Nghia Nhu Nguyen, Bao The Nguyen, Huyen Thi Ngoc Le
et al.
Background Liver fibrosis is a significant health burden in Vietnamese male adults, driven by high rates of hepatitis B and hepatitis C, excessive alcohol consumption, and genetic and environmental factors. Despite progress in diagnostic tools, there is a pressing need for cost-effective screening methods tailored to this high-risk group, particularly in resource-limited settings. Methods This study enrolled 952 Vietnamese male adults over 40 years old undergoing FibroScan, excluding those with conditions affecting test accuracy. Data on demographics, clinical history, and anthropometrics were collected, and fibrosis stages were classified using the METAVIR system. Model development combined Bayesian model averaging and forward stepwise methods, with predictive performance validated via receiver operating characteristic (ROC) analysis and area under the curve (AUC) estimation in the R environment. Results Among 952 male participants, the prevalence of liver fibrosis was 19.9%, with most cases classified as mild (F1). Multivariate analysis identified significant risk factors, including advanced age (odds ratio (OR) = 1.6; 95% confidence interval (CI) [1.02–2.51]), alcohol abuse (OR = 4.44; 95% CI [2.65–7.42]), hepatitis B (OR = 6.76; 95% CI [3.14–14.54], hepatitis C (OR = 33.04; 95% CI [5.26–207.42]), family history of cirrhosis (OR = 16.14; 95% CI [3.28–79.55]), and hepatic steatosis (OR = 4.02; 95% CI [2.57–6.28]). The predictive model demonstrated good discriminative performance with an AUC of 0.769 (95% CI [0.734–0.800]) and showed satisfactory calibration through bootstrap resampling, indicating close agreement between predicted and observed risks. Conclusion The current prevalence of liver fibrosis among Vietnamese male adults was found to be 19.9%, and the developed risk prediction model effectively identifies high-risk individuals, enabling early diagnosis and targeted prevention, particularly in resource-limited settings. However, the lack of external validation and the sample restricted to Vietnamese male adults limit the generalizability of the model, which should be further evaluated in other populations.
Isabella Frighetto Bomfiglio, Isabelli Seiler de Medeiros Mendes, Diego Bonatto
DNA cloning methods are fundamental tools in molecular biology, synthetic biology, and genetic engineering that enable precise DNA manipulation for various scientific and biotechnological applications. This review systematically summarizes the major restriction-free overlapping sequence cloning (RFOSC) techniques currently used in synthetic biology and examines their development, efficiency, practicality, and specific applications. In vitro methods, including Gibson Assembly, Circular Polymerase Extension Cloning (CPEC), Polymerase Incomplete Primer Extension (PIPE), Overlap Extension Cloning (OEC), Flap Endonuclease Cloning (FEN-Cloning), and commercially available techniques such as TOPO and In-Fusion, have been discussed alongside hybrid approaches such as Ligation-Independent Cloning (LIC), Sequence-Independent Cloning (SLIC), and T5 Exonuclease-Dependent Assembly (TEDA). Additionally, in vivo methods leveraging host recombination machinery, including Yeast Homologous Recombination (YHR), In Vivo Assembly (IVA), Transformation-Associated Recombination (TAR), and innovative approaches such as Multiple-Round In Vivo Site-Specific Assembly (MISSA) and Phage Enzyme-Assisted Direct Assembly (PEDA), are critically evaluated. The review highlights that method selection should consider the scale, complexity, cost, and specific needs of individual research projects, noting that no single technique is universally optimal. Future trends suggest the increased integration of enzymatic efficiency, host versatility, and automation, broadening the accessibility and capabilities of DNA assembly technologies.
Bioinsecticides based on the bacterium <i>Bacillus thuringiensis</i> (Bt) are widely used as safe alternatives to chemical insecticides. The insecticidal activity of Bt is occasioned by a protein toxin contained in parasporal crystals (Cry proteins) that are synthesized and laid down alongside the endospore during sporulation. The specificity of toxin action is associated with the subspecies of Bt and the individual Cry toxins they produce. Although a number of commercial Bt formulations are available to control moths, mosquitoes and beetles, there are none that control the red imported fire ant (RIFA) <i>Solenopsis invicta</i>. The present report is the first to describe the insecticidal activity of the Cry3A protein toxin, produced by <i>Bacillus thuringiensis</i> subsp. <i>tenebrionis</i> (Btt), against the RIFA as well as some of its key biochemical properties. Currently available commercial formulations of Btt are designed to control beetles such as the Colorado potato beetle, not ants. The Cry3A toxin (MW ~66 kDa) is embedded in a larger polypeptide (protoxin, MW ~73 kDa) and is released from the toxin enzymatically. Once activated, it can be administered to the RIFA as a soluble protein that most likely binds to an attendant receptor in the epithelial cells that line the wall of the larval ventriculus, killing the insect. Properly customized, the Cry3A toxin is a potential candidate for fire ant control.
Alex Ferreira da Silva, Franciele Jesus Lima, Alyne Riani Moreira
et al.
Aberrant Rho-associated kinase function could be associated with increased bone fragility. Since cigarette smoke (CS) exposure promotes the increase in bone fragility due to changes in bone tissue components, this study aimed to investigate how CS exposure could modulate the Rho kinase-associated bone structural changes. Mice were assigned to four groups: control; smoke; control with Rho kinase inhibitor administration; and smoke with a Rho kinase inhibitor. Bone samples were obtained to assess bone histomorphometry analysis, type I collagen composition, and MEPE expression in trabeculae. We observed that CS exposure induced decreased trabecular and osteoid thickness. A concomitant increase in the osteoclastic and erosion surfaces and a decrease in the mineralization surface were observed. Additionally, CS exposure decreased the type I collagen and MEPE expression. Rho kinase inhibitor administration recovered the bone mineralization and the collagen type I deposition. Conclusions: CS exposure increases Rho kinase activity in bone cells, leading to structural changes. The administration of a Rho GTPases inhibitor partially reverses these effects, likely due to the recovery in osteoblast activity.
Yutaro Hama, Yuko Fujioka, Hayashi Yamamoto
et al.
In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101. However, the structural basis and mechanism underlying the ULK complex assembly have yet to be fully clarified. Here, we predicted the core interactions organizing the ULK complex using AlphaFold, which proposed that the intrinsically disordered region of ATG13 engages the bases of the two UBL domains in the FIP200 dimer via two phenylalanines and also binds the tandem microtubule-interacting and transport domain of ULK1, thereby yielding the 1:1:2 stoichiometry of the ULK1–ATG13–FIP200 complex. We validated the predicted interactions by point mutations and demonstrated direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, wherein each interaction was additively important for autophagic flux. These results indicate that the ULK1–ATG13–FIP200 triadic interaction is crucial for autophagosome formation and provides a structural basis and insights into the regulation mechanism of autophagy initiation in mammals.
Tazarotene, a retinoid derivative, is widely used in treating skin conditions such as psoriasis and acne. Recent studies have demonstrated its potential as a promising therapeutic agent for treating melanoma in situ. Its primary mechanism of action involves the selective activation of retinoic acid receptors (RAR-β and RAR-γ), which play important roles in regulating cell growth, differentiation, and apoptosis. By activating these receptors, tazarotene influences the expression of several downstream inducible genes, such as tazarotene-induced gene-1 (<i>TIG1</i>), <i>TIG2</i>, and <i>TIG3</i>. These genes play crucial roles in regulating melanoma cell proliferation, invasiveness, and immune responses in the tumor microenvironment. This review aims to provide a comprehensive overview of the current status of retinoid derivatives—particularly tazarotene—in melanoma treatment and the latest research regarding their molecular mechanisms. We will explore how tazarotene suppresses melanoma growth through gene regulation mechanisms and discuss its potential role in immune responses within the tumor microenvironment. Additionally, we assess the advantages and challenges of using tazarotene as a topical treatment and explore its future clinical applications. These studies contribute to a wider understanding of tazarotene’s antitumor mechanisms, providing a solid theoretical foundation for its potential as a therapeutic option for melanoma in situ.
Nathaniel Linden-Santangeli, Jin Zhang, Boris Kramer
et al.
Mathematical models are indispensable to the system biology toolkit for studying the structure and behavior of intracellular signaling networks. A common approach to modeling is to develop a system of equations that encode the known biology using approximations and simplifying assumptions. As a result, the same signaling pathway can be represented by multiple models, each with its set of underlying assumptions, which opens up challenges for model selection and decreases certainty in model predictions. Here, we use Bayesian multimodel inference to develop a framework to increase certainty in systems biology models. Using models of the extracellular regulated kinase (ERK) pathway, we first show that multimodel inference increases predictive certainty and yields predictors that are robust to changes in the set of available models. We then show that predictions made with multimodel inference are robust to data uncertainties introduced by decreasing the measurement duration and reducing the sample size. Finally, we use multimodel inference to identify a new model to explain experimentally measured sub-cellular location-specific ERK activity dynamics. In summary, our framework highlights multimodel inference as a disciplined approach to increasing the certainty of intracellular signaling activity predictions.
Large language models (LLMs) have shown remarkable capabilities in general domains, but their application to multi-omics biology remains underexplored. To address this gap, we introduce Biology-Instructions, the first large-scale instruction-tuning dataset for multi-omics biological sequences, including DNA, RNA, proteins, and multi-molecules. This dataset bridges LLMs and complex biological sequence-related tasks, enhancing their versatility and reasoning while maintaining conversational fluency. We also highlight significant limitations of current state-of-the-art LLMs on multi-omics tasks without specialized training. To overcome this, we propose ChatMultiOmics, a strong baseline with a novel three-stage training pipeline, demonstrating superior biological understanding through Biology-Instructions. Both resources are publicly available, paving the way for better integration of LLMs in multi-omics analysis. The Biology-Instructions is publicly available at: https://github.com/hhnqqq/Biology-Instructions.
Large Language Models (LLMs), such as ChatGPT, have taken the world by storm and have passed certain forms of the Turing test. However, LLMs are not limited to human language and analyze sequential data, such as DNA, protein, and gene expression. The resulting foundation models can be repurposed to identify the complex patterns within the data, resulting in powerful, multi-purpose prediction tools able to explain cellular systems. This review outlines the different types of LLMs and showcases their recent uses in biology. Since LLMs have not yet been embraced by the plant community, we also cover how these models can be deployed for the plant kingdom.
AI-enabled synthetic biology has tremendous potential but also significantly increases biorisks and brings about a new set of dual use concerns. The picture is complicated given the vast innovations envisioned to emerge by combining emerging technologies, as AI-enabled synthetic biology potentially scales up bioengineering into industrial biomanufacturing. However, the literature review indicates that goals such as maintaining a reasonable scope for innovation, or more ambitiously to foster a huge bioeconomy don't necessarily contrast with biosafety, but need to go hand in hand. This paper presents a literature review of the issues and describes emerging frameworks for policy and practice that transverse the options of command-and control, stewardship, bottom-up, and laissez-faire governance. How to achieve early warning systems that enable prevention and mitigation of future AI-enabled biohazards from the lab, from deliberate misuse, or from the public realm, will constantly need to evolve, and adaptive, interactive approaches should emerge. Although biorisk is subject to an established governance regime, and scientists generally adhere to biosafety protocols, even experimental, but legitimate use by scientists could lead to unexpected developments. Recent advances in chatbots enabled by generative AI have revived fears that advanced biological insight can more easily get into the hands of malignant individuals or organizations. Given these sets of issues, society needs to rethink how AI-enabled synthetic biology should be governed. The suggested way to visualize the challenge at hand is whack-a-mole governance, although the emerging solutions are perhaps not so different either.
A biological circuit is a neural or biochemical cascade, taking inputs and producing outputs. How have biological circuits learned to solve environmental challenges over the history of life? The answer certainly follows Dobzhansky's famous quote that ``nothing in biology makes sense except in the light of evolution.'' But that quote leaves out the mechanistic basis by which natural selection's trial-and-error learning happens, which is exactly what we have to understand. How does the learning process that designs biological circuits actually work? How much insight can we gain about the form and function of biological circuits by studying the processes that have made those circuits? Because life's circuits must often solve the same problems as those faced by machine learning, such as environmental tracking, homeostatic control, dimensional reduction, or classification, we can begin by considering how machine learning designs computational circuits to solve problems. We can then ask: How much insight do those computational circuits provide about the design of biological circuits? How much does biology differ from computers in the particular circuit designs that it uses to solve problems? This article steps through two classic machine learning models to set the foundation for analyzing broad questions about the design of biological circuits. One insight is the surprising power of randomly connected networks. Another is the central role of internal models of the environment embedded within biological circuits, illustrated by a model of dimensional reduction and trend prediction. Overall, many challenges in biology have machine learning analogs, suggesting hypotheses about how biology's circuits are designed.
Background: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. Methods: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. Results: The expression of <i>CXCR2</i>, <i>SAA</i>, <i>COX1</i>, <i>PPARδ</i>, <i>PPARγ</i>, <i>Groγ</i>, <i>IL8</i>, <i>p21</i>, <i>c-myc</i>, <i>CD44</i> and <i>CSF1</i> was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that <i>CD44</i>, <i>IL8</i>, <i>CXCR2</i> and <i>c-myc</i> levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. Conclusion: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.
Majed Alluqmani, Abdulfatah M. Alayoubi, Jamil A. Hashmi
et al.
BackgroundVariants in a gene encoding sodium voltage-gated channel alpha subunit 1 (SCN1A) are known to cause a broad clinical spectrum of epilepsy and associated features, including Dravet syndrome (MIM 607208), non-Dravet developmental and epileptic encephalopathy (MIM 619317), familial febrile seizures (MIM 604403), familial hemiplegic migraine (MIM 609634), and generalized epilepsy with febrile seizures (MIM 604403).MethodsIn this study, we examined a patient with Parkinson’s disease (PD) without any clinical manifestations of epilepsy and associated features. Genomic nucleic acid was extracted, and a complete coding sequence of the human genome (whole-exome sequencing) was sequenced. Moreover, Sanger sequencing of variants of interest was performed to validate the exome-discovered variants.ResultsWe identified a heterozygous pathogenic missense mutation (c.1498C>T; p.Arg500Trp) in the SCN1A gene in the patient using the whole-exome sequencing approach. The onset of PD features in our patient occurred at the age of 30 years. Biochemical investigations were carried out to rule out any secondary cause of the disease, including Wilson's disease or another metabolic disorder. MRI of the brain and spinal images were unremarkable. Moreover, a dramatic response to carbidopa–levodopa treatment was also observed in the patient.ConclusionOur results suggest that the pathogenic variant in SCN1A may lead to PD features without epilepsy.
Motor ability decline remains a major threat to the quality of life of the elderly. Although the later stages of aging co-exist with degenerative pathologies, the long process of aging is more complicated than a simple and gradual degeneration. To combat senescence and the associated late-stage degeneration of the neuromuscular system, it is imperative to examine changes that occur during the long process of aging. Prior to late-stage degeneration, age-induced changes in the neuromuscular system trigger homeostatic plasticity. This unique phenomenon may be important for the maintenance of the neuromuscular system during the early stages of aging. In this review, we will focus on age-induced changes in neurotransmission at the neuromuscular junction, providing the potential mechanisms responsible for these changes. The goal is to highlight these key elements and their role in regulating neurotransmission, facilitating future research efforts to combat late-stage degeneration in the neuromuscular system by preserving the functional and structural integrity of these elements prior to the late stage of aging.
Graeme S. Cumming, Zoe G. Davies, Joern Fischer
et al.
Abstract This editorial reflects on the history of the conservation movement, the strong continuing influence of its colonial past, and the counter‐emergence of a more pluralistic and respectful worldview. Conservation Letters seeks to support and foster an ethical and inclusive discipline of conservation that discards elements of its colonial and racist history. This will involve broadening the disciplinary scope of “conservation” and paying greater attention to traditional ecological knowledge and nonwestern conservation approaches. We also see a particular need for theoretical advances that guide conservation practice by informing and connecting different kinds of expertise to understand social‐ecological interactions and their implications for both people and ecosystems. Conservation can and should play a vital role in securing the joint future of ecosystems and people, but it will only achieve its full potential if it retains its social license and stays relevant to emerging concerns and values.
General. Including nature conservation, geographical distribution
Mubarak Yakubova, Olga Manankova, Assel Mukasheva
et al.
The research problem described in this article is related to the security of an IP network that is set up between two cities using hosting. The network is used for transmitting telephone traffic between servers located in Germany and the Netherlands. The concern is that with the increasing adoption of IP telephony worldwide, the network might be vulnerable to hacking and unauthorized access, posing a threat to the privacy and security of the transmitted information. This article proposes a solution to address the security concerns of the IP network. After conducting an experiment and establishing a connection between the two servers using the WireShark sniffer, a dump of real traffic between the servers was obtained. Upon analysis, a vulnerability in the network was identified, which could potentially be exploited by malicious actors. To enhance the security of the network, this article suggests the implementation of the Transport Layer Security (TLS) protocol. TLS is a cryptographic protocol that provides secure communication over a computer network, ensuring data confidentiality and integrity during transmission. Integrating TLS into the network infrastructure, will protect the telephone traffic and prevent unauthorized access and eavesdropping.
BLT2 is a low-affinity leukotriene B4 receptor that plays an essential role in the pathogenesis of various inflammatory diseases, including asthma and cancer. BLT2 is minimally expressed in a normal internal environment but is overexpressed in a stress-induced inflammatory environment. Recent research indicated that human BLT2 has two distinct forms. Although their functions are likely to be different, very few studies investigated these differences. Therefore, this paper will discuss about the two distinct forms of human BLT2; the short-form of BLT2 and the long-form of BLT2.
Developing a robust understanding of Pacific halibut reproductive biology is essential to understanding the different components (e.g. maturity) that determine the reproductive output of the species and, therefore, for estimating the relative female spawning biomass. With these, effective and proactive management strategies can be designed and implemented to face the large-scale environmental changes to which high-latitude spawning fish are particularly vulnerable. To date, reproductive studies of Pacific halibut have mainly focused on population or regional scales, leaving the specific details of organism-level reproductive development unexamined. The work described here aimed to address information gaps in Pacific halibut reproductive biology by conducting a detailed histological examination of temporal changes in ovarian development over an annual reproductive cycle with special attention to the use of biological indicators (e.g. oocyte diameter, gonadosomatic index, hepatosomatic index, Fulton’s condition factor, somatic fat) in characterizing female developmental stages and reproductive phases. Our results provide a foundation for future studies directed at improving current maturity estimations by histological assessment and explore models that test the utility of biological indicators to predict maturity in this important fish species.
Science, General. Including nature conservation, geographical distribution