Exogenous Pressures Research Articles

TMET-24. MULTI-OMIC CHARACTERIZATION OF THE TEMPORAL METABOLIC ADAPTATIONS UNDERPINNING THERAPY RESISTANCE AND TUMOR RECURRENCE IN GLIOBLASTOMA

Abstract Therapy resistance and tumor recurrence are barriers to achieving long-term survival in cancer patients, particularly evident in glioblastoma (GBM), known for its dismal 5-year survival rate below 10%. Despite aggressive treatment regimens, including maximal resection, alkylating chemotherapy, and radiation, the majority of GBM patients experience relapse within 7-9 months post-initial intervention. Recurrent GBM poses surgical challenges and resists subsequent treatments, leading to an almost universally fatal outcome and an average survival of 12-18 months. Metabolic networks can serve as ancient stress-protection mechanisms that operate independently of genomic changes, offering an initial line of defense against exogenous pressures. Although the role of metabolism in cancer has gained prominence, our understanding of the metabolic adaptations following chemoradiotherapy and their contributions to therapy resistance and tumor recurrence in highly aggressive GBM tumors remains incomplete. We postulate that metabolic adaptations play a pivotal role in facilitating therapy resistance and GBM recurrence. Exploring the metabolic dependencies of these persistent cells may unveil vulnerabilities for therapeutic exploitation to counteract chemoradiotherapy resistance. We established clinically relevant patient-derived in vitro and in vivo models mirroring the standard GBM treatment protocol. Using state-of-the-art single-cell and bulk multi-omics technologies, we profiled the temporal transcriptomic and metabolomic adaptations from therapy-naïve primary GBM to chemoradiotherapy-resistant recurrent tumors. Our findings revealed unique metabolic transitions that occurred during chemoradiotherapy treatment in GBM cells that were conserved in vitro and in vivo across ten genetically diverse GBM patients. In a pre-clinical animal trial, a novel metabolism-targeting combinatorial treatment regimen prevented the emergence of recurrent tumors and significantly prolonged survival compared to chemoradiotherapy alone. Altogether, our results uncover distinct metabolic adaptations mediating therapy resistance and tumor recurrence in GBM. These findings emphasize the need to consider metabolic flexibility and dependencies for effective therapeutic strategies, offering potential avenues to overcome chemoresistance in recurrent GBM tumors.

Porcine blast injury model achieves prolonged elevation of intra-compartmental pressures without exogenous pressure manipulation

BackgroundMost existing animal models of acute compartment syndrome (ACS) rely on exogenous manipulation of intra-compartmental pressures to model ACS. The purpose of the current study was to evaluate the endogenous effect of a blast injury on porcine lower leg intra-compartmental pressures (ICP).MethodsThe hindlimb of juvenile Landrace pigs was fractured at the diaphyseal tibia and subjected to blasts of compressed air to mimic a blast injury. Injured and control legs underwent pre-operative continuous ICP monitoring. At 4.5 h post injury, the fracture was stabilized followed by closure of the anterior compartment fascia (continued compartment pressure model, CCPM) or four compartment fasciotomy. Pressure measurements were made after operative fixation. Select pigs in CCPM were harvested between 48 and 72 h post-injury to evaluate the duration of ICP elevation.ResultsPost-injury, the model created significantly elevated ICP compared to control limbs (54.5 ± 18.2 vs. 18.2 ± 4.9 mmHg; p < 0.001). Operative fixation and anterior compartment fascial closure further increased the ICP (Mean: 87.4 ± 42.5 mmHg) relative to the pre-operative state (p = 0.037). Fasciotomy returned baseline compartment pressures (Mean: 13.7 ± 10.2 mmHg) which were equivalent to control limbs (p = 0.117). Pressure measurements at the time of delayed harvest (48–72 h) demonstrated that elevated ICP persisted following injury (69.7 ± 55.12 mmHg).ConclusionThe current study demonstrates that a pilot porcine blast model elevates ICP comparable to existing animal models of compartment syndrome without exogenous ICP manipulation. ICP remained elevated at 48–72 h in the absence of fasciotomy.

Uncivilian Power Germany: Why States Violate their Foreign Policy Master Roles

ABSTRACT This paper explores the reasons why states occasionally do not adhere to the behavioural expectations as prescribed by their foreign policy master roles. To that end, it proposes four potential drivers for such ‘role violations’, namely: exogenous pressure, political survival, lack of issue salience and ensuing bureaucratic decision-making, and unclear role demands in ambiguous decision contexts. Empirically, the paper examines the plausibility of those drivers for the case of Germany’s abstention in the United Nations Security Council vote on resolution 1973 on Libya. It suggests that in that particular case considerations of political survival made civilian power Germany act out of character.

Between political legitimacy and strategic competitiveness: Overseas corporate social responsibility patterns of Chinese international contractors

This article examines the overseas corporate social responsibility (CSR) patterns of Chinese international contractors (CICs). Adopting an institutional and political economy approach, a unique dataset is constructed with country-specific contents drawn from CSR-related reports and website information of 50 top CICs. This dataset provides a foundation for systematic content analysis of CICs’ overseas CSR practices, revealing that both political legitimacy-seeking and strategic competitiveness-seeking motivations drive CICs’ CSR activities abroad, characterized by the prioritization of customer and community engagement. The findings highlight the coexistence of the exogenous pressures for the national image-building purpose and the endogenous awareness of CSR strategic importance for corporate internationalization. The hybridization of political and economic rationales is presented as the defining feature of CICs’ current overseas CSR patterns, with the balance between them being determined by stakeholder type and internal business needs influenced by corporate internationalization experience.

Academic integrity and the use of ChatGPT by EFL pre-service teachers

Academic integrity has been at the centre of the discussion of the adoption of Chat GPT by academics in their research. This study explored how academic integrity mitigates the desire to use ChatGPT in academic tasks by EFL Pre-service teachers, in consideration of the time factor, perceived peer influence, academic self-effectiveness, and self-esteem. The study utilized web-based questionnaires to elicit data from 300 EFL Pre-service teachers across educational fields drawn from different schools across the world. Analysis was conducted using relevant statistical measures to test the projected four hypotheses. The findings provide evidence in support of Hypothesis 1, with a statistically significant path coefficient (β) of 0.442, a t-value of 3.728, and a p-value of 0.000. The hypothesis acceptance implies that when academic integrity improves, the impact of the time-saving aspect of the use of ChatGPT Across educational fields study decreases. This suggests that EFL Pre-service teachers who have a firm dedication to academic honesty are less influenced by the tempting appeal of ChatGPT’s time-saving features, highlighting the ethical factors that influence their decision-making. The data also provide support for Hypothesis 2, indicating a substantial inverse relationship with a path coefficient (β) of 0.369, a t-value of 5.629, and a p-value of 0.001. These findings indicate that stronger adherence to academic integrity is linked to a diminished effect of colleagues on the choice to use ChatGPT in Academic tasks. The results suggest that a firm dedication to academic honesty serves as a protective barrier against exogenous pressures or influences from colleagues when it comes to embracing cutting-edge technology. However, in general, these findings revealed there was a negative association between academically related factors (e.g., time factor, sense of peer pressure, language study self-confidence, and academic language competence), as well as an attitude toward adoption of ChatGPT and commitment towards academic integrity.

Analysis of the Heterogeneous Coordination between Urban Development Levels and the Ecological Environment in the Chinese Grassland Region (2000–2020): A Case Study of the Inner Mongolia Autonomous Region

Scientifically identifying the impact of urban development levels on the ecological environment in China’s grassland regions from a classification perspective is crucial for stabilizing grassland ecosystems and optimizing urban development in grassland cities. Using the Inner Mongolia Autonomous Region as a case study, this research constructs a conceptual analysis framework for the coordinated state between the urban development level and the ecological environment in China’s grassland regions based on the theory of dual economic structures. Employing the Granger causality test, nonlinear fitting, and coupling coordination degree model methods, the heterogeneity and coordination between urban development levels and ecological environment in China’s grassland areas from 2000 to 2020 are comprehensively analyzed. The findings reveal the following: (1) Capital-type central cities and growing resource-based cities, with high levels of development, positively nurture the grassland ecology, exhibit high labor mobility, and experience low endogenous and exogenous pressures, resulting in high coordination. (2) Pure agro-pastoral cities, with low development levels, negatively impact the grassland ecology, have low labor mobility, and face high endogenous and exogenous pressures, resulting in low coordination. (3) Regional central cities, with moderate development levels, exert a neutral counterbalance effect on the grassland ecology, with opposing endogenous and exogenous pressures, leading to moderate coordination. (4) When the impact relationship ranges from “positive-neutral-negative,” the endogenous and exogenous pressures on the grassland ecology by declining resource-based cities and developing agro-pastoral cities are determined by their specific development levels, showing variations from “large → balance → small” to “small → balance → large,” with coordination fluctuating between “high-moderate-low”. (5) Special ecological cities are less affected by urban development levels, with coordination levels determined by the ecological foundation. Analyzing the heterogeneous coordination between urban development levels and the ecological environment for different types of cities in grassland regions is significant for improving the overall quality of the grassland ecological environment and exploring distinctive urban development models.

Network-based integration of omics, physiological and environmental data in real-world Elbe estuarine Zander

Coastal and estuarine environments are under endogenic and exogenic pressures jeopardizing survival and diversity of inhabiting biota. Information of possible synergistic effects of multiple (a)biotic stressors and holobiont interaction are largely missing in estuaries like the Elbe but are of importance to estimate unforeseen effects on animals' physiology. Here, we seek to leverage host-transcriptional RNA-seq and gill mucus microbial 16S rRNA metabarcoding data coupled with physiological and abiotic measurements in a network analysis approach to decipher the impact of multiple stressors on the health of juvenile Sander lucioperca along one of the largest European estuaries. We find mesohaline areas characterized by gill tissue specific transcriptional responses matching osmosensing and tissue remodeling. Liver transcriptomes instead emphasized that zander from highly turbid areas were undergoing starvation which was supported by compromised body condition. Potential pathogenic bacteria, including Shewanella, Acinetobacter, Aeromonas and Chryseobacterium, dominated the gill microbiome along the freshwater transition and oxygen minimum zone. Their occurrence coincided with a strong adaptive and innate transcriptional immune response in host gill and enhanced energy demand in liver tissue supporting their potential pathogenicity. Taken together, we show physiological responses of a fish species and its microbiome to abiotic factors whose impact is expected to increase with consequences of climate change. We further present a method for the close-meshed detection of the main stressors and bacterial species with disease potential in a highly productive ecosystem.

Unanticipated Outcomes

In contexts where political corruption is endemic, why would political elites build state capacity to prosecute corruption? Prior studies emphasize exogenous pressure from social movements or international organizations and the rise of political leaders committed to fighting corruption. While important, these factors are not sufficient to explain the case of Brazil, where politicians empowered investigative bureaucracies, even though several political elites later became victims of prosecution. Drawing on document analysis of charges and sentences and on 110 in-depth interviews with prosecutors, judges, and politicians, I develop a framework that focuses on the processes through which corruption is criminalized on the ground. By examining the initiatives of politicians in interaction with the actions of civil servants who investigate and prosecute cases of corruption, I show that political elites empowered investigators because, at the time, these steps seemed innocuous. Prosecutors later reframed how they talked about corruption—getting other colleagues to pay attention to this issue—and learned new strategies to uncover corruption schemes, but these changes happened under the radar: they were not visible to politicians. Popular pressure also led courts to broaden the definition of corruption and lower the threshold of evidence for it, but these decisions took place after the politicians’ actions.

Succinonitrile-Lithium Salt Complexes as Solid Catholytes for LLZO-Based Solid-State Batteries

The thermal and electrochemical properties of several succinonitrile (SN)-based organic ionic plastic crystals (OIPCs) containing lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), lithium bis(oxalate) borate (LiBOB) or mixtures of the two salts, were investigated with the goal of determining which is most promising for use as a catholyte in solid-state lithium batteries. The best combination of properties for this use was found for the mixture containing 3 mol% LiTFSI and 2 mol% LiBOB in SN. Based on these observations, several solid-state cells containing Al-substituted Li7La3Zr2O12 separators with composite cathodes consisting of LiNi0.33Mn0.33Co0.33O2 (NMC111), carbon black, and the succinonitrile-salt mixtures were assembled and cycled at room temperature, without exogenous pressure, using a simple design.

ОСОБЕННОСТИ РАССМОТРЕНИЯ ФИНАНСОВОЙ СИСТЕМЫ ГОСУДАРСТВА: ОРГАНИЗАЦИОННЫЙ И ПРАВОВОЙ АСПЕКТЫ

The article considers a number of organizational and legal aspects of the financial system of the state. The first group includes and disclosed five main components: corporate finance, investments, financial institutions, international finance, financial technology, as well as two basic functions - the accumulation and subsequent distribution of financial resources through specialized funds of funds and control over both the targeted spending of budget funds and the activities of subjects of financial legal relations. It was concluded that legal regulation in modern crisis conditions serves specific purposes, and the legislative framework strongly affects the issues of countering exogenous pressure on the domestic economy from unfriendly states.

Sociopolitical reputation and the reform of pharmacies in Greece and Portugal

AbstractThis article argues that differences in sociopolitical reputation can explain why interest groups fail or succeed in influencing policymakers and that therefore sociopolitical reputation is a useful addition to the conceptual toolbox of interest groups scholars. Focusing on pharmacies and their associations in Greece and Portugal between 2005 and 2021, this article uses the concept of sociopolitical reputation to explain why reform attempts to reduce pharmaceutical spending and increase competition in the pharmacy sector were successful in Portugal but not in Greece, even though pharmacists are a much stronger interest group in Portugal than in Greece and even though both countries were under significant exogenous pressure to introduce structural reforms in the wake of the Eurozone crisis.

Macroevolutionary Origins of Comparative Development

Abstract Advances in evolutionary theories (the Extended Synthesis) demonstrate that organisms systematically modify environments in ways that influence their own and other species’ evolution. This paper utilises these theories to examine the economic consequences of human dispersal from Africa. Evidence shows that early humans’ dispersal affected the adaptability of animal species to human environments and, through this, the extinction of large mammals during Homo sapiens’ out-of-Africa migration. Empirical analyses explore the variation in extinction rates as a source of exogenous pressure for cooperation and innovation among hunter-gatherers and examine the impact of extinction on long-run development. The results indicate that extinction affects economic performance by driving continental differences in biogeography, disease environments and institutions. Eurasia’s location along the out-of-Africa migratory path provided human and animal populations with co-evolutionary foundations for domestication and agriculture, which gave Eurasians technological and institutional advantages in comparative development.

Tit for tattling: Cooperation, communication, and how each could stabilize the other

Indirect reciprocity is a mechanism by which individuals cooperate with those who have cooperated with others. This creates a regime in which repeated interactions are not necessary to incent cooperation (as would be required for direct reciprocity). However, indirect reciprocity creates a new problem: how do agents know who has cooperated with others? To know this, agents would need to access some form of reputation information. Perhaps there is a communication system to disseminate reputation information, but how does it remain truthful and informative? Most papers assume the existence of a truthful, forthcoming, and informative communication system; in this paper, we seek to explain how such a communication system could remain evolutionarily stable in the absence of exogenous pressures. Specifically, we present three conditions that together maintain both the truthfulness of the communication system and the prevalence of cooperation: individuals (1) use a norm that rewards the behaviors that it prescribes (an aligned norm), (2) can signal not only about the actions of other agents, but also about their truthfulness (by acting as third party observers to an interaction), and (3) make occasional mistakes, demonstrating how error can create stability by introducing diversity.

Water sector resilience in the United Kingdom and Ireland: The COVID-19 challenge.

The outbreak of COVID-19 led to restrictions on movements and activities, which presented a serious challenge to the resilience of the water sector. It is essential to understand how successfully water companies responded to this unprecedented event so effective plans can be built for future disruptive events. This study aimed to evaluate how the water sectors in the UK and Ireland were affected from a holistic sustainability and resilience-based perspective. Using pre-COVID data for 18 indicators of company performance and comparing them to the first year of the pandemic, the direction and magnitudes of change varied across companies. Financial indicators were significantly negatively affected, with interest cover ratio, post-tax return on regulated equity, and operating profit, exhibiting the greatest average declines of 21%, 21%, and 18%, respectively, a trend that would be dangerous to provisions and company operations if continued. Despite this, service and environmental indicators improved during the first year of the pandemic, exemplified by unplanned outage, risk of sewer storm flooding, and water quality compliance risk decreasing by a mean average of 37%, 32%, and 27%, respectively. Analysis using the Hicks-Moorsteen Productivity Index concluded that average productivity increased by 35%. The results suggest that the water sector was relatively resilient to the COVID-19 pandemic in terms of services, but adverse effects may have manifested in a deteriorated financial position that could exacerbate future challenges arising from exogenous pressures such as climate change. Specific advice for the UK water sector is to scrutinize non-critical spending, such as shareholder payments, during periods of economic downturn to ensure essential capital projects can be carried out. Although results are temporal and indicator selection sensitive, we recommend that policy, regulation, and corporate culture embrace frameworks that support long-term resilience to since the relative success in response to COVID-19 does not guarantee future success against differing challenges. This study generates a timely yet tentative insight into the diverse performance of the water sector during the pandemic, pertinent to the water industry, regulators, academia, and the public.

Theorizing creative challenges: Why are social creativity and reimagined universities necessary for tackling society's problems?

We theorize that social creativity is necessary for addressing the creative challenges—grand opportunities and wicked problems—facing modern society. Our paper seeks to understand why social creativity is an important variable for a theory of creative challenges and why educational institutions can, if reimagined, be ideal for developing this capacity. Drawing on auto-ethnographic methods, we reflect on our five-year collaborative project focused on animating and integrating creativity, interdisciplinarity, design, and entrepreneurship for tackling creative challenges. Our findings yield insights about effective pedagogies and institutional configurations for reproducing social creativity. We find that modern traditional academic institutions, dominated by disciplinary structures, cultures, and exogenous pressures that hinder interdisciplinarity and design, insufficiently develop this necessary prosocial capacity. In contrast, we discuss reimagined academic configurations that balance and integrate both disciplinarity and interdisciplinarity. We contribute clarifying rationales for why social creativity, comprising interdisciplinarity, design thinking, and entrepreneurial acumen, as well as the university reimagined are critical for more complete theorizing about creative challenges. Those who research, practice, and make policy for social change should find our observations, reflections, and analysis useful.

Plastisphere showing unique microbiome and resistome different from activated sludge

Plastisphere (the biofilm on microplastics) in wastewater treatment plants (WWTPs) may enrich pathogens and antibiotic resistance genes (ARGs) which can cause risks to the ecological environment by discharging into receiving waters. However, the microbiome and resistome of plastisphere in activated sludge (AS) systems remain inconclusive. Here, metagenome was applied to investigate the microbial composition, functions and ARGs of the Polyvinyl chloride (PVC) plastisphere in lab-scale reactors, and revealed the effects of tetracycline (TC) and/or Cu(II) pressures on them. The results indicated that the plastisphere provided a new niche for microbiota showing unique functions distinct from the AS. Particularly, various potentially pathogenic bacteria tended to enrich in PVC plastisphere. Moreover, various ARGs were detected in plastisphere and AS, but the plastisphere had more potential ARGs hosts and a stronger correlation with ARGs. The ARGs abundances increased after exposure to TC and/or Cu(II) pressures, especially tetracycline resistance genes (TRGs), and the results further showed that TRGs with different resistance mechanisms were separately enriched in plastisphere and AS. Furthermore, the exogenous pressures from Cu(II) or/and TC also enhanced the association of potential pathogens with TRGs in PVC plastisphere. The findings contribute to assessing the potential risks of spreading pathogens and ARGs through microplastics in WWTPs.

Government responsiveness and citizen satisfaction: Evidence from environmental governance

AbstractPrior research has overlooked the dynamics between government responsiveness and citizen satisfaction. This article addresses this gap by examining (1) how styles of government responses affect citizen satisfaction differently and (2) how external events moderate the effects of government responsiveness on citizens. Drawing upon 79,360 environmental demands sent to local leaders in China and 100,905 Chinese citizens' environmental assessments collected from 2013 to 18, this study finds that actional and explanatory responses positively influence citizen satisfaction, while referral responses negatively affect citizen satisfaction. Moreover, these relationships are subject to the moderating effects of exogenous pressures. Top‐down pressure from the central government's environmental inspections and bottom‐up pressure from the environmental documentary Under the Dome represent two types of exogeneities during the study period. The findings corroborate a dynamic government‐citizen relationship that is shaped by government responding actions and sociopolitical changes.

Selected Articles from This Issue

Highlights| May 02 2022 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2022 American Association for Cancer Research2022American Association for Cancer Research Clin Cancer Res (2022) 28 (9): 1743. https://doi.org/10.1158/1078-0432.CCR-28-9-HI Related Content A commentary has been published: Targeted Analysis of Cell-free Circulating Tumor DNA is Suitable for Early Relapse and Actionable Target Detection in Patients with Neuroblastoma A commentary has been published: Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception A commentary has been published: Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors View more This is a commentary to: Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma View less Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record May 2 2022 Citation Selected Articles from This Issue. Clin Cancer Res 1 May 2022; 28 (9): 1743. https://doi.org/10.1158/1078-0432.CCR-28-9-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Encapsulation of anticancer medications within liposomes is a technique to facilitate drug transportation to the target and accumulation in tumors. Sato and colleagues evaluated the tolerability and efficacy of a liposomal formulation of eribulin (E7389-LF) in patients with advanced solid tumors. E7389-LF was well tolerated overall, and 4/21 of the patients treated achieved a partial response. Endothelial cell, vasculature, and immune-related biomarkers were increased after treatment. Thus E7389-LF may influence tumor vascular remodeling. These findings support further evaluation of E7389-LF for advanced solid tumors. Expansion cohorts are ongoing to evaluate the safety, efficacy, and pharmacodynamics of E7389-LF 2.0 mg/m2 every 3 weeks in specific tumor types. Molecular profiles in solid tumors dynamically evolve in response to endogenous and exogenous pressures. Lodrini and colleagues noninvasively monitored high-risk neuroblastoma evolution using droplet digital PCR assessing MYCN and ALK oncogene status in longitudinally collected biosamples to explore the clinical value of total... You do not currently have access to this content.

Capturing Stakeholders’ Challenges of the Food–Water–Energy Nexus—A Participatory Approach for Pune and the Bhima Basin, India

Systems models of the Food–Water–Energy (FWE) nexus face a conceptual difficulty: the systematic integration of local stakeholder perspectives into a coherent framework for analysis. We present a novel procedure to co-produce and systematize the real-life complexity of stakeholder knowledge and forge it into a clear-cut set of challenges. These are clustered into the Pressure–State–Response (PSIR) framework, which ultimately guides the development of a conceptual systems model closely attuned to the needs of local stakeholders. We apply this approach to the case of the emerging megacity Pune and the Bhima basin in India. Through stakeholder workshops, involving 75 resource users and experts, we identified 22 individual challenges. They include exogenous pressures, such as climate change and urbanization, and endogenous pressures, such as agricultural groundwater over-abstraction and land use change. These pressures alter the Bhima basin’s system state, characterized by inefficient water and energy supply systems and regional scarcity. The consequent impacts on society encompass the inadequate provision with food, water, and energy and livelihood challenges for farmers in the basin. An evaluation of policy responses within the conceptual systems model shows the complex cause–effect interactions between nexus subsystems. One single response action, such as the promotion of solar farming, can affect multiple challenges. The resulting concise picture of the regional FWE system serves resource users, policymakers, and researchers to evaluate long-term policies within the context of the urban FWE system. While the presented results are specific to the case study, the approach can be transferred to any other FWE nexus system.

Transdisciplinary, Co-Designed and Adaptive Management for the Sustainable Development of Rongcheng, a Coastal City in China in the Context of Human Activities and Climate Change

Half the population of China live in coastal zones where 70% of large cities are also located. Intensive human activities pose significant environmental and ecological hazards to these cities that are already vulnerable to natural hazards and climate change. The sustainable development of coastal cities is thus both a national and international issue. Rongcheng is a typical coastal city in east China. It is a national marine ranch demonstration area that is subjected to multi-stressors from human activities and climate change. The dominant economic sectors include aquaculture and fisheries, agriculture, shipping and tourism. A multitude of resulting pressures come mainly from intensified human activities, such as intensive aquaculture, overfishing, industrial pollutants, agricultural runoff, land reclamation and port expansion. In addition, Rongcheng is also facing exogenic pressures from extreme climate events such as intensified storms, storm surges, droughts and sea ice. A growing awareness of these problems brought together a trans-disciplinary group from local government, research institutions, local practitioners and coastal representatives to jointly explore and co-design adaptive coastal management options. In this transdisciplinary study, a social-ecological analysis based on a combination of the Systems Approach Framework and the Drivers-Pressures-States-Impacts-Responses framework was used to analyze and formulate an adaptive management plan for the sustainability of Rongcheng. More than 40 stakeholders including government, companies, civil society and institutions participated in the study through questionnaires and on-site meetings. A statistical analysis of the results identified urgent issues impeding the sustainable development of Rongcheng. The issues identified were poorly regulated aquaculture, loss of shoreline, and the decline of seagrass and cultural heritage. The study identified management options and measures, some of which were adopted by the local government in a co-designed management plan. The measures included upgrading of aquaculture industry, habitat conservation and restoration, and the development of cultural tourism. Another outcome was the increased knowledge exchange between stakeholders to inform management, policy, and decision making, as well as raised awareness of vulnerability to natural hazards and climate change. The success of this case study provides a reference for the adaptive management of other coastal cities and their sustainable development in a changing climate.