Glutathione-Conjugated Fluorometric Ratiometric NIR-Silicon Nanoparticles and Its Applications for In Vitro and In Vivo Imaging.

Glutathione (GSH), a tripeptide molecule, is the most abundant nonprotein biothiol in living cells, playing a crucial role in preventing oxidative damage to cellular components and maintaining intracellular redox homeostasis. As a thiol molecule, GSH contains a sulfhydryl (-SH) group that is vital for the body's response to reactive oxygen species (ROS). To confirm whether GSH can be used as a bioindicator or in the early diagnosis of cancers at the cellular level, it is essential to achieve highly selective detection and conjugation of GSH to silicon nanoparticles (SiNPs) under pathological conditions. We are herein excited to report a type of fluorescent ratiometric near-infrared silicon nanoparticle (NIR-SiNP) probe, that is, glutathione peptide conjugated (NIR-SiNPs-GSH), which simultaneously possess small pore sizes at an average of 6.7 nm, an emission of 670 nm, a bioimaging functionality of living cancer cells and animals, and favorable biocompatibility. Taking advantage of these virtues, we further manifest that such resulting NIR-SiNPs, NIR-SiNPs-GSH bioprobes are marvelously worthy for immunofluorescence imaging of cancer cells and living mice. Furthermore, it was shown that DAPI and probes could selectively stain malignant tumor cell nuclei, indicating the possibility for bioimaging and identification of cancer cells and animals. In summary, the suggested NIR-SiNPs-GSH probe has the potential to be a very effective chemical tool for early tumor detection in the future.

Comprehensive spatial distribution profiling of bioactive emodin in mouse organs using mass spectrometry imaging.

Emodin is an important anthraquinone compound with good anti-inflammatory activity in Chinese traditional medicine rhubarb. Detailed spatial distribution information in bio-tissues plays an important role in revealing the pharmacodynamics, toxicology and chemical mechanism of emodin. Herein, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) analytical method was established to obtain information on the spatial and temporal changes of emodin in multiple mouse tissue sections (heart, liver, spleen, lung, kidney, and brain) after intraperitoneal injection of emodin in mice. The measurements were accomplished in the negative ion mode in the range of m/z 250-285 Da with a spatial resolution on 40 µm. It was found that emodin was predominantly distributed in the arteriolar vascular region of the heart, the capsule region of the spleen, and the cortex of the kidney. Moreover, the MALDI-TOF-MSI result implied that emodin might be distributed in the brain. These more detailed spatial distribution information provides the significant reference for investigating the action mechanism of emodin, which cannot be obtained from conventional LC-MS analysis. The distribution trend of emodin in the results of MALDI-TOF-MSI analysis agreed with the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) results well, demonstrating the complementarity and reliability of the established MALDI-TOF-MSI method. Our work provided a label-free molecular imaging method to investigate the precise spatial distribution of emodin in various organs, which prove great potential in studying the effective substances and mechanism of rhubarb.

Direct and Rapid Visualization of the Spatial Distribution of Cholesterol in Alzheimer's and Cancer Tissue via MALDI Mass Spectrometry Imaging.

Cholesterol is a vital component of the central nervous system and tissues, and understanding its spatial distribution is crucial for biology, pathophysiology, and diagnostics. However, direct imaging of cholesterol using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) remains challenging and time-consuming due to the difficulty in ionizing the sterol molecule. To tackle this issue, a MALDI-MSI method is established for direct and rapid analysis of the spatial distribution of cholesterol in Alzheimer's disease (AD), different cancer tissues and organs via MALDI-MSI. This excellent imaging performance depends on the study and systemic optimization of various conditions that affect the imaging of MALDI-MSI. In this case, we report the distribution and levels of cholesterol across specific structures of the AD mouse brain and different tumor tissue and organs. According to the results, the content of cholesterol in the AD mouse cerebellum, especially in the arborvitae, was significantly higher than that in the wild type (WT) model. Furthermore, we successfully visualize the distribution of cholesterol in other organs, such as the heart, liver, spleen, kidney, pancreas, as well as tumor tissues parenchyma and interstitium using MALDI-MSI. Notably, the attribution of cholesterol MS/MS hydrocarbon fragments was systematically investigated. Our presented optimization strategy and established MALDI-MSI method can be easily generalized for different animal tissues or live samples, thereby facilitating the potential for applications of MALDI-MSI in clinical, medical and biological research.

Click Chemoselective Probe with a Photoswitchable Handle for Highly Sensitive Determination of Steroid Hormones in Food Samples.

Residues of endocrine disrupting steroid hormones in food might cause various diseases like cardiovascular diseases and breast and prostate cancers. Monitoring steroid hormone levels plays a vital role in ensuring food safety and exploring the pathogenic mechanism of steroid hormone-related diseases. Based on the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a novel chemoselective probe, Azo-N3, which contains a reactive site N3, an imidazolium salt-based MS tag, and an azobenzene-based photoswitchable handle, was designed and synthesized to label ethynyl-bearing steroid hormones. The probe Azo-N3 was applied for the highly selective and sensitive detection of four ethynyl-bearing steroid hormones in food samples (milk, egg, and pork) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ionization efficiency of the labeled analytes could be increased by 6-105-fold, and such a labeled method exhibited satisfactory detection limits (0.04-0.2 µg/L), recovery (80.6-122.4%), and precision (RSDs% lower than 6.9%). Interestingly, the efficient immobilization of the probe Azo-N3 onto α-cyclodextrin (α-CD)-modified magnetic particles to construct a solid supported chemoselective probe Fe3O4-CD-Azo-N3 and UV light-controlled release of the labeled analytes from a magnetic support can be achieved by taking advantage of the photoswitched host-guest inclusion between the azobenzene unit and α-CD. The potential applications of Fe3O4-CD-Azo-N3 for labeling, capturing, and the photocontrolled release of the labeled steroid hormones were fully investigated by mass spectrometry imaging analysis. This work not only provides a sensitive and accurate method to detect steroid hormones in food but also opens a new avenue in designing solid supported chemoselective probes.

Follow-up study of preterm infants with thyroid dysfunction after medication. / ç”²çŠ¶è ºåŠŸèƒ½å¼‚å¸¸æ—©äº§å„¿å¹²é¢„æ²»ç–—çš„éšè®¿ç ”ç©¶.

OBJECTIVES: To study the effect of levothyroxine sodium tablets on the growth and development and thyroid function in preterm infants with thyroid dysfunction. METHODS: A retrospective analysis was performed for 82 preterm infants who were born in the Department of Obstetrics of the First People's Hospital of Yunnan Province, from January 1, 2013 to December 31, 2017, and these infants were hospitalized after birth in the Department of Neonatology of the hospital. They were regularly followed up to observe growth and development and thyroid function at the outpatient service of the Department of Neonatology. According to thyroid function test results, they were divided into an abnormal thyroid function group (observation group; n=31) and a normal thyroid function group (control group; n=51). The infants in the observation group were given oral administration of levothyroxine sodium tablets, while those in the control group were not given any treatment. The two groups were compared in terms of the physical and intelligence development and thyroid function of preterm infants with various gestational ages (28-<32 weeks, 32-<34 weeks, and 34-<37 weeks) after regular follow-up to the corrected age of 12 months. RESULTS: There were no significant differences in physical development indices (body length, body weight, and head circumference) between the observation and control groups at various gestational ages after follow-up to the corrected age of 12 months (P>0.05). There were no significant differences between the two groups in the scores of each functional area of the Gesell Developmental Scale among the preterm infants with a gestational age of 28-<32 weeks and 32-<34 weeks after follow-up to the corrected age of 12 months (P>0.05). For the preterm infants with a gestational age of 34-<37 weeks, compared with the control group, the observation group had a significantly lower score of gross motor ability at the age of 3 and 12 months, significantly lower scores of fine motor ability, language ability, and adaptation ability at the age of 12 months (P<0.05), and a significantly lower score of personal-social ability at the age of 3 months (P<0.05). However, the score of personal-social ability in the observation group was not significantly different from the control group at the age of 12 months (P>0.05). After 2-4 weeks of treatment with levothyroxine sodium tablets, the thyroid function of the 31 preterm infants with thyroid dysfunction returned to normal. Among the 31 infants, 21 (68%) achieved complete drug withdrawal, with normal results of neonatal screening (100%); 10 infants (32%) failed to achieve drug withdrawal, and only 2 (20%) out of the 10 infants had normal neonatal screening results (P<0.05). CONCLUSIONS: Early diagnosis and reasonable treatment can reduce the impact on growth and development in preterm infants with thyroid dysfunction. Most preterm infants tend to have transient thyroid dysfunction, while those with positive results of neonatal screening are more likely to develop permanent thyroid dysfunction.

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

Clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma and nonmucinous adenocarcinoma: a surveillance, epidemiology, and end results (SEER) population-based study.

BACKGROUND: Mucinous adenocarcinoma (MC) is a rare histological subtype of colorectal adenocarcinoma. Previous studies investigating the prognosis of MC have conflicting results and the proper treatment of MC remains unclear. METHODS: This retrospective study presents the clinicopathological characteristics and prognosis of MC. This cohort study collected data from April 1 through August 01, 2018. This study used data on 107,735 patients with nonmucinous adenocarcinoma (NMC) and 9,494 with MC between 2009 and 2013 from the Surveillance, Epidemiology, and End Results program (SEER). Clinicopathological features were analyzed by chi-square test and survival curves by the Kaplan-Meier method. We used propensity score matching (PSM) to account for potential bias. Logistic regression and Cox proportional hazards models were used to compare and calculate adjusted risks of MC death. RESULTS: MC was more frequent in patients with older age, large tumor size and moderate tumor grade compared with NMC (P<0.001). Five-year survival was lower for MC patients than NMC patients (P<0.001). Older age, later tumor node metastasis (TNM) stage and multiple tumors indicated a poorer prognosis while surgery gave better survival outcomes [hazard ratio (HR) =0.38; 95% confidence interval (CI), 0.33 to 0.44; P<0.001]. Younger age, left-side colon location and early disease stage were associated with better survival after surgery (P<0.001). CONCLUSIONS: Age, TNM stage, tumor number and treatment were indicators of prognosis and surgery gave better survival for MC patients compared with those without surgery. Our study contributes to their clinical treatment.