The original article, which appeared online on 31 January 2026, described laboratory and animal experiments linking buparlisib, an investigational drug that targets the PI3K signaling pathway, to an unexpected mechanism of treatment resistance. According to the paper, exposure to the compound appeared to drive up levels of eukaryotic elongation factor-2, a molecular machine central to protein synthesis in cells. The authors argued that this upregulation contributed to treatment failure in lung cancer cells, a finding that, if confirmed, would have carried implications for how clinicians combine targeted therapies with other anticancer agents.

That conclusion is now formally withdrawn. In the retraction note, the Editor-in-Chief of the journal stated that the article has been retracted because the tumors presented in Figure 5 of the paper exceed the accepted limits for tumor burden. In animal cancer studies, tumor burden refers to the total volume or mass of tumor tissue carried by an experimental animal. Research ethics frameworks impose upper limits on how large tumors may be allowed to grow, both to protect animal welfare and to ensure that experiments remain within humane boundaries. When tumors surpass those limits, the study is considered to have breached the ethical standards under which animal research is permitted.

The editor’s decision was anchored explicitly in the ARRIVE 2.0 reporting guidelines, a widely adopted framework for the design, conduct and publication of animal research. ARRIVE, which stands for Animal Research: Reporting of In Vivo Experiments, was developed to improve the reproducibility and ethical rigor of studies involving animals. The updated 2.0 version, published in 2020 by Percie du Sert and colleagues in the journal PLoS Biology, sets out detailed expectations for how animal studies should be planned, reported and reviewed, including humane endpoints, welfare monitoring and limits on tumor growth. The retraction note states that, as a result of the excessive tumor burden shown in the paper, the study does not appear to meet the animal ethics standards described in those guidelines.

The retraction is notable for the response of the author team. According to the notice, Xu Li, speaking on behalf of all the authors, stated that they disagree with the retraction. Disagreement between authors and journals is not uncommon in retraction cases, and journals typically publish the authors’ position alongside the retraction notice to make the record transparent. In this instance, the journal has recorded the authors’ objection while still removing the article from the body of credible scientific literature, leaving readers to weigh the dispute for themselves.

The research behind the paper originated from a collaboration spanning several Chinese institutions. The author group included DanPing Wang, ChenLi Su, Xiao Zhang, Wei Mao, XiaoQiang Dai, Li Xu and XiaoMin Si. Affiliations listed for the team include the Department of Oncology at Xianyang Central Hospital in Shaanxi Province, the Clinical Medicine College at Shaanxi University of Chinese Medicine, and a key laboratory at Yangzhou University dedicated to integrated traditional Chinese and Western medicine in the control of senile diseases. DanPing Wang and ChenLi Su were identified as having contributed equally to the work, with correspondence directed to Li Xu and XiaoMin Si.

The scientific premise of the retracted study touched on a question of real clinical importance. Buparlisib is one of a family of PI3K inhibitors developed to disrupt signaling pathways that drive tumor growth and survival. Resistance to such targeted agents remains a major obstacle in oncology, and proposed mechanisms of resistance attract intense interest because they can suggest combination strategies to overcome treatment failure. Eukaryotic elongation factor-2, the molecule implicated in the paper, is an essential component of the translational apparatus that converts messenger RNA into protein, and its regulation has previously been linked to stress responses in cancer cells. A credible demonstration that a PI3K inhibitor induces this factor and thereby contributes to treatment failure would have been a meaningful addition to the resistance literature.

That potential contribution is now in doubt. Retractions serve a specific function in the scientific record: they alert readers that a published article’s findings can no longer be trusted as reliable, whether because of errors, ethical violations or misconduct. In this case, the stated reason is not fraud or data fabrication but a failure of animal ethics compliance, specifically tumor burden beyond accepted limits in the animal experiments underpinning Figure 5. The distinction matters, because it underscores that scientific publishing increasingly treats ethical compliance as inseparable from scientific validity. A result obtained outside accepted welfare boundaries is regarded not merely as ethically problematic but as unfit for the literature.

The case also illustrates the practical reach of the ARRIVE 2.0 guidelines, which have become a benchmark that editors and reviewers consult when evaluating animal studies. By citing the framework directly in the retraction notice, the journal signaled that deviations from those standards are grounds for withdrawal even after publication. For researchers working with tumor-bearing animals, the message is that monitoring tumor size against predefined humane limits is not an administrative formality but a condition of publication. Journals and their editors are prepared to retract work, years of effort and all, when the welfare thresholds written into those guidelines are crossed.

For the field of lung cancer research, the retraction removes one proposed mechanism of resistance to a PI3K-targeted therapy from the pool of evidence that other scientists might build upon. The original article remains accessible as a retracted document, clearly flagged, so that readers who encounter it can understand its status. The episode serves as a reminder that the credibility of cancer biology depends not only on the ingenuity of its hypotheses but on the rigor and ethics of the experiments that support them, and that the machinery of scientific self-correction, though sometimes contested by authors, continues to operate when standards are not met.

Subject of Research: Retraction of a lung cancer study on buparlisib-induced eukaryotic elongation factor-2 expression due to animal ethics violations

Article Title: Retraction Note: Buparlisib induces eukaryotic elongation factor-2 expression to cause treatment failure for lung cancer cells

Article References: Wang, D., Su, C., Zhang, X., Mao, W., Dai, X., Xu, L., & Si, X. (2026). Retraction Note: Buparlisib induces eukaryotic elongation factor-2 expression to cause treatment failure for lung cancer cells. Molecular Genetics and Genomics, 301(1), Article 195. https://doi.org/10.1007/s00438-026-02522-z

Image Credits: AI Generated

DOI: 10.1007/s00438-026-02522-z

Keywords: retraction, buparlisib, eukaryotic elongation factor-2, lung cancer, treatment failure, animal ethics, tumor burden, ARRIVE 2.0, PI3K inhibitor, Molecular Genetics and Genomics, research integrity, targeted therapy

Persister cells are not resistant bacteria in the classical genetic sense. Instead, they are metabolically quiescent variants within an otherwise genetically identical population that temporarily shut down the processes antibiotics usually attack. Because most antibiotics target actively growing cells—cell wall synthesis, DNA replication, protein production—dormant persisters simply wait out the assault and repopulate the infection afterward. The phenomenon was first described in the 1940s, yet the molecular switches that govern how many cells enter this state remain incompletely mapped, particularly in K. pneumoniae, a leading cause of hospital-acquired pneumonia, urinary tract infections, and bloodstream infections.

To find new regulators of persistence, the research team, led by Yanxin Sun and Yumei Zhang with collaborators across several institutions in Shandong and Zhejiang provinces, compared gene expression during the emergence and recovery of persister populations. One gene stood out: phoU, which encodes a protein belonging to the phosphate-specific transport system. PhoU had been implicated in persister formation in Escherichia coli before, but its role in K. pneumoniae—and the downstream pathway through which it might act—was unclear.

The researchers used CRISPR-Cas9 gene editing to delete phoU from K. pneumoniae strain ATCC 700603, creating a knockout strain they could compare directly with the wild-type parent. They also constructed a complemented strain in which phoU was restored, as well as overexpression strains carrying extra copies of phoU, metE, or phoA—two genes that would soon prove central to the story. This panel of strains allowed the team to separate the effects of losing the gene from the effects of the surrounding genome and to test whether specific downstream functions could rescue the knockout’s defects.

The first surprise was what did not change. The ΔphoU strain grew at essentially the same rate as the wild type and showed no meaningful shift in baseline antibiotic susceptibility. In other words, PhoU is not a general housekeeping factor and its absence does not make the bacterium more fragile in ordinary conditions. What changed was the knockout’s ability to form persisters. When cultures were exposed to levofloxacin, a fluoroquinolone that targets DNA gyrase, or tobramycin, an aminoglycoside that attacks the ribosome, the ΔphoU strain produced significantly fewer surviving persister cells than the wild-type or complemented strains. Two antibiotics with completely different cellular targets produced the same result, suggesting that PhoU influences a shared upstream state—dormancy itself—rather than a drug-specific defense.

To understand how a phosphate transport protein could control dormancy, the team turned to metabolomics and transcriptomics. Untargeted metabolomic profiling, later deposited in the EMBL-EBI MetaboLights database, and genome-wide expression analysis revealed that deleting phoU downregulated two genes in particular: metE, which encodes the cobalamin-independent methionine synthase responsible for producing the amino acid methionine, and phoA, which encodes alkaline phosphatase, a classic marker of the phosphate starvation response. Methionine biosynthesis has previously been tied to stress tolerance in other bacteria; impaired methionine synthesis can lead to homocysteine accumulation and heightened sensitivity to environmental stress. Alkaline phosphatase, meanwhile, connects PhoU to the Pho regulon, the phosphate-sensing network that is increasingly recognized as a regulator of bacterial virulence and survival physiology.

The team then asked whether PhoU’s effect on persisters ran through biofilms. Biofilms—structured bacterial communities wrapped in extracellular polymeric substances—are well known refuges for tolerant cells, and PhoU is a component of the phosphate system long linked to biofilm regulation. The ΔphoU strain indeed formed weaker biofilms and produced less extracellular polymeric substance than the wild type, the complemented strain, and the overexpression strains. But the researchers made a critical distinction here. When they restored metE or phoA expression in the knockout background, biofilm formation and persister levels both partially recovered, yet further analysis indicated that the reduction in persisters was primarily attributable to metabolic defects in the free-swimming, planktonic cells—specifically impaired methionine synthesis and a weakened stress response—rather than to the reduced biofilm mass itself. Biofilm deficiency, in their interpretation, is a parallel phenotype of phoU loss, not the cause of persister decline.

That distinction matters clinically. If persister formation depends on the metabolic state of individual planktonic cells rather than on the architecture of a biofilm, then anti-persister therapies need not penetrate or dismantle biofilms to be effective. Targeting PhoU or its downstream partners—MetE in methionine metabolism and PhoA in the phosphate stress response—could, in principle, strip K. pneumoniae populations of their dormancy capacity even outside the protective matrix of a biofilm. The authors frame PhoU and its transcriptional targets as potential therapeutic vulnerabilities: drug candidates that force persisters out of hiding, or adjuvants that make conventional antibiotics lethal to the full population rather than only its active fraction.

The study also fits into a broader reassessment of PhoU’s role in bacterial physiology. Once regarded largely as a passive scaffold in the phosphate transporter complex, PhoU has now been shown in several organisms to act as a regulatory node, influencing stress tolerance, antibiotic persistence, and even secondary metabolism. In K. pneumoniae, the new results position it as a transcriptional upregulator of metE and phoA, thereby supporting the stress-response capacity of planktonic cells and, ultimately, the pathogen’s ability to survive antibiotic challenge. Because PhoU is conserved across many bacterial species but absent from humans, it represents an attractive target for future drug development, although the authors note that restoring either downstream gene only partially rescues the persister defect—implying that PhoU’s influence extends beyond the two pathways characterized so far.

Limitations remain, as with any laboratory study. The work was performed in a single reference strain under defined culture conditions, and persister frequencies can vary enormously across clinical isolates and infection environments. The team also relied on a limited set of antibiotics, and it is not yet known whether PhoU governs tolerance to beta-lactams or other drug classes through the same pathway. Still, the convergence of genetic, metabolomic, and transcriptomic evidence gives the model considerable weight: by sustaining methionine synthesis and phosphate-linked stress responses, PhoU keeps a reservoir of K. pneumoniae cells poised to survive antibiotic treatment. As antibiotics continue to lose ground against multidrug-resistant Gram-negative pathogens, understanding the molecular choreography of persistence—and finding the proteins that choreograph it—may prove as important as discovering new drugs themselves. This study provides one more name for that choreography, and a promising one at that.

Subject of Research: The role of the phosphate transport protein PhoU in regulating antibiotic persister cell formation in Klebsiella pneumoniae.

Article Title: The phosphate specific transport system protein PhoU modulates persister cell formation of Klebsiella pneumoniae

Article References: Sun, Y., Xu, W., Chen, K., Hong, X., Sun, X., Ma, W., Wang, X., Cao, Q., Xue, Z., Zhou, B., Zhang, Y., Liu, Z., Cui, Z., Wang, D., Dong, Z., & Zhang, Y. (2026). The phosphate specific transport system protein PhoU modulates persister cell formation of Klebsiella pneumoniae. Molecular Genetics and Genomics, 301(1), Article 197. https://doi.org/10.1007/s00438-026-02509-w

Image Credits: AI Generated

DOI: 10.1007/s00438-026-02509-w

Keywords: Klebsiella pneumoniae, PhoU, persister cells, antibiotic tolerance, biofilm, metabolomics, CRISPR-Cas9, methionine synthesis, alkaline phosphatase, Pho regulon, antimicrobial resistance, Molecular Genetics and Genomics

Circular RNAs are an unusual class of molecules. Unlike ordinary linear messenger RNAs, which are transcribed, translated, and degraded in a straightforward sequence, circRNAs are formed when the splicing machinery of the cell joins the downstream end of an RNA molecule back to its upstream end, a process known as back-splicing. The result is a covalently closed loop with no free ends, which makes the molecule remarkably resistant to degradation by the exonucleases that normally chew up RNA. First noticed decades ago as rare splicing accidents, circRNAs are now recognized as abundant, conserved, and often functional components of the transcriptomes of animals and plants alike, with roles that include sponging microRNAs, modulating transcription, and in some cases even serving as templates for translation.

In the new work, Behzad Hajieghrari of Jahrom University and Mousa Torabi Giglou of the University of Mohaghegh Ardabili in Iran systematically reanalyzed strand-specific RNA sequencing data from rice exposed to simultaneous heat and drought stress. Because circRNAs lack the poly-A tails and defined ends of linear transcripts, detecting them requires specialized computational approaches. The researchers subjected the sequencing reads to rigorous quality control, mapped them to the rice genome, and then ran two independent circRNA prediction algorithms, CIRI2 and CIRCexplorer2, in parallel. Only candidates supported by both methods were retained, a dual-algorithm strategy designed to filter out false positives arising from repetitive sequence or misaligned reads. The screen yielded 208 high-confidence circRNAs distributed across all twelve rice chromosomes.

The comparative profiling revealed a striking pattern of stress-dependent circularization. Eighty-three circRNAs were detected exclusively in unstressed control samples, fifty-one appeared only in stressed samples, and seventy-four were shared between the two conditions. In other words, the circular transcriptome is not a static backdrop; it is remodeled when the plant senses combined stress. Junction-read analysis, which counts the sequencing reads that span the diagnostic back-splice junction, exposed a spectrum of circularization strength, from highly abundant circRNAs whose junction reads dominate their genomic loci to low-confidence candidates whose signals are partially masked by the background of linear transcripts from the same genes.

Genomic annotation showed that most of the identified circRNAs originated from exonic regions, with a substantial contribution from intergenic regions, and displayed a pronounced bias toward the negative DNA strand. Several host genes produced multiple distinct circRNA isoforms through alternative back-splicing, meaning that a single gene can generate a small family of circular molecules with potentially different regulatory partners. This isoform diversity adds a layer of complexity to the rice transcriptome that linear RNA analysis alone cannot capture, and it hints that alternative circularization may itself be a regulated process that the plant tunes under stress.

To infer what these circRNAs might be doing, the team performed functional enrichment analysis on their host genes. The results pointed to involvement in protein folding, nutrient reservoir activity, RNA degradation, and branched-chain amino acid catabolism. Each of these categories makes biological sense in the context of combined heat and drought. Protein folding machinery, including heat shock proteins, is central to surviving thermal damage; nutrient reservoir proteins reflect the metabolic reallocation that stress demands; RNA degradation pathways govern how quickly stress transcripts turn over; and amino acid catabolism connects to nitrogen mobilization and osmotic adjustment. The enrichment pattern suggests that circRNAs are not random byproducts but are embedded in the metabolic and proteostatic circuits that determine whether a rice plant tolerates or succumbs to compound stress.

Differential expression analysis between control and stressed libraries identified seven circRNAs specifically induced under combined heat and drought conditions. These stress-responsive candidates represent the most direct leads for future experimental work, since their induction implies that the plant actively upregulates their production as part of its adaptive program. Whether they act by sequestering microRNAs, interacting with RNA-binding proteins, or influencing the splicing of their own host genes remains to be determined, but their stress-specific behavior marks them as priority targets for functional validation.

The most intriguing part of the study concerns the predicted regulatory network built around these molecules. Drawing on the competing endogenous RNA, or ceRNA, hypothesis, the researchers predicted which microRNAs could bind each circRNA and which messenger RNAs those microRNAs could in turn regulate. In the ceRNA framework, a circRNA with binding sites for a particular microRNA can act as a molecular sponge, soaking up that microRNA and thereby relieving repression of the microRNA’s genuine mRNA targets. Network topology analysis of the resulting three-layer circRNA-microRNA-mRNA circuit pinpointed several microRNAs, including osa-miR414, osa-miR1439, and osa-miR2919, as candidate topological hubs, meaning they occupy central positions with many connections and could exert outsized influence over the network’s behavior. The predicted targets of these hub microRNAs encode stress-responsive transcription factors and signaling proteins, suggesting a plausible route by which circRNA abundance changes could ripple outward to reshape the expression of entire stress-response gene programs.

The authors are careful to frame these network findings as predictive. The ceRNA relationships were inferred computationally rather than demonstrated experimentally, and microRNA target prediction in plants, while reasonably accurate due to near-perfect base pairing requirements, still generates false positives. Nevertheless, the study delivers the first comprehensive map of circRNAs in rice under combined heat and drought stress, and it does so with a methodological transparency that should make follow-up work straightforward: the full lists of predicted circRNAs, their genomic coordinates, sequences, host gene annotations, differential expression results, and predicted interaction networks are all provided in supplementary data files. The researchers also note that the work received no external funding and was carried out with resources covered by the authors themselves.

The broader significance lies in what this means for crop improvement. Extreme weather events increasingly combine heat and water deficit during the rice growing season, and breeding for tolerance to each stress individually has not reliably produced varieties that withstand the combination. If circRNA-mediated regulation proves to be a genuine coordinating mechanism, it opens a new class of molecular markers and, eventually, engineering targets: circRNAs or the splicing elements that control their production could be tuned to bolster the plant’s post-transcriptional defenses. For now, the seven stress-induced circRNAs and the hub microRNAs osa-miR414, osa-miR1439, and osa-miR2919 constitute a concrete experimental agenda. Validating their interactions, confirming their sponging activity, and testing their effects on stress tolerance in living rice plants will determine whether these molecular rings are merely correlates of stress or true architects of the crop’s resilience.

Subject of Research: Circular RNA-mediated post-transcriptional regulation in rice under combined heat and drought stress

Article Title: Circular RNAs orchestrate integrated post-transcriptional responses to combined heat and drought stress in rice

Article References: Hajieghrari, B., & Giglou, M. T. (2026). Circular RNAs orchestrate integrated post-transcriptional responses to combined heat and drought stress in rice. Molecular Genetics and Genomics, 301(1), Article 183. https://doi.org/10.1007/s00438-026-02516-x

Image Credits: AI Generated

DOI: 10.1007/s00438-026-02516-x

Keywords: circular RNAs, rice, heat stress, drought stress, ceRNA network, microRNAs, back-splicing, RNA-seq, Oryza sativa, post-transcriptional regulation, plant stress responses, Molecular Genetics and Genomics