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BioTech
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BioTech: 5th Anniversary
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BioTech: 5th Anniversary

A special issue of BioTech (ISSN 2673-6284).

Deadline for manuscript submissions: 31 May 2026 | Viewed by 12580

Special Issue Editors

Prof. Dr. Massimo Negrini

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Guest Editor
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
Interests: non-coding RNA; microRNA; miRNA
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Francesco Secundo

E-Mail Website
Guest Editor
Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milan, Italy
Interests: biocatalysis; protein conformation; analysis of food samples
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gary Hardiman

E-Mail Website
Guest Editor
Faculty of Medicine, Health and Life Sciences Director of Research, School of Biological Sciences & Institute for Global Food Security, Belfast BT9 5DL, UK
Interests: adverse outcome pathways (AOP); transcriptomics (RNA-Seq); endocrine disrupting chemicals (EDC); genotype-phenotype mapping; gene-environment interactions (GxE)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to celebrate the fifth anniversary of BioTech!

Over the years, our journal has experienced steady growth in the number of scientific articles it has published. Despite being relatively young, BioTech has achieved its first Impact Factor, reflecting its increasing importance—an accomplishment that was by no means guaranteed. This success is due to the invaluable contributions of our Editorial Board Members and reviewers, who have dedicated their time and expertise selflessly. We extend our heartfelt gratitude to them, as well as to the authors who have entrusted BioTech with their research.

We would also like take this opportunity to thank our Editorial Office. Their dedication and support have ensured that the journal maintains a rigorous yet efficient peer-review process, allowing for the timely publication of high-quality research.

In today’s rapidly evolving world, where life sciences and cutting-edge technologies are combined to address global challenges, our upcoming Special Issue marks a significant milestone. It offers a unique platform on which to integrate diverse aspects of biotechnology, celebrating innovation and progress in the field.

We invite contributions spanning a wide range of topics, including the following:

- Red biotechnology (medical applications);

- White biotechnology (industrial and environmental applications);

- Green biotechnology (agriculture and sustainability);

- Computational biology, which intersects with all these areas;

- The regulation of biotechnology, including policies and ethical considerations.

As a multidisciplinary platform, BioTech not only bridges the gaps between different biotechnology fields but also integrates computational biology and regulatory perspectives. Our goal is to provide a comprehensive approach to tackling global challenges while maintaining the journal’s reputation as an authoritative and innovative voice in biotechnology.

We welcome original research articles and comprehensive reviews from all biotechnology disciplines to this Special Issue. Topics of interest include, but are not limited to the following:

- Advances in gene therapies and diagnostic strategies;

- Coding and noncoding RNAs as bioactive molecules in precision medicine;

- Application of artificial intelligence in biological systems;

- Optimization of bioproduction processes;

- Development of bioremediation systems ;

- Innovations in sustainable agriculture and food production;

- Research addressing the economic, social, and environmental impacts of biotechnological solutions.

We look forward to your contributions and to engaging with a dynamic scientific community in the pursuit of groundbreaking advancements. We are open to candidates interested in managing specific topics or Special Issues. With the continued support of our editorial team, we remain committed to ensuring a fair, rapid, and rigorous review process and publishing high-impact papers that drive innovation in the biotechnology field.

Sincerely,

Prof. Dr. Massimo Negrini, Editor-in-Chief
Prof. Dr. Francesco Secundo, Section Editor-in-Chief
Prof. Dr. Gary Hardiman, Section Editor-in-Chief
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. BioTech is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

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Research

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20 pages, 5618 KB  
Article
Transcriptomic Analysis Reveals an NRF2-Mediated Redox and Metabolic Reprogramming in Sorafenib-Resistant Hepatocellular Carcinoma Cells
by Angelo Michilli, Cristian Bassi, Farzaneh Moshiri, Bruno De Siena, Rosaria Marinaro, Elisa Callegari, Massimo Negrini and Silvia Sabbioni
BioTech 2026, 15(1), 18; https://doi.org/10.3390/biotech15010018 - 11 Feb 2026
Viewed by 905
Abstract
Despite the advent of immune checkpoint inhibitor-based regimens, sorafenib remains an important therapeutic option for patients with advanced hepatocellular carcinoma (HCC) who are ineligible for immunotherapy. However, its clinical efficacy is limited by the emergence of drug resistance, whose underlying molecular mechanisms remain [...] Read more.
Despite the advent of immune checkpoint inhibitor-based regimens, sorafenib remains an important therapeutic option for patients with advanced hepatocellular carcinoma (HCC) who are ineligible for immunotherapy. However, its clinical efficacy is limited by the emergence of drug resistance, whose underlying molecular mechanisms remain incompletely understood. To investigate these mechanisms, we established a murine model of acquired sorafenib resistance and performed comparative RNA sequencing of sorafenib-sensitive versus -resistant Hep55.1C hepatoma cells. Transcriptomic profiling revealed a distinct resistance-associated signature comprising 1264 significantly deregulated genes (adjusted p < 0.03, fold change > 3.0). Pathway analysis and Gene Set Enrichment Analyses (GSEA) indicated a coordinated downregulation of metabolic and intercellular signaling pathways, accompanied by marked upregulation of redox-regulatory, mitochondrial and cellular stress-response programs. Genes transcriptionally regulated by nuclear factor erythroid 2-related factor 2 (NRF2) including Gpx4, Txn1, Txnrd1, Hmox1, Fth1, Taldo1, Phgdh, and MafG, involved in antioxidant defense, ferroptosis suppression and metabolic rewiring, were all upregulated in resistant cells. Pharmacological inhibition of NRF2 activity using brusatol restored sensitivity to sorafenib, functionally implicating NRF2-dependent pathways in the maintenance of the resistant phenotype. These findings demonstrate that acquired sorafenib resistance in HCC is associated with a stable NRF2-driven transcriptional and metabolic reprogramming that enhances antioxidant capacity, suppresses ferroptosis and promotes tumor cell survival. Targeting NRF2-regulated redox metabolism may therefore represent a promising strategy to overcome therapeutic resistance in HCC. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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12 pages, 2048 KB  
Article
Recombinant Clostridium acetobutylicum Endoxylanase for Xylooligosaccharide Production from Pretreated Lignocellulosic Biomass
by Afifa Husna, Agustin Krisna Wardani, Chun-Yi Hu and Yo-Chia Chen
BioTech 2025, 14(4), 85; https://doi.org/10.3390/biotech14040085 - 30 Oct 2025
Viewed by 983
Abstract
Xylooligosaccharides (XOS) are functional oligosaccharides with recognized prebiotic properties and growing industrial relevance, typically obtained through enzymatic depolymerization of xylan-rich lignocellulosic substrates. In this study, a recombinant endo-β-1,4-xylanase (XynA) from Clostridium acetobutylicum was employed for XOS production. The xynA gene was cloned into [...] Read more.
Xylooligosaccharides (XOS) are functional oligosaccharides with recognized prebiotic properties and growing industrial relevance, typically obtained through enzymatic depolymerization of xylan-rich lignocellulosic substrates. In this study, a recombinant endo-β-1,4-xylanase (XynA) from Clostridium acetobutylicum was employed for XOS production. The xynA gene was cloned into the expression vector pET-21a(+) and heterologously expressed in Escherichia coli BL21(DE3) under induction with isopropyl β-D-1-thiogalactopyranoside (IPTG). The recombinant protein, with an estimated molecular mass of 37.5 kDa, was verified by SDS-PAGE and Western blot analysis. Functional characterization via thin-layer chromatography revealed that XynA efficiently hydrolyzed beechwood xylan and rye arabinoxylan, predominantly yielding xylobiose. Additionally, the enzyme catalyzed the conversion of xylotriose into xylobiose and trace amounts of xylose. Notably, XynA demonstrated hydrolytic activity against autohydrolysed and alkali-pretreated coconut husk biomass, facilitating the release of XOS. These results underscore the potential of C. acetobutylicum XynA as a biocatalyst for the valorization of lignocellulosic residues into high-value oligosaccharides. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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23 pages, 4560 KB  
Article
A Single-Nucleus Transcriptomic Atlas of the Mouse Lumbar Spinal Cord: Functional Implications of Non-Coding RNAs
by Pablo Ruiz-Amezcua, Miguel Nieto Hernández, Javier García Flores, Clara Plaza Alonso, David Reigada, Teresa Muñoz-Galdeano, Eva Vargas, Rodrigo M. Maza, Francisco J. Esteban and Manuel Nieto-Díaz
BioTech 2025, 14(3), 70; https://doi.org/10.3390/biotech14030070 - 3 Sep 2025
Viewed by 2485
Abstract
The adult lumbar spinal cord plays a critical role in locomotor control and somatosensory integration, whose transcriptional architecture under physiological conditions has been characterized in various studies with restricted numbers of individuals (up to four). Here, we present an integrative single-nucleus RNA sequencing [...] Read more.
The adult lumbar spinal cord plays a critical role in locomotor control and somatosensory integration, whose transcriptional architecture under physiological conditions has been characterized in various studies with restricted numbers of individuals (up to four). Here, we present an integrative single-nucleus RNA sequencing (snRNA-seq) atlas of the healthy adult mouse lumbar spinal cord, assembled from over 86,000 nuclei from 16 samples across five public datasets. Using a harmonized computational pipeline, we identify all major spinal cell lineages and resolve 17 transcriptionally distinct neuronal subtypes. A central novelty of our approach is the systematic inclusion of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and pseudogenes. By comparing transcriptomic analyses based on coding-only, non-coding-only, and combined gene sets, we show that ncRNAs, despite accounting to a 10% of the recorded information of each cell, contribute to cell type-specific signatures. This resource offers a high-resolution, ncRNA-inclusive reference for the adult spinal cord and provides a foundation for future studies on spinal plasticity, injury, and regeneration. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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11 pages, 1621 KB  
Article
Genomic Characterization of Linezolid-Resistant Clostridioides difficile Harboring cfr Variants
by Aikaterini Panou, Andigoni Malousi and Melina Kachrimanidou
BioTech 2025, 14(2), 42; https://doi.org/10.3390/biotech14020042 - 31 May 2025
Cited by 1 | Viewed by 1828
Abstract
The emergence of antimicrobial resistance (AMR) in Clostridium difficile (C. difficile), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant C. difficile, focusing on the distribution and [...] Read more.
The emergence of antimicrobial resistance (AMR) in Clostridium difficile (C. difficile), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant C. difficile, focusing on the distribution and mutational patterns of the chloramphenicol–florfenicol resistance (cfr) gene and its association with multidrug resistance. We analyzed 514 clinical isolates (354 from NCBI Pathogen Detection, 160 from EnteroBase), revealing distinct prevalence patterns among cfr subtypes: cfr(C) was dominant (156/354 NCBI strains; 101/160 EnteroBase strains), whereas cfr(B) frequently harbored missense mutations (p.R247K, p.V294I, and less commonly p.A334T). The cfr(E) subtype was exclusively identified in ribotype 027 (RT027) strains. Notably, cfr(C) exhibited a strong association with RT017, correlating with a conserved 99 bp genomic deletion. Phylogenetic analysis linked cfr-carriage to predominant sequence types (ST1 in NCBI strains, ST37 in EnteroBase isolates). Furthermore, the co-occurrence of cfr with additional AMR genes conferred resistance to macrolides (erythromycin, azithromycin) and tetracyclines, indicating a convergent evolution toward multidrug resistance. These findings underscore the interplay between cfr mutations, hypervirulent ribotypes, and AMR dissemination, necessitating enhanced surveillance to mitigate the spread of resistant C. difficile lineages. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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Review

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19 pages, 1018 KB  
Review
TG221: An Experimental Model for Liver Cancer Prevention and Treatment Approaches
by Elisa Callegari, Angelo Michilli, Farzaneh Moshiri, Bruno De Siena, Laura Gramantieri, Massimo Negrini and Silvia Sabbioni
BioTech 2026, 15(1), 9; https://doi.org/10.3390/biotech15010009 - 19 Jan 2026
Viewed by 747
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. It usually arises in cirrhotic liver, where chronic inflammation and fibrosis create a tumor-permissive microenvironment. Dysregulation of microRNAs (miRNAs), particularly upregulation of the oncomiR miR-221 and loss of the tumor suppressor miR-199a-3p represent [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. It usually arises in cirrhotic liver, where chronic inflammation and fibrosis create a tumor-permissive microenvironment. Dysregulation of microRNAs (miRNAs), particularly upregulation of the oncomiR miR-221 and loss of the tumor suppressor miR-199a-3p represent key drivers of liver carcinogenesis. The TG221 transgenic mouse, designed to overexpress miR-221 in hepatocytes, provides a relevant in vivo platform for mechanistic studies and for testing preventive and therapeutic approaches. The TG221 model recapitulates miR-221-driven tumorigenesis, including suppression of p27, p57 and Bmf. It is characterized by steatohepatitic injury and accelerated tumor formation after genotoxic challenge. In the cirrhotic CCl4-induced background, TG221 mice develop fibrosis and cirrhosis followed by dysplastic and malignant lesions, mirroring the natural history of human HCC. Metformin administered during early fibrosis prevented macroscopic tumor formation and suppressed PI3K/AKT/mTOR signaling. Anti-miR-221 and miR-199a-3p mimics reduced tumor burden, restored tumor-suppressive pathways and improved liver integrity, thus indicating feasible chemopreventive strategies. From a therapeutic point of view, miR-199a-3p replacement synergized with palbociclib and overcame sorafenib resistance. A miR-199a-3p-responsive oncolytic adenovirus achieved tumor-selective replication with minimal toxicity. This review highlights the importance of the TG221 transgenic mouse as a powerful model for studying miRNA-driven hepatocarcinogenesis and enables preclinical evaluation of RNA-based chemopreventive and therapeutic approaches. Metformin, miRNA inhibition, miRNA replacement and miRNA-guided viral therapies emerge as promising approaches for advancing precision prevention and treatment strategies in HCC. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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13 pages, 238 KB  
Review
Microbial Landscape of Pharmaceutical Failures: A 21-Year Review of FDA Enforcement Reports
by Luis Jimenez
BioTech 2026, 15(1), 8; https://doi.org/10.3390/biotech15010008 - 18 Jan 2026
Cited by 3 | Viewed by 1312
Abstract
By analyzing Food and Drug Administration (FDA) enforcement reports from 2004 to 2025, we can determine the incidence of microbial contamination in non-sterile and sterile drugs in the United States of America and, at the same time, compare the trends and patterns over [...] Read more.
By analyzing Food and Drug Administration (FDA) enforcement reports from 2004 to 2025, we can determine the incidence of microbial contamination in non-sterile and sterile drugs in the United States of America and, at the same time, compare the trends and patterns over a period of 21 years to determine the distribution and frequency of microbial contaminants. The most common microorganisms detected from 2019 to 2025 were the mold Aspergillus penicilloides, with 17 citations for sterile products, followed by 16 citations for non-sterile products of Burkholderia cepacia complex (BCC) bacteria. Analysis from the last 21 years revealed the dominant microbial contaminants belong to the BCC, reaching a maximum level between 2012 and 2019. Some of the previous microbial contaminants, such as Salmonella and Clostridium, decline in the 2019–2025 period, with no notifications issued. S. aureus and Pseudomonas contamination persisted through the years but at very low levels. Gram-negative bacteria contaminated non-sterile drugs more frequently than Gram-positive. A worrisome trend continued with unacceptable levels of enforcement reports not providing any information on the identity of the microbial contaminant. New species of Bacillus and Acetobacter nitrogenifigens were responsible for a significant increase in non-sterile drug recalls. The main driver for sterile product recalls over a 21-year period is the lack of assurance of sterility (LAS) where major failures in process design, control, and operational execution were not conducive to the control of microbial proliferation and destruction. Enforcement data analysis identified the problematic trends and patterns regarding microbial contamination of drugs, providing important information to optimize process control and provide a framework for optimizing risk mitigation. Although the 21-year landscape demonstrated that some microbial contaminants have been successfully mitigated, others remain resilient. The emergence of new contaminants highlights the evolving nature of microbial risk. The consistent problem with LAS is not only a major regulatory violation but also a potential catalyst for the next major healthcare-associated outbreak. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
32 pages, 957 KB  
Review
Broomrapes in Major Mediterranean Crops: From Management Strategies to Novel Approaches for Next-Generation Control
by Demosthenis Chachalis, Eleni Tani, Aliki Kapazoglou, Maria Gerakari, Angeliki Petraki, Francisco Pérez-Alfocea, Purificación A. Martínez-Melgarejo, Markus Albert, Khalil Khamassi and Mohamed Kharrat
BioTech 2025, 14(2), 40; https://doi.org/10.3390/biotech14020040 - 25 May 2025
Cited by 3 | Viewed by 2978
Abstract
Broomrapes (Orobanche and Phelipanche spp.) are parasitic weeds that significantly impact the productivity of major crops in the Mediterranean region, like tomato (Solanum spp.) and faba bean (Vicia faba) species. This review article extensively discusses management strategies to control [...] Read more.
Broomrapes (Orobanche and Phelipanche spp.) are parasitic weeds that significantly impact the productivity of major crops in the Mediterranean region, like tomato (Solanum spp.) and faba bean (Vicia faba) species. This review article extensively discusses management strategies to control broomrapes, which range from preventive measures to curative approaches. Additionally, it includes meaningful information on the intricate molecular mechanisms underlying the broomrape–host interaction, focusing on the host recognition of parasitic plant molecular patterns and the hormonal crosstalk that regulates the establishment of parasitism. Moreover, this article highlights the potential of breeding for resistance in cultivated crops, such as tomato and faba bean, as a sustainable, long-term solution to combat broomrape infestation. This review serves as a valuable resource for both researchers and farmers, offering insights for developing, implementing, and adapting effective and environmentally sustainable management practices for broomrape in Mediterranean agricultural systems. Full article
(This article belongs to the Special Issue BioTech: 5th Anniversary)
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