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Enterococcus faecalis is a newly emerged fish pathogen affecting many cultured fish species. The present work aimed to determine the cause of mortalities affecting the cultured Meagre farm and study the infectious agent virulence, disease pathology. Also, to determine the influence of infection on complement 3, cyclooxygenase, and lysozyme gene expression and concentrations in fish serum. The internal organs of diseased fish were severely congested with the presence of petechial haemorrhages on the liver, gonads, and all over the elementary tract. Thirty-one bacterial isolates were recovered from naturally infected fish; seventeen were identified biochemically as E. faecalis. Random E. faecalis isolate was verified for pathogenicity in meager fingerlings and was indeed pathogenic with lethal dose-fifty (LD50) estimated by 4.6 × 106 colony forming unit (CFU) fish−1. The posterior kidney and hepatopancreas of experimentally infected fish showed severe inflammation, necrosis, degeneration, and haemorrhage. Detachment of mucosa lining the stomach and intestine (intestinal villi and gastric glands) was prominent. The examined gastric tissues exhibited inflammation, leucocytic infiltration, and congestion. The expression of C3, Cox2, and Lyz was upregulated 24-h post-infection and then decreased near the baseline at 96 h. Serum C 3 and Lyz concentrations peaked at 24 h and 48 h after that decreased. IgM level gradually increased with time and peaked at 96 h. In conclusion, E. faecalis is assumed pathogenic for cultured meager, experimental infection stimulated immune systems and upregulated the expression of some immune-related genes. [ABSTRACT FROM AUTHOR]

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment. [ABSTRACT FROM AUTHOR]

Crop yields must drastically increase to meet the demands of a rapidly increasing global population. One current option being investigated is the augmentation of photosynthetic capacity by incorporating the C4 photosynthetic pathway into C3 crops such as rice to significantly increase production. Crops with improved photosynthetic mechanisms would make better use of the solar radiation that can be converted into yield. This will help to boost grain yield, reduce water loss, and increase nitrogen use efficiency, particularly in hot and dry conditions. Identifying and manipulating the genes required to install C4 photosynthesis in rice is a big challenge. However, the international C4 rice collaboration, is formed to test the possibility of incorporating the C4 mechanism into rice. This article summarizes the parameters that must be changed in rice in order for the C4 pathway to be successfully introduced. It also examines the biochemistry, physiology, molecular biology, and synthetic biology approaches between the C3 and C4 photosynthetic processes. [ABSTRACT FROM AUTHOR]

Purpose: The Indian pharmaceutical industry currently faces multiple challenges, including rising costs and slowing export growth, which in turn have limited its ability to expand presence in global canvas. Given the nature of sectoral dynamics, a pharmaceutical firm must undertake huge investments in R&D to introduce product innovation, in turn enhancing market share and sustaining profit streams. The development of novel medicines, confirmed by the granting of patent rights, provides a pharma company edge over its competitors. In addition, presence of innovator firms within the industry invigorates the sectoral value chain and raises efficiency. Hence, it is important to analyze whether granting patent rights enhances the exports of pharmaceutical products in the Indian context. Design/methodology/approach: The current study explored this question using a simultaneous-equation framework. Specifically, the authors use the methods developed by Davidson and MacKinnon (1993) and Greene (2003) to obtain heteroscedasticity-consistent estimates. The time-series properties of the data were further probed, and robust estimates were used to test the theory. Methods developed by Baltagi (1981) have been used further to refine the authors' estimations. Findings: After controlling for relevant variables, it is observed that granting of patents caused a significantly positive impact on pharmaceutical exports. Furthermore, the change in the patent administration regime had a significant impact on patent fillings, which further impacted their exportability. Compared to patents granted patents filed had a higher impact on pharmaceutical exports. Originality/value: This study attempts to apply the framework developed by Goldstein and Khan (1978) with necessary modifications to suit the context of a developing country. The application of the 3SLS method to estimate the export supply equation for pharmaceutical products is a novel approach to the research question in general and to the Indian context in particular. System autocorrelation and heteroscedasticity tests were performed to refine the results further. [ABSTRACT FROM AUTHOR]

Introduction: The role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN. Methods: Renal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. Results: During a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively). Conclusion: Complement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage. [ABSTRACT FROM AUTHOR]

Summary: In this essay we explore the structure of two new Christian movements that emerged as a result of a blending of Evangelicalism and Pentecostalism. These movements are ICF and C3, which we study in their German as well as European context. We triangulate theoretical concepts, our own empirical research and existing research on these movements. Referring to the theoretical framework of refiguration, we discuss the potential of the concepts 'eventisation', 'movement' and 'scenefication' from the sociology of religion as frameworks for understanding these typical movements. Our analysis of social form leads to reflections on the adaptability of concepts from confessional studies, such as confessional markers and congregationalism, in relation to the non-denominational self-description of these so-called lifestyle churches. In our conclusion, we explore implications and perspectives of the organisational shift caused by these emerging movements. [ABSTRACT FROM AUTHOR]

Purpose: Laminoplasty (LP) combined with C3 laminectomy (LN) can effectively achieve spinal cord decompression while maintaining the integrity of the posterior ligament-muscle complex, thereby minimizing cervical muscle damage. However, its necessity and safety remain controversial. This study aimed to compare the safety and efficacy of LP and LP combined with C3 LN in the treatment of patients with multilevel degenerative cervical spondylotic myelopathy (DCM). Methods: A systematic review and meta-analysis of the literature was performed. A search of PubMed, Web of Science, Embase, and the Cochrane Library databases was conducted from inception through December 2023 and updated in February 2024. Search terms included laminoplasty, laminectomy, C3 and degenerative cervical spondylosis. The literature search yielded 14 studies that met our inclusion criteria. Outcomes included radiographic results, neck pain, neurologic function, surgical parameters, and postoperative complications. We also assessed methodologic quality, publication bias, and quality of evidence. Results: Fourteen studies were identified, including 590 patients who underwent LP combined with C3 LN (modified group, MG) compared to 669 patients who underwent LP (traditional group, TG). The results of the study indicated a statistically significant improvement in cervical range of motion (WMD = 3.62, 95% CI: 0.39 to 6.85) and cervical sagittal angle (WMD = 2.07, 95% CI: 0.40 to 3.74) in the MG compared to the TG at the last follow-up (very low-level evidence). The TG had a higher number of patients with complications, especially C2-3 bone fusion. There was no significant difference found in improvement of neck pain, JOA, NDI, cSVA, T1 slope at latest follow-up. Conclusion: LP combined with C3 LN is an effective and necessary surgical method for multilevel DCM patients to maintain cervical sagittal balance. However, due to the low quality of evidence in existing studies, more and higher quality research on the technology is needed in the future. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) remains a significant public health concern, and prediction is an important objective, particularly in the early stages of pregnancy. Many studies have relied on cervical characteristics in the mid-trimester, with limited results. It is therefore crucial to identify novel biomarkers to enhance the ability to identify women at risk. The complement pathway is implicated in the process of placentation, and recent proteomics studies have highlighted the potential roles of some complement proteins in the pathophysiology of PTB. To determine the association between the occurrence of spontaneous preterm birth (sPTB) and the concentration of complement C3, factor B, and factor H in the blood of pregnant women during the first trimester. This prospective cohort study included women with singleton pregnancies, both with and without a history of sPTB, from two health institutions in Bucaramanga, Colombia. The outcome was sPTB before 37 weeks. A blood sample was obtained between 11 + 0 to 13 + 6 weeks. ELISA immunoassay was performed to quantify the levels of C3, factor B, and factor H. A total of 355 patients were analyzed, with a rate of sPTB of 7.6% (27/355). The median plasma concentration for C3, factor B, and factor H were 488.3 μg/mL, 352.6 μg/mL, and 413.2 μg/mL, respectively. The median concentration of factor H was found to be significantly lower in patients who delivered preterm compared to patients who delivered at term (382 μg/mL vs. 415 μg/mL; p = 0.034). This study identified a significant association between low first-trimester levels of factor H and sPTB before 37 weeks. These results provide relevant information about a new possible early biomarker for sPTB. However, the results must be confirmed in different settings, and the predictive value must be examined [ABSTRACT FROM AUTHOR]

Abstract Introduction The role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN. Methods Renal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. Results During a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P

Background:The autoimmune disease systemic lupus erythematosus (SLE) can cause multisystemic tissue damage because of the interaction between the autoantibodies and self-antigens. The complement system has a role in the development of the disease activity after its activation by the immune complexes. In addition to the impairment in the function of T and B cells. Objectives:The current study aimed to determine some hematological and immunological factors that could be indicated to disease activity. Materials and Methods:In this cross-sectional study, venous blood from 54 SLE patients, who were referred to Medical City, Baghdad Teaching Hospital, and 46 healthy subjects were withdrawn from January 2022 to July 2022. The levels of blood parameters such as erythrocyte sedimentation rate (ESR), white blood cells (WBC), and Hb were measured for the patients and controls. The levels of anti-dsDNA antibodies, C3, C4, IL-6, and IL-17a, were determined for patients and controls by enzyme-linked immunosorbent assay technique. Clinical diagnosis was made for all SLE patients according to the standards approved by the American College of Rheumatology, and the disease activity was determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Information such as age, history of diagnosis of the disease, and family history were collected by using a questionnaire provided for this study. Results:The age range shows a high rate of SLE disease in the age group 25–34, 24 (44.44%). The inactive group of patients was the largest among all patient’s groups (28 [51.85%]). ESR rate and WBCs count were significantly higher in patients. Anti-dsDNA antibodies were significantly high, with an average of 4.84 U/mL in patients compared to healthy controls. C3 and C4 showed an obvious reduction in the sera of patients (111.57, 0.278, respectively) compared to healthy people (126.08, 0.0489, respectively). Anti-dsDNA antibodies appeared with high significant levels in the active group of patients compared to other groups. For cytokines results, IL-6 was significantly high in patients (70.62 ng/l), and the levels of IL-6 and IL-17a were differentiated significantly with disease activity. Conclusions:CD3, C4, and dsDNA could be the most efficient indicators for disease diagnosis. However, dsDNA, IL-6, and IL-17a are the best to indicate disease activity.

In this article, we propose a new approach to estimating health-care demand. The aim of this paper is to determine the production costs of health care from the demand function of care. To do this, we used an approach based on structural equations where consumption and demand are estimated to capture the dynamics of health costs within a self-managed public hospital. Following this approach, based on the equilibrium between supply and demand of health care, we used the social and professional characteristics of beneficiary to estimate the demand function, which will approximate the cost of health care. The results showed that the demand for care is largely dependent on economic, demographic, and perception factors. Also, the back testing and corroboration tests of the predictions affirm that the functions developed will allow a better cost forecast for the hospital unit, able to propose a budgetary and partial cost approach in the future. Some limitations can be mentioned in connection with the accessibility to accounting data and also the ignorance of time dimension or dynamic evolution of cost demand.

Xiang Li,1 Mengtian Pan,1 Xinjuan Tian,1 Lele Zixin Yang,2 Jingjing Zhang,1 Dongmei Yan,3 Baohui Xu,4 Li Zhao,1 Weirong Fang1 1Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2The Pennsylvania State University, Eberly College of Science, State College, PA, USA; 3Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Surgery, Stanford University School of Medicine, Stanford, CA, USACorrespondence: Li Zhao; Weirong Fang, Email zhaoli@cpu.edu.cn; weirongfang@cpu.edu.cnBackground: Tripartite motif containing 59 (TRIM59) is a ubiquitin ligase and is involved in the pathogenesis of various diseases, including cancers, sepsis, and other immune-related diseases. However, it has not been defined whether TRIM59 plays a role in ischemic stroke in mice.Methods: This study determined the influence of Trim59 deficiency on experimental stroke outcomes and the cerebral proteomic profile using myeloid cell Trim59 conditional knockout (Trim59-cKO) mice and a label-free quantitative proteomic profiling technique. The possible mechanisms by which TRIM59 affected stroke onset were elucidated by in vivo and in vitro experiments.Results: Immunofluorescence staining results showed that TRIM59 expression was up-regulated after cerebral ischemia and co-localized with macrophages. Myeloid cell Trim59 deficiency exacerbated ischemic injury on day 3 after experimental stroke. In proteomic analysis, 23 differentially expressed proteins were identified in ischemic brain of Trim59-cKO mice as compared to Trim59flox/flox mice. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed proteins were enriched in complement and coagulation cascades. Protein–protein interaction analysis suggested the central role of clusterin in the interaction network. ELISA and Western blot assays confirmed the reduced levels of clusterin protein in the ischemic brains of Trim59-cKO mice. Further experimental results showed that clusterin was expressed in neurons. Conditional co-culture experiments of primary neurons and bone marrow-derived macrophages demonstrated that LPS stimulated macrophages to secrete complement C3. In addition, TRIM59 may affect the changes in clusterin expression in an indirect manner by influencing the secretion of complement C3 in macrophages. In vivo experiments also proved a significant increase in C3 levels in the brains of Trim59-cKO mice after ischemia.Conclusion: Myeloid cell Trim59 deficiency aggravated ischemic stroke outcomes in conjunction with a distinct cerebral proteomic profile, and the underlying mechanism may be related to the regulation of macrophage C3 expression by TRIM59.Keywords: Trim59, ischemic stroke, proteomic profile, complement and coagulation cascades, C3

Abstract IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients.

Emerging evidence indicates that activation of complement system leading to the formation of the membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1. C3−/−; 2. C7−/−; and 3. Cd59ab−/−) to evaluate the role of complement in severe COVID-19 pathogenesis. C3 deficient mice lack a key common component of all three complement activation pathways and are unable to generate C3 and C5 convertases. C7 deficient mice lack a complement protein needed for MAC formation. Cd59ab deficient mice lack an important inhibitor of MAC formation. We also used anti-C5 antibody to block and evaluate the therapeutic potential of inhibiting MAC formation. We demonstrate that inhibition of complement activation (in C3−/−) and MAC formation (in C3−/−. C7−/−, and anti-C5 antibody) attenuates severe COVID-19; whereas enhancement of MAC formation (Cd59ab−/−) accelerates severe COVID-19. The degree of MAC but not C3 deposits in the lungs of C3−/−, C7−/− mice, and Cd59ab−/− mice as compared to their control mice is associated with the attenuation or acceleration of SARS-CoV-2-induced disease. Further, the lack of terminal complement activation for the formation of MAC in C7 deficient mice protects endothelial dysfunction, which is associated with the attenuation of diseases and pathologic changes. Our results demonstrated the causative effect of MAC in severe COVID-19 and indicate a potential avenue for modulating the complement system and MAC formation in the treatment of severe COVID-19. [ABSTRACT FROM AUTHOR]

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc. [ABSTRACT FROM AUTHOR]

The ability to differentiate species is not adequate for modern forage breeding programs. The measurement of persistence is currently a bottleneck in the breeding system that limits the throughput of cultivars to the marketplace and prevents it from being selected as a trait. The use of hyperspectral data obtained through remote sensing offers the potential to reduce guesswork by identifying the distribution of pasture species, but only if such data alone can distinguish the subtle differences within species, i.e., cultivars. The implementation of this technology faces many challenges due to the spectral and temporal variability of species. To understand the spectral variability between and within species groups, differentiation using hyperspectral data from monoculture plots of turf species was utilized. Spectral data were collected over a year using an ASD FieldSpec® and canopy pasture probe (CAPP). The plots consisted of monocultures of various species, and cultivars (a total of 10 plots). Linear discriminant analysis (LDA) was conducted on the full spectrum and reduced band data. This technique successfully differentiated the species with high accuracy (>98%). We demonstrate the potential of hyperspectral data and analysis techniques to accurately separate differences down to cultivar level. We also show that diurnal variation is measurable in the spectra but does not preclude differentiation. [ABSTRACT FROM AUTHOR]

Most of the aquatic vegetation produces organic substances via the C3 photosynthetic pathway (mosses, isoetids—Lobelia dortmanna L., Luronium natans (L.) Raf., and vascular plants) or Crassulacean acid metabolism (CAM, e.g., Littorella uniflora (L.) Asch. and Isoëtes lacustris L.) or by their ability to use HCO3− via carbon concentration mechanisms (CCMs—some elodeids and charophytes). Differentiating these predominant photosynthetic pathways in aquatic vegetation based on their organic matter (OM) carbon stable isotopes (δ13CORG) is a complex task, in contrast to terrestrial plants. This study investigates the OM deposition, characterized by δ13CORG values in 10 macrophyte species with different photosynthetic pathways (C3, CAM, and CCM) collected from 14 softwater Lobelia lakes in northern Poland. The higher δ13CORG values distinguish the CCM group, indicating their use of 13C-enriched HCO3¯ in photosynthesis. CAM species show slightly higher δ13CORG values than C3, particularly in lower pH lakes. Principal component analysis of isotopic and environmental data did not yield clear distinctions by the groups, but still, they significantly differ in light of analyzed parameters and isotopic signals (PRMANOVA = 5.08, p < 0.01; K-W H = 27.01, p < 0.001). The first two PCA dimensions showed that the water pH and Ca2+ concentration positively influenced δ13C values. The influence of light conditions on δ13CORG values revealed by third PCA components seems to also be important. In summary, northern Polish Lobelia lakes serve as a key differentiation point between vegetation employing CCMs and those relying on C3/CAM photosynthesis without HCO3− utilization, providing insights into transitions in plant communities within these ecosystems. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Objective: The primary objective was to evaluate the impact of the upper instrumented level (UIV) being at C2 vs C3 in posterior cervical construct on patient reported outcomes (PROs) up to 24 months after surgery for cervical degenerative myelopathy (DCM). Secondary objectives were to compare operative time, intra-operative blood loss (IOBL), length of stay (LOS), adverse events (AEs) and re-operation. Methods: Patients who underwent a posterior cervical instrumented fusion (3 and + levels) with a C2 or C3 UIV, with 24 months follow-up were analyzed. PROs (NDI, EQ5D, SF-12 PCS/MCS, NRS arm/neck pain) were compared using ANCOVA. Operative duration, IOBL, AEs, and re-operation were compared. Subgroup analysis was performed on patient presenting with pre-operative malalignment (cervical sagittal vertical axis ≥40 mm and/or T1slope- cervical lordosis >15°). Results: 173 patients were included, of which 41 (24%) had a C2 UIV and 132 (76%) a C3 UIV. There was no statistically significant difference between the groups for the changes in PROs up to 24 months. Subgroup analysis of patients with pre-operative malalignment showed a trend towards greater improvement in the NDI at 12 months with a C2 UIV (P =.054). Operative time, IOBL and peri-operative AEs were more in C2 group (P <.05). There was no significant difference in LOS and re-operation (P >.05). Conclusion: In this observational study, up to 24 months after surgery for posterior cervical fusion in DCM greater than 3 levels, PROs appear to evolve similarly. [ABSTRACT FROM AUTHOR]

This study asked whether the P2X7 receptor was necessary and sufficient to trigger astrocyte polarization into neuroinflammatory activation states. Intravitreal injection of agonist BzATP increased gene expression of pan-astrocyte activation markers Gfap, Steap4, and Vim and A1-type astrocyte activation markers C3, Serping1, and H2T23, but also the Cd14 and Ptx3 genes usually associated with the A2-type astrocyte activation state and Tnfa, IL1a, and C1qa, assumed to be upstream of astrocyte activation in microglia. Correlation analysis of gene expression suggested the P2X7 receptor induced a mixed A1/A2-astrocyte activation state, although A1-state genes like C3 increased the most. A similar pattern of mixed glial activation genes occurred one day after intraocular pressure (IOP) was elevated in wild-type mice, but not in P2X7-/- mice, suggesting the P2X7 receptor is necessary for the glial activation that accompanies IOP elevation. In summary, this study suggests stimulation of the P2X7R is necessary and sufficient to trigger the astrocyte activation in the retina following IOP elevation, with a rise in markers for pan-, A1-, and A2-type astrocyte activation. The P2X7 receptor is expressed on microglia, optic nerve head astrocytes, and retinal ganglion cells (RGCs) in the retina, and can be stimulated by the mechanosensitive release of ATP that accompanies IOP elevation. Whether the P2X7 receptor connects this mechanosensitive ATP release to microglial and astrocyte polarization in glaucoma remains to be determined. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis and potentially life-threatening complications. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021. A recent expansion to its indication by the EMA has made pegcetacoplan available for the treatment of both complement inhibitor-naïve and -experienced patients with PNH who have hemolytic anemia, a similarly broad patient population as in the US. This approval was based on results from the Phase 3 PEGASUS study, where pegcetacoplan showed superiority over the C5 inhibitor eculizumab with regard to improving the hemoglobin level in patients with anemia despite eculizumab treatment, and the Phase 3 PRINCE study, where pegcetacoplan showed superiority over supportive care with regard to hemoglobin stabilization and improving the lactate dehydrogenase level in complement inhibitor-naïve patients. In light of this recent indication expansion by the EMA, this article describes how the strong efficacy of pegcetacoplan is linked to its mechanism of action, which provides broad hemolysis control over both intravascular and extravascular hemolysis to improve a range of disease markers and enhance patients' quality of life. Furthermore, additional data and learnings obtained from over 3 years of experience with pegcetacoplan are summarized, including long-term efficacy and safety results, real-world clinical experiences, pharmacokinetic characteristics, and extensive practical guidance for the first-to-market proximal complement inhibitor for PNH. [ABSTRACT FROM AUTHOR]

IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients. [ABSTRACT FROM AUTHOR]

To explore the regulatory effect of human epididymis protein 4 (HE4) on renal fibrosis in mice with lupus nephritis (LN) and the underlying mechanism. Ten-week old MRL/LPR mice were injected with HE4 shRNA adenovirus vector through the renal pelvis for 5 days. Renal tissues were extracted for HE and Masson staining to evaluate pathological changes and fibrosis in lupus nephritis mice. The level of urine protein was measured using a biochemical analyzer, while the expression level of HE4 and p-NF-κB p65 in renal tissues was visualized using an immunofluorescence assay. The level of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (Kim-1) was determined by the immunohistochemical assay. Western blotting was used to determine the levels of C3, HE4, matrix metalloproteinase-2 (MMP2), MMP9, p-p65, prss23, and prss35 in renal tissues. Compared to wild-type C57BL/6 mice, MRL/LPR mice showed a marked increase in the number of glomeruli, hyperplasic basement membrane, severe infiltration of inflammatory cells in renal tubules and glomeruli, obvious necrosis in glomeruli, elevated fibrosis levels, and increased levels of urine protein, β2-MG, NGAL, Kim-1, C3, HE4, MMP2, MMP9, and p-p65; and decreased levels of prss23 and prss35 were observed in MRL/LPR mice. After the administration of the HE4 shRNA adenovirus vector, the repaired structure of renal tubules and glomeruli improved infiltration of inflammatory cells, reduced collagen fiber and urine protein, suppressed levels of C3, HE4, MMP2, MMP9, and p-P65, and facilitated the expression of prss23 and prss35 which were observed. Silencing HE4 improved renal fibrosis and inhibited inflammation in mice with lupus nephritis, which may play a role in inhibiting C3/MMPs and promoting prss-related protein expression. [ABSTRACT FROM AUTHOR]

We estimate unsmoothed private equity net asset values (NAVs) at weekly frequency for individual funds. Using simulations and large samples of buyout and venture funds, we show that our method yields superior estimates of NAVs relative to simple approaches based on extrapolation of reported NAVs. The market beta of an average buyout (venture) fund is around 1.0 (1.4), and the total risk is 33 |$\%$| (40 |$\%$|⁠) per year. The risk-return profile of the funds varies significantly over time and across funds. Risk-taking and reporting quality appear to persist by manager. Authors have furnished an Internet Appendix , which is available on the Oxford University Press Web site next to the link to the final published paper online. [ABSTRACT FROM AUTHOR]

Econometrics is a branch of economics that uses mathematical and statistical methods to study quantitative and qualitative relationships within economic phenomena. The purpose of this article is to study the impact of the capital market (financial instruments) on economic growth in Kazakhstan and the CIS countries through an understanding of the concept of “econometrics”. The task of the study is to determine the dependence of gross domestic product as a resultant factor over the past 20 years. Methods. The article determines the assessment of the impact of financial factors on economic growth in the short term. An econometric model was used for this purpose. The resulting factor was the gross domestic product over the past 20 years. Results. The results indicate that the capital market influences economic growth in Kazakhstan and the CIS countries. This paper presents a model of the GDP function for the economy of Kazakhstan. In the course of the study, coefficients and variables of the model were estimated to predict the level and future changes in the country’s GDP. Thus, the size of the capital market (Y1) depends on the following variables tested in the model: the number of securities issuance transactions; the volume of securities issuance transactions; the number of transactions of non-residents with shares at the secondary auction of KASE; the rate of change of shares of leading issuers on KASE

This paper investigates the dynamics of market synchronicity and International Financial Reporting Standards (IFRS) adoption in Africa. It seeks to determine whether or not IFRS is an augmentor or inhibitor of market synchronicity in Africa. This study is not only a foundational study that unfolds the dynamics of market synchronicity and IFRS adoption in Africa but also extends the scope of synchronicity from firm-level assessment to country-level market synchronicity. It is one of the few studies which have shifted the literature on synchronicity from one largely limited to firm-level synchronicity to country-level synchronicity through analyses of cross-border market synchronisation. It employs Dynamic Ordinary Least Square (DOLS) and Generalised Method of Moments (GMM) to investigate the market synchronicity-IFRS nexus. The study uses monthly data from March 2005 to November 2021 in five African markets: Botswana, Ghana, Namibia, Nigeria, and South Africa generating 1005 observations in an 18-year data span. The paper reveals a significant negative consequence of IFRS on market synchronicity. Thus, IFRS exhibits an inhibition role in market synchronicity (reduces synchronicity) and improves price informativeness. A decreasing pattern was also observed immediately after IFRS was adopted by the stock markets and persisted for about five years. It implies that the price informativeness of stock markets through IFRS makes them good candidates for intra-Africa portfolio diversification due to reduced investors’ risk exposure to market synchronicity.

Background and Purpose: To deepen our knowledge of the role of complement in synaptic impairment in experimental autoimmune encephalomyelitis (EAE) mice, we investigated the distribution of C1q and C3 proteins and the role of complement as a promoter of glutamate release in purified nerve endings (synaptosomes) and astrocytic processes (gliosomes) isolated from the cortex of EAE mice at the acute stage of the disease (21 ± 1 day post‐immunization). Experimental Approach: EAE cortical synaptosomes and gliosomes were analysed for glutamate release efficiency (measured as release of preloaded [3H]D‐aspartate ([3H]D‐ASP)), C1q and C3 protein density, and for viability and ongoing apoptosis. Key Results: In healthy mice, complement releases [3H]D‐ASP from gliosomes more efficiently than from synaptosomes. The releasing activity occurs in a dilution‐dependent manner and involves the reversal of the excitatory amino acid transporters (EAATs). In EAE mice, the complement‐induced releasing activity is significantly reduced in cortical synaptosomes but amplified in cortical gliosomes. These adaptations are paralleled by decreased density of the EAAT2 protein in synaptosomes and increased EAAT1 staining in gliosomes. Concomitantly, PSD95, GFAP, and CD11b, but not SNAP25, proteins are overexpressed in the cortex of the EAE mice. Similarly, C1q and C3 protein immunostaining is increased in EAE cortical synaptosomes and gliosomes, although signs of ongoing apoptosis or altered viability are not detectable. Conclusion and Implications: Our results unveil a new noncanonical role of complement in the CNS of EAE mice relevant to disease progression and central synaptopathy that suggests new therapeutic targets for the management of MS. [ABSTRACT FROM AUTHOR]

This study contributes to the literature by investigating the intervening role of information and communication technology (ICT) diffusion on insurance and economic growth in Sub-Saharan Africa (SSA). This study uses the generalized method of moments technique based on 36 countries, spanning 2007–2020. First, the empirical findings reveal that insurance penetration (i.e. total, life and nonlife) and ICT diffusion induce economic growth in SSA. Second, the evidence suggests that ICT boosts the role of insurance in affecting economic growth. Third, the individual ICT variables such as fixed broadband, telephone and internet propel the impact of total and life penetration on growth. Additionally, fixed broadband was remarkable in enhancing the effect of nonlife penetration on growth. The findings imply that though insurance enhances economic growth, its impact is more revealing through the intervening role of ICT infrastructure. Therefore, insurers must embrace technology and leverage ICT development to improve their performance on growth. [ABSTRACT FROM AUTHOR]

Transgenic Arabidopsis thaliana (ecotype Columbia) was successfully transformed with the gene fructose-1,6-bisphosphatase (FBPase) and named as AtFBPase plants. Transgenic plants exhibited stable transformation, integration and significantly higher expressions for the transformed gene. Morphological evaluation of transgenic plants showed increased plant height (35 cm), number of leaves 25), chlorophyll contents (28%), water use efficiency (increased from 1.5 to 2.6 µmol CO2 µmol-1 H2O) and stomatal conductance (20%), which all resulted in an enhanced photosynthetic rate 2.7 µmol m-2 s-1) compared to wild type plants. This study suggests the vital role of FBPase gene in the modification of regulatory pathways to enhance the photosynthetic rate, which can also be utilised for economic crops in future. [ABSTRACT FROM AUTHOR]

With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the effects of peers on corporate payout policies in one of the largest emerging markets – India. It also examines the motives for mimicking payout decisions. Design/methodology/approach: The sample is composed of 3,024 non-financial and non-government firms listed on the National Stock Exchange (NSE) and Bombay Stock Exchange (BSE) for the period 1995 to 2020. To encounter the endogeneity problem, the instrumental variable technique based on peer firms' idiosyncratic risk is used to estimate the effects of peers on firms' payout policy. To define peer reference groups, the authors use the basic industry classification of the firms. Findings: The results indicate a significant positive impact of peers on firms' dividend policies in India. A firm with all dividend-paying peers is more likely to declare dividends than the one with no dividend-paying peers. Further, peer effects are found to be more pronounced amongst larger and older firms, thus supporting the rivalry theory of mimicking. Originality/value: To the best of the authors' knowledge, the present study is the first of its kind that attempts to understand peer effects on payout decisions in an emerging market India, that offers a unique institutional setting. Moreover, the authors extend the existing literature by investigating the peer effects on a firm's payout policies considering various firm-level characteristics, such as growth opportunity, cash holding, financial constraint and profitability, which previous studies have not taken into consideration. These results provide additional insights into the heterogeneity and motives behind peer effects. [ABSTRACT FROM AUTHOR]

Reviewing old protocols, it was found that Raji, a CR2-posistive cell line, binds both endogenous (e-C3) and exogenous C3 (i-C3). The processing of i-C3 to an i-C3b-like protein and their fixation to CR2 isoforms resulted in the formation of heterodimers whose units might be linked via thioester by low m.w. molecule(s). In an attempt to study the origin of the low m.w. molecules, it was found that they were detected following I12⁵-C3d treatment with NHS or hi-S. Indirect evidence would suggest that the products of C3 fragment fixation could have a short half-life and that the aromatic residues present in C3d might have different physico-chemical characteristics than those present in C3c. The surface hydrophobicity expressed by these aromatic residues could be required for the fixation of C3 or CR2 fragments to cell surface proteins.

Abstract Background Chronic inflammation is a factor in the pathogenesis of sarcopenia, which is characterized by low muscle mass and reduced strength. Complement C3 is important in the management of the immune network system. This study seeks to determine the relationship between serum C3 levels and body composition and sarcopenia-related status in community-dwelling older adults. Methods Study participants were 269 older adults living in rural Japan. A bioelectrical impedance analysis device was used to measure body composition parameters including body mass index (BMI), body fat percentage, waist-hip-ratio, and appendicular skeletal muscle mass index (SMI). Muscle function was measured by handgrip strength and 6-m walking speed. The correlation coefficients for C3 level and measurements were calculated using Pearson correlation analysis. Participants were categorized into normal, pre-sarcopenia, dynapenia, or sarcopenia groups. Sarcopenia was defined according to 2019 Asian Working Group for Sarcopenia definition, dynapenia was defined as low muscle function without low muscle mass, and pre-sarcopenia was defined as the presence of low muscle mass only. The C3 threshold score for sarcopenia status was evaluated by receiver operating characteristic curve (ROC) analysis. Results Significant positive correlations were found between C3 and BMI, body fat percentage, and waist-hip ratio in both sexes, and further positive correlations with SMI were found in women. The relationship with body fat percentage was particularly strong. Body composition measurements (BMI, body fat percentage, and waist- hip ratio) and C3 levels were lowest in the sarcopenia group compared with the others. ROC analysis showed that the significant threshold of C3 for discriminating between the normal and sarcopenia groups was 105 mg/dL. Multiple logistic regression analysis showed that participants with C3

OBJECTIVE: Both humoral and cellular immunity can be significantly influenced by the immunological responses to vaccination, and both responses are essential. Vaccination is the most consistent, safe, and cost-efficient practice for controlling the COVID-19 pandemic. PATIENTS AND METHODS: Blood samples were collected from participants who received two vaccine doses of COVID-19 Pfizer/BioNTech (BNT162b2) before and on days 7 and 10 after the first and second immunization. We evaluated some hematological and immunological markers responses to the 1st and 2nd doses of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine. RESULTS: In healthy subjects' neutrophil and WBC counts significantly increased compared to those after the first dose. The results of all first-group participant categories demonstrated no discernible variations in lymphocyte counts. There was no change in IgM or IgG in all second- group cohorts, except for a considerable rise in IgG levels in people with a history of coronavirus infection following the second dosage compared to baseline. After the second dose, CD4+ T-cell and CD8+ T-cell levels rose in all groups compared to before the immunization and after the first dosage. Data demonstrated a sub-stantial rise in neutrophil-lymphocyte ratio (NLR) after the second dose of the vaccine. Individuals who had previously had COVID-19 disease experienced a considerable increase in C3 and C4 levels after the first and second dosages compared to baseline. Additionally, compared to their levels after the first dosage, C4 levels increased significantly following the second dosage. Interleukin (IL)-6, IL-15, macrophage colony-stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10/CXCL10), and macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) levels were increased after boost correlated with Spike antibody levels, supporting their utility as indicators of successful humoral immunity development in response to vaccination. CONCLUSIONS: We can conclude that the Pfizer/BioNTech vaccine produced a more potent T-cell response than humoral ones. [ABSTRACT FROM AUTHOR]

The Calvin-Benson cycle (CBC) evolved over 2 billion years ago but has been subject to massive selection due to falling atmospheric carbon dioxide, rising atmospheric oxygen and changing nutrient and water availability. In addition, large groups of organisms have evolved carbon-concentrating mechanisms (CCMs) that operate upstream of the CBC. Most previous studies of CBC diversity focused on Rubisco kinetics and regulation. Quantitative metabolite profiling provides a top-down strategy to uncover inter-species diversity in CBC operation. CBC profiles were recently published for twenty species including terrestrial C 3 species, terrestrial C 4 species that operate a biochemical CCM, and cyanobacteria and green algae that operate different types of biophysical CCM. Distinctive profiles were found for species with different modes of photosynthesis, revealing that evolution of the various CCMs was accompanied by co-evolution of the CBC. Diversity was also found between species that share the same mode of photosynthesis, reflecting lineage-dependent diversity of the CBC. Connectivity analysis uncovers constraints due to pathway and thermodynamic topology, and reveals that cross-species diversity in the CBC is driven by changes in the balance between regulated enzymes and in the balance between the CBC and the light reactions or end-product synthesis. • Calvin-Benson cycle metabolites were profiled in 20 species. • Calvin-Benson cycle has co-evolved with CO 2 -concentrating mechanisms. • Substantial diversity between species with the same photosynthesis mode. [ABSTRACT FROM AUTHOR]

Les glomérulopathies à C3 sont des pathologies chroniques rares dont le diagnostic repose sur la présence de dépôts glomérulaires prédominants de C3. Elles représentent moins de 5 % des glomérulopathies primitives. Ce sont des néphropathies sévères touchant le plus souvent l'enfant et l'adulte jeune qui, au diagnostic, présentent un syndrome glomérulaire mais près de 50 % développent une insuffisance rénale terminale après dix ans d'évolution. Ces pathologies sont secondaires à une dérégulation de la C3 convertase alterne (C3bBb) aboutissant à une activité excessive de cette enzyme qui clive le C3. Les patients présentent fréquemment une baisse du C3 plasmatique et une augmentation du C5b-9 soluble. Cette dérégulation est majoritairement liée à la présence d'auto-anticorps dirigés contre la C3 convertase alterne : le C3 nephritic factor (C3NeF), ou d'anticorps anti-C3b, anti-facteur B, anti-C5 convertase (C5NeF) ou dirigés contre la protéine de régulation, le facteur H. Les anomalies génétiques sont rares et surtout identifiées dans les formes familiales. Le traitement n'est pas spécifique de la GC3. Il vise à contrôler l'inflammation glomérulaire et à éliminer les autoanticorps. L'éculizumab, qui bloque la cascade au niveau de C5, a montré un effet anti-inflammatoire histologique mais une efficacité clinique variable. Des essais cliniques de phase I/II, utilisant des inhibiteurs à différents niveaux de la cascade, représentent un espoir pour le traitement des GC3. C3 glomerulopathies are rare and chronic diseases which diagnostic is based on the presence of exclusive or predominant glomerular deposition of C3.They count for less than 5% of primitive glomerulopathies.They are severe and affect mainly children and young adults. The patients present with a glomerular syndrome at diagnosis but 30 to 50 % of them develop end stage renal disease after 10 years of evolution. C3 glomerulopathies occur secondarily to a dysregulated alternative C3 convertase leading to an excessive C3 cleavage. Thus, main of the patients exhibit low plasma levels of C3 with high soluble C5b9 in some of them. This dysregulation is mainly due to the presence of autoantibodies called C3 nephritic factor (C3NeF) and targeting the C3 convertase inducing an increase of its half life. Other autoantibodies target the components C3b and Factor B, the C5 convertase (C5 Nef) or the regulatory protein Factor H. Genetic abnormalities are rare and mainly found in familial forms. The treatment aims to decrease the glomerular inflammation and the production of the autoantibodies. Eculizumab which blocks the complement cascade at the level of C5 has shown good efficacy on the histological inflammatory lesions but heterogeneous effects at the clinical level. Multiple complement inhibitory drugs are currently tested in phase I/II and represent new hope for the C3G treatment. [ABSTRACT FROM AUTHOR]

This article is the first to study a nexus between financialization and circularity performance in the European region. To reflect the circularity performance, we use six different measures, including the amount of municipal waste, the number of circularity patents, the amount of circular material used, the rate of recycling waste, the rate of recycling biowaste, and the rate of recycling e-waste. By using various econometric techniques (namely a panel-corrected standard errors [PCSE] model, a feasible generalized least square estimates [FGLS] model, and the two-step General Method of Moment [the two-step GMM), our study indicates that financialization is an enabler for circularity. However, these results are only statistically significant for the financial institution's development, while the financial market has a positive yet insignificant impact on circularity performance. The development of the financial institution is reported to increase municipal waste and the amount of recycling biowaste and e-waste, thus promoting the path toward the circular economy. To shed light on the financialization-circularity nexus, we use the different dimensions of financialization dynamics and report heterogeneous influences on the different issues of circularity performance. Furthermore, the results from the dynamic fixed effects (DFE) in the autoregressive distributed lag (ARDL) method suggest that the impact of financial development only becomes apparent in the long term. [ABSTRACT FROM AUTHOR]

One of the hallmarks of type 1 but also type 2 diabetes is pancreatic islet inflammation, associated with altered pancreatic islet function and structure, if unresolved. IL-1ß is a proinflammatory cytokine which detrimentally affects ß-cell function. In the course of diabetes, complement components, including the central complement protein C3, are deregulated. Previously, we reported high C3 expression in human pancreatic islets, with upregulation after IL-1ß treatment. In the current investigation, using primary human and rodent material and CRISPR/Cas9 gene-edited ß-cells deficient in C3, or producing only cytosolic C3 from a noncanonical in-frame start codon, we report a protective effect of C3 against IL-1ß-induced ß-cell death, that is attributed to the cytosolic fraction of C3. Further investigation revealed that intracellular C3 alleviates IL-1ß-induced ß-cell death, by interaction with and inhibition of Fyn-related kinase (FRK), which is involved in the response of ß-cells to cytokines. Furthermore, these data were supported by increased ß-cell death in vivo in a ß-cell-specific C3 knockout mouse. Our data indicate that a functional, cytoprotective association exists between FRK and cytosolic C3. [ABSTRACT FROM AUTHOR]

This study aims to examine the existence of asymmetry and nonlinearity in the influence of global crude oil price shocks on the pricing of oil products in India during the period spanning from April 2000 to March 2022. Novel symmetry and linearity tests, notably slope and impulse response tests, were used for this purpose. The findings of the slope test indicate the absence of nonlinearity in the reaction of most oil product prices to global crude oil price shocks. In contrast, the results obtained from the impulse response test indicate that except for liquid petroleum gas, all oil product prices exhibit asymmetric responses to both positive and negative crude oil shocks of varying magnitudes. The results align with previous research on the transmission of crude oil prices to oil product prices. Furthermore, these findings confirm the existence of the rockets-and-feathers phenomenon within the Indian oil product market. From a policy perspective, the findings indicate that it would be prudent for the government to contemplate the implementation of tax reductions on oil products. This approach would aid in ensuring a symmetric response of oil product pricing to global changes in crude oil prices and is projected to decrease the welfare loss incurred by consumers as a result of asymmetry. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a prevalent cause of vision impairment, affecting millions worldwide. This chronic condition encompasses two main forms: non-exudative (dry) AMD and exudative (wet) AMD. Dry AMD, characterized by the accumulation of drusen and alterations in the retinal pigment epithelium, can evolve into geographic atrophy (GA), culminating in irreversible vision impairment. Despite its considerable impact, therapeutic options for GA were historically constrained until recent advancements emerged. This comprehensive review underscores the pivotal role of the complement system in the pathogenesis of GA. Recent breakthroughs in AMD management have introduced innovative therapeutic modalities targeting complement factors, notably pegcetacoplan and avacincaptad pegol, both of which have garnered FDA approval. These agents have exhibited efficacy in decelerating the growth of GA lesions, offering a promising avenue for GA treatment. Additionally, we delve into past and ongoing clinical trials investigating supplementary complement inhibitors, including IONIS-FB-LRx, NGM621, ANX007, danicopan and AVD-104, highlighting their potential to shape future research endeavours and treatment paradigms. Challenges such as dosing frequency, the risk of neovascular conversion, and interindividual variability in treatment response underscore the imperative for ongoing research and the refinement of therapeutic strategies. While further investigations are warranted to delineate optimal treatment regimens and address extant challenges, the development of complement inhibitors represent a promising stride toward preserving vision and enhancing outcomes for individuals afflicted by this debilitating condition. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated how the associations between tau and cognitive measures differ by sex in the preclinical Alzheimer's disease (AD) stage. METHODS: A total of 343 cognitively unimpaired, amyloid‐positive individuals (205 women, 138 men) who self‐identified as non‐Hispanic White from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study were included. We assessed sex‐stratified associations between 18F‐flortaucipir positron emission tomography (PET) standardized uptake value ratio (SUVR) in the meta‐temporal region and Preclinical Alzheimer's Cognitive Composite (PACC) and Computerized Cognitive Composite (C3) components. RESULTS: We observed that higher tau level was significantly associated with worse cognitive performance only in women: PACC and its components except for Mini‐Mental State Examination (MMSE) and C3 components: First Letter Name Recall (FNLT) and One‐Card Learning Reaction Time (OCL RT). These associations except for FNLT were apolipoprotein E (APOE) ε4 independent. DISCUSSION: Women show stronger associations between tau PET and cognitive outcomes in preclinical AD. These findings have important implications for sex‐specific tau‐targeted preventive AD clinical trials. Highlights: The tau positron emission tomography (PET) signal in the meta‐temporal region was associated with poor cognitive performance in preclinical Alzheimer's disease (AD).After sex stratification, the associations between regional tau PET and cognitive outcomes were observed only in women.The associations between tau PET and some cognitive outcomes were independent of apolipoprotein E (APOE) ε4. [ABSTRACT FROM AUTHOR]

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African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but becomes covalently deposited onto the surfaces of pathogens after proteolytic cleavage to C3b. Membrane-associated C3b triggers different complement-mediated effectors which promote pathogen clearance. To counter complement-mediated clearance, African trypanosomes have a cell surface receptor, ISG65, which binds to C3b and which decreases the rate of trypanosome clearance in an infection model. However, the mechanism by which ISG65 reduces C3b function has not been determined. We reveal through cryogenic electron microscopy that ISG65 has two distinct binding sites for C3b, only one of which is available in C3 and C3d. We show that ISG65 does not block the formation of C3b or the function of the C3 convertase which catalyses the surface deposition of C3b. However, we show that ISG65 forms a specific conjugate with C3b, perhaps acting as a decoy. ISG65 also occludes the binding sites for complement receptors 2 and 3, which may disrupt recruitment of immune cells, including B cells, phagocytes, and granulocytes. This suggests that ISG65 protects trypanosomes by combining multiple approaches to dampen the complement cascade.