Effects of changes in SHP2 expression on liver fibrosis by influencing the apoptosis of hepatic stellate cells.

Accumulating research has revealed that src-homology domain 2-containing protein tyrosine phosphatase-2 (SHP2), an oncogenic protein tyrosine phosphatase, is associated with liver fibrosis. Currently, it is still unclear whether SHP2 affects liver fibrosis by influencing the apoptosis of hepatic stellate cells (HSC). In present study, we investigate effects of SHP2 expression changes on liver fibrosis, with special emphasis on the apoptosis of HSC. Using adenovirus vector, wild-type SHP2 gene and short hairpin RNA targeting SHP2 were introduced into rats with liver fibrosis and LX-2 cells in vitro. The expressions of type I and III collagen, pathological and functional changes, collagen deposition in rat liver and apoptosis of LX-2 cells were detected by immunohistochemical and HE staining, automated biochemical analyzer, Masson trichrome staining, and TUNEL. This study showed that overexpression of SHP2 exacerbated dysfunction, inflammatory damage, collagen deposition and increased expression of type I and III collagen in rat liver reduced apoptosis of LX-2 cells. On the contrary, low expression of SHP2 alleviated the aforementioned detection indicators of rats and promoted apoptosis of LX-2 cells. In conclusion, the downregulation of SHP2 expression alleviates liver fibrosis by inducing the apoptosis of HSC, while overexpressed SHP2 exacerbates liver fibrosis by inhibiting the apoptosis of HSC.

iTreg cells-secreted IL10 alleviates lupus nephritis through inactivating lncRNA HAR1A transcription to suppress SMARCD1-mediated iNOS activation.

Lupus nephritis (LN) is a highly prevalent complication of systemic lupus erythematosus (SLE). Long non-coding RNAs (lncRNAs) are essential modulators in multiple types of human diseases, including LN. In the current study, we searched on online GEO database to select out lncRNAs that were differentially expressed in blood samples of LN patients. Through further RT-qPCR analysis, we found that lncRNA Highly Accelerated Region 1 A (HAR1A) is most significantly upregulated in blood samples of LN patients. Functionally, we detected that overexpression of HAR1A could aggravate LPS-induced injury and inflammation. According to the results of bioinformatics analysis and mechanism experiments, we determined that HAR1A binds with miR-149-3p to upregulate SMARCD1 through competing endogenous RNA (ceRNA) mechanism. It has been proven that iNOS is an inflammation inducer. Here, we found that HAR1A/miR-149-3p/SMARCD1 upregulates iNOS expression through enhancing H3K27ac level in iNOS promoter. Previously, we proved that CD8+CD103+ iTreg cells could alleviate glomerular endothelial cell injury. Moreover, we demonstrated that CD8 + CD103+ iTreg cells-secreted IL-10 downregulated HAR1A expression by impeding NF-κB pathway activation. In conclusion, this study provides evidences revealing a novel molecular pathway blocked by CD8+CD103+ iTreg cells in LN.

Screening and analysis of GULP1 downstream target genes based on transcriptomic sequencing.

GULP1 is an engulfment adaptor protein containing a phosphotyrosine-binding (PTB) domain, and existing studies have shown that it can promote glucose uptake in 3T3-L1 adipocytes. To further explore key metabolically related differential genes downstream of GULP1, this study conducted transcriptome analysis on adipocytes and skeletal muscle cells overexpressing GULP1. Subsequently, abnormally expressed genes were subjected to bioinformatic analysis, and real-time fluorescent quantitative PCR (qRT-PCR) was used for mutual validation with transcriptome sequencing. The results indicated that, with a threshold of P < 0.05 and |Log2FoldChange| ≥ 1 for screening differentially expressed genes, compared with control cells, there were 278 upregulated and 263 downregulated genes in adipocytes overexpressing GULP1. Metabolism-related GO (Gene Ontology) terms included cholesterol biosynthetic process, cholesterol metabolic process, response to lipopolysaccharide, lipid metabolic process, etc. A total of 52 metabolically related differentially expressed genes were enriched in 10 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, with lipid metabolism being highly enriched. In skeletal muscle cells overexpressing GULP1, there were 280 upregulated and 302 downregulated genes, with metabolism-related GO terms including hormone metabolic process, response to lipopolysaccharide, one-carbon metabolic process, etc. A total of 86 metabolically related differentially expressed genes were enriched in 10 KEGG pathways, with amino acid metabolism, lipid metabolism, and carbohydrate metabolism being highly enriched. GULP1's biological functions are extensive, including lipid metabolism and oncology. This study, through transcriptomics and bioinformatic analysis, identified key metabolically related differential genes downstream of GULP1, obtained metabolically related differential genes and signaling pathways after GULP1 overexpression, providing important theoretical basis for future research on GULP1 downstream target genes.

Research on advanced photoresponsive azobenzene hydrogels with push-pull electronic effects: a breakthrough in photoswitchable adhesive technologies.

Smart materials that adapt to various stimuli, such as light, hold immense potential across many fields. Photoresponsive molecules like azobenzenes, which undergo E-Z photoisomerization when exposed to light, are particularly valuable for applications in smart coatings, light-controlled adhesives, and photoresists in semiconductors and integrated circuits. Despite advances in using azobenzene moieties for stimuli-responsive adhesives, the role of push-pull electronic effects in regulating reversible adhesion remains largely unexplored. In this study, we investigate for the first time photo-controlled hydrogel adhesives of azobenzene with different push-pull electronic groups. We synthesized the monomers 4-methoxyazobenzene acrylate (ABOMe), azobenzene acrylate (ABH), and 4-nitroazobenzene acrylate (ABNO2), and examined their effects on reversible adhesion properties. By incorporating these azobenzene monomers into acrylamide, dialdehyde-functionalized poly(ethylene glycol), and [3-(methacryloylamino)propyl]-trimethylammonium chloride, we prepared ABOMe, ABH, and ABNO2 ionic hydrogels. Our research findings demonstrate that only the ABOMe ionic hydrogel exhibits reversible adhesion. This is due to its distinct transition state mechanism compared to ABH and ABNO2, which enables efficient E-Z photoisomerization and drives its reversible adhesion properties. Notably, the ABOMe ionic hydrogel reveals an outstanding skin adhesion strength of 360.7 ± 10.1 kPa, surpassing values reported in current literature. This exceptional adhesion is attributed to Schiff base reactions, monopole-quadrupole interactions, π-π interactions, and hydrogen bonding with skin amino acids. Additionally, the ABOMe hydrogel exhibits excellent reversible self-healing capabilities, significantly enhancing its potential for injectable medical applications. This research underscores the importance of integrating multifunctional properties into a single system, opening new possibilities for innovative and durable adhesive materials.

Defect Chemistry in High-Voltage Cathode Materials for Lithium-Ion Batteries.

High-voltage cathodes (HVCs) have emerged as a paramount role for the next-generation high-energy-density lithium-ion batteries (LIBs). However, the pursuit of HVCs comes with inherent challenges related to defective structures, which significantly impact the electrochemical performance of LIBs. The current obstacle lies in the lack of a comprehensive understanding of defects and their precise effects. This perspective aims to provide insights into defect chemistry for governing HVCs. The classifications, formation mechanisms, and evolution of defects are outlined to explore the intricate relationship between defects and electrochemical behavior. The pressing need for cutting-edge characterization techniques that comprehensively investigate defects across various temporal and spatial scales is emphasized. Building on these fundamental understandings, engineering strategies such as composition tailoring, morphology design, interface modification, and structural control to mitigate or utilize defects are thoroughly discussed for enhanced HVCs performance. These insights are expected to provide vital guidelines for developing high-performance HVCs for next-generation high-energy lithium-ion batteries.

Magnetic navigation-assisted colonoscopic enteral tube placement in swine (with video): a preliminary study.

BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

Quantitative and qualitative analysis of contrast-enhanced ultrasound for differentiating benign and malignant superficial enlarged lymph nodes.

Background: In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. Methods: This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. Results: There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Conclusions: Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.

Latest guideline of endoscopic submucosal dissection of early gastric cancer may not be suitable for Chinese patients: retrospective study findings from two centers.

BACKGROUND: To analyze the diagnostic efficiency of the four absolute endoscopic submucosal dissection (ESD) indications for lymph node metastasis (LNM) of Chinese patients with early gastric cancer (EGC). METHODS: We retrospectively analyzed EGC patients who underwent radical D2 gastrectomy from January 2019 to December 2022. We evaluated the rate of LNM, false-negative rate, and negative predictive value of the four ESD indications. RESULTS: Of enrolled 2722 EGC patients, 388 (14.3%) patients presented LNM. Tumor size > 2 cm, ulceration, submucosal invasion, undifferentiated type, and lymphovascular invasion were independent risk factors of LNM in patients with EGC. 1062 (39%) cases of EGC conformed to the four EDS indications; however, 4% of them had LNM. 451 cases were fully in accord with the fourth ESD indication (undifferentiated intramucosal carcinoma without ulceration and a maximum lesion diameter of ≤ 2 cm), and 35 of them had LNM, with a false-negative rate (FNR) of 9.02% and a negative predictive value (NPV) of 92.24%. There was significant difference among the four indications in terms of the rate of LNM (1.0% vs 1.5% vs 1.3% vs 7.8%, P < 0.001), FNR (1.03% vs 0.52% vs 0.26% vs 9.02%, P < 0.001), and NPV (98.99% vs 98.53% vs 98.75% vs 92.24%, P < 0.001). CONCLUSION: Overall, the fourth ESD indication was associated with a high rate of LNM compared to the other three indications. Thus, it might not be safe to classify it as an absolute indication in Chinese patients with EGC.

A novel compound heterozygous PCDH15 variants is associated with arRP in a Chinese pedigree.

BACKGROUND: Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 variants and RP. METHODS: In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing (WES). The variants were validated in the family members by Sanger sequencing and co-segregation analysis. RESULTS: Novel compound heterozygous, Frame shift variants of the PCDH15 gene, NM_001384140.1:c.4368 - 2147_4368-2131del and NM_001384140.1:c exon19:c.2505del: p. T836Lfs*6 were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species. CONCLUSION: This is the first study to identify novel compound heterozygous variants c.4368 - 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing variants, and extending the variant spectra. All above findings may be contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.

Stimuli-Responsive Nanomaterials for Tumor Immunotherapy.

Cancer remains a significant challenge in extending human life expectancy in the 21st century, with staggering numbers projected by the International Agency for Research on Cancer for upcoming years. While conventional cancer therapies exist, their limitations, in terms of efficacy and side effects, demand the development of novel treatments that selectively target cancer cells. Tumor immunotherapy has emerged as a promising approach, but low response rates and immune-related side effects present significant clinical challenges. Researchers have begun combining immunotherapy with nanomaterials to optimize tumor-killing effects. Stimuli-responsive nanomaterials have become a focus of cancer immunotherapy research due to their unique properties. These nanomaterials target specific signals in the tumor microenvironment, such as pH or temperature changes, to precisely deliver therapeutic agents and minimize damage to healthy tissue. This article reviews the recent developments and clinical applications of endogenous and exogenous stimuli-responsive nanomaterials for tumor immunotherapy, analyzing the advantages and limitations of these materials and highlighting their potential for enhancing the immune response to cancer and improving patient outcomes.

A new UiO-66-NH2 MOF-based nano-immobilized DFR enzyme as a biocatalyst for the synthesis of anthocyanidins.

Anthocyanidins and anthocyanins are one subclass of flavonoids in plants with diverse biological functions and have health-promoting effects. Dihydroflavonol 4-reductase (DFR) is one of the important enzymes involved in the biosynthesis of anthocyanidins and other flavonoids. Here, a new MOF-based nano-immobilized DFR enzyme acting as a nano-biocatalyst for the production of anthocyanidins in vitro was designed. We prepared UiO-66-NH2 MOF nano-carrier and recombinant DFR enzyme from genetic engineering. DFR@UiO-66-NH2 nano-immobilized enzyme was constructed based on covalent bonding under the optimum immobilization conditions of the enzyme/carrier ratio of 250 mg/g, 37 °C, pH 6.5 and fixation time of 10 min. DFR@UiO-66-NH2 was characterized and its catalytic function for the synthesis of anthocyanidins in vitro was testified using UPLC-QQQ-MS analysis. Compared with free DFR enzyme, the enzymatic reaction catalyzed by DFR@UiO-66-NH2 was more easily for manipulation in a wide range of reaction temperatures and pH values. DFR@UiO-66-NH2 had better thermal stability, enhanced adaptability, longer-term storage, outstanding tolerances to the influences of several organic reagents and Zn2+, Cu2+ and Fe2+ ions, and relatively good reusability. This work developed a new MOF-based nano-immobilized biocatalyst that had a good prospect of application in the green synthesis of anthocyanins in the future.

Demystifying In Situ Pyrolysis Chemistry for High-Performance Polyanionic Cathodes in Sodium-Ion Batteries.

The carbon coating strategy has emerged as an indispensable approach to improve the conductivity of polyanionic cathodes. However, owing to the complex reaction process between precursors of carbon and cathode, establishing a unified screening principle for carbonaceous precursors remains a technical challenge. Herein, we reveal that carbonaceous precursor pyrolysis chemistry undeniably influences the formation process and performance of Na3V2(PO4)3 (NVP) cathodes from in situ insights. By investigating three types of carbonaceous precursors, it is found that O/H-containing functional groups can provide more bonding sites for cathode precursors and generate a reducing atmosphere by pyrolysis, which is beneficial to the formation of polyanionic materials and a uniform carbon coating layer. Conversely, excessive pyrolysis of functional groups leads to a significant amount of gas, which is detrimental to the compactness of the carbon layer. Furthermore, the substantial presence of residual heteroatoms diminishes graphitization. In this case, it is demonstrated that carbon dots (CDs) precursors with suitable functional groups can comprehensively enhance the Na+ migration rate, reversibility, and interface stability of the cathode material. As a result, the NVP/CDs cathode displays outstanding capacity retention, maintaining 92% after 10,000 cycles at a high rate of 50 C. Altogether, these findings provide a valuable benchmark for carbon source selection for polyanionic cathodes.

Traditional Chinese-version reliability test of the Pieper-Zulkowski pressure ulcer knowledge: Psychometric and assessment.

This study was to translate the Pieper-Zulkowski pressure ulcer knowledge test (PZ-PUKT) into Traditional Chinese and evaluate its psychometric properties as well as identify the predictors of knowledge on pressure injury. The PZ-PUKT was translated into Traditional Chinese (TC-PZ-PUKT), and its content validity was evaluated. A total of 296 nurses participated in this study and completed the 72-item TC-PZ-PUKT online. The reliability of the TC-PZ-PUKT was analysed by evaluating its internal consistency and test-retest reliability. Hierarchical regression was used to determine factors associated with TC-PZ-PUKT scores. Content validity was achieved with a score of 0.986. Internal consistency was observed to be reliable, with a Cronbach's alpha of 0.858. The mean knowledge score on the TC-PZ-PUKT was 72.5%, with a 1-week test-retest reliability of r = 0.849. Education level, certification as a wound specialist and self-learning through reading articles, books or guidelines on pressure injury were significantly associated with TC-PZ-PUKT scores. The TC-PZ-PUKT is a valid and reliable tool. Education level, certification as a wound specialist and self-learning regarding pressure injury are related to knowledge of pressure injury.

Reducing anxiety and enhancing satisfaction in thyroid patients with DietLens application during radioactive iodine therapy: A quasi-experimental study.

Hyperthyroidism and thyroid cancer significantly impact health, and often require Radioactive Iodine (RAI) therapy. Anxiety is common in patients undergoing RAI, particularly related to dietary compliance. This study aimed to assess the effectiveness of the mobile health application, DietLens in reducing anxiety and increasing satisfaction in patients preparing for RAI therapy, focusing on low-iodine diet (LID). A quasi-experimental study was conducted in a Singapore tertiary hospital outpatient department from March 13, 2019 to March 27, 2020, involving patients scheduled for their first RAI treatment. Participants were divided into a control group receiving standard care and an intervention group using DietLens alongside standard care. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and satisfaction levels were measured through self-reported questionnaires. In the study, 56 participants were initially divided into control (n = 28) and intervention (n = 28) groups. After accounting for dropouts, 50 participants finished the study, with each group comprising 25 individuals. Anxiety levels were similar between groups pre-intervention. Post-intervention, the intervention group displayed a significant decrease in anxiety levels compared to the control group (independent t-test: t (48) = 2.50, p = 0.02). The multivariate linear regression analysis indicated that being in the intervention group was significantly associated with a decrease in post-intervention anxiety score (ß = -4.03, 95 % CI: -7.33 to -0.72, p = 0.02). Fisher's Exact Test revealed a borderline significant difference in satisfaction with educational materials and the overall treatment process, with 100 % of the intervention group expressing satisfaction compared to 80 % in the control group, resulting in a p-value of 0.052 in both instances. DietLens was effective in reducing anxiety and enhancing satisfaction related to RAI therapy preparation, particularly in managing a LID, highlighting a beneficial role for digital interventions in healthcare settings.

Quaternary phosphonium AIEgens nanoparticles as innovative agents for developing latent fingerprints.

Quaternary phosphonium salts, a significant category of organophosphorus compounds, have garnered substantial attention from chemists due to their wide range of applications across various research areas. These compounds are utilized in organic synthesis, catalysis, medicinal chemistry, natural materials, and coordination chemistry. Their versatility and effectiveness in these fields make them valuable tools in scientific research. Despite their extensive use in various applications, the potential of quaternary phosphonium compounds as fluorescent agents for revealing latent fingerprints (LFPs) remains largely unexplored, presenting an exciting opportunity for further research and development in forensic science. In this study, we designed molecules that combine the aggregation-induced emission (AIE) chromophore with triphenylphosphine to create a series of novel AIE amphiphiles, namely TPP1, TPP2, and TPP3. Through precise adjustment of the carbon chain length between the phenoxy group and the terminal triphenylphosphine, we were able to finely tune the nanostructures and hydrophobicity of the materials. TPP3 emerged as the optimal candidate, possessing the ideal particle size and hydrophobicity to effectively bind to LFPs, thus enabling efficient fingerprint visualization with enhanced fluorescence upon aggregation. Our findings introduce an innovative approach to fingerprint visualization, offering high selectivity, superior imaging of level 3 structures, and long-term effectiveness (up to 30 days). Additionally, TPP3's outstanding performance in imaging level 3 structures of LFPs is beneficial for analyzing incomplete LFPs and identifying individuals. By significantly improving the detection and analysis of LFPs, this approach ensures more accurate and reliable identification, making it invaluable for forensic investigations and security measures. The adaptability of these compounds to various fingerprint surfaces highlights their potential in diverse practical applications, enhancing their utility in both forensic science and security fields. This versatility allows for precise fingerprint visualization across different scenarios, making them a critical tool for advancing biometric and security technologies.

[Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Development of an hollow fiber solid phase microextraction method for the analysis of unbound fraction of imatinib and N-desmethyl imatinib in human plasma.

Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106 % with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r2=0.504) and NDI (r2=0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM.

Prognosis Prediction in Head and Neck Squamous Cell Carcinoma by Radiomics and Clinical Information.

(1) Background: head and neck squamous cell carcinoma (HNSCC) is a common cancer whose prognosis is affected by its heterogeneous nature. We aim to predict 5-year overall survival in HNSCC radiotherapy (RT) patients by integrating radiomic and clinical information in machine-learning models; (2) Methods: HNSCC radiotherapy planning computed tomography (CT) images with RT structures were obtained from The Cancer Imaging Archive. Radiomic features and clinical data were independently analyzed by five machine-learning algorithms. The results were enhanced through a voted ensembled approach. Subsequently, a probability-weighted enhanced model (PWEM) was generated by incorporating both models; (3) Results: a total of 299 cases were included in the analysis. By receiver operating characteristic (ROC) curve analysis, PWEM achieved an area under the curve (AUC) of 0.86, which outperformed both radiomic and clinical factor models. Mean decrease accuracy, mean decrease Gini, and a chi-square test identified T stage, age, and disease site as the most important clinical factors in prognosis prediction; (4) Conclusions: our radiomic-clinical combined model revealed superior performance when compared to radiomic and clinical factor models alone. Further prospective research with a larger sample size is warranted to implement the model for clinical use.

Precipitation contributes to alleviating pollution of rubber-derived chemicals in receiving watersheds: Combining confluent stormwater runoff from different functional areas.

The release of rubber-derived chemicals (RDCs) in road surface runoff has received significant attention. Urban surface runoff is often the confluence of stormwater runoff from specific areas. However, the impact of precipitation on RDCs contamination in confluent stormwater runoff and receiving watersheds remains poorly understood. Herein, we investigated the profiles of RDCs and their transformation products in confluent stormwater runoff and receiving rivers affected by precipitation events. The results showed that 34 RDCs are ubiquitously present in confluent stormwater runoff and surface water, with mean concentrations of 1.03-2749 and 0.28-436 ng/L, respectively. The most dominant target compounds in each category were N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, 2-benzothiazolol, and 1,3-diphenylguanidine. Total RDCs concentrations in confluent stormwater runoff decreased spatially from industrial areas to business districts to college towns. A significant decrease in RDCs levels in surface water after rainfall was observed (P < 0.01), indicating that precipitation contributes to alleviating RDCs pollution in receiving watersheds. To our knowledge, this is the first report of N,N'-ditolyl-p-phenylenediamine quinone (DTPD-Q) levels in surface waters in China. The annual mass load of ∑RDCs reached 72,818 kg/y in confluent stormwater runoff, while 38,799 kg/y in surface water. The monitoring of confluent stormwater runoff is an efficient measure for predicting contamination loads from RDCs in rivers. Risk assessment suggested that most RDCs posed at least medium risks to aquatic organisms, especially 6PPD-quinone. The findings help to understand the environmental fate and risks of RDCs in the confluent stormwater runoff and receiving environments after precipitation events.

Stereoconvergent and Enantioselective Synthesis of Z-Homoallylic Alcohols via Nickel-Catalyzed Reductive Coupling of Z/E-1,3-Dienes with Aldehydes.

Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral products─a crucial strategy for handling Z/E-mixed olefins, which are common but challenging substrates in organic synthesis. Herein, we report a stereoconvergent and highly enantioselective method for synthesizing Z-homoallylic alcohols via the nickel-catalyzed reductive coupling of Z/E-mixed 1,3-dienes with aldehydes. This process is enabled by an N-heterocyclic carbene ligand characterized by C2-symmetric backbone chirality and bulky 2,6-diisopropyl N-aryl substituents. Our method achieves excellent stereocontrol over both enantioselectivity and Z-selectivity in a single step, producing chiral Z-homoallylic alcohols that are valuable in natural products and pharmaceuticals.