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Yang Chen,1,* Li Wang,1,* Shi Luo,2 Jun Hu,3 Xing Huang,1 Pei-Wen Li,2 Yi Zhang,1 Chao Wu,1 Bo-Le Tian1 1Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China; 2Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, People’s Republic of China; 3Laboratory of Basic Scientific Research, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo-Le TianDepartment of Pancreatic Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Road, Chengdu, Sichuan Province 610041, People’s Republic of ChinaTel +86 13880683475Fax +86 28-85422475Email tianbolemed@163.comIntroduction: Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC.Methods: The PTX-loaded PEGylated liposomes were prepared by film dispersion-ultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes.Results: PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth.Conclusion: The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.Keywords: pancreas-targeting, tertiary amine, pancreatic duct adenocarcinoma, paclitaxel liposome, antitumor efficacy

Doris Sau-Fung Yu,1 Polly Wai-chi Li,1 Fan Zhang,2 Sheung-Tak Cheng,2 Tsz Kwan Ng,3 Katherine S Judge4 1The Nethersole School of Nursing, The Chinese University of Hong Kong, Shatin, Hong Kong; 2Department of Health and Physical Education, The Education University of Hong Kong, Tai Po, Hong Kong; 3Fong Shu Chuen District Elderly Community Centre, Tung Wah Group Hospital, Sheung Wan, Hong Kong; 4Department of Psychology, College of Sciences and Health Professions, Cleveland State University, Cleveland, OH, USACorrespondence: Doris Sau-Fung YuThe Nethersole School of Nursing, The Chinese University of Hong Kong, Rm. 729, Esther Lee Building, Shatin, New Territories, Hong KongTel +852 3 943 4289Fax +852 2 603 5269Email dyu@cuhk.edu.hkPurpose: As an intermediate prodromal stage of dementia, mild cognitive impairment (MCI) causes functional, emotional, and social challenges for both of the person with MCI (PwMCI) and their family caregiver. However, major attention has only been placed on the PwMCI’s for cognitive training. This study evaluated a more comprehensive intervention, which integrated both strength-based and empowerment approaches, to address their complex needs in a dyadic fashion.Patients and methods: This randomized controlled trial allocated 103 MCI patient-caregiver dyads to receive a 14-week dyadic strength-based empowerment program (D-StEP-MCI, n=52) or usual care (n=51). The D-StEP-MCI program consisted of group-based session to the PwMCI, home-based dyadic sessions, and telephone follow-up, with the activities supported the care dyads to navigate their own strengths and resources for integration, together with the trained skills, to optimize role and social engagement in everyday life. Dyadic health outcomes in terms of subjective and objective cognitive function, and neuro-psychiatric symptoms of PwMCI, stress in symptom management of their family caregivers, and depression of the dyads were evaluated at baseline, after the D-StEP-MCI and at 3 months thereafter.Results: By using general estimating equation, the D-StEP-MCI significantly improved the cognitive function, subjective memory, and mood status of the PwMCI, and the positive changes were maintained at the 3-month endpoints. It also has significantly positive effects on caregivers’ stress in symptom management and level of depression.Conclusion: Our findings showed the health benefit of combining strength-based and empowerment approach in supporting the disease adaptation of PwMCI and caregiver in a dyadic fashion. This study also supports the use of a social interaction approach to optimize the everyday engagement of the PwMCI.Keywords: mild cognitive impairment, caregiving, empowerment, strength-based, dyadic approach

Dan Song,1 Doris SF Yu,2 Polly WC Li,2 Guijuan He,1 Qiuhua Sun1 1School of Nursing, ZheJiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Nethersole School of Nursing, The Chinese University of Hong Kong, HKSARCorrespondence: Qiuhua SunSchool of Nursing, ZheJiang Chinese Medical University, Room 807, 23 Building, Hangzhou, People’s Republic of ChinaTel/Fax +86-571- 86613674Email sunqiuhua@zcmu.edu.cnPurpose: This study aimed to assess the health-related quality of life (HRQoL) and identify the important correlates of HRQoL in older Chinese adults with mild cognitive impairment (MCI).Patients and methods: A cross-sectional study design was adopted. A total of 204 older adults with MCI were enrolled in this study. HRQoL was evaluated by the Quality of Life–Alzheimer’s disease. Hierarchical regression analysis was conducted to investigate the sociodemographic, disease-related, psychological, and behavioral factors associated with the HRQoL of individuals with MCI.Results: Hierarchical regression analysis indicated that old age (Beta = −0.131, p =0.024), low income (Beta = 0.128, p = 0.032), depressive symptoms (Beta = −0.564, p < 0.001), and poor sleep quality (Beta = −0.169, p =0.004) were significantly associated with the HRQoL of individuals with MCI.Conclusion: Caring for older Chinese adults with MCI should focus on sociodemographically disadvantaged groups with advanced age and low income. Rehabilitation programs that effectively alleviate depressive symptoms and improve sleep quality should be applied to older adults with MCI to enhance their HRQoL.Keywords: mild cognitive impairment, health-related quality of life, correlates

Competing Interests: Conflict of interest: none declared.

We reported transport diagrams of self-assembled germanium (Ge) double quantum-dots (DQDs) using direct current measurement under illumination at wavelength (λ) of 850 nm and at the base temperature of 4.5 K. Ge DQDs with a coupling-barrier of Si, tunneling-barriers of Si 3 N 4 , and self-aligned p + -Si reservoirs were fabricated in a self-organized CMOS approach. Charge transport through the Ge-DQDs is facilitated by photon-assisted tunneling. Characteristic gate-controlled hexagonal-shaped cells over a wide range of hole occupancy are acquired thanks to hard-wall confinement. Large dimensions (ΔV G  > 200 mV) of hexagonal-shaped cells are favored for the operation of charge states, indicating that our Ge DQDs system is less susceptible to shot noises arising from external voltage sources. Estimated intra-QD and inter-QD charging energies are E C,R /E C,L  = 48.9 meV/42.7 meV and E Cm  = 7.8 meV, respectively., (© 2024. The Author(s).)

As an important process for enhancing aroma of Wuyi rock tea, roasting has gradually been applied to the processing of bud green tea (BGT). However, there is a lack of comprehensive research on the impact of roasting on BGT aroma. This research provides a detailed analysis of the changes in aroma perception and compounds during the low-temperature roasting process (105°C, 90 minutes) of BGT. First, the changes in aroma perception were studied using quantitative descriptive analysis (QDA). The aroma perception of BGT transformed from fresh to chestnut like. Next, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) analysis was conducted to characterize the volatile compounds during roasting. A total of 313 volatile compounds were identified, among which 72 showed significant differences. Compounds such as linalool, benzyl alcohol, ionone, and ethyl salicylate (floral aroma) and 2,6-dimethylpyrazine, 2,3-dimethylpyrazine, 2-acetylpyrrole, and 3-furfural (caramel-like aroma) were confirmed to be involved in the formation of the chestnut-like aroma during roasting process. In addition, representative aroma compounds with different characteristics were selected based on monomolecular olfactory results to simulate sensory-level aroma interactions. The results showed that fresh and tender aromas exhibited mutual enhancement at low concentrations, while sweet and chestnut-like aromas showed mutual enhancement at all concentrations., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: The Self-Care of Heart Failure Index (SCHFI) is a widely used instrument used to measure self-care in both research and clinical settings. The lack of a psychometric evaluation of the traditional Chinese version of the SCHFI (SCHFI-C) might limit its utilization in non-Mainland Chinese populations such as Hong Kong, Macau, and Taiwan., Objective: This study aimed to evaluate the psychometric properties of the SCHFI-C v.7.2., Methods: Participants included 365 adults with heart failure. Breslin's method of translation was used to translate the SCHFI v.7.2 into traditional Chinese. Exploratory factor analysis was conducted to examine the dimensionality structure of each scale. Then, composite reliability was calculated to assess the reliability of 3 scales. Construct validity was examined by hypothesis testing and known-group comparisons., Results: The results of exploratory factor analysis suggest its multidimensionality of each scale. More specifically, the findings indicated a unique internal structure of the self-care maintenance ("lifestyle-related behaviors" and "consulting behaviors") and self-care management ("self-reliance behaviors" and "help-seeking behaviors") scales. The composite reliability of 3 scales were 0.81, 0.88, and 0.82, respectively, reaching adequate level. As for construct validity, the significant associations between the 3 SCHFI domains and self-care confidence as well as significant group difference among patients of different ages and educational backgrounds supported good construct validity., Conclusions: This study provides evidence of the reliability and validity of the SCHFI-C v.7.2. The traditional SCHFI-C v.7.2 can serve as a valid and reliable outcome measure to evaluate the effects of self-care-promoting interventions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of dietary diversity on depressive symptoms remains one-sided. We aim to explore the associations between all aspects of dietary diversity and the risk of depressive symptoms in US adults and their dose-response relationships. We selected 16 820 adults from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. Depressive symptoms were assessed using patient health questionnaire-9 (PHQ-9). Dietary diversity contains four indexes: count (dietary diversity score, DDS), evenness (Healthy Food Diversity Index, HFDI), dissimilarity (Jaccard distance, JD), and quality (Healthy Eating Index, HEI). Binary logistic regression was conducted to assess relationships between the four aspects of dietary diversity and depressive symptoms in whole and subgrouped populations. A restricted cubic spline was performed to explore the dose-response relationships. We revealed that DDS [0.20 (0.05, 0.73)], HFDI [0.51 (0.28, 0.94)], and HEI [0.46 (0.26, 0.80)] were inversely associated with the risk of depressive symptoms for the highest VS lowest quintile, especially in females and elders. Analysis of dose-response relationships determined linear relationships of DDS, HEI and depressive symptoms, while an "L" shaped relationship of HFDI and depressive symptoms. Adequate dietary diversity showed a significant effect on decreasing the risk of depressive symptoms at a score of 4 in DDS, 0.3 in HFDI, and a score of 51 in HEI. In conclusion, this study found that higher levels of dietary diversity, including count, evenness, and quality, might be protective factors against depressive symptoms, especially in females and elders. The DDS, HFDI, and HEI scores are recommended as 4, 0.3, and 51, respectively. Further investigation is needed to validate our results.

We reported exciton binding-energy determination using tunneling-current spectroscopy of Germanium (Ge) quantum dot (QD) single-hole transistors (SHTs) operating in the few-hole regime, under 405-1550 nm wavelength (λ) illumination. When the photon energy is smaller than the bandgap energy (1.46 eV) of a 20 nm Ge QD (for instance, λ = 1310 nm and 1550 nm illuminations), there is no change in the peak voltages of tunneling current spectroscopy even when the irradiation power density reaches as high as 10 µW/µm 2 . In contrast, a considerable shift in the first hole-tunneling current peak towards positive V G is induced (ΔV G  ≈ 0.08 V at 0.33 nW/µm 2 and 0.15 V at 1.4 nW/µm 2 ) and even additional photocurrent peaks are created at higher positive V G values (ΔV G  ≈ 0.2 V at 10 nW/µm 2 irradiation) by illumination at λ = 850 nm (where the photon energy matches the bandgap energy of the 20 nm Ge QD). These experimental observations were further strengthened when Ge-QD SHTs were illuminated by λ = 405 nm lasers at much lower optical-power conditions. The newly-photogenerated current peaks are attributed to the contribution of exciton, biexciton, and positive trion complexes. Furthermore, the exciton binding energy can be determined by analyzing the tunneling current spectra., (© 2023. Springer Nature Limited.)

Background: The highly prevalent late-life loneliness, together with its deleterious health impacts, calls for increasing attention to the need for effective interventions targeting on this growing public health problem. With the increasing evidence on interventions for combating loneliness, it is timely to identify their comparative effectiveness., Objective: This systematic review, meta-analysis and network meta-analysis was to identify and compare the effects of various non-pharmacological interventions on loneliness in community-dwelling older adults., Methods: Systematic search was conducted in nine electronic databases from inception to 30th March 2023 for studies investigating the effects of non-pharmacological interventions on loneliness among community-dwelling older adults. The interventions were categorized according to the nature and purpose of use. Pairwise meta-analysis and network meta-analyses were sequentially performed to identify the effects of each category of interventions and their comparative intervention effectiveness, respectively. Meta-regression was performed to examine any influence of study design and participants' characteristics on the intervention effectiveness. The study protocol was registered at PROSPERO (CRD42022307621)., Results: A total of 60 studies with 13,295 participants were included. The interventions were categorized as psychological interventions, social support interventions (by digital and non-digital means), behavioral activation, exercise intervention with and without social engagement, multi-component intervention and health promotion. Pairwise meta-analysis identified the positive effect of psychological interventions (Hedges' g = -2.33; 95%CI [-4.40, -0.25]; Z = -2.20, p = 0.003), non-digital social support interventions (Hedges' g = -0.63; 95%CI [-1.16, -0.10]; Z = 2.33, p = 0.02) and multi-component interventions (Hedges' g = -0.28 95%CI [-0.54, -0.03]; Z = -2.15, p = 0.03) on reducing loneliness. Subgroup analysis provided additional insights: i) social support and exercise interventions which integrated active strategies to optimize the social engagement demonstrated more promising intervention effects; ii) behavioral activation and multicomponent interventions worked better for older adults who were male or reported loneliness, respectively, and iii) counseling-based psychological interventions was more effective than mind-body practice. Network meta-analysis consistently pointed to the greatest therapeutic benefits of psychological interventions, and this was followed by exercise-based interventions, non-digital social support interventions and behavioral activation. Meta-regression further suggested that the therapeutic effects of the tested interventions were independent of the various factors relating to study design and participants' characteristics., Conclusions: This review highlights the more superior effects of psychological interventions in improving loneliness among older adults. Interventions which have an attribute to optimize social dynamic and connectivity may also be effective., Tweetable Abstract: Psychological intervention is the best to beat late-life loneliness, but increasing social dynamic and connectivity may add an impact., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown., Objective: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis., Methods: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot., Results: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway., Conclusion: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Instant dark teas (IDTs) were individually liquid-state fermented using the fungi Aspergillus cristatus, Aspergillus niger , and Aspergillus tubingensis . To understand how the chemical constituents of IDTs were affected by the fungi, samples were collected and measured by liquid chromatography-tandem mass-tandem mass spectrometry (LC-MS/MS). Untargeted metabolomics analysis revealed that 1,380 chemical constituents were identified in positive and negative ion modes, and 858 kinds of chemical components were differential metabolites. Through cluster analysis, IDTs were different from the blank control, and their chemical constituents mostly included carboxylic acids and their derivatives, flavonoids, organooxygen compounds, and fatty acyls. And the metabolites of IDTs fermented by A. niger and A. tubingensis had a high degree of similarity and were classified into one category, which showed that the fungus used to ferment is critical to the formation of certain qualities of IDTs. The biosynthesis of flavonoids and phenylpropanoid, which involved nine different metabolites such as p-coumarate, p-coumaroyl-CoA, caffeate, ferulate, naringenin, kaempferol, leucocyanidin, cyanidin, and (-)-epicatechin, were significant pathways influencing the quality formation of IDTs. Quantification analysis indicated that the A. tubingensis fermented-IDT had the highest content of theaflavin, theabrownin, and caffeine, while the A. cristatus fermented-IDT had the lowest content of theabrownin, and caffeine. Overall, the results provided new insights into the relationship between the quality formation of IDTs and the microorganisms used in liquid-state fermentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liao, Zhao, Jia, Niu, Bouphun, Li, Chen, Chen, Tang, Zhao, Zou, Zhu and Xu.)

Objective: To evaluate the reliability and validity of the traditional Chinese version of the Mild Behavioral Impairment Checklist (MBI-C) among Hong Kong Chinese with mild cognitive impairment (MCI)., Methods: A total of 172 participants were recruited from 2 community facilities. Cronbach's alpha (α) was calculated to evaluate internal consistency. Intra-class correlation coefficient (ICC) was used to measure 2-week test-retest reliability. Construct validity was evaluated by conducting exploratory factor analysis to identify the internal structure of MBI-C, and assessing the correlation between theoretically related constructs, including objective and subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was assessed by its correlation with Neuropsychiatric Inventory Questionnaire (NPI-Q)., Results: The results revealed good internal consistency and test-retest reliability of the MBI-C. Item analysis identified 4 items with low item-to-total correlations. The EFA identified a seven-factor structure. Hypothesis testing identified its significant correlations with subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was supported by its significant correlation with the NPI-Q., Conclusions: The traditional Chinese version of MBI-C is a valid and reliable outcome measure to assess the severity of neuropsychiatric symptoms of the MCI population.

Vaccinated or not? This is an attitude survey for 'approach-avoidance conflict' under uncertainty. Therefore, measuring people's attitude toward COVID-19 vaccination is relatively distinctive from an attitude over a general conflict. An online survey of 3123 respondents from 30 provincial-level regions - out of 31 - on the Chinese mainland was conducted from January 22 to 27, 2021 to measure their willingness to be vaccinated. We found that over half of the respondents chose the options 'not to be vaccinated now' and 'wait and see before making a vaccination decision,' thereby indicating that people's willingness to be vaccinated is not as optimistic as anticipated in the early stage of vaccination in China. Hence, investigators should carefully select the measuring method to assess the 'true' levels of willingness to accept COVID-19 vaccines. Lastly, the relevant departments should fully predict obstacles to achieve immunity coverage and prepare for the 'vaccine hesitancy' of people in need.

Measuring motor performance in individuals with intellectual disabilities (ID) is quite challenging. The objective of this study was to compare the motor performances of individuals with ID and those with typical development (TD) during soccer dribbling through video-based behavior-coded movement assessment along with a wearable sensor. A cross-sectional research design was adopted. Adolescents with TD (N = 25) and ID (N = 29) participated in the straight-line and zigzag soccer dribbling tests. The dribbling performance was videotaped, and the footage was then analyzed with customized behavior-coding software. The coded parameters were the time for movement completion, the number of kicks, blocks, steps, the number of times the ball went out of bounds, the number of missed cones, and the trunk tilt angle. Participants with ID exhibited significantly poorer performance and demonstrated greater variances in many time and frequency domain parameters. It also revealed that participants with ID kicked with both feet while dribbling, whereas those with TD mainly used the dominant foot. The present findings demonstrated how the ID population differed from their peers in lower-extremity strategic control. The customized video-based behavior-coded approach provides an efficient and effective way to gather behavioral data and calculate performance parameter statistics in populations with intellectual disabilities.

Among all types of tea, black tea is produced in the largest amount worldwide, and its consumption is still increasing. Enzymatic fermentation is considered majorly contribute to quality formation of black tea, and the information about the roles of bacterial community in black tea processing is scarce. This study aimed to analyze the dynamic changes in composition, structure, and function of microbial communities during black tea processing and reveal the roles of bacterial community in black tea processing. Results showed that the genera Sphingomonas and Variovorax were dominant throughout the processing of black tea. Prediction function analysis of bacterial community showed that the mean proportions of glucuronoarabinoxylan endo - 1,4 - beta - xylanase, aminopeptidase B, phosphoserine phosphatase, homoserine O-acetyltransferase, glycolysis related enzymes, pyruvate dehydrogenase, tricarboxylic acid cycle related enzymes, and glyoxylate bypass were significantly elevated in the rolling and fermentation stages. The contents of amino acids, soluble sugar, theaflavins, thearubigins, and theabrownins increased greatly during the rolling and fermentation processes. Redundancy and Pearson's correlation analyses showed that the relative abundance of bacteria was closely related to the contents of water extract, tea polyphenols, epigallocatechin, epicatechin gallate, catechin gallate, thearubigins, theaflavins, and theabrownins. Overall, the findings provided new insights into the variation of bacterial community during black tea processing and improved our understanding of the core functional bacteria involved in black tea processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alkaline pectate lyase has developmental prospects in the textile, pulp, paper, and food industries. In this study, we selected BacPelA, the pectin lyase with the highest expression activity from Bacillus clausii, modified and expressed in Escherichia coli BL21(DE3). Through fragment replacement, the catalytic activity of the enzyme was significantly improved. The optimum pH and temperature of the modified pectin lyase (PGLA-rep4) were 11.0 and 70 °C, respectively. It also exhibited a superior ability to cleave methylated pectin. The enzyme activity of PGLA-rep4, measured at 235 nm with 0.2% apple pectin as the substrate, was 554.0 U/mL, and the specific enzyme activity after purification using a nickel column was 822.9 U/mg. After approximately 20 ns of molecular dynamics simulation, the structure of the pectin lyase PGLA-rep4 tended to be stable. The root mean square fluctuation (RMSF) values at the key catalytically active site, LYS168, were higher than those of the wildtype PGLA. In addition, PGLA-rep4 was relatively stable in the presence of metal ions. PGLA-rep4 has good enzymatic properties and activities and maintains a high pH and temperature. This study provides a successful strategy for enhancing the catalytic activity of PGLA-rep4, making it the ultimate candidate for degumming and various uses in the pulp, paper, and textile industries., (© 2022. The Author(s).)

Importance: Strategies that enhance self-care of patients with heart failure reduce mortality and health care use., Objective: To examine whether an empowerment-based self-care education program was more effective and cost-effective to improve self-care, health status, and hospital service use than a didactic education program in patients with heart failure., Design, Setting, and Participants: In this double-blind randomized clinical trial, a consecutive sample of 988 patients with heart failure from the cardiac clinics of 2 regional hospitals underwent eligibility screening from February 1, 2017, to May 31, 2019, using the criteria of age of 55 years or older, heart failure diagnosed 6 months before screening, and New York Heart Association class II to IV. A total of 236 participants were randomized to the empowerment (n = 118) or education (n = 118) group., Interventions: The 12-week, group-based, empowerment-based education program included self-care assessment, goal-orientated actions in symptom recognition and response, fluid and dietary modification, and lifestyle management. Didactic education covered the same topics without empowerment strategies., Main Outcomes and Measures: The primary outcome was self-care measured by the Self-care Heart Failure Index (SCHFI) maintenance, management, and symptom perception subscales at posttest and 3-month end points. Secondary outcomes included measures of knowledge, confidence, health-related quality of life, and health service use. Direct, indirect, and social costs of the 2 programs were collected for cost-effectiveness analysis., Results: A total of 236 Chinese patients (mean [SD] age, 70 [8.0] years; 149 [63.1%] men) were included in the study. The empowerment group reported significantly greater improvement in SCHFI management scores (mean difference, 13.76; 95% CI, 5.89-21.62; Cohen d = 0.46 at posttest and Cohen d = 0.35 at 3 months) and symptom perception scores (mean difference, 20.36; 95% CI, 13.98-26.75; Cohen d = 0.84 at posttest and Cohen d = 0.61 at 3 months). The empowerment group had lower risks of emergency department attendance (incidence rate ratio, 0.55; 95% CI, 0.31-0.95; P = .03) and hospital admission (incidence rate ratio, 0.38; 95% CI, 0.21-0.68; P = .001) and better improved self-care knowledge (change in score [empowerment minus education], 1.29; 95% CI, 0.48-2.09) and confidence (change in score [empowerment minus education], 7.98; 95% CI, 1.91-14.05). Empowerment was cost-saving and cost-effective at T2 compared with the education group for quality-adjusted life-years, with an incremental cost-effectiveness ratio of -114 485., Conclusion and Relevance: In this randomized clinical trial, an empowerment approach led to clinically relevant improvement in symptom perception and self-care management among patients with heart failure. Its cost-effectiveness in improving these prognostic factors also benefits the patient-reported outcome., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-16008254.

Aim: To systematically evaluate the medication safety and effectiveness of Oxcarbazepine (OXC) and carbamazepine (CBZ) for the treatment of post-stroke epilepsy (PSE)., Material and Methods: We searched Medline and other databases to identify the randomized controlled trials (RCTs) that compare the efficacies of OXC and CBZ in treating PSE. Two authors extracted and analyzed the data independently with Revman 5.3 software. The Q-test and I2 were used to test the statistical heterogeneity. The fixed or random effect models were selected according to heterogeneity., Results: Eight RCTs that include 671 patients were involved in this study. The meta-analyses result showed that the overall efficiency of OXC was significantly better than that of CBZ (OR=4.55, 95% confidence interval (CI) (3.04?6.81)), the overall adverse events (OR=0.27, 95% CI (0.18?0.42), and the incidence of vomiting (OR=0.28, 95% CI (0.09?0.85)) of OXC was significantly less than that of CBZ. No significant differences in the incidence of rash (OR=0.45, 95% CI (0.19?1.07)), lethargy (OR=0.49, 95% CI (0.16?1.45)), and dizziness (OR=0.51, 95% CI (0.20?1.35)) were detected between OXC and CBZ., Conclusion: OXC seems to be superior to CBZ in the treatment of PSE, with higher efficacy, and safety than the latter. However, more research on OXC and CBZ in the treatment of PSE is required in the later stage due to the sample size limitation of our study.

Background: Treatment decisions in patients undergoing non-cardiac surgery are based on clinical assessment. The Revised Cardiac Risk Index (RCRI) is pragmatic and widely used but has only moderate discrimination. We aimed to test the efficacy of the CHA 2 DS 2 -VASc score and the combination of CHA 2 DS 2 -VASc and RCRI to predict perioperative risks for non-cardiac surgery., Methods: This pre-specified analysis was performed in a retrospective cohort undergoing intra-abdominal surgery in our center from July 1st, 2007 to June 30th, 2008. The possible association between the baseline characteristics (as defined by CHA 2 DS 2 -VASc and RCRI) and the primary outcome of composite perioperative cardiac complications (myocardial infarction, cardiac ischemia, heart failure, arrhythmia, stroke, and/or death) and secondary outcomes of individual endpoints were explored using multivariate Logistic regression. The area under the receiver operating characteristic curve (C-statistic) was used for RCRI, CHA 2 DS 2 -VASc, and the combined models, and the net reclassification improvement (NRI) was calculated to assess the additional discriminative ability., Results: Of the 1079 patients (age 57.5 ± 17.0 years), 460 (42.6%) were women. A total of 83 patients (7.7%) reached the primary endpoint. Secondary outcomes included 52 cardiac ischemic events, 40 myocardial infarction, 20 atrial fibrillation, 18 heart failure, four strokes, and 30 deaths. The endpoint events increased with the RCRI and CHA 2 DS 2 -VASc grade elevated (P < 0.05 for trend). The RCRI showed a moderate predictive ability with a C-statistics of 0.668 (95%CI 0.610-0.725) for the composite cardiac outcome. The C-statistics for the CHA 2 DS 2 -VASc was 0.765 (95% CI 0.709-0.820), indicating better performance than the RCRI (p = 0.011). Adding the CHA 2 DS 2 -VASc to the RCRI further increased the C-statistic to 0.774(95%CI 0.719-0.829), improved sensitivity, negative predictive value, and enhanced reclassification in reference to RCRI. Similar performance of the combined scores was demonstrated in the analysis of individual secondary endpoints. The best cut-off of a total of 4 scores was suggested for the combined CHA 2 DS 2 -VASc and RCRI in the prediction of the perioperative cardiac outcomes., Conclusions: The CHA 2 DS 2 -VASc score significantly enhanced risk assessment for the composite perioperative cardiovascular outcome in comparison to traditional RCRI risk stratification. Incorporation of CHA 2 DS 2 -VASc scores into clinical-decision making to improve perioperative management in patients undergoing non-cardiac surgery warrants consideration., (© 2021. The Author(s).)

Thanks to their high conductivity and theoretical capacity, transition metal selenides have demanded significant research attention as prospective anodes for sodium-ion batteries. Nevertheless, their practical applications are hindered by finite cycle life and inferior rate performance because of large volume expansion, polyselenide dissolution, and sluggish dynamics. Herein, the nitrogen-doped carbon (NC)-coated FeSe 2 nanoparticles encapsulated in NC nanoboxes (termed FeSe 2 @NDC NBs) are fabricated through the facile thermal selenization of polydopamine-wrapped Prussian blue precursors. In this composite, the existing nitrogen-doped dual carbon layer improves the intrinsic conductivity and structural integrity, while the unique porous yolk-shell architecture significantly mitigates the volume swelling during the sodium/desodium process. Moreover, the derived Fe-N-C bonds can effectively capture polyselenide, as well as promote Na + transportation and good reversible conversion reaction. As expected, the FeSe 2 @NDC NBs deliver remarkable rate performance (374.9 mA h g -1 at 10.0 A g -1 ) and long-cycling stability (403.3 mA h g -1 over 2000 loops at 5.0 A g -1 ). When further coupled with a self-made Na 3 V 2 (PO 4 ) 3 @C cathode in sodium-ion full cells, FeSe 2 @NDC NBs also exhibit considerably high and stable sodium-storage performance.

Electrode materials with high conductivities that are compatible with flexible substrates are important for preparing high-capacitance electrode materials and improving the energy density of flexible supercapacitors. Here, we report the design and fabrication of a new type of flexible electrode based on nanosheet architectures of a Co-Fe alloy (FeCo-A) coated with ternary metal sulfide composites (FeCo-Ss) on silver-sputtered carbon cloth. The high conductivity of the flexible substrate and the iron-cobalt alloy skeleton enables good electron transmission through the material. In particular, the outer FeCo-S layer has an average thickness of ∼30 nm, providing many active sites. This layer also inhibits the oxidation of the alloy. The electrode material is close to 20 nm thick, which limits inaccessible volumes and promotes high utilization of FeCo-alloy@FeCo-sulfide (FeCo-A-S). The additive-free FeCo-A-S electrode has a high specific capacitance of 2932.2 F g -1 at 1.0 A g -1 and a superior rate capability. All-solid-state supercapacitors based on these electrodes have a high power density of 8000 W kg -1 and a high energy density of 46.1 W h kg -1 .

Semiconductor-based quantum registers require scalable quantum-dots (QDs) to be accurately located in close proximity to and independently addressable by external electrodes. Si-based QD qubits have been realized in various lithographically-defined Si/SiGe heterostructures and validated only for milli-Kelvin temperature operation. QD qubits have recently been explored in germanium (Ge) materials systems that are envisaged to operate at higher temperatures, relax lithographic-fabrication requirements, and scale up to large quantum systems. We report the unique scalability and tunability of Ge spherical-shaped QDs that are controllably located, closely coupled between each another, and self-aligned with control electrodes, using a coordinated combination of lithographic patterning and self-assembled growth. The core experimental design is based on the thermal oxidation of poly-SiGe spacer islands located at each sidewall corner or included-angle location of Si 3 N 4 /Si-ridges with specially designed fanout structures. Multiple Ge QDs with good tunability in QD sizes and self-aligned electrodes were controllably achieved. Spherical-shaped Ge QDs are closely coupled to each other via coupling barriers of Si 3 N 4 spacer layers/c-Si that are electrically tunable via self-aligned poly-Si or polycide electrodes. Our ability to place size-tunable spherical Ge QDs at any desired location, therefore, offers a large parameter space within which to design novel quantum electronic devices.

Transient receptor potential canonical (TRPC) channels, as important membrane proteins regulating intracellular calcium (Ca 2+ i ) signaling, are involved in a variety of physiological and pathological processes. Activation and regulation of TRPC are more dependent on membrane or intracellular signals. However, how extracellular signals regulate TRPC6 function remains to be further investigated. Here, we suggest that two distinct small molecules, M085 and GSK1702934A, directly activate TRPC6, both through a mechanism of stimulation of extracellular sites formed by the pore helix (PH) and transmembrane (TM) helix S6. In silico docking scanning of TRPC6 identified three extracellular sites that can bind small molecules, of which only mutations on residues of PH and S6 helix significantly reduced the apparent affinity of M085 and GSK1702934A and attenuated the maximal response of TRPC6 to these two chemicals by altering channel gating of TRPC6. Combing metadynamics, molecular dynamics simulations, and mutagenesis, we revealed that W679, E671, E672, and K675 in the PH and N701 and Y704 in the S6 helix constitute an orthosteric site for the recognition of these two agonists. The importance of this site was further confirmed by covalent modification of amino acid residing at the interface of the PH and S6 helix. Given that three structurally distinct agonists M085, GSK1702934A, and AM-0883, act at this site, as well as the occupancy of lipid molecules at this position found in other TRP subfamilies, it is suggested that the cavity formed by the PH and S6 has an important role in the regulation of TRP channel function by extracellular signals., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Transition metal and nitrogen co-doped carbon-based catalysts (TM-N-C) have become the most promising catalysts for Pt/C due to their wide range of sources, low cost, high catalytic activity, excellent stability and strong resistance to poisoning, especially Fe-N-C metal-organic frameworks (MOFs), which are some of the most promising precursors for the preparation of Fe-N-C catalysts due to their inherent properties, such as their highly ordered three-dimensional framework structure, controlled porosity, and tuneable chemistry. Based on these, in this paper, different iron sources were added to synthesis a sort of zeolitic imidazole frameworks (ZIF-8). Then the imidazole salt in ZIF-8 was rearranged into high N-doped carbon by high-temperature pyrolysis to prepare the Fe-N-C catalyst. We studied the physical characteristics of the catalysts by different iron sources and their effects on the catalytic properties of the oxygen reduction reaction (ORR). From the point of morphology, various iron sources have a positive influence on maintaining the morphology of ZIF-8 polyhedron. Fe-N/C-Fe(NO₃)₃ has the same anion as zinc nitrate, and can maintain a polyhedral morphology after high-temperature calcination. It had the highest ORR catalytic activity compared to the other four catalyst materials, which proved that there is a certain relationship between morphology and performance. This paper will provide a useful reference and new models for the development of high-performance ORR catalysts without precious metals.

Abstract: The aim of this investigation was to compare the diagnostic performance of radiographers and deep learning algorithms in pulmonary nodule/mass detection on chest radiograph.A test set of 100 chest radiographs containing 53 cases with no pathology (normal) and 47 abnormal cases (pulmonary nodules/masses) independently interpreted by 6 trained radiographers and deep learning algorithems in a random order. The diagnostic performances of both deep learning algorithms and trained radiographers for pulmonary nodules/masses detection were compared.QUIBIM Chest X-ray Classifier, a deep learning through mass algorithm that performs superiorly to practicing radiographers in the detection of pulmonary nodules/masses (AUCMass: 0.916 vs AUCTrained radiographer: 0.778, P < .001). In addition, heat-map algorithm could automatically detect and localize pulmonary nodules/masses in chest radiographs with high specificity.In conclusion, the deep-learning based computer-aided diagnosis system through 4 algorithms could potentially assist trained radiographers by increasing the confidence and access to chest radiograph interpretation in the age of digital age with the growing demand of medical imaging usage and radiologist burnout., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of this present research is to enhance the squalene production in Yarrowia lipolytica using pathway engineering and bioprocess engineering. Firstly, to improve the production of squalene, the endogenous HMG-CoA reductase (HMG1) was overexpressed in Y. lipolytica to yield 208.88 mg/L squalene. Secondly, the HMG1 and diacylglycerol acyltranferase (DGA1) were co-overexpressed, the derived recombinant Y. lipolytica SQ-1 strain produced 439.14 mg/L of squalene. Thirdly, by optimizing the fermentation medium, the improved titer of squalene with 514.34 mg/L was obtained by the engineered strain SQ-1 grown on YPD-80 medium. Finally, by optimizing the addition concentrations of acetate, citrate and terbinafine, the 731.18 mg/L squalene was produced in the engineered strain SQ-1 with the addition of 0.5 mg/L terbinafine. This work describes the highest reported squalene titer in Y. lipolytica to date. This study will provide the foundation for further engineering Y. lipolytica capable of cost-efficiently producing squalene., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Perioperative cardiovascular events constitute the majority of complications in noncardiac surgery. Older and female patients have been less investigated. We aimed to evaluate differences in perioperative cardiovascular outcomes by age and sex., Methods: We enrolled 1079 patients (57.5 ± 17.0 years, 42.6% women) undergoing intra-abdominal surgery from July 2007 to June 2008 and compared occurrence of perioperative cardiac events by age (≥65 vs. <65 years) and sex. Multivariable logistic regression was used to investigate associations between age, sex, and outcomes., Results: Age ≥65 years was associated with perioperative myocardial infarction (MI) (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.3-6.6) and total cardiovascular events (OR 2.4, 95% CI: 1.3-4.2). Age ≥65 years was associated with higher perioperative MI risks in men (OR 4.7, 95% CI: 1.3-17.6) than in women (OR 3.1, 95% CI: 1.2-8.3). Advanced age was associated with heart failure in women (OR 13.9, 95% CI: 1.7-110.5). Female sex was a risk factor for heart failure in elderly patients (OR 4.2, 95% CI: 1.1-15.7)., Conclusions: Advanced age appeared to be associated with increased perioperative cardiac risk but differed by sex. Tailored strategies should be considered with respect to the patient's sex.

Nucleotide oligomerization domain-like receptors (NLRs) and RIG-I-like receptors (RLRs) detect diverse pathogen-associated molecular patterns to activate the innate immune response. The role of mammalian NLR NOD1 in sensing bacteria is well established. Although several studies suggest NOD1 also plays a role in sensing viruses, the mechanisms behind this are still largely unknown. In this study, we report on the synergism and antagonism between NOD1 and MDA5 isoforms in teleost. In zebrafish, the overexpression of NOD1 enhances the antiviral response and mRNA abundances of key antiviral genes involved in RLR-mediated signaling, whereas the loss of NOD1 has the opposite effect. Notably, spring viremia of carp virus-infected NOD1 -/- zebrafish exhibit reduced survival compared with wild-type counterparts. Mechanistically, NOD1 targets MDA5 isoforms and TRAF3 to modulate the formation of MDA5-MAVS and TRAF3-MAVS complexes. The cumulative effects of NOD1 and MDA5a (MDA5 normal form) were observed for the binding with poly(I:C) and the formation of the MDA5a-MAVS complex, which led to increased transcription of type I IFNs and ISGs. However, the antagonism between NOD1 and MDA5b (MDA5 truncated form) was clearly observed during proteasomal degradation of NOD1 by MDA5b. In humans, the interactions between NOD1-MDA5 and NOD1-TRAF3 were confirmed. Furthermore, the roles that NOD1 plays in enhancing the binding of MDA5 to MAVS and poly(I:C) are also evolutionarily conserved across species. Taken together, our findings suggest that mutual regulation between NOD1 and MDA5 isoforms may play a crucial role in the innate immune response and that NOD1 acts as a positive regulator of MDA5/MAVS normal form-mediated immune signaling in vertebrates., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Objective: To evaluate efficacy of traditional Chinese medicine (TCM) for gastric precancerous lesion (GPL)., Method: Literature retrieval was conducted in seven databases from their inception through Dec. 24th, 2018. The Cochrane collaboration, Review Manager (RevMan5.3) and GRADE profiler software were conducted for this meta-analysis., Results: In primary outcomes, results of meta-analysis showed that TCM had superior to current routine pharmacotherapy (RP) in clinical efficacy, Helicobacter pylori (Hp) eradication rate, efficacy under endoscopy, and TCM syndrome efficacy. Meanwhile, no potential publication bias was detected by Begg's and Egger's tests. In secondary outcomes, compared with control groups, experimental groups were more positive effects on improvement of stomach distention, stomachache, and heartburn., Conclusion: Our findings indicated that TCM could have positive effects on GPL. However, further standardized RCTs of rigorous design should be required to obtain more forceful evidence., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown., Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development., Results: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC., Conclusions: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Hong-Wu Ma et al.)

Objective: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD., Methods: Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed., Results: Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination)., Conclusion: Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Activated carbon support Pd nanoparticles (NPs) modified by various WO₃-shaped catalysts were prepared and applied as an efficient anode catalyst for direct formic acid fuel cells. Three forms of WO₃ (nanosheets, nanoparticles, nanobars) modified activated carbon hybrids were first prepared via different syntheses, and then used as supports to synthesize three types of Pd-WO₃/C catalysts by a NaBH4 reduction method. The morphology, structure, and electrochemical performances of the as-prepared Pd-WO₃/C catalysts were characterized and analyzed. We can see that the noble metal particles loaded with activated carbon modified by WO₃ exhibit small particle size and uniform dispersion from the transmission electron microscope image. The synthesized composite catalysts was used for the formic acid electrooxidation and showed excellent catalytic performance. The oxidation peak current density of the Pd/WO₃-Nanosheets/C (40.04 mA·cm -2 was the highest, approximately 1.2 times that of Pd/C (33.00 mA·cm -2 . Additionally, the long-term stability ( i-t ) test results show that the Pd/WO₃-Nanosheets/C catalyst exhibits superior stability during formic acid electrooxidation. The reason for the increase in performance can be attributed to the following: the large specific surface area of WO₃ decreases the adsorption strength of intermediates such as CO ad on Pd and prevents the accumulation of poisonous intermediates, thereby promoting the oxidation reaction of formic acid in the direct pathway; the catalyst-support interaction between precious metal Pd and WO₃, substantially improving the catalytic performance of Pd-WO₃/C catalysts.

Due to their inherent physical properties, thin-film Si/SiGe heterostructures have specific thermal management applications in advanced integrated circuits and this in turn is essential not only to prevent a high local temperature and overheat inside the circuit, but also generate electricity through the Seebeck effect. Here, we were able to enhance the Seebeck effect in the germanium composite quantum dots (CQDs) embedded in silicon by increasing the number of thin silicon layers inside the dot (multi-fold CQD material). The Seebeck effect in the CQD structures and multi-layer boron atomic layer-doped SiGe epitaxial films was studied experimentally at temperatures in the range from 50 to 300 K and detailed calculations for the Seebeck coefficient employing different scattering mechanisms were made. Our results show that the Seebeck coefficient is enhanced up to ≈40% in a 3-fold CQD material with respect to 2-fold Ge/Si CQDs. This enhancement was precisely modeled by taking into account the scattering of phonons by inner boundaries and the carrier filtering by the CQD inclusions. Our model is also able to reproduce the observed temperature dependence of the Seebeck coefficient in the B atomic layer-doped SiGe fairly well. We expect that the phonon scattering techniques developed here could significantly improve the thermoelectric performance of Ge/Si materials through further optimization of the layer stacks inside the quantum dot and of the dopant concentrations.

Gemcitabine (Gem) is a standard first-line treatment for pancreatic cancer (PC). However, its chemotherapeutic efficacy is hampered by various limitations such as short half-life, metabolic inactivation, and lack of tumor localizing. We previously synthesized a lipophilic Gem derivative (Gem formyl hexadecyl ester, GemC16) that exhibited improved antitumor activity in vitro. In this study, a target ligand N,N-dimethyl-1,3-propanediamine was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol-2000)] (DSPE-PEG-NHS) to form DSPE-PEG-2N. Then, pancreas-targeting liposomes (2N-LPs) were prepared using the film dispersion-ultrasonic method. GemC16-loaded 2N-LPs displayed near-spherical shapes with an average size distribution of 157.2 nm (polydispersity index (PDI) = 0.201). The encapsulation efficiency of GemC16 was up to 97.3% with a loading capacity of 8.9%. In human PC cell line (BxPC-3) and rat pancreatic acinar cell line (AR42J), cellular uptake of 2N-LPs was significantly enhanced compared with that of unmodified PEG-LPs. 2N-LPs exhibited more potent in vitro cytotoxicity against BxPC-3 and AR42J cell lines than PEG-LPs. After systemic administration in mice, 2N-LPs remarkably increased drug distribution in the pancreas. In an orthotopic tumor mouse model of PC, GemC16-bearing liposomes were more effective in preventing tumor growth than free GemC16. Among these treatments, 2N-LPs showed the best curative effect. Together, 2N-LPs represent a promising nanocarrier to achieve pancreas-targeting drug delivery, and this work would provide new ideas for the chemotherapy of PC.

A new phenomenon of highly localized, nanoscale densification and crystallization of silicon-nitride (Si 3 N 4 ) layers has been observed. A drastic reduction in the thermal budget (temperature and processing time) for local densification and even nanocrystallization of low-pressure chemical vapor deposited amorphous Si 3 N 4 layers is mediated by the presence of Ge, Si, and O interstitials in close proximity to the Si 3 N 4 . The enhancement of localized densification and nanocrystallization observed in Si 3 N 4 layers appears to be catalyzed by proximal Ge quantum dots (QDs) 'migrating' through the Si 3 N 4 /Si layers and are influenced by the oxidation time and Ge QD size. Implications of the highly localized, nanoscale densification and crystallization of silicon-nitride (Si 3 N 4 ) layers for photonic and electronic device applications are discussed.

We report the novel tunability of the diameters and spacings of paired Ge double quantum dots (DQDs) using nano-spacer technology in combination with selective oxidation of Si 0.85 Ge 0.15 at high temperature. Pairs of spherical-shaped Ge QDs were formed by the selective oxidation of poly-SiGe spacer islands at each sidewall corner of the nano-patterned Si 3 N 4 /poly-Si ridges. The diameters of the Ge spherical QDs are essentially determined by geometrical conditions (height, width, and length) of the nano-patterned spacer islands of poly-SiGe, which are tunable by adjusting the process times of deposition and etch back for poly-SiGe spacer layers in combination with the exposure dose of electron-beam lithography. Most importantly, the separations between the Ge DQDs are controllable by adjusting the widths of the poly-Si/Si 3 N 4 ridges and the thermal oxidation times. Our self-organization and self-alignment approach achieved high symmetry within the Ge DQDs in terms of the individual QD diameters as well as the coupling barriers between the QDs and external electrodes in close proximity.

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels., Competing Interests: The authors declare no conflicts of interest.

The majority of Musashi 1 (Msi1)‑positive cells derived from mouse embryonic stem cells (mESCs) are prone to differentiate into neural epithelial‑like cells, and only a small proportion of Msi1‑positive cells differentiate into intestinal epithelial‑like cells. Whether inhibiting the phosphatidylinositol 3‑kinase (PI3K) signaling of mESCs can promote the differentiation of Msi1‑positive cells into intestinal epithelial‑like cells remains to be fully elucidated. In the present study, to inhibit PI3K signaling, mESCs were treated with LY294002. A pMsi1‑green fluorescence protein reporter plasmid was used to sort the Msi1‑positive cells from mESCs treated and untreated with LY294002 (5 µmol/l). The Msi1‑positive cells were hypodermically engrafted into the backs of non‑obese diabetic/severe combined immunodeficient mice. The presence of neural and intestinal epithelial‑like cells in the grafts was detected by reverse transcription‑quantitative polymerase chain reaction analysis and immunohistochemistry. Compared with the Msi1‑positive cells derived from mESCs without LY294002 treatment, Msi1‑positive cells derived from mESCs treated with LY294002 expressed higher levels of leucine‑rich repeat‑containing G‑protein coupled receptor, a marker of intestinal epithelial stem cells, and lower levels of Nestin, a marker of neural epithelial stem cells. The grafts from Msi1‑positive cells treated with LY294002 contained more intestinal epithelial‑like tissues and fewer neural epithelial‑like tissues, compared with those from untreated Msi1‑positive cells. LY294002 had the ability to promote the differentiation of mESCs into intestinal epithelial‑like tissues. The Msi1‑positive cells selected from the cell population derived from mESCs treated with LY294002 exhibited more characteristics of intestinal epithelial stem cells than those from the untreated group.

Background: Twitter messages (tweets) contain various types of topics in our daily life, which include health-related topics. Analysis of health-related tweets would help us understand health conditions and concerns encountered in our daily lives. In this paper we evaluate an approach to extracting causalities from tweets using natural language processing (NLP) techniques., Methods: Lexico-syntactic patterns based on dependency parser outputs are used for causality extraction. We focused on three health-related topics: "stress", "insomnia", and "headache." A large dataset consisting of 24 million tweets are used., Results: The results show the proposed approach achieved an average precision between 74.59 to 92.27% in comparisons with human annotations., Conclusions: Manual analysis on extracted causalities in tweets reveals interesting findings about expressions on health-related topic posted by Twitter users.

Genome editing for therapeutic applications often requires cleavage within a narrow sequence window. Here, to enable such high-precision targeting with zinc-finger nucleases (ZFNs), we have developed an expanded set of architectures that collectively increase the configurational options available for design by a factor of 64. These new architectures feature the functional attachment of the FokI cleavage domain to the amino terminus of one or both zinc-finger proteins (ZFPs) in the ZFN dimer, as well as the option to skip bases between the target triplets of otherwise adjacent fingers in each zinc-finger array. Using our new architectures, we demonstrate targeting of an arbitrarily chosen 28 bp genomic locus at a density that approaches 1.0 (i.e., efficient ZFNs available for targeting almost every base step). We show that these new architectures may be used for targeting three loci of therapeutic significance with a high degree of precision, efficiency, and specificity.

Background: Prolonged delay in seeking medical attention for acute myocardial infarction persists as a global phenomenon, which limits effective disease management. The effects of previous mass-media campaigns and psycho-educations have been minimal., Aims: This study aimed to develop a modeling-based narrative intervention, and to examine its feasibility and preliminary effects on care-seeking behavioral intention in Chinese acute myocardial infarction patients., Methods: The modeling-based narrative intervention was developed by integrating updated research evidence and participants' perspectives. Ten patients were invited to co-design the intervention. The narrative approach was adopted to engage patients in a mental rehearsal of the decision-making process through a virtual acute myocardial infarction attack experience. A pilot randomized controlled trial was adopted to examine the feasibility and preliminary effects of this intervention., Results: A total of 67 participants were randomly allocated to receive either the modeling-based narrative intervention ( n=34) or didactic education ( n=33). The intervention was feasible and well-accepted by the participants as evidenced by high attendance and participant satisfaction. They considered the intervention as informative and interesting. The majority of the participants in the intervention group expressed that they enjoyed the intervention. Although the preliminary data showed non-significant between-group differences, a more prominent improving trend for acute myocardial infarction knowledge, care-seeking attitudes and beliefs in the intervention group were evident., Conclusions: This study is the first of its kind to adopt a novel narrative approach to optimize care-seeking behaviors among patients with acute myocardial infarction. The preliminary findings showed that this approach was highly feasible and accepted by patients.

Background: Serum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy., Methods: Patients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value., Results: 30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, - 122-3p, and - 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, - 122-3p, - 486-3p, -451a, - 122-5p, - 3591-3p, - 486-5p, -151a-3p, -92a-3p, -320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, -151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52-0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, -451a, -151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation., Conclusion: These results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis., Trial Registration: Chinese Clinical Trial Registy ( ChiCTR-IOR-16008027 , Date of Registration:2016-03-01).

Background: Aging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, liver shows age-related dysregulation of lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In the fruit fly, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Compared to fat body, little is known about how oenocytes age and what are their roles in aging regulation. To characterize age- and stress-regulated gene expression in oenocytes, we performed cell-type-specific ribosome profiling (RiboTag) to examine the impacts of aging and oxidative stress on oenocyte translatome in Drosophila., Results: We show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, oxidative phosphorylation, ribosome, proteasome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and immune response pathways were up-regulated. In addition, most of the peroxisomal genes were down-regulated in aged oenocytes, including genes involved in peroxisomal biogenesis factors and fatty acid beta-oxidation. Many age-related mRNA translational changes in oenocytes are similar to aged mammalian liver, such as up-regulation of innate immune response and Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism. Furthermore, oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis)., Conclusions: Our oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes were altered in both oenocytes and liver during aging. Thus, our translatome analysis provide important genomic resource for future dissection of oenocyte function and its role in lipid metabolism, stress response and aging regulation.

In this study, the porous composite films of carboxymethyl chitosan/alginate/tranexamic acid were fabricated, with calcium chloride as the crosslinking agent and glycerin as a plasticizer. The composite films were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The properties of the composite films, including water absorption, air permeability, and cumulative release rate, were tested. In addition, their hemostatic performance was evaluated. The results showed that the appearance of the films with good adhesion was smooth and porous. FTIR showed that chemical crosslinking between carboxymethyl chitosan and sodium alginate was successful. The excellent cumulative release of tranexamic acid in the composite films (60⁻80%) gives the films a significant procoagulant effect. This has good prospects for the development of medical hemostasis materials.