Modern Plant Breeding Techniques in Crop Improvement and Genetic Diversity: From Molecular Markers and Gene Editing to Artificial Intelligence-A Critical Review.

With the development of new technologies in recent years, researchers have made significant progress in crop breeding. Modern breeding differs from traditional breeding because of great changes in technical means and breeding concepts. Whereas traditional breeding initially focused on high yields, modern breeding focuses on breeding orientations based on different crops' audiences or by-products. The process of modern breeding starts from the creation of material populations, which can be constructed by natural mutagenesis, chemical mutagenesis, physical mutagenesis transfer DNA (T-DNA), Tos17 (endogenous retrotransposon), etc. Then, gene function can be mined through QTL mapping, Bulked-segregant analysis (BSA), Genome-wide association studies (GWASs), RNA interference (RNAi), and gene editing. Then, at the transcriptional, post-transcriptional, and translational levels, the functions of genes are described in terms of post-translational aspects. This article mainly discusses the application of the above modern scientific and technological methods of breeding and the advantages and limitations of crop breeding and diversity. In particular, the development of gene editing technology has contributed to modern breeding research.

Bioinformatics in Russia: history and present-day landscape.

Bioinformatics has become an interdisciplinary subject due to its universal role in molecular biology research. The current status of Russia's bioinformatics research in Russia is not known. Here, we review the history of bioinformatics in Russia, present the current landscape, and highlight future directions and challenges. Bioinformatics research in Russia is driven by four major industries: information technology, pharmaceuticals, biotechnology, and agriculture. Over the past three decades, despite a delayed start, the field has gained momentum, especially in protein and nucleic acid research. Dedicated and shared centers for genomics, proteomics, and bioinformatics are active in different regions of Russia. Present-day bioinformatics in Russia is characterized by research issues related to genetics, metagenomics, OMICs, medical informatics, computational biology, environmental informatics, and structural bioinformatics. Notable developments are in the fields of software (tools, algorithms, and pipelines), use of high computation power (e.g. by the Siberian Supercomputer Center), and large-scale sequencing projects (the sequencing of 100 000 human genomes). Government funding is increasing, policies are being changed, and a National Genomic Information Database is being established. An increased focus on eukaryotic genome sequencing, the development of a common place for developers and researchers to share tools and data, and the use of biological modeling, machine learning, and biostatistics are key areas for future focus. Universities and research institutes have started to implement bioinformatics modules. A critical mass of bioinformaticians is essential to catch up with the global pace in the discipline.

Biovalorization of lignin-derived substrates to vanillylamine via a self-sufficient amino donor and cofactor recycling whole-cell platform.

Lignin valorization through bioconversion to high-value chemicals is crucial for sustainable bioprocessing. Vanillin (VN), a primary lignin derivative, can be transaminated into vanillylamine (VM), a key precursor for capsaicin and pharmaceuticals. This study established a novel self-sufficient redox-complementary whole-cell system, facilitating the recycling of L-alanine and cofactors for efficient VM biosynthesis. Ammonium formate (AF) was employed as amino donor and co-substrate. Recombinant E. coli strain, co-expressing ω-transaminase (CvTA), L-alanine dehydrogenase (ALD), and formate dehydrogenase (FDH), showed higher yield in shorter reaction time compared to the strain expressing only CvTA and ALD. Intermittent feeding strategy was developed to mitigate VN cytotoxicity problem and a remarkable yield of 97.3 ± 1.0% was achieved of VM from 60 mM VN under optimized biotransamination conditions (37 °C, pH 8.0, VN:AF = 1:5, and 1.5 mM NAD+). Notably, a double-plasmid E. coli recombinant harboring CvTA, ALD, FDH, and aromatic dioxygenase (ADO) was constructed to convert isoeugenol into VM with a 73.2 ± 1.1% yield. This efficient biotransamination platform not only offers a sustainable route to VM for capsaicin production but also promotes lignin valorization for a greener bioeconomy.

Optimization study and application of box-behnken model for probing eggshell supported transition metals based catalysts to synthesize hydrazone & dihydropyrimidinones.

Solid supported catalysts have several synthetic applications. Herein, finely ground eggshells were used as a solid support for the preparation of transition metal (Ni, Zn, Cu, Sn and Co) based catalysts to synthesize 2,4-dinitrophenylhydrazone (3) and dihydropyrimidinones (7 and 8). The effect of catalyst load, time and temperature on product yield was studied. Box Behnken Model was employed, and three predictors named catalyst amount (A), reaction time (B), and reaction temperature (C) were used to find the correlation of the predictors with the yield. Second order polynomial equation was used to estimate the effects of these factors. According to the statistical model, about 12% increase in yield was observed as a result of one-unit increase in reaction time while all other terms were kept constant. The values of S (18.1616) and R2 (71.2%) indicate that the statistical model gave an adequate fit to data. Quadratic model for the response surface was used for the analysis of variance (ANOVA) results, the larger F-values, and smaller p-values indicated that the predictors are in good agreement. The linear model terms of predictors were found to be significantly effective for yield (P < 0.05). The response surface and contour plots were also in agreement with the predicted model.

Multifaceted roles of zinc nanoparticles in alleviating heavy metal toxicity in plants: a comprehensive review and future perspectives.

Heavy metal (HM) toxicity is a serious concern across the globe owing to their harmful impacts on plants, animals, and humans. Zinc oxide nanoparticles (ZnO-NPs) have gained appreciable attention in mitigating the adverse effects of abiotic stresses. The exogenous application of ZnO-NPs induces tolerance against HMs by improving plant physiological, metabolic, and molecular responses. They also interact with potential osmolytes and phyto-hormones to regulate the plant performance under HM stress. Moreover, ZnO-NPs also work synergistically with microbes and gene expression which helps to withstand HM toxicity. Additionally, ZnO-NPs also restrict the uptake and accumulation of HMs in plants which improves the plant performance. This review highlights the promising role of ZnO-NPs in mitigating the adverse impacts of HMs in plants. In this review, we explained the different mechanisms mediated by ZnO-NPs to counter the toxic effects of HMs. We also discussed the interactions of ZnO-NPs with osmolytes, phytohormones, and microbes in mitigating the toxic effects of HMs in plants. This review will help to learn more about the role of ZnO-NPs to mitigate HM toxicity in plants. Therefore, it will provide new insights to ensure sustainable and safer production with ZnO-NPs in HM-polluted soils.

Epidemiological and clinical features of a large blastomycosis outbreak at a paper mill in Michigan.

BACKGROUND: Blastomycosis is an environmentally acquired fungal infection that can result in severe pulmonary illness and high hospitalization rates. In 2023, a blastomycosis outbreak was detected among workers at a paper mill in Delta County, Michigan. METHODS: We included patients with clinical and laboratory evidence of blastomycosis who had spent ≥40 hours in Delta County since September 1, 2022 and had illness onset December 1, 2022-July 1, 2023. We assessed epidemiological and clinical features of patients and evaluated factors associated with hospitalization. We performed whole-genome sequencing to characterize genetic relatedness of clinical isolates from eight patients. RESULTS: In total, 131 patients were identified; all had worked at or visited the mill. Sixteen patients (12%) were hospitalized; one died. Compared with non-hospitalized patients, more hospitalized patients had diabetes (p=0.03) and urine antigen titers above the lower limit of quantification (p<0.001). Hospitalized patients were also more likely to have had ≥1 healthcare visits before receiving a blastomycosis diagnostic test (p=0.02) and to have been treated with antibiotics prior to antifungal prescription (p=0.001). All sequenced isolates were identified as Blastomyces gilchristii and clustered into a distinct outbreak cluster. CONCLUSIONS: This was the largest documented blastomycosis outbreak in the United States. Epidemiologic evidence indicated exposures occurred at or near the mill, and genomic findings suggested a common exposure source. Patients with diabetes may have increased risk for hospitalization, and elevated urine antigen titers could indicate greater disease severity. Early suspicion of blastomycosis may prompt earlier diagnosis and treatment, potentially reducing unnecessary antibiotic prescriptions and improving patient outcomes.

Exploring synergistic inhibitory mechanisms of flavonoid mixtures on α-glucosidase by experimental analysis and molecular dynamics simulation.

The study was the first to evaluate the synergistic interaction of luteolin + quercetin, luteolin + 3-O-methylquercetin, and quercetin + 3-O-methylquercetin mixtures on α-glucosidase and the binding mechanisms were explored using both experimental and theoretical approaches. The results showed that three flavonoid mixtures exhibited a mixed type of inhibition and demonstrated the most potent synergistic effects on α-glucosidase inhibition at 6:4 ratio, with interaction index (γ) of 0.85, 0.78 and 0.73, respectively. The three mixtures had a great influence on α-glucosidase secondary structures. Molecular simulation further demonstrated that three flavonoid mixtures formed hydrophobic interactions and hydrogen bonds with amino acid residues at different sites of α-glucosidase. Collectively, luteolin + quercetin, luteolin + 3-O-methylquercetin and quercetin + 3-O-methylquercetin were found to inhibit α-glucosidase in a synergistic manner and can be potentially used for the development of hypoglycemic food products.

Redefining the Symphony of Light Aromatic Synthesis Beyond Fossil Fuels: A Journey Navigating through a Fe-Based/HZSM-5 Tandem Route for Syngas Conversion.

The escalating concerns about traditional reliance on fossil fuels and environmental issues associated with their exploitation have spurred efforts to explore eco-friendly alternative processes. Since then, in an era where the imperative for renewable practices is paramount, the aromatic synthesis industry has embarked on a journey to diversify its feedstock portfolio, offering a transformative pathway toward carbon neutrality stewardship. This Review delves into the dynamic landscape of aromatic synthesis, elucidating the pivotal role of renewable resources through syngas/CO2 utilization in reshaping the industry's net-zero carbon narrative. Through a meticulous examination of recent advancements, the current Review navigates the trajectory toward admissible aromatics production, highlighting the emergence of Fischer-Tropsch tandem catalysis as a game-changing approach. Scrutinizing the meliorated interplay of Fe-based catalysts and HZSM-5 molecular sieves would uncover the revolutionary potential of rationale design and optimization of integrated catalytic systems in driving the conversion of syngas/CO2 into aromatic hydrocarbons (especially BTX). In essence, the current Review would illuminate the path toward cutting-edge research through in-depth analysis of the transformative power of tandem catalysis and its capacity to propel carbon neutrality goals by unraveling the complexities of renewable aromatic synthesis and paving the way for a carbon-neutral and resilient tomorrow.

Genus Ribes: Ribes aureum, Ribes pauciflorum, Ribes triste, and Ribes dikuscha-Comparative Mass Spectrometric Study of Polyphenolic Composition and Other Bioactive Constituents.

This study presents the metabolomic profiles of the four Ribes species (Ribes pauciflorum Turcz., Ribes triste Pall., Ribes dicuscha Fisch., and Ribes aureum Purch.). The plant material was collected during two expeditions in the Russian Far East. Tandem mass spectrometry was used to detect target analytes. A total of 205 bioactive compounds (155 compounds from polyphenol group and 50 compounds from other chemical groups) were tentatively identified from the berries and extracts of the four Ribes species. For the first time, 29 chemical constituents from the polyphenol group were tentatively identified in the genus Ribes. The newly identified polyphenols include flavones, flavonols, flavan-3-ols, lignans, coumarins, stilbenes, and others. The other newly detected compounds in Ribes species are the naphthoquinone group (1,8-dihydroxy-anthraquinone, 1,3,6,8-tetrahydroxy-9(10H)-anthracenone, 8,8'-dihydroxy-2,2'-binaphthalene-1,1',4,4'-tetrone, etc.), polyhydroxycarboxylic acids, omega-3 fatty acids (stearidonic acid, linolenic acid), and others. Our results imply that Ribes species are rich in polyphenols, especially flavanols, anthocyanins, flavones, and flavan-3-ols. These results indicate the utility of Ribes species for the health and pharmaceutical industry.

Public health implications of antibiotic resistance in sewage water: an epidemiological perspective.

The emergence and rapid spread of antibiotic resistance pose a major threat to global health, attributing to misuse and overuse of antibiotics resulting in antibiotics-resistant bacteria through natural mutation or transfer of resistance genes. A cross-sectional study was carried out, in which a total of 36 samples were systematically collected; of these, 26 were derived from the wastewater efflux and 10 from the receiving waters at several critical junctures along the Sutlej River. Herein, this study elucidated elevated levels of antibiotic resistance among bacterial isolates sourced from urban wastewater. Escherichia coli (E. coli) was the highest at 90% among the isolates, followed by Klebsiella pneumoniae (K. pneumoniae) at 58%, Pseudomonas aeruginosa (P. aeruginosa) at 55%, and Salmonella spp. at 53%. Many antibiotics were found to be more resistant including Ciproflaxacin, Co-Trimaxazole, Ampicillin and Tetracycline. Several antibiotic-resistance genes were found in isolated bacterial spp., such as Aminoglycosides (aadA), Sulfonamides (Sul1, Sul3), Tetracyclines (Tet (A/B/D)) and Cephalosporins (Bla_CTM X) at 41%, 35%, 29% and 12% respectively. Furthermore, the development of innovative wastewater treatment models and surveillance programs are crucial to counteract the dissemination of antibiotic resistance. To investigate the genetic determinants of antibiotic resistance, molecular analysis was performed, including DNA isolation, PCR amplification, and sequence analysis. The study helps investigate a diverse range of ARBs and ARGs in wastewater, which highlights the need of better laws for antibiotic usage and wastewater treatment processes. This investigation also stresses on regular monitoring of ARBs and ARGs in sewage wastewater. Through proactive interventions and sustained scientific inquiry, we can strive toward preserving environmental integrity and public health for successive generations.

Elucidating the bioremediation potential of laccase and peroxidase enzymes from Bacillus ligniniphilus L1 in antibiotic degradation: A computationally guided study.

This study showcased the antibiotic degradation abilities of laccase and catalase-peroxidase from Bacillus ligniniphilus L1, an extremophile, against 18 common antibiotics using computationally guided approach. Molecular docking and simulation identified six enzyme-antibiotic complexes for laccase and four for catalase-peroxidase, demonstrating significant binding affinity and stability. Enzyme activity assays corroborated computational results, indicating both enzymes could degrade all tested antibiotics with varying efficiencies. L1 laccase outperformed commercial laccase against five antibiotics, notably vancomycin, levofloxacin, tobramycin, linezolid, and rifamycin, with enhanced degradation potential upon ABTS addition. Catalase-peroxidase from L1 exhibited superior degradation efficiency over commercial peroxidase against vancomycin, linezolid, tobramycin, and clindamycin. Overall, this study underscores the computational approach's utility in understanding enzyme-mediated antibiotic degradation, offering insights into environmental contaminant remediation.

Development of hybrid polyvinylpyrrolidone/carboxymethyl cellulose/collagen incorporated oregano scaffolds via direct ink write printing for potential wound healing applications.

Additive manufacturing can develop regenerative scaffolds for wound healing. 3D printing offers meticulous porosity, mechanical integrity, cell adhesion and cost-effectiveness. Herein, we prepared ink composed of carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), collagen, and oregano extract for the fabrication of tissue constructs. The blend was optimized to form a homogeneous ink and rheological characterization demonstrated shear thinning behavior. The scaffolds were printed using Direct Ink Write (DIW) at a flow speed of 4 mm3/s and a layer height of 0.18 mm. The fabricated scaffolds demonstrated an ultimate tensile strength (UTS) and toughness of 730 KPa and 2.72 MJ/m3, respectively. Scanning Electron Microscopy (SEM) revealed an average pore size of 300 ± 30 µm. Fourier transform infrared spectroscopy (FTIR) analysis confirmed that all materials were present. The contact angle of the composite scaffold was 68° ± 1°. Moreover, the scaffolds presented 82 % mass loss (degradation) in phosphate buffer saline (PBS) over 14 days. The composite scaffold exhibited inhibition zones of 9 mm and 12 mm against Staphylococcus aureus and Escherichia coli, respectively. The PVP/CMC/collagen/oregano 3D printed scaffolds exhibited excellent biocompatibility with the mesenchymal stem cells and humman dermal fibroblast cells, confirmed by water-soluble tetrazolium - 8 (WST-8) assay (test conducted for 7 days). The enhanced angiogenic potential of said scaffold was assesed by release of vascular endothelial growth factor followed by further validation through in-vivo CAM assay. Thus, confirming suitability for the potential wound healing application.

Embracing the sustainable horizons through bioenergy innovations: a path to a sustainable energy future.

The urgent need for mitigating climate change necessitates a transformative shift in energy production and consumption paradigms. Amidst this challenge, bioenergy emerges as a pivotal contributor to the global energy transition, offering a diverse array of solid, liquid, and gaseous fuels derived from biomass. This mini review delves into the unique potential of bioenergy innovations, particularly renewable diesel, bio jet fuel, and ethanol, to reduce greenhouse gas emissions and transform various industries. The article highlights critical technological advancements, supportive policies, and cross-sector collaboration essential for a sustainable energy transition. Specific challenges such as ensuring a consistent biomass feedstock supply, decentralizing processing units, and navigating complex regulatory frameworks are examined. Innovative solutions like decentralized biomass processing and enhanced biomass logistics are discussed as pathways to overcome these barriers. The review provides specific recommendations for near-term policies and strategies to support decentralized facilities, showcasing bioenergy's role in achieving a sustainable future.

Signatures of selection in Angus and Hanwoo beef cattle using imputed whole genome sequence data.

In this study, we detected signatures of selection in Hanwoo and Angus beef cattle using allele frequency and haplotype-based methods based on imputed whole genome sequence variants. Our dataset included 13,202 Angus animals with 10,057,633 imputed SNPs and 10,437 Hanwoo animals with 13,241,550 imputed SNPs. The dataset was subset down to 6,873,624 SNPs in common between the two populations to identify within population (runs of homozygosity, extended haplotype homozygosity) and between population signals of selection (allele fixation index, extended haplotype homozygosity). Assuming these selection signals were complementary to each other, they were combined into a decorrelated composite of multiple signals to identify regions under selection for each of the breeds. 27 genomic regions spanning 25.15 Mb and harboring 360 genes were identified in Angus on chromosomes 1,3, 4, 5, 6, 7, 8, 12, 13, 14, 16, 20, 21 and 28. Similarly, in Hanwoo, 59 genes and 17 genomic regions spanning 5.21 Mb on chromosomes 2, 4, 5, 6, 7, 8, 9, 10, 13, 17, 20 and 24 were identified. Apart from a small region on chromosome 13, there was no major overlap of selection signals between the two breeds reflecting their largely different selection histories, environmental challenges, breeding objectives and breed characteristics. Positional candidate genes identified in selected genomic regions in Angus have been previously associated with growth, immunity, reproductive development, feed efficiency and adaptation to environment while the candidate genes identified in Hanwoo included important genes regulating meat quality, fat deposition, cholesterol metabolism, lipid synthesis, neuronal development, and olfactory reception.

National income accounting attributes and economic welfare. Evidence from Pakistan.

Economic welfare is essential in the modern economy since it directly reflects the standard of living, distribution of resources, and general social satisfaction, which influences individual and social well-being. This study aims to explore the relationship between national income accounting different attributes and the economic welfare in Pakistan. However, this study used data from 1950 to 2022, and data was downloaded from the World Bank data portal. Regression analysis is used to investigate the relationship between them and is very effective in measuring the relationship between endogenous and exogenous variables. Moreover, generalized methods of movement (GMM) are used as the robustness of the regression. Our results show that foreign direct investment outflow, Gross domestic product growth rate, GDP per capita, higher Interest, market capitalization, and population growth have a significant negative on the unemployment rate, indicating the rise in these factors leads to a decrease in the employment rate in Pakistan. Trade and savings have a significant positive impact on the unemployment rate, indicating the rise in these factors leads to an increase in the unemployment rate for various reasons. Moreover, all the factors of national income accounting have a significant positive relationship with life expectancy, indicating that an increase in these factors leads to an increase in economic welfare and life expectancy due to better health facilities, many resources, and correct economic policies. However, foreign direct investment, inflation rate, lending interest rate, and population growth have significant positive effects on age dependency, indicating these factors increase the age dependency. Moreover, GDP growth and GDP per capita negatively impact age dependency. Similarly, all the national income accounting factors have a significant negative relationship with legal rights that leads to decreased legal rights. Moreover, due to better health facilities and health planning, there is a negative significant relationship between national income accounting attributes and motility rate among children. Our study advocated the implications for the policymakers and the government to make policies for the welfare and increase the social factors.

In vitro characterization of probiotic potential of Lactobacillus plantarum CM49 against selected cattle mastitogens.

BACKGROUND: Bovine mastitis results in significant economic losses for the dairy industry globally due to milk production losses and decreased herd efficiency. This research aimed to isolate, select, and characterize indigenous lactobacilli with probiotic properties. A total of 40 lactobacilli were isolated from healthy milk samples of cattle and identified at the species level through 16S rDNA sequencing. All isolates were initially screened for antimicrobial activity, and selected isolates underwent in vitro assessment of probiotic properties. RESULTS: Among the lactobacilli isolates, varying levels of activity (9 to 19 mm) against cattle mastitogens; Stapylococcus aureus (Staph. aureus), Escherichia coli (E. coli) and Streptococcus dysgalactiae (Strep. dysgalactiae) were observed in the well diffusion assay. These isolates demonstrated auto-aggregation (ranging from 14.29 ± 0.96% to 62.11 ± 1.09%) and co-aggregate (ranging from 9.21 ± 0.14% to 55.74 ± 0.74%) with mastitogens after 2 h. Lactobacillus (Lb.) plantarum CM49 showed sensitivity to most antibiotics tested and exhibited strong inhibitory effects, with mean log10 reductions of 3.46 for Staph. aureus, 2.82 for E. coli, and 1.45 for Strep. dysgalactiae in co-culture experiments. Furthermore, Lb. plantarum CM49 significantly decreased the adhesion rate of mastitogens on the bovine mammary cell line and mouse model, demonstrating its potential effectiveness in preventing mastitis. CONCLUSION: It is concluded that Lb. plantarum CM49 has remarkable probiotic potential with activity against cattle mastitogens in the laboratory and cell culture and competitively excludes mastitogens from bovine mammary cells and ameliorates Staph. aureus-induced mastitis in mice.

Selenium improved arsenic toxicity tolerance in two bell pepper (Capsicum annuum L.) varieties by modulating growth, ion uptake, photosynthesis, and antioxidant profile.

Bell pepper (Capsicum annuum L.); an important spice crop of the region is a rich source of vitamins and antioxidants having many health benefits. Many biotic and abiotic factors contribute towards growth and yield losses of this crop. Arsenic (As) toxicity is a global issue, but it is particularly critical in developing countries. The current study was designed to evaluate the efficacy of selenium (Se) in mitigating the toxic effects of As in two varieties (HSP-181 A and PS09979325) of Capsicum annuum L. Different concentrations of As (0, 50, and 100 µM) and Se (0, 5, and 10 µM) were tested using 14 days old seedlings of C. annuum L. The As stress caused a significant (P ≤ 0.001) reduction in growth, uptake of nutrients, and eco-physiological attributes in both varieties however, the response was specific. While the overproduction of osmo-protectants and antioxidants intensified the symptoms of oxidative stress. The maximum reduction in shoot length (45%), fresh weight (29%), and dry weight (36%) was observed in under 100 µM As stress. The organic acids exudation from the roots of both cultivars were significantly increased with the increase in As toxicity. The Se treatment significantly (p ≤ 0.001) improved growth, nutrient uptake, gas exchange attributes, antioxidant production, while decreased oxidative stress indicators, and As uptake in the roots and shoots of all the subjects under investigation. It is concluded from the results of this study that Se application increased photosynthetic efficiency and antioxidant activity while decreasing As levels, organic acid exudation, and oxidative stress indicators in plants. Overall, the var. PS09979325 performed better and may be a good candidate for future pepper breeding program.

Excessive Dynamic Airway Collapse After Entecavir Use in a Patient With Pegylated Interferon-Induced Undifferentiated Connective Tissue Disease and Entecavir Use to Prevent Hepatitis B Virus Reactivation Upon Giving Rituximab.

Pegylated interferon-alpha (PEG-IFN-α) is an antiviral medication used to treat chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. It may result in rare but severe side effects, such as undifferentiated connective tissue disease (UCTD) and excessive dynamic airway collapse (EDAC), which can occur as delayed complications of PEG-IFN-α-induced UCTD. In cases where these complications arise, entecavir, employed for treating HBV infection, may be considered. A 49-year-old female patient, monitored for nine years with HCV and a viral load of 1.5 million, genotype 3, and normal liver function tests (LFTs), possibly acquired the infection from her HCV-positive husband. The patient was initially treated with PEG-IFN-α (IFN-α-2b, 100 µg/week subcutaneously) and ribavirin (RBV, 500 mg/twice daily). Following the sixth injection, the patient exhibited symptoms, including shortness of breath and cough, leading to limited daily activities. Subsequent high-resolution computed tomography (HRCT) showed interstitial pneumonitis (IP) signs. She was given a high dose of steroids. Over the next two to four weeks, the patient experienced Raynaud's phenomenon, skin tightening, joint pains, and dryness of the eyes and mouth. The antinuclear antibody (ANA) test was negative, while the extractable nuclear antigen (ENA) test showed equivocal anti-Smith antibodies (6.38). Rheumatoid factor (RA) factors were mildly positive, and pulmonary function tests (PFTs) indicated a restrictive pattern. The patient was intolerant to hydroxychloroquine (HCQ) and azathioprine (Imuran) 500 mg, subsequently receiving mycophenolate mofetil 500 mg/thrice daily. Despite four years of treatment, UCTD due to PEG-IFN-α remained difficult to control; however, IP responded well to steroids. Rituximab pulse therapy was planned before the initiation; serological tests showed positive anti-HBs with a titer of 17.02, positive anti-HBc, but negative HBsAg and undetectable HBV viral load, indicating immunity to HBV due to natural infection. Given the potential for rituximab to cause immunosuppression and HBV reactivation, entecavir treatment was started and continued for 18 months. The patient was followed for another five years, during which her LFTs and viral markers showed stability. However, after nine years of PEG-IFN-α-induced UCTD disorder, she experienced a reoccurring cough but was unresponsive to steroids that were against her suspicion of a flare of IP. A subsequent dynamic CT scan detected a 75% trachea collapse while in a supine position, indicating a potential complication termed EDAC. This EDAC could not be linked to PEG-IFN-α-induced UCTD disorder or EDAC after the use of entecavir in a patient with PEG-IFN-α-induced UCTD disorder. Treatment of such complex patients requires flexible, specific treatment plans and continuous monitoring. This case emphasizes the need for caution in patients with a history of IFN-induced disease and the possibility of late effects and possible effects of the use of entecavir in a patient with PEG-IFN-α-induced UCTD. To the best of our knowledge, this is the first case reported as EDAC, a possible delayed complication of PEG-IFN-α plus ribavirin or entecavir in a patient with PEG-IFN-α-induced UCTD.