EPIC-1042 as a potent PTRF/Cavin1-caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for glioblastoma.

BACKGROUND: Temozolomide (TMZ) treatment efficacy in glioblastoma is determined by various mechanisms such as TMZ efflux, autophagy, base excision repair (BER) pathway, and the level of O6-methylguanine-DNA methyltransferase (MGMT). Here, we reported a novel small-molecular inhibitor (SMI) EPIC-1042 (C20H28N6) with the potential to decrease TMZ efflux and promote PARP1 degradation via autolysosomes in the early stage. METHODS: EPIC-1042 was obtained from receptor-based virtual screening. Co-immunoprecipitation and pull-down assays were applied to verify the blocking effect of EPIC-1042. Western blotting, co-immunoprecipitation, and immunofluorescence were used to elucidate the underlying mechanisms of EPIC-1042. In vivo experiments were performed to verify the efficacy of EPIC-1042 in sensitizing glioblastoma cells to TMZ. RESULTS: EPIC-1042 physically interrupted the interaction of PTRF/Cavin1 and caveolin-1, leading to reduced secretion of small extracellular vesicles (sEVs) to decrease TMZ efflux. It also induced PARP1 autophagic degradation via increased p62 expression that more p62 bound to PARP1 and specially promoted PARP1 translocation into autolysosomes for degradation in the early stage. Moreover, EPIC-1042 inhibited autophagy flux at last. The application of EPIC-1042 enhanced TMZ efficacy in glioblastoma in vivo. CONCLUSION: EPIC-1042 reinforced the effect of TMZ by preventing TMZ efflux, inducing PARP1 degradation via autolysosomes to perturb the BER pathway and recruitment of MGMT, and inhibiting autophagy flux in the later stage. Therefore, this study provided a novel therapeutic strategy using the combination of TMZ with EPIC-1042 for glioblastoma treatment.

Continuity of health care: measurement and application in two rural counties of Guangxi Province, China.

BACKGROUND: Continuity of care (COC) is highly regarded in health promotion and health system strengthening. However, there is a lack of multidimensional quantitative assessment of continuity, making it challenging to evaluate and compare. Our objective was to create a novel measurement for COC and apply it in two rural counties in China to assess its validity and feasibility in evaluating health system reform. METHOD: This study conducted a scoping literature review on COC, examining existing frameworks and indicators. Following an online expert poll, a composite indicator was developed using the analytical hierarchy process (AHP). The measurement tool was then applied to assess the current state of COC in two rural counties in China. In addition to descriptive analysis, demographic and economic characteristics were analyzed for their association with COC scores using t-tests and multiple linear regression models. RESULTS: The final COC measurement encompasses three dimensions, six sub-dimensions, and ten individual indicators, which integrated and improved the current frameworks and indicators. Relational continuity, informational continuity, and management continuity were identified as the primary dimensions of COC measurement. The COC score is 0.49 in County A and 0.41 in County B, with information continuity being the highest-scoring dimension. Notably, the disparity in continuity scores is most pronounced among individuals with varying attitudes towards health, demonstrating a positive correlation. CONCLUSION: The construction of the composite indicator in this study offers a scientific and effective metric for comprehensively measuring continuity of care. The empirical data analysis conducted in Western China serves as an illustrative application of the indicator, demonstrating its efficiency. The results obtained from this analysis provide a solid foundation and valuable reference for strengthening the health system.

A study on infectivity of asymptomatic SARS-CoV-2 carriers.

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

Data fusion for the measurement of potentially toxic elements in soil using portable spectrometers.

Soil contamination posed by potentially toxic elements is becoming more serious under continuously development of industrialization and the abuse of fertilizers and pesticides. The investigation of soil potentially toxic elements is therefore urgently needed to ensure human and other organisms' health. In this study, we investigated the feasibility of the separate and combined use of portable X-ray fluorescence (pXRF) and visible near-infrared reflectance (vis-NIR) sensors for measuring eight potentially toxic elements in soil. Low-level fusion was achieved by the direct combination of the pXRF and vis-NIR spectra; middle-level fusion was achieved by the combination of selected bands of the pXRF and vis-NIR spectra using the Boruta feature selection algorithm; and high-level fusion was conducted by outer-product analysis (OPA) and Granger-Ramanathan averaging (GRA). The estimation accuracy for the eight considered elements were in the following order: Zn > Cu > Ni > Cr > As > Cd > Pb > Hg. The measurement for Cu and Zn could be achieved by pXRF spectra alone with Lin's concordance correlation coefficient (LCCC) values of 0.96 and 0.98, and ratio of performance to interquartile distance (RPIQ) values of 2.36 and 2.69, respectively. The measurement of Ni had the highest model performance for high-level fusion GRA with LCCC of 0.89 and RPIQ of 3.42. The measurements of Cr using middle- and high-level fusion were similar, with LCCC of 0.86 and RPIQ of 2.97. The best estimation accuracy for As, Cd, and Pb were obtained by high-level fusion using OPA, with LCCC >0.72 and RPIQ >1.2. However, Hg measurement by these techniques failed, having an unacceptable performance of LCCC <0.20 and RPIQ <0.75. These results confirm the effectiveness of using portable spectrometers to determine the contents of several potentially toxic elements in soils.

The Emerging Roles of CIB1 in Cancer.

Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer's disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression.

Colorimetric aptasensor for progesterone detection based on surfactant-induced aggregation of gold nanoparticles.

This paper proposes an aptasensor for progesterone (P4) detection in human serum and urine based on the aggregating behavior of gold nanoparticles (AuNPs) controlled by the interactions among P4-binding aptamer, target P4 and cationic surfactant hexadecyltrimethylammonium bromide (CTAB). The aptamer can form an aptamer-P4 complex with P4, leaving CTAB free to aggregate AuNPs in this aptasensor. Thus, the sensing solution will turn from red (520 nm) to blue (650 nm) in the presence of P4 because P4 aptamers are used up firstly owing to the formation of an aptamer-P4 complex, leaving CTAB free to aggregate AuNPs. However, in the absence of P4, CTAB combines with aptamers so that AuNPs still remain dispersed. Therefore, this assay makes it possible to detect P4 not only by absorbance measurement but also through naked eyes. By monitoring the variation of absorbance and color, a CTAB-induced colorimetric assay for P4 detection was established with a detection limit of 0.89 nM. Besides, the absorbance ratio A650/A520 has a linear correlation with the P4 concentration of 0.89-500 nM. Due to the excellent recoveries in serum and urine, this biosensor has great potential with respect to the visual and instrumental detection of P4 in biological fluids.

Clinical Characteristics of Inpatients with Anaphylaxis in China.

OBJECTIVE: To analyze the clinical characteristics of inpatients with anaphylaxis and the factors that influenced those characteristics. METHODS: Using the patient records from 1990 to 2013 from three highly ranked Chinese hospitals, we retrospectively analyzed the characteristics of 108 inpatients with anaphylaxis (not anaphylaxis admitted). RESULTS: The mean patient age was 42 ± 20 years old and male-to-female ratio was 1 : 1.3. The number of patients with anaphylaxis increased gradually, and cases diagnosed after 2005 accounted for 68.5% of the 108 total cases. The most common trigger was medications. The most common clinical manifestations included cutaneous, nervous, respiratory, circulatory, and digestive signs and symptoms. Male patients were more likely to experience loss of consciousness. Multisystem involvement was more likely to develop in patients with low BP, whereas it was uncommon in those with anaphylaxis induced by antibiotics or anesthetics. Epinephrine was used as the first-line treatment for 56 cases. CONCLUSIONS: Inpatient with anaphylaxis was more common in female patients and the number increased gradually during the study period. The most common trigger was medications. Patients with low BP were prone to having multisystem involvement, whereas the cases of anaphylaxis induced by antibiotics and anesthetics were less likely to involve multiple organ systems.

[A clinical analysis of 40 cases of primary and secondary pulmonary lymphoma].

OBJECTIVE: To investigate the clinical manifestations, pathological types, treatment and prognosis of primary pulmonary lymphoma (PPL) and secondary pulmonary lymphoma (SPL). METHODS: The clinical data of 40 cases of PPL or SPL diagnosed from 2003 to 2013 in the Chinese PLA General Hospital were retrospectively analyzed. All cases were diagnosed via lung biopsy or surgical biopsy. RESULTS: There were 24 male and 16 female patients, aging from 15 to 84 years, including 10 patients with PPL and 30 with SPL. The main clinical manifestations of PPL were cough and chest pain, but 4 patients were asymptomatic. Chest CT showed lung mass in 8 patients and patchy opacities in 3. ¹8F-FDG PET/CT showed that the SUV(max) of lung lesions was 3.96-6.70 with a median value of 4.50. The pathological types of all PPL cases were non-Hodgkin lymphoma (NHL), and 4 patients were treated with surgery combined with chemotherapy, and 3 patients were treated with surgery alone. The main clinical manifestations of SPL were cough, superficial lymph node enlargement and fever, but 8 patients were asymptomatic. The chest CT revealed pleural effusions in 20, mediastinal and hilar lymph node enlargement in 14, patch opacities in 13 and multiple nodules in 6 patients. In addition to pulmonary involvement, PET/CT examination confirmed that cervical lymph nodes, thyroid, stomach and pancreas were also involved. The SUV(max) was from 2.40 to 19.60, with a median value of 5.70. Twenty-one cases of SPL were NHL and 9 were Hodgkin lymphomas (HL). Of these patients with SPL, 14 were treated with chemotherapy alone, 8 chemotherapy combined with radiotherapy, and 2 surgery combined with chemotherapy. The one-year survival rate of PPL was 100%, compared with 93.3% of SPL. The shortest survival time of PPL was 13 months, compared with 2 months of SPL. CONCLUSIONS: There were differences in the radiological features, pathological types and treatment between PPL and SPL. The chest CT manifestations of PPL were mainly lung masses, while those of SPL were mainly pleural involvement and mediastinal and hilar lymph node enlargement. The pathological type of PPL was all NHL while that of 9 cases of SPL was HL. Patients with PPL were mainly treated with surgical therapy, but SPL mainly with chemotherapy. PET/CT examination may be helpful for the diagnosis and staging of lung lymphoma. Since the misdiagnosis rate of pulmonary lymphoma was high, diagnosis must rely on lung tissue biopsy and immunohistochemistry. Compared with PPL, the prognosis of SPL is poorer.

Sweetened blood sweetens behavior. Ego depletion, glucose, guilt, and prosocial behavior.

Although guilt feels bad to the individual, it is good for society because guilty feelings can prompt people to perform good deeds. Previous research shows that fatigue decreases guilty feelings and helpful behavior. This present research tests whether glucose restores guilty feelings and increases helpful behavior. Depleted participants watched a movie about butchering animals for their meat or skin and were told to express no emotions, whereas non-depleted participants watched the same movie, but could express their emotions. Afterwards they drank a glucose or placebo beverage. Having participants play a game in which another person was punished for their errors induced guilt. Finally, participants played a dictator game in which they could leave lottery tickets for the next participant. Depleted participants felt less guilty and helped less than non-depleted participants, and those who consumed a placebo beverage felt less guilt and helped less than those who consumed a glucose beverage.

Washing the guilt away: effects of personal versus vicarious cleansing on guilty feelings and prosocial behavior.

For centuries people have washed away their guilt by washing their hands. Do people need to wash their own hands, or is it enough to watch other people wash their hands? To induce guilt, we had participants write about a past wrong they had committed. Next, they washed their hands, watched a washing-hands video, or watched a typing-hands video. After the study was over, participants could help a Ph.D. student complete her dissertation by taking some questionnaires home and returning them within 3 weeks. Results showed that guilt and helping behavior were lowest among participants who washed their hands, followed by participants who watched a washing-hands video, followed by participants who watched a typing-hands video. Guilt mediated the effects of cleansing on helping. These findings suggest that washing one's own hands, or even watching someone else wash their hands, can wash away one's guilt and lead to less helpful behavior.