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Historic districts are integral components of urban space, possessing diverse ecosystems that can offer various cultural services to the public. Urbanization and tourism development have led to the degradation of the ecological landscapes within historic districts, impacting sustainable development. Incorporating Cultural Ecosystem Services (CES) into the environmental research of historic districts can meet people's spiritual needs, enhance intangible benefits for humanity, and promote the conservation of the ecological environment within historic districts. Therefore, this study conducted perceptual quantification research on CES in four typical historic districts in Fuzhou City, crawling the online comment data through Python, mined its potential themes using Biterm Topic Model (BTM), and extracted and categorized the indicators of CES of historic districts by combining with expert consultation; meanwhile, the satisfaction of CES of historic districts is further explored with the help of two methods, namely, sentiment analysis and Importance-Performance analysis (IPA), and summarized the public perception of CES of historic districts. The results of the study show that: (1) the dimensions of public perception of CES in urban historic districts include Cultural Heritage, Leisure Tourism, Aesthetic Enjoyment, Spiritual Fulfillment, Inspiration, and Science Education six indicators, of which Leisure Tourism is most easily perceived by the public, but its satisfaction is not high; (2) the public's perception of positive emotions towards the CES of historic districts in Fuzhou is greater than negative emotions, with positive emotions accounting for 80.61%; (3) the public's overall satisfaction with the CES of Fuzhou's historic districts is high, and according to the final analysis results of the IPA, the four historic districts of Fuzhou are respectively proposed to improve the opinions. Based on big data, this study explores the public perception characteristics of CES in Fuzhou historic districts to promote its sustainable development and improve public well-being, which is of great significance to protecting the ecological environment of historic districts and improving the quality of cultural services., (© 2024. The Author(s).)

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities., (© 2023. The Author(s).)

China's internal migrants suffer from marginalised housing conditions, poor neighbourhood environments and residential segregation, which may have significant implications on health and well-being. Echoing recent calls for interdisciplinary research on migrant health and well-being, this study examines the associations and mechanisms of the impact of the residential environment on the health and well-being of Chinese migrants. We found that most of the relevant studies supported the "healthy migration effect", but the phenomenon was only applicable to migrants' self-reported physical health rather than mental health. The subjective well-being of migrants is lower than that of urban migrants. There is a debate between the effectiveness of residential environmental improvements and the ineffectiveness of residential environmental improvements in terms of the impact of the neighbourhood environment on migrants' health and well-being. Housing conditions and the neighbourhood's physical and social environment can enhance migrants' health and well-being by strengthening place attachment and social cohesion, building localised social capital and gaining neighbourhood social support. Residential segregation on the neighbourhood scale affects the health outcomes of migrant populations through the mechanism of relative deprivation. Our studies build a vivid and comprehensive picture of research to understand migration, urban life and health and well-being.

As humans spend more time indoors, ensuring acceptable indoor air quality (IAQ) through ubiquitous sensing systems has become a necessity. Although extensive studies have been conducted on the IAQ sensing systems, a holistic review of the performance and deployment of Ubiquitous IAQ Sensing (UIAQS) systems with associated requirements in IAQ sensing standards is still lacking. In this study, we first reviewed IAQ pollutants and other IAQ-related factors and the associated requirements in the prominent IAQ sensing standards. We found that while non-pollutant factors are influential on occupants' perception of IAQ and their satisfaction, they do not have evaluation metrics in the IAQ standards. Then, we systematically reviewed field studies on UIAQS technologies in the literature. Specific classes of information were recorded and analyzed further. We found that the majority of the UIAQS systems did not meet the requirements of the prominent IAQ sensing standards and identified four primary research gaps. We concluded that a new holistic and personalized approach that incorporates UIAQS measurements and subjective feedback is needed. This study provides valuable insights for researchers and policymakers to better improve UIAQS technologies by developing personalized IAQ sensors and sensing standards.

SignificanceOur work focuses on the critical longstanding question of the nontranscriptional role of p53 in tumor suppression. We demonstrate here that poly(ADP-ribose) polymerase (PARP)-dependent modification of p53 enables rapid recruitment of p53 to damage sites, where it in turn directs early repair pathway selection. Specifically, p53-mediated recruitment of 53BP1 at early time points promotes nonhomologous end joining over the more error-prone microhomology end-joining. Similarly, p53 directs nucleotide excision repair by mediating DDB1 recruitment. This property of p53 also correlates with tumor suppression in vivo. Our study provides mechanistic insight into how certain transcriptionally deficient p53 mutants may retain tumor-suppressive functions through regulating the DNA damage response.

Background: Many conservation management interventions have been set up to bring win-win outcomes for both biodiversity conservation and the well-being of the local communities. Nevertheless, the implementation process of marine protected areas (MPAs) can generate unexpected outcomes and fail to reach its objectives in addressing communities' challenges. Therefore, it is crucial to have a better understanding of how MPAs influence the socioeconomic aspects of the coastal communities. This paper describes the protocol to conduct a systematic review which aims to explore and review the evidence that reflects the outcomes of marine site protection on poverty reduction in terms of economic and material living standards among the coastal communities in Southeast Asia. The review question is "What are the outcomes of marine site protection implementation on poverty in terms of material and economic living standards of coastal communities in Southeast Asia?"., Methods: The systematic review uses rigorous search strategies and selection methods based on pre-defined eligibility criteria to identify and examine published journal articles and grey literature that are available on the review topic. Relevant studies and grey literature will be extracted from a recent systematic map of the evidence documenting the effect of marine or coastal nature conservation or natural resource management activities on human well-being in Southeast Asia. We will search online databases including Web of Science Core Collection, Ovid Medline ® , Environmental Complete, Scopus, as well as Google Scholar and sources of grey literature for any additional literature available since the evidence map was created. For this review, the populations of interest are from coastal communities in the Southeast Asia region. Comparators to marine site protection will be no intervention and/or pre-MPA implementation. The economic and material living standards, which are the poverty domains, will be evaluated as outcomes. Once we have identified relevant literature, we will perform a critical appraisal, data extraction, and synthesis appropriate to the type of literature found, to investigate the effect of marine site protection on poverty reduction., (© 2022. The Author(s).)

Protected areas in Malaysia have always been managed using top-down approach that often exclude the local communities, who are the main users of ecosystem services, from the planning and management. However, a newly established multiple-use marine park in Malaysia, Tun Mustapha Park (TMP), aims for inclusivity in managing the park. This research explores different participatory approaches (i.e. participatory mapping and Photovoice) to understand the ecosystem services and the dynamics surrounding the services in TMP. Community-based organisations and a mariculture farm in TMP were invited to participate in this work. The participants mapped the ecosystem services and provided in-depth qualitative data that supported the maps, besides highlighting ecological, sociocultural and economic issues surrounding the ecosystem services. Furthermore, the participants provided suggestions and recommendations that carry political effects. Therefore, the participatory approaches employed here had provided rich visual and spatial data to enhance the ecosystem-based management of TMP besides empowering the participants to voice out for their communities. The results generated from this work were also further utilised to fill in the gaps of knowledge in a separate ecosystem service assessment matrix. However, the output from participatory approaches should not be considered as the ultimate outcome but rather as supplement to the planning and management of TMP due to potential human errors and biases. Although the participatory approaches came with limitations and challenges that may have affected the findings here, these nonetheless had provided support to the capability of local communities to provide information crucial for management of protected areas as well as room for improvement for further work., Competing Interests: The authors declare that they do not have competing financial interests or personal relationships that could influence the work reported here.

The COVID-19 pandemic has caused (and continues to cause) severe disruption in global and local economies and has forced countries, societies, and individuals to adapt quickly to the unprecedented and unpredictable situations. Despite the obvious negative consequences of the pandemic, many have called for efforts to identify transformative opportunities for sustainable development throughout this disorderly time. In the present paper, we explore such potential opportunities in the context of an interdisciplinary, international research project, which is focusing on sustainable marine management in biosphere reserves and marine parks in Southeast Asia. During a virtual workshop conducted as part of the GCRF (Government's Global Challenges Research Fund) Blue Communities Project, future scenarios were developed depicting the potential effects of the COVID-19 pandemic on five case study sites. All of these sites are in areas of internationally recognized outstanding ecological value (Taka Bonerate Kepulauan-Selayar Biosphere Reserve, Indonesia; Tun Mustapha Park, Sabah, Malaysia; Palawan Biosphere Reserve, Philippines; North Devon Biosphere Reserve, United Kingdom; Cu Lao Cham-Hoi An Biosphere Reserve, Vietnam). At the macro-level, economies, governance structures, and societal norms are undergoing big changes. At the micro-level, the livelihoods, lifestyles, and backyards of local residents have to adapt. Collaboratively, we explored how COVID-19 posed challenges in our five case study sites, but we also focused on the potential COVID-19-related windows of opportunity for future sustainable development. Opportunities could be identified in all three pillars of sustainable development: the environment, the society, and the economy. Although remarkable similarities can be found across all five sites, we conclude that there cannot be a "one-size-fits-all" solution to turn the tide toward achieving sustainable development. Just as before the pandemic, sustainable development starts with engaging with and understanding local environments, challenges, and situations; building on local knowledge; and developing tailor-made solutions for the communities in situ ., 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 Richter, Avillanosa, Cheung, Goh, Johari, Kay, Maharja, Nguyễn, Pahl, Sugardjito, Sumeldan, van Nguyen, Vu, Wan Mohamad Ariffin and Austen.)

Transport planning and public health have been intertwined historically. The health impact of public transport services, such as social exclusion, is a widely discussed research topic. Social exclusion is a paramount concern for older adults' health in the wake of emerging global challenges. However, there remains a significant research gap on how psychosocial barriers faced by older adults in using public transport services influence the social exclusion behavior. The present research provides empirical evidence and shows the impact of certain psychosocial barriers of public transportation on older adults' social exclusion. A total of 243 Pakistani older adults (aged 60-89 years old) voluntarily participated in this cross-sectional study. The participants provided self-reports on their psychosocial barriers (including perceived norms, attitude, personal ability, habits, neighborhood social constraints, and intention) and the corresponding social exclusion. Partial Least Square Structural Equation Modeling (PLS-SEM) was utilized for the data analysis. The structural path model supported the significant associations between psychosocial barriers and social exclusion. Except for perceived descriptive norms, all other psychosocial barriers predicted older adults' social exclusion. The research portrays the significance of the psychosocial factors to examine social exclusion and offers practical implications for urban and transport planners. The concerned policymakers can use the research findings to develop age-sensitive, socially sustainable, and healthy cities.

Introduction: Coastal areas in Malaysia can have important impacts on the livelihoods and health of local communities. Efforts by Malaysian government to develop and improve the landscape and ecosystem have been planned; however, the progress has been relatively slow because some of the coastal areas are remote and relatively inaccessible. Thus, these coastal communities face various challenges in health, healthcare and quality of life. This paper presents a study protocol to examine the health status, healthcare utilisation, and quality of life among the coastal communities. In addition, the relationship between the community and their coastal environment is examined., Methodology and Analysis: The population of interest is the coastal communities residing within the Tun Mustapha Park in Sabah, Malaysia. The data collection is planned for a duration of 6 months and the findings are expected by December 2020. A random cluster sampling will be conducted at three districts of Sabah. This study will collect 600 adult respondents (300 households are estimated to be collected) at age of 18 and above. The project is a cross sectional study via face-to-face interview with administered questionnaires, anthropometrics measurements and observation of the living condition performed by trained interviewers.

A new cyclic decapeptide, trikoramide A ( 1 ), has been isolated from samples of the marine cyanobacterium Symploca hydnoides , collected from Bintan Island, Indonesia. Trikoramide A ( 1 ) is a C-prenylated cyclotryptophan-containing cyanobactin. Its planar structure was deduced by 1D and 2D NMR spectroscopy as well as HR-MS/MS data. In addition, its absolute configuration was determined by Marfey's method and 2D NOESY NMR spectroscopic analysis. Compound 1 possessed cytotoxicity against the MOLT-4 and AML2 cancer cell lines with IC 50 values of 4.8 and 8.2 μM, respectively.

We report the draft genome sequence of a marine bacterium, Bacillus sp. strain 007/AIA-02/001, isolated from the marine sponge Coelocarteria singaporensis , obtained from water off the coast of Singapore. The analysis of the bacterial genome using the bioinformatics tool antiSMASH 4.0.2 showed the presence of a number of unique natural product biosynthetic pathways., (Copyright © 2019 Ong et al.)

With 70% of the Earth's surface covered in water, the marine ecosystem offers immense opportunities for drug discovery and development. Due to the decreasing rate of novel natural product discovery from terrestrial sources in recent years, many researchers are beginning to look seaward for breakthroughs in new therapeutic agents. As part of an ongoing marine drug discovery programme in Singapore, an integrated approach of combining metabolomic and genomic techniques were initiated for uncovering novel anti-quorum sensing molecules from bacteria associated with subtidal samples collected in the Singapore Strait. Based on the culture-dependent method, a total of 102 marine bacteria strains were isolated and the identities of selected strains were established based on their 16S rRNA gene sequences. About 5% of the marine bacterial organic extracts showed quorum sensing inhibitory (QSI) activity in a dose-dependent manner based on the Pseudomonas aeruginosa QS reporter system. In addition, the extracts were subjected to mass spectrometry-based molecular networking and the genome of selected strains were analysed for known as well as new biosynthetic gene clusters. This study revealed that using integrated techniques, coupled with biological assays, can provide an effective and rapid prioritization of marine bacterial strains for downstream large-scale culturing for the purpose of isolation and structural elucidation of novel bioactive compounds.

Benderamide A ( 1 ), a ( S) -2,2-dimethyl-3-hydroxy-7-octynoic acid ( S -Dhoya)-containing cyclic depsipeptide that belongs to the kulolide superfamily, was isolated from a Singapore collection of cf. Lyngbya sp. marine cyanobacterium using a bioassay-guided approach. While the planar structure of 1 was elucidated using a combination of 1D and 2D NMR experiments and MS analysis, the absolute configuration was subsequently achieved using the results obtained from Marfey's analysis, comparative analysis of nuclear overhauser effect spectroscopy (NOESY) with the known compound 3 , and one dimensional-nuclear overhauser effect (1D-NOE). Although 1 did not display antiproliferative activity against MCF7 breast cancer cells, the presence of an Ala instead of Gly suggests a possible mechanistic pathway to explain the consequential decrease in cytotoxicity compared to the closely related 2 . In addition, results obtained from an LC⁻MS/MS-based molecular networking algorithm revealed two other closely related compounds encouraging further identification and isolation from the same marine cyanobacterium extract.

Heat shock response (HSR), in terms of transcription regulation of two heat shock proteins genes hsp70 and hsp90), was analysed in a widespread tropical copepod Pseudodiaptomus annandalei. The mRNA transcripts of both genes were quantified after copepods at a salinity of 20 underwent an acclimation process involving an initial acclimation temperature of 29 °C, followed by gradual thermal ramping to the target exposure temperature range of 24-36 °C. The respective cellular HSR and organismal metabolism, measured by respiratory activity at exposure temperatures, were compared. The fold change in mRNA expression for both hsp70 and hsp90 (8-9 fold) peaks at 32 °C, which is very close to 32.4 °C, the upper thermal optimum for respiration in the species. Unexpectedly, the modelled HSR curves peak at only 3 °C (hsp90) and 3.5 °C (hsp70) above the mean water temperature (29.32 °C) of the copepod in the field. We propose that copepods in tropical waters adopt a preparative HSR strategy, early at the upper limit of its thermal optimum, due to the narrow thermal range of its habitat thus precluding substantial energy demand at higher temperatures. However, the model suggests that the species could survive to at least 36 °C with short acclimation time. Nevertheless, the significant overlap between its thermal range of hsp synthesis and the narrow temperature range of its habitat also suggests that any unprecedented rise in sea temperature would have a detrimental effect on the species., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chemotoxicity due to unwanted p53 activation in the bone marrow remains an unmet clinical challenge. Doxorubicin, a first-line chemotherapy drug, often causes myelosuppression in patients, thus limiting its effectiveness. In this study, we discovered that C646, a reversible p300 inhibitor, downregulates p53 transcription and selectively protects noncancerous cells from p53-dependent apoptosis. C646 treatment blocked acetylation of specific lysine residues that regulate p53 activity. Exploitation of differential p53 genetic backgrounds between human hematopoietic and colorectal cancer cells improved the therapeutic index of doxorubicin with C646 cotreatment. C646 administration in mice afflicted with p53-mutant tumors protected them from doxorubicin-induced neutropenia and anemia while retaining antitumor efficacy. We deduce that temporary and reversible inhibition of p53 acetylation in cancer subjects, especially those with p53-mutant tumors, may protect them from severe chemotoxicity while allowing treatment regimens to effectively proceed. Cancer Res; 77(16); 4342-54. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Protein purification typically involves expressing a recombinant gene comprising a target protein fused to a suitable affinity tag. After purification, it is often desirable to remove the affinity tag to prevent interference with downstream functions of the target protein. This is mainly accomplished by placing a protease site between the tag and the target protein. Typically, a small oligopeptide 'stub' C-terminal to the cleavage site remains attached to the target protein due to the requirements of sequence-specific proteases. Furthermore, steric hindrance can also limit protease efficiency. Here, we show that respectively fusing the interacting ePDZ-b/ARVCF protein-peptide pair to the target protein and a protease enables efficient processing of a minimised sequence comprising only residues N-terminal to the cleavage site. Interaction of the protein-peptide pair enforces proximity of the protease and its minimised cleavage sequence, enhancing both catalysis of a sub-optimal site and overcoming steric hindrance. This facilitates the high yield purification of fully native target proteins without recourse to specialised purification columns., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Peptide motifs are crucial mediators of protein-protein interactions as well as sites of specific protease activity. The detection and characterization of these events is therefore indispensable for a detailed understanding of cellular regulation. Here, we present versatile and modular sensors that allow the user to detect protease activity and protein-peptide interactions, as well as to screen for inhibitors using chromogenic, fluorescent, or luminescent output.

Purpose: Retinitis pigmentosa (RP) is a blinding disease caused by the degeneration of photoreceptors. To further understand the process of degeneration in RP, the authors have traced activation patterns associated with rod and cone photoreceptor degeneration in a mouse model of RP METHODS: The authors used a double-mutant mouse, Rd-FTL, which contains a natural mutation, rd1, affecting the rod photoreceptors and an axon-targeted beta-galactosidase reporter system, which is under the regulation of the promoter of the c-fos gene. These mice allowed the authors to trace degeneration-related activity that corresponded to rod and cone death., Results: The authors traced cell death-associated activation in both rods and cones, allowing them to accurately determine the time course of cone degeneration in these mice. In the analysis of downstream activation patterns in the inner retina, they found that amacrine and ganglion cells maintain their photopic light-related activation until at least the initiation of cone degeneration. These cell populations then show increased activity during the peak time of cone cell degeneration. The authors also examined light-regulated functional activation of a subclass of amacrine cells, the dopaminergic amacrine cells. These cells showed light-induced functional activation after rod photoreceptor death and until the period of cone photoreceptor death, suggesting that they can be regulated by cone photoreceptors alone., Conclusions: These findings have helped to accurately trace the periods of photoreceptor degeneration in this model of RP and show that correct light-regulated inner retinal activation is maintained until the time of cone degeneration.