T Helper Cells Fate Mapping by Co-stimulatory Molecules and its Functions in Allograft Rejection and Tolerance

T cell differentiation is dictated by a combination of T cell receptor (TCR) interaction with an antigen-bound major histocompatibility complex (MHC), and co-stimulatory molecules signal. The co-stimulatory signal can be positive or negative, and amplifying or diminishing the initial signal. However, the secondary co-stimulatory signal is not obligatory and its necessity is dictated, in part, by the stage of T cell development. In the field of transplantation, directing the T cell differentiation process can lead to therapeutic possibilities that promote allograft tolerance, and hinder unfavorable alloimmune responses. Therefore, understanding the details of T cell differentiation process, including the influence of co-stimulatory signals, is of paramount importance. It is important to note there is functional overlap between co-stimulatory molecules. It has been observed that some co-stimulatory signals have different effects on different T cell subsets. Hence, blockade of a co-stimulatory signal pathway, as part of a therapeutic regimen in transplantation, may have far reaching effects beyond the initial therapeutic intent and inhibit co-stimulatory signals necessary for desirable regulatory responses. In this review, co-stimulatory molecules involved in the differentiation of naïve T cells into T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), inducible regulatory T cells (iTregs), and T helper 9 (Th9) cells and their overlap are discussed

Polymeric Triboelectric Nanogenerator: Effects Of Polymer Type, Geometry, And Porosity On Triboelectrification

Triboelectric nanogenerator (TENGs), based on the principles of triboelectrification and electrostatic induction, have recently been viewed as a promising approach to harvest mechanical energy, which would otherwise be wasted through dissipation to surrounding. Large contact area and large surface area have been identified as the basic design principles to promote the performances of TENGs. In this study, particulate leaching method was used to introduce and tailor the open-cell morphology of negative triboelectric layers in TENGs. The effects of material type, material geometry, open-cell morphology on the level of triboelectrification induced by mechanical motions were also investigated. Experimental results revealed that polyvinylidene fluoride (PVDF) performed better than high density polyethylene (HDPE) as the negative triboelectric layer of the TENG. Furthermore, increasing the contact area, reducing the thickness, and introducing fine pores would enhance the performances of TENGs

Evaluation of Run-Off Supply Projects in Hamadan Province (Iran)

ABSTRACT: Water resources project is for the control or use of water. Where utilization is proposed, the first question is usually how much water is needed .This is probably the most difficult of all the design problems to answer accurately because it involves social and economic aspect as well as engineering. In order to meet the various demands and of water requirements in Hamadan province which is situated in west of Iran, more than 28 projects were defined and studied, but only few of them were adopted. This paper presents a criteria based on the ratio of reservoir capacity to volume of earthen dam named as feasibility factor (F) for exact evaluation of different alternatives to assure the designer, so that, to obtain sufficient quantity of water in a form which can be easily and cheaply made fit for various uses

Growth and reproductive characteristics of Squalius Lepidus Heckel 1843 in the Dimeh spring of Zayandeh-Rud River

Population structure, growth, and reproductive characteristics of Kavar, Squalius lepidus, a native species of Cyprinidae family in Zayandeh-Rud River were investigated by monthly sampling from October 2006 to August 2007. A total of 415 individuals were collected. Age groups of males and females ranged between 1+ and 4+ . The male:female sex ratio was 1:3. The largest female was 163.0mm in fork length and 63.71g in weight; whereas the largest male was 156.0mm in fork length and 50.45g in weight. The minimum, maximum, and mean absolute fecundity was 1161, 12953, and 4279±2169, respectively, and relative fecundity was 148.4±49.3 eggs/g of body weight. Gonadostomatic Index (GSI) values suggested that spawning of Squalius lepidus occurs from May to June. Thus, Squalius lepidus is considered an intermittent spawner species. Growth parameters for both sexes were stated by the vonBertalanffy growth function as k = 0.162, L = 232mm, to = -0.427 years for females and k = 0.136, L =217mm, to =- 0.847 years for males. The weight-length relationship was described as W = 0.00005L 2.827 (r2= 0.860) for males and W = 0.00005 L2.855 (r2 = 0.859) for females. The slope of the regression line (b) fitted through the weight-length data suggested a negative allometric growth for both females and male (P<0.05)

Environmental damage of different waste treatment scenarios by considering avoided emissions based on system dynamics modeling

This study aims to develop a comprehensive model for life cycle assessment and environmental damage cost calculations considering avoided emissions in different waste management scenarios using the system dynamics (SD) approach. Our analysis reveals that under the business-as-usual (BAU) scenario for the period 2020–2050, the total net greenhouse gas (GHG) emissions reach 12.5 Mt, with the highest environmental damage cost being USD 689 million. In contrast, an integrated management strategy encompassing recycling, composting, anaerobic digestion, and incineration results in a 195% reduction in net GHG emissions compared to the BAU Scenario. Concurrently, the environmental damage cost drops to USD 277 million, incorporating USD 347 million in savings, leading to a net environmental damage cost of USD −71 million. The findings affirm that accounting for emissions avoided across various treatment methods offers a more accurate estimate of environmental damage costs. Additionally, policies centered on integrated waste management are more likely to achieve sustainability. The study also demonstrates the utility of the SD approach in providing a holistic view of waste management systems and in evaluating the effectiveness of various policy strategies for sustainable waste management

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNβ-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNβ-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells

Nitrogen effect on zinc biofortification of maize and cowpea in Zimbabwean smallholder farms

Agronomic biofortification of crops with zinc (Zn) can be enhanced under increased nitrogen (N) supply. Here, the effects of N fertilizer on grain Zn concentration of maize (Zea mays L.) and cowpea (Vigna unguiculata L.) were determined at two contrasting sites in Zimbabwe over two seasons. All treatments received soil and foliar zinc‐sulphate fertilizer. Seven N treatments, with three N rates (0, 45, and 90 kg ha−1 for maize; 0, 15, and 30 kg ha−1 for cowpea), two N forms (mineral and organic), and combinations thereof were used for each crop in a randomized complete block design (n = 4). Maize grain Zn concentrations increased from 27.2 to 39.3 mg kg−1 across sites. At 45 kg N ha−1, mineral N fertilizer increased maize grain Zn concentration more than organic N from cattle manure or a combination of mineral and organic N fertilizers. At 90 kg N ha−1, the three N fertilizer application strategies had similar effects on maize grain Zn concentration. Co‐application of N and Zn fertilizer was more effective at increasing Zn concentration in maize grain than Zn fertilizer alone. Increases in cowpea grain Zn concentration were less consistent, although grain Zn concentration increased from 39.8 to 52.7 mg kg−1 under optimal co‐applications of N and Zn. Future cost/benefit analyses of agronomic biofortification need to include information on benefits of agro‐fortified grain, complex farmer management decisions (including cost and access to both N and Zn fertilizers), as well as understanding of the spatial and site‐specific variation in fertilizer responses

Elucidating the source–sink relationships of zinc biofortification in wheat grains: a review

Zinc (Zn) concentration in wheat grains is generally low, with an average value of around 28–30 mg/kg. Therefore, increasing wheat grain Zn concentration for better human health is the focus of HarvestPlus global initiatives. Source–sink interactions have been intensively studied for decades to enhance crop yield potential, but less on grain nutritional quality. This review applies concepts of source, sink, and their interactions to the study of wheat grain Zn nutrition and biofortification. Increasing Zn sources to wheat (via soil and foliar application) could directly enlarge available Zn in vegetative tissues and grain Zn sink. Rational nitrogen (N) supply increases grain Zn accumulation (N‐Zn synergism), but phosphorus (P) input generally decreases (P‐Zn antagonism), and the potassium (K) effect is unclear. Conventional and genetic breeding have potential to stimulate Zn flow from source to sink (uptake from soil, root‐to‐shoot translocation, and remobilization). However, a rational manipulation to establish a well‐coordinated source–sink relationship is required to finally realize the grain Zn target (40–50 mg/kg) and increase on‐farm crop yield. Future studies should focus more on fertilization modes adopted by farmers (uses of compound, slow/controlled release, and organic and microbial fertilizers) and develop integrated agronomic and genetic strategies for Zn biofortification. A highly systematic and mechanistic model includes (a) migration paths of Zn (particularly from leaves to different grain parts) using isotopic labeling methods, (b) cross‐talks between Zn and carbon, N, P, K, or other divalent cations, (c) inherent physiological and biochemical processes of enzymes and signaling phytohormones, and (d) complex genetic systems governing Zn homeostasis and their relationships with other nutrients, signaling molecules, and increase or dilution/penalty of yield under different environmental conditions (soil, water, and future climatic changes) and managements (breeding and fertilization). These aspects require further elucidation to fully unravel the “black box” of Zn flow from source to sink

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI