Pediatr Nephrol. 2025 Jan 25. doi: 10.1007/s00467-025-06656-x. Online ahead of print.

ABSTRACT

BACKGROUND: Limited research exists regarding the genetic profile, clinical characteristics, and outcomes of refractory rickets in children from India.

METHODS: Patients with refractory rickets aged ≤ 18 years were enrolled. Data regarding clinical features, etiology, genotype-phenotype correlation, and estimated glomerular filtration rate (eGFR) were recorded.

RESULTS: Seventy-two patients with refractory rickets (non-nutritional, with normal kidney function at presentation) from 65 families attending the pediatric nephrology clinic from 2005-2024 were included. Median (IQR) age at first presentation was 2 (1, 4) years. Clinical features included failure-to-thrive (49 [68.1%]), polyuria (37 [51.4%]), nephrocalcinosis (33 [45.8%]), fractures (10 [13.9%]), and hypokalemic paralysis (4 [5.6%]). Major etiologies included distal renal tubular acidosis (dRTA) [34(47.2%)], hereditary hypophosphatemic rickets (11 [15.3%]), cystinosis (9 [12.5%]), Lowe syndrome (3 [4.2%]), vitamin D-dependent rickets (4 [5.5%]), and Fanconi-Bickel syndrome (3 [4.2%]). Next-generation sequencing identified 61 variants among 71 children tested (85.9%), of which 56 variants (among 55 children) were pathogenic (P)/likely-pathogenic (LP) (77.5% diagnostic-yield). P/LP variants included SLC4A1 (n = 14), CTNS (n = 9), PHEX (n = 8), WDR72 (n = 5), OCRL (n = 2), SLC2A2 (n = 3), ATP6V0A4 (n = 4), VDR (n = 3), CLDN16 (n = 2), ATP6V1B1 (n = 1), SLC12A1 (n = 1), CLCN5 (n = 1), SLC34A3 (n = 1), ATP7B (n = 1), and KCNJ1 (n = 1). Fifteen novel P/LP variants and five novel variants-of-uncertain-significance (VUS) were identified. c.2573C > A in exon 19 among SLC4A1-dRTA (n = 14) was a recurrent mutation. Five patients with cystinosis, two patients with SLC4A1-dRTA, two with WDR72-dRTA, and two with Bartter syndrome showed progression to CKD stage 2 or greater during follow-up.

CONCLUSIONS: dRTA, X-linked hypophosphatemic rickets, and cystinosis were common causes of refractory rickets. The c.2573C > A variant in exon 19 was a recurrent mutation in SLC4A1-dRTA.

PMID:39862309 | DOI:10.1007/s00467-025-06656-x

Pharmaceutics. 2025 Jan 3;17(1):52. doi: 10.3390/pharmaceutics17010052.

ABSTRACT

BACKGROUND: The Epstein-Barr virus (EBV) is intricately linked to a range of human malignancies, with EBV latent membrane protein 2A (LMP2A) emerging as a potential target antigen for immunotherapeutic strategies in the treatment of nasopharyngeal carcinoma (NPC).

METHODS: The modified vaccinia virus Ankara (MVA) is universally used in vector vaccine research because of its excellent safety profile and highly efficient recombinant gene expression. Here, we constructed a novel MVA-LMP2A recombinant virus and investigated its specific immune response induction and oncolytic effect.

RESULTS: An immunization dose of 2 × 107 PFU induced the highest specific immune response, which was no longer increased by boost injections after four doses. Three weeks post-final immunization, the specific immune response reached its peak. The MVA-LMP2A vaccine-induced LMP2A-specific cytotoxic T lymphocytes (CTLs), which exhibited substantial efficacy against target cells and effectively inhibited tumor growth.

CONCLUSIONS: Thus, the MVA-LMP2A recombinant virus effectively induces strong LMP2A-specific cellular and humoral immune responses and anti-tumor activity. This work provides a promising therapeutic strategy for developing NPC candidate vaccines, as well as a reference for the treatment of EBV LMP2-associated malignancies.

PMID:39861700 | DOI:10.3390/pharmaceutics17010052

Pharmaceuticals (Basel). 2025 Jan 3;18(1):45. doi: 10.3390/ph18010045.

ABSTRACT

BACKGROUND: Osteoporosis is characterized by the microstructural depletion of bone tissue and decreased bone density, leading to an increased risk of fractures. Cotoneaster wilsonii Nakai, an endemic species of the Korean Peninsula, grows wild in Ulleungdo. In this study, we aimed to investigate the effects of C. wilsonii and its components on osteoporosis.

METHODS AND RESULTS: The alkaline phosphatase (ALP) activity of C. wilsonii extracts and fractions was evaluated in MC3T3-E1 pre-osteoblasts, and the n-hexane fraction (CWH) showed the best properties for ALP activity. The effects of the CWH on bone formation were assessed in MC3T3-E1 cells and ovariectomized mice. Biochemical assays and histological analyses focused on the signaling activation of osteoblast differentiation and osteogenic markers, such as ALP, collagen, and osterix. The CWH significantly activated TGF-β and Wnt signaling, enhancing osteoblast differentiation and bone matrix formation. Notably, CWH treatment improved micro-CT indices, such as femoral bone density, and restored serum osteocalcin levels compared to OVX controls.

CONCLUSIONS: These results highlight the potential of the C. wilsonii Nakai n-hexane fraction as a promising therapeutic agent for managing osteoporosis.

PMID:39861108 | DOI:10.3390/ph18010045

Molecules. 2025 Jan 7;30(2):214. doi: 10.3390/molecules30020214.

ABSTRACT

Knowing which residues of a protein are important for its function is of paramount importance for understanding the molecular basis of this function and devising ways of modifying it for medical or biotechnological applications. Due to the difficulty in detecting these residues experimentally, prediction methods are essential to cope with the sequence deluge that is filling databases with uncharacterized protein sequences. Deep learning approaches are especially well suited for this task due to the large amounts of protein sequences for training them, the trivial codification of this sequence data to feed into these systems, and the intrinsic sequential nature of the data that makes them suitable for language models. As a consequence, deep learning-based approaches are being applied to the prediction of different types of functional sites and regions in proteins. This review aims to give an overview of the current landscape of methodologies so that interested users can have an idea of which kind of approaches are available for their proteins of interest. We also try to give an idea of how these systems work, as well as explain their limitations and high dependence on the training set so that users are aware of the quality of expected results.

PMID:39860084 | DOI:10.3390/molecules30020214

Int J Mol Sci. 2025 Jan 18;26(2):793. doi: 10.3390/ijms26020793.

ABSTRACT

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein. Using this model, we analyzed the implication of HERC1 E3 ubiquitin ligase in the activity of UPS, autophagy, and synaptic homeostasis in brain and muscle tissues. Regarding UPS, no differences were found in its activity nor in the specific gene expression in both brain and muscle tissues from tbl compared with the control littermates. Furthermore, the use of the specific UPS inhibitor (MG-132), did not alter the evoked neurotransmitter release in the levator auris longus (LAL) muscle. Interestingly, the expression of the autophagy-related gene p62 was significantly increased in the muscle of tbl compared to the control littermates. Indeed, impaired evoked neurotransmitter release was observed with the autophagy inhibitor Wortmannin. Finally, altered levels of Clathrin and Synaptophysin were detected in muscle tissues. Altogether, our findings show that HERC1 E3 ubiquitin ligase mutation found in tbl mice alters autophagy and vesicular recycling without affecting proteasomal function.

PMID:39859507 | DOI:10.3390/ijms26020793

Int J Mol Sci. 2025 Jan 15;26(2):686. doi: 10.3390/ijms26020686.

ABSTRACT

SARS-CoV-2 viral entry requires membrane fusion, which is facilitated by the fusion peptides within its spike protein. These predominantly hydrophobic peptides insert into target membranes; however, their precise mechanistic role in membrane fusion remains incompletely understood. Here, we investigate how FP1 (SFIEDLLFNKVTLADAGFIK), the N-terminal fusion peptide, modulates membrane stability and barrier function across various model membrane systems. Through a complementary suite of biophysical techniques-including electrophysiology, fluorescence spectroscopy, and atomic force microscopy-we demonstrate that FP1 significantly promotes pore formation and alters the membrane's mechanical properties. Our findings reveal that FP1 reduces the energy barrier for membrane defect formation and stimulates the appearance of stable conducting pores, with effects modulated by membrane composition and mechanical stress. The observed membrane-destabilizing activity suggests that, beyond its anchoring function, FP1 may facilitate viral fusion by locally disrupting membrane integrity. These results provide mechanistic insights into SARS-CoV-2 membrane fusion mechanisms and highlight the complex interplay between fusion peptides and target membranes during viral entry.

PMID:39859399 | DOI:10.3390/ijms26020686

Int J Mol Sci. 2025 Jan 7;26(2):448. doi: 10.3390/ijms26020448.

ABSTRACT

Mitophagy, an essential process within cellular autophagy, has a critical role in regulating key cellular functions such as reproduction, metabolism, and apoptosis. Its involvement in tumor development is complex and influenced by the cellular environment. Here, we conduct a comprehensive analysis of a mitophagy-related gene signature, composed of PRKN, PINK1, MAP1LC3A, SRC, BNIP3L, BECN1, and OPTN, across various cancer types, revealing significant differential expression patterns associated with molecular subtypes, stages, and patient outcomes. Pathway analysis revealed a complex interplay between the expression of the signature and potential effects on the activity of various cancer-related pathways in pan-cancer. Immune infiltration analysis linked the mitophagy signature with certain immune cell types, particularly OPTN with immune infiltration in melanoma. Methylation patterns correlated with gene expression and immune infiltration. Mutation analysis also showed frequent alterations in PRKN (34%), OPTN (21%), PINK1 (28%), and SRC (15%), with implications for the tumor microenvironment. We also found various correlations between the expression of the mitophagy-related genes and sensitivity in different drugs, suggesting that targeting this signature could improve therapy efficacy. Overall, our findings underscore the importance of mitophagy in cancer biology and drug resistance, as well as its potential for informing treatment strategies.

PMID:39859167 | DOI:10.3390/ijms26020448

Medicina (Kaunas). 2025 Jan 13;61(1):105. doi: 10.3390/medicina61010105.

ABSTRACT

Background and Objectives: The pathophysiology of arrhythmogenic cardiomyopathy (ACM), previously known as arrhythmogenic right ventricular cardiomyopathy (ARVC), and its specific biological features remain poorly understood. High-throughput plasma proteomic profiling, a powerful tool for gaining insights into disease pathophysiology at the systems biology level, has not been used to study ACM. This study aimed at characterizing plasmatic protein changes in patients with ACM, which were compared with those of healthy controls, and at exploring the potential role of the identified proteins as biomarkers for diagnosis and monitoring. Materials and Methods: Blood samples were collected from six ACM patients, four patients with other cardiomyopathies, and two healthy controls. Plasma was processed to remove high-abundance proteins and analyzed by two-dimensional gel electrophoresis. Differential protein expressions were assessed using PDQuest software, Bio-Rad US version 8.0.1. Results: The analysis revealed several proteins with altered expressions between ACM patients and controls, including plakophilin-2, junctional plakoglobin, desmoplakin, desmin, transmembrane protein 43, and lamin A/C. Conclusions: The plasma proteomic profiling of ACM suggests that ACM is a distinct disease entity characterized by a unique dysregulation of desmosomal proteins. The identification of plasma biomarkers associated with ACM underscores their potential to improve diagnostic accuracy and facilitate early intervention strategies. Further exploration of mutations in desmosomal proteins and their phosphorylation states may provide deeper insights into the pathophysiology of ACM.

PMID:39859087 | DOI:10.3390/medicina61010105

Microorganisms. 2025 Jan 16;13(1):176. doi: 10.3390/microorganisms13010176.

ABSTRACT

Antibiotic resistance is on the WHO's top 10 list of global public health threats due to its rapid emergence and spread but also because of the high morbidity and mortality associated with it. Amongst the main species driving this phenomenon is A. baumannii, a member of the ESKAPE group of medical assistance-associated infections causing species famous for its extensively drug-resistant phenotypes. Our findings note a 91.52% frequency of extensively drug-resistant carbapenem-resistant A. baumannii (XDR CRAB) phenotype amongst clinical isolates from multiple hospitals in two major cities from northwestern and central Romania, harboring multiple antibiotic resistance genes such as blaOXA-23-like in 108 (91.5%) isolates, blaOXA-24/40-like in 88 (74.6%) isolates, blaNDM in 29 (25%) isolates, ArmA in 75 (63.6%) isolates, and ant(3″)-I in 69 (58.5%) isolates and sul1 in 113 (95.76%) isolates. The isolates, although nearly identical in phenotype, displayed different genotypical profiles, with varying degrees of similarity across hospitals and cities, raising the possibility of both local outbreaks of a single clone and widespread dissemination of resistant isolates.

PMID:39858944 | DOI:10.3390/microorganisms13010176

Genes (Basel). 2024 Dec 29;16(1):37. doi: 10.3390/genes16010037.

ABSTRACT

Background/Objectives: Salivary gland carcinomas encompass a broad group of malignant lesions characterized by varied prognoses. Stem cells have been associated with the potential for self-renewal and differentiation to various subpopulations, resulting in histopathological variability and diverse biological behavior, features that characterize salivary gland carcinomas. This study aims to provide a thorough systematic review of immunohistochemical studies regarding the expression and prognostic significance of stem cell markers between different malignant salivary gland tumors (MSGTs). Methods: The English literature was searched via the databases MEDLINE/PubMed, EMBASE via OVID, Web of Science, Scopus, and CINHAL via EBSCO. The Joanna Briggs Institute Critical Appraisal Tool was used for risk of bias (RoB) assessment. Meta-analysis was conducted for markers evaluated in the same pair of diseases in at least two studies. Results: Fifty-four studies reported the expression of stem cell markers, e.g., c-KIT, CD44, CD133, CD24, ALDH1, BMI1, SOX2, OCT4, and NANOG, in various MSGTs. Low, moderate, and high RoB was observed in twenty-five, eleven, and eighteen studies, respectively. Meta-analysis revealed an outstanding discriminative ability of c-KIT for adenoid cystic carcinoma (AdCC) over polymorphous adenocarcinoma [P(LG)A] but did not confirm the prognostic significance of stem cell markers in MSGTs. Conclusions: This study indicated a possible link between stem cells and the histopathological heterogeneity and diverse biological behavior that characterize the MSGTs. c-KIT might be of diagnostic value in discriminating between AdCC and P(LG)A.

PMID:39858584 | DOI:10.3390/genes16010037

Genes (Basel). 2024 Dec 25;16(1):11. doi: 10.3390/genes16010011.

ABSTRACT

BACKGROUND/OBJECTIVES: A prominent endophenotype in Autism Spectrum Disorder (ASD) is the synaptic plasticity dysfunction, yet the molecular mechanism remains elusive. As a prototype, we investigate the postsynaptic signal transduction network in glutamatergic neurons and integrate single-cell nucleus transcriptomics data from the Prefrontal Cortex (PFC) to unveil the malfunction of translation control.

METHODS: We devise an innovative and highly dependable pipeline to transform our acquired signal transduction network into an mRNA Signaling-Regulatory Network (mSiReN) and analyze it at the RNA level. We employ Cell-Specific Network Inference via Integer Value Programming and Causal Reasoning (CS-NIVaCaR) to identify core modules and Cell-Specific Probabilistic Contextualization for mRNA Regulatory Networks (CS-ProComReN) to quantitatively reveal activated sub-pathways involving MAPK1, MKNK1, RPS6KA5, and MTOR across different cell types in ASD.

RESULTS: The results indicate that specific pivotal molecules, such as EIF4EBP1 and EIF4E, lacking Differential Expression (DE) characteristics and responsible for protein translation with long-term potentiation (LTP) or long-term depression (LTD), are dysregulated. We further uncover distinct activation patterns causally linked to the EIF4EBP1-EIF4E module in excitatory and inhibitory neurons.

CONCLUSIONS: Importantly, our work introduces a methodology for leveraging extensive transcriptomics data to parse the signal transduction network, transforming it into mSiReN, and mapping it back to the protein level. These algorithms can serve as potent tools in systems biology to analyze other omics and regulatory networks. Furthermore, the biomarkers within the activated sub-pathways, revealed by identifying convergent dysregulation, illuminate potential diagnostic and prognostic factors in ASD.

PMID:39858558 | DOI:10.3390/genes16010011

Biomolecules. 2025 Jan 9;15(1):89. doi: 10.3390/biom15010089.

ABSTRACT

Amylin and amyloid β belong to the same protein family and activate the same receptors. Amyloid β levels are elevated in Alzheimer's disease. Recent studies have demonstrated that amylin-based peptides can reduce the symptoms of Alzheimer's disease in animal models. Replica exchange molecular dynamics simulation machine learning, as well as other computational analyses, were applied to improve the understanding of the amino acid residues in these amylin-based peptides. Comparisons were made between amylin, amylin-based peptides, and amyloid β. These studies converged on amylin residues 10Q, 28S, 29S, 30T, 31N, 32V, 33G, 34S, and 35N (residues 10 and 28-35) being ranked highest, meaning that they were the most likely to be involved in activating the same targets as amyloid β. Surprisingly, the amyloid β signaling domain most closely matched amylin residues 29-35 in the simulated structures. These findings suggest important residues that are structurally similar between amylin and amyloid β and are thus implicated in the activation of the amylin receptor.

PMID:39858483 | DOI:10.3390/biom15010089

Biomolecules. 2024 Dec 24;15(1):1. doi: 10.3390/biom15010001.

ABSTRACT

This study examines the prevalence and the mechanisms of antibiotic resistance in Pseudomonas aeruginosa isolates collected from healthcare units in Northwestern Transylvania, Romania, between 2022 and 2023. Given the alarming rise in antibiotic resistance, the study screened 34 isolates for resistance to 10 antibiotics, 46 ARGs, and integrase genes using PCR analysis. The results reveal a concerning increase in multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates over the two-year period. Notably, the prevalence of ARGs encoding resistance to sulfonamides and beta-lactams, particularly sul1 and blaOXA-50, has shown a significant rise. Furthermore, the study detected the emergence of new resistance mechanisms in the same time interval. These include target protection and even more specific mechanisms, such as metallo-beta-lactamases or enzymes involved in the methylation of 23S rRNA. Statistical analysis further confirmed the correlation between Class I integrons and several ARGs, underscoring the role of horizontal gene transfer in the dissemination of resistance. These findings emphasize the urgent need for updated treatment strategies and monitoring programs to effectively combat the spread of ARGs in clinical settings.

PMID:39858396 | DOI:10.3390/biom15010001

Antioxidants (Basel). 2025 Jan 11;14(1):80. doi: 10.3390/antiox14010080.

ABSTRACT

Glucosinolates (GSLs) are nitrogen/sulfur-containing glycosides widely present in the order of Brassicales, particularly in the Brassicaceae family. Camelina (Camelina sativa (L.) Crantz) is an oilseed plant belonging to this family. Its seeds, in addition to a distinctive fatty acid composition, contain three aliphatic GSLs: glucoarabin, glucocamelinin, and homoglucocamelinin. Our study explored the impact of these GSLs purified from Camelina press cake, a by-product of Camelina oil production, on yeast chronological aging, which is the established model for simulating the aging of post-mitotic quiescent mammalian cells. Supplementing yeast cells with GSLs extends the chronological lifespan (CLS) in a dose-dependent manner. This enhancement relies on an improved mitochondrial respiration efficiency, resulting in a drastic decrease of superoxide anion levels and an increase in ATP production. Furthermore, GSL supplementation affects carbon metabolism. In particular, GSLs support the pro-longevity preservation of TCA cycle enzymatic activities and enhanced glycerol catabolism. These changes contribute positively to the phosphorylating respiration and to an increase in trehalose storage: both of which are longevity-promoting prerequisites.

PMID:39857414 | DOI:10.3390/antiox14010080

Nat Cancer. 2025 Jan 24. doi: 10.1038/s43018-024-00900-3. Online ahead of print.

ABSTRACT

Mutations in cancer risk genes increase susceptibility, but not all carriers develop cancer. Indeed, while DNA mutations are necessary drivers of cancer, only a small subset of mutated cells go on to cause the disease. To date, the mechanisms underlying individual cancer susceptibility remain unclear. Here, we took advantage of a unique mouse model of intrinsic developmental heterogeneity (Trim28+/D9) to investigate whether early-life epigenetic variation influences cancer susceptibility later in life. We found that heterozygosity of Trim28 is sufficient to generate two distinct early-life epigenetic states associated with differing cancer susceptibility. These developmentally primed states exhibit differential methylation patterns at typically silenced heterochromatin, detectable as early as 10 days of age. The differentially methylated loci are enriched for genes with known oncogenic potential, frequently mutated in human cancers and correlated with poor prognosis. This study provides genetic evidence that intrinsic developmental heterogeneity can prime individual, lifelong cancer susceptibility.

PMID:39856421 | DOI:10.1038/s43018-024-00900-3

Int J Obes (Lond). 2025 Jan 24. doi: 10.1038/s41366-025-01724-6. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysregulation, a defining feature of obesity, disrupts essential signalling pathways involved in nutrient sensing and mitochondria homeostasis. The nuclear factor erythroid 2-related factor 2 (NRF-2) serves as a pivotal regulator of the cellular stress response, and recent studies have implicated it in the pathogenesis of obesity, diabetes, and metabolic syndrome. Curcumin, a polyphenolic compound derived from turmeric, has been identified as a potent activator of NRF-2. Evidence suggests curcumin impacts obesity and metabolic disorders by modulating gut microbiota composition, increasing energy expenditure, and regulating lipid metabolism. Orlistat, an anti-obesity drug, inhibits fat absorption in the gastrointestinal tract, but its side effects limits its broader use.

OBJECTIVES: The present study aims to investigate the potential synergetic effect of a hybrid combination between orlistat and curcumin. Additionally, we provide a detailed understanding of the molecular mechanisms through which this combination mitigates glucose-induced lipid accumulation in Caenorhabditis elegans, with a focus on the role of the skinhead 1 (SKN-1) transcription factor, an orthologue of NRF2.

METHODS: We assessed the lipid accumulation and the changes in skn-1 transcriptional activity in C. elegans using confocal GFP-based detection, alongside mRNA expression analysis of genes from lipid metabolism and oxidative stress response in wild-type, QV225 and LD1 strains. Furthermore, we evaluated locomotion, chemotaxis and mitochondrial dynamics to enhance our understanding of the proposed molecular-based model.

RESULTS: Our findings reveal that the orlistat/curcumin combination exerts an anti-obesogenic effect through SKN-1/NRF2-dependent regulation of conserved genes involved in carbohydrate and lipid metabolism in C. elegans. Moreover, the combination stimulates mitochondrial potential, further contributing to the observed synergistic effects.

CONCLUSION: The hybrid combination of orlistat and curcumin demonstrates significant anti-obesity activity by regulating nutrient-sensing pathways through SKN-1/NRF-2 modulation. This approach may allow for the reduction of orlistat dosage, thereby minimizing its adverse effects while maintaining its therapeutic efficacy.

PMID:39856245 | DOI:10.1038/s41366-025-01724-6

Nat Commun. 2025 Jan 24;16(1):989. doi: 10.1038/s41467-025-55923-w.

ABSTRACT

NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that NKp46 is indispensable for expressing IL-2 receptor-α (IL-2Rα) by non-NK liver-resident type-1 innate lymphoid cells (ILC1s). Deletion of NKp46 reduces IL-2Rα on ILC1s by downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity in vitro and in vivo. The binding of anti-NKp46 antibody to NKp46 triggers the activation of NF-κB, the expression of IL-2Rα, interferon-γ (IFN-γ), tumor necrosis factor (TNF), proliferation, and cytotoxicity. Functionally, NKp46 expressed on mouse ILC1s interacts with tumor cells through cell-cell contact, increasing ILC1 production of IFN-γ and TNF, and enhancing cytotoxicity. In a mouse model of acute myeloid leukemia, deletion of NKp46 impairs the ability of ILC1s to control tumor growth and reduces survival. This can be reversed by injecting NKp46+ ILC1s into NKp46 knock-out mice. Human NKp46+ ILC1s exhibit stronger cytokine production and cytotoxicity than their NKp46- counterparts, suggesting that NKp46 plays a similar role in humans. These findings identify an NKp46-NF-κB-IL-2Rα axis and suggest that activating NKp46 with an anti-NKp46 antibody may provide a potential strategy for anti-tumor innate immunity.

PMID:39856052 | DOI:10.1038/s41467-025-55923-w

New Phytol. 2025 Jan 24. doi: 10.1111/nph.20420. Online ahead of print.

ABSTRACT

Temperature is a critical environmental factor affecting nearly all plant processes, including growth, development, and yield. Yet, despite decades of research, we lack the ability to predict plant performance at different temperatures, limiting the development of climate-resilient crops. Further, there is a pressing need to bridge the gap between the prediction of physiological and molecular traits to improve our understanding and manipulation of plant temperature responses. Here, we developed the first enzyme-constrained model of Arabidopsis thaliana's metabolism, facilitating predictions of growth-related phenotypes at different temperatures. We showed that the model can be employed for in silico identification of genes that affect plant growth at suboptimal growth temperature. Using mutant lines, we validated the genes predicted to affect plant growth, demonstrating the potential of metabolic modeling in accurately predicting plant thermal responses. The temperature-dependent enzyme-constrained metabolic model provides a template that can be used for developing sophisticated strategies to engineer climate-resilient crops.

PMID:39856022 | DOI:10.1111/nph.20420

Sheng Wu Gong Cheng Xue Bao. 2025 Jan 25;41(1):199-215. doi: 10.13345/j.cjb.240350.

ABSTRACT

Petroleum hydrocarbon pollution has become one of the global environmental problems, posing a serious threat to the environment and human health. Microbial remediation plays an important role in the remediation of petroleum hydrocarbon-contaminated environment. Nevertheless, the stress factors present in the environment polluted by petroleum hydrocarbons limit the effectiveness of microbial remediation. This paper reviews the common stress factors in petroleum hydrocarbon-polluted environment and the response mechanisms of microorganisms to these factors. Furthermore, we introduce the methods to improve microbial tolerance, such as irrational modification, rational modification based on systems biology tools or tolerance mechanisms, and the construction of microbial consortia. The application of these methods is expected to improve the viability and remediation efficiency of microorganisms in petroleum hydrocarbon-contaminated environment and provide new perspectives and technical support for environmental remediation.

PMID:39855688 | DOI:10.13345/j.cjb.240350

Biotechnol Adv. 2025 Jan 22:108520. doi: 10.1016/j.biotechadv.2025.108520. Online ahead of print.

ABSTRACT

Sustainable agriculture practices are indispensable for achieving a hunger-free world, especially as the global population continues to expand. Biotic stresses, such as pathogens, insects, and pests, severely threaten global food security and crop productivity. Traditional chemical pesticides, while effective, can lead to environmental degradation and increase pest resistance over time. Plant-derived natural products such as secondary metabolites like alkaloids, terpenoids, phenolics, and phytoalexins offer promising alternatives due to their ability to enhance plant immunity and inhibit pest activity. Recent advances in molecular biology and biotechnology have improved our understanding of how these natural compounds function at the cellular level, activating specific plant defense through complex biochemical pathways regulated by various transcription factors (TFs) such as MYB, WRKY, bHLH, bZIP, NAC, and AP2/ERF. Advancements in multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, have significantly improved the understanding of the regulatory networks that govern PSM synthesis. These integrative approaches have led to the discovery of novel insights into plant responses to biotic stresses, identifying key regulatory genes and pathways involved in plant defense. Advanced technologies like CRISPR/Cas9-mediated gene editing allow precise manipulation of PSM pathways, further enhancing plant resistance. Understanding the complex interaction between PSMs, TFs, and biotic stress responses not only advances plant biology but also provides feasible strategies for developing crops with improved resistance to pests and diseases, contributing to sustainable agriculture and food security. This review emphasizes the crucial role of PSMs, their biosynthetic pathways, the regulatory influence of TFs, and their potential applications in enhancing plant defense and sustainability. It also highlights the astounding potential of multi-omics approaches to discover gene functions and the metabolic engineering of genes associated with secondary metabolite biosynthesis. Taken together, this review provides new insights into research opportunities for enhancing biotic stress tolerance in crops through utilizing plant secondary metabolites.

PMID:39855404 | DOI:10.1016/j.biotechadv.2025.108520