Systems biology

The Python-based program, XMECP, is developed for realizing robust, efficient, and state-of-the-art minimum energy crossing point (MECP) optimization in multiscale complex systems. This article introduces the basic capabilities of the XMECP program by theoretically investigating the MECP mechanism of several example systems including (1) the photosensitization mechanism of benzophenone, (2) photoinduced proton-coupled electron transfer in the cytosine-guanine base pair in DNA, (3) the spin-flip process in oxygen activation catalyzed by an iron-containing 2-oxoglutarate-dependent oxygenase (Fe/2OGX), and (4) the photochemical pathway of flavoprotein adjusted by the intensity of an external electric field...

Chirality is a structural metric that connects biological and abiological forms of matter. Although much progress has been made in understanding the chemistry and physics of chiral inorganic nanoparticles over the past decade, almost nothing is known about chiral two-dimensional (2D) borophene nanoplatelets and their influence on complex biological networks. Borophene's polymorphic nature, derived from the bonding configurations among boron atoms, distinguishes it from other 2D materials and allows for further customization of its material properties...

Atherosclerosis remains a leading cause of cardiovascular disease (CVD) globally, with the complex interplay of inflammation and lipid metabolism at its core. Recent evidence suggests a role of B cells in the pathogenesis of atherosclerosis; however, this relationship remains poorly understood, particularly in the context of HIV. We review the multifaceted functions of B cells in atherosclerosis, with a specific focus on HIV. Unique to atherosclerosis is the pivotal role of natural antibodies, particularly those targeting oxidized epitopes abundant in modified lipoproteins and cellular debris...

We investigate the effects of uniform viscosity gradients on the spontaneous oscillations of an elastic, active filament in viscous fluids. Combining numerical simulations and linear stability analysis, we demonstrate that a viscosity gradient increasing from the filament's base to tip destabilises the system, facilitating its self-oscillation. This effect is elucidated through a reduced-order model, highlighting the delicate balance between destabilising active forces and stabilising viscous forces. Additionally, we reveal that while a perpendicular viscosity gradient to the filament's orientation minimally affects instability, it induces asymmetric ciliary beating, thus generating a net flow along the gradient...

During their biosynthesis, Sonic hedgehog (Shh) morphogens are covalently modified by cholesterol at the C-terminus and palmitate at the N-terminus. Although both lipids initially anchor Shh to the plasma membrane of producing cells, it later translocates to the extracellular compartment to direct developmental fates in cells expressing the Patched (Ptch) receptor. Possible release mechanisms for dually lipidated Hh/Shh into the extracellular compartment are currently under intense debate. In this paper, we describe the serum-dependent conversion of the dually lipidated cellular precursor into a soluble cholesteroylated variant (ShhC ) during its release...

Gap junctional connection (GJC) in the cumulus-oocyte complex (COC) provides necessary support for message communication and nutrient transmission required for mammalian oocyte maturation. Cyclic adenosine monophosphate (cAMP) is not only a prerequisite for regulating oocyte meiosis, but also the key intercellular factor for affecting GJC function in COCs. However, there are no reports on whether cAMP regulates connexin 37 (Cx37) expression, one of the main connexin proteins, in sheep COCs. In this study, the expression of Cx37 protein and gene in immature sheep COC was detected using immunohistochemistry and PCR...

The computer-assisted program SiD was developed to assess and select sperm in real time based on motility characteristics. To date, there are limited studies examining the correlation between AI-assisted sperm selection and ICSI outcomes. To address this limit, a total of 646 sibling MII oocytes were randomly divided into two groups as follows: the ICSI group (n = 320): ICSI performed with sperm selected by the embryologist and the ICSI-SiD group (n = 326): ICSI performed with sperm selected using SiD software...

With growing recognition and acknowledgement of the genuine complexity of proteomes, we are finally entering the post-proteogenomic era. Routine assessment of proteomes as inferred correlates of gene sequences (i.e., canonical 'proteins') cannot provide the necessary critical analysis of systems-level biology that is needed to understand underlying molecular mechanisms and pathways or identify the most selective biomarkers and therapeutic targets. These critical requirements demand the analysis of proteomes at the level of proteoforms/protein species, the actual active molecular players...

Iron-sulfur clusters play essential roles in biological systems, and thus synthetic [Fe4 S4 ] clusters have been an area of active research. Recent studies have demonstrated that soluble [Fe4 S4 ] clusters can serve as net H atom transfer mediators, improving the activity and selectivity of a homogeneous Mn CO2 reduction catalyst. Here, we demonstrate that incorporating these [Fe4 S4 ] clusters into a coordination polymer enables heterogeneous H atom transfer from an electrode surface to a Mn complex dissolved in solution...

Through the integration of CRISPR/Cpf1 with optogenetics and a reduction-responsive motif, we have developed a photoactivatable cross-linked crRNA that enables precise genome editing upon light exposure. This system also allows for termination of editing activity through external application of reducing agent. The dual-stimuli-responsive CRISPR/Cpf1 editing process operates in a unique OFF → ON → OFF sequence, making it a valuable tool for investigating time-sensitive biological events.

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Integration of multiple data sources presents a challenge for accurate prediction of molecular patho-phenotypic features in automated analysis of data from human model systems. Here, we applied a machine learning-based data integration to distinguish patho-phenotypic features at the subcellular level for dilated cardiomyopathy (DCM). We employed a human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of a DCM mutation in the sarcomere protein troponin T (TnT), TnT-R141W, compared to isogenic healthy (WT) control iPSC-CMs...

The application of pulsed electric fields (PEFs) is becoming a promising tool for application in biotechnology, and the food industry. However, real-time monitoring of the efficiency of PEF treatment conditions is challenging, especially at the industrial scale and in continuous production conditions.  To overcome this challenge, we have developed a straightforward setup capable of real-time detection of yeast biological autoluminescence (BAL) during pulsing. Saccharomyces cerevisiae culture was exposed to 8 pulses of 100 µs width with electric field strength magnitude 2-7 kV cm-1 ...

Human papillomavirus (HPV) is the most common sexually transmitted pathogen that causes anogenital disease. Cervical screening by cytology and HPV testing (co-testing) are important in prevention of cervical cancer. The Bethesda System category of atypical squamous cells (ASC) is used when a neoplastic process cannot be confidently identified. In such cases, the differential diagnosis is broad and includes benign conditions. Monitoring of ASC/SIL ratio is a commonly used laboratory quality assurance measure to prevent over- or under-use of this category...

Glioma is the most common malignant tumor of the nervous system in recent centuries, and the incidence rate of glioma is increasing year by year. Its invasive growth and malignant biological behaviors make it one of the most challenging malignant tumors. Maximizing the resection range (EOR) while minimizing the impact on normal brain tissue is crucial for patient prognosis. Changes in metabolites produced by tumor cells and their microenvironments might be important indicators. As a powerful spectroscopic technique, surface-enhanced Raman scattering (SERS) has many advantages, including ultra-high sensitivity, high specificity, and non-invasive features, which allow SERS technology to be widely applied in biomedicine, especially in the differential diagnosis of malignant tumor tissues...

Genome-scale metabolic models (GEMs) have been widely employed to predict microorganism behaviors. However, GEMs only consider stoichiometric constraints, leading to a linear increase in simulated growth and product yields as substrate uptake rates rise. This divergence from experimental measurements prompted the creation of enzyme-constrained models (ecModels) for various species, successfully enhancing chemical production. Building upon studies that allocate macromolecule resources, we developed a Python-based workflow (ECMpy) that constructs an enzyme-constrained model...

Polygalacturonase inhibiting proteins (PGIPs) are plant proteins involved in the inhibition of polygalacturonases (PGs), cell-wall degrading enzymes often secreted by phytopathogenic fungi. Previously, we confirmed that PGIP2 from Phaseolus vulgaris (PvPGIP2) can inhibit the growth of Aspergillus niger and Botrytis cinerea on agar plate. In this study, we further validated the feasibility of using PGIP as an environmental and ecological friendly agent to prevent fungal infection post-harvest. We found that application of either purified PGIP (full length PvPGIP2 or truncated tPvPGIP2_5-8), or PGIP-secreting Saccharomyces cerevisiae strains can effectively inhibit fungal growth and necrotic lesions on tobacco leaf...

The human body exploits its neural mechanisms to optimize actions. Rhythmic movements are optimal when their frequency is close to the natural frequency of the system. In a pendulum, gravity modulates this spontaneous frequency. Participants unconsciously adjust their natural pace when cyclically moving the arm in altered gravity. However, the timescale of this adaptation is unexplored. Participants performed cyclic movements before, during, and after fast transitions between hypergravity levels (1g-3g and 3g-1g) induced by a human centrifuge...

The role of neutrophils in tumor initiation stage is rarely reported because of the lack of suitable models. We found that neutrophils recruited in early tumor nodules induced by subcutaneous inoculation of B16 melanoma cells were able to attack tumor cells by trogocytosis. The anti-tumor immunotherapy like peritoneal injection with TLR9 agonist CpG oligodeoxynucleotide combined with transforming growth factor β2 inhibitor TIO3 could increase the trogocytic neutrophils in the nodules, as well as CD8+ T cells, natural killer (NK) cells, and their interferon-γ production...

Planar polarity is a commonly observed phenomenon in which proteins display a consistent asymmetry in their subcellular localization or activity across the plane of a tissue. During animal development, planar polarity is a fundamental mechanism for coordinating the behaviors of groups of cells to achieve anisotropic tissue remodeling, growth, and organization. Therefore, a primary focus of developmental biology research has been to understand the molecular mechanisms underlying planar polarity in a variety of systems to identify conserved principles of tissue organization...