Browse Articles

Spatiotemporal evolution and drivers of production-living-ecological land in the northern Tianshan Mountains using complex network analysis

Droplet growth, Ostwald’s rule, and emergence of order in Fused in Sarcoma

The low-complexity domain of Fused in Sarcoma (FUS-LC) undergoes phase separation, forming a dense, liquid-like phase that gradually matures into an ordered, gel-like state over long-time scales. During the maturation process, specific regions of the FUS-LC sequence-core-1, core-2, and core-3-become structured, giving rise to nonpolymorphic fibrils. Coarse-grained simulations predict that kinetically the least stable fibril-like core-3 forms first while the most stable core-1 appears last, in accord with Ostwald’s rule of stages. The fibril structure of the C-terminal core-3, predicted using AlphaFold, shows that a β -strand appears in this region early during droplet formation and triggers FUS-LC assembly. Multichain simulations, which ensure the equality of the chemical potentials between the phases, show that the dense phase forms through nucleation and coarsening, resembling Ostwald ripening. The approaches developed here are broadly applicable and could help uncover assembly mechanisms in other intrinsically disordered proteins like TDP-43, which shares key features with FUS-LC.

Ultraviolet light and polyethylene glycol as environmental cleaning agents to reduce contamination of Pseudogymnoascus destructans in bat hibernacula

Pathogens that persist in an environmental reservoir can drive host populations to extinction because host abundance does not limit pathogen survival or reproduction. Fungal pathogens are of particular conservation concern because many fungi are generalists that persist in the environment. One example is Pseudogymnoascus destructans , the causative agent of white-nose syndrome (WNS), which has caused severe declines in hibernating bat populations across North America. Treatment of environmental reservoirs could help reduce transmission of P. destructans , and thus, reduce bat population declines from WNS. We tested the efficacy of two environmental cleaning agents, ultraviolet-C radiation and polyethylene glycol, in three mines where P. destructans established an environmental reservoir and caused declines in winter colony size of hibernating bats in Ontario, Alabama, and Arkansas. We observed considerable variation between sites but, based on our experimental design, treatments did not reduce environmental P. destructans prevalence or load and there was no consistent pattern in response to the treatments across mines. More encouragingly, treatments did not impact non-target fungi or bacteria. Our results could reflect aspects of our experimental design, including relatively small treatment cells and the lack of an available assay to assess viability of P. destructans from swab samples. Among-site variation we observed, combined with positive results of these treatments in other studies, suggest that site-specific management responses may be important for reducing impacts of white-nose syndrome on bat populations.

Near-unity CO2-to-ethylene photoconversion over low coordination single-atom catalysts

Abstract Photocatalytic conversion of carbon dioxide to value-added chemicals, particularly multi-carbon products, offers a promising route toward carbon-neutral cycles. However, achieving high activity and selectivity remains extremely challenging due to the instability of key reaction intermediates and limited C–C coupling efficiency. Herein, we report a low-coordination manganese single-atom catalyst embedded in zinc sulfide (Mn 1 –ZnS v ) that enables efficient and selective CO 2 -to-C 2+ conversion. In-situ spectroscopic analyses and density functional theory calculations reveal that sulfur vacancies are created at the Mn single-atom coordination sites and induce the formation of coordination-unsaturated Mn-S 2 configuration. The asymmetric coordination environment of Mn modulates local charge distribution, strengthens *CO adsorption, and promotes *CO and *CHO coupling to form the *COCHO intermediate for efficient C–C coupling. As a result, the Mn 1 –ZnS v catalyst achieved 99.1% selectivity for ethylene with a formation rate of 76.6 μmol g -1 h -1 . This study highlights the critical role of atomic-level coordination engineering in advancing photocatalytic CO 2 -to-C 2+ conversion.

Multi-response optimization and machine learning-based prediction of straight-groove warm incremental sheet forming of AZ31 magnesium alloy

A fully synthetic Golden Gate assembly system for engineering a <i>Pseudomonas aeruginosa</i> phiKMV-like phage

Bacteriophages have applications in biotechnology, including human and veterinary medicine, agriculture, food safety, and biosecurity. One example of resurging importance is phage therapy, the use of phages to treat antibiotic-resistant bacterial infections. Phage therapy currently requires screening of environmental phages against the infecting strains for each individual patient, a laborious process that limits the development of standardized treatments. To overcome limitations of narrow host range inherent to many native phages, a robust genomic engineering platform is required which permits rapid and dependable genome production and engineering for nonmodel phage. Here, we describe an engineering platform for a phiKMV-like Pseudomonas aeruginosa phage, 41S1 that builds on previous work in the rapid assembly of small genomes through one-pot, High Complexity Golden Gate assembly (HC-GGA). This system divides the 41S1 genome into DNA fragments small enough to be conveniently synthesized and to avoid toxicity during DNA propagation, with all but one maintained in Escherichia coli . These fragments are readily assembled in a high accuracy, one-pot reaction; phages can be rescued by direct transformation into P. aeruginosa PAO1 or E. coli 10-beta cells. We demonstrate the precise generation of point mutations, DNA insertions, deletions, and the addition of fluorescence reporter genes that are expressed during phage replication. All viable genotypes could be generated with near 100% success rate with minimal screening. This system demonstrates the potential of HC-GGA for the rapid production and engineering of phages and provides a chassis for the development of phages that broadly target the opportunistic human pathogen P. aeruginosa .

Exploring the role of the key gene TNFAIP3 between periodontitis and influenza A through bioinformatic analysis and molecular docking

Recent studies have hinted at a link between periodontitis (PD) and influenza A (IA). Therefore, this study aims to identify key genes common to both diseases by studying Porphyromonas gingivalis ( P.gingivalis ) and the H1N1 virus, the main pathogen of PD and IA, evaluating the promise of these genes as biomarkers, and providing future therapeutic strategies for both diseases. Our research employs a wide range of methods, including bioinformatics analysis, drug prediction and molecular docking. Ultimately, machine learning algorithms identified TNFAIP3 as a common key gene for PD and IA, and further identified five drugs: Vemurafenib, Metformin, Dexamethasone, Tretinoin and Imatinib with potential for combined treatment of PD and IA. Our study reveals the shared mechanism and immune profile of TNFAIP3 as a key gene in PD and IA, which lays a theoretical foundation for future targeted therapies based on the shared mechanism of the two diseases.

Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation

Manual massage versus foam rolling within the NASM corrective framework: a trial for upper crossed syndrome rehabilitation in university students

Abstract Upper Crossed Syndrome (UCS) is a prevalent musculoskeletal dysfunction among sedentary young adults, marked by specific patterns of postural misalignment and muscular imbalance. Despite growing reliance on the National Academy of Sports Medicine (NASM) corrective exercise model in conservative management of UCS, a critical gap remains regarding the comparative effectiveness of different myofascial release (MFR) techniques in the foundational “Inhibit” phase. While foam rolling is widely employed for self-MFR, its ability to match the therapeutic depth of manual massage, particularly in accessing deep anterior musculature has yet to be empirically examined in controlled corrective programs. This quasi-experimental, two-arm parallel-group trial evaluated the differential impact of manual massage versus foam rolling within a 12-week NASM-based corrective exercise protocol among 30 male university students (aged 18–25) with diagnosed UCS. Participants were randomized into a Manual Massage Group (MMG) or a Foam Rolling Group (FRG), both performing identical Lengthen–Activate–Integrate phases. Primary outcome variables included postural parameters consisting of Forward Head Angle (FHA), Thoracic Kyphosis Angle (TKA), Rounded Shoulder Angle (RSA), pain intensity, shoulder internal and external range of motion (ROM), upper extremity function, and health-related quality of life. A 2 × 2 mixed-design ANOVA was conducted to evaluate interaction and main effects ( p  &lt; 0.05). Both groups demonstrated significant improvements over time ( p  &lt; 0.001) across all outcome measures. However, the MMG showed significantly greater improvements in RSA ( p  = 0.031), pain reduction ( p  = 0.003), shoulder external and internal ROM ( p  = 0.001 and p  = 0.016), and SF-36 physical and mental component scores ( p  = 0.001). No significant group-by-time interactions were observed for FHA, TKA, or upper extremity function scores. In the present study, integrating therapist-delivered manual massage was associated with greater improvements in reducing anterior postural deviations, alleviating pain, and enhancing functional mobility and quality of life in UCS populations. These findings support the targeted use of manual MFR in clinical and educational settings where deeper fascial release is warranted. Further research is recommended in diverse populations and long-term follow-ups.

Direct observation of liquid–liquid phase coexistence in deeply supercooled water using an accurate polarizable multipole model

Liquid water can be supercooled up to about 50 K below the melting point before undergoing homogeneous ice nucleation. Based on experimental thermodynamic observations and computer simulations, it was hypothesized that below this temperature and at pressures of several kbar, water undergoes a liquid–liquid phase transition (LLPT) and the transition line ends at a second critical point. However, challenges in experiments and simulations at such deep cooling leave doubts about the nature of the LLPT and the existence of the critical point. Here, we use molecular dynamics simulations with a highly accurate and computationally efficient polarizable water model to establish the character of the LLPT and identify the location of the second critical point. Our microsecond-long simulations provide direct evidence of a well-defined moving interface between low-density and high-density water at conditions near the phase boundary. This provides decisive proof of a first-order transition between two liquid phases with distinct free energy basins separated by a barrier, taking a major step toward resolving this long-standing debate. These results offer new perspectives on supercooled water under pressure simulated with an accurate and realistic model suitable for studies of water in confined geological and biological environments.

Identifying biomarkers for diagnosis and disease activity monitoring in PSC-IBD and UC through proteomic profiling: A prospective, biomarker discovery single-center study protocol

Inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC) are chronic inflammatory conditions with limited biomarker-driven diagnostic tools. Proteomic profiling offers a promising approach to uncover specific biomarkers that could refine diagnostic accuracy, monitor disease activity, and guide therapeutic strategies. Our primary aim is to identify novel biomarkers for PSC-IBD and conventional ulcerative colitis (UC) via proteomic approach. The secondary aim is to advance the etiopathogenic understanding of the diseases by linking specific proteomic profiles with disease phenotypes. This single-center, prospective, biomarker-discovery study will involve 50 participants with PSC-IBD, 50 with UC, and 50 healthy controls. Biopsy samples from five bowel segments will be analyzed for proteomic signatures by an untargeted approach. The findings will subsequently undergo multi-step external validation in separate cohorts of 30 patients with PSC-IBD and 30 with UC, utilizing targeted proteomics, immunohistochemistry, and ELISA in bowel mucosa and peripheral blood, respectively. This proposed study aims to identify novel biomarkers to improve the diagnostic accuracy of PSC-IBD and UC and refine the disease activity assessment. Its robust design and large sample size provide a strong foundation for successful biomarker identification, with the potential to enhance clinical management of patients.

Observation of topological braiding and dynamical criticality in time reflection and refraction

Phytochemical, in silico, and in vitro studies of wheatgrass (Triticum aestivum L.) juice powder

Caspase-3 cleaves and activates the NADase SARM1 to promote apoptosis, linking two cell death mechanisms

Two major mechanisms of axon degeneration have been identified. The first, a caspase-dependent apoptotic pathway, is a major mediator of developmental axon degeneration triggered by loss of trophic support. The second, a caspase-independent pathway mediated by the sterile alpha and HEAT/Armadillo motif containing 1 (SARM1) NADase, was found in studies of injury-induced Wallerian degeneration; it is also implicated in degeneration associated with traumatic brain injury, as well as some neurodegenerative diseases and neuropathies. Recent studies suggest that SARM1 functions as a metabolic sensor for the cellular nicotinamide mononucleotide/NAD+ ratio through its autoinhibitory armadillo repeats (ARM) domain. Here, we show a tight link between apoptotic and SARM1-dependent degeneration by demonstrating that SARM1 is activated during and contributes to apoptosis in neuroblastoma cells, macrophages, and T cells. Mechanistically, the key apoptotic protease caspase-3 cleaves SARM1 within its ARM domain, relieving its autoinhibition and activating its NAD+ hydrolase activity. Using a knock-in (KI) mouse model with a SARM1 mutation that prevents caspase-3 cleavage, we show that apoptosis promotion by SARM1 in macrophages and T cells requires its cleavage, whereas in neurons deprived of trophic support, activation of SARM1 occurs both with and without cleavage. Our study identifies a central role for SARM1 in apoptosis in some cells that is mediated by SARM1 activation through caspase-3 cleavage; it provides a model for dissecting the contributions of the two modes of SARM1 activation in different cellular contexts; and it has implications for the selection of ortho- versus allosteric SARM1 inhibitors for treating neurodegenerative diseases.

First record of the smallest extant brachiopod Gwynia capsula (Jeffreys, 1859) from the German Bight

We describe for the first time the occurrence of the smallest extant brachiopod, Gwynia capsula (Jeffreys, 1859), from the island of Helgoland. A single living specimen was found in dredged shell gravel from the Helgoland trench (“Tiefe Rinne”) mainly consisting of large dead shells of the bivalves Ostrea edulis and Modiolus modiolus . G. capsula was identified through its minute size and its characteristic submarginal ridges on the inside of the dorsal valve supporting the trocholophous lophophore of the animal. Among other localities, populations of G. capsula are known from British waters as well as the continental coasts of, e.g., France, Belgium and the Netherlands. However, the reproductive biology of the species makes it rather unlikely that larvae of G. capsula have reached Helgoland by natural drift. It is briefly discussed whether ship-based trading throughout the 19 th century may have had an influence here.

Interventional applications of a Stroke Heat Risk Prediction Model produce health benefits

Analysis of effects of elevation on the power output and efficiency of ground-mounted photovoltaic modules

Abstract This study examines the effects of elevation on the performance of ground-mounted photovoltaic modules, focusing on power output and efficiency. Outdoor experiments were conducted to assess the influence of varying mounting elevations on the electrical performance of PV modules. An experimental setup was deployed at the Hungarian University of Agriculture and Life Sciences (MATE), where three identical polycrystalline PV modules were installed at elevations of 0.7 m, 1.1 m, and 1.6 m above a concrete surface. All modules were south-facing with a fixed 45° tilt to ensure consistent solar exposure. Measurements of solar irradiance, ambient and module temperatures, voltage, and current were recorded from 10:00 to 16:00 under clear-sky conditions. The PV module elevated at 1.1 m demonstrated the highest mean power output (31.64 W) and efficiency (6.67%), outperforming the modules at 0.7 m (25.34 W; 5.36%) and 1.6 m (19.70 W; 4.29%). Enhanced airflow and moderate albedo at 1.1 m reduced cell temperatures, improving electrical performance. Statistical analysis using ANOVA and Tukey’s HSD confirmed that elevation height significantly influenced both power and efficiency ( p  &lt; 0.001). The results highlight that an elevation of approximately 1.1 m optimises convective cooling and irradiance capture, providing a cost-effective strategy to enhance PV energy yield and operational reliability. This system offers strong techno-economic and environmental viability, characterised by a $0.0843 kWh⁻¹ levelized cost of electricity, and a CO₂ mitigation of 577.78 kg over 25 years.

A quorum-sensing molecule from <i>Pseudomonas aeruginosa</i> induces defensive multicellularity in a coinfecting pathogen

Microorganisms commonly exist in polymicrobial communities, where they can respond to interspecies secreted molecules by altering behaviors and physiology; however, the underlying mechanisms remain underexplored. Here, we investigated interactions between Stenotrophomonas maltophilia and Pseudomonas aeruginosa , coinfecting opportunistic pathogens found in pneumonia and chronic lung infections, such as in cystic fibrosis. We found that S. maltophilia forms large protective multicellular aggregates upon exposure to P. aeruginosa secreted factors. Experimental evolution for lack of aggregation selected for fimbrial mutations and we found that fimbriae are required on both interacting S. maltophilia cells for aggregation. Untargeted metabolomics and targeted validations revealed that the quorum-sensing molecule Pseudomonas quinolone signal (PQS) directly induced S. maltophilia aggregation, and colocalized with the aggregates. Further, in coculture with P. aeruginosa , wild-type S. maltophilia formed aggregates, resulting in up to 75-fold increased survival from P. aeruginosa competition compared to fimbrial mutants. Finally, multiple other bacterial species similarly aggregated upon exposure to P. aeruginosa PQS, indicating a more general response. Collectively, our work identifies a multispecies interaction where a quorum-sensing molecule from a coinfecting pathogen is sensed as a “danger” signal, thereby inducing a protective multicellular response.

Defining the population of adolescents in need of comprehensive transitional care based on diagnosis, visit frequency, and disease complexity

Healthcare transition from pediatrics to adult care is a critical yet challenging process for adolescents with long-term medical conditions. This population-based cohort study aims to present a replicable method to identify and quantify adolescents in need of comprehensive transitional care. Using data from Danish national health registers, disease complexity was categorized by expert clinicians based on diagnoses indicative of a need for comprehensive transitional care and transfer to specialized adult healthcare. The study identified 4,677 adolescents requiring comprehensive transitional care from a background population of 418,994 Danish adolescents aged 16–17 years, corresponding to 1.1%. Analysis of outpatient visit data from tertiary hospitals revealed variability in the proportion of adolescents with comprehensive transitional care needs across Denmark’s four tertiary hospitals. For instance, 11.6% of outpatient visits at Aalborg University Hospital involved a comprehensive transition-requiring diagnosis, compared to 26.7% at Copenhagen University Hospital. While the method is intentionally specific and focused on adolescents with the most complex conditions, it offers a scalable framework that could be applied across broader clinical settings. We illustrate this by also applying the method within a pediatric department-based setting. This study provides al replicable framework to assess transition care needs at a population level, primarily identifying adolescents with the most complex conditions. Broader implementation across clinical settings may refine and inform equitable transitional strategies.

Copper-catalysed enantioconvergent N-alkylation of hydrazines with racemic α-haloamides to access enantioenriched hydrazines