The rapid emergence of breakthrough allosteric drugs, together with increasing emphasis on the molecular mechanisms of disease, underscores the critical importance of understanding biological processes at the molecular level. Among these, few concepts are as fundamental as the allosteric behavior of proteins. The importance of allostery was recognized decades ago; however, at the time proteins were viewed as static molecular structures rather than dynamic conformational ensembles that continuously interconvert among states with distinct free energies. The realization that proteins exist as dynamic conformational ensembles has transformed our understanding of oncogenic mutations, molecular recognition, protein regulation, and folding. These processes arise from the intrinsic allosteric nature of proteins embodied in their dynamic conformational ensembles. This conceptual advance has also accelerated the development of allosteric therapeutics. Here, we review the conceptual evolution of allostery from classical models to the conformational ensemble paradigm and discuss its implications for biology and modern drug discovery. We highlight breakthroughs in allosteric therapeutics, including a PROTAC that induces degradation of the Cyclin E-CDK2 complex; the pan-Ras molecular glue daraxonrasib for pancreatic cancer, whose allosteric mechanism is mediated through cyclophilin A rather than directly on Ras; a COP9 signalosome exosite-targeting agent; and other emerging modalities.
Colloid-facilitated transport plays a critical role in the long-distance transport of radionuclides in geological media, particularly in scenarios of nuclear waste disposal. Among various colloids, bentonite colloids formed from the swelling and dispersion of bentonite buffer material can significantly influence radionuclide transport due to their strong sorption capacity and high mobility. However, due to the media heterogeneity, sorption and desorption, traditional advection-dispersion models fail to capture the observed long-tailed desorption and retention behaviors of experimental breakthrough curves. To address this gap, we propose a fractional derivative-based co-transport model to capture the colloid-facilitated transport. In this framework, the retarded migration process of radioactive nuclides on the solid matrix is characterized by fractional derivatives and colloid-borne radionuclide transport is described by the classical advection-dispersion equation with first-order mass transfer between the free and colloid-associated radionuclide states. The specific contribution of the model lies in its phase-specific coupling of time-fractional memory and reversible kinetic exchange, which distinguishes the proposed framework from conventional single-equation fractional transport models and classical two-state kinetic models. The model was evaluated using column experiments of Sr transport facilitated by illite and bentonite colloids in saturated quartz sand. The results demonstrate that the proposed framework accurately characterizes both retention and fast-movement behaviors, providing solid accuracy and interpretability for modeling colloid-facilitated radionuclide transport in complex media. The proposed fractional-order framework provides a substantial improvement over classical integer-order models, enabling simultaneous representation of fast colloid-borne transport and long-tail retention. Quantitatively, the model reduces RMSE by approximately 51-77% across different colloid systems, demonstrating the effectiveness of fractional-order memory effects in describing heterogeneous radionuclide transport.
As Aboriginal women, Registered Nurses, and health promotion and public health academics, our perspectives are shaped by both our lived experiences and our professional practice. We have worked across clinical care, health promotion, public health, research, and academia, partnering with Aboriginal and Torres Strait Islander communities, health services, and organisations to improve health and wellbeing. These experiences have reinforced our understanding that meaningful and sustainable health promotion is built on relationships, trust, and shared decision-making, rather than simply the application of participatory methods. We wrote this commentary because we have become increasingly concerned that the term co-design is being used widely across research, policy and practice without always reflecting the principles it was intended to represent. Too often, co-design is reduced to consultation, workshops or the collection of community feedback, while decision-making power, and control remain with researchers, institutions or health services. In our experience, this not only undermines the intent of co-design but also risks reinforcing the very inequities that health promotion seeks to address. Our understanding of authentic co-design is informed by Aboriginal ways of knowing, being and doing, which recognise that relationships are not peripheral to the work; they are the work. Genuine partnership requires time to build trust, reciprocal relationships, mutual accountability, respect for community knowledge, and a willingness to share power throughout every stage of a project. These principles are not unique to Aboriginal and Torres Strait Islander contexts; rather, we believe they represent the foundations of effective health promotion with all communities. As nurses and health promoters, we have seen firsthand that programs developed with communities are more relevant, culturally safe, acceptable and sustainable than those developed for communities. Conversely, we have also witnessed the consequences of tokenistic engagement, where communities are invited to participate after key decisions have already been made. These experiences have shaped our conviction that authentic co-design is not a methodology to be applied, but a way of working that is grounded in humility, reciprocity and respect. We acknowledge that our perspectives are informed by our identities as Aboriginal women and by our professional experiences. While we do not claim to speak for all Aboriginal and Torres Strait Islander peoples or communities, we offer this commentary from a position of shared experience and commitment to strengthening health promotion practice. We hope this paper contributes to an ongoing conversation about moving beyond co-design as a buzzword and toward approaches that genuinely redistribute power, privilege community expertise and foster authentic relationships capable of creating meaningful and lasting health change.
The review is devoted to the use of artificial intelligence (AI) in scientific research and development to create new or repurpose authorized drug products, as well as to the use of AI-based solutions to discover new biomarkers and shorten the time to diagnosis of various diseases. The following areas of AI application are considered: the search for new pharmacologically active substances, the development of formulations and drug production technology, preclinical trials, and intelligent diagnostics (identification of new biomarkers; development of software products to interpret research results and increase diagnostic accuracy). Examples of AI use by leading pharmaceutical companies and a list of the most popular AI models in drug development are provided. The revolutionary contribution of AI in drug discovery lies in reducing the time to identify new drug candidate molecules by more rapidly identifying potential biotargets, performing virtual screening, optimizing promising candidates based on predictive data on pharmacokinetic and toxicological profiles, and searching for the optimal way to synthesize potential drugs. In addition, another area of AI application is the development of drug-delivery devices and systems that improve patient compliance and usability. This paper presents examples of AI use in intelligent diagnostics that prove their high accuracy and time efficiency compared to conventional methods of diagnostics, risk assessment, and prognosis in oncology, cardiology, and other areas of medicine. The implementation of AI technologies in medicine is intensifying, raising questions of ethics, the quality and adequacy of data, the effectiveness and safety of results for patients, personnel competence and readiness for change, as well as issues related to intellectual property rights.
Low-permeability water-sensitive sandstone reservoirs face challenges of low recovery efficiency and injection difficulties with conventional water flooding, necessitating the exploration of more effective displacement technologies. A systematic comparative analysis was conducted on water flooding, gas flooding, water-alternating-gas flooding, surfactant flooding, and CO2-surfactant hybrid flooding, focusing on oil recovery efficiency, displacement pressure differential, pore-scale crude oil mobilization characteristics, and reservoir permeability damage through core flooding experiments. The results indicate that water flooding mainly mobilized crude oil in medium-to-large pores and was difficult to sweep small pores. Furthermore, injecting low-salinity formation water intensified damage and possible pore-throat blockage, which reduced recovery efficiency from 32.6 to 25.9% and increased permeability damage to 40.6%. CO2 flooding mobilized crude oil in small pores, achieving a recovery efficiency of 52.7%, but was prone to early breakthrough and gas channeling issues. Water-alternating-gas flooding delayed early gas breakthrough and improved sweep efficiency in small pores. At a gas/water slug ratio of 1:1, recovery efficiency increased to 66.5%, and permeability damage decreased to 12.8%. The addition of surfactant significantly reduced oil-water interfacial tension and altered rock wettability, improving the range of pore sizes mobilized during displacement, recovery efficiency was 29.9% higher than that of water flooding. However, increasing concentration raised permeability damage to 19.6%. The favorable performance of CO2-surfactant hybrid flooding may be related to CO2-induced oil mobility improvement and surfactant-induced capillary resistance reduction, leading to broader oil mobilization from micropores to large pores. It achieved the highest recovery efficiency of 74.6% among the evaluated schemes, with breakthrough at 0.39 PV and a relatively low displacement pressure differential of 0.083 MPa. These results indicate that maintaining sufficient injected-water salinity with KCl addition is important for controlling water-sensitive damage, while WAG flooding with a gas/water slug ratio of 1:1 and CO2-surfactant hybrid flooding showed more favorable relationships among recovery enhancement, injectivity improvement, and permeability-damage control under the tested conditions.
Vitamin K was discovered during the 1930s when a strange haemorrhagic disorder was observed in chickens fed a cholesterol-free diet. A fat-soluble agent, present in green leafy vegetables and hog liver, was able to restore haemostasis in the chickens. The chemical structure and the physiological role of vitamin K were uncovered resulting in the Nobel Prize being awarded to Henrik Dam and Edward Doisy in 1943. The discovery of vitamin K led to a breakthrough in our understanding of the human coagulation system, where vitamin K plays a pivotal role in activating prothrombin and other coagulation factors. The prevention of vitamin K-dependent bleeding in newborns by vitamin K prophylaxis was introduced in the 1940s and is today a strong recommendation by the World Health Organization. Vitamin K also became crucial to the management of diseases with high risk of vitamin K deficiency due to malabsorption of fat. Later a new type of drug was developed, vitamin K antagonists, counteracting the physiologic effects of vitamin K for the prevention of thrombotic events. Recent research has indicated that vitamin K may have important functions beyond coagulation in extra-hepatic tissues by promoting healthy bone mineralization and preventing vascular calcification. Vitamin K was first discovered in the 1930s when scientists noticed bleeding problems in chickens lacking it. This breakthrough revealed its key role in blood clotting and led to life‐saving practices like giving newborns vitamin K to prevent bleeding. It also became essential for treating people with fat absorption issues and for developing drugs that reduce clotting risks. Today, research shows vitamin K may do more than help blood clot—it could support strong bones and protect blood vessels from harmful calcium buildup, making it important for overall health.
Haemophilia A and haemophilia B are rare bleeding disorders characterized by prolonged bleeding episodes, bruising, and spontaneous bleeds. As the treatment landscape evolves, real-world data are essential to assess disease management practices. This study aimed to describe clinical outcomes for haemophilia A and haemophilia B patients in a real-world setting. Data were drawn from the Adelphi Haemophilia Disease Specific Programme (DSP), a cross-sectional survey of physicians and their patients conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States between February 2020 and May 2021. Physicians provided data on patient demographics, clinical characteristics, bleed history, and treatment patterns. Analyses were descriptive. Overall, 75 physicians reported data for 739 patients with haemophilia A and 131 patients with haemophilia B, with a mean [standard deviation (SD)] age of 27 (14.9) and 25.5 (15.8) years. At data collection, the most common treatment received by haemophilia A patients was emicizumab (40%), while for haemophilia B, this was extended half-life factor (55%). Since switching to their current prophylactic treatment, 48% of haemophilia A patients and 54% of haemophilia B patients had experienced one or more episodes of breakthrough bleeding. Of these patients, the most common bleed type experienced in the 12 months prior to data collection was joint bleeds (53% of haemophilia A patients and 57% of haemophilia B patients). These findings highlight that despite prophylactic treatment, breakthrough bleeding, particularly within the joints, remains common, emphasizing the need for more effective therapeutic strategies.
Oil-in-water emulsions in oilfield wastewater are highly stable and difficult to separate, posing a major challenge for efficient wastewater treatment. Herein, an amino-functionalized zirconium-based metal-organic framework-coated stainless steel mesh membrane, denoted as ZMN-S, was fabricated through dopamine-assisted surface modification, in situ growth of zirconium-based metal-organic framework crystals, and postsynthetic ligand exchange. The structure, morphology, surface chemistry, and thermal stability of the membrane were systematically characterized by XRD, FTIR, SEM, EDS, XPS, laser confocal microscopy, and thermogravimetric analysis. The results confirmed that Zr-MOF crystals were uniformly anchored on the stainless steel mesh surface. After amino functionalization, the membrane retained good crystallinity and surface integrity, forming a micro/nanostructured interface enriched with hydrophilic functional groups. Separation experiments demonstrated that the ZMN-S membrane exhibited high separation performance toward various oil-in-water emulsions. The separation efficiency for a dichloromethane-in-water emulsion reached 99.51 ± 0.41%, with a water flux of 101.7 ± 1.9 L·m-2·h-1. Even for crude oil-in-water emulsion, the membrane maintained a separation efficiency of 97.81 ± 0.61%. After exposure to high-salinity and high-temperature conditions, the separation efficiencies remained as high as 96.51 ± 0.58% and 97.92 ± 0.63%, respectively, indicating favorable environmental adaptability. Based on calculations using the oil droplet deformation breakthrough pressure model, the critical breakthrough pressure of the ZMN-S membrane for an n-hexane oil-in-water emulsion is approximately 14.09 kPa, indicating that the membrane's pore structure and the hydrated underwater superoleophobic interface effectively prevent oil droplets from penetrating the membrane pores after deforming under pressure. Mechanistic analysis suggests that the hydrated membrane surface, oil droplet coalescence and demulsification, and pore-size sieving effect synergistically promote water permeation and oil droplet retention. This work provides a feasible strategy for constructing robust MOF-based membranes for efficient separation of stable oil-in-water emulsions.
Rich physical phenomena arise at novel magnetic topological surfaces and interfaces, which have become a highly pursued forefront for quantum science and technology. Major breakthroughs have been propelled by ever improving capabilities of realizing and manipulating, at the atomic level, unprecedented quantum behavior when emerging magnetic order, tunable spin-orbit coupling and topologically nontrivial states cooperate. In this Review, we focus on interface-modulated magnetism in tetradymite-based magnetic topological insulators and semimetals. We highlight nontrivial spin textures and dynamics that are enabled by synergy of complex crystalline phases, competing orders, engineered defects and symmetry breaking. We envision deeper understanding of interfacially coupled magnetism and topology to further boost fundamental discoveries and technological breakthroughs.
Evidence on whether influenza vaccination reduces disease severity in children with breakthrough infections in community settings is limited. This prospective study enrolled 388 children (aged 6 months-6 years) diagnosed with influenza at a community health center in Shenzhen from May 2024 to October 2025. Participants were grouped by vaccination status within the prior year: vaccinated (n=196) and unvaccinated (n=192). Clinical characteristics, healthcare utilization, and outcomes were compared. Vaccinated children showed significantly lower peak body temperature (38.81°C±0.58°C vs. 39.03°C±0.64°C), shorter fever duration (2.01±1.21 days vs. 2.45±1.55 days), and fewer symptoms like myalgia and gastrointestinal issues (all p<0.01). They also had fewer outpatient visits, lower outpatient costs, and markedly reduced rates of hospitalization (4.1% vs. 21.9%) and antibiotic use (5.6% vs. 15.1%) (all p<0.05). Influenza vaccination could mitigate symptoms, reduce hospitalization and antibiotic use, and lessen the healthcare burden from breakthrough infections.
Topical antibiotic and petrolatum ointments are commonly applied to surgical wounds to reduce surgical site infections (SSIs). However, their use may compromise adhesion of sterile dressings, increasing the risk of dressing displacement and wound contamination during postoperative care. A novel antibiotic-inoculated mastic gum adhesive was investigated for its ability to simultaneously offer antimicrobial prophylaxis and secure dressing fixation at the wound-skin interface. Mastic gum adhesive (MG; acting as control), bacitracin ointment (BO) alone, and mastic gum adhesive combined with bacitracin (MG+B) were evaluated using a synthetic surgical wound model designed to simulate dressing-related contamination. Following bacterial exposure, cultures were collected from contaminated dressings or from agar plates positioned beneath the skin substrates to assess breakthrough contamination. Bacterial contamination of synthetic wounds occurred in 28/30 (93%) MG control replicates, 14/24 (58%) BO replicates, and only 1/30 (3%) MG+B replicates. MG+B had significantly lower wound contamination rates compared with MG (p<0.001), BO (p<0.001) and ethanol (p <0.001). MG reduced bacterial growth by 1.19 log10 reduction (p=0.002 versus control), but MG+B showed a stronger inhibition of 3.19 log10 reduction (p=0.002 versus control; p<0.001 versus MG). MG+B combines the antimicrobial benefits of topical antibiotic ointments with the secure fixation of liquid adhesives. Results of this study indicated a statistically significant lower rate of bacterial breakthrough after contamination for MG+B compared to MG alone and to BO, warranting further investigation into MG+B as a strategy to reduce dressing-related contamination and SSI burden in clinical practice.
Access to anti-seizure medications (ASMs) is critically important to patients with epilepsy (PWE), given that missed doses can lead to breakthrough seizures, morbidity, or mortality. Numerous ASMs are subject to U.S. Drug Enforcement Administration (DEA) scheduling regulations. Controlled substance restrictions present barriers to timely medication access. Scheduling restricts ASM access in myriad ways: biometric data and/or physical signature requirements, refill-too-soon policies, and mail-order availability may be restricted. We hypothesized that ASM misuse is rare, but there is sparse literature available regarding real-world ASM use and clinical impact of restrictions. This survey study investigates whether ASM restrictions impact patient care and whether neurologists encounter patient misuse of ASMs in common practice. An anonymous IRB-approved electronic survey was directly distributed to neurologists and neurology clinicians who treat adult patients with epilepsy via email as well as indirectly via national neurology organization platforms. 236 participants completed the survey. 82% of respondents reported treating primarily PWE. 99% of participants reported having patients experience delayed ASM refills due to restrictions, and 96% reported breakthrough seizures among patients due to scheduled ASM restrictions. Perceived patient misuse of ASMs was generally low. There was a stark difference in reported misuse rates comparing clobazam to traditional benzodiazepines, with 8% reporting rare or occasional misuse of clobazam versus 79% reporting rare or occasional misuse of traditional benzodiazepines. Perceived misuse of non-benzodiazepine, non-gabapentinoid ASMs was very rare; 1% of participants perceived any instances of misuse with brivaracetam or lacosamide, and 0% reported any misuse with perampanel or cenobamate. Respondents reported high rates of medication access issues related to controlled substance restrictions and low rates of ASM misuse. Controlled substance restrictions create practical barriers to reliably obtaining scheduled ASM prescriptions that can result in increased risk of morbidity and mortality. Controlled substance restrictions warrant reevaluation for PWE given the specific risk-benefit tradeoffs for this life-threatening neurologic condition.
Flexible electronics represent a paradigm shift in modern electronics, with flexible sensors serving as pivotal components in these systems. Despite significant advances driven by innovations in materials, structures, hardware, and algorithms, conventional design approaches that focus on optimizing individual hierarchies have inherent performance trade-offs, limiting further development. This review contends that future performance enhancements can no longer rely solely on breakthroughs in separate components. Still, it must adopt a new co-design paradigm spanning the "materials-structure-hardware-algorithm" hierarchy. In this review, we systematically organized the research landscape and representative advances across these four key hierarchies, analyzed the importance and recent breakthroughs in hierarchical synergy, and established a forward-looking theoretical framework to foster innovation and development in the field of flexible sensing.
Current natural gas upgrading strategies primarily focus on CH4 recovery, treating C2H6 and C3H8 merely as impurities, which results in resource wastage. In this work, an advanced industrial operation, simultaneous separation of both pure CH4 and C3H8 from CH4/C2H6/C3H8 ternary gas mixture was realized. Herein, based on semi-empirical computational screening, the desired pore features were identified as an ideal nonpolar aromatic surface, a cage-like geometry, and a suitable pore size. A new material Ni-pza-ina was directionally designed and synthesized. Sorption and separation experiments demonstrated that Ni-pza-ina served the industrial operation well with superior separation performance compared to its parent analogue Ni-bdc-ina and many other materials. Molecular simulations elucidated that the shape/size matching and distinct affinity differences between C2H6 and C3H8 are the governing factors, which are responsible for the successful separation of CH4 (6.05 mmol g-1, purity > 99.5%) and C3H8 (0.90 mmol g-1, purity > 99.5%) from CH4/C2H6/C3H8 85:10:5 (v/v/v) ternary in the breakthrough experiment. Finally, the industrial viability of Ni-pza-ina was demonstrated through an industrial two-bed PSA process simulation, which achieved high recoveries of CH4 (69.17%) and C3H8 (92.69%) in a single cycle, underscoring its promise for realistic industrial application.
Recent breakthroughs in high energy density (HED) science, the study of materials at extreme conditions of pressure and temperature, are profoundly reshaping our understanding across multiple scientific fields. HED science encompasses extreme states of matter across plasma physics, warm dense matter, and condensed matter, bridging fields such as planetary science, materials science, and fusion energy research. Enabled by revolutionary technologies such as ultraintense laser-driven compression, novel insights are emerging from continuous developments. Historically anchored in plasma science, HED physics is evolving toward the understanding of new states of matter, following technological advances. In this Essay, I will present my view of HED science, with particular emphasis on a relatively new and unexplored area within the field that extends beyond plasma physics and warm dense matter, and includes condensed solid and liquid matter at extreme densities and (relatively) cold temperatures. Part of a series of Essays which concisely present author visions for the future of their field.
Colloidal transport and filtration in porous media are commonly described by single-collector models that assume an underlying homogeneous structure. We use microfluidic experiments, particle tracking, and simulations to observe pore-scale and macroscopic filtration. We show that colloidal trajectories in heterogeneous porous structures are inherently intermittent and composed of flights far from grains and dives near their surfaces, where attachment can occur. We propose a stochastic continuous-time random walk model to link this intermittent behavior to macroscopic deposition profiles and breakthrough curves.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, characterized by genetic heterogeneity and the accumulation of mutations in key oncogenes and tumor suppressor genes. CRISPR-Cas9 technology has greatly advanced genetic research by enabling precise genome editing. This review focuses on the innovative applications of CRISPR-Cas9 in CRC research, particularly its role in identifying novel therapeutic targets, elucidating mechanisms of drug resistance, and uncovering metabolic and stem cell pathway alterations in tumorigenesis. We highlight the diverse CRISPR systems, including Cas9, Cas12, Cas13, and advanced variants such as CRISPR activation (CRISPRa), CRISPR interference (CRISPRi), base editing, and prime editing, which have expanded gene knockout studies and enhanced our understanding of CRC. Despite these breakthroughs, challenges such as off-target effects and delivery limitations remain. Ongoing efforts to refine CRISPR technology aim to enhance its precision and clinical applicability, ultimately paving the way for more effective and personalized treatment strategies for CRC. In this review, we explore these advances and focus on the latest developments in CRISPR-based approaches for CRC treatment.
People living with HIV (PLWH) remain at increased risk of diffuse large B-cell lymphoma (DLBCL). Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) has emerged as a standard first-line option for DLBCL in the general population, but the pivotal POLARIX trial excluded PLWH, leaving limited evidence on feasibility with contemporary antiretroviral therapy (ART). A 61-year-old man presented with progressive anorexia and weight loss. With durable virologic suppression (plasma HIV-1 RNA below 20 copies/mL) and immune reconstitution (CD4+ T-cell count approximately 300 cells/µL) on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), he was diagnosed with nongerminal center B-cell DLBCL (Lugano stage II; International Prognostic Index score 2). Pola-R-CHP was administered every 21 days for six cycles (Cycle 1: inpatient and Cycles 2-6: outpatient), followed by two additional rituximab cycles, without ART modification. No grade 3-4 nonhematologic toxicity, febrile neutropenia, or serious infections occurred. HIV-1 RNA remained below 20 copies/mL throughout treatment, and CD4+ T-cell counts showed no clinically meaningful decline. End-of-treatment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET-CT) demonstrated a partial metabolic response with two small residual FDG-avid foci (∼1 cm; SUVmax ∼4-5). At the last follow-up, the patient had no clinical or radiologic evidence of progression. Outpatient-delivered Pola-R-CHP appeared feasible in PLWH with virologic suppression and immune reconstitution receiving BIC/FTC/TAF, without virologic breakthrough or unexpected toxicity. Prospective inclusion of PLWH in polatuzumab-containing frontline studies is warranted.
Precise determination of corneal refractive indices is essential for accurate refractive power calculations, personalized refractive surgery planning, and glaucoma management. However, current clinical methods fail to distinguish between the group refractive index ( n g ) for thickness quantification and the phase refractive index ( n p ) for optical power calculations, often relying on population-averaged constants that mask individual heterogeneity. We aim to develop a multimodal measurement system integrating spectral-domain optical coherence tomography (SD-OCT) and confocal scanning for the precise extraction of the n g , n p , and dispersion coefficients of corneal tissues. A dual-modality platform sharing an 860 nm source was constructed to jointly capture the optical path length (OPL) and confocal distance. A two-step progressive workflow was implemented: first, the n g and thickness were independently determined via the OPL method to serve as target ground truths for extracting tissue-specific dispersion through iterative optimization; second, these quantified priors were utilized to jointly decouple the in situ n g , n p , and thickness of intact corneas. System validation using optical window plates yielded a relative error of only 0.01% to 0.09% for n g and 0.17% to 5.74% for dispersion coefficients. For biological tissues, we report the first direct experimental measurement of phase dispersion for human lenticules ( - 0.014468 ± 0.004060    μ m - 1 ) and porcine sections ( - 0.010223 ± 0.002811    μ m - 1 ), where the human data showed high consistency with the theoretical Cauchy model ( - 0.014186    μ m - 1 ). Utilizing these priors, the system successfully decoupled the in situ parameters of whole porcine eyes, yielding n g of 1.3845 ± 0.0006 and an n p of 1.3757 ± 0.0006 . This technique successfully resolves the n g and n p decoupling challenge in corneal tissues, overcoming the limitations of relying on a single equivalent refractive index. By utilizing an empirically measured corneal dispersion coefficient as a mathematical constraint, the system enables the nondestructive decoupling of physical thickness, as well as phase and group refractive indices in situ. This breakthrough provides essential physical parameters to enhance clinical pachymetry precision and optimize personalized refractive surgery protocols.
Meningitis is one of the most striking manifestations of Streptococcus suis infection. Although multiple virulence-associated factors have been identified, the mechanisms underlying meningitis development remain incompletely understood. In S. suis, a srtBCD pilus gene cluster has been identified; our previous study suggested its association with bacterial virulence. In this study, we investigated the role of the srtBCD cluster in S. suis pathogenesis and confirmed that SBP2' was specifically localized on the bacterial surface and was found to be essential for full virulence in a murine infection model, whereas deletion of other minor subunits had minimal impact. Using brain microvascular endothelial cells (BMECs), microglia, and a BALB/c mouse model, we examined how SBP2' promotes the development of S. suis meningitis. Our results show that SBP2' enhances bacterial colonization of BMECs and recruits host plasminogen, facilitating extracellular matrix (ECM) degradation, and thereby promoting bacterial invasion. In addition, SBP2' enables S. suis to evade microglial phagocytosis and improves its intracellular survival. Importantly, a monoclonal antibody targeting SBP2' conferred significant immunoprotection in mice. Together, these findings identify SBP2' as an important virulence factor and plasminogen-binding receptor that facilitates S. suis traversal of the blood-brain barrier.IMPORTANCEStreptococcus suis is an important zoonotic bacterial pathogen that could lead to severe damage in the central nervous system, but the mechanism underlying the breakthrough of the blood-brain barrier is still unclear. Pili are commonly considered virulence factors and subunit vaccine candidates, but no pilus structure could be observed on the surface of S. suis serotype 2. In this study, we found that the srtBCD pilus cluster, which was considered a pseudogene because of the truncation of the major pilus subunit, could be expressed, and the truncated major pilus subunit could be detected on the cell surface and be involved in the pathogenesis of S. suis serotype 2. Notably, monoclonal antibodies targeting SBP2' provide immunoprotection in mice, reducing bacterial loads and brain damage. These findings identify SBP2' as a key virulence factor and therapeutic target, offering insights into S. suis meningitis mechanisms.