ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) analysis with a data mining strategy was established and applied for the metabolic profiling of FCAVA in rats. The data mining strategy, including diagnostic product ions and neutral loss filtering, improved structural elucidation of xenobiotics in rats after oral administration of FCAVA. RESULTS: A total of 228 xenobiotics, including 80 prototypes (10 unambiguous confirmed with reference standards) and 148 metabolites, were tentatively characterized in rat plasma, urine and fecal samples. Among them, 35 xenobiotics were found in plasma, 124 in urine and 156 in feces. The main biotransformation pathway of FCAVA metabolism was deglycosylation, methylation, glucuronidation and sulfation. The main compounds absorbed into the blood were neohesperidin and naringin, which have been reported to show significant anti-obesity effect. CONCLUSIONS: Collectively, this present study would be conducive to the discovery of active ingredients of FCAVA for the treatment of obesity and the development of quality control of FCAVA.

Metal-based nanomaterials as antimicrobial agents: A novel driveway to accelerate the aggravation of antibiotic resistance.

The consequences of antibiotic tolerance directly affect human health and result in socioeconomic loss. Nanomaterials as antimicrobial agents are considered a promising alternative to antibiotics and have been blended with various medical applications. However, with increasing evidence that metal-based nanomaterials may induce antibiotic tolerance, there is an urgent need to scrutinize how nanomaterial-induced microbial adaption affects the evolution and spread of antibiotic tolerance. Accordingly, within this investigation, we summarized the principal factors influencing the resistance development exposed to metal-based nanomaterials, including physicochemical properties, exposure scenario, as well as bacterial response. Furthermore, the mechanisms of metal-based nanomaterial-induced antibiotic resistance development were comprehensively elucidated from acquired resistance by horizontal transfer of antibiotic resistance genes (ARGs), intrinsic resistance by genetic mutation or upregulated resistance-related gene expression, and adaptive resistance by global evolution. Overall, our review raises concerns about the safety of nanomaterials as antimicrobial agents, which will facilitate assistance in the safe development of antibiotic-free antibacterial strategies.

Potential impact of platelet-to-lymphocyte ratio on prognosis in patients with colorectal cancer: A systematic review and meta-analysis.

Background: Numerous studies have confirmed that inflammation promotes the occurrence, development and prognosis of colorectal cancer (CRC). Objective: This study focuses on the potentially prognostic value of the platelet-to-lymphocyte ratio (PLR) in CRC patients. Data Sources: This study was registered at PROSPERO (ID: CRD42020219215). Relative studies were searched on PubMed, Cochrane Library, Embase, Web of Science, and clinical trial databases by two back-to-back reviewers. Study Selection and Intervention: Studies were screened according to the predetermined inclusion and exclusion criteria, comparing prognosis differences between low PLR levels and high PLR levels for CRC patients. Main Outcome Measures: Studies were integrated and compared to analyze the value of PLR in predicting overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), disease-free survival (DFS) and recurrence-free survival (RFS) of CRC. Results: Outcomes were compared using Review Manager (version 5.4) software from Cochrane Collaboration. A total of 27 literary works, including 13,330 patients, were incorporated into our study. The final results showed that higher PLR levels had worse OS (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.21-1.62, P < 0.00001), DFS (HR = 1.44, 95% CI = 1.09-1.90, P = 0.01) and RFS (HR = 1.48, 95% CI = 1.13-1.94, P = 0.005) than lower PLR levels, respectively. However, there was no evidence of significance for PFS (HR = 1.14, 95% CI = 0.84-1.54, P = 0.40) and CSS (HR = 1.16, 95% CI = 0.88-1.53, P = 0.28) in the final meta-analysis. Limitations: Our study has the following limitations. First of all, we only included literature published in English, which means that some publication bias may be inevitable. In addition, our study used aggregate data, not individual data; furthermore, we did not define the exact cut-off value representing the PLR level. Conclusion: An elevated PLR seems to be an adverse prognostic factor affecting survival outcomes in patients with CRC. Meanwhile, more prospective studies are required to confirm our conclusion.PROSPERO ID: CRD42020219215.

Sinomenine Derivatives: Synthesis, Antitumor Activity, and Apoptotic Induction in MCF-7 Cells via IL-6/PI3K/Akt/NF-κB Signaling Pathway.

Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4 a-i, 7 a-c and 11 a-c) as antitumor agents from this natural product. All compounds were prepared by modification at the C1 and C4 positions of the A ring, the C4 position of the A ring, and the C6 and C7 positions of the C ring, respectively. All the derivatives were subjected to in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western blot assays were carried out for active compound against MCF-7. Based on the screening results, most of the SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad-spectrum antitumor activity. Most notably, 11 c exhibited obvious antitumor activity in both cell lines with IC50 values less than 11 µM. Besides, 11 c induced apoptosis of MCF-7 in a dose-dependent manner. Western blot assay demonstrated that 11 c inhibited IL-6-mediated activation of PI3K/Akt pathway. A docking study revealed that 11 c had stronger binding interaction with the residues of IL-6 than SIN. All these results indicate that 11 c may be a potential anti-breast cancer agent by directly targeting IL-6.

Knowledge, training and willingness to perform bystander cardiopulmonary resuscitation among university students in Chongqing, China: a cross-sectional study.

OBJECTIVE: To evaluate knowledge of cardiopulmonary resuscitation (CPR) among Chinese college students and their attitude towards participating in CPR training and willingness to perform bystander CPR. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 1128 college students were selected through a multistage stratified random sampling method from 12 universities in Chongqing, China. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes included CPR knowledge and willingness to participate in training and perform bystander CPR; secondary outcomes included CPR training experience and obstacles to training and performing CPR. RESULTS: The average score on CPR knowledge was 2.078 (±1.342). Only 45.5% of the respondents were willing to participate in CPR training. Women, respondents who were postgraduate or above, with liberal arts as major and with high CPR knowledge level were more willing to participate in CPR training. A total of 47.2% of the respondents were willing to provide simple assistance, such as checking the consciousness and breathing of the patient and dialling 120 (medical emergency call). Only 34.1% indicated their willingness to perform bystander CPR on strangers. Perceived behavioural control, behavioural attitudes and subjective norms are positive predictors of willingness to provide bystander CPR. CONCLUSIONS: CPR knowledge and training rate were low among Chongqing college students. Willingness to participate in training and perform bystander CPR was also low. Improving legislation, strengthening training programmes, incorporating CPR training into the school curriculum and reshaping the social and public culture of offering timely help to those in need are recommended strategies to improve bystander CPR performance.

Ultrathin freestanding terahertz vector beam generators with free phase modulation.

Simultaneous control of phase and polarization offers a large degree of freedom to tailor the beam properties, for instance, enabling generation of structured beams such as vector beams and vector vortex beams. Here, we propose an ultrathin freestanding metasurface operating at the terahertz frequency for efficient generation of vector vortex beam with an arbitrarily defined topological charge from linearly polarized excitation. The metasurface is composed of bilayer metallic patterns separated by a thin quartz slab, with one layer determining the transmission polarization and the other controlling the transmission phase. The tightly cascaded two layers form a Fabry-Perot cavity to maximize the efficiency of the polarization and phase control. Two metasurfaces for generation of radially polarized vector beam with uniform phase and vortex phase are fabricated and tested at 0.14 THz. The experimental results successfully demonstrate the generation of high-quality vector beams with the desired phase. In the experiment, the ultrathin and freestanding properties allow the metasurface to be easily combined with other components, which shows great potential for the development of various compact terahertz systems.