Search

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt-catalyzed C-H activation/annulation strategy in high yield with excellent enantio- and diastereoselectivity (up to >99 % ee and >20 : 1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach. A key octahedral cobaltacycle intermediate was synthesized and characterized, providing valuable insights into the mode of enantio- and diastereocontrol of this protocol. Noteworthy photoluminescence quantum yields of up to 0.94 were measured, underscoring the potential of these compounds in the domain of organic fluorescent materials., (© 2024 Wiley-VCH GmbH.)

Axially chiral carboxylic acids are important motifs in chiral catalysts and ligands. We herein reported the synthesis of axially chiral carboxylic acids via Pd(II)-catalyzed atroposelective C-H olefination using carboxylic acid as the native directing group. A broad range of axial chiral biaryl-2-carboxylic acids were synthesized in good yields with high enantioselectivities (up to 84% yield with 99% ee). Gram-scale reaction and further transformation reactions also provide a platform for synthetic applications of this method.

The combination of achiral Cp*Rh(III) with chiral carboxylic acids (CCAs) represents an efficient catalytic system in transition metal-catalyzed enantioselective C-H activation. However, this hybrid catalysis is limited to redox-neutral C-H activation reactions and the adopt to oxidative enantioselective C-H activation remains elusive and pose a significant challenge. Herein, we describe the development of an electrochemical Cp*Rh(III)-catalyzed enantioselective C-H annulation of sulfoximines with alkynes enabled by chiral carboxylic acid (CCA) in an operationally friendly undivided cell at room temperature. A broad range of enantioenriched 1,2-benzothiazines are obtained in high yields with excellent enantioselectivities (up to 99 % yield and 98 : 2 er). The practicality of this method is demonstrated by scale-up reaction in a batch reactor with external circulation. A crucial chiral Cp*Rh(III) intermediate is isolated, characterized, and transformed, providing rational support for a Rh(III)/Rh(I) electrocatalytic cycle., (© 2024 Wiley‐VCH GmbH.)

The transplantation of engineered cells that secrete therapeutic proteins presents a promising method for addressing a range of chronic diseases. However, hydrogels used to encase and protect non-autologous cells from immune rejection often suffer from poor mechanical properties, insufficient oxygenation, and fibrotic encapsulation. Here, we introduce a composite encapsulation system comprising an oxygen-permeable silicone cryogel skeleton, a hydrogel matrix, and a fibrosis-resistant polymer coating. Cryogel skeletons enhance the fracture toughness of conventional alginate hydrogels by 23-fold and oxygen diffusion by 2.8-fold, effectively mitigating both implant fracture and hypoxia of encapsulated cells. Composite implants containing xenogeneic cells engineered to secrete erythropoietin significantly outperform unsupported alginate implants in therapeutic delivery over 8 weeks in immunocompetent mice. By improving mechanical resiliency and sustaining denser cell populations, silicone cryogel skeletons enable more durable and miniaturized therapeutic implants.

A microfluidic strategy of smart calcium alginate (CA) capsules is presented to immobilize Pseudomonas aeruginosa to treat oil slicks effectively. The capsule wall is embedded with poly (N-isopropyl acrylamide) sub-microspheres as thermo-responsive switches. CA capsules, with a diameter of 3.26 mm and a thin wall thickness about 12.8 μm, have satisfying monodispersity, cavity structure, and dense surface structures. The capsules possess excellent encapsulation of bacteria, which are fixed in a restricted space and become more aggregated. It overcomes the disadvantages of a long fermentation production cycle, easy loss of bacteria, and susceptibility to shear effect. The smart CA capsules immobilized with bacteria treat model wastewater containing soybean oil or diesel and display favorable fermentation ability. The capsules can effectively treat oil slicks with high concentration, and it is an economical way for processing oily wastewater. PRACTITIONER POINTS: A thermo-responsive calcium alginate capsule was prepared by microfluidic strategy. Pseudomonas aeruginosa is environmentally friendly in treating oil slicks. The capsules, immobilized bacteria, treat oil slicks effectively. This study provides an economical way for processing different oily water., (© 2024 Water Environment Federation.)

Objective: To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai. Methods: Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength. Results: A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR =1.41, 95% CI : 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR =1.67, 95% CI : 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR =1.30, 95% CI : 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR =1.57, 95% CI : 1.05-2.35; OR =2.40, 95% CI : 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P >0.05). Conclusions: This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

Objective: To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty. Methods: Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty. Results: A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR =0.743, 95% CI : 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR =0.509, 95% CI : 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions: Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

The narrative inquiry investigates the construction and evolution of a female Chinese language teacher's identity across her pre-service and in-service phases. Utilising data from interviews, class observation and written reflections, the research examines how internal and external aspects shape her identity development. It specifically explores the role of third positions, meta positions, and promoter positions drawing on the dialogical self theory. The findings reaffirm that a teacher's identity is fluid and influenced by personal and professional factors. Over time, however, strong teaching beliefs and a growth mindset emerge as pivotal drivers for sustained and positive teacher development. The paper concludes by offering implications for pre-service teacher education and female teachers' continuing professional development., 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 © 2024 Xing, Liu, Jiang and Hunt.)

A combination of accelerated population growth and severe droughts has created pressure on food security and driven the development of irrigation schemes across sub-Saharan Africa. Irrigation has been associated with increased malaria risk, but risk prediction remains difficult due to the heterogeneity of irrigation and the environment. While investigating transmission dynamics is helpful, malaria models cannot be applied directly in irrigated regions as they typically rely only on rainfall as a source of water to quantify larval habitats. By coupling a hydrologic model with an agent-based malaria model for a sugarcane plantation site in Arjo, Ethiopia, we demonstrated how incorporating hydrologic processes to estimate larval habitats can affect malaria transmission. Using the coupled model, we then examined the impact of an existing irrigation scheme on malaria transmission dynamics. The inclusion of hydrologic processes increased the variability of larval habitat area by around two-fold and resulted in reduction in malaria transmission by 60%. In addition, irrigation increased all habitat types in the dry season by up to 7.4 times. It converted temporary and semi-permanent habitats to permanent habitats during the rainy season, which grew by about 24%. Consequently, malaria transmission was sustained all-year round and intensified during the main transmission season, with the peak shifted forward by around 1 month. Lastly, we evaluated the spatiotemporal distribution of adult vectors under the effect of irrigation by resolving habitat heterogeneity. These findings could help larval source management by identifying transmission hotspots and prioritizing resources for malaria elimination planning., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2023 The Authors. GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

Immunogenicity is critical for biologics. However, reference biologics labeling documents do not necessarily mention immunogenicity impact, rendering the development of biosimilars more challenging. We aimed to investigate the comparative assessment of immunogenicity profiles between biosimilars and their respective reference biologics in the review reports of the biosimilar monoclonal antibody applications approved by the Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA) as of March 13, 2022, covering 22 applications approved between April 5, 2016, and December 17, 2021. The maximum differences in anti-drug antibody (ADA) and neutralizing antibody (NAb) incidences between biosimilars and reference products mostly fell within ± 15% (-13.6% to 12%) and ± 20% (-17.4% to 17.1%, except extreme values of -23.4% and 66.7%), respectively. In comparison with antineoplastic agents, more immunosuppressants had ADA-positive (11/11, 100.0% vs. 8/10, 80.0%)/NAb-positive (11/11, 100.0% vs. 3/10, 30.0%) subjects, and the distribution of the aforementioned incidence differences was wider. The investigated biosimilars with available data for analysis demonstrated a high degree of consistency with their reference products in terms of the impact on pharmacokinetic parameters. No increase in immunogenicity was found in available switching studies. Most (16/22, 72.7%) biosimilars were issued post-marketing requirements that were not directly related to immunogenicity concerns. The FDA considered the totality of evidence assessing clinical consequences of immunogenicity differences, if any. Additional information on titers and subgroup analysis may be warranted to elucidate the critical attributes of immunogenicity impact and to aid in forming cost-effective strategies for biosimilar development., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

A rapidly aging society and longer life expectancy are causing osteoporosis to become a global epidemic. Over the last five decades, a number of drugs aimed at reducing bone resorption or restoring bone mass have been developed, but their efficacy and safety are limited. Icaritin (ICT) is a natural compound extracted from anti-osteoporosis herb Epimedium spp. and has been shown to inhibit osteoclast differentiation. However, the molecular mechanism by which ICT weaken RANKL-induced osteoclast differentiation has not been completely investigated. Here, we evaluated the anti-osteoclastogenic effect of ICT in vitro and the potential drug candidate for treating osteoporosis in vivo . In vitro study, ICT was found to inhibit osteoclast formation and bone resorption function via downregulating transcription factors activated T cell cytoplasm 1 (NFATc1) and c-fos, which further downregulate osteoclastogenesis-specific gene. In addition, the enhanced mitochondrial mass and function required for osteoclast differentiation was mitigated by ICT. The histomorphological results from an in vivo study showed that ICT attenuated the bone loss associated with ovariectomy (OVX). Based on these results, we propose ICT as a promising new drug strategy for osteoporosis that inhibits osteoclast differentiation.

Land surface depressions play a central role in the transformation of rainfall to ponding, infiltration and runoff, yet digital elevation models (DEMs) used by spatially distributed hydrologic models that resolve land surface processes rarely capture land surface depressions at spatial scales relevant to this transformation. Methods to generate DEMs through processing of remote sensing data, such as optical and light detection and ranging (LiDAR) have favored surfaces without depressions to avoid adverse slopes that are problematic for many hydrologic routing methods. Here we present a new topographic conditioning workflow, Depression-Preserved DEM Processing (D2P) algorithm, which is designed to preserve physically meaningful surface depressions for depression-integrated and efficient hydrologic modeling. D2P includes several features: (1) an adaptive screening interval for delineation of depressions, (2) the ability to filter out anthropogenic land surface features (e.g., bridges), (3) the ability to blend river smoothing (e.g., a general downslope profile) and depression resolving functionality. From a case study in the Goodwin Creek Experimental Watershed, D2P successfully resolved 86% of the ponds at a DEM resolution of 10 m. Topographic conditioning was achieved with minimum impact as D2P reduced the number of modified cells from the original DEM by 51% compared to a conventional algorithm. Furthermore, hydrologic simulation using a D2P processed DEM resulted in a more robust characterization on surface water dynamics based on higher surface water storage as well as an attenuated and delayed peak streamflow., 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.

Purpose: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC., Materials and Methods: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62)., Results: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local., Conclusion: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.

Objective: To identify distinct frailty trajectories in a cohort of nationwide community adults aged 50 years and above, and explore the relationship between frailty trajectories and their socioeconomic characteristics and behavioral factors at baseline survey. Methods: Data were from the three waves of "Global Ageing and Adult Health Research" (SAGE) by World Health Organization in China. The frailty index is generated from 32 items. Group-based trajectory modeling using a censored normal model was conducted to identify the patterns in frailty progression over time. Multinomial logistic regression model was used to examine the effect of socioeconomic status and behavioral factors on the frailty trajectories. Results: A total of 4 303 adults aged 50 years and above with complete data from all three rounds of project were included in the final analysis. Three frailty trajectories were identified: low and stable trajectory (LT) (56.8%), moderately increased trajectory (MT) (34.4%) and highly increased trajectory (HT) (8.8%). The results of the multinomial logistic regression analysis showed that the HT group was more likely to be women ( OR =1.88, 95% CI :1.22-2.92) and rural residents ( OR =1.87, 95% CI :1.29-2.70) compared with the LT group. In terms of household wealth per capita, there was a clear gradient in OR s, the people with lower household wealth were more likely to be classified in the HT group. Conclusion: This study identified three patterns of progression of frailty trajectories in population aged 50 years and above in China and highlighted that interventions should target those vulnerable populations with rapid progression of frailty.

Food insecurity, recurrent famine, and poverty threaten the health of millions of African residents. Construction of dams and rural irrigation schemes is key to solving these problems. The sub-Saharan Africa International Center of Excellence for Malaria Research addresses major knowledge gaps and challenges in Plasmodium falciparum and Plasmodium vivax malaria control and elimination in malaria-endemic areas of Kenya and Ethiopia where major investments in water resource development are taking place. This article highlights progress of the International Center of Excellence for Malaria Research in malaria vector ecology and behavior, epidemiology, and pathogenesis since its inception in 2017. Studies conducted in four field sites in Kenya and Ethiopia show that dams and irrigation increased the abundance, stability, and productivity of larval habitats, resulting in increased malaria transmission and a greater disease burden. These field studies, together with hydrological and malaria transmission modeling, enhance the ability to predict the impact of water resource development projects on vector larval ecology and malaria risks, thereby facilitating the development of optimal water and environmental management practices in the context of malaria control efforts. Intersectoral collaborations and community engagement are crucial to develop and implement cost-effective malaria control strategies that meet food security needs while controlling malaria burden in local communities.

In this work, a 4'-(4-cynaophenyl)-4,2':6',4-terpyridine supported Cu I MOFs photocatalyst ( Cu I MOF ) was applied to the photocatalytic CO 2 reduction for the first time. The micro-structural and physicochemical properties of the Cu I MOF were systematically studied by the powder X-ray diffraction (PXRD), Single crystal X-ray diffraction (SCXRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), UV-Vis diffuse spectroscopy (UV-vis DRS), ns-level photoluminescence spectra (ns-level PL), Ultraviolet photoelectron spectroscopy (UPS), and N 2 adsorption-desorption test (BET-BJH). Moreover, the in situ diffuse reflectance infrared fourier transform spectroscopy ( in situ DRIFTS) was applied to investigate the adsorption and reaction intermediates of photocatalytic CO 2 reduction. As a result, Cu I MOF exhibited good performance and outstanding selectivity toward photocatalytic reduction of CO 2 to CO under full-spectrum and visible light illumination. Notably, 100% selective photocatalytic conversion of CO 2 to CO was achieved. Thus, the study presents the high selectivity and CO 2 reduction efficiency of Cu I MOF as a potential family of photocatalysts., 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 © 2022 Zhang, Wang, Liang, Jiang, Gong, Tian, Fu, Liao, Chen and Ma.)

A simple and versatile strategy for controlled production of monodisperse ethyl cellulose (EC) microcapsules by a single-stage emulsification method has been developed. Monodisperse oil-in-water emulsions, obtained by a microfluidic device, are used as templates for preparing EC microcapsules. Oil-soluble ethyl acetate (EA) is miscible with water, so the interfacial mass transfer between EA and water occurs sufficiently, which leads to water molecules pass through the phase interface and diffuse into emulsion interior. Water molecules aggregate at the interface, and some merge into a large water drop in the central position of the emulsion. After evaporation of EA solvent, monodisperse EC microcapsules create large numbers of pits on the surface with a hollow structure. Curcumin is used as a model drug and embedded in the hollow structure. EC microcapsules have good, sustained drug release efficacy in a simulated intestinal environment, and the release process of EC microcapsules containing 6.14% drug-loaded capacity is fully consistent with the vitro drug release model. Such simple techniques for making EC microcapsules may open a window to the controlled preparation of other multifunctional microcapsules. Besides, it offers theoretical guidance for the study of EC microcapsules as drug carriers and expanding clinical application of curcumin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Efforts to improve preservice teacher education have recently focused on developing teachers' adequate pedagogical knowledge (PK), content knowledge (CK), and pedagogical content knowledge (PCK), which are critical elements of teacher's professional knowledge, and important indicators of preparedness to teach. However, the development of the three knowledge domains of Chinese preservice English as a foreign language (EFL) teachers is surprisingly under-researched. To fill this gap, this study examined the development of the three knowledge domains of a group of Chinese preservice EFL teachers at different stages of a teacher education program. Specifically, it explored the relationship among the three knowledge domains, and the effects of learning opportunities on their development. Findings revealed that preservice EFL teachers at a later stage outperformed those at an earlier stage with regard to PK and PCK. Our findings also suggested that there were positive correlations among PK, CK, and PCK at different stages of the teacher education program. Furthermore, the findings showed that courses on CK, PK, and PCK, and teaching experience significantly influenced preservice EFL teachers' professional knowledge. However, the role of classroom observation was not significant. Implications for EFL teacher education and future research were also discussed., 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 © 2022 Liu, Jiang, Yang and Li.)

Purpose: Radiation therapy (RT) is essential to managing many pediatric malignancies but can provoke anxiety, fear, and discomfort for children owing to prolonged treatment time, extended course, and restrictive immobilization. Patients younger than 10 years frequently require daily general anesthesia (GA), which is resource intensive, expensive, potentially toxic, and anxiety and fear provoking. Audio-Visual Assisted Therapeutic Ambience in Radiation Therapy (AVATAR), a video streaming device, has been proposed as an alternative to anesthesia in patients aged 3 to 10 years. A pilot study evaluating the efficacy of this novel innovation is accruing, but patients younger than 3 years are ineligible., Methods and Materials: We simulated a 2-year-old with stage IV Wilms tumor for bilateral whole-lung and left-flank irradiation without GA. Using AVATAR, we attempted to deliver RT to this patient without sedation. Patient anxiety at the time of simulation and at the beginning, middle, and end of the treatment course was characterized using the validated Modified Yale Preoperative Anxiety Score (mYPAS) measurement tool., Results: Although the patient tolerated computed tomography simulation without GA or AVATAR use, his mYPAS of 14 out of 18 indicated significant anxiety. Using AVATAR, all treatments were delivered without GA; his mYPASs were 5 and 4 (the lowest possible) and 4 at the first, midcourse, and final treatments, indicating no significant anxiety and a decrease from the pre-AVATAR baseline. Without GA, the time to deliver RT decreased by 66% from 90 to 30 minutes., Conclusions: We describe an expanded, previously unreported indication for AVATAR by demonstrating the feasibility of this approach to reduce or omit anesthesia in appropriate younger patients currently excluded from ongoing trials. The financial and quality-of-life benefits (including decreased stress, anxiety, toxic effects, cost, and appointment time) of AVATAR use may be extendable to a younger patient population than previously thought. In older children, prospective validation is ongoing, but additional study in patients younger than 3 years is needed., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Curriculum reform urges teachers to constantly reflect on existing identities and develop probably whole new identities. Yet, in the wake of the poststructuralist view of identity as a complex matter of the social and the individual, of discourse and practice, and of agency and structure, teacher identity is a process of arguing for themselves and hence ethical and political in nature. Drawing on Foucault's notion of ethical self-formation and its adoption by Clarke (2009a) "Diagram for Doing Identity Work" in teacher education research, this 2-year-long case study explores how two Chinese English-as-foreign-language (EFL) teachers engaged in identity work in a changing curricular landscape. The analysis of narrative frames and semistructured interviews reveals the relations between the relative stable and the evolving elements of teachers' identity work, and the essential role of teachers' ethical agency based on reflective and critical responsiveness to the contextual reality and the dynamic power relations during the reform. The findings argue for the importance of nourishing teachers' reflective identity work and ethical agency during the turbulence of educational change., Competing Interests: The author declares 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 © 2022 Jiang.)

We evaluated the impact on survival of antithymocyte globulin conditioning (TLI-ATG) with radiation (RT) boost to high risk or residual disease before allogeneic hematopoietic cell transplant (allo-HCT) for adults with lymphoma (excluding mycosis fungoides and low-grade NHL other than SLL/CLL). Of 251 evaluable patients, 36 received an RT boost within 3 months of allo-HCT at our institution from 2001 to 2016. At the time of TLI-ATG, patients who received boost vs no boost had a lower rate of CR (11% vs 47%, p = 0.0003), higher rates of bulky disease (22% vs 4%, p < 0.0001), extranodal disease (39% vs 5%, p < 0.0001), and positive PET (75% vs 28%, p < 0.00001). In the boost group, the median (range) largest axial lesion diameter was 5.2 cm (1.8-22.3). Median follow-up was 50.2 months (range: 1-196). There was no significant difference in OS, time to recurrence, or time to graft failure with vs without boost. A trend toward higher percent donor CD3 + chimerism was seen with vs without boost (p = 0.0819). The worst boost-related toxicity was grade 2 dermatitis. RT boost may help successfully mitigate the risk of high risk or clinically evident residual disease in adults with lymphoma undergoing allo-HCT., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

BACKGROUND Moxibustion therapy has been found to ameliorate clinical symptoms of functional dyspepsia (FD). We aimed to examine the regulatory effect of moxibustion on the gastrointestinal (GI) motility in FD and explore the underlying mechanism based on the hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1). MATERIAL AND METHODS Moxibustion therapy was used in FD rats induced by using classic tail-pinch and irregular feeding. Weight gain and food intake were recorded weekly, followed by detecting gastric residual rate (GRR) and small intestine propulsion rate (IPR). Next, western blotting was performed to determine the expression levels of HCN1 in the gastric antrum. qRT-PCR was used to detect HCN1 in the small intestine and hypothalamic satiety center. Double immunolabeling was used for HCN1 and ICCs in gastric antrum and small intestine. RESULTS The obtained results suggested that moxibustion treatment could increase weight gain and food intake in FD rats. The GRR and IPR were compared among the groups, which showed that moxibustion treatment could decrease GRR and increase IPR. Moxibustion increased the expression of HCN1 in the gastric antrum, small intestine, and hypothalamic satiety center. Histologically, the co-expressions of HCN1 and ICCs tended to increase in gastric antrum and small intestine. Meanwhile, HCN channel inhibitor ZD7288 prevented the above-mentioned therapeutic effects of moxibustion. CONCLUSIONS The results of the present study suggest that moxibustion can effectively improve the GI motility of FD rats, which may be related to the upregulation of HCN1 expression in gastric antrum, small intestine, and satiety center.

Immunogenicity, the potential to elicit an antidrug immune response, is a critical concern in developing biological products, but its consequences are difficult to predict with animal studies. The aims of the present study are to investigate the evolution of immunogenicity information in labeling and to identify attributes associated with immunogenicity labeling updates. Biologics License Applications (BLAs) approved by the Center for Drug Evaluation and Research, US Food and Drug Administration between 2008 and 2017 were studied. A majority of BLAs described the incidence/prevalence of antidrug antibodies (ADAs) (94.9%) and neutralizing antibodies (NAbs) (68.4%) in their original labeling documents. However, less than one third of the BLAs mentioned the impact of ADAs/NAbs in the original (20.3%) and most recent (29.1%) labeling documents. BLAs with a priority review status (57.4% vs. 33.3%), orphan designation (61.5% vs. 34.2%), or a mention of ADA impact in the latest label (69.6% vs. 38.9%) had higher percentages of applications with postmarketing requirements (PMRs) directly related to immunogenicity concerns in comparison with applications without those characteristics. Among the BLAs with updated immunogenicity information, the mean time to the first update was 1,077 days, while that for BLAs with accelerated approval was shorter (709.1 ± 492.2 days vs. 1173.8 ± 661.8 days). The results suggest that there is a substantial amount of critical information lacking in the original labeling documents and an overdependence on PMRs for more evidence. Additional efforts should be made to investigate the impact of ADAs to provide timely information for improved patient care., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

As a relatively new dimension of student engagement, agentic engagement has received growing research interest in recent years, as it not only predicts academic achievement and other positive outcomes, but also benefits reciprocal teacher-student relations. In the educational context, teachers' teaching style exerts a crucial impact on students' engagement. However, research on how perceived teachers' teaching style influences students' agentic engagement is inconclusive. To address this lacuna, this study, taking an integrated perspective that draws on Self-determination Theory and Achievement Goal Theory, investigated the relationship of three types of teaching style (i.e., perceived autonomy support, social relatedness, and controlling) to university students' agentic engagement in EFL learning in China, especially through the mediation of mastery-approach goals and performance approach goals. Structural equation modeling showed that perceived autonomy support positively predicted agentic engagement through the mediation of mastery-approach goals, whereas perceived controlling negatively predicted agentic engagement through the mediation of performance-approach goals. Comparatively, the relationship of perceived social relatedness to agentic engagement was fully mediated by both mastery-approach and performance-approach goals. After discussing these results, practical implications as well as suggestions for future studies were given., 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 © 2021 Jiang and Zhang.)

Larval source management has gained renewed interest as a malaria control strategy in Africa but the widespread and transient nature of larval breeding sites poses a challenge to its implementation. To address this problem, we propose combining an integrated high resolution (50 m) distributed hydrological model and remotely sensed data to simulate potential malaria vector aquatic habitats. The novelty of our approach lies in its consideration of irrigation practices and its ability to resolve complex ponding processes that contribute to potential larval habitats. The simulation was performed for the year of 2018 using ParFlow-Common Land Model (CLM) in a sugarcane plantation in the Oromia region, Ethiopia to examine the effects of rainfall and irrigation. The model was calibrated using field observations of larval habitats to successfully predict ponding at all surveyed locations from the validation dataset. Results show that without irrigation, at least half of the area inside the farms had a 40% probability of potential larval habitat occurrence. With irrigation, the probability increased to 56%. Irrigation dampened the seasonality of the potential larval habitats such that the peak larval habitat occurrence window during the rainy season was extended into the dry season. Furthermore, the stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. Our study provides a hydrological perspective on the impact of environmental modification on malaria vector ecology, which can potentially inform malaria control strategies through better water management.

Efforts to improve student-teacher education have recently focused on developing adequate Pedagogical Content Knowledge (PCK) as a critical element for effective preparation. Despite many initiatives implemented in teacher education programs, however, their effectiveness in developing student-teachers' PCK and factors affecting the PCK development are under-researched and evidenced. Drawing upon theories about and research on PCK, this study examined whether a recently updated 2-year teacher education program could develop student-teachers' PCK effectively and explored what factors influencing the PCK development of student-teachers with different developmental trajectories. Forty English-as-foreign-language (EFL) student-teachers on the program were involved as participants. This study employed a longitudinal research design. Data were collected at four different stages along with the program through the content representation matrix, interviews with all the participants, and focus group interviews with four particularly sampled participants. Findings revealed that the current teacher education program successfully enhanced student-teachers' PCK and the factors influencing different PCK developmental trajectories were varied and personalized. Implications for teacher education are also discussed., 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 © 2021 Li, Liu and Jiang.)

Purpose: Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear., Methods: MHO was defined as participants with overweight and obesity (BMI ≥ 24.0 kg/m 2 , n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0 kg/m 2 , n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6 mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg during 5 years of follow-up., Results: Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005 mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status., Conclusions: MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults., Level of Evidence: III, cohort study.

This study aims to describe the clinical manifestations of diffuse pulmonary ossification, explore the diagnostic methods to reduce the misdiagnosis rate, and discuss its nursing treatment in the perioperative period. In The Fifth Central Hospital of Tianjin, one patient with diffuse pulmonary ossification, confirmed by surgical lung biopsy, was reported; and the clinical features and effective nursing methods are analysed. The patient was a 16-year teenager, who developed sudden convulsions without obvious cause with limited respiration. After the mental state was restored, the patient presented with chest tightness, shortness of breath, cough and expectoration. Hence, the subject was admitted in our hospital. Routine and imaging examinations failed to draw a definite diagnosis. Then, lung biopsy was performed, and a diagnosis of diffuse pulmonary ossification was made. Diffuse pulmonary ossification is very rare in clinical practice. The clinical manifestations are nonspecific, and imaging features are characterised by diffuse lung damages. Therefore, it is easily misdiagnosed as other interstitial lung diseases. Lung biopsy can be used to confirm this disease. Sequential acupoint stimulation by tapping the back can relieve cough and help patients recover quickly.

Ganoderma lucidum is widely recognized as a medicinal basidiomycete. It was previously reported that the plant hormone methyl jasmonate (MeJA) could induce the biosynthesis of ganoderic acids (GAs), which are the main active ingredients of G. lucidum . However, the regulatory mechanism is still unclear. In this study, integrated proteomics and metabolomics were employed on G. lucidum to globally identify differences in proteins and metabolites under MeJA treatment for 15 min (M15) and 24 h (M24). Our study successfully identified 209 differential abundance proteins (DAPs) in M15 and 202 DAPs in M24. We also identified 154 metabolites by GC-MS and 70 metabolites by LC-MS in M24 that are involved in several metabolic pathways. With an in-depth analysis, we found some DAPs and metabolites that are involved in the oxidoreduction process, secondary metabolism, energy metabolism, transcriptional and translational regulation, and protein synthesis. In particular, our results reveal that MeJA treatment leads to metabolic rearrangement that inhibited the normal glucose metabolism, energy supply, and protein synthesis of cells but promoted secondary metabolites, including GAs. In conclusion, our proteomics and metabolomics data further confirm the promoting effect of MeJA on the biosynthesis of GAs in G. lucidum and will provide a valuable resource for further investigation of the molecular mechanisms of MeJA signal response and GA biosynthesis in G. lucidum and other related species.

This study aims to explore the effect of sequential acupoint stimulation on the postoperative pulmonary function of patients with spontaneous pneumothorax who underwent video-assisted thoracoscopic surgery (VATS).Using a random number table, the patients were randomly divided into 2 groups: routine nursing group and sequential acupoint stimulation group. Patients in the routine nursing group received standard nursing care of thoracic surgery, while patients in the acupoint group received sequential acupoint stimulation on Shenshu (BL23), Gaohuang (BL43), Feishu (BL13), and Tiantu (CV22). Then, the maximal ventilatory volume (MVV), oxygen saturation (SpO2), postoperative drainage volume, postoperative drainage time, postoperative hospitalization days, and procalcitonin (PCT) were observed on the first, third, fifth and 30th day after VATS operation.On the fifth day after spontaneous pneumothorax was treated with VATS, MVV, and SpO2 of the sequential acupoint stimulation group were significantly higher than those of the routine nursing group (P < .05). On both the third day and fifth day after VATS, PCT of the sequential acupoint stimulation group was significantly lower than that of the routine nursing group (P < .01). Furthermore, the difference in postoperative drainage volume between the 2 groups was not statistically significant (P > .05), while chest tube drainage time (P < .01) and postoperative hospitalization days (P < .05) of the sequential acupoint stimulation group were significantly lower than those of the routine nursing group.In spontaneous pneumothorax patients who underwent VATS, sequential acupoint stimulation nursing was significantly more effective than routine postoperative nursing in promoting postoperative recovery of lung function, alleviating inflammatory response and shortening hospitalization days.

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.

Objective: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD)., Methods: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline. Coronary artery calcification (CAC) was assessed by electron beam or multi-slice computed tomography (EBCT/MSCT), abdominal aortic calcification (AAC) by lateral lumbar radiography, and cardiac valvular calcification (ValvC) by echocardiography. Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D and FGF-23 were evaluated. A logistic regression model was used to evaluate the association between risk factors and VC., Results: Of 1,497 patients, 1,493 (78.3% HD, 21.7% PD) had ≥1 baseline calcification image (final analysis cohort, FAC) and 1,423 (78.8% HD, 21.2% PD) had baseline calcification data complete (BCDC). Prevalence of VC was 77.4% in FAC (80.8% HD, 65.1% PD, p < .001) and 77.5% in BCDC (80.7% HD, 65.8% PD). The proportion of BCDC patients with single-site calcification were 20% for CAC, 4.3% for AAC, and 4.3% for cardiac valvular calcification (ValvC), respectively. Double site calcifications were 23.4% for CAC and AAC, 6.5% for CAC and ValvC, and 1.1% for AAC and ValvC, respectively. In total, 17.9% patients had calcification at all three sites., Conclusions: High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.

How cells drive the phospholipid signal response to heat stress (HS) to maintain cellular homeostasis is a fundamental issue in biology, but the regulatory mechanism of this fundamental process is unclear. Previous quantitative analyses of lipids showed that phosphatidylinositol (PI) accumulates after HS in Ganoderma lucidum, implying the inositol phospholipid signal may be associated with HS signal transduction. Here, we found that the PI-4-kinase and PI-4-phosphate-5-kinase activities are activated and that their lipid products PI-4-phosphate and PI-4,5-bisphosphate are increased under HS. Further experimental results showed that the cytosolic Ca 2+ ([Ca 2+ ] c ) and ganoderic acid (GA) contents induced by HS were decreased when cells were pretreated with Li + , an inhibitor of inositol monophosphatase, and this decrease could be rescued by PI and PI-4-phosphate. Furthermore, inhibition of PI-4-kinases resulted in a decrease in the Ca 2+ and GA contents under HS that could be rescued by PI-4-phosphate but not PI. However, the decrease in the Ca 2+ and GA contents by silencing of PI-4-phosphate-5-kinase could not be rescued by PI-4-phosphate. Taken together, our study reveals the essential role of the step converting PI to PI-4-phosphate and then to PI-4,5-bisphosphate in [Ca 2+ ] c signalling and GA biosynthesis under HS., (© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The aim of this study was to improve l-lactic acid production of Lactobacillus thermophilus SRZ50. For this purpose, high efficient heavy-ion mutagenesis technique was performed using SRZ50 as the original strain. To enhance the screening efficiency for high yield l-lactic acid producers, a scale-down from shake flask to microtiter plate was developed. The results showed that 24-well U-bottom MTPs could well alternate shake flasks for L. thermophilus cultivation as a scale-down tool due to its a very good comparability to the shake flasks. Based on this microtiter plate screening method, two high l-lactic acid productivity mutants, A59 and A69, were successfully screened out, which presented, respectively, 15.8 and 16.2% higher productivities than that of the original strain. Based on fed-batch fermentation, the A69 mutant can accumulate 114.2 g/L l-lactic acid at 96 h. Hence, the proposed traditional microbial breeding method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain lactic acid-overproducing strain., (© 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ganoderma lucidum has high commercial value because it produces many active compounds, such as ganoderic acids (GAs). Salicylic acid (SA) was previously reported to induce the biosynthesis of GA in G. lucidum. In this study, we found that SA induces GA biosynthesis by increasing ROS production, and further research found that NADPH oxidase-silenced strains exhibited a partial reduction in the response to SA, resulting in the induction of increased ROS production. Furthermore, the localization of ROS shows that mitochondria are sources of ROS production in response to SA treatment. An additional analysis focused on the relationship between SA-induced ROS production and mitochondrial functions, and the results showed that inhibitors of mitochondrial complexes I and II exert approximately 40-50% superimposed inhibitory effects on the respiration rate and H 2 O 2 content when co-administered with SA. However, no obvious superimposed inhibition effects were observed in the sample co-treated with mitochondrial complex III inhibitor and SA, implying that the inhibitor of mitochondrial complex III and SA might act on the same site in mitochondria. Additional experiments revealed that complex III activity was decreased 51%, 62% and 75% after treatment with 100, 200, and 400 µM SA, respectively. Our results highlight the finding that SA inhibits mitochondrial complex III activity to increase ROS generation. In addition, inhibition of mitochondrial complex III caused ROS accumulation, which plays an essential role in SA-mediated GA biosynthesis in G. lucidum. This conclusion was also demonstrated in complex III-silenced strains. To the best of our knowledge, this study provides the first demonstration that SA inhibits complex III activity to increase the ROS levels and thereby regulate secondary metabolite biosynthesis., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Tumor necrosis factor receptor-associated protein-1 (TRAP-1), a mitochondrial chaperone, contributes significantly to the progression of cancer. However, the understanding of its involvement in the clinicopathological characteristics and prognosis of colorectal cancer (CRC) remains limited. The aim of the present study was to assess the significance of TRAP-1 expression in CRC. The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry. The associations between TRAP-1 expression and the clinicopathological parameters and survival rates of patients was assessed. Out of 256 patients with CRC, TRAP-1 expression was detected in 203 (79.3%). TRAP-1 expression was significantly increased in cancerous tissue compared with that in corresponding paracancerous tissues (P<0.001). Overexpression of TRAP-1 was significantly associated with differentiation (P=0.011), depth of invasion (P=0.006), lymph node metastasis (P<0.001) and tumor-node-metastasis stage (P<0.001). In patients with high TRAP-1 expression, the 5-year overall survival (OS) rate was 38.0%, in contrast to 56.5% in patients with low TRAP-1 expression (P=0.003). Similarly, the 5-year progression-free survival (PFS) was 26.6% for patients with high TRAP-1 expression and 53.3% for patients with low TRAP-1 expression (P<0.001). Multivariate analyses indicated the TRAP-1 expression is an independent prognostic factor for poorer OS [P=0.015; hazard ratio (HR), 1.914] and PFS (P<0.001; HR, 2.534). Thus, TRAP-1 may serve as a potential biomarker for predicting the prognosis of patients with CRC. Specifically, overexpression of TRAP-1 may predict progression and poor survival in cases of CRC.

Aims: To explore the effects of a Traditional Chinese Medicine health educational intervention on the quality of life and self-care agency of elderly patients living with chronic cardiovascular disease., Background: Cardiovascular disease is a leading cause of morbidity and mortality worldwide. The secondary prevention and treatment for chronic cardiovascular disease emphasize the importance of lifestyle modification. However, behavior-changing is difficult and individual choices are influenced by broader environmental factors. The lifestyle intervention for the purpose of self-care enhancing should be considered the driving force from the cultural element., Methods: The study was conducted from April 2014 to October 2014. Ninety-eight community dwelling individuals with chronic cardiovascular disease were recruited from Shaoxing and randomized. 48 participants were in the intervention group with a 6-month Traditional Chinese Medicine health education and 50 participants were in the control group with routine care. The main measurements included health-related quality of life and self-care agency, which was assessed by the Short Form-36 Chinese version and the Exercise of Self-Care Agency Scale respectively, and were measured at the baseline and post intervention (6months after baseline)., Results: After 6months of intervention, the quality of life and self-care agency in the intervention group were significantly improved., Conclusions: The traditional Chinese medicine health education is an effective method for promoting quality of life and self-care agency in cardiovascular disease patients. It could be applied as adjunctive care for cardiovascular disease patients self-care supporting., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Phospholipid-mediated signal transduction plays a key role in responses to environmental changes, but little is known about the role of phospholipid signalling in microorganisms. Heat stress (HS) is one of the most important environmental factors. Our previous study found that HS could induce the biosynthesis of the secondary metabolites, ganoderic acids (GA). Here, we performed a comprehensive mass spectrometry-based analysis to investigate HS-induced lipid remodelling in Ganoderma lucidum. In particular, we observed a significant accumulation of phosphatidic acid (PA) on HS. Further genetic tests in which pld-silencing strains were constructed demonstrated that the accumulation of PA is dependent on HS-activated phospholipase D (PLD) hydrolysing phosphatidylethanolamine. Furthermore, we determined the role of PLD and PA in HS-induced secondary metabolism in G. lucidum. Exogenous 1-butanol, which decreased PLD-mediated formation of PA, reverses the increased GA biosynthesis that was elicited by HS. The pld-silenced strains partly blocked HS-induced GA biosynthesis, and this block can be reversed by adding PA. Taken together, our results suggest that PLD and PA are involved in the regulation of HS-induced secondary metabolism in G. lucidum. Our findings provide key insights into how microorganisms respond to heat stress and then consequently accumulate secondary metabolites by phospholipid remodelling., (© 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Aim: This study aimed to develop a prenatal nursing care catalogue of International Classification for Nursing Practice., Background: As a programme of the International Council of Nurses, International Classification for Nursing Practice aims to support standardized electronic nursing documentation and facilitate collection of comparable nursing data across settings. This initiative enables the study of relationships among nursing diagnoses, nursing interventions and nursing outcomes for best practice, healthcare management decisions, and policy development. The catalogues are usually focused on target populations. Pregnant women are the nursing population addressed in this project., Methods: According to the guidelines for catalogue development, three research steps have been adopted: (a) identifying relevant nursing diagnoses, interventions and outcomes; (b) developing a conceptual framework for the catalogue; (c) expert's validation., Results: This project established a prenatal nursing care catalogue with 228 terms in total, including 69 nursing diagnosis, 92 nursing interventions and 67 nursing outcomes, among them, 57 nursing terms were newly developed. All terms in the catalogue were organized by a framework with two main categories, i.e. Expected Changes of Pregnancy and Pregnancy at Risk. Each category had four domains, representing the physical, psychological, behavioral and environmental perspectives of nursing practice., Implications for Nursing Practice: This catalogue can ease the documentation workload among prenatal care nurses, and facilitate storage and retrieval of standardized data for many purposes, such as quality improvement, administration decision-support and researches. The documentations of prenatal care provided data that can be more fluently communicated, compared and evaluated across various healthcare providers and clinic settings., (© 2016 International Council of Nurses.)

Prognostic role of ankle-brachial index (ABI) in patients with chronic kidney disease (CKD) is controversial. We aimed to evaluate whether abnormal ABI was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by conducting a meta-analysis. We systematically searched Pubmed and Embase databases for prospective observational studies that investigated baseline abnormal ABI and subsequent cardiovascular or all-cause mortality risk in CKD patients with or without hemodialysis. An ABI value of 0.9 to 1.3 was defined as normal. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the abnormal vs. normal ABI category. Six studies enrolling 5820 patients were identified and analyzed. Overall, abnormal ABI was associated with an increased risk of all-cause mortality (HR 2.26; 95% CI 1.60-3.18) and cardiovascular mortality (HR 3.58; 95% CI 2.53-5.06). Subgroup analysis indicated that patients with abnormally low ABI increased by 2.45-fold all-cause mortality and 5.18-fold cardiovascular mortality. Similarly, an abnormally high ABI increased by 1.94-fold all-cause mortality and 4.04-fold cardiovascular mortality. In addition, the effect of abnormal ABI on all-cause mortality was more pronounced among hemodialysis patients (HR 3.06; 95% CI 2.30-4.07) but not in CKD patients (HR 1.42; 95% CI 0.98-2.05). Abnormally low and high ABI are independently associated with cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. This meta-analysis highlighted an U-shaped relationship between ABI and mortality risk in CKD patients undergoing hemodialysis. However, findings of this meta-analysis were undermined by the small number of included studies.

Vglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen. Mouse xenograft studies showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20 mg/kg/day) at day 21. Furthermore, the potential mechanisms involved in Vglycin-induced cell apoptosis were examined using cell cycle studies, ultrastructural examination, as well as apoptosis-associated pathway analysis. The results showed that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest. As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down-regulated in all three Vglycin-treated colon cancer cells, indicating that the CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in colon cancer cells was accompanied by alteration of the expression levels of the apoptosis-related proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3 activity. Together, our results suggest that Vglycin may be another plant-derived peptide that suppresses colon cancer, supporting the continued investigation of Vglycin as therapeutic agent for colon cancer. Impact statement The antidiabetic properties and the capability of inducing differentiation of human colon adenocarcinoma cells of Vglycin have been reported in our previous studies. However, the anticancer potential of Vglycin on colon cancer cells and its possible related mechanisms were still unknown. In this study, we found that Vglycin could reduce growth, viability, and colony formation or colony size of CT-26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1. The findings highlight the anticancer potential of Vglycin against colon cancer cells, and suggest Vglycin may be another colon cancer potential suppressive component of plant-derived peptides.

Ganoderma lucidum has become a potential model system for evaluating how environmental factors regulate the secondary metabolism of basidiomycetes. Heat stress (HS) is one of the most important environmental factors. It was previously reported that HS could induce the biosynthesis of ganoderic acids (GA). In this study, we found that HS increased GA biosynthesis and also significantly increased cell membrane fluidity. Furthermore, our results showed that addition of the membrane rigidifier dimethylsulfoxide (DMSO) could revert the increased GA biosynthesis elicited by HS. These results indicate that an increase in membrane fluidity is associated with HS-induced GA biosynthesis. Further evidence showed that the GA content was decreased in D9des-silenced strains and could be reverted to WT levels by addition of the membrane fluidizer benzyl alcohol (BA). In contrast, GA content was increased in D9des-overexpression strains and could be reverted to WT levels by the addition of DMSO. Furthermore, both membrane fluidity and GA biosynthesis induced by HS could be reverted by DMSO in WT and D9des-silenced strains. To the best of our knowledge, this is the first report demonstrating that membrane fluidity is involved in the regulation of heat stress induced secondary metabolism in filamentous fungi., (© 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Ganoderma lucidum is one of the most important medicinal fungi, but the lack of basic study on the fungus has hindered the further development of its value. To investigate the roles of the redox system in G. lucidum, acetic acid (HAc) was applied as a reactive oxygen species (ROS) stress inducer, and hydrogen-rich water (HRW) was used to relieve the ROS stress in this study. Our results demonstrate that the treatment of 5% HRW significantly decreased the ROS content, maintained biomass and polar growth morphology of mycelium, and decreased secondary metabolism under HAc-induced oxidative stress. Furthermore, the roles of HRW were largely dependent on restoring the glutathione system under HAc stress in G. lucidum. To provide further evidence, we used two glutathione peroxidase (GPX)-defective strains, the gpxi strain, the mercaptosuccinic acid (MS, a GPX inhibitor)-treated wide-type (WT) strain, and gpx overexpression strains for further research. The results show that HRW was unable to relieve the HAc-induced ROS overproduction, decreased biomass, mycelium morphology change and increased secondary metabolism biosynthesis in the absence of GPX function. The gpx overexpression strains exhibited resistance to HAc-induced oxidative stress. Thus, we propose that HRW regulates morphology, growth and secondary metabolism via glutathione peroxidase under HAc stress in the fungus G. lucidum. Furthermore, our research also provides a method to study the ROS system in other fungi., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

We demonstrate herein that salicylic acid (SA) can enhance ganoderic acid (GA) accumulation in the lingzhi or reishi medicinal mushroom Ganoderma lucidum. Following treatment with different concentrations of SA, the GA content was increased 22.72% to 43.04% compared with the control group. When the fungi were treated with 200 μmol/L SA at different times, the GA content was improved 10.21% to 35.24% compared with the control group. By choosing the optimum point based on response surface methodology, the GA content could be increased up to 229.03 μg/100 mg, which was improved 66.38% compared with the control group. When the fungi were treated with 200 μmol/L SA, the transcription levels of key genes in the GA biosynthesis pathway-squalene (SQ) synthase (sqs), lanosterol (Lano; osc), and hydroxy-3-methylglutaryl-coenzyme A reductase (hmgr)-were improved 119.6-, 3.2-, and 4.2-fold, respectively. In addition, following treatment with 100 μmol/L SA, the levels of Lano and SQ, which are intermediate metabolites of GA biosynthesis, were increased 2.8- and 1.4-fold, respectively. These results indicate that SA can regulate the expression of genes related to GA biosynthesis and increases the metabolic levels of Lano and SQ, thereby resulting in the accumulation of GA.

Ganoderma lucidum has been considered an emerging model species for studying how environmental factors regulate the growth, development, and secondary metabolism of Basidiomycetes. Heat stress, which is one of the most important environmental abiotic stresses, seriously affects the growth, development, and yield of microorganisms. Understanding the response to heat stress has gradually become a hotspot in microorganism research. But suitable reference genes for expression analysis under heat stress have not been reported in G. lucidum. In this study, we systematically identified 11 candidate reference genes that were measured using reverse transcriptase quantitative polymerase chain reaction, and the gene expression stability was analyzed under heat stress conditions using geNorm and NormFinder. The results show that 5 reference genes-CYP and TIF, followed by UCE2, ACTIN, and UBQ1-are the most stable genes under our experimental conditions. Moreover, the relative expression levels of 3 heat stress response genes (hsp17.4, hsp70, and hsp90) were analyzed under heat stress conditions with different normalization strategies. The results show that use of a gene with unstable expression (SAND) as the reference gene leads to biased data and misinterpretations of the target gene expression level under heat stress.