Browse Articles

A gustatory receptor–Akt axis couples nutrient sensing to hematopoiesis in the silkworm

Hematopoiesis is tightly linked to an organism’s metabolic state, yet the molecular sensors that convert nutrient availability into hematopoietic output remain poorly understood. Here, we identify a fructose-sensitive gustatory receptor, BmGr9, as a cell-intrinsic nutrient sensor that links circulating sugar levels to blood cell proliferation in the silkworm Bombyx mori . We show that fructose, whose concentration rises sharply after feeding, stimulates hematopoietic organ (HPO) proliferation through BmGr9-dependent Ca 2+ influx and activation of the Akt–ornithine decarboxylase/polyamine signaling pathway. CRISPR/Cas9-mediated knockout of BmGr9 reduces hemocyte production and impairs fructose-induced Akt phosphorylation and polyamine synthesis. We further demonstrate that the fat body polyol pathway produces fructose de novo, which then acts as an interorgan metabolic signal that promotes hematopoiesis and shapes gene expression in the wing-disc/hematopoietic complex. Together, these findings define a nutrient–receptor–signaling axis that mechanistically links dietary and endogenous fructose to hematopoietic proliferation. By revealing an unexpected systemic role for a gustatory receptor, our work expands the conceptual framework of nutrient sensing and suggests conserved principles by which metabolic state governs blood cell development across animals.

Bioinformatic identification of CD8+ T cell activation mediated by key genes in fecal microbiota transplantation for irritable bowel syndrome

Background The effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism. Methods Transcriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms. Results Ten key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation. Conclusion An association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.

Iron in breastfed infants and behavior at 3 years: a randomized trial

Abstract Breastfed infants are particularly vulnerable to iron deficiency, which is associated with impaired neurodevelopment. Iron supplementation reduces behavioral problems in certain risk groups, but effects in healthy infants are uncertain. This randomized, double-blind, placebo-controlled trial evaluated whether daily low-dose iron supplementation (7, 10, or 15 mg micronized microencapsulated ferric pyrophosphate, approximating 1 mg/kg, from 4 to 9 months of age) affects behavioral outcomes at 3 years. The study was conducted in Warsaw, Poland and Umeå, Sweden and included full-term, healthy, predominantly breastfed infants who were non-anemic at baseline. Behavioral problems were assessed using the Child Behavior Checklist (CBCL) at 3 years as a pre-specified secondary outcome. Of the 221 participants randomized, 133 (60%) completed the CBCL. Iron supplementation compared to placebo significantly reduced CBCL externalizing T-scores (mean [SD], 45.6 [8.5] vs. 48.6 [8.9], adjusted P = .006). Lower scores were also observed for aggressive behaviors (adjusted P = .0329). This pre-specified secondary outcome analysis found that low-dose iron supplementation in predominantly breastfed healthy infants between 4 and 9 months of age may contribute to fewer behavioral problems at 3 years of age. These findings suggest a potential beneficial effect, though cautious interpretation is warranted until replicated in future studies. Trial registration : clinicaltrials.gov; identifying number: NCT02242188; URL: http://www.clinicaltrials.gov/study/NCT02242188 ; Date of registration: 2014-09-14.

Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes

The mechanisms by which Wnt/β-catenin signaling regulates gene expression in a tissue- and context-specific manner remain poorly understood, limiting our ability to target the aberrant cell growth typical of many Wnt-driven cancers. Here, we focus on malignant liver tumors driven by activating CTNNB1 (β-catenin) mutations that nevertheless display distinct phenotypic states and Wnt outputs. By profiling patient-derived organoids via single-cell transcriptomics and chromatin dynamics, we identify subtype-specific transcriptional and epigenetic profiles. Using CUT&RUN, we show that β-catenin engages distinct genomic regions, dictated by differential association with TCF/LEF family transcription factors. Specifically, we define a sequence-specific regulatory element engaged by β-catenin only upon interaction with TCF7L2, revealing that partner choice, independent of CTNNB1 mutational status, ultimately determines cell fate. Our findings, validated across multiple tumor models and patient tissues, offer a framework for understanding how differential β-catenin-TCF/LEF interaction orchestrates context-specific Wnt signaling outcomes.

The role of attachment type and bone height in modulating stress distribution in mandibular overdentures: Insights from finite element analysis

Background Mandibular two-implant overdentures are considered the standard of care for edentulous patients. The attachment system and the shape of the bone crest can significantly influence biomechanical behaviours. This study aimed to evaluate stress distribution in mandibular implant-supported overdentures using locator and bar attachments across various bone crest designs. Materials and methods FEA was performed on mandibular overdentures supported by two implants. Three crest configurations (flat, convex, and irregular) were modelled with either bar or locator attachments. A vertical force of 100 N was applied in three loading conditions: anterior, unilateral molar, and bilateral molar. Maximum von Mises stresses and principal stresses were assessed. Results Anterior loading resulted in the highest stresses across all groups, with peak values reaching 12 N/mm² in the convex and irregular models. Bilateral molar loading consistently produced the lowest and most uniform stress distributions, while unilateral loading caused intermediate stress concentrations on the working side. Uneven platforms significantly increased stress levels, particularly under unilateral bar loading. Locator attachments showed slightly reduced stresses after bilateral loading in irregular crest configurations. Stress concentrations were primarily localized at the implant neck and prosthetic connectors. Conclusion Stress distribution in mandibular overdentures is significantly influenced by loading direction, crest shape, and attachment mechanism. Anterior loading poses the highest biomechanical risk, while bilateral posterior loading provides optimal conditions. Vertical discrepancies in implant platforms heighten stress concentrations, underscoring the importance of careful surgical planning. Locator attachments offer limited biomechanical advantages in uneven crest scenarios, supporting their use in anatomically challenging cases.

Impact of moderate alcohol consumption on visuo-motor skills in neurosurgical residents

Abstract Alcohol adversely affects cognitive and motor functions that are critical for surgical performance. Although its general physiological and neurocognitive effects are well documented, evidence regarding its impact on complex, high-precision tasks—such as surgical procedures—remains limited. In this study, nine neurosurgeons performed a series of standardized surgical tasks assessing fine motor skills, gross motor control, and hand–eye coordination under three conditions: sober, acutely influenced (blood alcohol concentration [BAC] ~ 1.0 g/kg), and during the elimination phase several hours after alcohol consumption (BAC ~ 0.6 g/kg), with blood samples collected in each condition for BAC determination in accordance with German forensic standards. Across all nine participants, a total of 189 tests were conducted and evaluated, taking into account both the time required to complete each task and the quality of task performance. Task quality declined in both the acutely influenced and elimination phases. Significant impairments in quality were observed in almost all tasks. During acute influence, tasks such as suturing took longer to complete, whereas others like drilling were performed more quickly. In the elimination phase, all tasks were completed faster than at baseline. These findings suggest that even moderate alcohol intake can have lasting effects on surgical precision and may have implications for patient safety in operative settings.

Expression of four mitochondrial tRNAs from only two loci

Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes after more than a billion years of gene loss. These ancient bacterial vestiges are often structurally aberrant and less stable than their bacterial or cytosolic tRNA counterparts. In some lineages, mitochondrial tRNAs (mt-tRNAs) have become so truncated that the loss of one or both arms has expanded our understanding of what constitutes a functional tRNA. Here, we report another radical departure from canonical tRNA gene architecture: two overlapping tRNAs produced from opposite strands of the same locus. These “mirror” tRNA pairs eliminate the need to retain separate loci for all tRNA genes, as a single locus can produce tRNAs to decode two different amino acids. We show that these mirror tRNAs are aminoacylated and demonstrate their presence in mitoribosomes. Furthermore, mirror tRNAs display strand-specific patterns of nucleotide modification and RNA editing, reflecting specific posttranscriptional maturation that depends on transcriptional orientation. This demonstration of functional, bidirectional tRNA expression reveals an unexpected strategy by which mitochondrial genomes maintain a complete set of tRNAs in the face of unrelenting gene loss. The presence of mirror tRNAs has broad implications for the evolution of tRNA-interacting enzymes, mitochondrial biology, and even the origins of the protein synthesis machinery itself.

Comparing the effects of analogical instruction with internal and external focus of attention on golf putting skill learning in children with developmental coordination disorder: Emphasizing mental representation structure

This study examined the effects of implicit learning-based instruction—analogy, external focus (EF), and their combination—on golf putting performance and learning in children with developmental coordination disorder (DCD). Given that internal focus of attention often competes with external focus by drawing attention to body movements, combining analogy with EF may help direct attention externally by simplifying movement execution. Sixty children aged 7–9 with DCD were randomly assigned to five groups: analogical instruction, EF, internal focus (IF), analogical-external focus (A-EF), and control. The IF group focused on their striking hand; the EF group focused on the putter’s path and target. The analogical group performed a pendulum-like swing based on a biomechanical metaphor. The A-EF group combined the pendulum analogy with EF instructions. The control group received no instructional cues. Participants completed a pretest, followed by three acquisition sessions (3 × 20 trials per session), immediate and delayed retention tests (72 hours post-practice), a transfer test (from a 5.5-meter distance), and an automaticity test under dual-task conditions. Results showed that, collapsed across acquisition sessions, both the external focus (EF) and combined analogy-external focus (A-EF) groups significantly outperformed the internal focus (IF) group. In retention, transfer, and dual-task performance, all three implicit learning groups (A, EF, A-EF) performed significantly better than the IF and control groups. These findings suggest that implicit instructional methods, particularly the combined approach, enhance motor learning in children with DCD, likely due to reduced reliance on working memory and greater automaticity of movement execution.

Genomic and bioreactor evaluation of newly isolated cellulase-producing bacteria

GREM1/FGFR1-activated myofibroblasts induce immunosuppression and accelerate metastasis in high-grade serous ovarian cancer

Joint effect of cancer-associated fibroblasts (CAFs) and regulatory T cells (Tregs) can drive immunosuppression in high-grade serous ovarian cancer (HGSOC), thereby promoting tumor metastasis and limiting the clinical benefit of PD-1/PD-L1 blockade. However, the mechanistic crosstalk between CAFs and Tregs remains unclear. By integrating bulk RNA-seq, single-cell RNA-seq datasets, and spatial transcriptomics datasets with functional assays, we identified a population of TGF-β1-driven Gremlin1 (GREM1) + myofibroblastic CAFs (myCAFs) enriched in HGSOC metastatic lesions. These GREM1 + myCAFs activated the FGFR1-MAPKs-NFκB-TDO2-kynurenine axis via autocrine signaling, promoting tumor growth, metastasis, and immune evasion characterized by the infiltration of CD4 + Tregs and dysfunctional CD8 + T cells. GREM1 knockdown suppressed tumor metastasis, restored antitumor T cells response, remodeled CAF subtype composition and potentiated anti-PD-1 therapy efficacy. This study highlights the pro-metastatic role of GREM1 + myCAFs across multiple tumors and provides a rationale for combining anti-PD-1 therapy for metastatic HGSOC.

Survival analysis of time to amputation following diabetic foot ulcer diagnosis among Indonesians

Background Diabetic foot ulcer (DFU) is a severe complication of diabetes that often leads to amputation and high mortality, yet survival outcomes and risk factors after DFU-related amputation remain poorly understood particularly in Indonesia. This study aims to determine the incidence rate (IR), survival rate and to identify factors associated with the survival of amputation among patients having DFU in Indonesia. Methods This retrospective cohort study included Type 2 Diabetes Mellitus (T2DM) patients with DFU admitted to the Margono Hospital in Central Java Indonesia. The primary outcome of this study was the times since diagnosis of DFU to amputation. This study outcome was conducted for 5-year survival (2019–2024), IR and survival rate of amputation. Multiple cox regression was performed to investigate factors associated with survival, quantified by adjusted hazard ratios (AHR) and their 95% CIs. Results This cohort comprised 878 DFU patients and followed up for 1,350.55 person-year within the study period. The overall amputation IR was 14.22 per 100 person-year (95% CI: 12.34–16.38) with the highest IR/100 population was 85.68 (95% CI: 73.49–99.90) occurred in the gangrene group. The overall survival rate within 1-year, 3-year and 5-year was 76.14% (95%CI: 72.82–79.11), 72.77% (95%CI: 69.08–76.10) and 71.18% (95% CI: 67.22–74.75) respectively with the highest five-year survival rates were observed among patients with cardiovascular disease (94.37%, 95% CI: 85.17–97.93). Factors that were associated with survival included patients who receiving insulin therapy (AHR: 5.51; 95% CI: 3.73–8.14), residing in rural areas (AHR: 4.14; 95% CI: 1.70–10.12), patients without neuropathy (AHR: 2.40; 95% CI: 1.30–4.42), those with underweight or normal BMI (AHR: 2.04; 95% CI: 1.40–2.98), and those without hypertension (AHR: 1.52; 95% CI: 1.03–2.22). Conclusions The study revealed that the rate of amputations was relatively high and highest survival rate was patients with cardiovascular disease. Receiving insulin therapy, staying in rural area, no-neuropathy, underweight and normal weight and no-hypertension showed more likely to amputation. Early detection of comorbidities is recommended to prevent amputation among patients with DFU.

Correcting motion-related B0 inhomogeneities in magnetic resonance imaging via combined spherical harmonics and AC/DC matrix coils using DL-based prediction–simulation study

Abstract MR data quality depends on static magnetic field (B 0 ) homogeneity. At the beginning of each session, a brief field map quantifies subject-specific B 0 variation, and shim coils are then set to counteract it. Conventional spherical-harmonic (SPH) shims have limited shimming power, motivating localized multi-coil (AC/DC) systems. However, subject motion can perturb the optimized field, necessitating real-time shim updates that require rapid tracking of B 0 changes. We simulated real-time shimming under motion using jointly first-order SPH and a 31-channel AC/DC matrix coil. Measured B 0 data initially shimmed with SPH were augmented with AC/DC terms in simulation, and real-time control was evaluated. Shimming with AC/DC coils added to the SPH coils improved field homogeneity, but motion eroded these gains. With simulated real-time updates informed by deep learning, B 0 homogeneity was effectively maintained even during substantial motion. Performance matched simulated navigator-like real-time shimming with gradient-echo and echo-planar imaging, while adding no extra scan time in main imaging sequences. Multi-coil shimming offers clear benefits, but the gains may be reduced if shim terms are not updated in real time. Deep-learning-driven prediction of B 0 changes provides a practical path to sequence-agnostic, motion-robust shimming across a broad range of MR protocols.

Social immunity can be a consequence and cause of social evolution

Many social insects respond to pathogens in ways that reduce pathogen transmission within their social groups, with behaviors such as grooming or removing infected individuals. This “social immunity” within a group has been compared to the immune response of multicellular organisms. However, we lack a theoretical framework for understanding both the possible evolutionary origins and consequences of social immunity. How restrictive are the conditions for the initial evolution of social immunity? Would we expect social immunity to influence or even coevolve with other aspects of social complexity, such as colony size or the number of castes? We developed a theoretical framework for examining the evolutionary scenarios that may link social immunity and social evolution. We found that: (1) social immunity can be favored in relatively simple social systems, where relatedness between group members can vary; (2) social immunity can coevolve with the age of colony maturation, leading to colonies that grow for a longer period before they start reproducing; and (3) social immunity often leads to the evolution of larger colonies, which can then select for more worker castes. These results suggest that social immunity can be both a consequence and a cause of social evolution.

Pairwise causal discovery in biochemical networks: A survey on directionality inference within complex networks from stationary observations

Metabolic networks map complex biochemical reactions within organisms, which is crucial for understanding cellular processes and metabolite flow. This study focuses on inferring the directionality of interactions in metabolomics networks. Given the challenge of using steady-state data, we benchmark various methods, including statistical scores and neural network approaches, on synthetic yet realistic biological models. Our findings highlight the relative success of a few methods in some cases where the interaction mechanism is known, whereas other methods show limited effectiveness.

An uncertainty-aware vision transformer–BiLSTM Bayesian framework for reliable clinical decision support using chest X-rays

Telocyte-derived pentraxin 3 enables vascular pruning as a key driver in infantile hemangioma regression

The natural course of infantile hemangioma (IH), a benign vascular infantile tumor, is marked by the initial rapid proliferation of dystrophic capillaries, followed by a regression phase, which is either spontaneous or induced by the first line treatment propranolol. Although endothelial cells have been at the center of most studies, the role of stromal cells in this vascular remodeling has remained unclear. Telocytes, which are stromal cells that may be targeted by propranolol, are involved in tissue organization and angiogenesis, suggesting their role in vascular remodeling during the regression of IH. To assess changes in vascular architecture of IH and the role of telocytes, we used Skin-iDISCO + 3-Dimensions (3D) sample imaging and in vitro models with patient-derived telocytes. Perivascular telocytes exhibited increased dendricity during regression, indicating their activation. Telocytes secretome profiling revealed a complex inhibitory program, with pentraxin 3 (PTX3) emerging as a central effector. 3D multicellular disease models demonstrated a paracrine effect blocking endothelial fibroblast growth factor receptors (FGFR) signaling via FGF2–PTX3 interaction, thereby strongly regulating endothelial proliferation, sprouting, and activation. In vitro mechanistic study and collagen IV staining analysis revealed that vascular regression is at least partially due to vascular pruning. These findings highlight the pivotal role of telocytes in orchestrating vascular remodeling during IH regression, opening therapeutic perspectives for inducing vascular normalization in pathological angiogenesis, including cancer.

Barriers to adherence to endotracheal tube suctioning guidelines among intensive care nurses at a Tanzanian national hospital: A qualitative study

Background Endotracheal tube suctioning (ETS) is a critical procedure for mechanically ventilated patients. Evidence-based guidelines exist to ensure its safe performance; however, adherence remains suboptimal, especially in resource-limited settings. This study aimed to explore the barriers to ETS guideline adherence among ICU nurses at Muhimbili National Hospital (MNH), Tanzania. Methods An exploratory qualitative study was conducted in the medical and surgical ICUs of MNH. Seventeen ICU nurses with ≥1 year of experience were purposively sampled. Semi-structured interviews were performed, audio-recorded, transcribed verbatim, and analyzed using inductive thematic analysis following Braun and Clarke’s framework. Results Three key barriers emerged: (1) Resource scarcity, including critical shortages of staff, equipment, and supplies; (2) Human and behavioral challenges, such as knowledge deficits and resistance to change away from routine practice; and (3) Guideline accessibility and usability, concerning poor accessibility and a perception that guidelines were not tailored to the local context. Conclusion Non-adherence to ETS guidelines primarily reflects systemic constraints rather than individual neglect. Strengthening adherence requires multi-level interventions: improving staffing and resources, providing continuous training, and adapting international guidelines to the local context.

Evaluating the printability and buildability of earth-based fiber–biopolymer composites for 3D printing applications

Structural basis of long-range transcription–translation coupling

Structures recently have been reported of molecular assemblies that mediate transcription–translation coupling in Escherichia coli . In these molecular assemblies, termed “coupled transcription–translation complexes” or “TTC-B,” RNA polymerase (RNAP) directly interacts with the ribosome, the transcription elongation factor NusG or its paralog RfaH forms a bridge between RNAP and ribosome, and the transcription elongation factor NusA optionally forms a second bridge between RNAP and ribosome. Here, we report structures of coupled transcription–translation complexes having mRNA spacers between RNAP and ribosome longer than the maximum-length mRNA spacer compatible with formation of TTC-B. The results define a class of coupled transcription–translation complex, termed “TTC-LC,” where “LC” denotes “long-range coupling.” TTC-LC differs from TTC-B by a ~60° rotation and ~70 Å translation of RNAP relative to ribosome, resulting in loss of direct interactions between RNAP and ribosome and creation of a ~70 Å gap between RNAP and ribosome. TTC-LC accommodates long mRNA spacers by looping out mRNA from the gap between RNAP and ribosome. We present evidence that TTC-LC is a functional intermediate in assembling and disassembling TTC-B, mediating pre-TTC-B transcription–translation coupling before a ribosome catches up to RNAP, and mediating post-TTC-B transcription–translation coupling after a ribosome stops moving and RNAP continues moving. We show that TTC-B, but not TTC-LC, is severely defective in RNA-hairpin-dependent transcription termination, and that both TTC-B and TTC-LC are severely defective in Rho-dependent transcription termination.

The effect of student-led healthcare career experience activity on nursing students’ professional commitment: Study protocol for a randomized cross-over trial

Background Career experience is a valuable approach to stimulate students’ learning interest and reshape their understanding of career pathways. However, the interaction effects between implementers and experiencers, particularly the benefits of the implementers, remain poorly understood. Furthermore, the role of peer-assisted learning in enhancing the effectiveness of career experience activities has not been thoroughly explored. This study aims to evaluate the impact of student-led healthcare career experience activity on nursing students’ professional commitment, academic self-efficacy and learning burnout. Methods This is the study protocol for an open-label, randomized stepped-wedge crossover trial. This study will be set in a medical vocational college in China and will include 110 nursing students, who will be randomly allocated (1:1:1) to one of three groups. In a sequential, stepped-wedge manner, the groups will cross over from control conditions (Waitlist and Observer) to the intervention, where they will lead a healthcare career experience activity. The primary outcome of professional commitment, as well as the secondary outcomes of academic self-efficacy and learning burnout, will be measured via self-reported questionnaires at baseline and three subsequent time points (after the 4th, 8th, and 12th activity sessions). Data will be analyzed using Generalized Estimating Equation (GEE) analysis. Conclusion This protocol details a student-led healthcare career experience activity, grounded in Kolb’s Experiential Learning Theory and Life Cycle Theory, and designed to enhance nursing students’ professional commitment. This trial is expected to provide empirical evidence on the feasibility of this peer-assisted learning model applied in a student-led nursing educational scenario, which facilitates both peer-to-peer and near-peer interactions. Furthermore, the outcomes are expected to inform the future development of student-led educational strategies. Trial registration This study is registered in Chinese Clinical Trial Registry (ChiCTR2300070880). https://www.chictr.org.cn/bin/project/edit?pid=195337