FeSA­Ir/Metallene Nanozymes Induce Sequential Ferroptosis­Pyroptosis for Multi­Immunogenic Responses Against Lung Metastasis.

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O2 and 1O2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition.

A novel strategy for improving bowel preparation based on social software-enhanced education: A prospective, multicenter, randomized controlled study.

BACKGROUND AND AIM: The compliance and timeliness of oral laxatives have always been the key factors restricting bowel preparation (BP). We have constructed a novel enhanced-educational content and process based on social software (SS) for BP to optimize these issues. METHODS: A multicenter, prospective, randomized controlled study was conducted at 13 hospitals in China from December 2019 to December 2020. A total of 1774 enrollees received standard instructions for BP and were randomly assigned (1:1) to the SS group (SSG) that received a smartphone-based enhanced-education strategy starting 4 h before colonoscopy or the control group (CG). RESULTS: A total of 3034 consecutive outpatient colonoscopy patients were assessed for eligibility, and 1774 were enrolled and randomly assigned. Ultimately, data from 1747 (SSG vs CG: 875 vs 872) enrollees were collected. The BP adequacy rate was 92.22% (95% CI: 90.46-93.98) in the SSG vs 88.05% (95% CI: 85.91-90.18) in the CG (P = 0.005), and the total Boston Bowel Preparation Scale scores (6.89 ± 1.15 vs 6.67 ± 1.15, P < 0.001) of those in the SSG were significantly higher than those in the CG. The average number of polyps detected in the SSG was considerably higher than that in the CG (0.84 ± 2.00 vs 0.53 ± 1.19, P = 0.037), and the average diameter of the polyps was significantly lower than that of the control group (4.0 ± 2.5 vs 4.9 ± 3.7, P < 0.001). CONCLUSIONS: This SS-enhanced education strategy can improve the BP adequacy rate and increase the average number of polyps detected, especially those of small diameter.

Application of root cause analysis and TEAMSTEPPS post intravesical gas explosion during transurethral resection of the prostate: a rare case report.

BACKGROUND: An intravesical gas explosion is a rare complication of transurethral resection of the prostate (TURP). It was first reported in English literature in 1926, and up to 2022 were only forty-one cases. Injury from an intravesical gas explosion, in the most severe cases appearing as extraperitoneal or intraperitoneal bladder rupture needed emergent repair surgery. CASE PRESENTATION: We present a case of a 75-year-old man who suffered an intravesical gas explosion during TURP. The patient underwent an emergent exploratory laparotomy for bladder repair and was transferred to the intensive care unit for further observation and treatment. Under the medical team's care for up to sixty days, the patient recovered smoothly without clinical sequelae. CONCLUSIONS: This case report presents an example of a rare complication of intravesical gas explosion during TURP, utilizing root cause analysis (RCA) to comprehend causal relationships and team strategies and tools to improve performance and patient safety (TeamSTEPPS) method delivers four teamwork skills that can be utilized during surgery and five recommendations to avoid gas explosions during TURP to prevent the recurrence of medical errors. In modern healthcare systems, promoting patient safety is crucial. Once complications appear, RCA and TeamSTEPPS are helpful means to support the healthcare team reflect and improve as a team.

Multi-Functional Integration of Phosphor, Initiator, and Crosslinker for the Photo-Polymerization of Flexible Phosphorescent Polymer Gels.

A general approach to constructing room temperature phosphorescence (RTP) materials involves the incorporation of a phosphorescent emitter into a rigid host or polymers with high glass transition temperature. However, these materials often suffer from poor processability and suboptimal mechanical properties, limiting their practical applications. In this work, we developed benzothiadiazole-based dialkene (BTD-HEA), a multifunctional phosphorescent emitter with a remarkable yield of intersystem crossing (ΦISC, 99.83 %). Its high triplet exciton generation ability and dialkene structure enable BTD-HEA to act as a photoinitiator and crosslinker, efficiently initiating the polymerization of various monomers within 120 seconds. A range of flexible phosphorescence gels, including hydrogels, organogels, ionogels, and aerogels were fabricated, which exhibit outstanding stretchability and recoverability. Furthermore, the unique fluorescent-phosphorescent colorimetric properties of the gels provide a more sensitive method for the visual determination of the polymerization process. Notably, the phosphorescent emission intensity of the hydrogel can be increased by the formation of ice, allowing for the precise detection of hydrogel freezing. The versatility of this emitter paves the way for fabricating various flexible phosphorescence gels with diverse morphologies using microfluidics, film-shearing, roll coating process, and two/three-dimensional printing, showcasing its potential applications in the fields of bioimaging and bioengineering.

Biomimetic Metal-Pyrimidine Nanoflowers: Enzyme Immobilization Platforms with Boosted Activity.

For the enzyme immobilization platform, enhancing enzyme activity retention while improving enzyme stability remains a challenge for sensitive sensing analysis. Herein, an in situ biomimetic immobilized enzyme carrier (metal-pyrimidine nanoflowers, MPNFs) synthesized by the coordination of DNA base derivative (2-aminopyrimidine) with Zn2+ in the aqueous phase at room temperature is developed. The biocompatibility of 2-aminopyrimidine and the hydrophilicity and green synthetic conditions of MPNFs allows the immobilized enzymes to retain above 91.2% catalytic activity. On this basis, a cascade catalytic platform is constructed by simultaneously immobilizing acetylcholinesterase (AChE), choline oxidase (CHO), and horseradish peroxidase (HRP) in MPNFs (AChE/CHO/HRP@MPNFs) for organophosphorus pesticides (OPs) colorimetric biosensing detection. The assay could specifically detect parathion-methyl within 13 min with a wider linear range (0.1-1000.0 nm) and a lower limit of detection (LOD) (0.032 nm). The remarkable stability of the immobilized enzymes is also achieved under harsh environments, room temperature storage, and recycling. Furthermore, a portable and cost-effective biosensing platform is developed by integrating AChE/CHO/HRP@MPNFs with a smartphone-assisted paper device for the on-site detection of OPs. Overall, the high catalytic activity retention and the enhanced detection performance demonstrate that MPNF is a robust carrier in enzyme immobilization and holds great promise in biosensing and other field applications.

Designing Clinical MRI for Enhanced Workflow and Value.

MRI is an expensive and traditionally time-intensive modality in imaging. With the paradigm shift toward value-based healthcare, radiology departments must examine the entire MRI process cycle to identify opportunities to optimize efficiency and enhance value for patients. Digital tools such as "frictionless scheduling" prioritize patient preference and convenience, thereby delivering patient-centered care. Recent advances in conventional and deep learning-based accelerated image reconstruction methods have reduced image acquisition time to such a degree that so-called nongradient time now constitutes a major percentage of total room time. For this reason, architectural design strategies that reconfigure patient preparation processes and decrease the turnaround time between scans can substantially impact overall throughput while also improving patient comfort and privacy. Real-time informatics tools that provide an enterprise-wide overview of MRI workflow and Picture Archiving and Communication System (PACS)-integrated instant messaging can complement these efforts by offering transparent, situational data and facilitating communication between radiology team members. Finally, long-term investment in training, recruiting, and retaining a highly skilled technologist workforce is essential for building a pipeline and team of technologists committed to excellence. Here, we highlight various opportunities for optimizing MRI workflow and enhancing value by offering many of our own on-the-ground experiences and conclude by anticipating some of the future directions for process improvement and innovation in clinical MR imaging. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.

Nutraceutical delivery systems to improve the bioaccessibility and bioavailability of lycopene: A review.

Lycopene is a promising biological functional component with various biological activities and excellent pharmacological activities. However, its low water solubility and stability lead to low oral bioavailability, which limits its edible and medicinal research. Then, it is necessary to explore effective methods to protect lycopene from destruction and further exploit its potential benefits. The absorption of lycopene in vivo is affected by solubility, stability, isomer type, emulsifying ability, difficulty in forming micelles in vivo, and interaction with food components. Emulsions, pickering emulsions, micelles, liposomes, bigels, beasds, solid dispersions, microcapsules, nanoparticles, electrospinning and other drug delivery systems can be used as good strategies to improve the stability and bioavailability of lycopene. In this paper, the absorption process of lycopene in vivo and the factors affecting its bioavailability were discussed, and the preparation strategies for improving the stability, bioavailability, and health benefits of lycopene were reviewed, to provide some clues and references for the full utilization of lycopene in the field of health. However, there are still various unresolved mysteries regarding the metabolism of lycopene. The safety and in vivo studies of various preparations should be further explored, and the above technologies also face the challenge of industrial production.

Metabolic Profiling of Endophytic Bacteria in Relation to Their Potential Application as Components of Multi-Task Biopreparations.

Agricultural crops are exposed to various abiotic and biotic stresses that can constrain crop productivity. Focusing on a limited subset of key groups of organisms has the potential to facilitate the monitoring of the functions of human-managed ecosystems. Endophytic bacteria can enhance plant stress resistance and can help plants to cope with the negative impacts of stress factors through the induction of different mechanisms, influencing plant biochemistry and physiology. In this study, we characterise endophytic bacteria isolated from different plants based on their metabolic activity and ability to synthesise 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD), the activity of hydrolytic exoenzymes, the total phenolic compounds (TPC) and iron-complexing compounds (ICC). Test GEN III MicroPlate indicated that the evaluated endophytes are highly metabolically active, and the best used substrates were amino acids, which may be important in selecting potential carrier components for bacteria in biopreparations. The ACCD activity of strain ES2 (Stenotrophomonas maltophilia) was the highest, whereas that of strain ZR5 (Delftia acidovorans) was the lowest. Overall, the obtained results indicated that ∼91.3% of the isolates were capable of producing at least one of the four hydrolytic enzymes. In addition, most of the tested strains produced ICC and TPC, which play a significant role in reducing stress in plants. The results of this study suggest that the tested endophytic bacterial strains can potentially be used to mitigate climate change-associated stresses in plants and to inhibit plant pathogens.

CRISPR-ENHANCE: An enhanced nucleic acid detection platform using Cas12a.

Rapid detection of nucleic acids is essential for clinical diagnosis of a wide range of infectious and non-infectious diseases. CRISPR-based diagnostic platforms are well-established for rapid and specific detection of nucleic acids but suffer from a low detection sensitivity without a target pre-amplification step. Our recently developed detection system, called CRISPR-ENHANCE, employs engineered crRNAs and optimized conditions to achieve a significantly higher sensitivity and enable femtomolar levels of nucleic acid detection even without target pre-amplification. Using the CRISPR-ENHANCE platform and following the methodology detailed in this paper, nucleic acid detection for low copy numbers can be achieved in less than an hour through either a fluorescence-based detection or a lateral flow assay. The step-by-step instructions provided, in addition to describing how to perform both assays, incorporate details on a LAMP/RT-LAMP-based target amplification step to enable detection of RNA, ssDNA and dsDNA. Furthermore, a protocol for in-house expression and purification of LbCas12a using CL7/lm7-based affinity chromatography, which has been used to achieve a high yield and purity of the enzyme in a single-step, is provided.

Learning to deep learning: statistics and a paradigm test in selecting a UNet architecture to enhance MRI.

OBJECTIVE: This study aims to assess the statistical significance of training parameters in 240 dense UNets (DUNets) used for enhancing low Signal-to-Noise Ratio (SNR) and undersampled MRI in various acquisition protocols. The objective is to determine the validity of differences between different DUNet configurations and their impact on image quality metrics. MATERIALS AND METHODS: To achieve this, we trained all DUNets using the same learning rate and number of epochs, with variations in 5 acquisition protocols, 24 loss function weightings, and 2 ground truths. We calculated evaluation metrics for two metric regions of interest (ROI). We employed both Analysis of Variance (ANOVA) and Mixed Effects Model (MEM) to assess the statistical significance of the independent parameters, aiming to compare their efficacy in revealing differences and interactions among fixed parameters. RESULTS: ANOVA analysis showed that, except for the acquisition protocol, fixed variables were statistically insignificant. In contrast, MEM analysis revealed that all fixed parameters and their interactions held statistical significance. This emphasizes the need for advanced statistical analysis in comparative studies, where MEM can uncover finer distinctions often overlooked by ANOVA. DISCUSSION: These findings highlight the importance of utilizing appropriate statistical analysis when comparing different deep learning models. Additionally, the surprising effectiveness of the UNet architecture in enhancing various acquisition protocols underscores the potential for developing improved methods for characterizing and training deep learning models. This study serves as a stepping stone toward enhancing the transparency and comparability of deep learning techniques for medical imaging applications.

Tumor segmentation via enhanced area growth algorithm for lung CT images.

BACKGROUND: Since lung tumors are in dynamic conditions, the study of tumor growth and its changes is of great importance in primary diagnosis. METHODS: Enhanced area growth (EAG) algorithm is introduced to segment the lung tumor in 2D and 3D modes on 60 patients CT images from four different databases by MATLAB software. The contrast augmentation, color intensity and maximum primary tumor radius determination, thresholding, start and neighbor points' designation in an array, and then modifying the points in the braid on average are the early steps of the proposed algorithm. To determine the new tumor boundaries, the maximum distance from the color-intensity center point of the primary tumor to the modified points is appointed via considering a larger target region and new threshold. The tumor center is divided into different subsections and then all previous stages are repeated from new designated points to define diverse boundaries for the tumor. An interpolation between these boundaries creates a new tumor boundary. The intersections with the tumor boundaries are firmed for edge correction phase, after drawing diverse lines from the tumor center at relevant angles. Each of the new regions is annexed to the core region to achieve a segmented tumor surface by meeting certain conditions. RESULTS: The multipoint-growth-starting-point grouping fashioned a desired consequence in the precise delineation of the tumor. The proposed algorithm enhanced tumor identification by more than 16% with a reasonable accuracy acceptance rate. At the same time, it largely assurances the independence of the last outcome from the starting point. By significance difference of p < 0.05, the dice coefficients were 0.80 ± 0.02 and 0.92 ± 0.03, respectively, for primary and enhanced algorithms. Lung area determination alongside automatic thresholding and also starting from several points along with edge improvement may reduce human errors in radiologists' interpretation of tumor areas and selection of the algorithm's starting point. CONCLUSIONS: The proposed algorithm enhanced tumor detection by more than 18% with a sufficient acceptance ratio of accuracy. Since the enhanced algorithm is independent of matrix size and image thickness, it is very likely that it can be easily applied to other contiguous tumor images. TRIAL REGISTRATION: PAZHOUHAN, PAZHOUHAN98000032. Registered 4 January 2021, http://pazhouhan.gerums.ac.ir/webreclist/view.action?webreclist_code=19300.

Pashto Handwritten Invariant Character Trajectory Prediction Using a Customized Deep Learning Technique.

Before the 19th century, all communication and official records relied on handwritten documents, cherished as valuable artefacts by different ethnic groups. While significant efforts have been made to automate the transcription of major languages like English, French, Arabic, and Chinese, there has been less research on regional and minor languages, despite their importance from geographical and historical perspectives. This research focuses on detecting and recognizing Pashto handwritten characters and ligatures, which is essential for preserving this regional cursive language in Pakistan and its status as the national language of Afghanistan. Deep learning techniques were employed to detect and recognize Pashto characters and ligatures, utilizing a newly developed dataset specific to Pashto. A further enhancement was done on the dataset by implementing data augmentation, i.e., scaling and rotation on Pashto handwritten characters and ligatures, which gave us many variations of a single trajectory. Different morphological operations for minimizing gaps in the trajectories were also performed. The median filter was used for the removal of different noises. This dataset will be combined with the existing PHWD-V2 dataset. Various deep-learning techniques were evaluated, including VGG19, MobileNetV2, MobileNetV3, and a customized CNN. The customized CNN demonstrated the highest accuracy and minimal loss, achieving a training accuracy of 93.98%, validation accuracy of 92.08% and testing accuracy of 92.99%.

Enhancement Effects and Mechanism Studies of Two Bismuth-Based Materials Assisted by DMSO and Glycerol in GC-Rich PCR.

Polymerase chain reaction (PCR) has extensive bioanalytical applications in molecular diagnostics and genomic research studies for rapid detection and precise genomic amplification. Routine integrations for analytical workflow indicate certain limitations, including low specificity, efficiency, and sensitivity in conventional PCR, particularly towards amplifying high guanine-cytosine (GC) content. Further, there are many ways to enhance the reaction, for example, using different PCR strategies such as hot-start/touchdown PCR or adding some special modifications or additives such as organic solvents or compatible solutes, which can improve PCR yield. Due to the widespread use of bismuth-based materials in biomedicine, which have not yet been used for PCR optimization, this attracts our attention. In this study, two bismuth-based materials that are inexpensive and readily available were used to optimize GC-rich PCR. The results demonstrated that ammonium bismuth citrate and bismuth subcarbonate effectively enhanced PCR amplification of the GNAS1 promoter region (∼84% GC) and APOE (75.5% GC) gene of Homo sapiens mediated by Ex Taq DNA polymerase within the appropriate concentration range. Combining DMSO and glycerol additives was critical in obtaining the target amplicons. Thus, the solvents mixed with 3% DMSO and 5% glycerol were used in bismuth-based materials. That allowed for better dispersion of bismuth subcarbonate. As for the enhanced mechanisms, the surface interaction of PCR components, including Taq polymerase, primer, and products with bismuth-based materials, was maybe the main reason. The addition of materials can reduce the melting temperature (Tm), adsorb polymerase and modulate the amount of active polymerase in PCR, facilize the dissociation of DNA products, and enhance the specificity and efficiency of PCR. This work provided a class of candidate enhancers for PCR, deepened our understanding of the enhancement mechanisms of PCR, and also explored a new application field for bismuth-based materials.

Effects of enhance recovery after surgery nursing program on the surgical site wound infection in patients undergoing laparoscopic hepatectomy for hepatocellular carcinoma: A meta-analysis.

Our study aimed to investigate the effects of an enhanced recovery after surgery (ERAS) nursing program on surgical site wound infections (SSWI) and postoperative complications in patients undergoing laparoscopic hepatectomy (LH) for hepatocellular carcinoma. Computer searches of the PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases were conducted to gather randomised controlled trials (RCTs) that were published from inception to September 2023. The target studies evaluated the effects of the ERAS nursing program in patients undergoing LH for hepatocellular carcinoma. Two independent authors screened the literature, extracted the data and performed quality assessments. Dichotomous variables were analysed using odds ratios (ORs) and 95% confidence intervals (CIs), as effect analysis statistics. Stata software (version 17.0) was used for data analysis. Eleven RCTs with 765 patients were included, with 383 patients in the ERAS group and 382 in the control group. The results revealed that the incidence of SSWI (OR = 0.32, 95%CI:0.15-0.71, p = 0.004) and postoperative complications (OR = 0.23, 95%CI:0.15-0.34, p < 0.001) were both significantly reduced in the ERAS group, compared with the control group. The ERAS nursing program, when applied to patients undergoing laparoscopic hepatic cancer resection, can effectively reduce the incidence of SSWI and postoperative complications, thus promoting postoperative recovery.

Effects of using educational technology tools to enhance EFL students' speaking performance.

Educational speaking technology is a digital expertise used to enhance speaking performance. This research examined the effects of using educational speaking technology tools: FORVO, YouGlish, and OALD 8th ed. to enhance students' speaking performance. A quasi-experimental pretest-posttest two groups design was used. Test, questionnaire, interview, and teacher-log were used to gather the data from 82 first-year Information communication and Technology (IT) students selected through comprehensive sampling. The experimental group students had learned speaking skills through educational speaking technology tools while the control group students learned using the conventional method. When the quantitative data were analyzed through independent samples T-test, the qualitative data were analyzed through thematic analysis. The findings of the study uncovered that there was a statistical difference between the experimental and control group students in their speaking performance. Accordingly, the learners who had learned through educational speaking technology have enhanced their speaking performance compared to the students that learned conventionally. Predominantly, students who learned through educational speaking technology were fluent, coherent, and accurate in their speech, rich in lexical resources, used a variety of grammatical ranges, and better in pronunciation. Besides, the students' have positive perceptions towards using educational speaking technology tools. Consequently, this study recommends researchers, teachers, and students to make the use of educational technology and to go in line with the state of the art.

Early removal of drains and lines after liver transplantation to reduce the length of hospital stay and enhance recovery - A systematic review of the literature and expert panel recommendations.

BACKGROUND: The timing of removing abdominal drains, central venous catheters (CVC), and urinary catheters (UC) on post liver transplantation (LT) outcomes is not well elucidated. OBJECTIVES: To provide international expert panel recommendations and guidelines on time of drain and catheter removal as a part of an ERAS protocol to reduce the length of hospital stay and enhance recovery. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Papers considered were those reporting one or more outcomes of interest related to drainage and line removal in the setting of LT. POSPERO Protocol ID: CRD42021238349 RESULTS: On analyzing five relevant studies pertaining to drains in patients undergoing LT (four retrospectives and one prospective), the length of hospital and/or ICU stay was similar or shorter, and postoperative morbidity and mortality were lower in those without drains. No studies pertaining specifically to the time of removal of drains, CVC's, or UC's in LT were found. Studies in patients undergoing major abdominal surgery or hepatectomies recommend early removal of CVC and UC to reduce catheter-associated infections. CONCLUSIONS: Based more on expert recommendation, we propose that abdominal drains, if placed during LT, should be removed by postoperative day 5 after LT, based on quantity and fluid characteristics (Quality of Evidence; Low to Moderate | Grade of Recommendation; Strong). Larger studies are needed to more reliably determine indications for early drain and line removal in an ERAS protocol setting.

Reposition of the anti-inflammatory drug diacerein in an in-vivo colorectal cancer model.

Excessive interleukin (IL)-6 production is a driver for malignancy and drug resistance in colorectal cancer (CRC). Our study investigated a seven-week post-treatment with the anti-inflammatory drug, Diacerein (Diac), alone or in combination with 5-fluorouracil (5-FU), using a 1,2-dimethylhydrazine (DMH) rat model of CRC. Diac alone and 5-FU+Diac reduced serum levels of carcino-embryonic antigen (CEA), while all regimens decreased serum levels of colon cancer-specific antigen (CCSA), a more specific CRC biomarker. Additionally, Diac, 5-FU and their combination suppressed colonic content/gene expression of IL-6, its downstream oncogene, Kirsten rat sarcoma viral oncogene homolog (K-Ras), and consequently Notch intracellular domain and nuclear factor-kappa B (NF-κB) p65. In turn, NF-κB downstream factors, viz., matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), c-Myc, and B-cell lymphoma-2 (Bcl-2) were also downregulated, while E-cadherin was elevated. Additionally, the drugs reduced the immunoreactivity of CD31 to prove their anti-angiogenic effect, while the TUNEL assay confirmed the apoptotic effect. The apoptotic effect was confirmed by transferase dUTP nick-end labeling assay. Moreover, these drugs inhibited colon content of p-Akt, ß-catenin, and cyclin D1 immunoreactivity. The drugs also activated the tumor suppressor glycogen synthase kinase 3- ß (GSK3-ß) and upregulated the expression of the Nur77 gene, which represents the second arm of IL-6 signaling. However, only 5-FU upregulated miR-200a, another K-Ras downstream factor. The in-vitro cytotoxic and migration/invasion assays verified the molecular trajectories. Accordingly, we evaluated the antineoplastic effect of Diac alone and its possible chemosensitization effect when added to 5-FU. This combination may target critical oncogenic pathways, including the IL-6/K-Ras/Notch/NF-κB p65 axis, p-Akt/GSK3-ß/ß-catenin/cyclin D-1 hub, and Nur77.

Mean force based temperature accelerated sliced sampling: Efficient reconstruction of high dimensional free energy landscapes.

Temperature accelerated sliced sampling (TASS) is an efficient method to compute high dimensional free energy landscapes. The original TASS method employs the weighted histogram analysis method (WHAM) which is an iterative post-processing to reweight and stitch high dimensional probability distributions in sliced windows that are obtained in the presence of restraining biases. The WHAM necessitates that TASS windows lie close to each other for proper overlap of distributions and span the collective variable space of interest. On the other hand, increase in number of TASS windows implies more number of simulations, and thus it affects the efficiency of the method. To overcome this problem, we propose herein a new mean-force (MF) based reweighting scheme called TASS-MF, which enables accurate computation with a fewer number of windows devoid of the WHAM post-processing. Application of the technique is demonstrated for alanine di- and tripeptides in vacuo to compute their two- and four-dimensional free energy landscapes, the latter of which is formidable in conventional umbrella sampling and metadynamics. The landscapes are computed within a kcal mol-1 accuracy, ensuring a safe usage for broad applications in computational chemistry.

The "Why" of Drinking Matters: A Meta-Analysis of the Association Between Drinking Motives and Drinking Outcomes.

BACKGROUND: Knowledge of how drinking motives are differentially associated with alcohol use (e.g., frequency, quantity) and drinking problems is critical in understanding risky drinking and the development of alcohol use disorder. The purpose of this paper was to use meta-analytic techniques to answer 2 overarching questions: (a) Which types of drinking motives (i.e., enhancement, coping, social, conformity) are most strongly associated with alcohol use and drinking problems? and (b) What are the most likely mechanisms (alcohol use or drinking problems) through which motives may be indirectly associated with outcomes? METHOD: A comprehensive literature search identified 229 studies that met inclusion criteria (254 samples; N = 130,705) with a subset containing longitudinal data (k = 5; N = 6283). Data were analyzed using 2-stage meta-analytic structural equation modeling. RESULTS: Results showed that both enhancement and coping motives were the strongest predictors of drinking problems, but only enhancement motives were the strongest predictor of alcohol use. Enhancement and social motives were indirectly associated with alcohol use through drinking problems and with drinking problems through alcohol use, whereas coping motives were only indirectly associated with alcohol use through drinking problems, although the results differed for cross-sectional and longitudinal data. CONCLUSION: Overall, findings from this meta-analysis provide evidence that drinking motives differentially predict alcohol use outcomes through unique direct and indirect pathways.

Phytoremediation of multiple persistent pollutants co-contaminated soil by HhSSB transformed plant.

The high toxicity of persistent pollutants limits the phytoremediation of pollutants-contaminated soil. In this study, heterologous expressing Halorhodospira halophila single-stranded DNA binding protein gene (HhSSB) improves tolerance to 2,4,6-trinitrotoluene (TNT), 2,4,6-trichlorophenol (2,4,6-TCP), and thiocyanate (SCN-) in A. thaliana and tall fescue (Festuca arundinacea). The HhSSB transformed Arabidopsis, and tall fescue also exhibited enhanced phytoremediation of TNT, 2,4,6-TCP, and SCN- separately contaminated soil and co-contaminated soil compared to control plants. TNT assay was selected to explore the mechanism of how HhSSB enhances the phytoremediation of persistent pollutants. Our result indicates that HhSSB enhances the phytoremediation of TNT by enhancing the transformation of TNT in Arabidopsis. Moreover, transcriptomics and comet analysis revealed that HhSSB improves TNT tolerance through three pathways: strengthening the defense system, enhancing the ROS scavenging system, and reducing DNA damage. These results presented here would be particularly useful for further studies in the remediation of soil contaminated by organic and inorganic pollutants.