Advancements in inhibitors of crucial enzymes in the cysteine biosynthetic pathway: Serine acetyltransferase and O-acetylserine sulfhydrylase.

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.

Brucella Seropositivity at a Tertiary Care Hospital in Chandigarh.

There are reports that the neglected zoonotic tropical disease brucellosis is reemerging today. Serological tests are being widely used in the diagnosis of brucellosis. In the present study, we performed a standard agglutination test (SAT) on 1348 suspected cases of brucellosis during the period of four years from April 2018 to March 2022. We noticed an increase in seropositivity from 2.6% in the year 2018-19 to 7.4% in the year 2021-22. We also noticed a spike in seropositivity in the years 2019-20 (12.5%). Our study shows the recent trend in seropositivity of the disease in Chandigarh and, hence, can be a meaningful addition to the existing serological diagnostic data related to brucellosis.

Adipose Tissue Segmentation after Lung Slice Localization in Chest CT Images Based on ConvBiGRU and Multi-Module UNet.

The distribution of adipose tissue in the lungs is intricately linked to a variety of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Accurate detection and quantitative analysis of subcutaneous and visceral adipose tissue surrounding the lungs are essential for effectively diagnosing and managing these diseases. However, there remains a noticeable scarcity of studies focusing on adipose tissue within the lungs on a global scale. Thus, this paper introduces a ConvBiGRU model for localizing lung slices and a multi-module UNet-based model for segmenting subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), contributing to the analysis of lung adipose tissue and the auxiliary diagnosis of lung diseases. In this study, we propose a bidirectional gated recurrent unit (BiGRU) structure for precise lung slice localization and a modified multi-module UNet model for accurate SAT and VAT segmentations, incorporating an additive weight penalty term for model refinement. For segmentation, we integrate attention, competition, and multi-resolution mechanisms within the UNet architecture to optimize performance and conduct a comparative analysis of its impact on SAT and VAT. The proposed model achieves satisfactory results across multiple performance metrics, including the Dice Score (92.0% for SAT and 82.7% for VAT), F1 Score (82.2% for SAT and 78.8% for VAT), Precision (96.7% for SAT and 78.9% for VAT), and Recall (75.8% for SAT and 79.1% for VAT). Overall, the proposed localization and segmentation framework exhibits high accuracy and reliability, validating its potential application in computer-aided diagnosis (CAD) for medical tasks in this domain.

Silencing HEATR1 Rescues Cisplatin Resistance of Non-Small Cell Lung Cancer by Inducing Ferroptosis via the p53/SAT1/ALOX15 Axis.

BACKGROUND: Cisplatin (DDP) is a commonly used chemotherapy agent. However, its resistance to the drug is a major challenge in its clinical application. Earlier research has suggested a connection between HEATR1 and chemoresistance in cancer. However, additional investigation is needed to better understand its involvement in resistance to DDP. In this study, we aimed to determine the regulatory effect of HEATR1 on the resistance of cisplatin in NSCLC. METHODS: We collected specimens of both DDP-resistant and non-resistant NSCLC to examine the expression of HEATR1. Additionally, we established cisplatin-resistant cells of NSCLC using the A549 cell line. Cell ability was examined by CCK-8 assay. Cell apoptosis and lipid ROS were examined by flow cytometry. The expressions of HEATR1, p53, SAT1, and ALOX15 were determined by qRT-PCR and Western blot. The tumor xenograft experiment was conducted to assess the impact of silencing HEATR1 on cisplatin resistance in vivo in NSCLC. RESULTS: The expression levels of HEATR1 were found to be significantly elevated in DDP-resistant tissues and cells of NSCLC as compared to non-resistant counterparts. Conversely, the expression levels of p53, SAT1, and ALOX15 were observed to be reduced in DDP-resistant cells. Through the inhibition of HEATR1, the proliferation of DDP-resistant cells was significantly suppressed, while the generation of lipid ROS was enhanced. This effect was achieved by activating ferroptosis and the p53/SAT1/ALOX15 pathway, as demonstrated both in vitro and in vivo. Conversely, the overexpression of HEATR1 exhibited opposite effects. Furthermore, the silencing of p53 and ALOX15 reversed the oncogenic effects of HEATR1 and inhibited ferroptosis in DDP-resistant NSCLC cells, suggesting the involvement of p53 and ALOX15 in HEATR1-mediated DDP resistance. CONCLUSION: Finally, the findings revealed that HEATR1 silencing reduced DDP resistance in NSCLC by inducing ferroptosis via the p53/SAT1/ALOX15 axis. HEATR1 might become a potential target for overcoming DDP resistance in NSCLC treatment.

Targeting SAT1 prevents osteoporosis through promoting osteoclast apoptosis.

Osteoporosis is a systemic bone disease characterized by decreased bone mass that is tightly regulated by the coordinated actions of osteoclasts and osteoblasts. Apoptosis as a precise programmed cell death involves a cascade of gene expression events which are mechanistically linked to the regulation of bone metabolism. Nevertheless, the critical biomolecules involved in regulating cell apoptosis in osteoporosis remain unknown. To gain a deeper insight into the relationship between apoptosis and osteoporosis, this study integrated the sequencing results of human samples and using a machine learning workflow to overcome the limitations of a single study. Among all immune cell populations, we assessed the apoptotic level and portrayed the distinct subtypes and lineage differentiation of monocytic cells in osteoporotic tissues. Osteoclasts expressed a higher level of Spermidine/spermine-N1-Acetyltransferase1 (SAT1) during osteoclastogenesis which prevented osteoclasts apoptosis and facilitate osteoporosis progression. In addition, Berenil, one potent SAT1 inhibitor, increased osteoclast apoptosis and reversed the bone loss in the femurs of a murine ovariectomy model. In summary, Berenil promotes osteoclast apoptosis, inhibits the bone resorption and improves the abnormal bone structure in vitro and in vivo models by targeting SAT1, demonstrating its potential as a precise therapeutic strategy for clinical osteoporosis treatment.

A Review of the Paradigmatic Role of Adipose Tissue in Renal Cancer: Fat Measurement and Tumor Behavior Features.

(1) Background: Renal-cell carcinoma (RCC) incidence has been steadily rising, with obesity identified as a potential risk factor. However, the relationship between obesity and RCC prognosis remains unclear. This systematic review aims to investigate the impact of different adipose tissue measurements on RCC behavior and prognosis. (2) Methods: A search of MEDLINE databases identified 20 eligible studies focusing on various fat measurements, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PRAT), and the Mayo adhesive probability (MAP) score. (3) Results: The review revealed conflicting findings regarding the association between adipose tissue measurements and RCC outcomes. While some studies suggested a protective role of certain fat deposits, particularly VAT, against disease progression and mortality, others reported contradictory results across different adipose metrics and RCC subtypes. (4) Conclusions: Methodological variations and limitations, such as retrospective designs and sample size constraints, pose challenges to standardization and generalizability. Further research is needed to understand these associations better and establish standardized approaches for adiposity assessment in RCC patients, which could inform clinical practice and therapeutic decision-making.

Translational validity of neuropsychological tasks of sustained attention between rodents and humans: A systematic review of three rodent tasks.

Atypical sustained attention is a symptom in a number of neurological and psychological conditions. Investigations into its neural underpinnings are required for improved management and treatment. Rodents are useful in investigating the neurobiology underlying atypical sustained attention and several rodent tasks have been developed for use in touchscreen testing platforms that mimic methodology used in human clinical attention assessment. This systematic review was conducted to assess how translatable these rodent tasks are to equivalent clinical human tasks. Studies using the rodent Continuous Performance Task (rCPT), Sustained Attention Task (SAT), and 5-choice CPT (5C-CPT) were sought and screened. Included in the review were 138 studies, using the rCPT (n = 21), SAT (n = 90), and 5C-CPT (n = 27). Translatability between rodent and human studies was assessed based on (1) methodological similarity, (2) performance similarity, and (3) replication of results. The 5C-CPT was found to be the most translatable cross-species paradigm with good utility, while the rCPT and SAT require adaptation and further development to meet these translatability benchmarks. With greater replication and more consistent results, greater confidence in the translation of sustained attention results between species will be engendered.

Chimeric Porcine Parvovirus VP2 Virus-like Particles with Epitopes of South African Serotype 2 Foot-and-Mouth Disease Virus Elicits Specific Humoral and Cellular Responses in Mice.

Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21-40 of VP1) and/or the B-cell epitope (amino acids 135-174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2-23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.

Determination of low concentrations of glucose through colorimetric analysis using CoFe2O4 magnetic catalyst and SAT-3.

Natural enzyme mimics have attracted attention as alternatives to natural peroxidases. Among these, magnetic nanoparticles, especially ferrites, have attracted attention because of their unique electronic and physical structures, which are expected to be applied in various fields, including high-frequency magnetic materials, biomaterials, gas sensors, and semiconductor photocatalysts. The structural properties of the synthesized catalysts were investigated using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The prepared CoFe2O4 exhibited a spinel ferrite structure and formed a wood-flake-like bulk structure. In this study, magnetic CoFe2O4 was prepared using a precipitation method as a natural enzyme mimetic. CoFe2O4 showed excellent peroxidase-like activity, as demonstrated by the Michaelis-Menten constant (Km) and the maximum velocity (Vmax). The linear ranges of the calibration curves for H2O2 and glucose were in the range of 0-500 µM, and the detection limits were 1.83 and 5.91 µM, respectively. This analytical method was applied for the determination of glucose in human serum, and the results were satisfactory and consistent with certified values. The performance of this sensor was comparable to or superior to those of several other sensors commonly used for glucose analysis, indicating that its practical application is feasible.

Seroprevalence and molecular detection of foot and mouth disease virus in cattle in selected districts of Wolaita Zone, Southern Ethiopia.

Foot and mouth disease (FMD) is a highly contagious, endemic, and acute viral cattle ailment that causes major economic damage in Ethiopia. Although several serotypes of the FMD virus have been detected in Ethiopia, there is no documented information about the disease's current serostatus and serotypes circulating in the Wolaita zone. Thus, from March to December 2022, a cross-sectional study was conducted to evaluate FMDV seroprevalence, molecular detection, and serotype identification in three Wolaita Zone sites. A multistage sample procedure was used to choose three peasant associations from each study region, namely Wolaita Sodo, Offa district, and Boloso sore district. A systematic random sampling technique was employed to pick 384 cattle from the population for the seroprevalence research, and 10 epithelial tissue samples were purposefully taken from outbreak individuals for molecular detection of FMDV. The sera were examined using 3ABC FMD NSP Competition ELISA to find antibodies against FMDV non-structural proteins, whereas epithelial tissue samples were analyzed for molecular detection using real-time RT-PCR, and sandwich ELISA was used to determine the circulating serotypes. A multivariable logistic regression model was used to evaluate the associated risk variables. The total seroprevalence of FMD in cattle was 46.88% (95% CI 41.86-51.88), with Wolaita Sodo Town having the highest seroprevalence (63.28%). As a consequence, multivariable logistic regression analysis revealed that animal age, herd size, and interaction with wildlife were all substantially related to FMD seroprevalence (p < 0.05). During molecular detection, only SAT-2 serotypes were found in 10 tissue samples. Thus, investigating FMD outbreaks and identifying serotypes and risk factors for seropositivity are critical steps in developing effective control and prevention strategies based on the kind of circulating serotype. Moreover, further research for animal species other than cattle was encouraged.

Corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

BACKGROUND: In this study, we investigated whether Exo regulate the proliferation and invasion of PC. METHODS: In this study, we isolated the Eriobotrya japonica Exo using Ultra-high speed centrifugal method. Mass spectrum were used for Exo active components analysis. PC (Capan-1 and Bxpc-3) cells proliferation, migration, and apoptosis were detected using CCK8, ethynyldeoxyuridine, transwell, wound healing, and flow cytometry analyses. We also constructed a lung metastatic mouse model and subcutaneous tumor model to illustrate the regulation effect of Exo or active components. Proteomics were used to reveal the regulatory mechanism responsible for the observed effects. RESULTS: We isolated Eriobotrya japonica Exo and found that Exo treatment significantly suppressed cell migration and proliferation in both in vivo and in vitro using Capan-1. Mass spectrum for Exo active components analysis found that Exo contains high amounts of corosolic acid (CRA). The further study found that CRA treatment inhibit the proliferation, migration, and increased cell death of both Capan-1 and Bxpc-3 cells in a concentration-dependent manner. In vivo experiments confirmed that CRA inhibited pulmonary metastasis by decreasing the number of metastatic foci. Cell proteomics analysis showed that CRA treatment induced spermidine/spermine N1-acetyltransferase 1 (SAT1)-dependent ferroptosis. Treatment with the ferroptosis suppressor ferrostatin-1 significantly reversed CRA-induced cell apoptosis. CONCLUSION: The data suggested that corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

The Association of Body Composition Parameters Measured by Computed Tomography with Cancer Stage, Prognosis, and Survival in Patients with Renal Cell Carcinoma.

OBJECTIVE: This study aims to investigate the association of preoperative body composition parameters, measured by computed tomography in patients undergoing surgery for renal cell carcinoma, with its stage and to survey the relationship with postoperative hospitalization duration and survival. METHODS: Demographic data, pathology results, cancer stages, and hospitalization duration of 104 patients undergoing surgery at the urology clinic due to renal cell carcinoma between 2019 and 2023 were analyzed retrospectively. On computed tomography scans acquired during diagnosis, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue, and skeletal muscle area were measured. The ratios of body composition parameters were computed. RESULTS: When the correlation between survival time and body composition in deceased patients was analysed, a moderate but significant correlation was observed between skeletal muscle area value and total adipose tissue / skeletal muscle area ratio (r=0.630, p=0.001; r=0.598, p=0.002). A significant and strong correlation was observed between total adipose tissue value and survival (r=0.704, p<0.001). Subcutaneous adipose tissue / skeletal muscle area was found to be an independent risk factor associated with mortality, and a ratio of 0.98 or less increased the mortality risk approximately 16-fold. CONCLUSION: The relationship between body composition parameters measured by computed tomography, which can be easily evaluated pre-treatment, and mortality, postoperative recovery and length of hospital stay can be evaluated, giving clinicians an idea about the potential difficulties that patients may encounter during the treatment process. For this purpose, the subcutaneous adipose tissue / skeletal muscle area ratio is the most helpful parameter that can be used.

Calcium Chloride Treatment Enhances Antigen Production in Foot-and-Mouth Disease Vaccines for Serotypes SAT1 and SAT3.

Foot-and-mouth disease (FMD) is a highly contagious viral infection causing acute and severe vesicular lesions in cattle and pigs, which has prompted global vaccination policies. This study presents a technique for enhancing antigen yield in SAT1 BOT and SAT3 ZIM by treatment with calcium chloride (CaCl2). We tested changes in cell viability in BHK-21 suspension cells treated with varying concentrations of CaCl2. The optimal CaCl2 concentration was determined based on antigen yield. The timing of CaCl2 supplementation relative to FMD virus inoculation was tested. Finally, the optimal medium for antigen production was identified. We observed a concentration-dependent decrease in BHK-21 cell viability at >7.5 mM CaCl2. A CaCl2 concentration of 3 mM yielded the most antigens. CaCl2 supplementation relative to FMD virus infection was optimal 2 h before or with viral inoculation. CD-BHK 21 medium supplemented with CaCl2 was the most productive medium. Specifically, SAT1 BOT and SAT3 ZIM showed improved antigen production in CD-BHK 21 medium with 3 mM CaCl2, while Provero-1 and Cellvento BHK-200 media showed no significant enhancement. Overall, CaCl2 supplementation enhanced FMD antigen productivity. This study provides a useful framework for enhancing antigen production efficiently in the FMD vaccine industry.

Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer.

Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.

The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling.

Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 (SAT1), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1, which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A. MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Non-redundant implicational base of formal context with constraints using SAT.

An implicational base is knowledge extracted from a formal context. The implicational base of a formal context consists of attribute implications which are sound, complete, and non-redundant regarding to the formal context. Non-redundant means that each attribute implication in the implication base cannot be inferred from the others. However, sometimes some attribute implications in the implication base can be inferred from the others together with a prior knowledge. Regarding knowledge discovery, such attribute implications should be not considered as new knowledge and ignored from the implicational base. In other words, such attribute implications are redundant based on prior knowledge. One sort of prior knowledge is a set of constraints that restricts some attributes in data. In formal context, constraints restrict some attributes of objects in the formal context. This article proposes a method to generate non-redundant implication base of a formal context with some constraints which restricting the formal context. In this case, non-redundant implicational base means that the implicational base does not contain all attribute implications which can be inferred from the others together with information of the constraints. This article also proposes a formulation to check the redundant attribute implications and encoding the problem into satisfiability (SAT) problem such that the problem can be solved by SAT Solver, a software which can solve a SAT problem. After implementation, an experiment shows that the proposed method is able to check the redundant attribute implication and generates a non-redundant implicational base of formal context with constraints.

Blastocoel fluid aspiration improves vitrification outcomes and produces similar sexing results of in vitro-produced cattle embryos compared to microblade biopsy.

The potential applications of in vitro-produced (IVP) cattle embryos are significantly enhanced when combined with genotype selection and cryopreservation techniques. While trophectoderm (TE) biopsies are frequently used for genotyping, cell-free DNA (cfDNA) found in blastocoele fluid (BF) arises as a less-invasive method. Moreover, the blastocoel collapse produced by BF aspiration could be beneficial for embryo cryotolerance. This study was conducted to test the BF as a source of cell free-DNA (cfDNA) and to compare the BF to the TE biopsy in terms of sexing efficiency/accuracy, embryo survival and gene expression after vitrification/warming. IVP day 7 expanded blastocysts were artificially collapsed by aspiration of BF (VIT-Collapsed) or biopsied (VIT-Biopsied). After sample collection, embryos were vitrified/warmed by the Cryotop method and individually cultured in vitro. Intact fresh non-vitrified and vitrified/warmed blastocysts served as Fresh Control and VIT-Control, respectively. After sex identification of BF or TE biopsies and the corresponding surviving embryos, amplification efficiency and sexing accuracy were assessed. There were no differences between the BF and TE biopsy samples in terms of sexing accuracy or efficiency. Although all vitrified groups showed lower post-warming re-expansion rates (p < 0.05), the blastocyst re-expansion rates in the VIT-Collapsed group were comparable to those in the Fresh Control group whereas biopsied blastocysts showed the lowest (p < 0.05) re-expansion rates. VIT-Collapsed blastocysts had hatching rates that were comparable to those of Fresh Control blastocysts but significantly higher than those of the other vitrification treatments. Proapoptotic gene BAX was overexpressed in VIT-Biopsied embryos, whereas BCL2 transcripts were more abundant in the VIT-Collapsed group. On the other hand, VIT-Biopsied embryos showed altered ATP1B1- and AQP3-mRNA levels. The analysis of the cfDNA present in the BF is an efficient, minimally invasive approach to sex IVP cattle embryos. Besides, the artificial collapse of blastocoel prior to vitrification resulted in higher re-expansion and hatching ability than when embryos were vitrified after being biopsied.

Adipose tissue indices predict prognosis in hodgkin lymphoma.

INTRODUCTION BACKGROUND: This study evaluated the impact of adipose tissue indices on prognosis of HL. METHODS: Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival. RESULTS: For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant. CONCLUSION: SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.

The Potential Role of SCFAs in Modulating Cardiometabolic Risk by Interacting with Adiposity Parameters and Diet.

The main objective of this cross-sectional study was to analyze the influence of lifestyle factors (diet, physical activity, sleep) that can affect the concentration of fecal short-chain fatty acids (SCFAs) and SCFAs' potential role in modulating cardiometabolic disease risk by interacting with biochemical and body composition parameters. The study comprised 77 healthy, non-obese individuals aged 30-45 years who were assessed for the concentration of SCFAs in stool, diet, physical activity level, and sleep duration. Moreover, body composition measurement and patients' biochemical parameters were included in the analysis. We have indicated a significant negative correlation between several SCFAs (especially acetic acid (AA), isobutyric acid (IBA), butyric acid (BA), propionic acid (PA), isovaleric acid (IVA) and valeric acid (VA)) with BMI, VAT/SAT ratio (visceral to subcutaneous fat ratio), and percentage of fat mass in a group of females enrolled in the study as well as with waist circumference (WC) in case of both sexes included in the study. Moreover, the results of our study acknowledged the importance of a diet in shaping the SCFA profile-we noticed significant negative associations between energy and fat intake and some SCFAs in males (IBA, IVA, VA, isocaproic acid (ICA)). Further, we indicated that a high intake of fiber (insoluble and soluble) in both males and females results in an elevated concentration of the vast majority of SCFAs and the amount of SCFAs in total. This effect was particularly noticeable in the case of the soluble fraction of fiber. These correlations reflect the fact that diet shapes the composition of the gut microbiota and SCFAs (main microbial metabolites) are synthesized from dietary fiber. In addition, we noticed that in a group of women, the concentration of AA, PA, and ICA as well as the total concentration of SCFAs showed a significant positive association with their sleep duration. We concluded that SCFAs can have a potential role in modulating cardiometabolic disease risk by interacting with adiposity parameters and diet. In addition, this potential direct link between diet and SCFAs may at least partly contribute to sleep improvement.