Browse Articles

Mechanisms of permselectivity of connexin hemichannels to small molecules

Unveiling the Role of Excited‐State Dipole Moment: Governing Non‐Sacrificial H ₂ O ₂ Generation on Porphyrin Photocatalysts

Abstract H 2 O 2 production via the simultaneous oxygen reduction reaction (ORR) and water oxidation reaction (WOR) on organic photocatalysts theoretically achieves 100% atom economy. However, the charge separation and transfer mechanism in such organic systems remains poorly understood, especially as organic molecular designs based on ground‐state dipole moments (µ g ) often fail to predict photocatalytic behavior. Here, we synthesize a series of carboxyl‐modified tetraphenylporphyrin supramolecular photocatalysts (TPP‐(COOH) n , where n  = 1∼4, 8) to investigate the structure‐activity relationship. The H 2 O 2 generation activity follows the order TPP‐(COOH) 2  < TPP‐(COOH) < TPP‐(COOH) 3  < TPP‐(COOH) 8  < TPP‐(COOH) 4 , increasing with the excited‐state dipole moment (µ e ) rather than the traditionally considered µ g or number of ‐COOH groups. The µ e , influenced by O 2p‐band center shifts from carboxyl substitution, is demonstrated to govern the charge separation and transfer via an internal electric field. Moreover, exciton dissociation studies indicated that low‐dielectric TPP‐(COOH) n exhibits notably prolonged excitonic lifetimes (ca. 5 ns), making µ e the key activity determinant. Based on this insight, we designed a high‐µ e phthalocyanine supramolecular photocatalyst (H 2 Pc(COOH) 8 ), achieving an unprecedented H 2 O 2 production rate of 58 mM·h −1 ·g −1 and a quantum efficiency (QE) of 18.7% at 420 nm. This study establishes µ e as a predictive parameter for H 2 O 2 generation on organic photocatalysts.

DNA N6-methyladenine modifications of Acidithiobacillus ferrooxidans response to copper stress

High concentrations of copper ions have long been recognized as a key factor limiting the efficiency of bioleaching due to the metal toxicity to microorganisms. In order to identify new determinants of copper resistance, we assessed the impact of different copper ion concentrations on the bioleaching model organism Acidithiobacillus ferrooxidans . Furthermore, we employed 6mA IP-seq technique to evaluate changes in the 6mA methylation levels of A. ferrooxidans under two conditions: iron oxidation and sulfur oxidation, both under copper stress. The results indicated that as the concentration of copper ions in the growth environment increased, the copper toxicity significantly inhibited the growth of A. ferrooxidans . The maximum tolerable copper ion concentration for iron-grown and sulfur-grown A. ferrooxidans was found to be 100 mM. Under 100 mM Cu 2+ exposure, 184 and 242 differentially methylated genes were identified in the iron oxidation and sulfur oxidation A. ferrooxidans , respectively(P < 0.01). From the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis, under iron oxidation conditions, 130 differentially methylated genes were annotated and mapped into 7 KEGG pathways, while under sulfur oxidation conditions, 188 differentially methylated genes were annotated and mapped into 4 KEGG pathways (P < 0.05). Several differentially methylated genes were found to be associated with the following responses to copper stress: iron-sulfur oxidation acceleration, amino acid synthesis, and activation of the RND-type efflux system, polypeptide-based copper resistance systems, and metal ATPases to expel copper ions. In summary, the 6mA methylation levels in A. ferrooxidans change under copper stress, and these changes are widely present in various copper resistance genes. This study reveals a novel copper resistance mechanism in A. ferrooxidans , providing new insights for enhancing bioleaching efficiency and demonstrating significant implications for advancing biometallurgy.

Development of an inhibitory TTC7B selective nanobody that blocks EFR3 recruitment of PI4KA

Thermomagnetic Bistability, Colossal Negative Thermal Expansion, and THz‐Heat‐Induced Switching in Cu‐Nitroxide Complex

Abstract Bistability in molecule‐based magnets is crucial for their applications in functional devices, and thermally induced excited spin state trapping (TIESST) represents a promising route to maintain two distinct spin states for a significant period of time. Heterospin compounds based on Cu(II) and nitroxide radicals demonstrate highly tunable non‐classical spin transitions, nevertheless they did not reveal TIESST effects up to date. Here, we report the first Cu(II)‐nitroxide complex that exhibits TIESST‐driven bistability up to 116 K. The TIESST temperature is close to temperatures of the spin transition, which is accompanied by a hysteresis of 30 K ( T 1/2↑ = 144 K, T 1/2↓ = 114 K). The trapped excited state features a very slow relaxation that exceeds 9 h at 95 K. Fast switching is also feasible for this complex: almost complete conversion from the ground to excited state occurs in a single THz pulse within 50 ms. The slow relaxation and preservation of the crystal quality enabled us to perform an XRD study and demonstrate that the trapped and stable phases coexist during the transition. It was demonstrated, that relaxation of excited state proceeds via an autocatalytic mechanism, previously unreported for spin‐crossover systems, which introduces a new paradigm in spin relaxation dynamics.

A study protocol to explore the effectiveness and implementation of mobile community outreach services for women who use drugs in Baltimore, Maryland: The SHOUT Study

The opioid overdose crisis has continued to affect women who use drugs (WWUD), particularly in urban cities such as Baltimore, Maryland, where fatal overdose rates rank among the highest in the nation. Despite evidence demonstrating the impact of mobile health services in serving underserved populations, few interventions are specifically tailored to meet the unique needs of WWUD. The Sustained Harm Reduction OUTreach (SHOUT) study evaluates the effectiveness and implementation of a harm reduction–based mobile outreach service operated by a community-based organization serving WWUD in Southwest Baltimore. The “intervention group” consists of WWUD recruited within the organization’s catchment area, while the “control group” comprises those recruited from neighborhoods outside of the organization’s catchment area. The study’s three aims are: (1) to conduct in-depth interviews with WWUD (N=12) to assess the feasibility of using a modified respondent-driven sampling (RDS) method; (2) to conduct a prospective cohort study comparing intervention (N=250) and control (N=150) groups over 18 months to assess nonfatal overdose and healthcare access outcomes; and (3) to evaluate intervention implementation using the RE-AIM framework. The study is guided by Andersen’s Behavioral Model for Vulnerable Populations and Rhodes’s Risk Environment Framework. Preliminary findings suggest that a modified RDS approach is both feasible and acceptable among WWUD. Aim 2 will examine the effect of mobile services on reducing nonfatal overdoses by promoting harm reduction practices within participants’ social and physical environments. Aim 3 will incorporate qualitative and cost-effectiveness analyses to contextualize the program’s impact and sustainability. This study addresses critical service gaps for WWUD by integrating and providing low-barrier harm reduction services offered on an accessible mobile van. Findings will inform scalable, community-driven strategies to reduce overdose mortality and improve health equity among structurally vulnerable populations. Strengths, limitations, and plans for results dissemination are discussed.

Molecular insights into the substrate recognition and quasi-unidirectional catalysis of OpaE, an atypical fungal enzyme from the Asp/Glu racemase family

HLA-B*44 is associated with a more than twentyfold increase in cyclic citrullinated peptide antibody serum level in Croatian patients with seropositive rheumatoid arthritis

Objectives To determine whether any of the HLA-A*, HLA-B* and HLA-DR* alleles in seropositive rheumatoid arthritis (RA) can be associated with the extreme serum levels of rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (anti-CCP). Methods This was a retrospective cross-sectional study of adult patients. Demographic data, HLA typing data and RF and anti-CCP levels were collected and analysed. Results HLA-A*02, HLA-B*44 and HLA-DRB1*04 were more prevalent in patients from the RA cohort compared to healthy controls. Intra-cohort analysis revealed that HLA-B*44 had an increased frequency of a twenty-fold increase in anti-CCP (P = 0.033) and HLA-A*03 had a borderline (P = 0.063) frequency. HLA-A*03 was more frequent in the groups with >3-fold and >10-fold anti-CCP levels, while HLA-DRB1*04 was of borderline significance at >3-fold anti-CCP increase (P = 0.053). HLA-B*08 showed a lower frequency of 3-, 10- and 20-fold increase in anti-CCP serum levels. Carriers of B*44 (OR = 5.58; P = 0.030), DRB1*04 (OR = 3.89; P = 0.027) or A*03 (OR = 2.71; P = 0.023) were statistically significantly more likely to have a 20-fold increase in anti-CCP levels over the diagnostic threshold. None of the alleles increased the likelihood of having high or extreme RF levels. Conclusions HLA-B*44 is associated with a twenty-fold increase in anti-CCP serum levels. HLA-A*03 and HLA-DRB1*04 have a positive trend towards a twenty-fold increase in anti-CCP levels. Earlier aggressive therapy in these patients can prevent such an extreme increase in antibody levels.

Purinergic ecto-enzyme CD73 is a context-dependent tumor suppressor in colorectal cancer

Study on the performance of Type II vertical rescue timber shores based on experiment and simulation

Structural instability poses significant risks at earthquake rescue sites, where Type II vertical timber shores play a pivotal bridging role in rapidly securing operational space safety. To systematically evaluate their structural performance and failure mechanisms, this study employed a self-developed hydraulic testing apparatus to conduct compressive bearing capacity tests on three Type II vertical shore configurations: Double T-A, Double T-B, and Two-Post. Vertical downward displacement-controlled loading was applied until failure. Concurrently, refined finite element models incorporating key joint contact characteristics (wedges, plywood gussets, nails) were established using Abaqus software for numerical simulation. Experimental and simulation results demonstrated strong agreement, revealing that: The Two-Post shore exhibited the highest ultimate bearing capacity (239.0 kN), significantly outperforming the Double T-B (200.8 kN) and Double T-A (190.9 kN) types. Failure was typically preceded by audible cracks from wedge cracking, plywood gusset expansion, and buckling of posts near the mid-span. The yield point was identified on the load-displacement curves via the farthest point method. Integrating the Allowable Stress Design (ASD) method and site-specific human-machine-environment factors (psychological impact coefficient C p , wood moisture defect coefficient C m , load duration coefficient C d ), a safety factor K  = 2.0 is proposed for calculating the design bearing capacity ( F d  =  F u / 2.0). This research elucidates the failure mechanism of Type II vertical timber shores, confirms the superiority of the Two-Post configuration, emphasizes the critical influence of load centering on support effectiveness, and provides essential experimental data and a theoretical basis for the safe design and application of timber shoring systems in earthquake rescue operations.

Biochemical characterization of the full-length isoform of soluble adenylyl cyclase

Bioinformatics‐Driven Design of Peptides for Membrane Stabilization During Cryopreservation

Abstract During cryopreservation, cooling triggers membrane phase transitions from a liquid‐crystalline to a gel phase, compromising membrane permeability, impairing water exchange, ultimately leading to cell death. Group 3 late embryogenesis abundant (G3LEA) proteins stabilize cell membranes under adverse circumstances through their functional 11‐mer repeats. Thus, we conducted a bioinformatics analysis of 11‐mer repeats across LEA proteins and identified AKE, a class A α‐helix peptide that lowers the gel‐to‐liquid crystalline phase transition temperature ( T m ). Structural optimization further established a key design principle: a class A α‐helix with a charge‐segregated structure, featuring two positively charged faces separated by hydrophobic and negatively charged regions, designed to enhance membrane interactions by promoting electrostatic binding to phospholipid head groups while allowing hydrophobic regions to associate with lipid tails, potentially strengthening overall membrane affinity. Results confirmed that substituting lysine with arginine, which carries a more delocalized and stable positive charge, strengthened electrostatic interactions and reduced free energy. The optimized peptide, ARE, lowered  T m  and reduced the extent of phase transition improved water permeability and osmotic resistance, leading to a 52% enhancement in post‐thaw red blood cell recovery. By integrating structural design with charge modulation, this study provides a framework for developing membrane stabilizers through rational peptide engineering.

Performance optimization and mechanism study of asphalt mixtures modified with ZM additive

To enhance the high-temperature stability, low-temperature crack resistance, moisture susceptibility, and fatigue life of asphalt mixtures, this study systematically investigates the effects of Zhongmao Modifier (ZM), a solid granular direct-to-asphalt polymer–resin additive produced by Zhongmao Company (Shenyang, China), dosage and mixing process parameters on the pavement performance of asphalt mixtures and elucidates the underlying mechanisms. Orthogonal experiments determined the optimal mixing parameters as a mixing temperature of 170°C, dry mixing time of 180 s, and wet mixing time of 240 s. Experimental results show that the ZM modifier significantly improves the dynamic stability and rutting resistance of the mixture, with dynamic stability increasing to 5245 and rut depth decreasing to 2.26 mm at a dosage of 0.5%. The low-temperature flexural strain increases while the bending stiffness decreases, indicating improved crack resistance. In terms of moisture stability, both the retained stability and freeze–thaw splitting strength ratio outperform those of the base asphalt, reaching 88% and 90%, respectively. Fatigue test results reveal that the ZM modifier markedly extends fatigue life, with a maximum increase of 128.9%, and reduces fatigue sensitivity to the stress ratio. Displacement evolution analysis indicates that the modifier enhances inter-aggregate bonding, increases failure displacement, prolongs the stable phase, and significantly improves overall durability. Mechanistic analysis suggests that the polymer–resin components of the ZM modifier form a stable elastic network within the asphalt matrix and strengthen the interfacial bonding between asphalt and aggregates, thereby improving high-temperature stability and durability while maintaining low-temperature flexibility. The findings provide theoretical support and practical guidance for the broader application of ZM-modified asphalt mixtures in real-world pavement engineering, particularly for enhancing the performance and service life of road surfaces under varying environmental conditions.

Molecular interactions of the NaV1.5 C-terminal domain: CaM sequestered the IQ motif from the CTD

RETRACTED: Natural gas price prediction based on artificial intelligence models

The natural gas supply crisis triggered by the Russia–Ukraine conflict has laid bare the energy market’s extreme vulnerability in the face of geopolitical risk, highlighting the need for accurate multi-step gas price forecasting. However, most AI-based energy price studies have a gap: they focus on single-step prediction or homogeneous model comparisons, lacking analysis of performance degradation in multi-step dynamic frameworks. This study takes daily natural gas price data from the Henry Hub in the United States from 1997 to 2024 as the research object, constructs a multi-step prediction framework with a step size ranging from 1 to 4 days, and systematically compares the prediction performances of four artificial intelligence models: feedforward neural network, support vector machine, random forest, and long short-term memory network. The quantitative results show that, across all prediction cycles, the long short-term memory model has the lowest error rate. For example, in one-step forecasting, its Mean Absolute Percentage Error is 8.53%. Practically, the findings matter. Taking European governments facing natural gas shortages in the Russia-Ukraine conflict as an example, LSTM models can be used for multi-step prediction to forecast price fluctuations 2–4 days in advance, optimizing import reserve strategies to avoid supply disruptions; energy traders can use this to design robust futures arbitrage portfolios. In summary, the research provides a scientific basis and reference for government energy security policy-making and institutional investor trading.

Lipopolysaccharide-induced cytokine signaling activates a temporal innate defense program and represses pancreatic β-cell identity

Mechanistic insight into the antidiabetic effects of Ficus hispida fruits: Inhibition of intestinal glucose absorption and pancreatic beta-cell apoptosis

The worldwide health impact of Type 2 diabetes mellitus (T2DM) is marked by the dysregulation of glucose metabolism caused by α-glucosidase-mediated carbohydrate degradation and pancreatic β-cell apoptosis through caspase-3 activation. This study aimed to thoroughly investigate the potential roles and mechanisms of Ficus hispida fruits methanolic extract (FhME) and its phytoconstituents in combating T2DM by experimental and computational methods. In-vitro investigations demonstrated that, FhME exhibited notable α-glucosidase inhibitory activity compared to acarbose, as indicated by its low IC 50 value of 850 µg/mL. Furthermore, phytochemical analysis of FhME using the HPLC-DAD technique, combined with a review of previous literature, identified and quantified a total of 26 polyphenolic compounds. The network pharmacological investigation of FhME phytoconstituents identified 70 target genes associated with T2DM, where caspase-3 emerged as a key target. GO enrichment analysis, conducted using SRplot, highlighted key pathways, including apoptosis, lipid and atherosclerosis, and chemical carcinogenesis-receptor activation. Subsequently, molecular docking of caspase-3 with phytochemicals demonstrated strong binding affinity. Post-docking MM-GBSA study identified alpinumisoflavone and chlorogenic acid as exceptionally stable compounds. Molecular dynamics simulations conducted over 200 ns demonstrated that gallic acid and alpinumisoflavone produced the most stable complexes with caspase-3. These findings designate F. hispida fruits as a potential natural medicinal agent for Type 2 diabetes treatment, functioning through dual mechanisms of α-glucosidase inhibition and caspase-3 modulation of the apoptotic signaling pathway of the beta cells.

Viral interference of nucleocytoplasmic transport

Site‐Specific Recognition of Inosine‐Modified RNA by Deoxyribozyme with Distant Cleavage Site

Abstract We report an RNA‐cleaving DNAzyme (RCD), RCD‐I4T3, discovered through in vitro selection, that can specifically recognize an inosine‐modified site in RNA and cleave at a remote site (eight nucleotides downstream of the inosine). RCD‐I4T3 represents the first DNAzyme with spatially separated domains for target recognition and catalytic cleavage, functionally analogous to Type IIS restriction endonucleases and endonuclease V, which is not previously observed in DNA catalysts. The RCD‐I4T3 serves as a potent RNA‐cleaving tool, exhibiting an observed rate constant ( k obs ) of 1.9 × 10 −2 min −1 for inosine‐modified RNA, and successfully targeting natural inosine‐containing mRNA fragments with high specificity. This modular architecture minimizes the off‐target activity through stringent two‐step validation (i.e., recognition and cleavage) and enables independent functional optimization. The unique structural and mechanistic features of RCD‐I4T3 expand the functional repertoire of DNAzymes for biological applications.

Distribution and characteristics of rearranged hopanes in the black shale of the Chang 9 member, the Upper Triassic Yanchang Formation in the Ansai area, Ordos Basin, North China

Shale samples from source rocks of the Upper Triassic Yanchang Formation (Chang 9 member) in the Ansai area, Ordos Basin, North China, were analyzed using gas chromatography – mass spectrometry (GC-MS) to investigate the distribution, abundance, and enrichment mechanisms of rearranged hopanes. Four rearranged hopane series were detected, with all four present simultaneously in individual samples. Analysis of the C₃₀ hopane series (regular C₃₀H, diahopane C₃₀D, and neohopane C₃₀E) using a ternary diagram revealed a distinct linear trend, demonstrating a systematic, inverse relationship between the abundance of regular hopane and the combined abundance of its rearranged counterparts. These results provide strong evidence that C₃₀D and C₃₀E in the Chang 9 shales are diagenetic products derived from C₃₀H, sharing a common biological precursor. Both diasteranes and regular steranes with the ββ configuration were correlated positively in abundance with rearranged hopanes, further supporting a common origin linked to specific organism assemblages rather than widespread organisms. Samples deposited under highly saline, suboxic sedimentary environments displayed relatively high abundances of rearranged hopanes, indicating the critical role of depositional conditions in their enrichment. Multi-proxy analysis revealed a complex, non-linear control of thermal maturity on rearranged hopane abundance. The C₃₀ Rearranged Hopane Index showed statistically significant positive correlations with multiple maturity parameters (including sterane and hopane isomerization ratios), indicating maturity as a primary driver in the early oil window. However, this trend diverged at higher maturity levels, suggesting that other factors, such as the catalytic activity of the mineral matrix, become dominant. Our findings establish a robust biomarker-based framework for interpreting oil-source correlations and informing petroleum exploration in the Ordos Basin, particularly for the Chang 9 member source rocks.