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β-Branched aromatic α-amino acids are valuable building blocks in natural products and pharmaceutically active compounds. However, their chemical or enzymatic synthesis is challenging due to the presence of two stereocenters. We design phenylalanine ammonia lyases (PAL) variants for the direct asymmetric synthesis of β-branched aromatic α-amino acids. Based on extensive computational analyses, we unravel the enigma behind PAL's inability to accept β-methyl cinnamic acid (β-MeCA) as substrate and achieve the synthesis of the corresponding amino acids of β-MeCA and analogs using a double (PcPAL-L256V-I460V) and a triple mutant (PcPAL-F137V-L256V-I460V). The reactions are scaled-up using an optimized E. coli based whole-cell biotransformation system to produce ten β-branched phenylalanine analogs with high diastereoselectivity (dr > 20:1) and enantioselectivity (ee > 99.5%) in yields ranging from 41-71%. Moreover, we decipher the mechanism of PcPAL-L256V-I460V for the acceptance of β-MeCA and converting it with excellent stereoselectivity by computational simulations. Thus, this study offers an efficient method for synthesizing β-branched aromatic α-amino acids. β-Branched aromatic α-amino acids are valuable building blocks in natural products and pharmaceutically active compounds, but their synthesis is challenging due to the presence of two stereocenters. Here, the authors design phenylalanine ammonia lyases variants for the direct asymmetric synthesis of β-branched aromatic α-amino acids and reveal the reasons for enzyme's inability to accept β-methyl cinnamic acid. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, the expression, biological function and potential molecular mechanisms of a novel long non-coding RNA 495810 were detected in hepatocellular carcinoma cells. The results demonstrate a significant up-regulation of long non-coding RNA 495810 in hepatocellular carcinoma, and hepatocellular carcinoma patients with higher long non-coding RNA 495810 shows poorer overall survival and disease-free survival than those with lower long non-coding RNA 495810 level. Moreover, long non-coding RNA 495810 overexpression promotes the proliferation and migration, and blocks apoptosis and cell cycle arrest of hepatocellular carcinoma cells; while knock it down get the opposite results. Mechanistically, long non-coding RNA 495810 directly binds and up-regulates fatty acid binding protein 5 expression. In further, it was found that fatty acid binding protein 5 is up-regulated in hepatocellular carcinoma and associates with poor prognosis. More importantly, fatty acid binding protein 5 knockdown reverses the enhanced abilities of proliferation and metastasis induced by long non-coding RNA 495810 overexpression. These results reveal a novel mechanism of hepatocellular carcinoma metastasis guided by long non-coding RNA, providing a potential target for the treatment of liver cancer. Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are frequently dysregulated in human cancers and play an important role in the initiation and progression of HCC. Here, we investigated the expression of a new reported lncRNA495810 in our previous study by analyzing the publicly available datasets and using RT-qPCR assay. The cell proliferation experiment, cell cycle and apoptosis assay, wound healing assay, cell migration assay were used to explore the biological function of lncRNA495810 in HCC. The western blot, RNA pull down and RNA immunoprecipitation (RIP) detection were used to investigate the potential molecular mechanisms of lncRNA495810. The results demonstrated that lncRNA495810 was significantly upregulated in hepatocellular carcinoma and associated with poor prognosis of hepatocellular carcinoma patients. Moreover, it proved that lncRNA495810 promotes the proliferation and metastasis of hepatoma cells by directly binding and upregulating the expression of fatty acid-binding protein 5. These results reveal the oncogenic roles of lncRNA495810 in HCC and provide a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Cardiac stereotactic body radiotherapy (CSBRT) is an emerging and promising noninvasive technique for treating refractory arrhythmias utilizing highly precise, single or limited‐fraction high‐dose irradiations. This method promises to revolutionize the treatment of cardiac conditions by delivering targeted therapy with minimal exposure to surrounding healthy tissues. However, the dynamic nature of cardiorespiratory motion poses significant challenges to the precise delivery of dose in CSBRT, introducing potential variabilities that can impact treatment efficacy. The complexities of the influence of cardiorespiratory motion on dose distribution are compounded by interplay and blurring effects, introducing additional layers of dose uncertainty. These effects, critical to the understanding and improvement of the accuracy of CSBRT, remain unexplored, presenting a gap in current clinical literature.To investigate the cardiorespiratory motion characteristics in arrhythmia patients and the dosimetric impact of interplay and blurring effects induced by cardiorespiratory motion on CSBRT plan quality.The position and volume variations in the substrate target and cardiac substructures were evaluated in 12 arrhythmia patients using displacement maximum (DMX) and volume metrics. Moreover, a four‐dimensional (4D) dose reconstruction approach was employed to examine the dose uncertainty of the cardiorespiratory motion.Cardiac pulsation induced lower DMX than respiratory motion but increased the coefficient of variation and relative range in cardiac substructure volumes. The mean DMX of the substrate target was 0.52 cm (range: 0.26–0.80 cm) for cardiac pulsation and 0.82 cm (range: 0.32–2.05 cm) for respiratory motion. The mean DMX of the cardiac structure ranged from 0.15 to 1.56 cm during cardiac pulsation and from 0.35 to 1.89 cm during respiratory motion. Cardiac pulsation resulted in an average deviation of –0.73% (range: –4.01%–4.47%) in V25 between the 3D and 4D doses. The mean deviations in the homogeneity index (HI) and gradient index (GI) were 1.70% (range: –3.10%–4.36%) and 0.03 (range: –0.14–0.11), respectively. For cardiac substructures, the deviations in D50 due to cardiac pulsation ranged from –1.88% to 1.44%, whereas the deviations in Dmax ranged from –2.96% to 0.88% of the prescription dose. By contrast, the respiratory motion led to a mean deviation of –1.50% (range: –10.73%–4.23%) in V25. The mean deviations in HI and GI due to respiratory motion were 4.43% (range: –3.89%–13.98%) and 0.18 (range: –0.01–0.47) (p < 0.05), respectively. Furthermore, the deviations in D50 and Dmax in cardiac substructures for the respiratory motion ranged from –0.28% to 4.24% and –4.12% to 1.16%, respectively.Cardiorespiratory motion characteristics vary among patients, with the respiratory motion being more significant. The intricate cardiorespiratory motion characteristics and CSBRT plan complexity can induce substantial dose uncertainty. Therefore, assessing individual motion characteristics and 4D dose reconstruction techniques is critical for implementing CSBRT without compromising efficacy and safety. [ABSTRACT FROM AUTHOR]

Exploring the possible catalytic effect of black phosphorus quantum dots (BPQDs) with specific exposed planes on chemiluminescence (CL) to improve CL intensity and achieve excellent analytical performance is one of the latest research hotspots. Herein, uniform BPQDs with highly exposed (113) facets and an average size of 2.2 nm were fabricated via a facile ultrasonic exfoliation strategy. The enhanced CL intensity in the BPQDs–luminol–K3Fe-(CN)6 system is attributed to the catalytic effect of BPQDs. The catalytic mechanism of BPQDs involved in luminol–K3Fe-(CN)6 CL is revealed by theoretical calculations, which show an adsorption Gibbs free energy for oxygen of −0.86 eV, accompanied by the separation of electron–hole pairs (e––h+). In other words, after being irradiated by the CL generated from luminol and K3Fe-(CN)6, the BPQDs effectively catalyze the decomposition of dissolved oxygen to produce superoxide radical anions, which further react with luminol to increase CL emission. The noticeable suppression of the CL signal in the presence of dopamine acquired under mild conditions makes it attractive for biosensor applications, deepening the understanding of BPQDs as efficient catalysts and promoting the potential development of BPQD-based materials in the fields of photonics, biomedicine, and electronics. [ABSTRACT FROM AUTHOR]

Purpose: This review provides an overview of recent advances in electrochemical sensors for analyte detection in saliva, highlighting their potential applications in diagnostics and health care. The purpose of this paper is to summarize the current state of the field, identify challenges and limitations and discuss future prospects for the development of saliva-based electrochemical sensors. Design/methodology/approach: The paper reviews relevant literature and research articles to examine the latest developments in electrochemical sensing technologies for saliva analysis. It explores the use of various electrode materials, including carbon nanomaterial, metal nanoparticles and conducting polymers, as well as the integration of microfluidics, lab-on-a-chip (LOC) devices and wearable/implantable technologies. The design and fabrication methodologies used in these sensors are discussed, along with sample preparation techniques and biorecognition elements for enhancing sensor performance. Findings: Electrochemical sensors for salivary analyte detection have demonstrated excellent potential for noninvasive, rapid and cost-effective diagnostics. Recent advancements have resulted in improved sensor selectivity, stability, sensitivity and compatibility with complex saliva samples. Integration with microfluidics and LOC technologies has shown promise in enhancing sensor efficiency and accuracy. In addition, wearable and implantable sensors enable continuous, real-time monitoring of salivary analytes, opening new avenues for personalized health care and disease management. Originality/value: This review presents an up-to-date overview of electrochemical sensors for analyte detection in saliva, offering insights into their design, fabrication and performance. It highlights the originality and value of integrating electrochemical sensing with microfluidics, wearable/implantable technologies and point-of-care testing platforms. The review also identifies challenges and limitations, such as interference from other saliva components and the need for improved stability and reproducibility. Future prospects include the development of novel microfluidic devices, advanced materials and user-friendly diagnostic devices to unlock the full potential of saliva-based electrochemical sensing in clinical practice. [ABSTRACT FROM AUTHOR]

Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.

By highly efficient ligand-exchange strategy, atomically precise Au8Pd1(PPh3)82+ (PPh3 = triphenylphosphine) cluster can be transformed into a Au8Pd1(DPPF)42+ (DPPF = 1,1'-bis(diphenylphosphino)ferrocene) cluster that can maintain the atomic-packing structure but overcome the lability of Au8Pd1(PPh3)82+. Catalytic evaluation for the CO2 hydrogenation coupled with o-phenylenediamine demonstrates that the Au8Pd1(DPPF)42+ catalyst can remarkably enhance both activity and stability compared to the Au8Pd1(PPh3)82+ catalyst. More notably, the direct construction of a two-dimensional metal-organic framework (2D MOF) can be elaborately accomplished in the formylation process of o-phenylenediamine, CO2 and H2 with zinc nitrate enabled by the Au8Pd1(DPPF)42+ catalyst. The 2D MOF further enables the capture and transformation of CO2 to combine in the organic synthesis with epoxides under mild conditions.This work provides opportunities for creating highly active cluster sites for the chemical recycling of CO2., (© 2024 Wiley‐VCH GmbH.)

Background: Cardiac stereotactic body radiotherapy (CSBRT) with photons efficaciously and safely treats cardiovascular arrhythmias. Proton therapy, with its unique physical and radiobiological properties, can offer advantages over traditional photon-based therapies in certain clinical scenarios, particularly pediatric tumors and those in anatomically challenging areas. However, dose uncertainties induced by cardiorespiratory motion are unknown., Objective: This study investigated the effect of cardiorespiratory motion on intensity-modulated proton therapy (IMPT) and the effectiveness of motion-encompassing methods., Methods: We retrospectively included 12 patients with refractory arrhythmia who underwent CSBRT with four-dimensional computed tomography (4DCT) and 4D cardiac CT (4DcCT). Proton plans were simulated using an IBA accelerator based on the 4D average CT. The prescription was 25 Gy in a single fraction, with all plans normalized to ensure that 95% of the target volume received the prescribed dose. 4D dose reconstruction was performed to generate 4D accumulated and dynamic doses. Furthermore, dose uncertainties due to the interplay effect of the substrate target and organs at risk (OARs) were assessed. The differences between internal organs at risk volume (IRV) and OAR real (manually contoured on average CT) were compared. In 4D dynamic dose, meeting prescription requirements entails V 25 and D 95 reaching 95% and 25 Gy, respectively., Results: The 4D dynamic dose significantly differed from the 3D static dose. The mean V 25 and D 95 were 89.23% and 24.69 Gy, respectively, in 4DCT and 94.35% and 24.99 Gy, respectively, in 4DcCT. Eleven patients in 4DCT and six in 4DcCT failed to meet the prescription requirements. Critical organs showed varying dose increases. All metrics, except for D mean and D 50 , significantly changed in 4DCT; in 4DcCT, only D 50 remained unchanged with regards to the target dose uncertainties induced by the interplay effect. The interplay effect was only significant for the D max values of several OARs. Generally, respiratory motion caused a more pronounced interplay effect than cardiac pulsation. Neither IRV nor OAR real effectively evaluated the dose discrepancies of the OARs., Conclusions: Complex cardiorespiratory motion can introduce dose uncertainties during IMPT. Motion-encompassing techniques may mitigate but cannot entirely compensate for the dose discrepancies. Individualized 4D dose assessments are recommended to verify the effectiveness and safety of CSBRT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Li, Xiao, Wang, He, Luo, Chen, Li, Zhang, Qin, Song, Li and Bai.)

Objective: This research investigates the role of human factors of all hierarchical levels in radiotherapy safety incidents and examines their interconnections., Methods: Utilizing the human factor analysis and classification system (HFACS) and Bayesian network (BN) methodologies, we created a BN-HFACS model to comprehensively analyze human factors, integrating the hierarchical structure. We examined 81 radiotherapy incidents from the radiation oncology incident learning system (RO-ILS), conducting a qualitative analysis using HFACS. Subsequently, parametric learning was applied to the derived data, and the prior probabilities of human factors were calculated at each BN-HFACS model level. Finally, a sensitivity analysis was conducted to identify the human factors with the greatest influence on unsafe acts., Results: The majority of safety incidents reported on RO-ILS were traced back to the treatment planning phase, with skill errors and habitual violations being the primary unsafe acts causing these incidents. The sensitivity analysis highlighted that the condition of the operators, personnel factors, and environmental factors significantly influenced the occurrence of incidents. Additionally, it underscored the importance of organizational climate and organizational process in triggering unsafe acts., Conclusion: Our findings suggest a strong association between upper-level human factors and unsafe acts among radiotherapy incidents in RO-ILS. To enhance radiation therapy safety and reduce incidents, interventions targeting these key factors are recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Peng, Luo, Wei, Li, Wang, Xiao, Li and Bai.)