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Abstract Background 18F-FDG PET/CT provides precise information about dissemination of lymphoma lesions. Dmax, defined as distance between the two lesions that were farthest apart by PET/CT, was found to be a promising predictor of Diffuse large B-cell lymphoma (DLBCL) outcome in a small size of clinical trial data. We analyzed the impact of Dmax on the outcome of a large real-world DLBCL cohort. Methods Data of newly diagnosed DLBCL at the Third Affiliated Hospital of Soochow University were retrospectively collected. Baseline Dmax, clinical data and survival information were recorded. A metabolic parameter, metabolic bulk volume (MBV), was also measured to verify the independent impact of Dmax. Results Optimal cut-off values for Dmax and MBV were 45.34 cm and 21.65 cm3. With a median follow-up of 32 months, Dmax significantly impacted progression-free survival (PFS) and overall survival (OS) in 253 DLBCL patients. For Dmaxlow and Dmaxhigh groups, estimated 3-year OS were 87.0% and 53.8% (p

In this study, 86 new seco-lupane triterpenoid derivatives were designed, synthesized, and characterized, and their protective activities against ischemia-reperfusion injury were investigated in vitro and in vivo. Structure–activity relationship studies revealed that most target compounds could protect cardiomyocytes against hypoxia/reoxygenation-induced injury in vitro, with compound 85 being the most active and exhibiting more potent protective activity than clinical first-line drugs. Furthermore, all thiophene derivatives exhibited stronger protective activity than furan, pyridine, and pyrazine derivatives, and the protective activity gradually increased with the extension of the alkyl chain and changed in the substituent. The data from the in-vitro and in-vivo experiments revealed that compound 85 protected mitochondria from damage by inhibiting excessive production of oxidative stressors, such as intracellular ROS, which in turn inhibited the apoptosis and necrotize of cardiomyocytes and reduced infarct size, thereby protecting normal cardiac function. It was associated with enhanced activation of the PI3K/AKT-mediated HIF-1α signaling pathway. Therefore, compound 85 acts as an oxidative stress inhibitor, blocks ROS production, protects mitochondria and cells from myocardial ischemia/reperfusion (MI/R) injury, and represents an effective new drug for treating MI/R injury.

Objective: To improve the yield and antibacterial rate of antimicrobial peptides from Pleurotus tuber-regium mycelium （PTRM-AMPs）. Methods: Taking the yield and the antibacterial rate of PTRM-AMPs against Staphylococcus aureus and Escherichia coli as evaluation indexes, on the basis of protease screening, the extraction process of PTRM-AMPs was optimized, and the minimum inhibitory concentration of PTRM-AMPs was determined. Results: The optimum technological conditions for the preparation of PTRM-AMPs by alkaline protease hydrolysis were as follows: the enzymatic hydrolysis temperature was 39.5 ℃, the enzymatic hydrolysis time was 3.2 h, the pH value was 11.1, the solid-liquid ratio was 1∶20 （g/mL）, and the enzyme addition was 6 000 U/g. Under these conditions, the actual antibacterial rates of PTRM-AMPs against S. aureus and E. coli were 74.17% and 86.22% respectively, and the yield of PTRM-AMPs was 22.67%. The MIC values of PTRM-AMPs against S. aureus and E. coli were 5.0, 2.5 mg/mL respectively. Conclusion: PTRM-AMPs has significant antibacterial activity, especially against E. coli.

The rapid economic growth and environmental concerns have led to high demands on paper and paper-based products in terms of variety, quantity, quality, and specialty. Enhancement and functionalization with additives are constantly required. Moving away from traditional petroleum-based additives, researchers have attempted to use “green” nanoadditives by introducing renewable environmentally friendly nanocellulose. This article studies the functions of nanocellulose as bio-additives (enhancer, retention and filtration reagent, and coating aid) in paper and paper products, and overviews the research development of nanocellulose-based additives and their applications in the paper industry for both efficient production and paper functionalization. The review shows that (1) a variety of nanocellulose-based bioadditives have been reported for various applications in paper and paper-based products, while commercially viable developments are to be advanced; (2) nanocellulose was mostly formulated with other polymer and particles as additives to achieve their synergistic effects; (3) major interests have concentrated on the nanocellulose in the specialty papers as representing more value added products and in the efficient utilization of recycled fibers, which remains most attractive and promising for future development. This report shall provide most useful database information for researchers and industries for paper recycling and enhancement, and paper-based products innovation and application.

The present study investigated the lasting effects of sickness presenteeism on well-being and innovative job performance in the demanding Chinese work context compounded with the precarities of the post-pandemic business environment. Adopting the conservation of resources (COR) theory perspective, especially its proposition of compensation of resources, we incorporated social resources at work (supervisory support and collegial support) as joint moderators in the presenteeism–outcomes relationship. We employed a panel design in which all variables were measured twice with 6 months in between. Data were obtained from 323 Chinese employees working in diverse industries in Taiwan. We found that after controlling for the baseline level of well-being, presenteeism did not have a lasting effect on employees' exhaustion. However, presenteeism did have a negative lasting effect on employees' innovative behavior 6 months later. Moreover, we found a significant three-way interaction of presenteeism, supervisory support, and collegial support on employees' innovative job performance, after controlling for the baseline level of performance. Specifically, when working under illness, employees displayed the best innovative performance with high levels of both supervisory and collegial support, the worst performance with both support being low, and the intermediate when any one of the support being high. This can be taken as the preliminary evidence to support the COR proposition of resource caravans, showing that supervisory support and collegial support compensated for each other as critical resources in alleviating the impact of working under sickness on employees' innovative performance. Theoretical implications of the findings are discussed, taking into account the macro-cultural context of the East Asian Confucian societies. We also reflected on the managerial implications of the lasting damages of sickness presenteeism and benefits of mobilizing social resources on employees' well-being and performance.

A glucose microcirculation compartmental model (GMCM) for predicting blood glucose concentrations from the reference interstitial fluid (ISF) glucose concentrations was proposed before. It was used to compensate the delay error in ISF in order to improve the prediction accuracy and to facilitate the clinical application of continuous blood glucose monitoring. In this paper, many physiological parameters in GMCM reflecting delay and transport properties were discussed in details. The significance and influence of the parameters, diffusion distance (x), pressure gradient-driven transport ratio (RStarling), blood flow velocity (F), glucose capillary permeability (P), glucose diffusion coefficient (D), on the model were simulated and analysed. One group of blood (ISF) glucose values was set as input for the model with one varied parameter and other fixed parameters to predict ISF (blood) glucose concentrations. The results verified that F and P have much influence on the model and others play more minor roles. And some have positive influence on the model, like P, while others have a reverse effect, like F. All parameters can be modulated for different species or different physiological status during the model application.

BACKGROUND:The purpose of the study is to elicit the epigenetic mechanism involving CCCTC binding factor (CTCF)-mediated chromatin remodeling that regulates PAX6 gene interaction with differentiation-associated genes to control corneal epithelial differentiation. METHODS:Cell cycle progression and specific keratin expressions were measured to monitor changes of differentiation-induced primary human limbal stem/progenitor (HLS/P), human corneal epithelial (HCE) and human telomerase-immortalized corneal epithelial (HTCE) cells. PAX6-interactive and differentiation-associated genes in chromatin remodeling mediated by the epigenetic factor CTCF were detected by circular chromosome conformation capture (4C) and ChIP (Chromatin immunoprecipitation)-on-chip approaches, and verified by FISH (Fluorescent in situ hybridization). Furthermore, CTCF activities were altered by CTCF-shRNA to study the effect of CTCF on mediating interaction of Pax6 and differentiation-associated genes in corneal epithelial cell fate. RESULTS:Our results demonstrated that differentiation-induced human corneal epithelial cells expressed typical corneal epithelial characteristics including morphological changes, increased keratin12 expression and G0/G1 accumulations. Expressions of CTCF and PAX6 were suppressed and elevated following the process of differentiation, respectively. During corneal epithelial cell differentiation, differentiation-induced RCN1 and ADAM17 were found interacting with PAX6 in the process of CTCF-mediated chromatin remodeling detected by 4C and verified by ChIP-on-chip and FISH. Diminished CTCF mRNA with CTCF-shRNA in HTCE cells weakened the interaction of PAX6 gene in controlling RCN1/ADAM17 and enhanced early onset of the genes in cell differentiation. CONCLUSION:Our results explain how epigenetic factor CTCF-mediated chromatin remodeling regulates interactions between eye-specific PAX6 and those genes that are induced/associated with cell differentiation to modulate corneal epithelial cell-specific differentiation.

One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.

Objectives: The questionnaire of occupational stress index (OSI) has been popular in the workplace, and it has been tailored for bus drivers in Taiwan. Nevertheless, its outcomes for participants are based on self-evaluations, thus validation by their physiological stress biomarker is warranted and this is the main goal of this study. Methods: A cross-sectional study of sixty-three city bus drivers and fifty-four supporting staffs for comparison was conducted. Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured concentrations of these biological measures were logarithmically transformed before the statistical analysis where various scores of stressor factors, moderators, and stress effects of each OSI domain were analyzed by applying multiple linear regression models. Results: For drivers, the elevated 24-hour urine cortisol level was associated with a worker's relationship with their supervisor and any life change events in the most recent 3 months. The DHEA-S level was higher in drivers of younger age as well as drivers with more concerns relating to their salary and bonuses. Non-drivers showed no association between any stressor or satisfaction and urine cortisol and blood DHEA-S levels. Conclusion: Measurements of biomarkers may offer additional stress evaluations with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may result from stressors like income security. Prevention efforts towards occupational stress and life events and health promotional efforts for aged driver were important anti-stress remedies.

The aim of the study was to explore the association between the severity of psychosomatic symptoms and perceived work stress among male police officers in southern Taiwan. By stratified random sampling, a total of 698 male police officers were recruited into this study (the response rate was 73.4%; 512 of 698). A structured self-administered questionnaire on demographic and working characteristics, the severity of psychosomatic symptoms, perceived work stress, and social support was used to collect data anonymously. The results of multiple regression analysis revealed that (1) the police officers who perceived high-work stress reported more severe psychosomatic symptoms than those who perceived low-work stress; and (2) perceived social support had a moderating effect on the association between severity of psychosomatic symptoms and perceived work stress. Perceived work stress is an indicator of psychosomatic symptoms in police officers. Strategies for reducing psychosomatic symptoms of police officers include police administrators taking into account the level of work stress as well as more attention being paid to the resources of social support.

Chan Ding training is beneficial to health and emotional wellbeing. More and more people have taken up this practice over the past few years. A major training method of Chan Ding is to focus on the ten Mailuns, i.e., energy points, and to maintain physical stillness. In this article, wireless wearable accelerometers were used to detect physical stillness, and the created physical stillness index (PSI) was also shown. Ninety college students participated in this study. Primarily, accelerometers used on the arms and chest were examined. The results showed that the PSI values on the arms were higher than that of the chest, when participants moved their bodies in three different ways, left-right, anterior-posterior, and hand, movements with natural breathing. Then, they were divided into three groups to practice Chan Ding for approximately thirty minutes. Participants without any Chan Ding experience were in Group I. Participants with one year of Chan Ding experience were in Group II, and participants with over three year of experience were in Group III. The Chinese Happiness Inventory (CHI) was also conducted. Results showed that the PSI of the three groups measured during 20–30 min were 0.123 ± 0.155, 0.012 ± 0.013, and 0.001 ± 0.0003, respectively (p < 0.001 ***). The averaged CHI scores of the three groups were 10.13, 17.17, and 25.53, respectively (p < 0.001 ***). Correlation coefficients between PSI and CHI of the three groups were −0.440, −0.369, and −0.537, respectively (p < 0.01 **). PSI value and the wearable accelerometer that are presently available on the market could be used to evaluate the quality of the physical stillness of the participants during Chan Ding practice.

Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively.

Epigenetic factor CTCF (CCCTC binding factor) plays important roles in genetic controls of the cell fate. Previous studies found in corneal epithelial cells that CTCF is regulated by epidermal growth factor (EGF) through activation of NF-κB p65/p50. It also found that CTCF is suppressed in ultraviolet (UV) stress-induced corneal epithelial cells. However, it is still unknown how UV stress down-regulates CTCF affecting the cell fate. In the present study, we report that regulation of CTCF by extracellular stress signals is dependent upon activations of an oxidative stress-regulated protein Bcl-3. We found that activated Bcl-3 was able to bind to the κB sites identified in the CTCF promoter region. Bcl-3 was activated by UV irradiation to interact with NF-κB p50 by forming a Bcl-3/p50 heterodimer complex. The Bcl-3/p50 complex suppressed CTCF promoter activity to down-regulate CTCF transcription. Unlike the effect of EGF, UV stress-induced Bcl-3 activation suppressed CTCF activity without involving the IκBα and p65 pathway. Thus, results of the study reveal a novel mechanism for regulatory control of CTCF in UV stress-induced human corneal epithelial cells, which requires activation and formation of Bcl-3/p50 complex through a noncanonical NF-κB pathway.