Component C3 Research Articles

Histologic and Clinical Outcomes of Patients Developing Post-Liver Transplant Plasma Cell-Rich Rejection.

Plasma cell-rich rejection (PCCR), also known as "plasma cell hepatitis" or "de novo autoimmune hepatitis," is a cause of allograft dysfunction occurring post-liver transplantation (LT). Patients often develop allograft failure and may require repeat LT. PCRR may fall within the spectrum of different histologies associated with antibody-mediated rejection (AMR), which is associated with donor-specific antibodies (DSAs) and positive complement component C4 (C4d) immunostaining. We sought to analyze the histologic and clinical outcomes of patients having biopsy-proven PCRR as well as to examine its C4d staining and DSA profiles. We identified patients having PCRR between 2000 and 2020 using the electronic pathology database at our institution. We included patients who underwent at least one follow-up liver biopsy after establishing the PCRR diagnosis to assess future histologic progression and outcomes. Mean fluorescence intensity for at least one single DSA of 2,000 or higher was considered positive. Histologic diagnosis of PCRR was independently made by an experienced liver pathologist. A total of 35 patients were included in the study. Hepatitis C virus was the most common etiology for LT (59.5%). Mean ± SD age at LT was 49.0 ± 12.7 years. Forty percent of patients developed PCRR within 2 years of LT. Most patients (68.5%) had negative outcomes, with progression from PCRR to cirrhosis or chronic ductopenic rejection (CDR). Patients who had hepatitis C virus were more likely to develop cirrhosis rather than CDR following the PCRR diagnosis (P = .01). Twenty-three (65.7%) patients had at least one prior episode of T-cell-mediated rejection before being diagnosed with PCRR. DSAs were positive in 16 of 19 patients assessed, and C4d immunostaining was positive in 9 of 10 patients. Development of PCRR negatively affects liver allograft outcomes and patient survival after LT. The presence of DSA and C4d in PCRR patients supports it to be within the histologic spectrum of AMR.

The use of the drug Elizaria – a biosimilar of the original eculizumab in atypical hemolytic-uremic syndrome due to mutation of the С3 gene in children: clinical observation and literature review

This article presents the features of atypical haemolytic-uremic syndrome (ORPHA 544472) in children. Atypical haemolytic-uremic syndrome (aHUS) is defined by a triad: haemolytic anaemia, thrombocytopenia and acute kidney injury in pediatric and adult patients. The OMIM catalogue presents the phenotypic series of aHUS with mutations of the C3, CFB, CFH, CFHR1, CFHR3, DGKE, MCP, THBD genes. Atypical haemolytic-uremic syndrome is often associated with gene mutations in proteins and activators that regulate complement. We report the case of a girl who had a manifestation of aHUS at 8 years 5 months of age and a severe relapse at 8 years 10 months of age. The relapse was characterised by manifestations of haemolytic anaemia, thrombocytopenia, acute renal damage, severe arterial hypertension, high lactate dehydrogenase and membrane attack complex levels and low C3 component. After 5 courses of haemodialysis, 3 haemodiafiltration, diuresis increased and biochemical parameters improved. We presented with ASUS in a child associated with a p.Cys1101Tyr C3 gene mutation. We used a complement inhibitor, Elizaria®, a biosimilar to the original drug eculizumab, to treat a child with atypical haemolytic-uremic syndrome due to the C3 gene mutation. The complement system inhibitor therapy with Elizaria preserved the health and life of a sick girl with a severe relapse of aHUS.

Urine proteome profile in primary podocytopathies

BACKGROUND. Primary focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN) are diseases with primary podocyte damage with high proteinuria and nephrotic syndrome. While the mechanisms in primary MN are well understood, the pathogenesis of primary FSGS is still unknown, and therefore, the search for biomarkers that could expand ourunderstanding of its pathogenetic mechanisms. THE AIM: to determine the urine proteomic profile of patients with primary podocytopathies – FSGS in comparison with MN. PATIENTS AND METHODS. The study included 48 patients with a morphologically confirmed diagnosis of CGN occurring with nephrotic syndrome – 32 men and 16 women. In 18 patients, a decrease in glomerular filtration rate < 60 ml/min/1.73 m2 was observed. The histological diagnosis was confirmed by biopsy: 31 patients had FSGS, 17 patients with MN were included as a comparison group. The study of the urinary proteome was carried out by high performance liquid chromatography/mass spectrometry. RESULTS. In patients with FSGS, compared with the MN group, an increased content of 22 different proteins was noted, the most abundant were apolipoprotein A-I, hemopexin, vitronectin, pigment epithelial growth factor, components of the complement system (C3, C4b, factors B and H), retinol – and vitamin D-binding proteins, alpha-2-HS-glycoprotein, histidine-rich glycoprotein, plasma C1 protease inhibitor. In MN, increased urinary excretion of the complement component C2, fibrinogen alpha chain, osteopontin, and the SH3 domain-binding glutamic acid-rich-like protein 3, was detected. CONCLUSION. The proteomic profile of urine in FSGS, compared to MN, reflects the activation of variety of pathological processes – podocyte damage, involvement of parietal epithelial cells, tubulo-interstitial damage, accumulation of extracellular matrix, and complement activation process.

Control of Mycobacterium avium subsp. paratuberculosis load within infected bovine monocyte-derived macrophages is associated with host genetics.

The genetic loci influencing individual resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are still largely unknown. In the current study, we searched for genetic loci associated with resistance to MAP infection by evaluating the performance of monocyte-derived macrophages (MDMs) isolated from the peripheral blood of 75 healthy Holsteins cows and infected ex vivo with MAP. Bacterial load (log colony-forming units, log CFUs) within MDMs was quantified at 2h and 7 days p. i. using a BACTEC MGIT 960 instrument. In addition, the expression levels of some genes with important roles in the innate immune response including epiregulin (EREG), complement component C3 (C3), galectin-9 (Gal9), and nitric oxide (NO-) were measured in the supernatant of the infected cells. DNA from peripheral blood samples of the animals included in the study was isolated and genotyped with the EuroG MD bead Chip (44,779 single nucleotide-polymorphisms, SNPs). Linear mixed models were used to calculate the heritability (h2 ) estimates for each indicator of MDM performance, MAP load within MDMs and EREG, C3, Gal9, and NO-expression. After performing a genome-wide association study, the only phenotypes that showed SNPs with a significant association were the bacterial load within MDMs at 2h (h2 = 0. 87) and 7 days (h2 = 0.83) p.i. A total of 6 SNPs, 5 candidate genes, and one microRNA on the Bos taurus chromosomes BTA2, BTA17, BTA18, and BTA21 were associated with MAP load at 2h p.i. Overlap was seen in two SNPs associated with the log CFUs at 2h and 7d p.i. The identified SNPs had negative regression coefficients, and were, therefore, associated with a low bacterial load within MDMs. Some of the identified SNPs were located within QTLs previously associated with longevity, reproductive, and udder health traits. Some of the identified candidate genes; Oxysterol Binding Protein Like 6, Cysteine and Serine Rich Nuclear Protein 3, and the Coiled-Coil Domain Containing 92 regulate cellular cholesterol trafficking and efflux, apoptosis, and interferon production, respectively. Taken together, our results define a heritable and distinct immunogenetic profile in MAP-infected macrophages designed to limit bacterial load early after infection.

Process water from hydrothermal carbonization: The impacts on the aquatic dissolved organic matter feature and microbial network at the soil-water interface

This study aimed to explore the effects of process water generated by hydrothermal carbonization (HTC-PW) at 180 °C and 260 °C on the soil-water environment. The input of HTC-PW changed the aquatic DOM components, such as the C1–C3 component decreased by 51.92–100%, and the C4 component increased by 81.40–100%. HTC-PW promoted the development of Proteobacteria and Firmicutes with relative abundance ratios of 1.75–2.31 and 1.4−3.25 times higher than CK, with a positive association revealed with the carbon conversion indicators. Furthermore, Proteobacteria play a critical role in bacterial networks exposed to high-temperature HTC-PW due to the facilitated nutrient exchange and metabolite. The prevalence of Ciliophora and Chlorophyta positively correlated with the nutrient compounds of HTC-PW. Moreover, the higher percentage of positive correlation in fungal networks was 75.26%, which implicated that microbial cooperation of fungi was more pronounced on an equal footing exposed to low-temperature HTC-PW. This study provides a theoretical basis for analyzing the potential ecological effects of HTC-PW in the soil-water environment associated with HTC applications, intending to provide parameters and guidance for the rational disposal of HTC-PW.

Characterizing the effects of stormwater runoff on dissolved organic matter in an urban river (Jiujiang, Jiangxi province, China) using spectral analysis.

The effect of stormwater runoff on dissolved organic matter (DOM) in rivers is one of the central topics in water environment research. Jiujiang is one of the first cities established in the green development demonstration zone of the Yangtze River Economic Belt (Jiangxi Province, China). Three-dimensional excitation-emission matrix fluorescence with parallel factor analysis (3DEEM-PARAFAC) and ultraviolet-visible (UV-Vis) spectroscopy were used to explore the effects of runoff on organic matter in Shili River (Jiujiang, Jiangxi Province, China). The results show that the runoff led to an increase of some critical pollutants and DOM concentrations, especially in the middle reaches of the river. The concentration and relative molecular weight of DOM in water increased as a result of runoff. Three humic-like (C1-C3) and two protein-like (C4 and C5) components of DOM were identified using the PARAFAC model. The sources of the three humic-like components (C1, C2, C3) were consistent, unlike those of the protein-like component C4. Compared with the pre-rainfall period, the content of humus compounds flowing into the river through the early rainwater runoff was lower, which caused the relative content and proportion of humic substances little change and protein-like species increasing. The DOM mainly derived from autochthonous sources, and runoff had limited effect on its characteristics. Jiujiang is a key demonstration city for Yangtze River conservation. Rainwater runoff is one of the pollution sources of urban rivers, which leads to the deterioration of water quality and influences the distribution characteristics of DOM in water bodies. The PARAFAC components could adequately represent different indicators and sources of DOM in urban rivers, providing an important reference for urban river management.

L-ficolin-MASP arm of the complement system in schizophrenia

The abnormal neurodevelopment secondary to in utero adversities, such as hypoxia, malnutrition and maternal infections, underlies schizophrenia (SZ) etiology. As the genes of MBL-associated serine proteases (MASP) of the complement lectin pathway, MASP1 and MASP2, are expressed in the developing cortex and are functionally important for neuronal migration, we hypothesize that the malfunction ofl-ficolin-MASP arm may also be involved in schizophrenia pathophysiology as it was shown for MBL-MASP complexes. We investigated serum l-ficolin and plasma MASP-2 levels, the activity of l-ficolin-bound MASP-2, as well as an array of the complement-related variables in chronic schizophrenic patients in the acute phase of the disease and controls without physical or mental diagnoses.The median concentration of l-ficolin in Armenian controls was 3.66 μg/ml and similar to those reported for other Caucasian populations. SZ-cases had ∼40 % increase in serum l-ficolin (median 5.08 μg/ml; P < 0.0024). In the pooled sample, l-ficolin level was higher in males than in females (P < 0.0031), but this gender dichotomy was not affecting the variable association with schizophrenia (P < 0.016). Remarkably, MASP-2 plasma concentration showed gender-dependent significant variability in the group of patients but not in controls. When adjusted for gender and gender*diagnosis interaction, a significantly high MASP-2 level in female patients versus female controls was observed (median: 362 ng/ml versus 260 ng/ml, respectively; P < 0.0020). A significant increase in l-ficolin-bound MASP-2 activity was also observed in schizophrenia (on the median, cases vs controls: 7.60 vs 6.50 RU; P < 0.021). Correlation analyses of the levels of l-ficolin and MASP-2, l-ficolin-(MASP-2) activity and the demographic data did not show any significant association with the age of individuals, family history, age at onset and duration of the illness, and smoking. Noteworthy, the levels of l-ficolin and MASP-2 in circulation were significantly associated with the type of schizophrenia (paranoid SZ-cases had much higher l-ficolin (P < 0.0035) and lower MASP-2 levels than the other types combined (P < 0.049)). Correlations were also found between: (i) the classical pathway functional activity and l-ficolin level (rs = 0.19, P < 0.010); (ii) the alternative pathway functional activity and MASP-2 level (rs = 0.26, P < 0.00035); (iii) the activity of l-ficolin-bound MASP2 and the downstream C2 component haemolytic activity (rs = −0.19, P < 0.017); and (iv) l-ficolin and the upstream C-reactive protein (CRP) serum concentrations (r = 0.28, P < 0.018).Overall, the results showed l-ficolin-related lectin pathway alterations in schizophrenia pathophysiology. It is likely that in addition to the MBL-MASP component over-activity reported previously, the alterations of the lectin pathway in schizophrenia also involve variations of l-ficolin-(MASP-2) on protein concentration and activity levels.

Targeted O-glycoproteomics for the development of diagnostic markers for advanced colorectal cancer.

Aberrant glycosylation is a prominent feature of cancer, that can be used as targets to improve the existing cancer biomarkers, and help to assess metastasis risks, and therapeutic effects. We developed a targeted O-glycoproteomics method using serum specimens, and evaluated its utility in identifying advanced colorectal cancer (CRC) markers. To this end, we combined consecutive lectin affinity purification using Maclura pomifera lectin (MPL), jacalin, and Sambucus nigra lectin, which have affinities for the following O-glycans, that have received attention as cancer-related antigens, Tn (GalNAc-Ser/Thr), Sialyl Tn (Siaα2-6GalNAc-Ser/Thr), T (Galβ1-3GalNAc-Ser/Thr), Sialyl T (Siaα2-3Galβ1-GalNAc-Ser/Thr), and di-Sialyl T (Siaα2-3Galβ1-3[Siaα2-6] GalNAc-Ser/Thr), with a unique O-glycoproteomics approach. A total of 2,068 O-glycoforms derived from 265 proteins were identified in healthy individuals and patients with advanced CRC, of which 44 CRC-specific O-glycoforms were extracted. Particularly, five glycoproteins with T, Sialyl T, and di-Sialyl T antigens in specific peptide regions were evaluated quantitatively and statistically. We found that fibulin-2 (FBLN2) (aa330-349)/T antigen (area under the curve [AUC] = 0.92); macrophage colony-stimulating factor 1 (CSF1) (aa370-395)/(T + di-Sialyl T) (AUC = 0.94); macrophage mannose receptor 1 (MRC1) (aa1083-1101 and aa1215-1229)/T (AUC = 0.96 and 0.99); fibrinogen alpha chain (FGA) (aa354-367, aa511-527 and aa559-573)/Sialyl T (AUC = 0.98, 0.90 and 0.94); and complement component C7 (C7) (aa692-701)/di-Sialyl T (AUC = 1.00), can have high diagnostic efficacy to strategically predict advanced CRC groups. Hence, they could be promising markers for detection of advanced CRC, and provide new clinical test indicators along with lectins, such as MPL and jacalin. Our O-glycoproteomics platform provides a novel tool and resource, for researchers and clinicians seeking to better understand and treat advanced CRC.

Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury.

The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here, we analyzed the effects of local versus peripheral sources of C3 expression in a model of acute bacterial pneumonia induced by Pseudomonas aeruginosa. Whereas mice with global C3 deficiency had severe pneumonia-induced lung injury, those deficient only in liver-derived C3 remained protected, comparable to wild-type mice. Human lung transcriptome analysis showed that secretory epithelial cells, such as club cells, express high levels of C3 mRNA. Mice with tamoxifen-induced C3 gene ablation from club cells in the lung had worse pulmonary injury compared with similarly treated controls, despite maintaining normal circulating C3 levels. Last, in both the mouse pneumonia model and cultured primary human airway epithelial cells, we showed that stress-induced death associated with C3 deficiency parallels that seen in Factor B deficiency rather than C3a receptor deficiency. Moreover, C3-mediated reduction in epithelial cell death requires alternative pathway component Factor B.Thus, our findings suggest that a pathway reliant on locally derived C3 and Factor B protects the lung mucosal barrier.

Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity.

Inflammation plays a fundamental role in the development of several metabolic diseases, including obesity and type 2 diabetes (T2D); the complement system has been implicated in their development. People of Black African (BA) ethnicity are disproportionately affected by T2D and other metabolic diseases but the impact of ethnicity on the complement system has not been explored. We investigated ethnic differences in complement biomarkers and activation status between men of BA and White European (WE) ethnicity and explored their association with parameters of metabolic health. We measured a panel of 15 complement components, regulators, and activation products in fasting plasma from 89 BA and 96 WE men. Ethnic differences were statistically validated. Association of complement biomarkers with metabolic health indices (BMI, waist circumference, insulin resistance, and HbA1c) were assessed in the groups. Plasma levels of the key complement components C3 and C4, the regulators clusterin and properdin and the activation marker iC3b were significantly higher in BA compared to WE men after age adjustment, while FD levels were significantly lower. C3 and C4 levels positively correlated with some or all markers of metabolic dysfunction in both ethnic groups while FD was inversely associated with HbA1c in both groups, and clusterin and properdin were inversely associated with some markers of metabolic dysfunction only in the WE group. Our findings of increased levels of complement components and activation products in BA compared to WE men suggest differences in complement regulation that may impact susceptibility to poor metabolic health.

The Case | A benign reason behind a malignant finding

A 21-year-old man presented to the office for deranged kidney function. He was diagnosed to have C3 glomerulonephritis at the age of 18 years when he presented to his first physician with hypertension. Laboratory parameters showed high serum creatinine (2.7 mg/dl), low serum albumin (2.9 g/dl), low total protein (5.2 g/dl), dysmorphic red blood cells on urinalysis, high 24-hour urine protein (5.7 g/d), low complement C3 (32 mg/dl), and low 50% hemolytic complement (10 U/ml). Kidney biopsy showed a membranoproliferative pattern of injury with 3+ reactivity for complement C3 and significant chronic changes. There was moderate tubulointerstitial fibrosis and 30% of all sampled glomeruli were globally sclerosed. Clinically, there were no signs of atypical hemolytic uremic syndrome and pathologically no evidence of thrombotic microangiopathy. He was started on steroids and mycophenolate mofetil, which were discontinued after 3 months in view of intolerable side effects. Thereafter, ravulizumab, a new complement component C5 inhibitor with a longer half-life, was started and he received 4 infusions (3 doses of 3300 mg and 1 dose of 2700 mg at 8 weekly intervals) until his recent visit to the office. Laboratory parameters at that time showed persistently high serum creatinine (2.3 mg/dl), high 24-hour urine protein (6 g/d), and dysmorphic red blood cells on urinalysis; however, 50% hemolytic complement (40 U/ml) and complement C3 (117 mg/dl) normalized. A repeat kidney biopsy was done in view of no clinical response to therapy, and the direct immunofluorescence findings of pretreatment and post-treatment kidney biopsies are shown in Figure 1.

Design, Synthesis of Dioxopiperidinamide Derivatives by Amide Coupling Reaction and Study of Their Biological Activity

AbstractA series of fifteen dioxopiperidinamide derivatives synthesized and their spectra chemical data were reported. An alternative amide coupling reaction has been followed by using 3‐aminopiperidine‐2,6‐dione through amide bond functionalization between N‐Ethyl‐N′‐(3‐dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) and Hydroxybenzotriazole (HOBt). All the designed compounds were docked in to the active sites of 2 A73: Human Complement Component C3. All the docked compounds is favorable to make both hydrogen and hydrophobic interaction with amino acids located at the binding site. The most of potential compounds (E)‐N‐(2,6‐dioxopiperidin‐3‐yl)‐3‐(m‐tolyl)acrylamide (4 g), (E)‐3‐(4‐bromophenyl)‐N‐(2,6‐dioxopiperidin‐3‐yl)acrylamide (4 h) and N‐(2,6‐dioxopiperidin‐3‐yl)‐3‐methyl‐4‐oxo‐4,6,7,8,9,10‐hexahydrothieno [2′,3′:4,5]pyrimido[1,2‐a]azepine‐2‐carboxamide (7) studied for their anticancer activity on the THP‐1 cancer cells line. It was also further established their Anti‐inflammatory activity and Antioxidant activity with the comparable efficiency against those of clinically used drugs.

Structural modelling of human complement FHR1 and two of its synthetic derivatives provides insight into their in-vivo functions

Human complement is the first line of defence against invading pathogens and is involved in tissue homeostasis. Complement-targeted therapies to treat several diseases caused by a dysregulated complement are highly desirable. Despite huge efforts invested in their development, only very few are currently available, and a deeper understanding of the numerous interactions and complement regulation mechanisms is indispensable. Two important complement regulators are human Factor H (FH) and Factor H-related protein 1 (FHR1). MFHR1 and MFHR13, two promising therapeutic candidates based on these regulators, combine the dimerization and C5-regulatory domains of FHR1 with the central C3-regulatory and cell surface-recognition domains of FH. Here, we used AlphaFold2 to model the structure of these two synthetic regulators. Moreover, we used AlphaFold-Multimer (AFM) to study possible interactions of C3 fragments and membrane attack complex (MAC) components C5, C7 and C9 in complex with FHR1, MFHR1, MFHR13 as well as the best-known MAC regulators vitronectin (Vn), clusterin and CD59, whose experimental structures remain undetermined. AFM successfully predicted the binding interfaces of FHR1 and the synthetic regulators with C3 fragments and suggested binding to C3. The models revealed structural differences in binding to these ligands through different interfaces. Additionally, AFM predictions of Vn, clusterin or CD59 with C7 or C9 agreed with previously published experimental results. Because the role of FHR1 as MAC regulator has been controversial, we analysed possible interactions with C5, C7 and C9. AFM predicted interactions of FHR1 with proteins of the terminal complement complex (TCC) as indicated by experimental observations, and located the interfaces in FHR11–2 and FHR14–5. According to AFM prediction, FHR1 might partially block the C3b binding site in C5, inhibiting C5 activation, and block C5b-7 complex formation and C9 polymerization, with similar mechanisms of action as clusterin and vitronectin. Here, we generate hypotheses and give the basis for the design of rational approaches to understand the molecular mechanism of MAC inhibition, which will facilitate the development of further complement therapeutics.

Association of Proliferative Diabetic Retinopathy in the Elderly with the Blood Complement System

A common complication of diabetes mellitus, mainly type 2, is diabetic retinopathy, among which the most unfavorable form for complete loss of vision is considered to be proliferative diabetic retinopathy. The participation of the complement system in the development of proliferative diabetic retinopathy is mainly devoted to experimental work on a limited number of blood complement components and without assessing their risk in the pathogenesis of the disease. The purpose of the study was to determine the association of components of the blood serum complement system with the development of proliferative diabetic retinopathy in the elderly. In clinical conditions, 115 patients 60–74 years old suffering from proliferative diabetic retinopathy and 48 patients of the same age with the absence of this ophthalmopathology were examined. The components of the blood complement system were studied by enzyme immunoassay and hemolytic method. The relative risk of the influence of the complement components was calculated according to the generally accepted method. There was a statistically significant increase in the blood serum of patients with proliferative diabetic retinopathy of most components of the complement system, with the exception of the C1 ing. and C5 components. The content of the C3a component increased especially to 127.6 ± 4.7 ng / ml versus 30.4 ± 3.5 ng/ml in the control, the C5a component to 5.6 ± 0.5 ng/ml versus 2.4 ± 0.3 ng/ml, and factor H to 228.7 ± 4.9 versus 106.3 ± 3.8 mng / ml, respectively. The highest value of the relative risk among the studied components is inherent in the C3a component of the blood complement with a reliable confidence interval of 4,451–5,103. The development of proliferative diabetic retinopathy in the elderly is associated with an increased content of C3a, C5a components and factor H in the blood serum, which can be used to develop targeted therapy for this disease.

Reactive molecular dynamics study on catalytic pyrolysis and steam reforming of hydrocarbon fuel

The strong endothermic capability of catalytic steam reforming highlights its potential for improving the heat sink of hydrocarbon fuels. To explore the complex interaction between catalytic pyrolysis and steam reforming reactions, as well as their contributions to the heat sink of fuels, the reactive force-field molecular dynamics (ReaxFF-MD) simulation is employed in this work to investigate the palladium-catalyzed pyrolysis and steam reforming of n-dodecane (n-C12H26). The results show that pyrolysis reaction supplies C1 and C2 components, and then participates in the steam reforming generating more than 90% of aldehyde groups. Meanwhile, compared to catalytic pyrolysis reaction, the catalytic steam reforming containing 25 n-C12H26 and 300 H2O reduces 40.54% of carbon atoms deposited inside the palladium lattice, and improves the heat sink from 254.18 kcal/mol to 386.03 kcal/mol. Furthermore, our simulated results quantitatively describe the detailed contributions of catalytic pyrolysis and steam reforming to the simulation process. With more H2O added, the proportion of steam reforming gradually increases, which reaches 35.08% in the system containing 25 n-dodecane and 300 H2O. Moreover, the contribution of H atoms in the formation of H2 also indicates the variation in the proportion of steam reforming.

Distinct differences in surface-water dissolved organic matter between the East China Sea and Okinawa Trough: Source and hydrological effects

Cross-shelf transport plays an important role in marine carbon cycles. In this study, we examined the concentration and optical composition of dissolved organic matter (DOM) in 33 surface water samples collected along a transect from the East China Sea (ECS) to the Okinawa Trough (OT) in spring 2021. Compared to OT waters, ECS waters are characterized by higher dissolved organic carbon (DOC) concentration (111.55 ± 13.30 vs. 72.52 ± 5.01 μmol L−1), chromophoric DOM concentration (0.44 ± 0.15 vs. 0.12 ± 0.03 m−1 for a350), aromaticity (1.07 ± 0.11 vs. 0.64 ± 0.08 L mg−1C m−1 for SUVA254), and humification index (1.04 ± 0.25 vs. 0.58 ± 0.07). Fluorescence components C1, C3, and C4 displayed similar regional trends with the highest intensity in the inner shelf, followed by the outer shelf and then OT, whereas C2 had the highest intensity in the outer shelf, followed by the inner shelf and then OT. Comparison of the inner and outer ECS shelves revealed similar DOC concentrations, but different optical parameters (i.e., a350, S275–295, HIX, BIX, C1-C4 intensity). Our study suggests that: 1) active carbon cycling alters surface water DOM compositions in the ECS shelf, which is not reflected by total DOC concentrations, likely due to an offset effect between terrestrial DOM removal and marine DOM production; and 2) DOM is well mixed in the ECS shelf, but hardly passes across the OT owing to the strong barrier effect of the Kuroshio Current during the sampling season. Investigation of DOM biogeochemistry in other seasons and different water depth is necessary as the Changjiang Diluted Current and Kuroshio Current are weaker in winter and stronger in summer, respectively, which affects the spatial and temporal distribution of water DOM in the ECS-OT regions.

Protein Expression and Bioinformatics Study of Granulosa Cells of Polycystic Ovary Syndrome Expressed Under the Influence of DHEA.

The reproductive system is heavily dependent on ovarian follicles, which are made up of germ cells (oocytes) and granulosa cells (GCs), including cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Understanding their normal and steroid-induced functions is the key to understanding the pathophysiology of endocrinal diseases in women. This study investigated the differentially expressed proteins by CGCs and MGCs of patients with polycystic ovarian syndrome (PCOS) and without subsequent exposure to dehydroepiandrosterone sulfate (DHEAS) and functional differentiation. The present study was observational and experimental study carried out in hospital involving 80 female patients undergoing IVF for infertility. In this study, we isolated CGCs and MGCs from the follicular fluid of both PCOS and non-PCOS patients undergoing in vitro fertilization (IVF). The cells were cultured and treated with DHEAS for 48 hours, and these cells were extracted, digested, and analyzed by tandem mass spectrometry followed by processing of the results using open-source bioinformatics tools. The present investigation discovered 276 and 341 proteins in CGCs and MGCs, respectively. DHEAS reduced the number of proteins expressed by CGCs and MGCs to 34 and 57 from 91 and 94, respectively. Venn results of CGCs revealed 49, 53, 36, and 21 proteins in normal CGCs, PCOS-CGCs, post-DHEAS, and PCOS-CGCs, respectively. Venn analysis of MGCs showed 51 proteins specific to PCOS and 29 shared by normal and PCOS samples after DHEAS therapy. MGCs express the most binding and catalytic proteins, whereas CGCs express transporter-related proteins. A protein pathway study demonstrated considerable differences between normal and PCOS samples, while DHEAS-treated samples of both cell lines showed distinct pathways. String findings identified important network route components such as albumin, actin, apolipoprotein, complement component C3, and heat shock protein. This is the first study to show how DHEAS-induced stress affects the expression of proteins by MGCs and CGCs isolated from normal and PCOS patients. Further studies are recommended to identify PCOS biomarkers from CGCs and MGCs expressed under the influence of DHEAS.

“PNH is getting very popular!”: New clinical trial data and management insights from ASH 2023

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells that leaves red blood cells (RBCs) susceptible to complement-mediated lysis, with clinical manifestations that can include anemia, hemoglobinuria, and thrombosis. Inhibition of the terminal complement component C5 with eculizumab or ravulizumab can control intravascular hemolysis (IVH) and improve clinical parameters, patient survival, and quality of life (QoL). However, terminal complement inhibition alone may leave RBCs vulnerable to extravascular hemolysis (EVH) and persistent anemia in a minority of patients. This report focuses on clinical trial and real-world data presented at the recent annual meeting of the American Society of Hematology (ASH) for currently available and novel complement inhibitors in PNH.

Seasonal and diel modulation of DOM in a mangrove-dominated estuary.

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m3 s-1), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters.

Anatomy of a Gaussian giant: supercritical level-sets of the free field on regular graphs

We study the level-set of the zero-average Gaussian Free Field on a uniform random d-regular graph above an arbitrary level h∈(−∞,h⋆), where h⋆ is the level-set percolation threshold of the GFF on the d-regular tree Td. We prove that w.h.p as the number n of vertices of the graph diverges, the GFF has a unique giant connected component C1(n) of size η(h)n+o(n), where η(h) is the probability that the root percolates in the corresponding GFF level-set on Td. This gives a positive answer to the conjecture of [4] for most regular graphs. We also prove that the second largest component has size Θ(logn). Moreover, we show that C1(n) shares the following similarities with the giant component of the supercritical Erdős-Rényi random graph. First, the diameter and the typical distance between vertices are Θ(logn). Second, the 2-core and the kernel encompass a given positive proportion of the vertices. Third, the local structure is a branching process conditioned to survive, namely the level-set percolation cluster of the root in Td (in the Erdős-Rényi case, it is known to be a Galton-Watson tree with a Poisson distribution for the offspring).