Heterogeneous vs homogenous photocatalysis: what dominates in the degradation of methyl orange and methylene blue mixtures?

Photocatalysis has been oft proposed as a green solution for pollution remediation, however, majority of the existing literature only studies the degradation of solitary analytes. The degradation of mixtures of organic contaminants is inherently more complicated due to a variety of photochemical processes that occur in parallel. Here, we describe a model system comprised of methylene blue and methyl orange dyes whose degradation carried out by two common photocatalysts, P25 TiO2 and g-C3N4. With P25 TiO2 as the catalyst, the degradation rate of methyl orange slowed by 50% when degraded in a mixture compared to when alone. Control experiments with radical scavengers showed this to occur due to competition between the dyes for oxidative photogenerated species. In the presence of g-C3N4, methyl orange's degradation rate in the mixture increased by 2300% due to two homogeneous photocatalysis processes sensitized by methylene blue. Homogenous photocatalysis was found to be fast relative to heterogeneous photocatalysis by g-C3N4 but slow relative to photocatalysis by P25 TiO2 and explains the change observed between the two catalysts. Changes in dye adsorption to the catalyst when in a mixture were also explored but not found to coincide with changes in degradation rate.

"Building palliative care capacity in cancer treatment centres: a participatory action research".

INTRODUCTION: There is a significant lack of palliative care access and service delivery in the Indian cancer institutes. In this paper, we describe the development, implementation, and evaluation of a palliative care capacity-building program in Indian cancer institutes. METHODS: Participatory action research method was used to develop, implement and evaluate the outcomes of the palliative care capacity-building program. Participants were healthcare practitioners from various cancer institutes in India. Training and education in palliative care, infrastructure for palliative care provision, and opioid availability were identified as key requisites for capacity-building. Researchers developed interventions towards capacity building, which were modified and further developed after each cycle of the capacity-building program. Qualitative content analysis was used to develop an action plan to build capacity. Descriptive statistics were used to measure the outcomes of the action plan. RESULTS: Seventy-three healthcare practitioners from 31 cancer treatment centres in India were purposively recruited between 2016 and 2020. The outcome indicators of the project were defined a priori, and were audited by an independent auditor. The three cycles of the program resulted in the development of palliative care services in 23 of the 31 institutes enrolled in the program. Stand-alone palliative care outpatient services were established in all the 23 centres, with the required infrastructure and manpower being provided by the organization. Morphine availability improved and use increased in these centres, which was an indication of improved pain management skills among the participants. The initiation and continuation of education, training, and advocacy activities in 20 centres suggested that healthcare providers continued to remain engaged with the program even after the cessation of their training cycle. CONCLUSION: This program illustrates how a transformational change at the organizational and individual level can lead to the development of sustained provision of palliative care services in cancer institutes.

Controlled hierarchical assembly of gold nanoparticles in macroscopic films: from densely packed monolayers to networks of micropores and nanobundles.

The present study demonstrates the ability of excess, weakly amphiphilic n-alkanethiols (n = 4, 12, 18) and solvent composition to tune through a wide range of large-scale, macroscopic architectures formed by alkanethiol-capped Au nanoparticles (NPs). Both the alkanethiols and NPs are significantly hydrophobic species and compete for surface area at an air-water interface. When solutions of the two species are spread on a large (50 cm2) water surface in a Teflon well, a thin film forms and exhibits co-existing macroscopic regions with various distinct NP self-assembled architectures, namely a close packed monolayer, a network phase characterized by micron-sized pores (micropores) surrounded by quasi-linear bundles of nanoparticles, and finally aggregates. We hypothesize that the co-existence of various NP architectures results from fast, non-uniform evaporation across the large water surface. When solutions are instead deposited on a smaller (5 cm2) water surface contained within a Teflon ring to control the water surface curvature and the evaporation rate is slowed, we show for the first time that NPs form macroscopically uniform self-assemblies whose architectures can be tuned from monolayers → monolayers with micropores → extended micropore/NP bundle networks by varying excess alkanethiol concentration and solvent composition. We propose that competition between NPs and excess alkanethiols for water surface area, and alkanethiol self-assembly as well as solvent dewetting play important roles in the formation of the network phase, and discuss a potential mechanism for its formation.

The Functional Living Index-Cancer is a reliable and valid instrument in Chinese cancer patients.

PURPOSE: To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. METHODS: The English FLIC was translated into Traditional Chinese by the standard forward-backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. RESULTS: We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. CONCLUSIONS: The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.

The English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) were valid and reliable and provided comparable scores in Asian breast cancer patients.

OBJECTIVE: To examine the measurement properties of and comparability between the English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) in breast cancer patients in Singapore. METHODS: This is an observational study of 269 patients. Known-group validity and responsiveness of the EQ-5D utility index and visual analog scale (VAS) were assessed in relation to various clinical characteristics and longitudinal change in performance status, respectively. Convergent and divergent validity was examined by correlation coefficients between the EQ-5D and a breast cancer-specific instrument. Test-retest reliability was evaluated. The two language versions were compared by multiple regression analyses. RESULTS: For both English and Chinese versions, the EQ-5D utility index and VAS demonstrated known-group validity and convergent and divergent validity, and presented sufficient test-retest reliability (intraclass correlation = 0.72 to 0.83). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. In the comparison analyses of the utility index and VAS between the two language versions, borderline results were obtained, and equivalence cannot be definitely confirmed. CONCLUSION: The five-level EQ-5D is valid, responsive, and reliable in assessing health outcome of breast cancer patients. The English and Chinese versions provide comparable measurement results.

Comparison of the measurement properties between a short and generic instrument, the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) questionnaire, and a longer and disease-specific instrument, the Functional Assessment of Cancer Therapy-Breast (FACT-B), in Asian breast cancer patients.

PURPOSE: To compare the measurement precision and related properties between the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) questionnaire and the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire in assessing breast cancer patients. METHODS: An observational study of 269 Singaporean breast cancer patients. To compare discriminative ability and responsiveness, the effect sizes (in standard deviation) of the EQ-5D-5L and the FACT-B in relation to health indicators and the change in performance status or quality of life were estimated. Test-retest reliability was examined using the intraclass correlation (ICC). RESULTS: Using performance status, evidence of disease, and treatment status as the criteria, the differences (FACT-B minus EQ-5D-5L) in the effect size for discriminative ability were negative or closed to zero, and the 90% confidence intervals totally fell within the zone that indicated the non-inferiority of the EQ-5D-5L. For responsiveness and test-retest reliability, the confidence intervals of the differences in effect size and ICC overlapped the non-inferiority margin; thus, non-inferiority in these two aspects could neither be confirmed nor rejected. CONCLUSIONS: The EQ-5D-5L was non-inferior to the FACT-B in discriminating breast cancer patients with different health conditions cross-sectionally. The EQ-5D-5L serves as a reasonable alternative or supplementary instrument to the FACT-B in assessing breast cancer patients' health outcomes.

Understanding the concept of a "good death" among bereaved family caregivers of cancer patients in Singapore.

OBJECTIVE: The aim of this study was to examine the concept of a good death from the perspectives of both the dying person and the family caregiver, as perceived by bereaved family caregivers of advanced cancer patients. METHOD: The data were gathered from five focus group discussions and one face-to-face qualitative interview conducted over 8 months among 18 bereaved family caregivers recruited from a local hospice. The transcripts of the focus groups and the interview were entered into NVivo Version 8 and were analyzed using the thematic approach. RESULTS: A good death may be understood as having the biopsychosocial and spiritual aspects of life handled well at the end of life. Five major themes were identified. These were preparation for death, family and social relationships, moments at or near death, comfort and physical care, and spiritual well-being. Differences were also noted in what is important at the end of life between the patients and caregivers. Having a quick death with little suffering was perceived to be good by the patient, but the family caregiver wanted to be able to say a final goodbye to the patient. Patients tend to prefer not to die in their children's presence but the children wished to be present for the final moment. In addition, family caregivers reported it was important for them to be able to give the patients permission to die, to feel recognized for the efforts made, and to have had a fulfilling caregiving experience. SIGNIFICANCE OF RESULTS: Whereas there are global attributes of a good death, our findings suggest that patients and family caregivers may define a good death differently. Therefore, there is a need to respect, address, and reconcile the differences, so that all parties may have a good experience at the end of a person's life.

The physician-patient relationship in treatment decision making at the end of life: a pilot study of cancer patients in a Southeast Asian society.

BACKGROUND: The traditional relationship between patient and physician in East Asian society has often been described as "paternalistic." However, in an increasingly Westernized world, our knowledge of how patients perceive the role of the physician in their decision making regarding treatment is lacking. OBJECTIVE: This article is part of a larger pilot study exploring the patient-physician dynamic on decision making among Southeast Asian palliative cancer patients. We explore: (1) influence of physicians, (2) the effect of symptom control and quality of life, and (3) dynamics and communication of physicians. DESIGN: An interviewer-administered questionnaire was distributed, with 18 questions related to physician-patient interactions asked. Most questions followed a three point scale: "agree," "neutral," and "disagree," and spontaneous answers beyond this framework were recorded. SETTING/PARTICIPANTS: Thirty patients from the palliative care service were interviewed, including inpatients at Singapore General Hospital and those attending outpatient clinics at the National Cancer Centre. RESULTS: Patients said that they themselves and their physicians were the main influences (80% each), over family members (48.3%). Some patients (26.7%) felt that symptoms were not well controlled, and 42.9% identified low mood or anxiety. Some patients (44.8%) felt that their condition had an effect on decision making. Most patients (89.3%) had a good relationship with the staff, with >80% being comfortable with discussions held. However, 20.7% of patients felt dissatisfied with the information provided, and 62.1% of patients wanted full disclosure of information. SIGNIFICANCE OF RESULTS: Patients appeared to place highest regard in both autonomy and physician input in making decisions, accompanied by an increased desire for more information. These reflect deviation away from traditional thinking of paternalistic doctoring in East Asia.

Supportive, palliative, and end-of-life care for patients with cancer in Asia: resource-stratified guidelines from the Asian Oncology Summit 2012.

The burden of cancer in Asia is high; 6·1 million new cases were diagnosed in the continent in 2008, which accounted for 48% of new cases worldwide. Deaths from cancer are expected to continue to rise because of ageing populations and modifiable risk factors such as tobacco and alcohol use, diet, and obesity. Most patients who are diagnosed with cancer in Asia have advanced disease that is not amenable to curative treatment, which means that they are likely to have pain and other symptoms and psychosocial concerns. These burdens vary with the economic and political situation of the different countries and are affected by such factors as an absence of screening programmes, insufficient cancer diagnostic and treatment services (especially in sparsely populated and rural areas), legal restrictions on access to drugs to relieve pain, and a medical culture in which quality-of-life considerations are undervalued in relation to imperatives to treat. These issues could be ameliorated by increased investment in cancer screening, removal of restrictions on prescription of opioids, and improvements in medical education to increase recognition of treatment futility. Supportive, palliative, and end-of-life care offer the potential to enhance quality of life, improve pain control, and reduce suffering for patients with cancer and their families, and to give patients a dignified death. All patients should have access to such care-in resource-rich regions these services should be integrated into oncology services, whereas in resource-poor regions they should be the main focus of treatment. The form of care should depend on the economic circumstances within and across countries, and recommendations are made across four resource classifications (basic to maximal) to take account of the diversity of settings in Asia.

Injectable thermosensitive hydrogel to modulate tolerogenic dendritic cells under hyperglycemic condition.

Hyperglycemia associated with diabetes mellitus is a significant risk factor for periodontitis and it polarizes the immune cells towards an inflammatory state. Specific biomaterials can deliver therapeutic or immunomodulatory agents to regulate the excessive periodontal inflammation. Dendritic cells (DCs) bridge the innate and adaptive immune systems and are crucially involved in periodontitis. Thus, targeting DCs is an attractive treatment option for diabetic periodontitis, which, by modulating the downstream adaptive immune cells could regulate the host immune responses. In this study, a chitosan-based thermosensitive injectable self-assembled hydrogel (TISH) was developed to modulate DCs towards a tolerogenic phenotype, which can induce regulatory T-cells to attenuate inflammation and promote healing. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and resveratrol were loaded into TISH (TISH(G + R)) and were sustainably released. TISH demonstrated good biocompatibility and cell penetration in its porous structure. DCs grown in TISH(G + R) under an in vitro hyperglycemic condition showed reduced maturation and activation markers such as CD80, CD83 and CD86, while simultaneously upregulated tolerogenic genes such as FOXP3, SOCS3, TGFß and IL10. Co-culture of these tolerogenic DCs with naïve T-cells induced regulatory T-cells differentiation, evidenced by elevated gene expressions of FOXP3, TGFß and IL-10. In vivo subcutaneous injection of TISH (G + R) into the mice showed significant infiltration of DCs and regulatory T-cells. In conclusion, TISH was developed and optimized as an injectable hydrogel to modulate DCs towards the tolerogenic phenotype and induce regulatory T-cells under hyperglycemia. TISH has promising potential to improve periodontal parameters in diabetic periodontitis.

Painting and Poetry From a Bereaved Family and the Caring Physician.

This is a case description and personal account shared by a palliative care physician whose team provided specialist palliative care support to a patient who attempted immolation. This case depicts a family at risk of complicated grief due to the violent nature of self-inflicted burns and the lingering social stigmatization of suicide. Here, we explore important psycho-emotional considerations and share our experience using art and poetry to build therapeutic connections with the grieving family.

Clinical activities that contributed to the effectiveness of a cardiologist-pharmacist collaborative care model in managing diabetes.

OBJECTIVES: The primary objectives of this study were to evaluate the change in glycated haemoglobin (HbA1c) and its association to clinical activities. The secondary objective was to elucidate moderators of the relationship between pharmacist-involved collaborative care (PCC) and change in HbA1c. METHODS: This study was a retrospective cohort study conducted in a tertiary hospital over 12 months. Individuals with Type 2 diabetes, aged ≥21 years with established cardiovascular diseases were included while individuals with incomplete care documentation or missing data related to cardiovascular diseases were excluded. Individuals under the care of PCC were matched 1:1 based on baseline HbA1c with an eligible person who received care from the cardiologists (CC). Changes in mean HbA1c were analysed using linear mixed model. Linear regression was used to determine clinical activities that associated with improvement in HbA1c. Moderation analyses were conducted using the MacArthur framework. KEY FINDINGS: A total of 420 participants (PCC:210, CC:210) were analysed. The mean age of the participants was 65.6 ± 11.1 years, with the majority being male and Chinese. The mean HbA1c among participants in the PCC group decreased significantly after 6 months (PCC: -0.4% versus CC: -0.1%, P = 0.016), with maintenance of improvement at 12 months (PCC: -0.4% versus CC: -0.2%, P < 0.001). Frequencies of lifestyle counselling, reinforcement of visits to healthcare providers, health education, resolution of drug-related problems, emphasis on medication adherence, dose adjustments and advice on self-care techniques were significantly higher in the intervention group (P < 0.001). CONCLUSION: Improvements in HbA1c were associated with the provision of health education and medication adjustments.

Measurement properties of the English and Chinese versions of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in Asian breast cancer patients.

The objective of the study was to examine the measurement properties of and comparability between the English and Chinese versions of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in breast cancer patients in Singapore. This is an observational study of 271 Singaporean breast cancer patients. The known-group validity of FACT-B total score and Trial Outcome Index (TOI) were assessed in relation to performance status, evidence of disease, and treatment status cross-sectionally; responsiveness to change was assessed in relation to change in performance status longitudinally. Internal consistency and test-retest reliability were evaluated by the Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Multiple regression analyses were performed to compare the scores on the two language versions, adjusting for covariates. The FACT-B total score and TOI demonstrated known-group validity in differentiating patients with different clinical status. They showed high internal consistency and test-retest reliability, with Cronbach's alpha ranging from 0.87 to 0.91 and ICC ranging from 0.82 to 0.89. The English version was responsive to the change in performance status. The Chinese version was shown to be responsive to decline in performance status but the sample size of Chinese-speaking patients who improved in performance status was too small (N = 6) for conclusive analysis about responsiveness to improvement. Two items concerning sexuality had a high item non-response rate (50.2 and 14.4%). No practically significant difference was found in the total score and TOI between the two language versions despite minor differences in two of the 37 items. The English and Chinese versions of the FACT-B are valid, responsive, and reliable instruments in assessing health-related quality of life in breast cancer patients in Singapore. Data collected from the English and Chinese versions can be pooled and either version could be used for bilingual patients.

Cross Country Comparison of Expert Assessments of the Quality of Death and Dying 2021.

CONTEXT: Few efforts have attempted to quantify how well countries deliver end-of-life (EOL) care. OBJECTIVES: To score, grade, and rank countries (and Hong Kong and Taiwan) on the quality of EOL care based on assessments from country experts using a novel preference-based scoring algorithm. METHODS: We fielded a survey to country experts around the world, asking them to assess the performance of their country on 13 key indicators of EOL care. Results were combined with preference weights from caregiver-proxies of recently deceased patients to generate a preference-weighted summary score. The scores were then converted to grades (from A-F) and a ranking was created for all included countries. RESULTS: The final sample included responses from 181 experts representing 81 countries with 2 or more experts reporting. The 6 countries who received the highest assessment scores and a grade of A were United Kingdom, Ireland, Taiwan, Australia, Republic of Korea, and Costa Rica. Only Costa Rica (upper middle) is not a high income country. Not until Uganda (ranked 31st) does a low-income country appear on the ranking. Based on the assessment scores, twenty-one countries received a failing grade, with only two - Czech Republic (66th), and Portugal (75th) - being high income countries. CONCLUSION: This study provides an example of how a preference-based scoring algorithm and input from key stakeholders can be used to assess EOL health system performance. Results highlight the large disparities in assessments of the quality of EOL care across countries, and especially between the highest income countries and others.

PDMS hydrogel-coated tissue culture plates for studying the impact of substrate stiffness on dendritic cell function.

The mechanical properties of polydimethylsiloxane hydrogels can be tuned to mimic physiological tensions, an underappreciated environmental parameter in immunology studies. We describe a workflow to prepare PDMS-coated tissue culture plates with biologically relevant substrate stiffness, and the use of these hydrogel plates to condition isolated primary splenic CD11c+ dendritic cells (DC). Finally, we suggest downstream applications to study the impact of substrate stiffness on DC function and metabolism. The protocol could be adapted to study other mechanosensitive immune cell subsets. For complete details on the use and execution of this protocol, please refer to Chakraborty et al. (2021).

What do renal health-care professionals in Singapore think of advance care planning for patients with end-stage renal disease?

AIM: Previous studies have focused either on advance medical directives rather than advance care planning (ACP), or on patient's perspectives on ACP rather than those of the health-care providers. This study aimed to explore the knowledge, attitudes and experience of renal health-care professionals in Singapore on ACP for patients with end-stage renal failure. METHODS: A 41-item questionnaire was distributed to physicians, nurses, medical social workers (MSW) and other allied health professionals working in renal units. The questionnaire had four sections: demographics of the respondents, knowledge of, attitudes to and experience with ACP. RESULTS: Of a total of 620 survey forms, 562 were returned, giving a response rate of 90.6%. Medical social workers and physicians had higher knowledge scores than the rest. Of doctors and MSW, 82.4% and 100%, respectively, considered ACP discussions as part of their role, but only 37.1% of nurses and 38.1% of other allied health-care professionals thought likewise. Nurses appeared to be the least confident in conducting ACP discussions, and most fearful of upsetting patients and families. Medical social workers were the most confident. The main barriers for physicians appeared to be lack of time, concerns regarding family backlash and the perception that patients were not prepared to discuss ACP. CONCLUSION: Training of renal health-care professionals in ACP should aim to correct misunderstandings surrounding ACP, address potential barriers and impart communication skills. In particular, renal nurses will need encouragement to initiate discussions and be equipped with the skills to do so.

Biomaterial Properties Modulating Bone Regeneration.

Biomaterial scaffolds have been gaining momentum in the past several decades for their potential applications in the area of tissue engineering. They function as three-dimensional porous constructs to temporarily support the attachment of cells, subsequently influencing cell behaviors such as proliferation and differentiation to repair or regenerate defective tissues. In addition, scaffolds can also serve as delivery vehicles to achieve sustained release of encapsulated growth factors or therapeutic agents to further modulate the regeneration process. Given the limitations of current bone grafts used clinically in bone repair, alternatives such as biomaterial scaffolds have emerged as potential bone graft substitutes. This review summarizes how physicochemical properties of biomaterial scaffolds can influence cell behavior and its downstream effect, particularly in its application to bone regeneration.

Preparedness to Face the COVID-19 Pandemic in Hospice and Palliative Care Services in the Asia-Pacific Region: A Rapid Online Survey.

BACKGROUND: Hospice and palliative care services provision for COVID-19 patients is crucial to improve their life quality. There is limited evidence on COVID-19 preparedness of such services in the Asia-Pacific region. AIM: To evaluate the preparedness and capacity of hospice and palliative care services in the Asia-Pacific region to respond to the COVID-19 pandemic. METHOD: An online cross-sectional survey was developed based on methodology guidance. Asia-Pacific Hospice and Palliative Care Network subscribers (n = 1551) and organizational members (n = 185) were emailed. Descriptive analysis was undertaken. RESULTS: Ninety-seven respondents completed the survey. Around half of services were hospital-based (n = 47, 48%), and public-funded (n = 46, 47%). Half of services reported to have confirmed cases (n = 47, 49%) and the majority of the confirmed cases were patients (n = 28, 61%). Staff perceived moderate risk of being infected by COVID-19 (median: 7/10). > 85% of respondents reported they had up-to-date contact list for staff and patients, one-third revealed challenges to keep record of relatives who visited the services (n = 30, 31%), and of patients visited in communities (n = 29, 30%). Majority of services (60%) obtained adequate resources for infection control except face mask. More than half had no guidance on Do Not Resuscitate orders (n = 59, 66%) or on bereavement care for family members (n = 44, 51%). CONCLUSION: Recommendations to strengthen the preparedness of palliative care services include: 1) improving the access to face mask; 2) acquiring stress management protocols for staff when unavailable; 3) reinforcing the contact tracing system for relatives and visits in the community and 4) developing guidance on patient and family care during patient's dying trajectory.

Glucose oxidase kinetics using MnO2 nanosheets: confirming Michaelis-Menten kinetics and quantifying decreasing enzyme performance with increasing buffer concentration.

MnO2 nanosheets and ultraviolet-visible (UV-Vis) absorbance spectroscopy are used to study glucose oxidase (GOx) kinetics. Glucose oxidation by GOx produces H2O2, which rapidly decomposes the nanosheets and reduces their absorption. This direct approach for monitoring glucose oxidation enables simpler, real time kinetics analysis compared to methods that employ additional enzymes. Using this approach, the present study confirms that GOx kinetics is consistent with the Michaelis-Menten (MM) model, and reveals that the MM constant increases by an order of magnitude with increasing buffer concentration. Since larger MM constants imply higher enzyme substrate concentrations are required to achieve the same rate of product formation, increasing MM constants imply decreasing enzyme performance. These results demonstrate the facility of using MnO2 nanosheets to study GOx kinetics and, given the widespread applications of enzymes with buffers, the important sensitivity of enzyme-buffer systems on buffer concentration.

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function.

Stiffness in the tissue microenvironment changes in most diseases and immunological conditions, but its direct influence on the immune system is poorly understood. Here, we show that static tension impacts immune cell function, maturation, and metabolism. Bone-marrow-derived and/or splenic dendritic cells (DCs) grown in vitro at physiological resting stiffness have reduced proliferation, activation, and cytokine production compared with cells grown under higher stiffness, mimicking fibro-inflammatory disease. Consistently, DCs grown under higher stiffness show increased activation and flux of major glucose metabolic pathways. In DC models of autoimmune diabetes and tumor immunotherapy, tension primes DCs to elicit an adaptive immune response. Mechanistic workup identifies the Hippo-signaling molecule, TAZ, as well as Ca2+-related ion channels, including potentially PIEZO1, as important effectors impacting DC metabolism and function under tension. Tension also directs the phenotypes of monocyte-derived DCs in humans. Thus, mechanical stiffness is a critical environmental cue of DCs and innate immunity.