BackgroundCytotoxic drug residues in pharmacy intravenous admixture services (PIVAS) have always been a major problem for pharmaceutical workers and the PIVAS environment,which is not only pollutes ...the PIVAS environment, but also causes serious harm to the life and health of the staff. This study aimed to establish an ultra-high performance liquid chromatography quadrupole orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap-HRMS) method for the rapid detection and monitor of 15 cytotoxic drugs. MethodsUPLC-Q/Orbitrap-HRMS method was used to establish a rapid detection method for 15 cytotoxic drugs such as cytarabine, gemcitabine and so on. The daily precision and accuracy of this method were verified by injecting four concentrations of standard solution on the same day, and the same four concentrations of standard solution were injected within three days respectively to verify the daily precision of this method. The signal-to-noise ratio (SNR) of 10:1 was calculated as the limit of quantity. The mixed standard solution of 15 cytotoxic drugs with concentrations of 0.5, 1, 3, 10, 30, 100, 300, and 1,000 ng/mL was configured and detected by this method for linearity and range.The stability of this method was investigated using a mixture of 15 drugs (15MIX) standard solutions at high concentration (300 ng/mL) and low concentration (10 ng/mL) at room temperature for 12 and 24 hours, respectively. A standard solution of each drug, 15MIX and blank solution were taken to verify the exclusivity of the method. ResultsThe results showed that the method had good specificity, and the intraday precision of all drugs was less than 10% and the intraday precision was less than 15%. At the same time, the standard curve had good linearity, R2 was greater than 0.99, and the limit of quantification of most drugs was about 1 ng/mL. ConclusionsIn this study, an UPLC-Q/Orbitrap-HRMS method was established for the rapid detection of 15 cytotoxic drugs, providing technical support for the monitoring of cytotoxic drug residues in PIVAS, which is of great significance for environmental contamination mornitoring as well as occupational exposure alert.
For the design and optimization of functional peptides, unravelling the structures of individual building blocks as well as the properties of the ensemble is paramount. TI＇R1, derived from human ...transthyretin, is a fibril-forming peptide implicated in diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The functional peptide TTR1-RGD, based on a TFR1 scaffold, was designed to specifically interact with cells. Here, we used scanning tunneling microscopy （STM） to analyze the assembly structures of TTRl-related peptides with both the reverse sequence and the modified forward sequence. The site- specific analyses show the following： i） The TIR1 peptide is involved in assembly, nearly covering the entire length within the ordered 3-sheet structures, ii） For TTR1-RGD peptide assemblies, the TTR1 motif forms the ordered 3-sheet while the RGDS motif adopts a flexible conformation allowing it to promote cell adhesion. The key site is clearly identified as the linker residue Gly13. iii） Close inspection of the forward and reverse peptide assemblies show that in spite of the difference in chemistry, they display similar assembling characteristics, illustrating the robust nature of these peptides, iv） Glycine linker residues are included in the ~-strands, which strongly suggests that the sequence could be optimized by adding more linker residues. These garnered insights into the assembled structures of these peptides help unravel the mechanism driving peptide assemblies and instruct the rational design and optimization of sequence- programmed peptide architectures.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To assess the key factors influencing the effectiveness of nirmatrelvir/ritonavir in treating elderly patients with COVID-19.
This study was conducted on patients aged ≥60 who were admitted to the ...Second Affiliated Hospital of Soochow University for COVID-19 infection and were treated with nirmatrelvir/ritonavir. Clinical information was collected from patients and steady-state blood concentrations of nirmatrelvir and ritonavir were measured. Factors associated with treatment effects were searched by univariate and multivariate analysis.
A total of 68 (51 males and 17 females) patients had a median age of 80 (73.0-84.8) years were enrolled in this study. The blood concentration measurements (trough concentrations) of nirmatrelvir and ritonavir were 5.1 (2.6-7.1) and 0.4 (0.2-0.9) μg/mL, respectively. Adverse drug reaction was reported in 4 (5.9%) patients. Univariate analysis showed that age, clinical classification, APACHE II score, total bilirubin (TBil), aspartate transaminase (AST), lactate dehydrogenase (LDH), and total cholesterol (TC) were significantly associated with the effectiveness of treatment (P value <0.05). Concentration of nirmatrelvir was also associated with treatment outcome (P value <0.1). Based on the results of univariate analysis, the above factors were introduced into the multiple linear regression equation as independent variables, and the results showed that clinical classification was included in the regression equation model and was the most important factor affecting the treatment outcome. By receiver operating characteristic curve analysis, the area under curve of age + biochemical indicators + APACHE II score + clinical classification was 0.968 (95% CI = 0.919-1.000; P <0.0001). Among the 68 patients included in the study, 4 cases experienced adverse drug reactions.
Age, clinical classification, APACHE II score, TBil, AST, LDH, and TC were significantly associated with the effectiveness of treatment in elderly patients with COVID-19.
Based on the finite-volume coastal ocean model （FVCOM）, a three-dimensional numerical model FVCOM was built to simulate the ocean dynamics in pre-dam and post-dam conditions in Bachimen （BCM）. The ...domain decomposition method, which is effective in describing the conservation of volume and non-conservation of mechanical energy in the utilization of tidal energy, was employed to estimate the theoretical tidal energy resources and developable energy resources, and to analyze the hydrodynamic effect of the tidal power station. This innovative approach has the advantage of linking physical oceanography with engineering problems. The results indicate that the theoretical annual tidal energy resources is about 2x 108 kwh under the influence of tidal power station; Optimized power installation is confirmed according to power generation curve from numerical analysis; the developable resources is about 38.2% of theoretical tidal energy resources with the employment of one-way electricity generation. The electricity generation time and power are 3479 hours and 2.55~104KW, respectively. The power station has no effect on the tide pattern which is semi-diumal tide in both two conditions, but the amplitudes of main constituents apparently decrease in the area near the dam, with the ME decreasing the most, about 62.92 cm. The tidal prism shrinks to 2.28×107 m3, but can still meet the flow requirement for tidal power generation. The existence of station increases the flow rate along the waterway and enhances the residual current. There are two opposite vortexes formed on the east side beside the dam of the station, which leads to pollutants gathering.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, chemical reduced graphene-silver nanoparticles hybrid （AgNPs@CR-GO） with close-packed AgNPs structure was used as a conductive matrix to adsorb enzyme and facilitate the electron ...transfer between im- mobilized enzyme and electrode. A facile route to prepare AgNPs@CR-GO was designed involving in β-cyclodextrin （β-CD） as reducing and stabilizing agent. The morphologies of AgNPs were regulated and controlled by various experimental factors. To fabricate the bioelectrode, AgNPs@CR-GO was modified on glassy carbon electrode followed by immobilization of glucose oxidase （GOx） or laccase. It was demonstrated by electrochemical testing that the electrode with close-packed AgNPs provided high GOx loading （Г=4.80 × 10^- l0 mol·cm^-2） and fast electron transfer rate （ks=5.76 s^-1）. By employing GOx based-electrode as anode and laccase based-electrode as cathode, the assembled enzymatic biofuel cell exhibited a maximum power density of 77.437 μW·cm^-2 and an open-circuit voltage of 0.705 V.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The current management of advanced esophageal squamous cell carcinoma (ESCC) remains unsatisfactory. We investigated the safety, efficacy, and biomarkers of SHR-1210, an anti-PD-1 antibody, in ...patients with recurrent or metastatic ESCC.
This study was part of a phase I trial in China. Patients with advanced ESCC who were refractory or intolerant to previous chemotherapy were enrolled. Eligible patients received intravenous SHR-1210 at a dose of 60 mg, with escalation to 200 and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The associations between candidate biomarkers (PD-L1 and somatic mutation load) and the efficacy of SHR-1210 were also explored.
Between May 11, 2016, and December 9, 2016, a total of 30 patients from one site in China were enrolled. Ten patients (33.3%) had an independently assessed objective response. Median progression-free survival was 3.6 months (95% CI, 0-7.2). Three (10.0%) treatment-related grade 3 adverse events were reported: two (6.7%) pneumonitis and one (3.3%) increased cardiac troponin I. No grade 4 or grade 5 treatment-related adverse events were reported. The exome sequencing and analysis showed that the mutational burden and the potential mutation-associated neoantigen count were associated with better responses. An objective response was more common in patients with PD-L1-positive tumors as defined by ≥5% staining (7 of 15 patients) than in those with PD-L1-negative tumors (1 of 9 patients).
In this population of ESCC patients, SHR-1210 had a manageable safety profile and promising antitumor activity.
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Hydrogels are made tough to resist crack propagation. However, for seamless integration into devices and machines, it necessitates robustness against cyclic loads. Central to this objective is ...enhancing fatigue resistance, an indispensable attribute facilitating the optimal performance of hydrogels within a multitude of biological contexts, spanning various plant and animal tissues, as well as diverse biomedical and engineering areas. In this review, recent research concerning the fatigue behavior of hydrogels, presenting a comprehensive consolidation of the inherent mechanisms that underpin diverse strategies aimed at fortifying fatigue resistance, is summarized. A critical facet in the architectural blueprint of fatigue‐resistant hydrogels is emphasized, involving the imposition of spatial constraints upon the main chains at the crack tips, thereby effectuating a protracted delay in their fracture initiation during prolonged cyclic loading. The integration of multiscale mechanisms encompassing networks, interactions, media, and structures stands as a pivotal factor in the design of fatigue‐resistant hydrogels. It is hoped that the review will considerably propel the pragmatic deployment of fatigue‐resistant hydrogels across a diverse array of applications, thus catalyzing advancements in multiple fields.
To address the escalating demands for fatigue resistance in hydrogels, particularly in emerging applications such as biomedical and engineering fields, a comprehensive summary of cutting‐edge strategies for designing fatigue‐resistant hydrogels is presented. Additionally, a general principle for the design of fatigue‐resistant hydrogels to cater to these evolving requirements is provided.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Driving style is an important factor in driving psychology, which is useful for effectively evaluating driving behaviors. Exploring driving style in a Chinese sample could help understand the overall ...situation of Chinese drivers. This study aims to develop a measurement of driving style fit for the Chinese situation and to validate the validity and reliability of this scale. In this study, 296 drivers from China completed the Chinese version of the multidimensional driving style inventory (MDSI), the Big Five Inventory (BFI), and the Driver Behavior Questionnaire (DBQ) as well as several questions about socio-demographic information. After testing the assumed structure by a confirmatory factor analysis, and adjusting the structure, a brief version of Chinese version of MDSI with twelve items categorized into four driving styles, namely, risky style, angry- high-velocity style, careful style and anxious style was revised. The validity and reliability of the scales were acceptable. The results showed that driving styles were closely correlated with self-reported driving behaviors. Specifically, risky style, angry- high-velocity style, and anxious style are all positively associated with dangerous driving behaviors. Meanwhile, careful style was positively associated with positive driving behaviors and negatively correlated with dangerous driving behaviors. Anxious was also found to be negatively associated with fines. For personality, we found a positive relationship between risky, angry- high-velocity, careful and anxious styles and the personality traits that often have negative effects on driving, such as extraversion and neuroticism. Meanwhile, these three styles were negatively correlated with conscientiousness and agreeableness in general. In addition, careful style was positively correlated with conscientiousness and agreeableness. The current study shows convincing evidence for the validity and reliability of the brief MDSI-C and develops a useful tool for identify the driving style of Chinese drivers for future research and relevant departments of road safety.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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