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Preprint ARTICLE | doi:10.20944/preprints202410.0341.v1

Acute and Chronic Resistance Training, Acute Endurance Exercise, nor physiologically Plausible Lactate In Vitro Affect Skeletal Muscle Lactylation

Madison L. Mattingly, Derick A. Anglin, Bradley A. Ruple, Maira C. Scarpelli, Joao G. Bergamasco, Joshua S. Godwin, C. Brooks Mobley, Andrew Dandridge Frugé, Cleiton A. Libardi, Michael D. Roberts

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: skeletal muscle; hypertrophy; protein acetylation; protein lactylation

Online: 4 October 2024 (14:51:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202410.0316.v1

Mitochondrial Genomes of Mammals from the Brazilian Cerrado and Phylogenetic Considerations for the Orders Artiodactyla, Carnivora, and Chiroptera (Chordata: Mammalia)

Luiz Guilherme Pereira Pimentel, Rafael Augusto Silva Soares, Priscila Martins de Assis, Iuri Batista da Silva, Igor Henrique Rodrigues-Oliveira, Renan Rodrigues Rocha, Vinicius Gonçalves de Miranda, Laiena Luz Bassam, Karine Frehner Kavalco, Fabiano Bezerra Menegídio, Caroline Garcia, Rubens Pasa

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Mitogenomes; mtDNA; Biodiversity; Brazilian Savanna; phylogenetics

Online: 4 October 2024 (11:18:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202410.0206.v1

Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action

Yeon Jeong Kim, Sitansu Sekhar Nanda, Seung Yeon Pyo, Jin-Yeong Han, Tae Heung Kang, Fen Jiang, Sang Seok Koh

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: TEM; PAUF; TMA; TLR; M2 macrophages

Online: 3 October 2024 (10:17:50 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202410.0063.v1

The phi027 Bacteriophage Influences Physiology and Virulence of the Lysogenic Strain of Clostridioides difficile

Natalia Frankowska, Klaudia Szarek, Adam Iwanicki, Dorota Wultańska, Hanna Pituch, Monika Kabała, Alessandro Negri, Michał Obuchowski, Krzysztof Hinc

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Bacteriophage; Clostridioides difficile; CRISPR-Cpf1; sporulation; adhesion; cytotoxicity

Online: 3 October 2024 (08:00:07 CEST)

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Preprint REVIEW | doi:10.20944/preprints202410.0083.v1

Functions of TAM Receptors and Their Ligands Protein S and Gas6 in Atherosclerosis and Cardiovascular Disease

Teagan Prouse, Samarpan Majumder, Rinku Majumder

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Protein S; Gas6; atherosclerosis; TAM receptors; cardiovascular disease; myocardial infarction; apoptosis

Online: 2 October 2024 (07:57:34 CEST)

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Preprint REVIEW | doi:10.20944/preprints202410.0069.v1

Uncovering the Significance of CBX3 as an up-and-coming Biomarker in Cardiovascular Health

Muhammad Aamir Wahab, Nunzio Del Gaudio, Biagio Gargiulo, Vincenzo Quagliariello, Nicola Maurea, Michele Grieco, Angela Nebbioso, Lucia Altucci, Mariarosaria Conte

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: CBX3; cardiovascular disease; epigenetics; vascular smooth muscle cells; vascular remodeling; inflammation; pathway; chromatin; treatment(s)

Online: 1 October 2024 (13:23:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202410.0041.v1

Exploring the Therapeutic Potential of Nicotinamide‐N‐Methyltransferase in Clear Cell Renal Cell Carcinoma

MINGYU KIM, Hyung Ho Lee, So Dam Won, Yeon Sue Jang, Baek Gil Kim, Nam Hoon Cho, Young Deuk Choi, Hyun Ho Han, Jin Soo Chung

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: NNMT; ccRCC; biomarker

Online: 1 October 2024 (10:44:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2119.v1

Genome-wide Identification and Characterization of the Terpenoid Synthase Gene Family in Physcomitrella patens

Wei Ma, Xiukun Wan, Ge Yao, Penggang Han, Hui Jiang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Physcomitrella patens; Terpene Synthase; Abiotic Stress; Gene Family; Expression Analysis

Online: 29 September 2024 (11:01:19 CEST)

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Terpenoids are crucial secondary metabolites found in plants, essential for numerous physiological functions such as defense strategies, signal communication, and adaptation to environmental stresses. The enzymes referred to as Terpene Synthases (TPS) play crucial roles in the production of these compounds, fulfilling an essential role throughout the entire biosynthetic pathway.Despite their importance, systematic studies on the TPS genome in Physcomitrium patens (P. patens) remain inadequate. This research offers an extensive bioinformatics evaluation of the TPS genes in P. patens, aiming to clarify their possible functions in plant development, growth, and responses to stress. Preliminary examinations were conducted on the physicochemical characteristics, secondary protein structures, subcellular distribution, and genetic configurations of the TPS genes in P. patens. Initial analyses were performed on the physicochemical properties, protein secondary structures, subcellular localization, and gene structures of the TPS genes in P. patens. The findings demonstrate that TPS family members are dispersed across six chromosomes, with ten TPS family members identified. Analysis of conserved motifs revealed that the PpTPS members exhibit high sequence conservation, suggesting that these enzymes maintain stable structural characteristics during terpene synthesis. Further examination of evolutionary pressures indicated that TPS family members are predominantly subjected to purifying selection, which helps preserve the structural stability of TPS enzymes. Furthermore, an analysis of cis-acting elements indicated that TPS genes might respond to various factors, including light, plant hormones, tissue development, and environmental stressors. This suggests that TPS genes could be vital in managing how plants adapt to changes in their environment. Tissue expression profiling revealed that TPS family members have significant functions across various developmental stages and tissues. This is demonstrated by qRT-PCR analyses, indicating that the expression of the PpTPS gene is influenced by abscisic acid (ABA), methyl jasmonate (MeJA), sodium chloride (NaCl), and polyethylene glycol (PEG). The findings suggest that the PpTPS genes could play an essential role in the functional development of plant leaves and in their responses to abiotic stress.In summary, this research presents a comprehensive examination of the TPS family members in P. patens, yielding important perspectives on the functions of the PpTPS7 and PpTPS8 genes in the development of leaves and responses to abiotic stress.The findings contribute to a deeper understanding of the functions and regulatory mechanisms of TPS genes and present new perspectives and strategies for the enhancement and application of P. patens.

Preprint BRIEF REPORT | doi:10.20944/preprints202409.0995.v2

Knee Joint Response to Mechanical Loading: Bounding Mechanotransduction with Rehabilitation

Bartłomiej Kacprzak, Mikołaj Stańczak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: knee joint; mechanical loading; mechanotransduction; molecular biology

Online: 29 September 2024 (04:19:40 CEST)

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The knee joint, a crucial element in human locomotion, is subjected to various mechanical loads during daily activities and athletic pursuits. It functions as a complex, weight-bearing structure, facilitating movement and absorbing the stresses and strains imposed by physical activities. This review delves into the knee joint's response to mechanical loading, with a particular emphasis on mechanotransduction—the intricate process by which cells within the joint convert mechanical stimuli into biochemical signals. These signals initiate a cascade of cellular responses that are fundamental to maintaining joint health, promoting repair, and adapting to changes in the mechanical environment. Understanding the underlying mechanisms of mechanotransduction is essential for developing effective rehabilitation strategies aimed at treating knee joint injuries and managing degenerative conditions such as osteoarthritis. These strategies are crucial in clinical settings to enhance recovery, improve joint function, and mitigate pain and disability associated with knee joint disorders. This comprehensive review synthesizes current research on the cellular and molecular pathways involved in knee joint mechanotransduction. It evaluates the impact of different mechanical loading modalities—such as compression, tension, shear, and hydrostatic pressure—on the various tissues within the knee joint, including cartilage, synovium, ligaments, and tendons. By examining how these different loading conditions affect cellular behavior and tissue integrity, the review aims to provide a nuanced understanding of the biomechanical and biological responses of the knee joint to mechanical stress. Furthermore, the review discusses the implications of these findings for rehabilitation practices. It explores how knowledge of mechanotransduction can be applied to develop targeted therapeutic interventions, including controlled loading protocols, exercise regimens, manual therapy techniques, and the use of orthotic devices. By leveraging these insights, clinicians can optimize rehabilitation strategies to enhance tissue repair, restore function, and prevent further joint degeneration. Mechanotransduction in the knee joint involves several key cellular components, such as mechanoreceptors, ion channels, and signaling pathways that are activated by mechanical stimuli. These components play significant roles in regulating the functions of chondrocytes, synoviocytes, and fibroblasts—the primary cell types within the knee joint. For instance, chondrocytes, which are the main cellular component of cartilage, respond to mechanical loading by adjusting the synthesis and degradation of extracellular matrix components, thereby maintaining cartilage integrity and function. The synovial fluid, produced by synoviocytes, lubricates the joint and provides essential nutrients to the avascular cartilage. Mechanical loading affects synoviocytes, modulating the production of synovial fluid components such as hyaluronic acid and lubricin, which are critical for joint lubrication and protection against wear. Similarly, fibroblasts in ligaments and tendons respond to mechanical stress by altering collagen production and remodeling the extracellular matrix, which is vital for maintaining the strength and elasticity of these structures. This review also addresses the role of various signaling pathways, including the MAPK, NF-κB, and Wnt pathways, in mediating the cellular responses to mechanical stimuli. These pathways orchestrate the complex interactions between mechanical forces and cellular activities, influencing gene expression, protein synthesis, and cellular metabolism. By understanding these pathways, researchers and clinicians can identify potential targets for therapeutic interventions aimed at enhancing mechanotransduction and promoting tissue repair. In summary, this review highlights the importance of mechanotransduction in the knee joint's response to mechanical loading and underscores its relevance in designing effective rehabilitation approaches. Through a detailed analysis of current research, it aims to bridge the gap between basic mechanobiology and clinical practice, offering a comprehensive framework for understanding and improving knee joint health. By integrating insights from mechanobiology into rehabilitation strategies, clinicians can develop more effective treatments to support knee joint recovery, enhance functional outcomes, and prevent long-term degeneration.

Preprint REVIEW | doi:10.20944/preprints202409.2204.v1

miR-181a: Regulatory Roles, Cancer-Associated Signaling Pathway Disruptions, and Therapeutic Potential

Grace McIntyre, Zoe Jackson, Jose Colina, Sreeja Sekhar, Analisa DiFeo

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: biomarker; cancer; miR-181a; microRNA; microRNA therapeutics; microRNA processing; microRNA regulation; signaling pathways; signal transduction ;

Online: 29 September 2024 (03:50:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2212.v1

Differential Expression of mRNA Splicing Isoforms Generates Transcript Length Variants in Atherosclerosis Progression

Miguel Hueso, Adrian Mallen, Estanis Navarro

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: 5’ UTR lengthening; 3’ UTR lengthening; alternative splicing; atherosclerosis; mRNA isoforms

Online: 29 September 2024 (03:18:37 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2139.v1

Cancer, Deuterium, and Gut Microbes: A Novel Perspective

Stephanie Seneff, Anthony Kyriakopoulos

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Microbiome; Deuterium; Cancer; Warburg effect; Deuterium depleted water; Lactate; Formate; Short chain fatty acids; Apoptosis; Autophagy. ;

Online: 27 September 2024 (00:14:26 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2146.v1

Determination of PAH Contamination in Breast Milk Samples from Hungarian Volunteering Mothers, Using HPLC/FLD

Bernard Collins Anditi, Viktória Poór, Dénes Szerencsés, István Szabó, Mátyás Wahr, Anikó Kőnig-Péter, Timea Dergez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: polycyclic aromatic hydrocarbon (PAH); HPLC-FLD; breast milk; total PAHs; Incremental Life Risk Calculation (IRCL)

Online: 26 September 2024 (16:00:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2052.v1

Cutaneous Manifestations in Costello Syndrome: From Atopic Dermatitis to Cutaneous Papilloma

Michelle Robert Anthony, Chris Farkouh, Parsa Abdi, Faiza Amatul-Hadi, Amritpal Kooner, Conor Dolehide

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: eczema; atopic dermatitis; chronic dermatoses; Costello syndrome RASopathy; Noonan syndrome; Cardio-facial-cutaneous syndrome; Cutaneous papilloma; HRAS; William syndrome; Beckwith-Wiedemann syndrome

Online: 26 September 2024 (07:40:15 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2042.v1

Progress in Precision Medicine for Head and Neck Cancer

Sanaz Vakili, Amir Barzegar Behrooz, Rachel Wichelo, Alexandra Fernades, Abdul-Hamid Emwas, Mariusz Jaremko, Jarosław Markowski, Marek J. Łos, Saeid Ghavami, Rui Vitorino

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Precision Medicine; Biomarkers; Genetic Alterations; Head and Neck Cancer; Targeted Therapy

Online: 25 September 2024 (17:07:36 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202401.0546.v3

Trans-eQTLs Can Be Used to Identify Tissue-Specific Gene Regulatory Networks

Majid Nikpay

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: trans-eQTLs; tissue specificity; gene regulatory network; scale-free network; Mendelian randomization

Online: 25 September 2024 (12:40:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1984.v1

The Microbiota of the Outer Gut Mucus Layer of the Migrating Northeast Arctic Cod (Gadus morhua) as Determined by Shotgun DNA Sequencing

Typhaine Le Doujet, Peik Haugen

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Northeast Arctic cod microbiome; Adherent bacteria; Autochthonous; Mucus microbiota; Intestinal tract; NGS; Metagenome assembled genomes; MAGs

Online: 25 September 2024 (12:17:17 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1937.v1

Redox Signaling in Endosomes on the Example of EGF Receptors

Dana Maureen Hebchen, Katrin Schröder

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: early endosomes; redoxosomes; trans-activation; EGFR; reactive oxygen species

Online: 25 September 2024 (11:39:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1790.v1

Structural Basis of the Activity of HER2-Targeting Construct Composed of DARPin G3 and Albumin-Binding Domains

Anastasia G. Konshina, Eduard V. Bocharov, Elena V. Konovalova, Alexey A. Schulga, Vladimir Tolmachev, Sergey M. Deyev, Roman G. Efremov

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Scaffold proteins; HER2; tumor targeting; NMR; molecular modeling; protein-protein interactions

Online: 24 September 2024 (05:01:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1839.v1

Ex Vivo Intestinal Organoid Models: Current State-of-the-Art and Challenges in Disease Modelling and Therapeutic Testing

Sarron Randall-Demllo, Ghanyah Al-Qadami, Anita E. Raposo, Chenkai Ma, Ilka Priebe, Maryam Hor, Rajvinder Singh, Kim Y.C. Fung

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: intestinal organoid; 3D culture; colorectal cancer; organ-on-a-chip; disease modelling; therapeutic screening; ex vivo models

Online: 24 September 2024 (04:46:40 CEST)

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Preprint REVIEW | doi:10.20944/preprints202406.1284.v3

Is Deuterium Fractionation a Major Controlling Factor in Human Metabolism and Cancer? An Essential Role for Proline

Stephanie Seneff

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: collagen; cancer; deuterium; glycolysis; mitochondria; lactate; nicotinamide adenine dinucleotide; proline; Warburg effect; yeast

Online: 23 September 2024 (14:29:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1721.v1

Deciphering the Anti-Inflammatory Mechanisms of Cirsium japonicum by Combining Network Pharmacology, Molecular Docking and In Vitro Experimental Evaluation

Jiaxue Wang, Hui Tao, Zhenlong Wang, Wei An, Ya Zhao, Bing Han, Jinquan Wang, Xiuzhu Sun, Xiumin Wang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cirsii japonicum; network pharmacology; anti-inflammatory activity; molecular docking; cellular experiment

Online: 23 September 2024 (11:56:21 CEST)

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Cirsium japonicum, a traditional herb, exhibits significant anti-inflammatory activity; however, the main components and potential mechanisms of C. japonicum remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of Cirsium japonicum through network pharmacology and cellular experiments. The effective components and potential targets for anti-inflammatory activity of C. japonicum were identified using traditional Chinese medicine systematic pharmacology database, TCMSP analysis platform, and GeneCards database. The drug-component-target-disease network diagram was constructed using Cytoscape3.8.0 software, while the protein interaction network diagram was created using STRING database and Cytoscape3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using DAVID database. Molecular docking between key targets and active components was constructed with AutoDock software to determine the best binding target. Results revealed that 14 active components of C. japonicum targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed that strong affinity between sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferator-activated receptor α recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of C. japonicum, inhibited the release of lipopolysaccharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that C. japonicum may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component in C. japonicum, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of C. japonicum in treatment of inflammatory conditions.

Preprint REVIEW | doi:10.20944/preprints202409.1648.v1

Peptidergic GPCRs Signaling Systems and Cancer: Into New Pharmacological Approaches.

Francisco David Rodriguez, Rafael Coveñas

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: G-protein-coupled receptors (GPCR); Peptide; Cell growth; Apoptosis; Peptide antagonists; Peptide signaling pathways; Cancer; Cancer therapy; Drug design

Online: 23 September 2024 (10:01:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1655.v1

Under Normoxia Simvastatin Shifts Lipid Metabolism of B16.F10 Melanoma Cells to Support Their Aggressiveness

Giorgiana Gabriela Negrea, Loredana Balacescu, Alina Sesarman, Manuela Banciu

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: simvastatin; normoxia; hipoxia inducible factor 1; transcriptomics; unsaturated fatty acids; prostaglandins

Online: 23 September 2024 (08:45:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1609.v1

Unlocking the Therapeutic Potential of Oxystelma esculentum: A Phytochemical Treasure Trove with Anticancer and Lactogenic Properties

Maryem Safdar, Khalil Ahmad, Muhammad Younus Khan, Ghulam Sarwar, Muhammad Junaid Rao, Aqleem Abbas, Muhammad Taimoor Shakeel, Salma Batool, Abdulwahed Fahad Alrefaei, Mikhlid H. Almutairi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Phytochemical screening; Cytotoxicity; Anticancer activity; Lactogenic activity; Galactagogue; Prolactin; Brine shrimp lethality assay; FTIR spectroscopy; Medicinal plants; Natural products ;

Online: 20 September 2024 (09:43:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.1688.v2

A Compendium of G-flipon Biological Functions that have Experimental Validation

Alan Herbert

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Flipons; G-Quadruplex; Triplex; Z-DNA; Proliferation; Transcription; Translation; Repair; Repression; Sister chromatids; CTCG; Chromatin Loops; Class Switch Recombination; HIV

Online: 19 September 2024 (11:28:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1424.v1

’Seeing is Believing’: How Neutron Crystallography Informs Enzyme Mechanism by Visualizing Unique Water Species

Qun Wan, Brad C. Bennett

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: neutron diffraction; deuterium; hydronium; protein structure; enzyme catalysis; H/D exchange

Online: 18 September 2024 (15:28:49 CEST)

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Hydrogen is the lightest atom and composes roughly half of the atomic content in macromolecules, yet their location can only be inferred or predicted in most macromolecular structures. This is because hydrogen can rarely be directly observed by the most common structure determination techniques (such as X-ray crystallography and electron cryo-microscopy). However, knowledge of hydrogen atom positions, especially for enzymes, can reveal protonation states of titratable active site residues, hydrogen bonding patterns, and the orientation of water molecules. Though we know they are present, this vital layer of information, which can inform a myriad of biological processes, is frustratingly invisible to us. The good news is that, even at modest resolution, neutron crystallography (NC) can reveal this layer and has emerged this century as a powerful tool for elucidating enzyme catalytic mechanisms. Due to its strong and coherent scattering of neutrons, incorporation of deuterium into the protein crystal amplifies the power of NC. This is especially true when solvation and the specific participation of key water molecules are crucial for catalysis. Neutron data allow the modeling of all three atoms in water molecules and have even revealed previously unobserved and unique species such as hydronium (D3O+) and deuteroxide (OD-) ions as well as lone deuterons (D+). Herein, we briefly review why neutrons are ideal probes for identifying catalytically important water molecules and these unique water-like species, limitations in interpretation, and four vignettes of enzyme success stories from disparate research groups. One of these groups was that of Dr. Chris G. Dealwis, who died unexpectedly in 2022. As a memorial appreciation of his scientific career, we will also highlight his interest and contributions to the neutron crystallography field. As both the authors were mentored by Chris, we feel we have a unique perspective on his love of molecular structure and admiration for neutrons as a tool to query those structures.

Preprint REVIEW | doi:10.20944/preprints202409.1391.v1

FGFR2 in the Development and Progression of Cutaneous Squamous Cell Cancer

Ethan M. Kallenberger, Alok Khandelwal, Priyatosh Nath, Shaun A. Nguyen, John DiGiovanni, Cherie-Ann O. Nathan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cutaneous Squamous Cell Carcinoma; Fibroblast Growth Factor Receptor 2; Treatment Resistance; Epithelial Mesenchymal Transition; Metastasis; Immunosuppression

Online: 18 September 2024 (11:16:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1191.v1

G4 Biology and Scope for Potential Therapeutic Intervention against Multiple Disease Adversaries

Saleem Y Bhat

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: replication; G4 DNA; helicases; Drug discovery

Online: 17 September 2024 (04:57:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1179.v1

Dysregulated Expression of Selected miRNAs in Human Papillomavirus-Positive Patients with Benign Prostatic Hyperplasia/Prostatitis and Prostate Cancer

Sandra Viridiana Salgado-Hernández, Lucero Martínez-Retamoza, Rodolfo Ocadiz-Delgado, Salvador Pérez-Mora, Gladys Cedeño-Arboleda, María del Consuelo Gómez-García, Patricio Gariglio, David Guillermo Pérez-Ishiwara

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: HPV; prostate cancer; BPH; prostatitis; miRNAs; inflammation; proliferation; apoptosis; angiogenesis; metastasis

Online: 16 September 2024 (12:29:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1202.v1

Interplay Between the Circadian Clock and Sirtuins

Yan Zhuang, Yantong Zhang, Chao Liu, Yingbin Zhong

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: circadian clock; circadian rhythm; clock gene; sirtuin; metabolism

Online: 16 September 2024 (09:59:47 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1194.v1

Molecular Mechanism of Processing Ubiquitinated Substrates by p97 and Its Main Cofactors

Abolfazl Mirzadeh, Mohsen Kazemi, Isabelle Rouiller

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: p97; cofactors; substrate processing; Single particle cryo_electron microscopy

Online: 16 September 2024 (09:59:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1115.v1

Combined Expression of DNMT3B and PFKFB4 in Hepatoblastoma Predicts Metastatic Outcome

Christophe Desterke, Raquel Francés, Claudia Monge, Agnès Marchio, Pascal Pineau, Jorge Mata-Garrido

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Hepatoblastoma; Metastasis; CHIC Risk; Metabolism; Epigenetics; DNA Methylation; Glycolysis; Transcriptome

Online: 15 September 2024 (07:32:32 CEST)

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(1) Background: Hepatoblastoma is the most common primary liver cancer in children. Nowadays, poor outcome occurs essentially for patients with distant metastases; (2) Methods: Starting from Mammalian Metabolic Enzyme Database over expression of metabolic enzymes was searched in hepatoblastoma tumors as compared to noncancerous liver tissue in transcriptome dataset GSE131329. With overexpressed enzymes, Elasticnet machine learning tuning was performed according to metastasis status outcome. With significant enzymes a metabolic expression score was computed and integrated in multivariate clinical-biological logistic model; (3) Results: Forty-one overexpressed enzymes discriminate hepatoblastoma tumors and noncancerous liver tissues. Eighteen of them predict metastasis status (AUC 0.90) with 85.7% of sensibility and 92.3% of specificity. Elasticnet machine learning model tuning highlighted major importance of DNMT3B and PFKFB4 expression to predict metastasis. Role of these two enzymes was confirmed by univariate analyses with respective p-values: 0.0058 and 0.0091. Metabolic score computed with combined expression of DNMT3B and PFKFB4 discriminates metastasis status and high-risk CHIC score by univariate analysis (p-value=0.005). Meta.score was found more sensitive than C1/C2 classifier to predict metastasis status (accuracy: 0.72 versus 0.55). Integration of meta.score (DNMT3B, PFKFB4) with epidemiological parameters: gender, age at diagnosis, histological types, and clinical PRETEXT stages in a multivariate model confirmed independent adverse role of meta.score to predict metastasis status (multivariate p-value=0.003, odds ratio: 2.12); (4) Conclusions: Based on metabolic enzyme expression program of hepatoblastoma, we characterized a dual overexpression of PFKFB4 and DNMT3B in samples of patients at risk of metastasis (High risk CHIC stratification). With combined tumor expression of DNMT3B and PFKFB4 a meta.score was computed and this parameter was confirmed as an independent adverse score to predict metastatic status during hepatoblastoma.

Preprint ARTICLE | doi:10.20944/preprints202409.1112.v1

Genetic Variation Study of Several Romanian Pepper (Capsicum annuum L.) Varieties Revealed by Molecular Markers and Whole Genome Resequencing

Anca Amalia UDRIȘTE, Mihaela IORDĂCHESCU, Liliana BĂDULESCU

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Capsicum annuum; south-east Romania; molecular markers; Sanger sequencing; Whole Genome Resequencing

Online: 15 September 2024 (07:32:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1060.v1

Evaluation of the Antifungal Activity of Eugenol against the Candida albicans Genomic DNA

Danyelle Gomes de Sousa, Francisca Alves dos Santos, Dárcio Luiz de Sousa Júnior, Tássia Thaís Al Yafawi, Irwin Rose Alencar de Menezes, Henrique Douglas Melo Coutinho, Maria Karollyna do Nascimento Silva Leandro

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cell death; eugenol; fungal DNA

Online: 14 September 2024 (10:08:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1037.v1

Co-extraction of DNA and RNA from Candida albicans Using a Chemical Method in Conjunction with Silicon Carbide with Few Cells

Elizabeth Cristina Vieira de Freitas, Francisca Alves dos Santos, Maria Raíssa Vieira Lopes, Dárcio Luiz de Sousa Júnior, Tássia Thaís Al Yafawi, Ana Carolina Ferreira Araújo, Priscilla Ramos Freitas, Irwin Rose Alencar de Menezes, Henrique Douglas Melo Coutinho, Maria Karollyna do Nascimento Silva Leandro

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Chloriform-phenol; Extraction; Nucleic acids

Online: 13 September 2024 (11:32:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.0951.v1

The Emerging Role of Long Noncoding RNAs’ in Sorafenib Resistance within Hepatocellular Carcinoma

Puneet Vij, Mohammad Shabir Hussain, Sanjaya Kumar Satapathy, Everardo Cobos, Manish Kumar Tripathi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Long noncoding RNA (LncRNA); Sorafenib Resistance; Hepatocellular Carcinoma (HCC); EGFR; Autophagy; VEGFA; Proteomics; Renal Cell Carcinoma (RCC)

Online: 13 September 2024 (04:17:59 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202409.0995.v1

Knee Joint Response to Mechanical Loading: Bounding Mechanotransduction with Rehabilitation

Bartłomiej Kacprzak, Mikołaj Stańczak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: knee joint; molecular biology; cell biology; mechanotransduction

Online: 12 September 2024 (12:56:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0926.v1

Genome Sequencing Reveals the Potential of Enterobacter sp. strain UNJFSC003 for Hydrocarbon Bioremediation

Gianmarco Castillo, Sergio Eduardo Contreras-Liza, Carlos I. Arbizu, Pedro Manuel Rodriguez-Grados

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: NGS; genomics; microbiology; benzo[a]pyrene; hydrocarbon and bioremediation; Molecular Docking

Online: 12 September 2024 (10:49:15 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0918.v1

Endothelin-1 as an Activator of Pro-inflammatory Microglia Cells

Yaritza Inostroza-Nieves, Shakira Bou, Jose Alvarado-Perez, Diego Capo-Ruiz, Jessica Garcia, Jean P Moliere, Claudia P Arenas

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: endothelin; inflammation; microglia; multiple sclerosis; reactive oxygen species

Online: 11 September 2024 (17:10:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0912.v1

Ellagic Acid Mitigates Cadmium Exposure-Induced Apoptosis in HT22 Cells via Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Activating Nrf2/Ho-1 Pathway

Yue Liu, Chunhong Chen, Zhihui Hao, Jianzhong Shen, Shusheng Tang, Chongshan Dai

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cadmium; Ellagic acid; JNK pathway; Oxidative stress; Apoptosis; Nrf2/HO-1 pathway

Online: 11 September 2024 (14:12:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0747.v1

Impact of Tube Additives on Baseline Cell-Free DNA, Blood Nuclease Activity, and DNA Degradation in Serum and Plasma Samples

Gustavo Barcelos Barra, Ticiane Henriques Santa Rita, Rafael Henriques Jacomo, Lídia Freire Abdalla Nery

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cell-Free DNA; Serum; EDTA Plasma; Heparin Plasma; Citrate Plasma; Nuclease Activity; DNase Activity

Online: 10 September 2024 (09:00:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0741.v1

The Effects of swnK Gene Function of Endophytic Fungi Alternaria oxytropis OW 7.8 on its Swainsonine Biosynthesis

Yinzhe Li, Fan Yang, Ping Lu, Weifu Wang, Li Zhu, Le Kai, Lu Bai

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Alternaria oxytropis OW 7.8; swainsonine; swnK gene; biosynthesis pathway

Online: 10 September 2024 (09:00:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0756.v1

PTSD Increases Risk for Hypertension Development Through PVN Activation and Vascular Dysfunction in Sprague Dawley Rats

Xinqian Chen, Xin Yan, Chunxiu Yu, Qing-Hui Chen, Lanrong Bi, Zhiying Shan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: posttraumatic stress disorder; single prolonged stress; paraventricular nucleus; oxidative stress; vascular dysfunction; vascular inflammation; hypertension

Online: 10 September 2024 (08:54:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0699.v1

Activated Metabolic Transcriptional Program in Tumor Cells from Hepatoblastoma

Claudia Monge, Raquel Francés, Agnes Marchio, Pascal Pineau, Christophe Desterke, Jorge Mata-Garrido

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hepatoblastoma; epigenetics; one-carbon; metabolism; cancer; DNA methylation

Online: 10 September 2024 (03:36:54 CEST)

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(1) Background: Hepatoblastoma is the most common primary liver malignancy in children. During its development, metabolic reprogramming becomes particularly relevant due to the liver's intrinsic metabolic functions. Enhanced glycolysis, glutaminolysis, and fatty acid synthesis have been implicated in the proliferation and survival of hepatoblastoma cells. In this study we screened altered over expression of metabolic enzymes in hepatoblastoma tumors at tissue and single cell level. A hepatoblastoma tumor expression metabolic score was established and validated by machine learning; (2) Methods: Starting from Mammalian Metabolic Enzyme Database, bulk RNA-sequencing from GSE104766 dataset was investigated by supervised analyses (tumors versus adjacent liver tissue). Overexpressed enzymes in hepatoblastoma tumors were functionally enriched on KEGG metabolic database to draw a metabolic network with Cytoscape. Activated metabolic markers were used to compute a single-cell metabolic score in human and PDX hepatoblastoma samples from GSE180665 dataset (sc-RNAseq). ROC and area under curve (AUC) were computed on metabolic score. Elasticnet model tuning for metabolic marker expression was performed with r-caret on single cell transcriptome and revealed importance of individual marker to predict tumor cell status; (3) Results: Differential expression analysis on bulk transcriptome identified 287 significantly regulated enzymes between tumor and adjacent liver tissues: 59 of them were found overexpressed in tumors. 45 of the 59 over expressed enzymes were recognized in KEGG database which highlighted a main metabolic network enriched in amino acid metabolism but also carbohydrate, steroid, one carbon, purine, and glucoaminoglycan metabolisms. Based on expression of the 59 over expressed enzymes, the single cell metabolism score computed on GSE180665 dataset allowed to predict tumor cell status with and AUC of 0.98 (sensibility 0.93, specificity: 0.94). Elasticnet model tuned at 0.97 of AUC on individual marker single cell expression ranked top tumor predictive markers by decreasing importance: FKBP10, ATP1A2, NT5DC2, UGT3A2, PYCR1, CKB, GPX7, DNMT3B, GSTP1, and OXCT1; (4) Conclusion: An activated metabolic transcriptional program potentially affecting epigenetic functions was observed by bulk RNAseq in tumors of hepatoblastoma and confirmed at single cell levels in tumor cells.

Preprint ARTICLE | doi:10.20944/preprints202409.0689.v1

Evaluating Changes in the Local Protein Physicochemical Environment induced by Molecular Dynamics Simulation

Chuyi Wang, Khalid Mahmood, Daniel Park

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: molecular dynamics simulation; protein; single amino acid substitution; protein local physicochemical environment; tensors; variant effect prediction; FireProtDB

Online: 9 September 2024 (12:43:25 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202408.0190.v3

Cell Biology of Knee Joint Injuries: Early Mechanical Loading Perspective

Bartłomiej Kacprzak, Mikołaj Stańczak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: knee joint; cell biology; mechanical loading

Online: 9 September 2024 (09:21:05 CEST)

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Knee joint injuries, including those affecting the anterior cruciate ligament (ACL), meniscus, and cartilage, present complex challenges in sports medicine and orthopedics due to the intricate cellular and molecular mechanisms involved in tissue damage and repair. Understanding the molecular biology underpinning these processes is crucial for developing effective therapeutic and rehabilitation strategies. This systematic review investigates the impact of mechanical loading on the cellular responses during knee joint injury repair, with a particular focus on the molecular pathways involved in tissue regeneration. Mechanical loading plays a dual role, where controlled early loading can promote tissue repair, while excessive or inappropriate loading can exacerbate tissue damage. Fibroblasts, chondrocytes, and mesenchymal stem cells (MSCs) are central to the repair process, and their activation, proliferation, and differentiation are regulated by key molecular pathways. Upon injury, mechanotransduction pathways such as the integrin/FAK signaling axis are activated, which convert mechanical signals into biochemical responses that regulate cell adhesion, migration, and extracellular matrix (ECM) synthesis. Additionally, mechanosensitive ion channels like Piezo1 and TRPV4 modulate intracellular calcium levels, triggering downstream signaling cascades such as calmodulin/CaMKII, which regulate gene transcription and cellular responses to mechanical stress. The YAP/TAZ pathway, a critical component of the Hippo signaling pathway, responds to mechanical stimuli and regulates cell proliferation and ECM production in fibroblasts and chondrocytes. YAP/TAZ translocate to the nucleus in response to mechanical loading, where they interact with transcription factors such as TEAD, promoting the expression of genes involved in collagen synthesis and tissue repair. In parallel, growth factors like transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF) activate the TGF-β/Smad and PI3K/Akt signaling pathways, driving MSC differentiation into fibroblasts and chondrocytes, essential for ligament and cartilage repair. Mechanical loading also influences the inflammatory response at the injury site by modulating immune cell activity. Early mechanical loading can shift macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, mediated by growth factors such as TGF-β and interleukin-10 (IL-10). This phenotypic switch promotes tissue regeneration by enhancing ECM synthesis and resolving inflammation, which is crucial for long-term joint health. Matrix metalloproteinases (MMPs), regulated by NF-κB and MAPK pathways, play a role in ECM remodeling, where an imbalance between MMPs and their inhibitors (TIMPs) can lead to excessive matrix degradation, impeding tissue repair. Furthermore, Wnt/β-catenin signaling is activated in response to moderate mechanical loading, promoting chondrocyte proliferation and enhancing cartilage repair by upregulating type II collagen and aggrecan synthesis. However, dysregulation of Wnt signaling under excessive mechanical stress can lead to chondrocyte hypertrophy and cartilage degradation, contributing to osteoarthritis development. This review also explores emerging therapeutic strategies that leverage the molecular biology of knee joint repair, including biologics like platelet-rich plasma (PRP) and MSC-derived exosomes, which deliver bioactive molecules that activate critical regenerative pathways such as TGF-β/Smad and PI3K/Akt. Gene therapies targeting Wnt signaling or YAP/TAZ offer potential for enhancing tissue regeneration by modulating mechanotransduction and repair processes at the molecular level. In conclusion, the molecular biology of cellular responses to mechanical loading is central to knee joint repair following injuries. By understanding these processes and targeting specific molecular pathways, clinicians can optimize rehabilitation protocols and develop novel therapeutic approaches that enhance tissue regeneration, prevent chronic degeneration, and restore joint function. This comprehensive synthesis highlights the importance of integrating molecular insights into treatment strategies for ACL, meniscal, and cartilage injuries to improve patient outcomes.

Preprint REVIEW | doi:10.20944/preprints202409.0627.v1

Interplay Between Epithelial-Mesenchymal Transition and Cancer Stem Cells: Unveiling Potential Therapeutic Avenues

Subhajit Chatterjee

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Epithelial-mesenchymal transition (EMT); Cancer stem cells (CSCs); Hypoxia; Plasticity; Cancer signaling pathways; miRNA; Therapeutic avenues

Online: 9 September 2024 (07:14:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0482.v1

Anticonvulsant Interactions: Common Interactions with Other Commonly Used Drugs

Richard Murdoch Montgomery

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Anticonvulsants; drug interactions; pharmacokinetics; pharmacodynamics; epilepsy; polypharmacy; adverse effects

Online: 6 September 2024 (07:36:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0418.v1

Epigenetics in Psychiatry: Implications for Genomics, Evolution, Inheritance Patterns, and Biomarker Development

Richard Murdoch Montgomery

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Epigenetics; Psychiatry; Genomics; Evolution; Inheritance Patterns; Biomarkers; DNA Methylation; Histone Modifications; Non-Coding RNAs; Depression; Schizophrenia; PTSD; EEG; Artificial Intelligence; Epigenetic Therapies; Epigenetic Inheritance

Online: 6 September 2024 (05:30:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0477.v1

Shedding Light on tRNA-Derived Fragment Repertoire in Facs Blood Cells

Alexander Andreevich Artamonov, Kirill Kondratov, Egor Bystritsky, Yuriy Nikitin, Anastasiya Velmiskina, Sergei Mosenko, Irina Polkovnikova, Anna Asinovskaya, Svetlana Apalko, Natalya Sushentseva, Andrej Mixajlovich Ivanov, Sergey Shcherbak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: tRNA fragment; blood cells; severe COVID-19; sRNA NGS; RBC; ymphocytes; monocytes

Online: 5 September 2024 (14:57:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0462.v1

Somatic Landscape of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Actionable Targets

Shruthi Kondaboina, Oscar Parrish, Carolina Angelica Parada, Manuel Ferreira Jr

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Intracranial epidermoid cysts; rare cancers; whole-exome sequencing; targeted therapy

Online: 5 September 2024 (12:10:35 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202409.0446.v1

Molecular Aspects of Cartilage Microfracturation: Rehabilitation Insights.

Bartłomiej Kacprzak, Mikołaj Stańczak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: knee joint; cartilage; molecular biology; biochemistry

Online: 5 September 2024 (11:02:11 CEST)

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Cartilage microfracturation is a surgical technique specifically designed to address chondral defects, which are injuries to the cartilage that covers the ends of bones in joints. These defects can result from traumatic injuries, degenerative conditions such as osteoarthritis, or congenital abnormalities. The primary objective of microfracture surgery is to promote the regeneration of functional cartilage tissue, thereby restoring joint function, alleviating pain, and enhancing mobility. The procedure involves creating small, controlled perforations, or microfractures, in the subchondral bone plate beneath the damaged cartilage. This process, performed with precision to minimize damage to surrounding healthy tissue, penetrates the subchondral bone to reach the bone marrow, which is rich in mesenchymal stem cells (MSCs). MSCs are multipotent cells capable of differentiating into various cell types, including chondrocytes, which are essential for cartilage production. The microfractures provide an access pathway for MSCs, allowing them to migrate from the bone marrow to the defect site. Once at the site, these stem cells differentiate into chondrocytes and initiate the formation of new cartilage tissue. This newly formed tissue helps fill the defect, aiming to restore the smooth surface of the cartilage and improve the joint's structural integrity. Understanding the molecular processes involved in cartilage repair is crucial for optimizing rehabilitation strategies and improving clinical outcomes. These processes include the regulation of various signaling pathways that control stem cell migration, differentiation, and extracellular matrix (ECM) synthesis. Growth factors such as transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs) play pivotal roles in these pathways, guiding MSCs in their transformation into functional cartilage cells. Additionally, the role of the ECM, composed primarily of collagen type II and proteoglycans like aggrecan, is paramount in providing structural support and biochemical signals. The ECM supports the newly differentiated chondrocytes and helps maintain the cartilage's mechanical properties. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are crucial in ECM remodeling, ensuring the balance between synthesis and degradation of the matrix to support tissue repair and integrity. Angiogenesis and vascularization are also critical aspects of the molecular repair process. The initial phase of cartilage repair often includes transient vascularization facilitated by vascular endothelial growth factor (VEGF), ensuring that the newly formed tissue receives adequate nutrients and oxygen. However, as the repair tissue matures, it transitions back to an avascular state characteristic of healthy articular cartilage, which is essential for maintaining its mechanical properties and longevity. Rehabilitation strategies following microfracture surgery are meticulously crafted to facilitate recovery and functional restoration. These strategies include early mobilization techniques, controlled mechanical loading, biological augmentation, nutritional support, and advanced therapeutic modalities. Early mobilization with gentle passive range-of-motion exercises promotes synovial fluid circulation within the joint, preventing adhesions and joint stiffness, and delivering essential nutrients and growth factors. Controlled mechanical loading through gradual weight-bearing activities helps condition the repaired tissue, stimulating chondrocyte proliferation and ECM production while ensuring proper integration and function. Biological augmentation, including platelet-rich plasma (PRP) and hyaluronic acid (HA), supports cartilage repair by enhancing cellular activities and ECM formation. PRP, rich in growth factors, promotes cell proliferation and matrix synthesis, while HA injections improve joint lubrication, reduce pain, and provide a scaffold for new tissue growth. Nutritional support, including amino acids, vitamins, minerals, glucosamine, chondroitin sulfate, and antioxidants, plays a vital role in collagen synthesis and overall cartilage maintenance, protecting chondrocytes from oxidative stress and modulating inflammation. Advanced therapeutic modalities such as low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields (PEMF), photobiomodulation therapy, and cryotherapy offer additional benefits by enhancing chondrocyte activity, reducing inflammation, and promoting ECM production. These modalities work through various molecular mechanisms, such as activating signaling pathways and modulating gene expression, to improve the quality and durability of the repaired cartilage. By comprehensively understanding the molecular and practical aspects of cartilage repair, clinicians can develop more effective treatment plans that optimize cartilage healing and improve patient outcomes. The integration of molecular insights with advanced rehabilitation techniques holds the promise of revolutionizing cartilage repair, offering hope for those suffering from debilitating joint conditions. This review aims to bridge the gap between molecular biology and clinical practice, providing a roadmap for optimizing cartilage repair strategies and ensuring long-term success for patients.

Preprint ARTICLE | doi:10.20944/preprints202409.0421.v1

Novel Drug-like HsrA Inhibitors Exhibit Potent Narrow-Spectrum Antimicrobial Activities against Helicobacter pylori

Javier Casado, Irene Olivan-Muro, Sonia Algarate, Eduardo Chueca, Sandra Salillas, Adrián Velázquez-Campoy, Elena Piazuelo, María F. Fillat, Javier Sancho, Ángel Lanas, Andrés González

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Helicobacter pylori; antimicrobial resistance; narrow-spectrum antibiotic; antibacterial target; response regulator; HsrA; Campylobacter jejuni

Online: 5 September 2024 (10:22:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0375.v1

Epigenetic Reprogramming and Inheritance of the Cellular Differentiation Status Following Transient Expression of a Nonfunctional DN Rb Mutant in Murine MSCs

Baryshev Mikhail, Irina Maksimova, Ilona Sasoveca

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Rb1; MSCs; Cebpa; epigenetic reprogramming; DNMTs; adipogenesis

Online: 5 September 2024 (07:12:27 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0270.v1

Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy

Yusuf Lukman, Abdulhaqeem Yusuf

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Human papillomavirus; HPV 16 oncoproteins; Capsaicin; E6 and E7 oncoproteins; Molecular docking; ADMET studies; Molecular dynamic simulations

Online: 5 September 2024 (06:59:08 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0342.v1

Modeling Enzyme Dynamics in Metabolomics: A Topological Approach to Visualizing Adaptive Network Interactions Under Environmental Disturbances

Richard Murdoch Montgomery

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Enzyme dynamics; Metabolomics; Topological manifold; Differential equations; Network modeling; Environmental disturbances; Systems biology; Enzyme interactions; Compensatory mechanisms

Online: 5 September 2024 (05:01:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0317.v1

Green Synthesis of Silver Oxide Nanoparticles from Mauritia flexuosa Fruit Extract: Characterization and Bioactivity Assessment

Linda P. Guamán, Johana Zúñiga-Miranda, David Vaca-Vega, Karla Vizuete, Saskya E. Carrera-Pacheco, Rebeca Gonzalez-Pastor, Jorge Heredia-Moya, Arianna Mayorga-Ramos, Carlos Barba-Ostria, Elena Coyago-Cruz, Alexis Debut

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Silver nanoparticles; Mauritia flexuosa; biological activity; green synthesis; anti-tumor; multidrug-resistant bacteria; antibacterial agent

Online: 4 September 2024 (08:32:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0132.v1

Bromelain: Unveiling Its Potential as a Natural Anti-inflammatory Agent through Effective Binding to Apoptosis-Associated Speck-Like Containing CARD (ASC)

Ivan ferrari

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Apoptosis-associated speck-like containing; Bromelain; HDOCK SERVER

Online: 3 September 2024 (10:59:04 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.0202.v1

Basic Guide for Approaching Drug Delivery with Extracellular Vesicles

Sergey Brezgin, Oleg Danilik, Alexandra Yudaeva, Artyom Kachanov, Anastasiya Kostyusheva, Ivan Karandashov, Natalia Ponomareva, Andrey A Zamyatnin Jr., Alessandro Parodi, Vladimir Chulanov, Dmitry Kostyushev

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: targeted drug delivery; nanotherapeutics; surface display

Online: 3 September 2024 (09:49:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0125.v1

Evaluation of the Use of Cell Lines in Studies of Selenium‐Dependent Glutathione Peroxidase 2 (GPX2) Involvement in Colorectal Cancer

R Steven Esworthy

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: selenium‐dependent glutathione peroxidase; peroxiredoxins; NADPH oxidase 1; colorectal cancer; cell lines; public databases

Online: 2 September 2024 (16:41:50 CEST)

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Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Preprint ARTICLE | doi:10.20944/preprints202409.0031.v1

Whole-Genome Sequencing, Phenotypic Characterization, and Antifungal Susceptibility Profiles of Three Aspergillus hortae Clinical Isolates from Colombia

Santiago Marín-Carvajal, Mariana Quiceno-Torres, Maria Camila Zuleta, Susana Torres, Álvaro Leon Rúa, Ana Maria García, Clayton Luiz Borges, Angela Maria López, Juan Guillermo McEwen, Orville Hernandez Ruiz, Oscar Mauricio Gómez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Aspergillus hortae; Genome; Pathogenic fungi; antifungals susceptibility

Online: 2 September 2024 (12:27:06 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.1936.v2

Artificial Intelligence in Cryo-EM Protein Particle Picking: Recent Advances and Remaining Challenges

Ashwin Dhakal, Rajan Gyawali, Liguo Wang, Jianlin Cheng

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cryo-Electron Microscopy; Protein Particle Picking; Artificial Intelligence; Machine Learning; Structural Biology

Online: 2 September 2024 (05:09:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.2249.v1

Addressing Antibiotic Resistance with Bacterial Cytological Profiling: A High-Throughput Method for Antibiotic Discovery

Jhonatan Salgado, James Rayner, Nikola Ojkic

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: antibiotic resistance; bacterial cytological profiling; high-throughput screens; antibiotic mechanism of action; bacterial priority pathogen list; cell segmentation; machine learning; deep learning

Online: 30 August 2024 (23:41:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.2140.v1

Single−molecule Level Quantification Reveals the Interaction between Melittin and Lipopolysaccharide by Atomic Force Microscopy

Sheng Huang, Guoqi Su, Li Yang, Liangguang Yue, Li Chen, Jinxiu Huang, Feiyun Yang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: melittin; lipopolysaccharide; atomic force microscopy; interaction force; kinetics characteristics

Online: 30 August 2024 (03:37:03 CEST)

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The interaction forces and mechanical properties of the interaction between melittin (Mel) and lipopolysaccharide (LPS) are considered a crucial driving force for Mel in killing Gram−negative bacteria (GNB). However, how their interaction forces are performed at the single−molecule level and the dissociation kinetic characteristics of the Mel/LPS complex remain poorly understood. In this study, the single−molecule level interaction forces between Mel and LPSs from E. coil K−12, O55:B5, O111:B4, and O128:B12 were explored using atomic force microscopy (AFM) based single−molecule force spectroscopy (SMFS). Further, the AFM−based dynamic force spectroscopy (DFS) and advanced analytical model were employed to investigate the kinetic characteristics of the Mel/LPSs complex dissociation. The results indicated that Mel could interact with both rough (R)−form LPS (E. coli K−12) and smooth (S)−form LPSs (E. coli O55:B5, O111:B4, O128:B12), and the S−form LPSs showed a more robust interaction with Mel than R−form LPS, and a slight difference existed in the interaction forces between Mel and diverse S−form LPSs. The Mel interacts with S−form LPSs showed greater specific and non−specific interaction forces than R−form LPS (p < 0.05), as determined by AFM−based SMFS. However, there was no significant difference in the specific and non−specific interaction forces among the three S−form LPSs (p > 0.05), indicating the variability of O−antigen could not affect the interaction between Mel and LPSs. The DFS result showed that the Mel/S−form LPSs complexes had a lower dissociation rate constant (koff), a shorter energy barrier width (xβ), a longer bond lifetime (τoff), and a higher height of the energy barrier (∆G), demonstrating that Mel could interact with S−form LPSs to form more stable complexes. In conclusion, this study promotes our knowledge of the interaction micromechanics and kinetics characteristics between Mel and LPS at the single−molecule level. Moreover, it can help us design and evaluate new anti−GNB drugs.

Preprint ARTICLE | doi:10.20944/preprints202408.2191.v1

Assessment of Serum Lipid Profile Variations in Sudanese Pregnant Women Across the Second and Third Trimesters

Waleed A. Salim, Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Serum Lipid Profile; Pregnancy; Hyperlipidemia; Second Trimester; Third Trimester; Sudanese Women; Lipid Metabolism

Online: 29 August 2024 (15:44:26 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.2103.v1

Exploring the Role of p53 in Radiosensitivity: A Key Player in Cancer Therapy

Tusher -Al-Arafat, Aihong Mao, Takanori Katsube, Bing Wang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: radiation; p53; radiosensitivity; cancer therapy; DNA damage and repair; Apoptosis

Online: 29 August 2024 (12:07:42 CEST)

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Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome,” p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of radiation response in cancer cells and developing more effective therapeutic approaches in cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Preprint ARTICLE | doi:10.20944/preprints202408.2062.v1

Deciphering Epigenetic Mechanisms: The Role of DNA Methylation in Driving Phenotypic Diversity and Evolutionary Adaptation in Chickpea (Cicer arietinum)

Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA Methylation; Phenotypic Diversity; Chickpea (Cicer arietinum); Epigenetics; Evolutionary Biology; Plant Genetics; Bisulfite Sequencing

Online: 29 August 2024 (09:55:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1963.v1

How Trustworthy Are Genomic Sequences of SARS-CoV-2 in GenBank?

Xuhua Xia

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; GenBank; data validation; genome; genomic analysis

Online: 28 August 2024 (12:37:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1939.v1

Overcoming Therapy Resistance in Colorectal Cancer: Targeting Rac1 Signaling Pathway as a Potential Therapeutic Approach

Luciano E Anselmino, Florencia Malizia, Aylén Avila, Nahuel Cesatti Laluce, Macarena Mamberto, Lucía C Zanotti, Cecilia Farré, Mauricio Menacho Márquez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: colorectal cancer; resistance; small GTPases; Rac1; repositioning

Online: 27 August 2024 (16:43:31 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.1936.v1

Artificial Intelligence in Cryo-EM Protein Particle Picking: The Hope, Hype, and Hurdles

Ashwin Dhakal, Rajan Gyawali, Liguo Wang, Jianlin Cheng

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cryo-Electron Microscopy; Protein Particle Picking; Artificial Intelligence; Machine Learning; Structural Biology

Online: 27 August 2024 (16:38:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1913.v1

Rice Husk Silica Liquid Enhances Autophagy and Reduces Overactive Immune Responses via TLR-7 Signaling in Lupus-Prone Models

Chieh Kao, Shih-Wei Wang, Po-Chun Chen, Chun-Yung Huang, Yu-Feng Wei, Cheng-Hsun Ho, Yong-Han Hong

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Systemic lupus erythematosus; Rice husk silica liquid; Toll-like receptor 7; Autophagy; Inflammation; TNF-α

Online: 27 August 2024 (10:17:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1865.v1

Structural Analysis and Substrate Specificity of D-carbamoylase from Pseudomonas

Marina Paronyan, HAYKANUSH KOLOYAN, Hovsep Aganyants, ARTUR HAMBARDZUMYAN, TIGRAN SOGHOMONYAN, SONA AVETISYAN, SERGEI KOCHAROV, HENRY PANOSYAN, Vehary Sakanyan, ANICHKA HOVSEPYAN

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: D-carbamoylase; homology modeling; molecular docking; molecular dynamics; N-carbamoyl-D-alanine; N-carbamoyl-D-tryptophan; inclusion bodies; Pseudomonas

Online: 27 August 2024 (03:15:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1873.v1

Uncovering DNA Methylation Landscapes to Decipher Evolutionary Footprints of Phenotypic Diversity in Chickpea

Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA Methylation; Phenotypic Diversity; Chickpea (Cicer arietinum); Epigenetics; Evolutionary Biology; Plant Genetics; Bisulfite Sequencing

Online: 27 August 2024 (00:35:54 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1804.v1

A Comprehensive Transcriptomic and Proteomics Analysis of Candidate Secretory Proteins in Rose Grain Aphid, Metopolophium dirhodum (Walker)

Atsbha Gebreslasie Gebrekidan, Yong Zhang, Julian Chen

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Metopolophium dirhodum; unigene; transcriptome; proteome; salivary protein

Online: 26 August 2024 (16:58:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1748.v1

Biochemical Characterization of Escherichia coli FtsZ Protein Using Native 1 PAGE, Size-Exclusion Chromatography, Sedimentation Gradient, Chemical 2 Cross-Linking and Protein-Protein Interaction Prediction

Nelson Araujo, Marcelo Veloso, Luis Pouchucq

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: FtsZ; Oligomers; friction quotient; sedimentation quotient

Online: 24 August 2024 (00:32:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1714.v1

Supplementation with Pentadecylresorcinol to a High-Fat Diet Increases the Predicted Representation of Enzymes and Metabolic Pathways for Vitamin B12 Synthesis by the Gut Microbiota of C57BL6 Mice

Anastasia A. Zabolotneva, Mikhail D. Makeev, Anastasia V. Fesenko, Sergey A. Roumiantsev, Aleksandr V. Shestopalov

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alkylresorcinols; pentadecylresorcinol; vitamin B12; prediction of the gut microbiome functions; prebiotics; probiotics

Online: 23 August 2024 (18:52:45 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.1688.v1

A Compendium of G-flipon Biological Functions that have Experimental Validation

Alan Herbert

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Flipons; G-Quadruplex; Triplex; Z-DNA; Proliferation; Transcription; Translation; Repair; Repression; Sister chromatids; CTCG; Chromatin Loops; Class Switch Recombination

Online: 23 August 2024 (12:23:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1609.v1

Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis

Mi Ran Choi, Hye Jin Chang, Jeong-Hyeon Heo, Sun Hyung Yum, Eunae Jo, Miran Kim, Sang-Rae Lee

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Endometriosis; endometrium; menstrual cycle; long noncoding RNA; neighboring gene

Online: 23 August 2024 (10:12:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1619.v1

Epigenetic Reprogramming of Aging: Reversing the Clock for Regenerative Medicine

Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Epigenetic Reprogramming; Aging; Regenerative Medicine; DNA Methylation; Cellular Rejuvenation; CRISPR-Cas9; Senescence

Online: 22 August 2024 (06:02:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1593.v1

Uncovering DNA Methylation Landscapes to Decipher Evolutionary Footprints of Phenotypic Diversity in Chickpea

Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: DNA Methylation; Phenotypic Diversity; Chickpea (Cicer arietinum); Epigenetics; Evolutionary Biology; Plant Genetics; Bisulfite Sequencing

Online: 21 August 2024 (17:02:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1474.v1

Novel Galectins Purified from the Sponge Chondrilla australiensis: Unique Structural Features and Cytotoxic Effects on Colorectal Cancer Cells Mediated by TF-Antigen Binding

Ryuhei Hayashi, Kenichi Kamata, Marco Gerdol, Yuki Fujii, Takashi Hayashi, Yuto Onoda, Nanae Kobayashi, Satoshi Furushima, Ryuya Ishiwata, Mayuka Ohkawa, Naoko Masuda, Yuka Niimi, Masao Yamada, Daisuke Adachi, Sarkar M. A. Kawsar, Sultana Rajia, Imtiaj Hasan, Somrita Padma, Bishnu Pada Chatterjee, Yuji Ise, Riku Chida, Kayo Hasehira, Nobumitsu Miyanishi, Tatsuya Kawasaki, Yukiko Ogawa, Hideaki Fujita, Alberto Pallavicini, Yasuhiro Ozeki

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Chondrilla australiensis; galectin; Porifera; TF-antigen; signal peptide; cytotoxicity

Online: 21 August 2024 (03:47:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1279.v1

An Investigation of the Effect of the Traditional Naxi Herbal Formula Against Liver Cancer through Network Pharmacology, Molecular Docking and In Vitro Experiments

Xiuxiang Yan, Angkhana Inta, Xuefei Yang, Hataichanok Pandith, Terd Disayathanoowat, Lixin Yang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Network pharmacology; Molecular docking; In vitro experiments; Underlying mechanism; The formula Chong-Lou-Yao-Fang; Traditional Naxi herbal formula; Liver cancer

Online: 20 August 2024 (05:08:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1282.v1

Computational Identification of Promising CRYGD Inhibitors for Cataract Treatment

Maedeh Dahaghin, Ali Rahmani

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cataract; CRYGD; Molecular docking; Molecular dynamics; Crystallin; Protein aggregation

Online: 19 August 2024 (09:15:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1219.v1

Roles of Mature Domain Targeting Signals for Protein Translocation and Secretion in Lactococcus lactis

Mai Ngoc Hoang, Clemens Peterbauer

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Lactococcus lactis; secretory proteins; signal peptide; mature domains; hydrophobic patches; SecA

Online: 16 August 2024 (08:28:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0976.v1

Computationally Rationalising the Conformational Dynamics of Pseudo-Endocannabinoid Receptors CB₁ and CB₂ with Cannabidiol

Ikechukwu Achilonu

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Pseudo-Endocannabinoid Receptors; Cannabis; Cannabidiol; Computational Biology; Induced-Fit Docking; Molecular Dynamic Simulations

Online: 16 August 2024 (03:05:49 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202408.1117.v1

Molecular Biology of ACL Graft Healing: Early Mechanical Loading Perspective.

Mikołaj Stańczak, Bartłomiej Kacprzak

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: knee joint; ACL graft; molecular biology; mechanotransduction

Online: 15 August 2024 (22:45:23 CEST)

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The Anterior Cruciate Ligament (ACL) is a crucial stabilizing ligament in the knee, essential for maintaining knee joint stability and proper biomechanical function. ACL rupture is one of the most common injuries, especially prevalent among athletes participating in high-demand sports that involve pivoting, cutting, and jumping. Such injuries not only lead to immediate functional impairment but also predispose individuals to long-term consequences, including osteoarthritis if left untreated. ACL reconstruction using a graft, whether autograft or allograft, has become the gold standard treatment method aimed at restoring knee stability and function. However, the postoperative healing process of the graft within the bone tunnel presents significant challenges due to its complexity. This healing involves a coordinated sequence of molecular and cellular events, including inflammation, proliferation, and remodeling phases. These phases are governed by a myriad of molecular signals, growth factors, and cellular interactions that ultimately determine the success of the graft integration and the restoration of ligamentous function. The review article "Molecular Biology of ACL Graft Healing: Early Mechanical Loading Perspective" delves deeply into these intricate biological processes. It provides a comprehensive analysis of the underlying molecular mechanisms that facilitate graft healing. Furthermore, it emphasizes the critical role of early mechanical loading in this context. Mechanical loading, when applied appropriately, has been shown to positively influence graft healing by enhancing cellular responses, collagen fiber alignment, and overall biomechanical properties of the graft. By exploring the impact of early mechanical loading, the review sheds light on how mechanical stimuli can be optimized to improve clinical outcomes. This understanding is vital for developing effective rehabilitation protocols that promote faster and more robust graft healing. The article offers valuable insights for clinicians and researchers, aiming to bridge the gap between molecular biology and practical rehabilitation strategies in ACL reconstruction. Overall, this review underscores the importance of an integrated approach that considers both the biological and mechanical aspects of ACL graft healing. Such an approach holds promise for advancing patient care and improving the success rates of ACL reconstruction surgeries.

Preprint REVIEW | doi:10.20944/preprints202403.0467.v2

Exploring the Role of Circulating Cell-Free DNA in Disease Diagnosis and Therapy

Mohammad Odah

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: circulating cell-free DNA (ccfDNA); molecular diagnostics; liquid biopsies; cancer biomarkers; genomic sequencing; bioinformatics; personalized medicine

Online: 15 August 2024 (16:34:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.1156.v1

The Multifaceted Role of S6K1 in Cellular Regulation: Structural Insights, Isoform-Specific Functions, and Therapeutic Potential

Oreoluwa Elizabeth Folajimi, Benjamin Ayodipupo Babalola, Aduragbemi Alabi, Taiwo Funlola Akintola

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: S6K1; cellular regulation; subcellular localization; cancer; tissue-specific expression; regulation of S6K1

Online: 15 August 2024 (14:46:56 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1078.v1

Grammar-Based Computational Framework for Predicting Pseudoknots of K-Type and M-Type in RNA Secondary Structures

Christos Pavlatos

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA structure prediction; K-type pseudoknots; M-type pseudoknots; syntactic pattern recognition; context-free grammar; secondary structure; computational biology

Online: 14 August 2024 (14:39:34 CEST)

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Understanding the structural intricacies of RNA molecules is essential for deciphering numerous biological processes. Traditionally, scientists have relied on experimental methods to gain insights and draw conclusions. However, the recent advent of advanced computational techniques has significantly accelerated and refined the accuracy of research results in several areas. A particularly challenging aspect of RNA analysis is the prediction of its secondary structure, which is crucial for elucidating its functional role in biological systems. This paper deals with the prediction of pseudoknots in RNA, focusing on two types of pseudoknots: K-type and M-type pseudoknots. Pseudoknots are complex RNA formations in which nucleotides in a loop form base pairs with nucleotides outside the loop and thus contribute to essential biological functions. Accurate prediction of these structures is crucial for understanding RNA dynamics and interactions. Building on our previous work in which we developed a framework for the recognition of H- and L-type pseudoknots, an extended grammar-based framework tailored to the prediction of K- and M-type pseudoknots is proposed. This approach uses syntactic pattern recognition techniques and provides a systematic method to identify and characterize these complex RNA structures. Our framework uses context-free grammars (CFGs) to model RNA sequences and predict the occurrence of pseudoknots. By formulating specific grammatical rules for type K and type M pseudoknots, we enable efficient parsing of RNA sequences to recognize potential pseudoknot configurations. This method ensures an exhaustive exploration of possible pseudoknot structures within a reasonable time frame. In addition, the proposed method incorporates essential concepts of biology, such as base pairing optimization and free energy reduction, to improve the accuracy of pseudoknot prediction. These principles are crucial to ensure that the predicted structures are biologically plausible. By embedding these principles into our grammar-based framework, we aim to predict RNA conformations that are both theoretically sound and biologically relevant.

Preprint BRIEF REPORT | doi:10.20944/preprints202405.1036.v2

A Metagenomics Pipeline to Characterize Self-Collected Vaginal Microbiome Samples

Krystal Thomas-White, Evann E Hilt, Genevieve Olmschenk, Maryann Gong, Caleb Philips, Courtney Jarvis, Nicholas Sanford, Jennifer White, Pita Navarro

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: vaginal microbiome; shotgun metagenomic sequencing; vaginitis

Online: 14 August 2024 (12:30:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0912.v2

Comparative Analysis of Rapid and Less Invasive Methods for A2A2 Dairy Cattle Genotyping and A2 Milk Purity Detection

Leandra Oliveira Xavier Albiero, Rafaela Ansiliero, Aniela Pinto Kempka

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: A2A2 dairy cows; Genotyping; ELISA; LFIA; Comparison of methods; Facilitated analysis

Online: 14 August 2024 (11:56:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.0989.v1

MicroRNA in human umbilical cord blood

Tengye Yu, Yin Yuan

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: microRNA; umbilical cord blood; biomarker; neonatal diseases; neonatal development

Online: 14 August 2024 (09:10:24 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0953.v1

Collagen I Exacerbates Palmitate-Induced Cell Death in HepG2 Cells via Integrin-Mediated Death

Tumisang Edward Maseko, Eva Peterová, Moustafa Elkalaf, Darja Koutová, Jan Melek, Pavla Staňková, Veronika Špalková, Reem Matar, Halka Lotková, Zuzana Červinková, Otto Kučera

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: in vitro NAFLD models; collagen I; palmitate; lipotoxicity; α2β1 receptors; integrin-mediated death; HepG2 cells

Online: 14 August 2024 (07:15:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0912.v1

Comparative Analysis of Rapid and Less Invasive Methods for A2A2 Dairy Cattle Genotyping and A2 Milk Purity Detection

Aniela Pinto Kempka, Leandra Oliveira Xavier Albiero, Rafaela Ansiliero

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: A2A2 dairy cows; Genotyping; ELISA; LFIA; Comparison of methods; Facilitated analysis

Online: 13 August 2024 (13:13:29 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.0784.v1

Enzyme Catalysis for Sustainable Value Creation using Renewable Biobased Resources

Roland Wohlgemuth

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: biomanufacturing; biocatalysis; enzymes; industrial biotechnology; sustainable chemistry; white biotechnology; green chemistry

Online: 12 August 2024 (10:29:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0655.v1

Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway

Anna Koppin, Leah Chase

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SLC7A11; xCT; System xc-; endoplasmic reticulum acetylation; trafficking; glycosylation

Online: 12 August 2024 (02:51:29 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0690.v1

Metalloproteomics Reveals Multi-Level Stress Response in Escherichia Coli When Exposed to Arsenite

James Larson, Brett Sather, Lu Wang, Jade Westrum, Monika Tokmina-Lukaszewska, Jordan Pauley, Valérie Copié, Timothy R McDermott, Brian Bothner

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: arsenic; bacteria; metalloproteome; metal; TCA cycle; iron-sulfur cluster; molybdenum cofactor

Online: 9 August 2024 (08:30:15 CEST)

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Preprint REVIEW | doi:10.20944/preprints202408.0509.v1

Post-Translational Modifications of Cysteine Residues in Plant Proteins and Their Impact on the Regulation of Metabolism and Signal Transduction

Charlie Boutin, Camille Clément, Jean Rivoal

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: post-translational modification; cysteine; regulation; signal transduction; metabolism; thiol; redox modification

Online: 7 August 2024 (14:09:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0402.v1

Of SINEs, LINEs and Leeches: Identification and Molecular Characterization of Transposable Elements in Leech Genomes

Christian Müller

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: transposable elements; SINE; LINE; hirudin gene; leeches

Online: 6 August 2024 (08:42:34 CEST)

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Biology and Life Sciences