Browse Articles

Capped high-force integrin bond lifetimes and spacing-tuned binding frequency drive rapid fibroblast migration

Cell migration relies on balancing focal adhesion (FA) stability—necessary for traction generation—and turnover—essential for forward translocation. Here, we dissect how integrin binding frequency and force-dependent bond duration jointly regulate this balance in fibroblasts. Using block copolymer micelle nanolithography, we create gold nanoparticle (Au NP) arrays with controlled spacings to vary integrin–ligand binding frequency. In parallel, tension gauge tethers (TGTs) with defined force threshold limit bond lifetime of high-force integrins under cellular traction. We find that intermediate ligand spacing coupled with a moderate rupture threshold dramatically accelerates fibroblast migration—up to twelvefold faster than on denser or sparser substrates. These conditions foster rapid FA turnover and support a dendritic actin architecture driven by lamellipodia, challenging the longstanding view of fibroblasts as inherently slow, mesenchymal movers. Knockout and blocking experiments further identify α5β1 as the mechanically dominant integrin subtype that plays a pivotal role in supporting this rapid migration. Mechanistically, FAs remain sufficiently stable to generate traction but also disassemble quickly, fostering continuous protrusion–retraction cycles essential for high-speed migration. These findings refine the classic biphasic model of cell migration into a two-dimensional framework that considers ligand spacing (binding frequency) and TGT force thresholds (binding duration). Beyond expanding fundamental understanding of integrin mechanobiology, our results provide broad avenues for tissue engineering and therapeutic applications, where finely tuned adhesion mechanics can markedly modulate cell speed and phenotype.

Wireless in-body sensing through genetically engineered bacteria

Abstract This paper introduces a class of wireless implantable sensors that integrate genetically engineered cells capable of detecting specific molecules for continuous monitoring. While synthetic biology enables cells to sense molecular targets, wireless communication of this information remains a challenge. Electromagnetic (EM) waves at cellular-scale wavelengths are strongly attenuated in tissue, necessitating centimeter-scale wavelengths for in-body links. Aligning cellular responses with these longer EM wavelengths enables effective interaction. In this work, the response of Escherichia coli is harnessed to trigger the controlled degradation of a passive microwave antenna, which is then monitored via backscatter communication. This approach converts cellular activity into detectable EM signals, eliminating the need for batteries or circuits. We demonstrate a wireless link between a passive, cell-based sensor in a human body phantom and an external receiver, achieving molecular-level sensing at 25 mm implant depth. Future implementations could couple bacterial responses to diverse molecular targets.

A machine learning model and molecular clusters of epigenetic chromatin regulators in tuberculosis based on bioinformatics and clinical samples

Abstract The role of chromatin regulators (CRs) in mediating epigenetic changes during tuberculosis (TB) infection remains poorly understood. This study aimed to determine the efficacy of CRs in diagnosing TB and characterizing its heterogeneity. GSE83456 dataset was analyzed to identify differentially expressed CRs (DE-CRs) and immune cell infiltration in patients with TB. Consensus clustering was used to classify patients with TB based on DE-CR expression patterns. The optimal machine learning model was selected from four algorithms (Random Forest (RF), Support Vector Machine (SVM), Generalized Linear Model (GLM), and eXtreme Gradient Boosting (XGB)) to differentiate between the molecular clusters. Validation was performed using an external dataset (GSE152532). Blood samples were collected from healthy individuals and patients with pulmonary TB (PTB) or tuberculous meningitis (TBM). Analysis identified 15 DE-CRs, which were used to stratify patients with TB into two distinct molecular clusters exhibiting divergent immune microenvironment characteristics. The XGB model exhibited superior performance in distinguishing these clusters (area under the receiver operating characteristic curve = 0.965). From this model, a five-gene signature ( DHRS9 , HIST1H2BK , C16orf74 , SLC30A1 , and GBP1 ) was identified. This signature effectively predicted TB subtypes and was significantly associated with active TB (ATB) in an external validation set. Clinically, IFIT3 expression was validated as being significantly elevated in the blood of patients with TB (including PTB and TBM) compared to healthy controls, thereby confirming its potential role as a pan-TB biomarker. Our study revealed that CRs are closely associated with immune infiltration and heterogeneity in TB. We developed a robust XGBoost model based on a five-gene signature for accurate TB subtyping and disease-status assessment. Elevated IFIT3 expression underscores the value of CRs as novel biomarkers for TB diagnosis.

Opportunistic screening of type 2 diabetes with deep metric learning using electronic health records

Study on the influence of pore dip angle on acoustic emission characteristics of sandstone with composite defects

Rock defects are a key internal factor leading to deformation and failure under load. This study investigates red sandstone specimens with combined pore–fracture defects at different pore dip angles through uniaxial compression tests, while employing Acoustic Emission monitoring to capture the failure process. The evolution of AE characteristic parameters and rock failure modes is analyzed. The results indicate that: (1) the presence of pores prolongs both the time to failure and the onset of the AE burst stage, with longer durations observed at higher pore dip angles; (2) AE signal amplitude and frequency vary significantly across different loading stages, and the b-value exhibits an “increase–fluctuation–decrease” trend, with the decreasing stage serving as a precursor to rock instability; (3) pore dip angle strongly influences crack propagation types: dip angles of 0°–30° favor axial cracks and through-going wing cracks, 45°–75° angles tend to induce co-planar and wing crack connectivity, while 90° angles cause crack deviation, hindering through-going failure; (4) intact rock fails in a tensile–shear mixed mode, whereas the number of shear cracks in rocks with pores initially increases and then decreases with dip angle, reaching a maximum at 45°, resulting in shear-dominated failure. These findings reveal the failure characteristics and AE evolution patterns of rocks with combined pore–fracture defects at different pore dip angles, providing insights for the identification of precursors to rock failure and for disaster prevention and mitigation.

Genome integrity relies on rapid recycling of DNA Pol III in bacteria

DNA replication requires precise coordination between DNA unwinding and DNA synthesis. In all domains of life, protein–protein interactions at the replisome maintain proximity between the enzymes that catalyze these two activities. Surprisingly, in bacteria, the replicative DNA polymerase (Pol III), responsible for DNA synthesis, is exchanged every few seconds. How processive synthesis is maintained under these conditions has remained unclear. Here, we use single-molecule microscopy in live cells to show that Pol III rapidly rebinds the replisome within seconds of dissociation. This fast recruitment is driven by an interaction with single-stranded DNA–binding protein (SSB), which enhances Pol III target search efficiency by ~20-fold. Disrupting this mechanism alters replisome stoichiometry, causes single-stranded DNA (ssDNA) accumulation, depletes free SSB, and leads to helicase disassembly and DNA breakage, culminating in genome instability. Our findings reveal a mechanism by which fast polymerase recycling sustains continuous DNA replication and genome integrity.

3D spatial organization of heterogeneous nkx2.5+ progenitors in the zebrafish heart field pre-patterns cardiovascular development

Glutamate, NAA, and energy metabolism in clinical high risk and first episode psychosis

Abstract Regulation of brain glutamate is closely related to brain energy metabolism. Changes in both central glutamatergic function and peripheral energy metabolism have been implicated in psychosis risk, onset and long-term illness, but there is a lack of empirical evidence to link these processes. We investigated the relationships between glutamate and N -acetyl-aspartate (NAA, a potential marker of neuronal metabolic integrity) in the anterior cingulate cortex (ACC), measured using proton magnetic resonance spectroscopy ( 1 H-MRS), and peripheral markers of energy metabolism (mitochondrial complex I–V content, pyruvate and lactate) in individuals either at clinical high risk for psychosis or in the first episode of psychosis ( N  = 36) and healthy controls ( N  = 20). ACC Glx (glutamate + glutamine) levels were positively related with principal components relating to mitochondrial complex content, and this relationship did not differ between groups. These findings are consistent with the importance of mitochondrial ATP generation in regulating glutamatergic neurotransmission. While we did not find evidence that this relationship is disrupted in clinical high risk or first episode psychosis, further work is required to understand the mechanisms linking glutamate and energy metabolism in psychosis, including studies in larger cohorts, later stages of illness or in individuals with greater illness burden.

Utilization of Allium peels to improve soil water holding capacity and rice growth under water stress conditions

Abstract Water scarcity hampered rice production and jeopardized worldwide food security. Under conditions of water scarcity, this research investigates the effect of four different Allium peels on soil water holding capacity (WHC) and rice seedlings development. Physicochemical analysis of red, yellow onions, and garlic peels was performed, and their application for growing rice in soil irrigated with 50% field capacity compared to the well-irrigated control group was achieved. Garlic peels contained the least sulphur (0.007 g/g), while red onion peels contained the most (0.147 g/g). The contents of crude fiber, ash, carbohydrates, proteins, phenolic, and flavonoids varied between species. The application of garlic peel to soil resulted in a 60% increase in the soil WHC, which was directly proportional to the fiber content of each peel. Rice seedlings cultivated in pots supplemented with different peels, especially the garlic peel, exhibited substantial growth when subjected to restricted water regimes. Rice plant pigment fractions and hydration status were drastically reduced due to water constraints; however, the addition of garlic and onion peels supplements mitigated this effect. Most especially, supplementing soil with garlic peels caused an enhancement of 66.7% and 80.22% in length and fresh weight of shoot, 59.9% and 87.3% in chlorophyll a and b. The carotenoids, water content, proline, protein, enzymatic antioxidants, and non-protein thiols were all increased by these peels, while rice leaf oxidative impairment (lipooxygenase, lipid peroxidation, and H 2 O 2 ) was decreased. ISSR analysis detects a positive correlation between genomic profiles of plants cultivated in different peel-amended soils. Agro-waste may support soil management, promote rice growth in conditions of limited irrigation water, and provide solutions for water scarcity and waste management. Water conservation and sustainable agriculture are made possible by this novel method.

Predicting IVF outcomes using a logistic regression–ABC hybrid model: A proof-of-concept study on supplement associations

Machine learning models are increasingly applied to assisted reproductive technologies (ART), yet most studies rely on conventional algorithms with limited optimization. This proof-of-concept study investigates whether a hybrid Logistic Regression–Artificial Bee Colony (LR–ABC) framework can enhance predictive performance in in vitro fertilization (IVF) outcomes while producing interpretable, hypothesis-driven associations with nutritional and pharmaceutical supplement use. A retrospective dataset of 162 women undergoing IVF was analyzed. Clinical, demographic, and supplement variables were preprocessed into 21 predictors. Four algorithms (K-Nearest Neighbors, Classification and Regression Tree, Support Vector Machine, and Random Forest) were implemented alongside their LR–ABC hybrid counterparts. Model performance was evaluated using 5-fold cross-validation with Synthetic Minority Over-sampling Technique (SMOTE) to address class imbalance. Local Interpretable Model-agnostic Explanations (LIME) were applied to improve interpretability. Across all algorithm models, LR–ABC hybrids outperformed their baseline models (e.g., Random Forest: 85.2% → 91.36% accuracy). LIME explanations identified omega-3, folic acid, and dietician support as influential features in individual predictions. However, given the small sample size, binary representation of supplements, and absence of external validation, the observed improvements and associations should be regarded as exploratory rather than definitive. The LR–ABC hybrid model demonstrates methodological potential for improving prediction and interpretability in IVF research. Findings regarding supplement associations are hypothesis-generating, not clinically directive. Future studies with larger, multi-center datasets including detailed dosage and dietary data are needed to validate and extend this framework.

DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains

Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2’s reported neutral lipase activity. Here, we find recombinant human DDHD2 preferentially hydrolyzes diacylglycerol (DAG) over phospholipids, with a slight preference for DAG over triacylglycerol (TAG). DDHD2 also exhibits transacylase activity, which enables transfer of acyl chains from TAGs to DAGs and monoacylglycerols to remodel the acyl chains of TAGs. A predicted hydrophobic amphipathic helix on DDHD2 is essential for lipid droplet binding in vitro and in cells, and its lack reduces the enzymatic activity and TAG acyl chain remodeling. Adipose triglyceride lipase, but not hormone sensitive lipase, also has transacylation activity and can remodel TAG acyl chains, but to a lesser extent than DDHD2. Taken together, this provides evidence that DDHD2 is a neutral lipid lipase and transacylase whose broad specificity enables TAG acyl-chain remodeling.

Stiffening iron particles to modulate physical interactions

Optically isotropic fast phase modulation in 3D blue phase photonic crystals

Abstract Blue Phase (BP) liquid crystals are self-assembled 3D photonic structures that uniquely combine optical isotropy with ultrafast electro-optical switching. Their cubic symmetry enables polarization-independent behavior, while sub-millisecond response times make them highly attractive for dynamic photonic applications. However, their practical use has typically been limited by their tendency to form disordered polycrystalline domains, resulting in scattering and poor optical performance. In this work, we realized large-area monocrystalline BP structures with a photonic stopband positioned entirely outside the visible range. This eliminates structural coloration and enables a fully transparent, broadband operation without parasitic reflection. The cubic symmetry ensures the system remains optically isotropic, supporting polarization-independent modulation. We demonstrate a fast phase modulator based on this monocrystalline BP platform. The device achieves phase modulation with sub-millisecond response times and polarization independence, representing a significant advancement over traditional LCs. Our findings position monocrystalline BPs as a robust and versatile platform for reconfigurable optics. The combination of fast response, polarization independence, and optical transparency opens new pathways for advanced applications in adaptive optics, beam steering, dynamic holography, and transparent optical systems such as AR/VR and laser-based technologies.

Modulation of experimental Alzheimer’s disease in rats through donepezil-loaded CSF implant

Abstract Alzheimer’s disease (AD) is a growing challenge worldwide, with current treatments largely symptomatic and limited. The current study aimed to introduce coated nanoporous membranes for localized drug delivery of donepezil, combining both antifouling activity and sustained drug release, unlike traditional Alzheimer’s treatments that rely on systemic administration. Nanoporous membranes were prepared by electrochemical anodization, coated with Polymethyl methacrylate (PMMA) or a PMMA/polyurethane (PU) mixture to mitigate biofouling. The fabricated nanoporous membranes before and after coating were characterized using SEM/EDX, FTIR, BET, and contact angle measurements. In vitro drug release and release kinetics were studied in artificial cerebrospinal fluid (ACSF). Coated and donepezil loaded membranes were implanted on the dura surface in Wistar rats AD model via intracerebral streptozotocin (STZ) injection. The activity was evaluated on behavioral, biochemical and histological levels. PMMA enhanced membrane hydrophobicity (contact angle increased from 62.8° to 79°) and sustained drug release over 7 days, making it the preferred coating. The PMMA membrane demonstrated a reduction in beta-amyloid levels without being loaded with donepezil, while the donepezil-loaded membrane showed cognitive function improvement in Morris water maze and Y-maze. Acetylcholinesterase activity was elevated after STZ-induction of AD and got ameliorated by the membranes implantation. Brain-Derived Neurotrophic Factor (BDNF) was lowered by STZ, while increased in treated animals. Histological examination revealed the neuronal regeneration after donepezil-loaded PMMA coated membrane. These findings suggest that coated nanoporous membranes are promising systems for localized active donepezil drug delivery for AD-like symptoms modulation in STZ-induced AD model, warranting further validation in other AD paradigms.

GerPaCyst - The trial protocol of the prospective, multicenter, interdisciplinary German Pancreas Club Cyst Registry

Introduction Cystic lesions of the pancreas have continued to present a clinical challenge for the past decades now. The increasing rate of detection, the lack of high-quality data on the natural biology of pancreatic cysts and the resulting difficulty to predict malignant transformation in different types of pancreatic cysts make patients with these diseases hard to manage. The German Pancreas Club Cyst Registry (GerPaCyst) (DRKS00025927) aims to establish a platform to discover and survey the natural and specific biology of pancreatic cysts such as IPMNs (main and branch ducts), SCNs, SPPT and MCNs, in a multicenter manner. Materials and methods This manuscript is written according to the SPIRIT guidelines (See S2 and S3 Tables). Ethical approval was obtained from the University of Luebeck (2020-20-225) and all participating centers. In GerPaCyst patients aged ≥18 years with a pancreatic cyst under surveillance or scheduled for surgery should be enrolled. Participating centers will complete an electronic Case Report Form (eCRF) via REDCap which is designed as a longitudinal study minimizing the input of repeated measures. Changes in patient baseline data, cyst characteristics, both endoscopic and imaging data will be entered typically every 6–12 months during patient follow-up. Biobanking will be performed, when available. Duration of observation per patient is up to a maximum of 20 years or until end of follow-up or death. Results The primary goal is to assess and calculate individual risk models for malignancy/high-grade dysplasia based on the collected clinical, molecular and imaging data (multi-omics prediction models) for each included cyst entity, therefore the primary outcome of this trial is the development of high-grade dysplasia/invasive cancer during follow-up or the absence of it. The secondary outcomes are death, quality of life measured by EQ-5D-5L questionnaire, end-of-follow up and perioperative characteristics, if applicable such as complications, length of hospital stay and clavien-dindo classification. Another goal will be to build a multicenter, interdisciplinary database to generate high-quality cyst biology data, which can then be used for further research questions. Additionally, this database will be utilized for registry- based interventional trials in the future. Discussion GerPaCyst will provide a valuable platform for clinical outcomes research. Fundamental factors affecting the development of pancreatic cysts over time will be identified. New research questions might be answered during the study period and will be made available through continuous publications. Trial registration The study was prospectively registered at the German Clinical Trial Register (DRKS) under DRKS00025927 on September 14 th , 2021, before inclusion of the first patient. The Universal Trial Number (UTN) is U1111-1302–9822.

An AINTEGUMENTA phosphoswitch controls bilateral stem cell activity during secondary growth

Plant stem cells have the remarkable ability to give rise to distinct tissues and organs throughout development. Two concentric cylinders of actively dividing stem cells are the main drivers of radial thickening during secondary growth, each producing distinct vascular cell types toward the inside and the outside. While the molecular mechanisms underlying their initiation have been well studied, it remains unclear how these stem cell layers determine which cell type is generated. Here, we demonstrate that the cross-talk between the ERECTA (ER) receptor pathway and auxin signaling controls the amount and choice of output tissue in these two stem cell regions. Mechanistically, we show that the ER pathway phosphorylates the transcription factor AINTEGUMENTA (ANT), thereby modulating bilateral stem cell activity and favoring the differentiation of only one type of cell. Our results thus show that the phosphorylation status of ANT regulates root girth and biomass accumulation by influencing bilateral stem cell production. This highlights the critical role of posttranslational modifications in plant growth and development.

Crossover interference mediates multiscale patterning along meiotic chromosomes

Abstract Meiotic crossover interference is a one-dimensional spatial patterning process that produces evenly-spaced crossovers. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process sets up two interdigitated patterns, of shorter and longer periodicity, by “two-tiered” patterning. Both tiers comprise clustered assemblies of three types of molecules (“triads”) representing the three major components of meiotic chromosomes (crossover recombination, axes, and the synaptonemal complex). One tier of triads occurs at sites of majority (“canonical”) crossovers. Second tier triads are more widely spaced but also exhibit interference, dependent on the same functions as canonical crossover interference. Diverse lines of evidence suggest that second tier triads arise at sites of previously mysterious “minority” crossovers. Finally, conserved protein remodeler Pch2/TRIP13 modulates the abundance of triad components, specifically in longer periodicity triads, dynamically in real time. Potential roles of triad structure, mechanisms of two-tiered patterning, and the nature of minority crossovers are discussed.

Immunogenicity and safety in animals of a lyophilized live attenuated hepatitis A vaccine following stabilizer optimization

Catalytic activity of FAHD1 correlates with nuclear morphology and proteomic states in human osteosarcoma cells

Burden of sickle cell anemia in Africa: A systematic review and meta-analysis

Introduction Sickle Cell Anemia (SCA) is a significant genetic disorder in Africa; however, comprehensive data on its prevalence and geographic distribution remain limited. We aimed to estimate the pooled prevalence of SCA (HbSS) in African populations and examine regional, demographic, and temporal variations from 1994–2024. Methods We systematically searched PubMed, Scopus, Google Scholar, and BASE databases for studies reporting SCA prevalence in African populations. Screening and quality assessments were performed using JBI tools. A random-effects meta-analysis with logit transformation was performed, with subgroup analyses by region, age, sex, and study design. Meta-regression explored heterogeneity sources, including geographic region, age category, diagnostic method, study design, and publication year. Results From 115 studies with 1,203,839 participants and 17,458 confirmed HbSS cases, the pooled prevalence was 1.43% (95% CI: 1.08%–1.88%), with substantial heterogeneity (I 2  = 99.1%) and a prediction interval of 0.21%–8.91%. Central Africa showed the highest prevalence (1.99%), and Southern Africa showed the lowest (0.59%). Children exhibited a higher prevalence (1.65%) than adults (0.45%), while sex differences were non-significant (males 2.71%, females 1.74%; p = 0.694). The prevalence has remained stable over three decades despite a six-fold increase in research output, although wide prediction intervals indicated substantial between-study variability. Electrophoretic techniques predominated (86.4% of cases). Diagnostic method (χ² = 16.73, p = 0.033) and age category (χ² = 33.66, p < 0.0001) significantly moderated the prevalence. The multivariable meta-regression was marginally significant (χ² = 29.01, p = 0.066), but substantial residual heterogeneity persisted (I 2  = 98.6%). Leave-one-out sensitivity analysis showed that no single study significantly impacted the pooled estimates. Conclusion SCA represents a substantial and geographically variable public health challenge across Africa. These findings highlight the need for region-specific interventions, expanded newborn screening programs, improved diagnostic accessibility with quality assurance for point-of-care technologies, and continued surveillance to address geographic gaps.