An adsorption-catalysis-sensitization integrated composite, Au@ZIF-8, was constructed. Under mild conditions, Au@ZIF-8 converts 4-nitrophenol to 4-aminophenol and reduces N-nitrosodimethylamine to highly ionizable dimethylamine, transforming a latent carcinogenic hazard into a detoxified and readily detectable surrogate. This programmed workflow boosts LC-MS/MS sensitivity by nearly 50-fold and establishes a general MOF-based strategy for surveillance and control of nitro impurities.

Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization,which must be monitored and controlled.The study established an o-phenylenediamine(OPD)derivatization HPLC-MS/MS method for the detection of these degradation products,enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution.The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone(3-DG),3-deoxygalactosone(3-DGal),4-deoxyglucosone(4-DG),and 3,4-dideoxyglucosone-3-ene(3,4-DGE),along with two monocarbonyl degradation products,furfural and 5-hydroxymethylfurfural.The quantitative method for 3-DG,3-DGal,3,4-DGE and their structural analog,glucosone,was validated.3-DG,3-DGal,and glucosone exhibited good linear relationships within the range of 5-150 ng/mL,while 3,4-DGE showed good linearity in the range of 1-150 ng/mL.The spiked recovery rates for all compounds were between 86.8%and 100.0%.The detection limits for glucosone,3-DG,and 3-DGal were approximately 2.4 ng/mL,and approximately 0.5 ng/mL for 3,4-DGE.The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution,providing an important basis for the q uality control.

The evaluation of compound genotoxicity is of great significance for drug safety assurance, and the existing evaluation methods have the problems of false-positive/negative, low throughput, or complicated operation. Although enzyme-linked immunosorbent assays (ELISA) kits targeting some genotoxic targets have high throughput, there are limitations in sensitivity and stability due to the use of horseradish peroxidase (HRP). In this study, an integrated evaluation platform based on novel sea urchin-like platinum-coated gold nanoparticles (Pt/Au NPs) was developed to address the above problems. Pt/Au NPs nanozymes were synthesized by deposition of a platinum layer on the surface of gold seeds. The nanozymes exhibited excellent peroxidase activity as well as superior stability compared to natural enzymes. Pt/Au NPs nano-enzymes were replaced for the construction of nano-enzyme-linked immunosorbent assay (NLISA), which has better sensitivity and stability, decreasing the acquired amount of test compounds. Through quantification of genotoxicity damage markers, phosphorylated histone H2AX (γH2AX) and phosphorylated histone H3 (p-H3) in metabolic human hepatocytes, this study has proposed a "see-saw" model to differentiate the genotoxic compounds of DNA breakage or aneuploidy: the breakage agent can significantly increase γH2AX levels, whereas the aneuploidy agent can increase p-H3 levels. Therefore, this microplate-based high-throughput colorimetric detection method can provide an efficient assessment tool for drug safety.

β-thalassemia is one of the most prevalent single-gene recessive disorders worldwide, characterized by the impaired synthesis of β-globin chains, which leads to ineffective erythropoiesis and results in anemia and iron overload, along with various complications. Therefore, establishing animal models that closely resemble β-thalassemia is essential for studying the pathogenesis and treatment of this disease. This article reviews the molecular mechanisms underlying β-thalassemia; highlights the research advancements of several common clinical treatment methods; and provides a summary of prevalent animal models of β-thalassemia, including mice, rabbits, and cynomolgus monkeys. Although the mouse model reproduces certain pathological characteristics of β-thalassemia, it is limited in its ability to correct specific gene mutations, making it less effective for certain aspects of the disease. In contrast, the rabbit model, which more closely resembles human physiology, offers an improved approximation. Furthermore, the cynomolgus monkey model outperforms both the mouse and rabbit models in exhibiting the severe phenotype of β-thalassemia, thanks to its notable genetic and physiological similarities to humans. This article aims to provide a comprehensive reference for researchers conducting animal experimental studies in relation to β-thalassemia.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 107 to 1 × 1010 colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

As an important component of the tumor microenvironment, the extracellular matrix (ECM) generally undergoes extensive remodeling, acting as a shield to block drug delivery and immune recognition. Currently, ECM-clearing strategies for tumor treatment still face challenges. In this work, a type of europium metal-organic nanowire was prepared for targeting the highly expressed sialic acid (SA) on glycoproteins within the ECM. The nanowire, termed TFE, was prepared by coordination reaction of thiodiacetic acid (TDA) with Fe3+ and Eu3+. Eu3+ can competitively chelate to the highly expressed SA in ECM, leading to the release of Eu3+ from TFE. The precursors of the TFE can be injected directly into the tumor site, forming a gel-like morphology within ∼1 min. The TFE can effectively encapsulate cancer cells, disrupt the ECM integrity, and stimulate immune recognition and ferroptosis. Moreover, the TFE demonstrated dual diagnostic and therapeutic capabilities by embedding fluorescent drugs, such as doxorubicin (DOX), enabling ECM-targeted theranostics.

The effectiveness of ultraviolet advanced oxidation processes (UV-AOPs) was influenced by the prevalence of dissolved organic matter (DOM) in natural water bodies. This study investigated the impact of humic acid (HA), fulvic acid (FA), and extracellular organic matter (EOM) on the degradation of Ciprofloxacin (CIP) by UV222/Sodium Percarbonate (UV222/SPC) and UV222. The results demonstrated that all three types of DOMs suppressed CIP degradation in UV222/SPC, with EOM exhibiting stronger inhibitory effects than HA and FA. This suppression primarily arose from DOM's light-shielding properties and scavenging of hydroxyl radicals (center dot OH) and carbonate radicals (COs center dot-), which outweighed the compensatory effects of DOM-photosensitized reactive species. In contrast, EOM enhanced direct UV222 photolysis of CIP due to its high absorption coefficient at 222 nm, which promoted the generation of excited triplet state EOM (3EOM*) and singlet oxygen (1O2) via photosensitization. These reactive species compensated for EOM's light-shielding effect, enabling efficient indirect photodegradation of CIP. The organic matter in EOM rather than NO3-promoted the degradation of CIP in UV222. The fluorescence spectra and dissolved organic carbon (DOC) changes of DOM were analyzed in depth. In addition, both COs center dot- and center dot OH contribute to CIP degradation in UV222/SPC, with the second-order rate constant of COs center dot- with CIP measured at 4.79 x 108 M-1 s-1 . UV222/SPC showed lower energy consumption than UV254/SPC in treating the real water sample. This study deepens the understanding of the impact of DOM in UV222 water purification.

Lipid nanoparticles (LNPs) are emerging as one of the most promising drug delivery systems. The long-circulating effect of intact LNPs (i-LNPs) is the key to efficacy and toxicity in vivo. However, the significant challenge is specific and sensitive detection of i-LNPs. Herein, a dual-recognition fluorescence enzyme-linked immunosorbent assay (DR-FELISA) was developed to directly isolate and detect i-LNPs by combining dual-recognition separation with a one-step signal amplification strategy. The microplates captured and enriched i-LNPs through antibody-antigen reaction. Dual-chol probes were spontaneously introduced into the lipid bilayer of captured i-LNPs, converting the detection of i-LNPs into the detection of double-cholesterol probes. Finally, the end of the dual-chol probes initiated the localized scaffolding autocatalytic DNA circuits (SADC) system for further signal amplification. The SADC system provides a sensitive and efficient amplifier through localized network structures and self-assembled triggers. Simultaneous recognition of i-LNPs surface PEG-lipid and lipid bilayer structures significantly eliminates interference from biological samples. i-LNPs were detected with high selectivity, ranging from 0.2 to 1.25 mg/mL with a limit of detection of 0.1 mg/mL. Moreover, this method allows the isolation and quantitative analysis of different formulations of i-LNPs in serum samples with a satisfactory recovery rate ranging from 94.8 to 116.3%. Thus, the DR-FELISA method provides an advanced platform for the exclusive and sensitive detection of i-LNPs, providing new insights for the study of the quality and intracorporal process of complex formulations.

Pancreatic cancer (PC) is highly malignancy with poor survival. Ferroptosis offers a novel therapeutic target for cancer treatment and glutathione peroxidase 4 (GPX4) shields tumor cells from ferroptosis damage. Although Sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the development of pancreatic cancer, its underlying mechanisms remain unclear. This research aims to explore the role of SREBP1 in ferroptosis by using its inhibitor Fatostatin. In this study, Fatostatin was found to inhibit the proliferation and clonogenicity of pancreatic cancer cell lines. This was accompanied by a reduction in intracellular lipid synthesis, increased iron accumulation, elevated levels of reactive oxygen species (ROS), and accumulation of malondialdehyde (MDA). The JASPAR database shows that there is a binding site of the SREBP1 on the promoter region of GPX4. What's more, it was verified that SREBP1 can transcriptionally regulate GPX4 by CHIP. In vivo experiments further revealed that Fatostatin could suppress the growth of subcutaneous tumors in nude mice. In conclusion, our study suggests that Fatostatin may inhibit pancreatic cancer cell proliferation by inducing ferroptosis through the SREBP1/GPX4 pathway. These findings shed light on the therapeutic potential of Fatostatin and lay the groundwork for future investigations into its mechanism of action in pancreatic cancer.

Genotoxic impurities (GTIs) occurred in drugs, and food and environment pose a threat to human health. Accurate and sensitive evaluation of GTIs is of significance. Ames assay is the existing gold standard method. However, the pathogenic bacteria model lacks metabolic enzymes and requires mass GTIs, leading to insufficient safety, accuracy, and sensitivity. Whole-cell microbial sensors (WCMSs) can use normal strains to simulate the metabolic environment, achieving safe, sensitive, and high-throughput detection and evaluation for GTIs. Here, based on whether GTIs causing DNA alkylation required metabolic enzymes or not, two DNA repair-responsive engineered WCMS systems were constructed including Escherichia coli-WCMS and yeast-WCMS. A DNA repair-responsive promoter as a sensing element was coupled with an enhanced green fluorescent protein as a reporter to construct plasmids for introduction into WCMS. The ada promoter was screened out in the E. coli-WCMS, while the MAG1 promoter was selected for the yeast-WCMS. Different E. coli and yeast strains were modified by gene knockout and mutation to eliminate the interference and enhance the GTI retention in cells and further improved the sensitivity. Finally, GTI consumption of WCMS for the evaluation of methyl methanesulfonate (MMS) and nitrosamines was decreased to 0.46-8.53 μg and 0.068 ng-2.65 μg, respectively, decreasing 2-3 orders of magnitude compared to traditional methods. This study provided a novel approach to measure GTIs with different DNA damage pathways at a molecular level and facilitated the high-throughput screening and sensitive evaluation of GTIs.

Objective To determine the content of 10 chiral amino acids in cetrorelix acetate based on the pre-column derivatization HPLC method.Methods After hydrolysis of cetrorelix acetate,Marfey’s method was used for the pre-column derivatization reaction.Hedera ODS-2 C18 column （4.6mm×250 mm,5μm） was used,with gradient elution of 0.065%formic acid solution and acetonitrile as the mobile phase.The detection wavelength of the ultraviolet detector was 340 nm.Results All the 10 chiral amino acids in cetrorelix acetate were well separated.The concentration of LOD and LOQ were 0.68μmol·L -1 and 2.04μmol·L -1 respectively.The linear range was 10.20～24.49μmol·L -1 .Conclusion This method is specific and accurate for the simultaneous content determination of the 10 chiral amino acids in cetrorelix acetate.

The γH2AX is a type of confined target in nuclei which is highly expressed around the damaged DNA during genotoxicity and has therefore been identified as a marker of genotoxicity. Convenient and intuitive in situ real-time detection of γH2AX is crucial for an accurate assessment of genotoxicity. Selective and nondestructive surface-enhanced Raman spectroscopy (SERS) is suitable to achieve this goal. However, the detection of substances in the nucleus by SERS is still limited due to the contradiction of probes between the nuclei entry efficiency and signal enhancement. This study utilized the characteristics of γH2AX as a confined target and constructed a γH2AX immunosensor based on gold nanoprobes with a small size (15 nm), which was modified with the TAT nuclear targeting peptide to ensure high nuclei entry efficiency. Once DNA damage was induced, the local overexpression of γH2AX further recruited the probe through immune recognition, so that hot spots could be assembled in situ to generate strong Raman signals, which were applied to evaluate the genotoxicity of drug impurities. This study proposed a novel SERS detection strategy, characterized by confined target-induced size conversion and hot spot formation, for in situ real-time analysis of intranuclear targets at the single-living-cell level, which intelligently simplified the structure of SERS probes and the operation process.

目的 建立高效液相色谱-蒸发光散射检测法测定发酵工艺来源的N-乙酰氨基葡萄糖中的葡萄糖和氨基葡萄糖的含量.方法 采用Asahipak NH2P-50 4E(4.6 mm×250 mm,5μm)色谱柱,以乙腈-水(80∶20)为流动相,流速为1.0 mL·mii-1,柱温为30℃;使用蒸发光散射检测器,载气为空气,气体压力为350 kPa,漂移管温度为80℃,增益为5.结果 N-乙酰氨基葡萄糖与葡萄糖和氨基葡萄糖之间分离度良好,葡萄糖在76.12～304.50 μg·mL-1、氨基葡萄糖在124.68～498.71 μg·mL-1、N-乙酰氨基葡萄糖在150.15～600.60 μg·mL-1与峰面积线性关系良好,R2均大于0.9990.结论 本方法准确、简便,可用于发酵工艺来源的N-乙酰氨基葡萄糖中葡萄糖和氨基葡萄糖的检测.

目的 建立高效液相色谱-串联质谱法检测三甲基间苯三酚原料药中的基因毒性杂质N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)的含量.方法 色谱柱为Inertsil ODS-3(150 mm×4.6 mm,5μm),流动相为0.1％甲酸溶液(A)-甲醇(B),按程序进行梯度洗脱,在大气压化学电离源下以正离子、多重反应监测模式进行检测.结果 NDMA和NDEA的检测限分别为0.8454 ng·mL-1和0.2340 ng·mL-1,定量限分别为2.818 ng·mL-1和0.7800 ng·mL-1,线性范围分别为2.818～18.79 ng·mL-1和0.7800～5.200 ng·mL-1.结论 该方法专属性强,灵敏度高,适用于三甲基间苯三酚原料药中NDMA和NDEA的测定.

Two kinds of Luminescent metal organic framework (LMOF) based probes were developed as fluorescent oligonucleotide indicators for ratio-metric microRNA (miRNA) sensing. One LMOF (AuNCs@ZIF-8) is ZIF-8 encapsulated with gold nanoclusters (AuNCs). Another LMOF (Zn(2)Ph(2)Da) is prepared by using 2, 2'-dithiodi-benzoic acid (dtba) and 1, 10-phenanthroline (phen) as ligands, and Zn2+ as metal center. Both of them possess fluorescence emission behavior and fluorescence quenching ability toward adsorbed fluorophore labeled miRNA aptamers. When target miRNAs hybridize with aptamers, the fluorescence of labeled fluorophores would recover. Meanwhile, the fluorescence intensity of LMOFs keeps unchanged. For enhancing miRNA detection sensitivity, novel fluorophore-labeled aptamers (SYBR-dsDNA-Aps) composed of miRNA aptamers and dsDNA fragments embedded with SYBR Green I molecules were designed and optimized. The detection of miR-21 and miR-155 in the blood serum of breast cancer bearing mice or inflammatory rats prove that prepared fluorescent oligonucleotide indicators could be promising choices for ratiometric miRNA sensing.

药物色谱分析实验是药学专业学生一门重要的基础性实验课程,以往的实验教学模式缺乏有效的教学手段,难以满足企业对具有优秀科学素养药学人才的需求.分析传统药物色谱分析课程教学模式中存在的问题,探讨改革教学模式的必要性,构建以"APP教学平台""虚拟仿真实验教学平台"和"开放式实验教学平台"为基础的新型实验教学模式,从而培养学生的创新意识,提高学生的实践能力.

This article describes the visual detection of bongkrekic acid (BA) by cysteamine modified gold nanoparticles (CS-AuNPs) as colorimetric probes. Polycarboxyl structured BA induces the aggregation of CS-AuNPs through electrostatic interaction, which results in the color change of CS-AuNPs from wine-red to blue-violet. The ratio of absorbance at 650 nm and 524 nm (A650/A524) increases linearly in the 0.18-1.64 mu M BA concentration range, and the detection limit is 3.43 nM. Moreover, when combined with solid phase extraction (SPE), the method can also be used for specific detection of BA in complex food matrix (tremella). The recoveries in urine, serum, and tremella ranged from 89.31% to 109.63%. Interestingly, a smartphone application (APP) was applied to identify the R, G, and B values of the solution, and the quantitative curve was established by calculating the gray value. This approach was then used to quantify the BA in the sample solution. The linear range of APP detecting is 0.10 mu M-1.44 mu M and the detection limit is 12.33 nM. This method can be used not only for food safety monitoring, but also for preliminary clinical screening of BA poisoning.

Nitrite, a type of food additive, has been proved convertible to genotoxic nitrosamines in the gastrointestinal tract by intestinal flora. There is no appropriate method for in situ detection of nitrosamines. Herein, plasmid-introduced Saccharomyces cerevisiae, which can respond to nitrosamine-induced DNA damage and activate pMAG1-based DNA damage repair (DDR), was designed as whole-cell biosensors (WCBs) for monitoring the in situ generated nitrosamines by a reporter gene expressing enhanced green fluorescent protein (EGFP). In order to protect the validity of WCBs (pMAG1 yeast) from the gastric acid environment, a type of metal-organic gel (MOG), coordinated by Fe3+ and 2,2'-thiodiacetic acid (TDA), was prepared to embed the WCBs. The MOG(Fe-TDA) is gastric acid resistant and can deliver the pMAG1 yeast to the gut without compromising the performance of pMAG1 yeast to detect in situ generated nitrosamines. The genotoxicity of nitrosamines converted from nitrite was successfully detected in the gastrointestinal tract of mice.

Sialic acid (SA) is overexpressed on cell membranes of tumor cells, and increased serum SA concentration has been observed in tumor-bearing patients. Herein, a series of lanthanide-containing bimetallic complexes (TDA-M-Lns) for targeting SA were prepared via coordination among luminescent lanthanide ions (Ln3+ = Tb3+, Eu3+, Dy3+, or Sm3+), metal ion quenchers (M2+ = Cu2+ or Co2+), and the organic ligand 2,2'-thiodiacetic acid (TDA). SA can competitively coordinate with Ln3+, resulting in the "signal-on" of the Ln3+. Therefore, the TDA-M-Lns can be simply used for cost-saving detection of SA in the blood samples. Among the TDA-M-Lns, TDA-Co-Eu showed the highest sensitivity to detect SA in the blood of tumor-bearing mice. Furthermore, the TDA-Co-Eu was successfully used to target SA and deposit Eu3+ on the surfaces of tumor cells for the inhibition of tumor cell growth and migration. The therapeutic effect of TDA-Co-Eu on a Balb/c mouse liver tumor model was evaluated. It was proved that TDA-Co-Eu can be applied for SA detection as well as for inhibiting tumor growth.

建立了测定D-色氨酸甲酯盐酸盐中左旋异构体的手性高效液相色谱方法.采用EnantioPak Y5(4.6 mm×250 mm,5μm)色谱柱,以正己烷(含0.1％二乙胺)-乙醇(80:20)为流动相,检测波长280 nm.D-色氨酸甲酯盐酸盐与其左旋异构体之间分离度良好,L-色氨酸甲酯盐酸盐在0.9927～14.8905μg·mL-1浓度范围内线性关系良好;D-色氨酸甲酯盐酸盐在0.9839～14.7588μg·mL-1浓度范围内线性关系良好,R2均为0.9998.本方法准确、简便,可以用于D-色氨酸甲酯盐酸盐中左旋异构体的质量研究.