Relative Levels Research Articles

P219 Prognostic potential of mucosal proteins in Ulcerative Colitis

Abstract Background Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value. Methods Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of >2 courses of corticosteroids, or a cumulative dose of >2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC). Results 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83). Conclusion We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.

Perceptions and reality in fisher coexistence with aquatic predators in the Peruvian Amazon

AbstractHumans and large aquatic predators compete for fish and negative interactions are widely reported as ‘human–wildlife conflicts’. When aquatic predators are perceived to damage fisheries or fishing equipment, lethal control can occur. The perceptions and reality of damage are infrequently compared, but this relationship is key to determining how negative outcomes can be mitigated. We examine coexistence between people and six large aquatic piscivores (two caiman, two dolphins, two otters) in Amazonian Peru. We determine the extent of damage to fishing equipment caused by each species and compare this to the amount of damage perceived by fishers. Giant otter populations have recently recovered in some areas, so we expected different perceptions relating to experiences with otters. We trained fishers to complete fishing registers (n = 278, 1173 h of fishing) to record damage to nets by wildlife. We interviewed 302 people from three sites to determine perceptions of damage by predators, and attitudes towards giant otters. Rates of damage to nets reflected the presence and populations of different aquatic predators at each site, but when present, dolphins and caimans damaged nets more than otters, which rarely damaged nets. People living where giant otters had recently recovered perceived higher relative levels of damage to nets by them and had more negative attitudes about them, compared to people from areas where giant otters had been present for longer, aquatic predators were more abundant, and community resource management was longer‐established. Better knowledge and more experience with a species may lead to more accurate perceptions of damage and increased tolerance. Where humans and animals compete for natural resources, conflict mitigation rarely includes better resource management. If tolerance of predators is greater where predators are common, and resources have not been overexploited, resource management may yield greater gains for stakeholders than other commonly prescribed forms of mitigation.

Effects of Background Color on Growth, Stress, Biochemical, Hematological, and Immunological Responses, and Expression of Growth-Related Genes in Oscar Fish (Astronotus ocellatus)

The aim of the current study was to assess the impacts of tank color on the growth, stress, biochemical, hematological, and immunological responses, and expression of growth-related genes in juvenile Oscar (Astronotus ocellatus). Therefore, a total of 120 fish (9.14 ± 0.34 g) were distributed into 12 aquariums (60 × 50 × 35 cm) and divided into four treatments (aquariums with blue, white, yellow, and red colors) in three replicates (10 fish per aquarium). The fish were daily hand-fed ad libitum in three meals at 7:00, 12:00, and 17:00 hr for 56 days. Results showed that Oscar fish cultured in the red aquariums had higher final weight and weight gain and lower feed conversion ratio. Plasma cortisol, glucose, and lactate values of fish were significantly higher, and the amount of white blood cells was lower in the blue aquariums compared to other tank colors. Plasma triglyceride values were significantly higher in the white and yellow groups than the blue aquariums. Moreover, fish cultured in yellow and red aquariums had significantly higher melatonin levels than the blue aquariums. Plasma cholesterol, total protein, albumin, complement 3, and total immunoglobulin values were highest in Oscar fish cultured in the red aquariums. Also, lysozyme and alternative complement (ACH50) activities and complement 4 values of fish cultured in yellow and red aquariums were meaningfully higher compared to blue and white groups. Growth hormone relative gene expression levels were meaningfully higher in Oscar fish cultured in white, yellow, and red aquariums than the blue aquariums. Furthermore, insulin-like growth factor-1 (IGF-1) relative gene expression levels were significantly higher in fish cultured in yellow and red aquariums compared to those cultured in blue and white tank colors. Thus, the most suitable tank color for rearing juvenile A. ocellatus is red, while blue tank color is unsuitable.

Nuclear translocation of STAT5 initiates iron overload in huntington's disease by up-regulating IRP1 expression.

Mutant huntingtin (mHtt) proteins interact to form aggregates, disrupting cellular functions including transcriptional dysregulation and iron imbalance in patients with Huntington's disease (HD) and mouse disease models. Previous studies have indicated that mHtt may lead to abnormal iron homeostasis by upregulating the expression of iron response protein 1 (IRP1) in the striatum and cortex of N171-82Q HD transgenic mice, as well as in HEK293 cells expressing the N-terminal fragment of mHtt containing 160 CAG repeats. However, the mechanism underlying the upregulation of IRP1 remains unclear. We investigated the levels and phosphorylation status of signal transducer and activator of transcription 5 (STAT5) in the brains of N171-82Q HD transgenic mice using immunohistochemistry staining. We also assessed the nuclear localization of STAT5 protein through western blot and immunofluorescence, and measured the relative RNA expression levels of STAT5 and IRP1 using RT-PCR in both N171-82Q HD transgenic mice and HEK293 cells expressing the N-terminal fragment of huntingtin. Our findings demonstrate that the transcription factor STAT5 regulates the transcription of the IPR1 gene in HEK293 cells. Notably, both the brains of N171-82Q mice and 160Q HEK293 cells exhibited increased nuclear content of STAT5, despite unchanged total STAT5 expression. These results suggest that mHtt promotes the nuclear translocation of STAT5, leading to enhanced expression of IRP1. The nuclear translocation of STAT5 initiates abnormal iron homeostatic pathways, characterized by elevated IRP1 expression, increased levels of transferrin and transferrin receptor, and iron accumulation in the brains of HD mice. These findings provide valuable insights into potential therapeutic strategies targeting iron homeostasis in HD.

A Study on the Operational Efficiency of National Supercomputer Resources Based on DEA Model

As a measure to improve the operational efficiency of the Korean supercomputer joint utilization resources, an efficiency analysis using DEA was conducted to derive the improvement level of the input and output factors of the operation plans of seven specialized centers. The factors that constitute the objective function of efficiency were identified through the operation plans submitted by the specialized centers, and DEA analyzed the improvement factors and levels of inefficient specialized centers through the CCR and BCC models, and then conducted an additional super-efficiency analysis to compare the relative efficiency levels among the efficiency groups. As a result of the analysis, the inefficiency of specialized centers in the meteorological/climate/environmental fields was identified from the reference group, and the need for improvement and the level of improvement of input and output variables were identified. In addition, the authors suggested ways to improve the establishment of resources and operational targets, such as a joint utilization ratio to secure financial efficiency at the government level in establishing a joint utilization resource.

The concept of the «International Rule of Law»

The article is devoted to the elucidation and exposition of the concept of the «international rule of law», the analysis of approaches to its definition and the formulation of its definition. It is emphasized that the international rule of law is among those concepts that have been consistently «hanging in the air» to some extent since the post-World War II period. It is noted that, unlike in the case of defining the «classic» (domestic) rule of law, there is a lack of consensus within the scientific community regarding the definition of the international rule of law. The trends on which a certain unanimity is forming within the scientific and scholarly community are identified. The limits of the influence of the domestic rule of law theory on the international rule of law theory are revealed.
 The approaches to defining the concept of the international rule of law, as well as its «narrow» and «broad» meanings, are analyzed. It is stated that despite inconsistencies in the scientific doctrine, full adherence to the international rule of law is an «ideal,» and this «ideal» is associated with a human being, their rights, and freedoms. It has been proved that the narrow concept in the era of human rights law cannot be fully considered to be the «international rule of law», since human rights are an integral element of the latter. It is stated that contemporary theories of the rule of law and constitutionalism converge on the idea that human dignity, freedom, and human rights form the basis of all other obligations of the state. It is noted that the international analogue of the «rule of law, not individuals» would be the «rule of law, not states», which implies two aspects: it is not only about the impossibility for the hegemonic state to arbitrarily dictate its will to other states, but also the impossibility to dictate it to individuals.
 The authors distinguish between the concepts of «international rule of law», «rule of international law», and «rule of law in international relations». The requirements of the international rule of law in the practice of international bodies are highlighted. Based on the analysis of scientific approaches and the practice of international bodies, the authors’ own definition of the «international rule of law» is provided as a civilization-wide conceptual tool that represents a set of values, doctrines, and principles, the main requirement of which is the restrictions arising from the dignity, freedoms, and fundamental rights of every individual, in order to delineate the limits of power of states concerning an individual - both at the level of relations between subjects of international law and at the level of relations between certain subjects of international law and certain individuals.

Measurements of cadmium levels in relation to tobacco dependence and as a function of cytisine administration

Cigarette smoking delivers a number of heavy metals, including cadmium (Cd), into the body. Bioaccumulation may result in an increase in pathological consequences over time. The assessment of changes in serum Cd concentrations during the treatment of cigarette dependence with cytisine was performed for the first time. Parameters assessing smoking habits, strength of addiction, and effectiveness of therapy were analyzed. Cd was determined before, during, and after the end of treatment. The serum Cd levels were significantly higher in the smokers than in the nonsmokers. Significant differences in Cd concentrations between sampling times in smokers were observed. Individuals who stopped smoking had significantly lower Cd concentrations compared to baseline. A significant positive correlation between the serum Cd before treatment and smoking urges was also obtained. Additionally, salivary Cd determinations were performed before treatment to evaluate the use of this method to assess cigarette addiction. Our findings indicate that Cd can be used as a biomarker of smoking addiction, and provide an alternative assessment of tobacco smoke exposure to other methods. The results provide new knowledge related to Cd concentrations in human body fluids and may play a role in monitoring and assessing the efficacy of cytisine for smoking cessation.

Salivary Th17 cytokine, human β-defensin 1–3, and salivary scavenger and agglutinin levels in Crohn’s disease

ObjectivesCrohn’s disease patients, who are prone to develop periodontal diseases, may carry genetic defects in their Th17 cytokine, human beta-defensin (hBD) 1–3, and salivary and scavenger agglutinin (SALSA) expressions. Biochemical composition of saliva reflects the oral consequences of systemic immune response modifications. Our aim was to evaluate the salivary Th17 cytokine, epithelial hBD 1–3, and SALSA levels in relation to Crohn’s disease.Materials and methodsThis cross-sectional study included 42 Crohn’s disease patients and 34 systemically healthy controls. Periodontal and dental indexes were measured, and stimulated saliva samples were collected. Salivary Th17 cytokine levels were analyzed by multiplex technique, and hBD 1–3 and SALSA levels by enzyme-linked immunosorbent assay.ResultsThere were 19 gingivitis and 11 initial periodontitis patients in the Crohn’s disease group, and 15 gingivitis and 4 initial periodontitis in the control group. In comparison to controls, higher salivary Th17 cytokine levels were observed in Crohn’s disease patients. No statistical difference was observed between Crohn’s disease and control groups in terms of their salivary hBD 1–3 and SALSA levels. Based on the regression analysis, there is no independent association between Crohn’s disease and salivary Th17 cytokine levels.ConclusionsCrohn’s disease does not relate to salivary antimicrobial hBD 1–3 or SALSA levels. While Crohn’s disease patients have higher salivary Th17 cytokine levels in comparison to systemically healthy controls, an independent association between Crohn’s disease and Th17 cytokine profile is still missing.Clinical relevanceDiminished Th17 cytokine response in Crohn’s disease, which might be related to genetic susceptibility, can be also visualized in saliva.

The Peri-Implant Microbiome-A Possible Factor Determining the Success of Surgical Peri-Implantitis Treatment?

The objective was to assess the effect of peri-implantitis surgery on the peri-implant microbiome with a follow-up of one year. A total of 25 peri-implantitis patients in whom non-surgical treatment has failed to solve peri-implantitis underwent resective surgical treatment. Their peri-implant pockets were sampled prior to surgical treatment (T0) and one year post treatment (T12). The natural dentition was sampled to analyse similarities and differences with the peri-implantitis samples. Treatment success was recorded. The change in microbial relative abundance levels was evaluated. The microbiota was analysed by sequencing the amplified V3-V4 region of the 16S rRNA genes. Sequence data were binned to amplicon sequence variants that were assigned to bacterial genera. Group differences were analysed using principal coordinate analysis, Wilcoxon signed rank tests, and t-tests. Beta diversity analyses reported a significant separation between peri-implantitis and natural dentition samples on T0 and T12, along with significant separations between successfully and non-successfully treated patients. Eubacterium was significantly lower on T12 compared to T0 for the peri-implantitis samples. Treponema and Eubacterium abundance levels were significantly lower in patients with treatment success on T0 and T12 versus no treatment success. Therefore, lower baseline levels of Treponema and Eubacterium seem to be associated with treatment success of peri-implantitis surgery. This study might aid clinicians in determining which peri-implantitis cases might be suitable for treatment and give a prognosis with regard to treatment success.

Strategic Significance of Joint Committees for Cooperation Between Three Seas Initiative’s Countries and the United Arab Emirates

The 21st century has brought many changes both in Central and Eastern Europe (CEE) and in the Middle East, where the United Arab Emirates demonstrates its will play the role of a leader in many initiatives in the international arena. In 2016, 12 CEE countries launched the Three Seas Initiative (3SI) for the implementation of strategic economic projects to adapt to new international challenges. This research paper aims to find an answer to the research question of what is the Joint Committees’ – J(E)C role and significance for relations between the United Arab Emirates and Three Seas Initiative countries? To achieve the set research goal, both quantitative and qualitative methods were applied, considering the quantitative potential of the analysed countries’ power to adapt to the international environment and influence its players. Then, a comparative analysis was used in terms of J(E)C sessions, top-level visits, and trade trends. The research findings show that the most important thing to achieve the strategic level of relations is the political will and the appropriate strategy. However, countries with high potential, and perceived power, do not need J(E)C for the stable development of economic cooperation. The research results indicate that in strategic partnership with the UAE, Austria has a role and position in energy and Romania in transport. On the other hand, Poland connecting both strategic routes appear as an economic hub.

The Clinical Instructors' Caring Behavior as Perceived by Nursing Students of Selected Medical Schools in China

This study aimed to investigate nursing students’ perceptions of the clinical instructors’ caring behavior. The researchers tried to examine the role of socio-demographic profile in terms of age, gender, and year level in relation to the respondents’ caring behavior perceptions. This descriptive correlational study used a thirty (30) item questionnaire as the main gathering tool. The said questionnaire was distributed to 72 nursing students who were enrolled at selected medical schools in China for the 2022-2023 academic year. Data results were statistically analysed and interpreted using appropriate statistical tools, including the Percentage-Frequency Distribution Method, the Weighted Mean Formula and the Chi-Square Test. The results showed that the majority of the respondents belonged to the age bracket of 20-25 years (46, 63.9%), most were females (58, 80.6%), and there were more third year (junior) nursing students (29, 40.3%). This suggested that the majority of the nursing students studying at the selected medical schools were females, aged between 20-25 years and there were more junior students compared to sophomores and seniors. Results of the questionnaire revealed that with the average mean score of 2.72 in level 2 (sophomores), 2.96 in level 3 (juniors) and 3.15 in level 4 (seniors), the respondents had rated slightly agree on all the observed indicators of clinical instructors’ caring behavior perceptions. Thus, this depicted that the respondents had positive perceptions of their clinical instructors’ caring behavior. The results of the correlation between the independent and dependent variables pointed out that aside from their year level, which has a p-value of <0.010, no other independent variables were significantly associated with the respondents' perceptions of the caring behavior of their clinical instructors since the p values of their age (0.081) and gender (0.689) did exceed the 0.05 level of significance. Thus, this revealed that only the year level of the students is significantly associated with caring behavior perceptions demonstrated by the clinical instructors, which has a p-value of <0.010. To all clinical instructors, this study suggests that further training of nursing students regarding the significance of caring is needed for them to be able to learn about the essence of caring in nursing and to be well-molded individuals who will give quality nursing care to individuals, families and communities. Thus, the care demonstrated by the clinical instructors will serve as a guide to nursing students in giving quality nursing care to their clients in various settings. One limitation of the present study is that only a few respondents were surveyed, and information regarding the impact of clinical instructors’ caring behavior towards nursing students was limited; hence, for future studies, greater sample size is recommended, and other confounding factors should also be investigated.

Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

Effects of nano silicon fertilizer on the lodging resistance characteristics of wheat basal second stem node

The application of nano fertilizers is one of the hotspots in current agricultural production. In this study, nano silicon materials were mixed with compound fertilizers to make nano silicon fertilizer. The effects of different amounts of nano silicon application on the breaking-resistance strength, lodging-resistance index, lignin accumulation, lignin synthesis related enzymes, and the relative expression of lignin synthesis related genes in the second stem node of wheat were mainly studied. Four treatments were set up: CK (750 kg·ha−1 compound fertilizer), T1 (750 kg·ha−1 compound fertilizer + 0.9 kg·ha−1 nano silicon), T2 (750 kg·ha−1 compound fertilizer + 1.8 kg·ha−1 nano silicon), T3 (750 kg·ha−1 compound fertilizer + 2.7 kg·ha−1 nano silicon). The results of the two-year experiment showed that the breaking-resistance strength, lodging-resistance index, lignin accumulation in the second stem node of wheat treated with nano silicon fertilizer were higher than CK. In the first year of the experiment, the lignin accumulation of T2 was 130.73%, 5.14% and 7.25% higher than that of CK, T1 and T3 respectively at the maturity stage. In the second year of the experiment, the lignin accumulation of T2 was 20.33%, 11.19% and 9.89% higher than that of CK, T1 and T3 respectively at the maturity stage. And the activities of PAL, 4CL, CAD, and related gene expression levels were also higher than CK. And among them, T2 performed the best, indicating that the application of nano silicon fertilizer is beneficial for improving the lodging resistance of wheat stems and is of great significance for improving the quality of wheat.

SPATIAL VARIABILITY OF METHANE EMISSIONS FROM SOILS OF WET FORESTS: A BRIEF REVIEW

SPATIAL VARIABILITY OF METHANE EMISSIONS FROM SOILS OF WET FORESTS: A BRIEF REVIEW

Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy.

Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored. To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use. The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower. Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.

A 1500-year multi-proxy record of subtropical mangrove dynamics in relation to sea level and climate changes on Babitonga Bay, Southern Brazil

Climatic changes and sea level variations have had a significant impact on the mangroves along the Brazilian coast during the Holocene. The present study focused on understanding the specific factors that have determined the establishment and expansion of mangroves in a subtropical estuary of southern Brazil (Babitonga Bay, State of Santa Catarina-SC), as well as their response to climate change and sea level variations during the late-Holocene. In this study, we carried out sedimentary analysis, palynology, and radiocarbon dating (C-14) to paleoenvironmental reconstruction of the last 1500 cal. year BP. Three facies associations were identified, indicating a progradational succession where a tidal flat was developed at the margin of the estuary. During the first phase, between at least 1440 and ±1286 cal. year BP, the area was characterized by a subtidal environment. The presence of Laguncularia pollen grains since ± 1390 cal. year BP indicated favorable conditions for mangrove establishment in proximity to the study site. Subsequently, around ± 1286 cal. year BP, the tidal flat developed, reaching the present-day shoreline, facilitated by the relative sea level drop. Avicennia trees were established on the tidal flat since ± 1273 cal. year BP, and the establishment of Rhizophora trees occurred in the most recent decades. This mangrove succession developed in Babitonga Bay following a temperature gradient, associated with low-temperature tolerance, and likely its establishment is associated with a temperature increase during the late-Holocene, that caused a migration of the southern limit of the mangrove in the subtropical zone to higher latitudes. Furthermore, the relatively slow expansion of mangroves upstream of Babitonga Bay also may have been controlled by the suitable salinity and substrate conditions, which were favored by the relative sea-level fall during the late-Holocene.

Rumen-protected methionine supplementation alters lipid profile of preimplantation embryo and endometrial tissue of Holstein cows.

Our objective is to evaluate the effects of feeding rumen-protected Met (RPM) throughout the transition period and early lactation on the lipid profile of the preimplantation embryos and the endometrial tissue of Holstein cows. Treatments consisted of feeding a total mixed ration with top-dressed RPM (Smartamine® M, Adisseo, Alpharetta, GA, United States; MET; n = 11; RPM at a rate of 0.08% of DM: Lys:Met = 2.8:1) or not (CON; n = 9, Lys:Met = 3.5:1). Endometrial biopsies were performed at 15, 30, and 73 days in milk (DIM). Prior to the endometrial biopsy at 73 DIM, preimplantation embryos were harvested via flushing. Endometrial lipid profiles were analyzed using multiple reaction monitoring-profiling and lipid profiles of embryos were acquired using matrix assisted laser desorption/ionization mass spectrometry. Relative intensities levels were used for principal component analysis. Embryos from cows in MET had greater concentration of polyunsaturated lipids than embryos from cows in CON. The endometrial tissue samples from cows in MET had lesser concentrations of unsaturated and monounsaturated lipids at 15 DIM, and greater concentration of saturated, unsaturated (specifically diacylglycerol), and monounsaturated (primarily ceramides) lipids at 30 DIM than the endometrial tissue samples from cows in CON. In conclusion, feeding RPM during the transition period and early lactation altered specific lipid classes and lipid unsaturation level of preimplantation embryos and endometrial tissue.

Expression of AHR-regulated and PD-L1-regulated microRNAs in squamous cell lung cancer

Introduction. Despite modern advances in research into the risk of development, immunological control and treatment options for lung cancer (LC), it is the leading cause of death from cancer. Tobacco smoking remains the predominant risk factor for the development of lung cancer, especially one of its aggressive subtypes, squamous cell lung cancer (SCLC). Benzo[a]pyrene, a component of cigarette smoke, promotes the activation of the aryl-hydrocarbon receptor (AhR). AhR regulates the expression of many oncogenes, including PD-L1, the positive status of which is an indication for immunotherapy, one of the main treatment strategies for SCLC. However, to improve the effectiveness of treatment of SCLC, further search for new diagnostic, prognostic and therapeutic markers is necessary. MicroRNAs (miRs), which are highly stable and present in biological fluids, can act as such markers.Objective. Search for microRNAs that could potentially serve as diagnostic markers or therapeutic targets for SCLC. For this purpose, microRNAs were selected whose promoter regions contain AhR binding sites or whose target is PD-L1.Materials and methods. A biocollection of tumor and conditionally normal lung tissue samples (n = 40) was collected at the thoracic department of the Novosibirsk Clinical Oncology Dispensary. The relative levels of selected miRNAs were examined using real-time reverse transcription-PCR (RT-PCR) technique.Results. The levels of miR-342 and miR-181a in SCLC tissues were reduced by 3 times relative to conditionally normal tissue. The expression of miR-181a and miR-155 is associated with tumor size (lower levels in tumors larger than 3 cm) and the presence of metastases in the lymph nodes (3- and 2-fold lower levels in cases with metastases). The level of miR-146a decreased by 3 times in patients with metastatic lesions of lymph nodes. A significant relationship between the levels of miR-93, miR-181a and miR-155 and the expression status of PD-L1 was also found.Conclusions. The expression profile of miR-146a, miR-93, miR-181a and miR-155 differs in SCLC patients depending on PD-L1 status and the presence or absence of lymph node metastases.

High-Throughput Glycan Profiling of Human Serum IgG Subclasses Using Parallel Reaction Monitoring Peptide Bond Fragmentation of Glycopeptides and Microflow LC-MS.

LC-MS-based N-glycosylation profiling in four human serum IgG subclasses (IgG1, IgG2, IgG3, and IgG4) often requires additional affinity-based enrichment of specific IgG subclasses, owing to the high amino acid sequence similarity of Fc glycopeptides among subclasses. Notably, for IgG4 and the major allotype of IgG3, the glycopeptide precursors share identical retention time and mass and therefore cannot be distinguished based on precursor or glycan fragmentation. Here, we developed a parallel reaction monitoring (PRM)-based method for quantifying Fc glycopeptides through combined transitions generated from both glycosidic and peptide bond fragmentation. The latter enables the subpopulation of IgG3 and IgG4 to be directly distinguished according to mass differences without requiring further enrichment of specific IgG subclasses. In addition, a multinozzle electrospray emitter coupled to a capillary flow liquid chromatograph was used to increase the robustness and detection sensitivity of the method for low-yield peptide backbone fragment ions. The gradient was optimized to decrease the overall run time and make the method compatible with high-throughput analysis. We demonstrated that this method can be used to effectively monitor the relative levels of 13 representative glycoforms, with a good limit of detection for individual IgG subclasses.

Distinctive physiological and molecular responses of foxtail millet and maize to nicosulfuron.

Nicosulfuron is the leading acetolactate synthase inhibitor herbicide product, and widely used to control gramineous weeds. Here, we investigated the metabolic process of nicosulfuron into foxtail millet and maize, in order to clarify the mechanism of the difference in sensitivity of foxtail millet and maize to nicosulfuron from the perspective of physiological metabolism and provide a theoretical basis for the breeding of nicosulfuron-resistant foxtail millet varieties. We treated foxtail millet (Zhangzagu 10, Jingu 21) and maize (Nongda 108, Ditian 8) with various doses of nicosulfuron in both pot and field experiments. The malonaldehyde (MDA) content, target enzymes, detoxification enzymes, and antioxidant enzymes, as well as related gene expression levels in the leaf tissues of foxtail millet and maize were measured, and the yield was determined after maturity. The results showed that the recommended dose of nicosulfuron caused Zhangzagu 10 and Jingu 21 to fail to harvest; the yield of the sensitive maize variety (Ditian 8) decreased by 37.09%, whereas that of the resistant maize variety (Nongda 108) did not decrease. Nicosulfuron stress increased the CYP450 enzyme activity, MDA content, and antioxidant enzyme activity of foxtail millet and maize, reduced the acetolactate synthase (ALS) activity and ALS gene expression of foxtail millet and Ditian 8, and reduced the glutathione S-transferase (GST) activity and GST gene expression of foxtail millet. In conclusion, target enzymes, detoxification enzymes, and antioxidant enzymes were involved in the detoxification metabolism of nicosulfuron in plants. ALS and GST are the main factors responsible for the metabolic differences among foxtail millet, sensitive maize varieties, and resistant maize varieties. These findings offer valuable insights for exploring the target resistance (TSR) and non-target resistance (NTSR) mechanisms in foxtail millet under herbicide stress and provides theoretical basis for future research of develop foxtail millet germplasm with diverse herbicide resistance traits.