Covalent organic framework based microspheres as an anode material for rechargeable sodium batteries

Covalent organic frameworks (COFs) promise several benefits as materials in terms of gas adsorption, for use in optoelectronic devices, etc. However, the energy storage ability of COFs has not been well studied, especially in sodium batteries. In this report, for the first time, a covalent organic framework (COF), TFPB-TAPT COF, is used as an anode with high capacity in sodium batteries. The TFPB-TAPT COF exhibits an initial reversible capacity of 246 mA h g−1 and a capacity of 125 mA h g−1 is retained after 500 cycles. The TFPB-TAPT COF further exhibits Na+ ion storage capability at different current rates. The Na+ ion storage viability of the TFPB-TAPT COF arises mainly because of its open ordered nanoporous framework, which provides reversible accommodation for ions. This work opens up a promising new approach for further utilization of COFs as electrode materials in rechargeable sodium batteries

A Combined Transcriptomics and Lipidomics Analysis of Subcutaneous, Epididymal and Mesenteric Adipose Tissue Reveals Marked Functional Differences

Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and α-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and α-linolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis

Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas

Glioblastomas are among the most incurable cancers. Our past findings indicated that glioblastoma cells, but not neurons or glia, require the transcription factor ATF5 (activating transcription factor 5) for survival. However, it was unknown whether interference with ATF5 function can prevent or promote regression/eradication of malignant gliomas in vivo. To address this issue, we created a mouse model by crossing a human glial fibrillary acidic protein (GFAP) promoter-tetracycline transactivator mouse line with tetracycline operon-dominant negative-ATF5 (d/n-ATF5) mice to establish bi-transgenic mice. In this model, d/n-ATF5 expression is controlled by doxycycline and the promoter for GFAP, a marker for stem/progenitor cells as well as gliomas. Endogenous gliomas were produced with high efficiency by retroviral delivery of platelet-derived growth factor (PDGF)-B and p53-short hairpin RNA (shRNA) in adult bi-transgenic mice in which expression of d/n-ATF5 was spatially and temporally regulated. Induction of d/n-ATF5 before delivery of PDGF-B/p53-shRNA virus greatly reduced the proportion of mice that formed tumors. Moreover, d/n-ATF5 induction after tumor formation led to regression/eradication of detectable gliomas without evident damage to normal brain cells in all 24 mice assessed

Cancer stem cell metabolism: A potential target for cancer therapy

© 2016 The Author(s). Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells. This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy

Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3

Background: Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available. Methods: We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated. Findings: Since the development and implementation of the SDGs in 2015, global health spending has increased, reaching$7·9 trillion (95% uncertainty interval 7·8–8·0) in 2017 and is expected to increase to $11·0 trillion (10·7–11·2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was$20·2 billion (17·0–25·0) and on tuberculosis it was $10·9 billion (10·3–11·8), and in malaria-endemic countries spending on malaria was$5·1 billion (4·9–5·4). Development assistance for health was $40·6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019,$374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81·6% (81·6–81·7) in 2015 to 83·1% (82·8–83·3) in 2030. Interpretation: Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed. Funding: The Bill & Melinda Gates Foundatio

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019.

BACKGROUND: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. METHODS: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). FINDINGS: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1-38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78-0·91) per female living with HIV in 2019, 0·99 male infections (0·91-1·10) for every female infection, and 1·02 male deaths (0·95-1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58-35·43, and a 39·66% decrease in deaths, 36·49-42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05-0·06) and the global incidence-to-mortality ratio was 1·94 (1·76-2·12). No regions met suggested thresholds for progress. INTERPRETATION: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. FUNDING: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Fracture behavior of laser-clad joint of Stellite 21 on AISI 316L stainless steel

Present paper paper describes microstructural and mechanical characterization of laser-clad composite joint made of Stellite 21 and type 316L stainless steel (SS). The study has been broadly performed on two kinds of laser-clad specimens viz. (i) involving direct deposition of Stellite 21 on SS and (ii) involving gradient in chemical composition across substrate/clad interface. Both kinds of specimens exhibited nearly similar tensile strength, which was higher than that of SS in the interface region. Inter-dendritic carbides provided low energy fracture path in laser-clad deposits of Stellite 21. Both direct and graded interfaces of laser-clad specimens exhibited superior fatigue strength than the SS substrate. Instrumented impact testing brought out distinct difference in the mode of crack propagation across direct and the graded clad specimens. In contrast to initiation-controlled brittle crack propagation across the interface region in "direct clad" specimens, crack propagation across "graded interface" was marked with significant plastic deformation. (C) 201

The novel-molecule T11TS facilitated arousal of glioma-mediated dormancy of bone-marrow hematopoietic stem-cells

Aim: T11TS, a potent anti-gliomagenic glycoprotein, stimulates both peripheral and intracranial immune response. The status of bone marrow hematopoietic stem cells (BMHSCs), the cradle of regeneration of all blood cells, during gliomagenic global immune devastations has not yet been investigated. Therefore, we aimed to delineate the effects of T11TS on immature and mature compartments of hematopoietic machinery.Methods: Flowcytometric analysis of cultured BMHSCs was evaluated for assesing the expression pattern of early hematopoietic stem cells (HSCs) markers such as CD34+, Sca-1+, c-kit+ and also Angiopoietin-1 and Tie-2 both in normal, glioma, and in T11TS treated glioma-bearing animals. Immunofluresenece imaging and western blot analyses of BMHSCs were also carried out.Results: There was significant downregulation of HSCs-markers CD34+, Sca-1+, c-kit+ in ethyl nitrosourea-induced glioma-bearing animals followed by an increase in the expression level of Ang-1 and Tie-2 that determines the quiescence and self-renewability of stem cells. T11TS administration reversed the gliomagenic transformation of expression of the above mentioned markers. The results flowcytometric-analysis was also well corroborated with immunofluorescence imaging and western blot analysis.Conclusion: Collectively, the above experimental evidence hints towards gliomagenic maneuver of receptor expression of HSCs to derange the systemic immunity and T11TS mediated manipulation towards revival/rejuvenation of the same

Organic piezoelectric materials: milestones and potential

Research on the piezoelectric response of biomolecules has intensified following demonstration of open circuit voltages of over 20 V in biopiezoelectric generators. Organic piezoelectric nanotubes, fibers, and micro-islands have been grown and studied; however, the lack of fundamental understanding of the piezoelectric effect in nature hinders the rational design of biomaterials to provide a tailor-made piezoelectric response. Advances in high performance computing have facilitated the use of quantum mechanical calculations to predict the full piezoelectric tensor of biomolecular crystals, including amino acids and small peptides. By identifying directions of high piezoelectric response, the simulations can guide experimental crystal growth, device fabrication and electrical testing, which have led to the demonstration of unprecedented piezoelectric responses in organic crystals on the order of 200 pC/N. These large responses arise from strong supramolecular dipoles, which can be tuned by molecular chemistry and packing, opening new opportunities for the realization of technologically useful piezoelectric devices from renewable materials. The amino acids predicted to exhibit the highest piezoelectric response, such as glycine, hydroxyproline and lysine, are anticipated to be used to engineer highly piezoelectric peptides in the future. With improved scaling of advanced computational methods, such as density functional perturbation theory, the research community can begin to efficiently screen peptide structures for enhanced electromechanical properties. This capability will accelerate the experimental development of devices and provide much-needed insight into the evolution of a hierarchical relation in biological materials starting from strongly piezoelectric building blocks.</p