MITOL deficiency triggers hematopoietic stem cell apoptosis via ER stress response.

Hematopoietic stem cell (HSC) divisional fate and function are determined by cellular metabolism, yet the contribution of specific cellular organelles and metabolic pathways to blood maintenance and stress-induced responses in the bone marrow remains poorly understood. The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 (encoded by the Mitol gene) is known to regulate mitochondrial and endoplasmic reticulum (ER) interaction and to promote cell survival. Here, we investigated the functional involvement of MITOL in HSC maintenance by generating MX1-cre inducible Mitol knockout mice. MITOL deletion in the bone marrow resulted in HSC exhaustion and impairment of bone marrow reconstitution capability in vivo. Interestingly, MITOL loss did not induce major mitochondrial dysfunction in hematopoietic stem and progenitor cells. In contrast, MITOL deletion induced prolonged ER stress in HSCs, which triggered cellular apoptosis regulated by IRE1α. In line, dampening of ER stress signaling by IRE1α inihibitor KIRA6 partially rescued apoptosis of long-term-reconstituting HSC. In summary, our observations indicate that MITOL is a principal regulator of hematopoietic homeostasis and protects blood stem cells from cell death through its function in ER stress signaling.

ATP citrate lyase controls hematopoietic stem cell fate and supports bone marrow regeneration.

In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCRhigh ) were enriched within the stem cell fraction at the expense of more proliferative EPCRLow HSCs. These EPCRHigh HSCs were initially more primitive than EPCRLow HSCs and enabled stem cell expansion by enhancing histone acetylation, due to increased activity of ACLY in the early phase of hematopoietic regeneration. In the late phase of recovery, HSCs enhanced differentiation potential by increasing the accessibility of cis-regulatory elements in progenitor cell-related genes, such as CD48. In conditions of reduced mitochondrial metabolism and ACLY activity, these HSCs maintained stem cell phenotypes, while ACLY-dependent histone acetylation promoted differentiation into CD48+ progenitor cells. Collectively, these results indicate that the dynamic control of ACLY-dependent metabolism and epigenetic alterations is essential for HSC regulation during hematopoietic regeneration.

Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve.

Spatially selective vagus nerve stimulation (sVNS) offers a promising approach for addressing heart disease with enhanced precision. Despite its therapeutic potential, VNS is limited by off-target effects and the need for time-consuming titration. Our research aimed to determine the spatial organization of cardiac afferent and efferent fibres within the vagus nerve of pigs to achieve targeted neuromodulation. Using trial-and-error sVNS in vivo and ex vivo micro-computed tomography fascicle tracing, we found significant spatial separation between cardiac afferent and cardiac efferent fibres at the mid-cervical level and they were localized on average on opposite sides of the nerve cross-section. This was consistent between both in vivo and ex vivo methods. Specifically, cardiac afferent fibres were located near pulmonary fibres, consistent with findings of cardiopulmonary convergent circuits and, notably, cardiac efferent fascicles were exclusive. These cardiac efferent regions were located in close proximity to the recurrent laryngeal regions. This is consistent with the roughly equitable spread across the nerve of the afferent and efferent fibres. Our study demonstrated that targeted neuromodulation via sVNS could achieve scalable heart rate decreases without eliciting cardiac afferent-related reflexes; this is desirable for reducing sympathetic overactivation associated with heart disease. These findings indicate that understanding the spatial organization of cardiac-related fibres within the vagus nerve can lead to more precise and effective VNS therapy, minimizing off-target effects and potentially mitigating the need for titration. KEY POINTS: Spatially selective vagus nerve stimulation (sVNS) presents a promising approach for addressing chronic heart disease with enhanced precision. Our study reveals significant spatial separation between cardiac afferent and efferent fibres in the vagus nerve, particularly at the mid-cervical level. Utilizing trial-and-error sVNS in vivo and micro-computed tomography fascicle tracing, we demonstrate the potential for targeted neuromodulation, achieving therapeutic effects such as scalable heart rate decrease without stimulating cardiac afferent-related reflexes. This spatial understanding opens avenues for more effective VNS therapy, minimizing off-target effects and potentially eliminating the need for titration, thereby expediting therapeutic outcomes in myocardial infarction and related conditions.

Recent Advances on Nitrogen-Doped Porous Carbons Towards Electrochemical Supercapacitor Applications.

Due to ever-increasing global energy demands and dwindling resources, there is a growing need to develop materials that can fulfil the World's pressing energy requirements. Electrochemical energy storage devices have gained significant interest due to their exceptional storage properties, where the electrode material is a crucial determinant of device performance. Hence, it is essential to develop 3-D hierarchical materials at low cost with precisely controlled porosity and composition to achieve high energy storage capabilities. After presenting the brief updates on porous carbons (PCs), then this review will focus on the nitrogen (N) doped porous carbon materials (NPC) for electrochemical supercapacitors as the NPCs play a vital role in supercapacitor applications in the field of energy storage. Therefore, this review highlights recent advances in NPCs, including developments in the synthesis of NPCs that have created new methods for controlling their morphology, composition, and pore structure, which can significantly enhance their electrochemical performance. The investigated N-doped materials a wide range of specific surface areas, ranging from 181.5 to 3709 m2 g-1 , signifies a substantial increase in the available electrochemically active surface area, which is crucial for efficient energy storage. Moreover, these materials display notable specific capacitance values, ranging from 58.7 to 754.4 F g-1 , highlighting their remarkable capability to effectively store electrical energy. The outstanding electrochemical performance of these materials is attributed to the synergy between heteroatoms, particularly N, and the carbon framework in N-doped porous carbons. This synergy brings about several beneficial effects including, enhanced pseudo-capacitance, improved electrical conductivity, and increased electrochemically active surface area. As a result, these materials emerge as promising candidates for high-performance supercapacitor electrodes. The challenges and outlook in NPCs for supercapacitor applications are also presented. Overall, this review will provide valuable insights for researchers in electrochemical energy storage and offers a basis for fabricating highly effective and feasible supercapacitor electrodes.

Synthesis of Electrical Conductive Metal-Organic Frameworks for Electrochemical Applications.

Electrical conductivity is very important property of nanomaterials for using wide range of applications especially energy applications. Metal-organic frameworks (MOFs) are notorious for their low electrical conductivity and less considered for usage in pristine forms. However, the advantages of high surface area, porosity and confined catalytic active sites motivated researchers to improve the conductivity of MOFs. Therefore, 2D electrical conductive MOFs (ECMOF) have been widely synthesized by developing the effective synthetic strategies. In this article, we have summarized the recent trends in developing the 2D ECMOFs, following the summary of potential applications in the various fields with future perspectives.

2D MXenes Nanosheets for Advanced Energy Conversion and Storage Devices: Recent Advances and Future Prospects.

Since the initial MXenes were discovered in 2011, several MXene compositions constructed using combinations of various transition metals have been developed. MXenes are ideal candidates for different applications in energy conversion and storage, because of their unique and interesting characteristics, which included good electrical conductivity, hydrophilicity, and simplicity of large-scale synthesis. Herein, we study the current developments in two-dimensional (2D) MXene nanosheets for energy storage and conversion technologies. First, we discuss the introduction to energy storage and conversion devices. Later, we emphasized on 2D MXenes and some specific properties of MXenes. Subsequently, research advances in MXene-based electrode materials for energy storage such as supercapacitors and rechargeable batteries is summarized. We provide the relevant energy storage processes, common challenges, and potential approaches to an acceptable solution for 2D MXene-based energy storage. In addition, recent advances for MXenes used in energy conversion devices like solar cells, fuel cells and catalysis is also summarized. Finally, the future prospective of growing MXene-based energy conversion and storage are highlighted.

Recent Advances of Transition Metal Dichalcogenides-Based Materials for Energy Storage Devices, in View of Monovalent to Divalent Ions.

The fast growth of electrochemical energy storage (EES) systems necessitates using innovative, high-performance electrode materials. Among the various EES devices, rechargeable batteries (RBs) with potential features like high energy density and extensive lifetime are well suited to meet rapidly increasing energy demands. Layered transition metal dichalcogenides (TMDs), typical two dimensional (2D) nanomaterial, are considered auspicious materials for RBs because of their layered structures and large specific surface areas (SSA) that benefit quick ion transportation. This review summarizes and highlights recent advances in TMDs with improved performance for various RBs. Through novel engineering and functionalization used for high-performance RBs, we briefly discuss the properties, characterizations, and electrochemistry phenomena of TMDs. We summarised that engineering with multiple techniques, like nanocomposites used for TMDs receives special attention. In conclusion, the recent issues and promising upcoming research openings for developing TMDs-based electrodes for RBs are discussed.

Chemistry Aspects and Designing Strategies of Flexible Materials for High-Performance Flexible Lithium-Ion Batteries.

In recent years, flexible and wearable electronics such as smart cards, smart fabrics, bio-sensors, soft robotics, and internet-linked electronics have impacted our lives. In order to meet the requirements of more flexible and adaptable paradigm shifts, wearable products may need to be seamlessly integrated. A great deal of effort has been made in the last two decades to develop flexible lithium-ion batteries (FLIBs). The selection of suitable flexible materials is important for the development of flexible electrolytes self-supported and supported electrodes. This review is focused on the critical discussion of the factors that evaluate the flexibility of the materials and their potential path toward achieving the FLIBs. Following this analysis, we present how to evaluate the flexibility of the battery materials and FLIBs. We describe the chemistry of carbon-based materials, covalent-organic frameworks (COFs), metal-organic frameworks (MOFs), and MXene-based materials and their flexible cell design that represented excellent electrochemical performances during bending. Furthermore, the application of state-of-the-art solid polymer and solid electrolytes to accelerate the development of FLIBs is introduced. Analyzing the contributions and developments of different countries has also been highlighted in the past decade. In addition, the prospects and potential of flexible materials and their engineering are also discussed, providing the roadmap for further developments in this fast-evolving field of FLIB research.

Valorization of Peanut Skin as Agricultural Waste Using Various Extraction Methods: A Review.

Peanuts (Arachis hypogea) can be made into various products, from oil to butter to roasted snack peanuts and candies, all from the kernels. However, the skin is usually thrown away, used as cheap animal feed, or as one of the ingredients in plant fertilizer due to its little value on the market. For the past ten years, studies have been conducted to determine the full extent of the skin's bioactive substance repertoire and its powerful antioxidant potential. Alternatively, researchers reported that peanut skin could be used and be profitable in a less-intensive extraction technique. Therefore, this review explores the conventional and green extraction of peanut oil, peanut production, peanut physicochemical characteristics, antioxidant activity, and the prospects of valorization of peanut skin. The significance of the valorization of peanut skin is that it contains high antioxidant capacity, catechin, epicatechin resveratrol, and procyanidins, which are also advantageous. It could be exploited in sustainable extraction, notably in the pharmaceutical industries.

Ribosome Incorporation Induces EMT-like Phenomenon with Cell Cycle Arrest in Human Breast Cancer Cell.

Although ribosomes are generally known to be a translational machinery, some ribosomal proteins also have accessory functions involving early development and differentiation. Previously, we reported that ribosome incorporation into human dermal fibroblasts generated embryoid body-like cell clusters, altered cellular fate, and differentiated into cells of all 3 germ layers. However, the molecular phenomena induced by ribosome incorporation in the cell remained unknown. Here, we demonstrate that ribosome incorporation into human breast cancer cell MCF7 leads to ribosome-induced cell clusters (RICs) formation accompanying with epithelial-mesenchymal transition (EMT)-like gene expression. Following ribosome incorporation, MCF7 cells cease proliferation, which is caused by inhibition of cell cycle transition from G0 to G1 phase. Further, MCF7 RICs show induced expression of EMT markers, TGF-ß1 and Snail along with autophagy markers and tumor suppressor gene p53. These findings indicate that the incorporation of ribosome into cancer cells induces an EMT-like phenomenon and changes the cancer cell characteristics.

Metal-Organic Frameworks Derived Electrocatalysts for Oxygen and Carbon Dioxide Reduction Reaction.

The increasing demands of energy and environmental concerns have motivated researchers to cultivate renewable energy resources for replacing conventional fossil fuels. The modern energy conversion and storage devices required high efficient and stable electrocatalysts to fulfil the market demands. In previous years, we are witness for considerable developments of scientific attention in Metal-organic Frameworks (MOFs) and their derived nanomaterials in electrocatalysis. In current review article, we have discussed the progress of optimistic strategies and approaches for the manufacturing of MOF-derived functional materials and their presentation as electrocatalysts for significant energy related reactions. MOFs functioning as a self-sacrificing template bid different benefits for the preparation of metal nanostructures, metal oxides and carbon-abundant materials promoting through the porous structure, organic functionalities, abundance of metal sites and large surface area. Thorough study for the recent advancement in the MOF-derived materials, metal-coordinated N-doped carbons with single-atom active sites are emerging candidates for future commercial applications. However, there are some tasks that should be addressed, to attain improved, appreciative and controlled structural parameters for catalytic and chemical behavior.

Retrospective analysis of direct antiglobulin test positivity at tertiary academic hospital over 10 years.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years. STUDY DESIGN AND METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed. RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively. CONCLUSION: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.

Health-related quality of life of Malaysian patients with chronic non-malignant pain and its associated factors: a cross-sectional study.

BACKGROUND: Chronic pain has a major impact on a patient's quality of life, affecting physical and psychological functioning. It has debilitating consequences on social and economic aspects too. This study aimed to explore the status of health-related quality of life (HRQoL) of Malaysian patients suffering from chronic non-malignant pain. METHODS: Four hospitals offering pain clinic services were involved in this multicentre cross-sectional study conducted between June and September 2020. Adult patients who had been diagnosed with non-malignant chronic pain lasting for at least three months and able to communicate in English or Malay language were recruited in this study. Participants were informed about the study and were made aware that their participation was entirely voluntary. A battery of questionnaires consists of the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and the EuroQol visual analogue scale (EQ VAS), the Pain Self-Efficacy questionnaire (PSEQ) and the Pain Catastrophizing Scale (PCS) were self-administered by the patients. Besides, a structured questionnaire was used to collect their socio-demographic information, pain condition, sleep quality and working status. Participants' usage of pain medications was quantified using the Quantitative Analgesic Questionnaire (QAQ). RESULTS: A total of 255 patients participated in this study. A median EQ-5D index value of 0.669 (IQR: 0.475, 0.799) and a median EQ VAS score of 60.0 (IQR: 50.0, 80.0) were recorded. Malay ethnicity (Adj. B: 0.77; 95% CI: 0.029, 0.126; p = 0.002) and a higher level of self-efficacy (Adj. B: 0.008; 95% CI: 0.006, 0.011; p < 0.001) were predictors of a better HRQoL, while suffering from pain in the back and lower limb region (Adj. B: -0.089; 95% CI: - 0.142, - 0.036; p = 0.001), the use of a larger amount of pain medications (Adj. B: -0.013; 95% CI: - 0.019, - 0.006; p < 0.001), and a higher degree of pain magnification (Adj. B: -0.015; 95% CI: - 0.023, - 0.008; p < 0.001) were associated with a poorer HRQoL. CONCLUSIONS: These findings suggested that Malay ethnicity and a higher level of self-efficacy were predictors of a better HRQoL in patients with chronic pain, whereas pain-related factors such as higher usage of medication, specific pain site and pain magnification style were predictors of poorer HRQoL.

HUWE1 promotes EGFR ubiquitination and degradation to protect against renal tubulointerstitial fibrosis.

Injury of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. HUWE1, an E3 ubiquitin ligase, acts by participating in ubiquitination and degradation of its target proteins. However, the detailed mechanisms by which HUWE1 might regulate fibrosis in renal tubular epithelial cells have not been established. Here, the possible regulation of renal tubulointerstitial fibrosis by HUWE1 was investigated by examining the expression of HUWE1 and EGFR in unilateral ureteral obstruction (UUO) mice. Markedly consistent reciprocal changes in HUWE1 and EGFR expression were observed at the protein and mRNA levels in the kidney after UUO injury. Expression of HUWE1 inhibited TGF-ß-induced injury to HK-2 cells, while HUWE1 overexpression decreased the expression of EGFR. Further analysis indicated that HUWE1 physically interacted with EGFR and promoted its ubiquitination and degradation. HUWE1 expression also showed clinical relevance in renal disease, as it notably decreased in multiple types of clinical nephropathy, while EGFR expression significantly increased when compared to the normal kidney. Therefore, this study demonstrated that HUWE1, which serves as an E3 ubiquitin ligase specific for EGFR, promotes EGFR ubiquitination and degradation, thereby regulating EGFR expression and providing protection against kidney injury.

Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas.

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

Tongue ulcer in a patient with COVID-19: a case presentation.

BACKGROUND: The emergence of COVID-19 has devastated many parts of the world. From asymptomatic to symptomatic, the virus causes a wide spectrum of presentations. COVID-19 patients may present with oral manifestations. In Afghanistan, where COVID-19 has severely strained the health care system, much of the population lacks proper oral hygiene. This makes the oral cavity a perfect site for SARS-CoV-2 to manifest clinical signs. CASE PRESENTATION: A 62-year-old male was evaluated in the Dentistry Teaching Clinic of Kabul University of Medical Sciences for a painful erosive lesion on dorsal surface of his tongue. He also complained of fever, cough, and taste alteration. He was referred to Afghan Japan Hospital for COVID-19 testing and tested positive. He was followed on for the treatment of SARS-CoV2. After 2 weeks, the patient tested negative and returned to the dentistry clinic for follow-up. Although there were no other signs of COVID-19, the painful erosive lesion on his tongue persisted. Oral evaluation were performed and the patient was advised to practice good hygiene. After 10 days, we observed an asymptomatic geographic tongue without fever and myalgias and the lesion of dorsal surface of tongue improved from severe condition to moderate. CONCLUSION: In conclusion, patients with suspected or confirmed SARS-CoV-2 should be screened for symptoms and physical findings in the oral mucosa To prevent such an outcome, awareness programs need to be implemented for the diagnosis and management of clinical symptoms among patients.

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells.

Secreted proteoglycan molecule Tsukushi (TSK) regulates various developmental processes, such as early body patterning and neural plate formation by interacting with major signaling pathways like Wnt, BMP, Notch etc. In central nervous system, TSK inhibits Wnt signaling to control chick retinal development. It also plays important roles for axon guidance and anterior commissure formation in mouse brain. In the present study, we investigated the role of TSK for the development and proper functioning of mouse hippocampus. We found that TSK expression is prominent at hippocampal regions of early postnatal mouse until postnatal day 15 and gradually declines at later stages. Hippocampal dimensions are affected in TSK knockout mice (TSK-KO) as shown by reduced size of hippocampus and dentate gyrus (DG). Interestingly, neural stem cell (NSC) density at the neural niche of DG was higher in TSK-KO compared with wild-type. The ratio of proliferating NSCs as well as the rate of overall cell proliferation was also higher in TSK-KO hippocampus. Our in vitro study also suggests an increased number of neural stem/progenitor cells residing in TSK-KO hippocampus. Finally, we found that the terminal differentiation of NSCs in TSK-KO was disturbed as the differentiation to neuronal cell lineage was increased while the percentages of astrocytes and oligodendrocytes were decreased. Overall, our study establishes the involvement of TSK in hippocampal development, NSC maintenance and terminal differentiation at perinatal stages.

Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain.

Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH-/- ), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH-/- . These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self-renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.

Synthesis and translation of research and innovations from polio eradication (STRIPE): initial findings from a global mixed methods study.

BACKGROUND: Lessons from polio eradication efforts and the Global Polio Eradication Initiative (GPEI) are useful for improving health service delivery and outcomes globally. The Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) is a multi-phase project which aims to map, package and disseminate knowledge from polio eradication initiatives as academic and training programs. This paper discusses initial findings from the knowledge mapping around polio eradication activities across a multi-country context. METHODS: The knowledge mapping phase (January 2018 - December 2019) encompassed four research activities (scoping review, survey, key informant interviews (KIIs), health system analyses). This paper utilized a sequential mixed method design combining data from the survey and KIIs. The survey included individuals involved in polio eradication between 1988 and 2019, and described the contexts, implementation strategies, intended and unintended outcomes of polio eradication activities across levels. KIIs were conducted among a nested sample in seven countries (Afghanistan, Bangladesh, the Democratic Republic of Congo, Ethiopia, India, Indonesia, Nigeria) and at the global level to further explore these domains. RESULTS: The survey generated 3955 unique responses, mainly sub-national actors representing experience in over 74 countries; 194 KIIs were conducted. External factors including social, political, and economic factors were the most frequently cited barriers to eradication, followed by the process of implementing activities, including program execution, planning, monitoring, and stakeholder engagement. Key informants described common strategies for addressing these barriers, e.g. generating political will, engaging communities, capacity-building in planning and measurement, and adapting delivery strategies. The polio program positively affected health systems by investing in system structures and governance, however, long-term effects have been mixed as some countries have struggled to institutionalize program assets. CONCLUSION: Understanding the implementing context is critical for identifying threats and opportunities to global health programs. Common implementation strategies emerged across countries; however, these strategies were only effective where organizational and individual capacity were sufficient, and where strategies were appropriately tailored to the sociopolitical context. To maximize gains, readiness assessments at different levels should predate future global health programs and initiatives should consider system integration earlier to ensure program institutionalization and minimize system distortions.

Electrochemiluminescent immunosensor for prostate specific antigen based upon luminol functionalized platinum nanoparticles loaded on graphene.

A novel label-free electrochemiluminescent (ECL) immunosensor based upon luminol functionalized platinum nanoparticles loaded on graphene sheets (Lu-Pt@GS) as sensing platform was fabricated for highly sensitive and selective determination of prostate specific antigen (PSA). In this work, for the first time luminol was employed as both ECL luminescence reagent and reductants to in-situ reduce H2PtCl6 forming Pt NPs on surface of GS. A great deal of luminol could be attached onto the surface of Pt NPs within the reduction process, which can generate strong ECL emission. Pt NPs not only could enhance ECL signals of luminol but supply active sites for the immobilization of PSA antibodies with micro friendly environment. For preventing the consecutive reaction among luminol and H2O2, single-step cycle pulse was adopted, resulting in stable and strong ECL signals. Under optimized experimental conditions, the proposed ECL immunosensor acquired a wide linear range of 1 pg/mL to 10 ng/mL with a relatively low detection limit of 0.3 pg/mL for PSA. Furthermore, due to high sensitivity, simplicity and cost-effectiveness, the designed immunosensor provides a new method for detecting other important biomarkers in clinical analysis.