Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Diversity of Homologous Oxidoreductases—Tuning of Substrate Specificity by a FAD-Stacking Residue for Iron Acquisition and Flavodoxin Reduction

Although bacterial thioredoxin reductase-like ferredoxin/flavodoxin NAD(P)+ oxidoreductases (FNRs) are similar in terms of primary sequences and structures, they participate in diverse biological processes by catalyzing a range of different redox reactions. Many of the reactions are critical for the growth, survival of, and infection by pathogens, and insight into the structural basis for substrate preference, specificity, and reaction kinetics is crucial for the detailed understanding of these redox pathways. Bacillus cereus (Bc) encodes three FNR paralogs, two of which have assigned distinct biological functions in bacillithiol disulfide reduction and flavodoxin (Fld) reduction. Bc FNR2, the endogenous reductase of the Fld-like protein NrdI, belongs to a distinct phylogenetic cluster of homologous oxidoreductases containing a conserved His residue stacking the FAD cofactor. In this study, we have assigned a function to FNR1, in which the His residue is replaced by a conserved Val, in the reduction of the heme-degrading monooxygenase IsdG, ultimately facilitating the release of iron in an important iron acquisition pathway. The Bc IsdG structure was solved, and IsdG-FNR1 interactions were proposed through protein–protein docking. Mutational studies and bioinformatics analyses confirmed the importance of the conserved FAD-stacking residues on the respective reaction rates, proposing a division of FNRs into four functionally unique sequence similarity clusters likely related to the nature of this residue.
A Retrospective Analysis Comparing VATS Cost Discrepancies and Outcomes in Primary Lung Cancer vs. Second Primary Lung Cancer Patients

This study aimed to compare the outcomes and cost differences between primary lung cancer (PLC) and second primary lung cancer (SPLC) patients who underwent video-assisted thoracoscopic surgery (VATS). This was a retrospective analysis of 124 patients with lung cancer stages I, II, and III who underwent VATS between January 2018 and January 2023. The patients were divided into two groups based on their cancer status that was matched by age and gender: the PLC group (n = 62) and the SPLC group (n = 62). The results showed that there was no significant difference in the clinical characteristics between the 2 groups, except for the Charlson Comorbidity Index (CCI), with a score above 3 in 62.9% of PLC patients and 80.6% among SPLC patients (p = 0.028). Regarding the surgical outcomes, the operative time for the VATS intervention was significantly higher in the SPLC group, with a median of 300 min, compared with 260 min in the PLC group (p = 0.001), varying by the cancer staging as well. The average duration of hospitalization was significantly longer before and after surgery among patients with SPLC (6.1 days after surgery), compared with 4.2 days after surgery in the PLC group (0.006). Regarding the cost analysis, the total hospitalization cost was significantly higher in the SPLC group (15,400 RON vs. 12,800 RON; p = 0.007). Lastly, there was a significant difference in the survival probability between the two patient groups (log-rank p-value = 0.038). The 2-year survival was 41.9% among PLC patients and only 24.2% among those with SPLC. At the 5-year follow-up, there were only 1.6% survivors in the SPLC group, compared with 11.3% in the PLC group (p-value = 0.028). In conclusion, this study found that VATS is a safe and effective surgical approach for both PLC and SPLC patients. However, SPLC patients have a higher VATS operating time and require more healthcare resources than PLC patients, resulting in higher hospitalization costs. These findings suggest that careful pre-operative evaluation and individualized surgical planning are necessary to optimize the outcomes and cost-effectiveness of VATS for lung cancer patients. Nevertheless, the 5-year survival remains very low and concerning.
Circadian Rhythm Does Not Affect the miRNA Cargo of Bovine Raw Milk Extracellular Vesicles

Extracellular vesicles (EVs) and their microRNA (miRNA) cargo have been proposed as possible mammary gland health biomarkers in cattle. However, throughout the day, the biologically active milk components, such as miRNAs, may change due to the dynamic nature of milk. The current study aimed to evaluate the circadian fluctuation of milk EVs miRNA cargo to assess the feasibility of milk EVs as future biomarkers for mammary gland health management. Milk from four healthy dairy cows was collected for four consecutive days in the two daily milking sessions in the morning and the evening. The isolated EVs were heterogeneous, intact, and carried the EV protein markers CD9, CD81, and TSG101, as shown by transmission electron microscopy and western blot. The miRNA sequencing results demonstrate that the abundance of miRNA cargo in milk EVs remained stable, unlike other milk components, such as somatic cells, that changed during milking sessions. These findings indicated that the miRNA cargo within milk EVs remains stable irrespective of the time of day, suggesting their potential utility as diagnostic markers for mammary gland health.
Drone Observation for the Quantitative Study of Complex Multilevel Societies

Simple Summary Multilevel societies are the most complex social structures in animals. They are social structures with nested levels of social organization, where stable “core units” gather to form higher-level groups. Such multiple-unit groups usually become very large (usually 100–1000 individuals), making it difficult to conduct observations. Most previous studies lack numerical definitions and descriptions; thus, it is largely unknown how and why animals, including humans, form multilevel societies. Aerial observation from unmanned aerial vehicles (drones) is a powerful method of capturing the spatial structures and movements of large animal groups. Recent advances in drone technology and its application have led to new discoveries, such as the spatial structure of multiunit groups and the underlying mechanisms of collective behavior. We review how previous studies have utilized drones and how drone applications have contributed to the understanding of multilevel societies. We will further discuss the potential opportunities and challenges with regard to drone observations in future studies. Abstract Unmanned aerial vehicles (drones) have recently been used in various behavioral ecology studies. However, their application has been limited to single groups, and most studies have not implemented individual identification. A multilevel society refers to a social structure in which small stable “core units” gather and make a larger, multiple-unit group. Here, we introduce recent applications of drone technology and individual identification to complex social structures involving multiple groups, such as multilevel societies. Drones made it possible to obtain the identification, accurate positioning, or movement of more than a hundred individuals in a multilevel social group. In addition, in multilevel social groups, drones facilitate the observation of heterogeneous spatial positioning patterns and mechanisms of behavioral propagation, which are different from those in a single-level group. Such findings may contribute to the quantitative definition and assessment of multilevel societies and enhance our understanding of mechanisms of multiple group aggregation. The application of drones to various species may resolve various questions related to multilevel societies.
Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution

The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (β: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.
Integrated Transcriptome and Metabolome Dynamic Analysis of Galls Induced by the Gall Mite Aceria pallida on Lycium barbarum Reveals the Molecular Mechanism Underlying Gall Formation and Development

Galls have become the best model for exploring plant–gall inducer relationships, with most studies focusing on gall-inducing insects but few on gall mites. The gall mite Aceria pallida is a major pest of wolfberry, usually inducing galls on its leaves. For a better understanding of gall mite growth and development, the dynamics of the morphological and molecular characteristics and phytohormones of galls induced by A. pallida were studied by histological observation, transcriptomics and metabolomics. The galls developed from cell elongation of the epidermis and cell hyperplasia of mesophylls. The galls grew quickly, within 9 days, and the mite population increased rapidly within 18 days. The genes involved in chlorophyll biosynthesis, photosynthesis and phytohormone synthesis were significantly downregulated in galled tissues, but the genes associated with mitochondrial energy metabolism, transmembrane transport, carbohydrates and amino acid synthesis were distinctly upregulated. The levels of carbohydrates, amino acids and their derivatives, and indole-3-acetic acid (IAA) and cytokinins (CKs), were markedly enhanced in galled tissues. Interestingly, much higher contents of IAA and CKs were detected in gall mites than in plant tissues. These results suggest that galls act as nutrient sinks and favor increased accumulation of nutrients for mites, and that gall mites may contribute IAA and CKs during gall formation.
Toxicity of Metal Ions Released from a Fixed Orthodontic Appliance to Gastrointestinal Tract Cell Lines

The mechanism of toxicity and cellular response to metal ions present in the environment is still a very current area of research. In this work, which is a continuation of the study of the toxicity of metal ions released by fixed orthodontic appliances, eluates of archwires, brackets, ligatures, and bands are used to test the prooxidant effect, cytotoxicity, and genotoxicity on cell lines of the gastrointestinal tract. Eluates obtained after three immersion periods (3, 7, and 14 days) and with known amounts and types of metal ions were used. Four cell lines—CAL 27 (human tongue), Hep-G2 (liver), AGS (stomach) and CaCo-2 (colon)—were treated with each type of eluate at four concentrations (0.1×, 0.5×, 1.0×, and 2.0×) for 24 h. Most eluates had toxic effects on CAL 27 cells over the entire concentration range regardless of exposure time, while CaCo-2 proved to be the most resistant. In AGS and Hep-G2 cells, all samples tested induced free radical formation, with the highest concentration (2×) causing a decrease in free radicals formed compared to the lowest concentrations. Eluates containing Cr, Mn, and Al showed a slight pro-oxidant effect on DNA (on plasmid φX-174 RF I) and slight genotoxicity (comet assay), but these effects are not so great that the human body could not “resist” them. Statistical analysis of data on chemical composition, cytotoxicity, ROS, genotoxicity, and prooxidative DNA damage shows the influence of metal ions present in some eluates on the toxicity obtained. Fe and Ni are responsible for the production of ROS, while Mn and Cr have a great influence on hydroxyl radicals, which cause single-strand breaks in supercoiled plasmid DNA in addition to the production of ROS. On the other hand, Fe, Cr, Mn, and Al are responsible for the cytotoxic effect of the studied eluates. The obtained results confirm that this type of research is useful and brings us closer to more accurate in vivo conditions.
Spontaneous EBV-Reactivation during B Cell Differentiation as a Model for Polymorphic EBV-Driven Lymphoproliferation

Simple Summary Epstein-Barr virus (EBV) infects a high proportion of the human population. After initial infection, EBV is maintained in healthy individuals in an inactive latent state in memory B-cells of the immune system. Reactivation of EBV from latency can drive B-cell tumours. EBV mimics immune signals to drive B-cells into specific activation states, expanding the virally infected B-cell population. Here we use a laboratory model of the human memory B-cell immune response to study the frequency and patterns of B-cell activation that occur upon spontaneous EBV reactivation. To do this we use single cell analysis of RNA expression. Consistent with the high prevalence of latent EBV infection we find evidence of EBV in cells from all eight healthy adult donors tested. While the extent varies between donors, we identify four recurrent cell states that EBV-associated B-cells adopt upon viral reactivation. Our results establish a model for studying polymorphic EBV-driven B-cell lymphoproliferation. Abstract Epstein-Barr virus (EBV)-driven B cell neoplasms arise from the reactivation of latently infected B cells. In a subset of patients, EBV was seen to drive a polymorphous lymphoproliferative disorder (LPD) in which B cell differentiation was retained. In this work, spontaneous EBV reactivation following B cell mitogen stimulation was shown to provide a potential model of polymorphic EBV-driven LPD. Here, we developed an in vitro model of plasma cell (PC) differentiation from peripheral blood memory B cells. To assess the frequency and phenotypes of EBV-associated populations derived during differentiation, we analysed eight differentiations during the PC stage with a targeted single-cell gene expression panel. We identified subpopulations of EBV-gene expressing cells with PC and/or B cell expression features in differentiations from all tested donors. EBV-associated cells varied in frequency, ranging from 3–28% of cells. Most EBV-associated cells expressed PC genes such as XBP1 or MZB1, and in all samples these included a quiescent PC fraction that lacked cell a cycle gene expression. With increasing EBV-associated cells, populations with B cell features became prominent, co-expressing a germinal centre (GC) and activating B cell gene patterns. The presence of highly proliferative EBV-associated cells was linked to retained MS4A1/CD20 expression and IGHM and IGHD co-expression, while IGHM class-switched cells were enriched in quiescent PC fractions. Thus, patterns of gene expression in primary EBV reactivation were shown to include features related to GC B cells, which was also observed in EBV-transformed lymphoblastoid cell lines. This suggests a particular association between spontaneously developing EBV-expansions and IgM+ IgD+ non-switched B cells.
Seed Priming with MeJa Prevents Salt-Induced Growth Inhibition and Oxidative Damage in Sorghum bicolor by Inducing the Expression of Jasmonic Acid Biosynthesis Genes

Salinity is one of the major detrimental abiotic stresses at the forefront of deterring crop productivity globally. Although the exogenous application of phytohormones has formerly proven efficacious to plants, their effect on the moderately stress-tolerant crop “Sorghum bicolor” remains elusive. To investigate this, S. bicolor seeds primed with methyl jasmonate (0; 10 and 15 μM MeJa) were exposed to salt (200 mM NaCl) stress, and their morpho-physiological, biochemical, and molecular attributes were measured. Salt stress significantly decreased shoot length and fresh weight by 50%, whereas dry weight and chlorophyll content were decreased by more than 40%. Furthermore, salt-stress-induced oxidative damage was evident by the formation of brown formazan spots (indicative of H2O2 production) on sorghum leaves and a more than 30% increase in MDA content. However, priming with MeJa improved growth, increased chlorophyll content, and prevented oxidative damage under salt stress. While 15 µM MeJa maintained proline content to the same level as the salt-stressed samples, total soluble sugars were maintained under 10 µM MeJa, indicating a high degree of osmotic adjustment. Shriveling and thinning of the epidermis and xylem tissues due to salt stress was prevented by MeJa, followed by a more than 70% decrease in the Na+/K+ ratio. MeJa also reversed the FTIR spectral shifts observed for salt-stressed plants. Furthermore, salt stress induced the expression of the jasmonic acid biosynthesis genes; linoleate 92-lipoxygenase 3, allene oxide synthase 1, allene oxide cyclase, and 12-oxophytodienoate reductase 1. In MeJa-primed plants, their expression was reduced, except for the 12-oxophytodienoate reductase 1 transcript, which further increased by 67%. These findings suggest that MeJa conferred salt-stress tolerance to S. bicolor through osmoregulation and synthesis of JA-related metabolites.
Efficacy of Immune Checkpoint Blockade and Biomarkers of Response in Lymphoma: A Narrative Review

Immune checkpoint blockade (ICB) has revolutionized the prognosis of several advanced-stage solid tumors. However, its success has been far more limited in hematological malignancies and is mostly restricted to classical Hodgkin lymphoma (cHL) and primary mediastinal B cell lymphoma (PMBCL). In patients with non-Hodgkin lymphoma (NHL), response to PD-1/PD-L1 ICB monotherapy has been relatively limited, although some subtypes are more sensitive than others. Numerous predictive biomarkers have been investigated in solid malignancies, such as PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability (MSI), among others. This review aims to appraise the current knowledge on PD-1/PD-L1 ICB efficacy in lymphoma when used either as monotherapy or combined with other agents, and describes potential biomarkers of response in this specific setting.
The Relationship Between Perceived Discrimination, Acculturation Attitudes, and Adaptation among Anglophone African Immigrants in Russia: The Moderating Role of Neuroticism

Background Perceived discrimination is an acculturative stressor that negatively predicts psychological and socio-cultural adaptation, partially mediated by the individual’s acculturation attitudes. However, despite being under similar conditions of high perceived discrimination, some African immigrants in Russia appear to adapt more successfully than others. Why the individual differences? Neuroticism is a trait that intensifies the experience of negative emotions and sensitivity to stress. Perhaps it amplifies the reaction to acculturative stressors (e.g., perceived discrimination) in terms of acculturation attitudes, with significant implications for adaptation. Objective This study sought to determine whether the personality trait of neuroticism influences how African immigrants in Russia react to perceived discrimination in terms of their acculturation attitudes and how this may relate to adaptation. Design A moderated mediation analysis was carried out, investigating neuroticism as a moderator in the relationship between perceived discrimination, acculturation attitudes, and adaptation of African immigrants in Russia (N = 157). Results Perceived discrimination was found to be strongly associated with poor psychological and sociocultural adaptation, which was partially mediated by the integration attitude; neuroticism strengthened this indirect negative association. Conclusion When highly neurotic African immigrants perceived elevated levels of discrimination, they were more averse to adopting a positive attitude toward integration, and as a result, were more maladapted. This result suggests that the differences in the levels of adaptation among African immigrants in Russia under similar conditions of high perceived discrimination may be partially due to their levels of neuroticism.
Nailfold Videocapillaroscopy in Patients with Rheumatoid Arthritis and Psoriatic Arthropathy on ANTI-TNF-ALPHA Therapy

Videocapillaroscopy is a simple, non-invasive investigation that allows the “in vivo” study of the nailfold capillaries. This method is inexpensive, easily accepted by patients and the results can be easily interpreted. It is mainly used in patients with Raynaud’s phenomenon and systemic sclerosis, but this examination can also be performed on patients who are suspected of having microcirculation alterations, such as rheumatoid arthritis and psoriatic arthritis. It may aid in the diagnosis, evaluation and prognosis of other rheumatic diseases, besides systemic sclerosis. The aim of this study is to identify the nailfold videocapillaroscopic abnormalities in rheumatoid arthritis and psoriatic arthritis patients and analyze the correlation between their evolution and 12 months of anti-TNF-α therapy. The abnormal capillaroscopic findings comprised widened, dilated or giant capillaries and the distortion of the normal nailfold architecture, avascular areas, hemorrhages and neoangiogenesis. Overall, capillary density, dilated capillaries, giant capillaries, elongated capillaries and angiogenesis significantly improved after 12 months. Moreover, no avascular areas were found after 12 months of anti-TNF treatment.
Treatment and Prevention of Postoperative Leakage after Gastrectomy for Gastric Cancer

Anastomotic leakage is one of the common causes of serious morbidity and death after gastrectomy. The use of surgical treatment for leakage decreased due to the development of nonsurgical management. However, if nonsurgical management fails to control the spread of intra-abdominal infection, emergency surgical treatment is required. The authors wished to determine in which cases surgical treatment is needed for postoperative leakage and to identify treatment and prevention strategies. If a patient’s vital signs are stable, local abscesses can be cured by conservative treatment after percutaneous drain insertion; if there is no improvement in anastomotic leakage, endoscopic treatment such as clipping, vacuum, and stent placement can be performed. If a patient’s vital signs are unstable or patient shows diffuse peritonitis, surgical treatment should be performed. A surgical plan can be established according to leakage location. The duodenal stump may first require conservative treatment. It is recommended that surgical treatment be attempted first for anastomotic leakage of gastrojejunostomy site and gastric stump in remnant stomach. In conclusion, the need for surgical treatment is determined depending on vital signs and presence of diffuse peritonitis. During surgical treatment, a strategic approach is required according to the patient’s condition and the anatomical location of leakage.