Direct correlation of electrochemical behaviors with anti-thrombogenicity of semiconducting titanium oxide films

Biomaterials-associated thrombosis is dependent critically upon electrochemical response of fibrinogen on material surface. The relationship between the response and anti-thrombogenicity of biomaterials is not well-established. Titanium oxide appears to have good anti-thrombogenicity and little is known about its underlying essential chemistry. We correlate their anti-thrombogenicity directly to electrochemical behaviors in fibrinogen containing buffer solution. High degree of inherent n-type doping was noted to contribute the impedance preventing charge transfer from fibrinogen into film (namely its activation) and consequently reduced degree of anti-thrombogenicity. The impedance was the result of high donor carrier density as well as negative flat band potential

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

Single-cell sequencing revealed metabolic reprogramming and its transcription factor regulatory network in prostate cancer

Background/Aims: Prostate cancer is the most frequently diagnosed cancer among men in the United States and is the second leading cause of cancer-related deaths in men. The incidence of prostate cancer is gradually rising due to factors such as aging demographics and changes in dietary habits. The objective of this study is to investigate the metabolic reprogramming changes occurring in prostate cancer and identify potential therapeutic targets. Methods: In this study, we utilized single-cell sequencing to comprehensively characterize the alterations in metabolism and the regulatory role of transcription factors in various subtypes of prostate cancer. Results: In comparison to benign prostate tissue, prostate cancer displayed substantial metabolic variations, notably exhibiting heightened activity in fatty acid metabolism and cholesterol metabolism. This metabolic reprogramming not only influenced cellular energy utilization but also potentially impacted the activity of the androgen receptor (AR) pathway through the synthesis of endogenous steroid hormones. Through our analysis of transcription factor activity, we identified the crucial role of SREBPs, which are transcription factors associated with lipid metabolism, in prostate cancer. Encouragingly, the inhibitor Betulin effectively suppresses prostate cancer growth, highlighting its potential as a therapeutic agent for prostate cancer treatment

A four-stage DEA-based efficiency evaluation of public hospitals in China after the implementation of new medical reforms.

This study applied the non-parametric four-stage data envelopment analysis method (Four-Stage DEA) to measure the relative efficiencies of Chinese public hospitals from 2010 to 2016, and to determine how efficiencies were affected by eight factors. A sample of public hospitals (n = 84) was selected from Chongqing, China, including general hospitals and traditional Chinese medicine hospitals graded level 2 or above. The Four-Stage-DEA method was chosen since it enables the control of the impact of environment factors on efficiency evaluation results. Data on the number of staff, government financial subsidies, the number of beds and fixed assets were used as input whereas the number of out-patients and emergency department patients and visits, the number of discharged patients, medical and health service income and hospital bed utilization rate were chosen as study outputs. As relevant environmental variables, we selected GDP per capita, permanent population, population density, number of hospitals and number of available sickbeds in local medical institutions. The relative efficiencies (i.e. technical, pure technical, scale) of sample hospitals were also calculated to analyze the change between the first stage and fourth stage every year. The study found that Four-Stage-DEA can effectively filter the impact of environmental factors on evaluation results, which sets it apart from other models commonly used in existing studies

Responsive surface charge transfer doping effect of reductive bio-molecules (glucose, fucoidan, and heparin) contacting on semiconducting titanium oxide films

National Natural Science Foundation of China [20973134, 20603027]; Sichuan Youth Science & Technology Foundation for Distinguished Young Scholars [2012JQ0001]; Fundamental Research Funds for the Central Universities [SWJTU11ZT11]Titanium oxide films appear to have extensive potentials in various applications largely because of its unique semiconducting properties. Usually, attentions are paid to characterize or tailor their surface electronic states, depending upon specific working circumstances as well as the requirements by their functional performances. Nevertheless, very rarely concern has been taken to the responsive effect on their electronic surface states when they come into contact with surrounding environments, which actually plays an important or even decisive role in their subsequent functions. For instance, cases like biomedical application could normally render the surface sequentially contacting with varying ambient media. In this study, we implemented initial contacting titanium oxide film with three representative bio-molecules (glucose, fucoidan, and heparin), and investigated the responsive effect of charge transfer doping on its electronic properties and its bio-performance. It was shown that the contacting imposed apparently n-type surface-charge-transfer-doping effect on the titanium oxide films. Their surface resistivity increased; their photo-luminance emissions were obviously quenched; their hydrophilic properties were improved; and denaturalization of fibrinogen on the surface was suppressed. Electrons were assigned to inject into titanium oxide film to produce the n-type doping effect. Our finding suggests that the semiconductor biomaterials surface properties and performances might be largely or even decisively influenced by the initial contacting of ambient conditions

Testing Chemotherapeutic Agents in the Feather Follicle Identifies a Selective Blockade of Cell Proliferation and a Key Role for Sonic Hedgehog Signaling in Chemotherapy-Induced Tissue Damage

Chemotherapeutic agents induce complex tissue responses in vivo and damage normal organ functions. Here we use the feather follicle to investigate details of this damage response. We show that cyclophosphamide treatment, which causes chemotherapy-induced alopecia in mice and man, induces distinct defects in feather formation: feather branching is transiently and reversibly disrupted, thus leaving a morphological record of the impact of chemotherapeutic agents, whereas the rachis (feather axis) remains unperturbed. Similar defects are observed in feathers treated with 5-fluorouracil or taxol but not with doxorubicin or arabinofuranosyl cytidine (Ara-C). Selective blockade of cell proliferation was seen in the feather branching area, along with a downregulation of sonic hedgehog (Shh) transcription, but not in the equally proliferative rachis. Local delivery of the Shh inhibitor, cyclopamine, or Shh silencing both recapitulated this effect. In mouse hair follicles, those chemotherapeutic agents that disrupted feather formation also downregulated Shh gene expression and induced hair loss, whereas doxorubicin or Ara-C did not. Our results reveal a mechanism through which chemotherapeutic agents damage rapidly proliferating epithelial tissue, namely via the cell population–specific, Shh-dependent inhibition of proliferation. This mechanism may be targeted by future strategies to manage chemotherapy-induced tissue damage

Direct correlation of electrochemical behaviors with anti-thrombogenicity of semiconducting titanium oxide films

National Natural Science Foundation of China [20973134, 20603027]; Sichuan Youth Science & Technology Foundation for Distinguished Young Scholars [2012JQ0001]; State Key Laboratory of Physical Chemistry of the Solid Surface of China; Fundamental Research Funds for the Central Universities [SWJTU11ZT11]Biomaterials-associated thrombosis is dependent critically upon electrochemical response of fibrinogen on material surface. The relationship between the response and anti-thrombogenicity of biomaterials is not well-established. Titanium oxide appears to have good anti-thrombogenicity and little is known about its underlying essential chemistry. We correlate their anti-thrombogenicity directly to electrochemical behaviors in fibrinogen containing buffer solution. High degree of inherent n-type doping was noted to contribute the impedance preventing charge transfer from fibrinogen into film (namely its activation) and consequently reduced degree of anti-thrombogenicity. The impedance was the result of high donor carrier density as well as negative flat band potential

Application of All-Ages Lead Model Based on Monte Carlo Simulation of Preschool Children’s Exposure to Lead in Guangdong Province, China

Introduction: Lead (Pb) poisoning in children is a major public health issue worldwide. The physiologically based pharmacokinetic model (PBPK model) has been extensively utilized in Pb exposure risk assessment and can connect external exposure with biological monitoring data. This study aimed to combine a Monte Carlo simulation with the all-ages lead model (ALLM) to quantify the heterogeneity and uncertainty of certain parameters in the population. The parameters of the all-ages lead model based on Monte Carlo simulation (ALLM + MC) were localized in Guangdong Province. Our study discusses the practicability of the application of the localized ALLM + MC in Guangdong Province. Methods: A local sensitivity analysis was used to assess the impact of pharmacokinetic parameters on the prediction of blood lead level (BLL). Environmental Pb concentration, exposure parameters, and sensitive parameters were included in the ALLM + MC, and the differences between the ALLM- and the ALLM + MC-predicted values were compared. Additionally, we localized the exposure parameters in the ALLM + MC and used them to evaluate BLL in preschool children from Guangdong Province. Finally, we compared the predictive values to those observed in the literature. Results: The predictive values of ALLM and ALLM + MC had a significant correlation (r = 0.969, p p = 0.749). Except for children aged 5–6, the difference between the predictive and the observed values was less than 1 μg/dL. The root mean square error (RMSE) and the mean deviation (RMD) of ALLM and ALLM + MC were reduced by 24.73% and 32.83%, respectively. Conclusions: The localized ALLM + MC is more suitable for predicting the BLL of preschool children in Guangdong Province, which can be used to explain the heterogeneity and uncertainty of parameters in the population. The ALLM + MC has fewer time, space, and financial restrictions, making it more appropriate for determining the BLLs in large populations. The use of ALLM + MC would improve the feasibility of regular and long-term blood Pb detection

Inhibition of Shh Signaling through MAPK Activation Controls Chemotherapy-Induced Alopecia

Chemotherapy-induced hair loss (alopecia) (CIA) remains a major unsolved problem in clinical oncology. CIA is often considered to be a consequence of the antimitotic and apoptosis-promoting properties of chemotherapy drugs acting on rapidly proliferating hair matrix keratinocytes. Here, we show that in a mouse model of CIA, the downregulation of Shh signaling in the hair matrix is a critical early event. Inhibition of Shh signaling recapitulated key morphological and functional features of CIA, whereas recombinant Shh protein partially rescued hair loss. Phosphoproteomics analysis revealed that activation of the MAPK pathway is a key upstream event, which can be further manipulated to rescue CIA. Finally, in organ-cultured human scalp hair follicles as well as in patients undergoing chemotherapy, reduced expression of SHH gene correlates with chemotherapy-induced hair follicle damage or the degree of CIA, respectively. Our work revealed that Shh signaling is an evolutionarily conserved key target in CIA pathobiology. Specifically targeting the intrafollicular MAPK-Shh axis may provide a promising strategy to manage CIA

E-Cadherin–Mediated Cell Contact Controls the Epidermal Damage Response in Radiation Dermatitis

Radiotherapy is a primary oncological treatment modality that also damages normal tissue, including the skin, and causes radiation dermatitis (RD). Here, we explore the mechanism of acute epidermal damage in radiation dermatitis. Two distinctive phases in the damage response were identified: an early destructive phase, where a burst of reactive oxygen species induces loss of E-cadherin-mediated cell contact, followed by a regenerative phase, during which Wnt and Hippo signaling are activated. A blocking peptide, as well as a neutralizing antibody to E-cadherin, works synergistically with ionizing radiation to promote the epidermal damage. In addition, ROS disassembles adherens junctions in epithelial cells via posttranslational mechanisms, that is, activation of Src/Abl kinases and degradation of β-catenin/E-cadherin. The key role of tyrosine kinases in this process is further substantiated by the rescue effect of the tyrosine kinase inhibitor genistein, and the more specific Src/Abl kinase inhibitor dasatinib: both reduced ROS-induced degradation of β-catenin/E-cadherin in vitro and ameliorated skin damage in rodent models. Finally, we confirm that the same key molecular events are also seen in human radiation dermatitis. Therefore, we propose that loss of cell contact in epidermal keratinocytes through reactive oxygen species-mediated disassembly of adherens junctions is pivotal for the acute epidermal damage in radiation dermatitis