Agriculture is at the pivot point between anthroposphere, biosphere, and atmosphere. Innovative solutions are needed to reduce agricultural emissions and improve sustainability. Microalgae animal feed could be such a solution. This study aimed to evaluate the effects of 10 freshwater microalgae: Auxenochlorella protothecoides, Chlamydomonas pulvinate, Chlorella luteoviridis, Chlorella variabilis, Euglena mutabilis, Parachlorella kessleri, Stichococcus bacillaris, Tetradesmus acuminatus, Tetradesmus obliquus, and Tetraselmis gracilis, on ruminal methane (CH4) production, nutrient digestibility, and rumen fermentation using the in vitro Hohenheim gas test. The microalgae were cultured in a carbon dioxide (CO2) incubator at 2% CO2, at the optimal conditions for each strain. The highest producers were P. kessleri and T. obliquus, with a biomass concentration of 0.69 and 0.73 g/L·d, respectively. Their PUFA contents ranged from 33.2% to 69.1% of total fatty acids. Microalgae were tested at a 15% replacement in a control basal diet of 40.0% DM grass silage, 40.0% maize silage, 15% hay, and 5% concentrate. Data were analyzed using a mixed model in R. Ruminal CH4 production was reduced by 15.4%, 17.4%, and 16.4% in diets containing A. protothecoides, C. luteoviridis, and P. kessleri, respectively, compared with the control diet. Similarly, these diets reduced in vitro organic matter digestibility by 3.5%, 5.2%, and 5.4%, respectively. However, only A. protothecoides reduced CH4/CO2 ratio by 3.5% compared with the control diet. Propionate molar proportion was decreased by 2.4, 3.0, 2.5, and 2.5 percentage points for diets containing Ch. pulvinate, E. mutabilis, P. kessleri, and T. obliquus, respectively. Marginal effects of dietary variables were analyzed using the generalized additive model framework, revealing a negative relationship between dietary PUFA, sulfur content, and CH4 production, and a negative relationship between dietary PUFA and CH4/CO2 ratio. Incorporating high-PUFA microalgae in ruminant diets shows potential for reducing enteric CH4 emissions, warranting further investigation.

• Klíčová slova
• PUFA, methane mitigation, microalgae, rumen fermentation, ruminant,
• MeSH
• bachor * metabolismus   MeSH
• dieta veterinární   MeSH
• fermentace MeSH
• krmivo pro zvířata MeSH
• methan * metabolismus   MeSH
• mikrořasy * metabolismus   MeSH
• siláž MeSH
• skot MeSH
• sladká voda MeSH
• trávení MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methan * MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

• Klíčová slova
• autophagy, functional characterization, genetic variants, pancreatic cancer, polymorphisms, susceptibility,
• MeSH
• autofagie * genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom slinivky břišní * genetika   patologie   MeSH
• forkhead transkripční faktory MeSH
• genetická predispozice k nemoci * MeSH
• hepatocytární jaderný faktor 3-alfa genetika   metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXA1 protein, human MeSH Prohlížeč
• FOXP3 protein, human MeSH Prohlížeč
• hepatocytární jaderný faktor 3-alfa MeSH
• nádorové biomarkery * MeSH
• nádorové supresorové proteiny * MeSH
• TP63 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

• MeSH
• Achillova šlacha diagnostické zobrazování   MeSH
• axiální spondyloartritida diagnostické zobrazování   MeSH
• dospělí MeSH
• entezopatie * diagnostické zobrazování   MeSH
• fyzikální vyšetření * MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• psoriatická artritida diagnostické zobrazování   komplikace   MeSH
• spondylartritida * diagnostické zobrazování   komplikace   MeSH
• ultrasonografie * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

• MeSH
• emoce MeSH
• lidé MeSH
• mínění MeSH
• mravy MeSH
• odpor * MeSH
• zlost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat.

• MeSH
• COVID-19 * epidemiologie   MeSH
• lidé MeSH
• pandemie prevence a kontrola   MeSH
• průzkumy a dotazníky MeSH
• sociální chování MeSH
• sociální normy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• genetické lokusy MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mnohočetný myelom * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Recent advances in the field of skin patches have promoted the development of wearable and implantable bioelectronics for long-term, continuous healthcare management and targeted therapy. However, the design of electronic skin (e-skin) patches with stretchable components is still challenging and requires an in-depth understanding of the skin-attachable substrate layer, functional biomaterials and advanced self-powered electronics. In this comprehensive review, we present the evolution of skin patches from functional nanostructured materials to multi-functional and stimuli-responsive patches towards flexible substrates and emerging biomaterials for e-skin patches, including the material selection, structure design and promising applications. Stretchable sensors and self-powered e-skin patches are also discussed, ranging from electrical stimulation for clinical procedures to continuous health monitoring and integrated systems for comprehensive healthcare management. Moreover, an integrated energy harvester with bioelectronics enables the fabrication of self-powered electronic skin patches, which can effectively solve the energy supply and overcome the drawbacks induced by bulky battery-driven devices. However, to realize the full potential offered by these advancements, several challenges must be addressed for next-generation e-skin patches. Finally, future opportunities and positive outlooks are presented on the future directions of bioelectronics. It is believed that innovative material design, structure engineering, and in-depth study of fundamental principles can foster the rapid evolution of electronic skin patches, and eventually enable self-powered close-looped bioelectronic systems to benefit mankind.

• MeSH
• elektronika MeSH
• nositelná elektronika * MeSH
• protézy a implantáty MeSH
• zdroje elektrické energie MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

• Klíčová slova
• autophagy, genetic susceptibility, genetic variants, multiple myeloma,
• MeSH
• autofagie MeSH
• biologické markery MeSH
• imunoglobulin M MeSH
• leukocyty mononukleární patologie   MeSH
• lidé MeSH
• mnohočetný myelom * genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• biologické markery MeSH
• imunoglobulin M MeSH

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.

• Klíčová slova
• TTFT, chronic lymphocytic leukemia, genetic variants, overall survival, polygenic risk score, susceptibility,
• MeSH
• celogenomová asociační studie MeSH
• chronická lymfatická leukemie * genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• progrese nemoci MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.

• Klíčová slova
• genetic variants, multiple myeloma, obesity, susceptibility,
• MeSH
• celogenomová asociační studie * metody   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mnohočetný myelom * genetika   MeSH
• obezita komplikace   genetika   MeSH
• rizikové faktory MeSH
• transportní proteiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• POC5 protein, human MeSH Prohlížeč
• transportní proteiny MeSH