Integrating interventions supported by development assistance for health into local health system: evidence from a China-World Bank-UK rural health system strengthening project (1998-2007).

INTRODUCTION: To empirically investigate sustainability of development assistance for health (DAH), we conducted a retrospective case study on the Basic Health Services Project (BHSP) for rural health system strengthening, supported by the World Bank and the UK in China between 1998 and 2007. Specifically, this study examines the integration of the BHSP interventions into China's health system. METHODS: From December 2021 to December 2022, we reviewed 64 published papers and project or policy documents, and conducted semistructured interviews with 22 key informants, ranging from managers of donor agencies and the government to township-level hospital directors. From February to March 2023, the data were analysed under an analytical framework for integration of targeted health interventions into health systems. RESULTS: Evidence of the BHSP shows that the integration outcomes can vary by the levels of integration (national or subnational), geographical coverage (project areas or both project and non-project areas) and approach to integration (policy or routinisation). The country's health system reform facilitated the integration of the interventions relevant to the reform policies, as the BHSP was one of the pilot schemes. However, interventions incompatible with this broad context were integrated to a limited extent. This integration occurred through embedding the project within the existing system, with a higher degree of embeddedness leading to smoother integration. Cross-sectoral leading groups and a technical support system heightened the project visibility and enabled contextualised local adaptation, contributing to the smooth integration of the project interventions. CONCLUSION: The DAH-supported interventions can achieve sustainability by being integrated into the local health system. This integration can take various forms to improve health outcomes, including being accepted and internalised, modified as well as innovated and expanded. The host country and development partners can promote DAH sustainability by contextually integrating these interventions within the project scope.

Development assistance, donor-recipient dynamic, and domestic policy: a case study of two health interventions supported by World Bank-UK and Global Fund in China.

BACKGROUND: This study views sustainability after the exit of development assistance for health (DAH) as a shared responsibility between donors and recipients and sees transitioning DAH-supported interventions into domestic health policy as a pathway to this sustainability. It aims to uncover and understand the reemergent aspects of the donor-recipient dynamic in DAH and how they contribute to formulating domestic health policy and post-DAH sustainability. METHODS: We conducted a case study on two DAH-supported interventions: medical financial assistance in the Basic Health Services Project supported by the World Bank and UK (1998-2007) and civil society engagement in the HIV/AIDS Rolling Continuation Channel supported by the Global Fund (2010-2013) in China. From December 2021 to December 2022, we analyzed 129 documents and interviewed 46 key informants. Our data collection and coding were guided by a conceptual framework based on Walt and Gilson's health policy analysis model and the World Health Organization's health system building blocks. We used process tracing for analysis. RESULTS: According to the collected data, our case study identified three reemergent, interrelated aspects of donor-recipient dynamics: different preferences and compromise, partnership dialogues, and responsiveness to the changing context. In the case of medical financial assistance, the dynamic was characterized by long-term commitment to addressing local needs, on-site mutual learning and understanding, and local expertise cultivation and knowledge generation, enabling proactive responses to the changing context. In contrast, the dynamic in the case of HIV/AIDS civil society engagement marginalized genuine civil society engagement, lacked sufficient dialogue, and exhibited a passive response to the context. These differences led to varying outcomes in transnational policy diffusion and sustainability of DAH-supported interventions between the cases. CONCLUSIONS: Given the similarities in potential alternative factors observed in the two cases, we emphasize the significance of the donor-recipient dynamic in transnational policy diffusion through DAH. The study implies that achieving post-DAH sustainability requires a balance between donor priorities and recipient ownership to address local needs, partnership dialogues for mutual understanding and learning, and collaborative international-domestic expert partnerships to identify and respond to contextual enablers and barriers.

Adapting national data systems for donor transition: comparative analysis of experience from Georgia and China.

Health management information systems (HMISs) are essential in programme planning, budgeting, monitoring and evidence-informed decision-making. This paper focuses on donor transitions in two upper-middle-income countries, China and Georgia, and explores how national HMIS adaptations were made and what facilitated or limited successful and sustainable transitions. This comparative analytical case study uses a policy triangle framework and a mixed-methods approach to explore how and why adaptations in the HMIS occurred under the Gavi Alliance and the Global Fund-supported programmes in China and Georgia. A review of published and grey literature, key informant interviews and administrative data analysis informed the study findings. Contextual factors such as the global and country context, and health system and programme needs drove HMIS developments. Other factors included accountability on a national and international level; improvements in HMIS governance by establishing national regulations for clear mandates of data collection and reporting rules and creating institutional spaces for data use; investing in hardware, software and human resources to ensure regular and reliable data generation; and capacitating national players to use data in evidence-based decision-making for programme and transition planning, budgeting and outcome monitoring. Not all the HMIS initiatives supported by donors were sustained and transitioned. For the successful adaptation and sustainable transition, five interlinked and closely coordinated support areas need to be considered: (1) coupling programme design with a good understanding of the country context while considering domestic and external demands for information, (2) regulating appropriate governance and management arrangements enhancing country ownership, (3) avoiding silo HMIS solutions and taking integrative approach, (4) ensuring the transition of funding onto domestic budget and enforcing fulfilment of the government's financial commitments and finally (5) investing in technologies and skilled human resources for the HMIS throughout all levels of the health system. Neglecting any of these elements risks not delivering sustainable outcomes.

External technical assistance and its contribution to donor transition and long-term sustainability: experience from China and Georgia.

External technical assistance has played a vital role in facilitating the transitions of donor-supported health projects/programmes (or their key components) to domestic health systems in China and Georgia. Despite large differences in size and socio-political systems, these two upper-middle-income countries have both undergone similar trajectories of 'graduating' from external assistance for health and gradually established strong national ownership in programme financing and policymaking over the recent decades. Although there have been many documented challenges in achieving effective and sustainable technical assistance, the legacy of technical assistance practices in China and Georgia provides many important lessons for improving technical assistance outcomes and achieving more successful donor transitions with long-term sustainability. In this innovation and practice report, we have selected five projects/programmes in China and Georgia supported by the following external health partners: the World Bank and the UK Department for International Development, Gavi Alliance and the Global Fund to Fight AIDS, Tuberculosis and Malaria. These five projects/programmes covered different health focus areas, ranging from rural health system strengthening to opioid substitution therapy. We discuss three innovative practices of technical assistance identified by the cross-country research teams: (1) talent cultivation for key decision-makers and other important stakeholders in the health system; (2) long-term partnerships between external and domestic experts; and (3) evidence-based policy advocacy nurtured by local experiences. However, the main challenge of implementation is insufficient domestic budgets for capacity building during and post-transition. We further identify two enablers for these practices to facilitate donor transition: (1) a project/programme governance structure integrated into the national health system and (2) a donor-recipient dynamic that enabled deep and far-reaching engagements with external and domestic stakeholders. Our findings shed light on the practices of technical assistance that strengthen long-term post-transition sustainability across multiple settings, particularly in middle-income countries.

The associations between social support change and physical activity trajectory from late adolescence to young adulthood.

BACKGROUND: Previous research examined the associations between social support and physical activity. However, little is known about the associations between social support change and trajectories of physical activity during the transition from late adolescence to young adulthood. METHODS: The current study sought to examine these issues among 434 Chinese college students (Mage = 19.15, SDage = 0.61; 46.1% male), who completed questionnaires regarding demographics, physical activity, family support change, and peer support change across three waves (the data from one of the waves was retrospective). RESULTS: After controlling for covariates, the findings revealed that: (a) there was an increase in overall physical activity and duration, but a decrease in frequency during the transition from late adolescence (the second year of high school) to young adulthood (the third year of college); (b) family support change did not contribute to trajectories of physical activity, while peer support change significantly predicted the trajectory of overall physical activity, duration, and frequency. CONCLUSIONS: The findings extend the literature on physical activity from a developmental perspective by revealing different trends among physical activity duration and frequency, and unpacking different effects of family and peer support change on trajectories of physical activity.

Effects of personal and interpersonal factors on changes of food choices and physical activity among college students.

BACKGROUND: Health behaviors developed in the college years tend to persist in adulthood. However, distinct changing patterns of food choices and physical activity (PA) and their predictors are still less clear among college students. The current study sought to explore changes of food choices and PA, as well as the effects of personal and interpersonal factors. METHOD: Two-wave longitudinal data was collected from a sample of 431 Chinese college students (Mean baseline age = 19.15 ± 0.61 years; 45.7% male). A validated self-reported food frequency questionnaire was used to assess the frequency of food choices. The Chinese revised version of physical activity rating scale was used to assess physical activity. Latent profile analysis, latent transition analysis, and multinomial logistic regression analysis were used to analyze the data. RESULTS: Two profiles of food choices, i.e., Avoiding staples (5.1% at Time 1) and Varied diet (94.9% at Time 1), were identified at both timepoints. 90.9% remained the same profiles over time, 63.6% participants in the Avoiding staples profile shifted to the Varied diet profile, and only 6.3% of those in the Varied diet profile shifted to the Avoiding staples profile. Negative body shape-related belief was related to the translation from the Varied diet profile to the Avoiding staples profile. Further, four profiles of PA, i.e., Inactives (51.0% at Time 1), Low activies (26.0% at Time 1), Moderate activies (15.3% at Time 1), and Activies (7.7% at Time 1), were identified at both timepoints. 50.8% remained the same profiles over time, 38.6% Inactivies shifted to the other profiles, and 48.5% Activies shifted to the other profiles over time. Participants with higher self-efficacy showed an increase in PA over time, and those with lower self-efficacy and lower peer support showed a decrease in PA over time. CONCLUSIONS: Overall, most of college students remained the same food choices profiles, and body shape-related belief contributed to changes in food choices profiles. About half of college students experienced changes in PA, and the predictors of such changes were peer support and self-efficacy. The findings extend the understanding of the personal and interpersonal predictors of health behaviors among college students from a dynamic perspective.

Sensory circuitry controls cytosolic calcium-mediated phytochrome B phototransduction.

Although Ca2+ has long been recognized as an obligatory intermediate in visual transduction, its role in plant phototransduction remains elusive. Here, we report a Ca2+ signaling that controls photoreceptor phyB nuclear translocation in etiolated seedlings during dark-to-light transition. Red light stimulates acute cytosolic Ca2+ increases via phyB, which are sensed by Ca2+-binding protein kinases, CPK6 and CPK12 (CPK6/12). Upon Ca2+ activation, CPK6/12 in turn directly interact with and phosphorylate photo-activated phyB at Ser80/Ser106 to initiate phyB nuclear import. Non-phosphorylatable mutation, phyBS80A/S106A, abolishes nuclear translocation and fails to complement phyB mutant, which is fully restored by combining phyBS80A/S106A with a nuclear localization signal. We further show that CPK6/12 function specifically in the early phyB-mediated cotyledon expansion, while Ser80/Ser106 phosphorylation generally governs phyB nuclear translocation. Our results uncover a biochemical regulatory loop centered in phyB phototransduction and provide a paradigm for linking ubiquitous Ca2+ increases to specific responses in sensory stimulus processing.

Integration of light and temperature sensing by liquid-liquid phase separation of phytochrome B.

Light and temperature in plants are perceived by a common receptor, phytochrome B (phyB). How phyB distinguishes these signals remains elusive. Here, we report that phyB spontaneously undergoes phase separation to assemble liquid-like droplets. This capacity is driven by its C terminus through self-association, whereas the intrinsically disordered N-terminal extension (NTE) functions as a biophysical modulator of phase separation. Light exposure triggers a conformational change to subsequently alter phyB condensate assembly, while temperature sensation is directly mediated by the NTE to modulate the phase behavior of phyB droplets. Multiple signaling components are selectively incorporated into phyB droplets to form concentrated microreactors, allowing switch-like control of phyB signaling activity through phase transitions. Therefore, light and temperature cues are separately read out by phyB via allosteric changes and spontaneous phase separation, respectively. We provide a conceptual framework showing how the distinct but highly correlated physical signals are interpreted and sorted by one receptor.

Lack of ethylene does not affect reproductive success and synergid cell death in Arabidopsis.

The signaling pathway of the gaseous hormone ethylene is involved in plant reproduction, growth, development, and stress responses. During reproduction, the two synergid cells of the angiosperm female gametophyte both undergo programmed cell death (PCD)/degeneration but in a different manner: PCD/degeneration of one synergid facilitates pollen tube rupture and thereby the release of sperm cells, while PCD/degeneration of the other synergid blocks supernumerary pollen tubes. Ethylene signaling was postulated to participate in some of the synergid cell functions, such as pollen tube attraction and the induction of PCD/degeneration. However, ethylene-mediated induction of synergid PCD/degeneration and the role of ethylene itself have not been firmly established. Here, we employed the CRISPR/Cas9 technology to knock out the five ethylene-biosynthesis 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes and created Arabidopsis mutants free of ethylene production. The ethylene-free mutant plants showed normal triple responses when treated with ethylene rather than 1-aminocyclopropane-1-carboxylic acid, but had increased lateral root density and enlarged petal sizes, which are typical phenotypes of mutants defective in ethylene signaling. Using these ethylene-free plants, we further demonstrated that production of ethylene is not necessarily required to trigger PCD/degeneration of the two synergid cells, but certain components of ethylene signaling including transcription factors ETHYLENE-INSENSITIVE 3 (EIN3) and EIN3-LIKE 1 (EIL1) are necessary for the death of the persistent synergid cell.

Touch-induced seedling morphological changes are determined by ethylene-regulated pectin degradation.

How mechanical forces regulate plant growth is a fascinating and long-standing question. After germination underground, buried seedlings have to dynamically adjust their growth to respond to mechanical stimulation from soil barriers. Here, we designed a lid touch assay and used atomic force microscopy to investigate the mechanical responses of seedlings during soil emergence. Touching seedlings induced increases in cell wall stiffness and decreases in cell elongation, which were correlated with pectin degradation. We revealed that PGX3, which encodes a polygalacturonase, mediates touch-imposed alterations in the pectin matrix and the mechanics of morphogenesis. Furthermore, we found that ethylene signaling is activated by touch, and the transcription factor EIN3 directly associates with PGX3 promoter and is required for touch-repressed PGX3 expression. By uncovering the link between mechanical forces and cell wall remodeling established via the EIN3-PGX3 module, this work represents a key step in understanding the molecular framework of touch-induced morphological changes.

Allosteric deactivation of PIFs and EIN3 by microproteins in light control of plant development.

Buried seedlings undergo dramatic developmental transitions when they emerge from soil into sunlight. As central transcription factors suppressing light responses, PHYTOCHROME-INTERACTING FACTORs (PIFs) and ETHYLENE-INSENSITIVE 3 (EIN3) actively function in darkness and must be promptly repressed upon light to initiate deetiolation. Microproteins are evolutionarily conserved small single-domain proteins that act as posttranslational regulators in eukaryotes. Although hundreds to thousands of microproteins are predicted to exist in plants, their target molecules, biological roles, and mechanisms of action remain largely unknown. Here, we show that two microproteins, miP1a and miP1b (miP1a/b), are robustly stimulated in the dark-to-light transition. miP1a/b are primarily expressed in cotyledons and hypocotyl, exhibiting tissue-specific patterns similar to those of PIFs and EIN3 We demonstrate that PIFs and EIN3 assemble functional oligomers by self-interaction, while miP1a/b directly interact with and disrupt the oligomerization of PIFs and EIN3 by forming nonfunctional protein complexes. As a result, the DNA binding capacity and transcriptional activity of PIFs and EIN3 are predominantly suppressed. These biochemical findings are further supported by genetic evidence. miP1a/b positively regulate photomorphogenic development, and constitutively expressing miP1a/b rescues the delayed apical hook unfolding and cotyledon development of plants overexpressing PIFs and EIN3 Our study reveals that microproteins provide a temporal and negative control of the master transcription factors' oligomerization to achieve timely developmental transitions upon environmental changes.

Oligomerization and Photo-Deoligomerization of HOOKLESS1 Controls Plant Differential Cell Growth.

Apical hook curvature is crucial for buried seedling survival and a superb model for dissecting differential cell growth. HOOKLESS1 (HLS1) is essential for apical hook formation, acting as a hub integrating various external and internal signals. However, its functional mechanism remains unclear. Here, we demonstrate that HLS1 protein is present as an oligomer in the nucleus of dark-grown seedlings. Oligomerization is required for HLS1 activation, as the mutated HLS1 protein abolishing self-association exists as nonfunctional monomers. Upon light exposure, photoreceptor phyB translocates into the nucleus and interacts with HLS1, disrupting the self-association and oligomerization of HLS1 to initiate hook unfolding. Remarkably, genetic expression of nuclear-localized phyB is sufficient to inactivate HLS1, resulting in compromised hook curvature in etiolated seedlings. Together, we conclude that HLS1 protein is active as oligomeric form in darkness and achieves allosteric photo-deactivation upon light, providing intriguing mechanistic insight into the molecular switch for developmental transition.

Genome-wide regulation of light-controlled seedling morphogenesis by three families of transcription factors.

Three families of transcription factors have been reported to play key roles in light control of Arabidopsis seedling morphogenesis. Among them, bHLH protein PIFs and plant-specific protein EIN3/EIN3-LIKE 1 (EIN3/EIL1) accumulate in the dark to maintain skotomorphogenesis. On the other hand, HY5 and HY5 HOMOLOG (HYH), two related bZIP proteins, are stabilized in light and promote photomorphogenic development. To systemically investigate the transcriptional regulation of light-controlled seedling morphogenesis, we generated HY5ox/pifQein3eil1, which contained mutations of EIN3/EIL1 and four PIF genes (pifQein3eil1) and overexpression of HY5 Our results show that dark-grown HY5ox/pifQein3eil1 seedlings display a photomorphogenesis highly similar to that of wild-type seedlings grown in continuous light, with remarkably enhanced photomorphogenic phenotypes compared with the pifQ mutants. Consistent with the genetic evidence, transcriptome analysis indicated that PIFs, EIN3/EIL1, and HY5 are dominant transcription factors in collectively mediating a wide range of light-caused genome-wide transcriptional changes. Moreover, PIFs and EIN3/EIL1 independently control the expression of light-regulated genes such as HLS1 to cooperatively regulate apical hook formation, hypocotyl elongation, and cotyledon opening and expansion. This study illustrates a comprehensive regulatory network of transcription activities that correspond to specific morphological aspects in seedling skotomorphogenesis and photomorphogenesis.