A comparative study of two thienopyrimidine Schiff base probes for sequential monitoring of Ga3+ and Pd2.

Two Schiff base probes (S1 and S2) were prepared and synthesized by incorporating thienopyrimidine into salicylaldehyde or 3-ethoxysalicylaldehyde individually, with the aim of detecting Ga3+ and Pd2+ sequentially. Upon chelation with Ga3+, S1 and S2 exhibited fluorescence enhancement in DMSO/H2O buffer. Both S1-Ga3+ and S2-Ga3+ were quenched by Pd2+. The limit of detection for S1 in response to Ga3+ and Pd2+ was 2.86 × 10-7 and 4.4 × 10-9 M, respectively. For S2, the limit of detection for Ga3+ and Pd2+ was 4.15 × 10-8 and 3.0 × 10-9 M, respectively. Furthermore, the complexation ratios of both S1 and S2 with Ga3+ and Pd2+ were determined to be 1:2 through Job's plots, ESI-MS analysis, and theoretical calculations. Two molecular logic gates were constructed, leveraging the response behaviors of S1 and S2. Moreover, the potential utility of S1 and S2 for monitoring Ga3+ and Pd2+ in domestic water was verified.

Thienopyrimidine-derived multifunctional fluorescence sensor for the detection of Cu2+, Fe3+, and PPi in different solvents.

Hydrazine substituted thienopyrimidine, a new fluorophore, was used to synthesize a novel Schiff base R1 as a chemosensor via the condensation with p-formyltriphenylamine, and the structure was confirmed using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) analysis. When treated with Cu2+ in dimethylsulfoxide (DMSO)/H2O buffer, R1 showed a phenomenon of fluorescence quenching, which was reversible with the action of ethylenediaminetetraacetic acid (EDTA). When treated with Fe3+ in dimethylformamide (DMF)/H2O buffer, R1 exhibited the same phenomenon, but fluorescence was recovered with inorganic pyrophosphate (PPi) quantitatively. The complexation ratios for R1-Cu2+ and R1-Fe3+ were both 1:2, which were manifested by MS titrations and corresponding Job's plots. The limits of detection of R1 for Cu2+ and Fe3+ were 3.11 × 10-8 and 1.24 × 10-7 M, respectively. The sensing mechanism of R1 toward Cu2+ and Fe3+ was confirmed using density functional theory calculations and electrostatic potential analysis. Test strips of R1 were fabricated successfully for on-site detection of Cu2+ and Fe3+. In addition, R1 was applied to recognize Cu2+ and Fe3+ in actual water samples with satisfactory recovery.

Immunotherapy combined with targeted therapy in advanced small cell carcinoma of the ovary of hypercalcemic type: A case of overall survival lasting for over 5 years.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly aggressive ovarian malignant neoplasm lacking a unified clinical management process. Most patients are diagnosed at an advanced stage and have an extremely poor prognosis with an overall probability of survival less than 10 %. Here, we describe the case of a patient with advanced SCCOHT achieved a survival of over 5 years after receiving multiple cycles of immunotherapy combined with anti-angiogenic therapy or CDK4/6 inhibitors. At the same time, we also summarized the case reports and clinical trials of immunotherapy in SCCOHT.

The comparative study of two new Schiff bases derived from 5-(thiophene-2-yl)isoxazole as "Off-On-Off" fluorescence sensors for the sequential detection of Ga3+ and Fe3+ ions.

Two new Schiff bases, TIC ((E)-N'-(2-hydroxybenzylidene)-5-(thiophene-2-yl)isoxazole-3-carbohydrazide) and TIE ((E)-N'-(3-ethoxy-2-hydroxybenzylidene)-5-(thiophene-2-yl)isoxazole-3-carbohydrazide), have been designed and synthesized as chemosensors for distinct recognition of Ga3+ and Fe3+ ions. TIE demonstrated a prominent "turn on" response characterized by clear distinguished fluorescence when coordination with Ga3+ ions in the DMSO/H2O buffer solution. In comparison, TIC also showed "turn on" response of blue fluorescence which was more selective and sensitive than that of TIE due to the steric hindrance of ethoxy group of TIE. The newly formed complexes TIC-Ga3+ and TIE-Ga3+ may act as selective "turn-off" fluorescent probes towards Fe3+ ions. Limits of detection of TIC and TIE towards Ga3+ ions were 7.8809 × 10-9 M and 2.6277 × 10-8 M, respectively. Limits of detection of TIC-Ga3+ and TIE-Ga3+ towards Fe3+ ions were 8.6562 × 10-9 M and 3.3764 × 10-7 M, respectively. The molar ratio of the complex between the sensor and Ga3+ or Fe3+ ions were all 1:2 determined through Job's Plot, mass spectrometry, and theoretical calculations. Both sensors were utilized for the determination of target ions in environment water samples, and the portable paper sensors for detecting Ga3+ ions have been successfully developed.

Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type.

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.

A new Schiff base derived from 5-(thiophene-2-yl)oxazole as "off-on-off" fluorescence sensor for monitoring indium and ferric ions sequentially and its application.

A new Schiff base sensor (E)-N'-((8-hydroxy-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methylene)-5-(thiophen-2-yl)oxazole-4-carbohydrazide (TOQ) was synthesized and found to emit yellowish green fluorescence upon introduction of In3+. Furthermore, the resulting complex TOQ-In3+ was quenched selectively by Fe3+. The detection limits of TOQ for In3+ and Fe3+ were 1.75 × 10-10 M and 8.45 × 10-9 M, respectively. The complex stoichiometry of TOQ with target ions was determined to be 1:2 via Job's plot analysis, which further was verified by ESI-MS titration and theoretical calculations. Moreover, TOQ can be used for the determination of target ions in environmental water samples. A portable paper sensor of TOQ was successfully developed for detecting In3+ to assess its applicability.

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer.

BACKGROUND: Although the use of PARP inhibitor has received considerable amount of attention in ovarian cancer, PARP inhibitor resistance still emerges with disease progression. PI3K/AKT pathway inhibitors have been proposed to synergize with PARP inhibition to slow tumor growth, but the exact molecular mechanisms are still elusive. METHODS: Utilizing tumor samples from recurrent EOC patients with platinum resistance and prior PARP inhibitor use, Mini PDX and PDX models were established to study the anti-tumor effect of AKT inhibitor (LAE003) and LAE003/PARP inhibitor (Olaparib) in combination. Five ovarian cancer cell lines were treated with Olaparib or LAE003 or in combination in vitro. Cell viability and apoptosis rate were measured after the treatments. Combination index by the Chou-Talalay was used to evaluate in vitro combination effect of Olaparib and LAE003. The protein expression level of PARP1 and PAR was measured by Western blot in cell lines and by immunohistochemistry in PDX tumor tissues. RESULTS: Tumor cells from two out of five platinum-resistant ovarian cancer patients previously treated with PARP inhibitor were sensitive to AKT inhibition in Mini-PDX study. Inhibition of AKT further increased the response of tumor cells to Olaparib in a PDX model derived from a recurrent platinum-resistant ovarian cancer patient. Additive anti-proliferation effect of LAE003 and Olaparib was also observed in three ovarian cancer cell lines with high PARP1 protein level. Interestingly, mechanism study revealed that AKT inhibition decreased PARP enzyme activity as measured by PAR level and/or reduced PARP1 protein level in the tumor cell lines and PDX tumor tissues, which may explain the observed combined anti-tumor effect of LAE003 and Olaparib. CONCLUSION: Collectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients.

A multi-institutional and cross-sectional study on empathy in Chinese medical students: differences by student cadre or not, future career preference, and father's education status.

BACKGROUND: The aims of this study were to examine the factor structure of the Chinese version of the Jefferson Scale of Empathy for medical students (JSE-S) and investigate differences in empathy scores among Chinese medical students according to gender, student cadre or not, future career preference, and parents' education. METHODS: Medical students from three universities completed an online questionnaire containing the JSE-S. Exploratory factor analysis was conducted to determine the factor structure, and group comparisons of empathy scores were examined via t-tests and analysis of variance. RESULTS: Four factors emerged from the factor analysis: "perspective taking," "compassionate care," "standing in the patient's shoes," and an uninterpretable factor. The results indicated that students who were female, held positions as student cadres, preferred to become a doctor, and whose fathers had a high school education or below tended to have more empathy. CONCLUSIONS: Overall, the findings provide information on the dimensions of empathy applicable to Chinese medical students and confirm the factors found in the original measure. The dimensions have implications for developing empathy among medical students throughout the world. Educators can use the information to design interventions to foster empathy among students in the context of medical education reform in many countries, including China.

Empathy in Chinese eight-year medical program students: differences by school year, educational stage, and future career preference.

BACKGROUD: To examine the psychometric properties of a Chinese translation of the Jefferson Scale of Empathy (Student-version, JSE-S), and to study differences in empathy scores among eight-year undergraduate medical students across gender, year of study, and future career preference. METHODS: The JSE-S was administered to 442 participants from December 2016 to July 2017, who were all first- to seventh-year students on an eight-year medical education course at Fudan University. Factor analysis was used to examine the underlying components of the Chinese version of the JSE-S. The data analyses comprised a t-test and analyses of variance. RESULTS: Factor analysis confirmed four components: perspective taking, compassionate care, ability to stand in patient's shoes, and difficulties in adopting patient's perspective. The lowest empathy score was found in the seventh-year students (99.5), while a decline was found across school years. Students in clinical training (sixth/seventh year) had lower empathy than students in premedical study (first/second year), basic medicine (third/fourth year), and clinical medicine (fifth year). Statistically significant differences in empathy mean scores were found in respect of future career preference but not gender. Students who preferred not to become doctors had lower empathy than students who preferred to become doctors, who were undecided, and who did not specify. CONCLUSIONS: The findings support the construct validity and reliability of the Chinese version of the JSE-S for medical students. The study also revealed the features of empathy in eight-year program students, and provided a reliable reference to design interventions to cultivate empathy among Chinese medical students.