Biological Conditions Research Articles

Discovery and binding mode of small molecule inhibitors of the apo form of human TDO2.

Tryptophan-2,3-dioxygenase (TDO2) and indoleamine-2,3-dioxygenase (IDO1) are structurally distinct heme enzymes that catalyze the conversion of L-tryptophan to N-formyl-kynurenine, and play important roles in metabolism, inflammation, and tumor immune surveillance. The enzymes can adopt an inactive, heme-free (apo) state or an active, heme-containing (holo) state, with the balance between them varying dynamically according to biological conditions. Inhibitors of holo-TDO2 are known but, despite several advantages of the heme-free state as a drug target, no inhibitors of apo-TDO2 have been reported. We describe the discovery of the first apo-TDO2 binding inhibitors, to our knowledge, and their inhibition of cellular TDO2 activity at low nanomolar concentrations. The crystal structure of a potent, small molecule inhibitor bound to apo-TDO2 reveals its detailed binding interactions within the large, hydrophobic heme binding pocket of the active site.

Abstract A012: g3bp1-mediated stress granule formation drives melanoma initiation in zebrafish

Abstract Stress granules confer cancer cells the ability to withstand harsh biological conditions and impart tumorigenic translational states through mRNA sequestration. Despite advances in in vitro knowledge, mechanistic understanding of the endogenous influence of stress granules during tumorigenesis in vivo remains understudied. To address this, we use a zebrafish melanoma model where oncogenic human BRAF V600E is driven by the melanocyte master regulator mitfa in a p53 -/- background. Through vector-based genetic engineering, endogenous melanoma induction in these zebrafish can be developmentally staged from single cell to tumor. BRAF V600E ::p53 -/- melanocytes form a cancerized field (CF), from which a subset upregulate the melanocyte master regulator mitfa, creating a cancer precursor zone (CPZ). Transformation of CPZ cells to an embryonic, neural crest-like state facilitates their formation of an early tumor patch that inevitable develops into an overt tumor. Single cell RNAseq analysis of cells representing each melanoma stage showed that CPZ cells upregulate core stress granule markers, including g3bp1, tia1, tia1l, and nufip2. Immunostaining of g3bp1 in CF, CPZ, patch, and tumor cells revealed a significant induction of stress granules from the CF to CPZ transition (2 vs 10 stress granules/cell; N=3; p=0.034) that persists during the patch and tumor stage, indicating cell stress accompanies melanoma initiation and progression. Genetic disruption of g3bp1 through cell autonomous, melanocyte-specific CRISPR editing in zebrafish (N=10-13) causes delayed CPZ onset (P=0.012) and fewer CPZs to form (P=0.021). In turn, g3bp1-edited zebrafish have delayed tumor formation (P=0.026) and develop fewer tumors (P=0.006). To decipher the RNAs sequestered by stress granules during melanomagenesis, we performed RIPseq for G3BP1 in human A375 melanoma cells stressed with sodium arsenite. RNAs significantly bound to G3BP1 upon stress induction include major tumor suppressors, such as CDKN2A, RBM5, BIK, and RHOB. Together, these results suggest that endogenous g3bp1-mediated stress granule formation in melanoma initiating cells is tumorigenic in vivo and operates through the sequestration of tumor suppressive RNAs. Citation Format: Kyle D Drake, Emily Formato, Leonard Zon. g3bp1-mediated stress granule formation drives melanoma initiation in zebrafish [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A012.

A Bioconductor/R Workflow for the Detection and Visualization of Differential Chromatin Loops

Background Chromatin loops play a critical role in gene regulation by connecting regulatory loci and gene promoters. The identification of changes in chromatin looping between cell types or biological conditions is an important task for understanding gene regulation; however, the manipulation, statistical analysis, and visualization of data sets describing 3D chromatin structure is challenging due to the large and complex nature of the relevant data sets. Methods Here, we describe a workflow for identifying and visualizing differential chromatin loops from Hi-C data from two biological conditions using the ‘mariner’, ‘DESeq2’ and ‘plotgardener’ Bioconductor/R packages. The workflow assumes that Hi-C data has been processed into ‘.hic’ or ‘.cool’ files and that loops have been identified using an existing loop-calling algorithm. Results First, the ‘mariner’ package is used to merge redundant loop calls and extract interaction frequency counts. Next, ‘DESeq2’ is used to identify loops that exhibit differential contact frequencies between conditions. Finally, ‘plotgardener’ is used to visualize differential loops. Conclusion Chromatin interaction data is an important modality for understanding the mechanisms of transcriptional regulation. The workflow presented here outlines the use of ‘mariner’ as a tool to manipulate, extract, and aggregate chromatin interaction data, ‘DESeq2’ to perform differential analysis of these data across conditions, samples, and replicates, and ‘plotgardener’ to explore and visualize the results.

The Coordinated Changes in Platelet Glycan Patterns with Blood Serotonin and Exosomes

The structures of glycans, specifically their terminal positions, play an important role as ligands for receptors in regulating the adhesion ability of platelets. Recent advances in our understanding of free/unbound serotonin (5-HT) in blood plasma at supraphysiological levels implicate it as one of the most profound influencers in remodeling the platelet’s surface N-glycans. Proteomic analysis of the membrane vesicles identified enzymes, specifically glycosyltransferases, only on the surface of the platelets isolated from the supraphysiological level of 5-HT-containing blood plasma. However, these enzymes can only be effective on the cell surface under certain biological conditions, such as the level of their substrates, temperature, and pH of the environment. We hypothesize that exosomes released from various cells coordinate the required criteria for the enzymatic reaction on the platelet surface. The elevated plasma 5-HT level also accelerates the release of exosomes from various cells, as reported. This review summarizes the findings from a wide range of literature and proposes mechanisms to coordinate the exosomes and plasma 5-HT in remodeling the structures of N-glycans to make platelets more prone to aggregation.

A Review on Exploring the Potential of Vincamine and Melatonin as an Effective Anti-depressant Agent.

Depression is a prevalent psychiatric disorder and one of the leading causes of disability around the world. Herbal and synthetic medications used to treat depression, may interrupt the therapy process and cause adverse effects. Currently, the use of medicinal and phytochemical plants, which have various therapeutic effects and has potential strategy for treating depression. According to the studies, medicinal plants have a variety of effects on the brain system and have antidepressant properties such as synaptic modulation of serotonin, noradrenalin and dopamine as well as inflammatory mediators. According to the literature review, Vinca Rosea extract has a variety of pharmacological activities, but there is no evidence of its antidepressant properties. The main aim of the present study is to gather data from the literature review regarding the antidepressant activity of vincamine alone and along with melatonin. According to the review antidepressant activity of various medications can be tested using two different types of studies, including in-vivo and in-vitro. Clinical and preclinical research suggests that one of the main mediators in the pathophysiology of depression seems to be stress. Depression can be evaluated using experimental methods based on a variety of physical indicators, including locomotor activity, rearing, faeces, and the quantity of entries in the centre square (in-vivo and in-vitro). Biological conditions can be used to find it as well. It has been successfully concluded that vincamine, either alone or in combination with melatonin, may provide a potential role as an antidepressant. According to the Globe Health Organization, depression will become the most common cause of loss of interest in working in the world. As a result, depression research is one of the most significant ways in which we might create new treatments in the form of vincamine and combination with melatonin for depression and improve existing therapies to make them work better for depressed people. It will also aid in the development and creation of novel ways for the better treatment of depression.

The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies.

Cancer, the second greatest cause of mortality worldwide, frequently causes bone me-tastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord com-pression. These injurious incidents leave uncomfortably large holes in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and ex-hibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various bio-logical processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.

Analysis of External Environmental Design Factors on Mosquito Breeding in Sikka Regency, East Nusa Tenggara

Factors such as environmental temperature, rainfall, location of waste disposal sites, sunlight exposure, water flow, as well as chemical, biological, and socio-cultural conditions play a crucial role in the development of malaria cases. This study specifically aims to analyze the influence of environmental elements on the number of malaria and dengue fever (DF) cases in Sikka Regency, as well as to evaluate the physical design elements of the area that can reduce DF cases in the region. The research was conducted in several locations within Sikka Regency, taking into account the differences in location and the distance between buildings in relation to thermal characteristics. The results indicate that areas located more than 500 meters above sea level did not experience malaria or DF cases, which is also influenced by the outdoor environmental design, such as building density and vegetation size, affecting light intensity. Lower light intensity increases humidity, which accelerates mosquito breeding.

Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis.

Data overlapping of different biological conditions prevents personalized medical decision-making. For example, when the neutrophil percentages of surviving septic patients overlap with those of non-survivors, no individualized assessment is possible. To ameliorate this problem, an immunological method was explored in the context of sepsis. Blood leukocyte counts and relative percentages as well as the serum concentration of several proteins were investigated with 4072 longitudinal samples collected from 331 hospitalized patients classified as septic (n=286), non-septic (n=43), or not assigned (n=2). Two methodological approaches were evaluated: (i) a reductionist alternative, which analyzed variables in isolation; and (ii) a non-reductionist version, which examined interactions among six (leukocyte-, bacterial-, temporal-, personalized-, population-, and outcome-related) dimensions. The reductionist approach did not distinguish outcomes: the leukocyte and serum protein data of survivors and non-survivors overlapped. In contrast, the non-reductionist alternative differentiated several data groups, of which at least one was only composed of survivors (a finding observable since hospitalization day 1). Hence, the non-reductionist approach promoted personalized medical practices: every patient classified within a subset associated with 100% survival subset was likely to survive. The non-reductionist method also revealed five inflammatory or disease-related stages (provisionally named 'early inflammation, early immunocompetence, intermediary immuno-suppression, late immuno-suppression, or other'). Mortality data validated these labels: both 'suppression' subsets revealed 100% mortality, the 'immunocompetence' group exhibited 100% survival, while the remaining sets reported two-digit mortality percentages. While the 'intermediary' suppression expressed an impaired monocyte-related function, the 'late' suppression displayed renal-related dysfunctions, as indicated by high concentrations of urea and creatinine. The data-driven differentiation of five data groups may foster early and non-overlapping biomedical decision-making, both upon admission and throughout their hospitalization. This approach could evaluate therapies, at personalized level, earlier. To ascertain repeatability and investigate the dynamics of the 'other' group, additional studies are recommended.

Discovery of Mycobacterium avium subsp. paratuberculosis Lytic Phages with Extensive Host Range Across Rapid- and Slow-Growing Pathogenic Mycobacterial Species

Background/Objectives: Developing interventions for Johne’s disease, which focuses on controlling Mycobacterium avium subsp. paratuberculosis (MAP) in contaminated environments by treating infected cows and preventing transmission from diseased animals, is a critical priority. Bacteriophage (phage) therapy, an emerging biological intervention, offers a promising alternative for the treatment and management of MAP infections. Methods: In this study, we generated an MAP-specific lytic phage library aimed at characterizing the therapeutic potential of phages under environmental and biological conditions that mimic those encountered in infected cattle such as ruminal fluid, milk, colostrum, and the bovine intestinal epithelium, a key site of MAP colonization and, later, transmission. Results: Our library contains a diverse collection of phages that have demonstrated robust lytic activity against MAP. The host range of these phages was thoroughly assessed, revealing that several isolates produce clear plaques on a range of MAP strains, as well as other pathogenic non-tuberculous mycobacterial (NTM) species and M. tuberculosis strains. This broad host range expands the therapeutic potential of the phage collection, positioning it as a potential cross-species antimicrobial tool. In vitro tests under conditions replicating the rumen, milk, and colostrum environments show that selected phages maintain stability and lytic efficacy, even in the presence of complex biological fluids. Furthermore, a subset of these phages was capable of preventing MAP colonization and invasion in cultured bovine epithelial cells, suggesting their potential for direct prophylactic application in cattle. Conclusions. Our collection of MAP phages represents a valuable source that can be developed into probiotic-like preparations, offering a cost-effective solution for prophylaxis and control of Johne’s disease.

Functionalized Nanodiamonds for Targeted Neuronal Electromagnetic Signal Detection.

Intracellular sensing technologies necessitate a delicate balance of spatial resolution, sensitivity, biocompatibility, and stability. While existing methods partially fulfill these criteria, none offer a comprehensive solution. Nanodiamonds (NDs) harboring nitrogen-vacancy (NV) centers have emerged as promising candidates due to their sensing capabilities under biological conditions and their ability to meet all aforementioned requirements. This study focuses on expanding the application of NDs and NV center-based sensing to neuronal contexts by investigating their functionalization and subsequent effects on three distinct cell lines relevant to neurodegenerative disease research. Our study concentrates on positioning fluorescent NDs (FNDs) with NV center point defects onto neuronal cell surfaces. Achieving this through specific antibody attachment enhances the proximity of FND to neurites, facilitating the detection of local action potentials. Targeting voltage-dependent calcium channels (Cav2.2) with biotin-streptavidin-bound antibodies enables the precise positioning of FNDs. The functionalized FNDs (f-FNDs) show increased size and zeta potential, confirming the antibody presence without compromising cell viability. Two-color confocal imaging and co-localization algorithms are employed to further attest to the success of the functionalization. The f-FNDs are applied to cell cultures of three cell lines: SH-SY5Y, differentiated dopaminergic neurons, and hippocampal rat neurons; their biocompatibility and effects on synaptic activity are explored. Moreover, preliminary total internal reflection fluorescence - optically detected magnetic resonance (TIRF-ODMR) experiments across cellular sites demonstrate the magnetic field sensitivity of our sensor network. The successful establishment of this sensor network provides a platform for characterizing neuronal signaling in healthy models and conditions mimicking Parkinson's disease.

Ecological success of extreme halophiles subjected to recurrent osmotic disturbances is primarily driven by congeneric species replacement.

To understand how extreme halophiles respond to recurrent disturbances, we challenged the communities thriving in salt-saturated (~36% salts) ~230L brine mesocosms to repeated dilutions down to 13% (D13 mesocosm) or 20% (D20 mesocosm) salts each time mesocosms reached salt saturation due to evaporation (for 10 and 17cycles, respectively) over 813days. Depending on the magnitude of dilution, the most prevalent species, Haloquadratum walsbyi and Salinibacter ruber, either increased in dominance by replacing less competitive populations (for D20, moderate stress conditions), or severely decreased in abundance and were eventually replaced by other congeneric species better adapted to the higher osmotic stress (for D13, strong stress conditions). Congeneric species replacement was commonly observed within additional abundant genera in response to changes in environmental or biological conditions (e.g. phage predation) within the same system and under a controlled perturbation of a relevant environmental parameter. Therefore, a genus is an ecologically important level of diversity organization, not just a taxonomic rank, that persists in the environment based on congeneric species replacement due to relatively high functional overlap (gene sharing), with important consequences for the success of the lineage, and similar to the success of a species via strain-replacement. Further, our results showed that successful species were typically accompanied by the emergence of their own viral cohorts, whose intra-cohort diversity appeared to strongly covary with, and likely drive, the intra-host diversity. Collectively, our results show that brine communities are ecologically resilient and continuously adapting to changing environments by transitioning to alternative stable states.

Cenchrus spinifex Invasion Alters Soil Nitrogen Dynamics and Competition

Invasive plants often alter biological soil conditions to increase their own competitiveness. Through indoor simulated nitrogen deposition culture experiments, we investigated the differences in growth indicators and nutrient content levels between the invasive plant Cenchrus spinifex Cav. and the native symbiotic plant Agropyron cristatum (L.) Gaertn. under diverse nitrogen application modes and planting-competition ratios. Furthermore, we examined the alterations in key microbial communities involved in soil nitrogen cycling of C. spinifex. The results indicated that the invasion of C. spinifex could inhibit the growth of native plants, and in fact altered the accumulation and transformation processes related to soil nitrogen, resulting in reduced rates of soil nitrogen transformation. The overarching aim of this research was to construct a theoretical foundation for the scientific comprehension of the invasion mechanisms of C. spinifex, in order to better prevent the further spread of this invasive plant and mitigate its pernicious impact on the current environment.

Association between the Planetary Health Diet Index and biological aging among the U.S. population.

The Planetary Health Diet (PHD) is a novel dietary pattern proposed by the EAT-Lancet Commission in 2019, yet a limited study has investigated the anti-aging effects of PHD to date. This study aimed to explore the association between adherence to PHD, as quantified by the Planetary Health Diet Index (PHDI), and biological aging in American populations. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) for 1999-2018. Food consumption information was relied on two 24-h diet recall questionnaires. The biological aging condition was comprehensively assessed by four biological markers, including phenotypic age, biological age, telomere length, and klotho concentration. Weighted multivariate linear models, restricted cubic spline (RCS), and subgroup analysis were subsequently carried out to evaluate the influence of PHDI on biological aging. 44,925 participants with complete data were finally enrolled in our study. The fully adjusted models showed decreased 0.20 years in phenotypic age [-0.20 (-0.31, -0.10)] and declined 0.54 years in biological age [-0.54 (-0.69, -0.38)] correlated with PHDI per 10 scores increment. Klotho concentration [6.2 (1.0, 11.0)] was positively related to PHDI. In Model 2, telomere length increased by 0.02 bp for every 10-point rise in PHDI. Besides, the RCS analysis results exhibited a curvilinear relationship between PHDI and four indicators. Our study explored a significant correlation between PHDI and biological aging, indicating that adherence to PHD may prevent biological aging.

Its Role In Self Regulated Learning Case Study On Junior High School Students Of It Madani Islamic School

Adolescence is a critical period for student education, where students are in the transition period of childhood to adulthood that undergoes changes in their biological, cognitive and socio-emotional conditions. Based on the stage of development, junior high school students should be able to have responsibility in learning, students are able to manage themselves in their way of learning. The focus of this study aims to examine the role of personality type (based on the STIFIn method) and school climate on the self-regulated learning of SMP IT Madani Islamic School students. Sampling in this study used a total sampling involving 300 students. Data collection uses personality type data (based on the STFIn method), school climate scale and self-regulated learning scale. The data analysis technique used in this study is multiple regression analysis. The results showed that STIFIn personality type and school climate played a significant role in self-regulated learning with a value of F = 44,707 and a value of p<.05. Personality type and school climate made an effective contribution of 26.2% to self-regulated learning.

Surface Functionalization of Gold Nanoparticles Using Alkyne Derivatives: Applications in Chemical Sensing.

Colloidal gold nanoparticles (AuNPs) are important nanomaterials for chemical sensing and therapeutics. For their application, it is vital to develop a reliable and robust surface functionalization method that can be applied to diverse functional molecules and offer better stability under harsh biological conditions. Currently, thiol (SH) is the most commonly used functional group for forming stable covalent bonds with AuNPs. However, thiolated molecules typically require complicated preparation procedures, are susceptible to oxidation, and are not compatible with many electrophiles and reducing groups. In this study, we report that surface functionalization of AuNPs can be achieved using alkyne derivatives, which exhibit several advantages over classical thiolation and peptide-bond methods, including straightforward preparation of alkyne derivatives, rapid and simple conjugation in buffers and complex media, higher conjugation efficiency, long-term stability, and resistance to decomposition under harsh conditions. Several alkynylated biotin and fluorescein derivatives are prepared, and the alkynylated-AuNPs are characterized using a lateral flow assay, gel electrophoresis, and spectroscopy techniques to investigate the conjugation efficiencies, size distributions, protein interaction properties, and binding mode of the Au-alkyne bond. We also demonstrate that alkynylated-AuNPs can be used for the sensitive detection of hydrogen peroxide and streptavidin proteins.

FLASHQuant: A Fast Algorithm for Proteoform Quantification in Top-Down Proteomics.

Accurate quantification of individual proteoforms is a crucial step in identifying proteome-wide alterations in different biological conditions. Intact proteoforms have been analyzed predominantly by liquid chromatography-mass spectrometry (LC-MS)-based top-down proteomics (TDP) and quantified primarily by the label-free quantification (LFQ) method, as it requires no additional costly labeling. In TDP, due to frequent coelution and complex signal structures, overlapping signals deriving from multiple proteoforms complicate accurate quantification. Here, we introduce FLASHQuant for MS1-level LFQ analysis in TDP, which is capable of automatically resolving and quantifying coeluting proteoforms. In benchmark tests performed with both spike-in proteins and proteome-level mixture data sets, FLASHQuant was shown to perform highly accurate and reproducible quantification in short runtimes of just a few minutes per LC-MS run. In particular, it was demonstrated that resolving overlapping proteoforms boosts the quantification accuracy. FLASHQuant is publicly available as platform-independent open-source software at https://openms.org/flashquant/, accompanied by the simple alignment algorithm ConsensusFeatureGroupDetector for multiple LC-MS runs.

Machine Learning Aided Design and Optimization of Antifouling Surfaces.

Antifouling surfaces, renowned for their strong surface resistance to proteins, cells, or tissues in various biological and environmental conditions, have broad applications in implanted devices, antibacterial coatings, biosensors, responsive materials, water treatment, and lab-on-a-chip. While extensive experimental research exists on antifouling surfaces, machine learning studies on this topic are relatively few. This perspective specifically focuses on exploring the complex relationships between the composition, structure, and properties of antifouling surfaces, examining how these factors correlate with surface hydration and protein adsorption. Different machine learning models have been developed to analyze and predict single and multiple protein adsorptions on various types of surfaces, ranging from structureless surfaces to well-ordered and rigid self-assembled monolayers, dynamically ordered polymer brushes, and complex filtration membranes. These models not only identify key descriptors or functional groups critical for antifouling performance (surface hydration, protein adsorption) but also predict the antifouling properties for a specific surface. Recognizing current challenges, this perspective delineates future research directions in the antifouling field. By leveraging and comparing current machine learning approaches, it aims to advance both the design and fundamental understanding of antifouling surfaces, thereby pushing the boundaries of innovation in this critical field.

Enhancing Gentamicin Antibacterial Activity by Co-Encapsulation with Thymoquinone in Liposomal Formulation

Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes’ stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ’s efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.

A Gender Perspective on Coloproctological Diseases: A Narrative Review on Female Disorders.

Coloproctological diseases, including both benign and malignant conditions, are among the most common diagnoses in clinical practice. Several disorders affect both men and women, while others are unique to women, or women are at a greater risk of developing them. This is due to anatomical, biological, and social conditions and also due to females' exclusive capabilities of reproduction and pregnancy. In this context, the same proctological disease could differ between men and women, who can experience different perceptions of health and sickness. There is a raised awareness about the impact of different diseases in women and a growing need for a personalized approach to women's health. In this review, we aim to summarize the specific features of the main coloproctological diseases, specifically in the female population. This includes common complaints during pregnancy, conditions linked to vaginal delivery, functional consequences after colorectal resections, and conditions presenting a gender disposition.

ZMAP toolset: model-based analysis of large-scale proteomic data via a variance stabilizing z-transformation

Isobaric labeling-based mass spectrometry (ILMS) has been widely used to quantify, on a proteome-wide scale, the relative protein abundance in different biological conditions. However, large-scale ILMS data sets typically involve multiple runs of mass spectrometry, bringing great computational difficulty to the integration of ILMS samples. We present zMAP, a toolset that makes ILMS intensities comparable across mass spectrometry runs by modeling the associated mean-variance dependence and accordingly applying a variance stabilizing z-transformation. The practical utility of zMAP is demonstrated in several case studies involving the dynamics of cell differentiation and the heterogeneity across cancer patients.