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Rapid, accurate, and reliable detection of pathogenic bacteria remains a critical need in clinical, food, and environmental monitoring. In today's context, nucleic acid amplification-mediated biosensing have emerged as a prominent approach to improve detection sensitivity, whereas dual-mode signal readout approaches have more enhanced analytical robustness and reliability. This review outlines recent advances in nucleic acid signal amplification strategies, including enzyme-based methods like LAMP, RPA, and RCA, as well as enzyme-free approaches like HCR, CHA, and EDR. Special attention is given to incorporating these amplification methods into dual-mode biosensing systems that combine both optical and electrochemical transduction mechanisms. This integration enables complementary signal generation and improves detection accuracy by reducing false-positive and false-negative results. This study critically examines the advancement of nucleic acid signal amplification strategies (NASAS)-mediated dual-mode sensing systems for detecting major pathogenic bacteria, including Escherichia coli, Salmonella, Listeria monocytogenes, Staphylococcus aureus, and Vibrio species, focusing on selectivity, sensitivity, assay design, and real-sample applicability. Finally, the review highlights present challenges related to system integration, standardization, and point-of-care applications. Additionally, it outlines potential future directions for rendering nucleic acid amplification-based dual-mode probes into practical diagnostic devices. Overall, this study affords a comprehensive synthesis of emerging approaches and design mechanisms for next-generation diagnostic scaffold for pathogen analysis.

Mood disorders, including major depressive disorder, bipolar disorder, generalized anxiety disorder, and posttraumatic stress disorder, constitute a primary source of global disability, and with conventional monoamine-targeted pharmacotherapy, approximately one-third of patients remain with treatment-resistant disease. Over the past decade, the microbiota-gut-brain axis (MGBA) has emerged as a systems-level pathophysiological framework that explains the chronic neuroinflammation, hypothalamic-pituitary-adrenal axis hyperactivity, and impaired neuroplasticity that characterize treatment-resistant mood disorders. Short-chain fatty acids (SCFAs) are key molecular mediators in MGBA signaling, exerting epigenetic regulation through the inhibition of histone deacetylase, suppression of microglial toll-like receptor 4/nuclear factor-kappa B signaling, reinforcement of intestinal and blood-brain barrier integrity, and rebalancing of tryptophan-kynurenine metabolism. A few small randomized controlled trials and meta-analyses have reported that restoring SCFA output using next-generation psychobiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila, and Clostridium butyricum), prebiotic-rich dietary patterns, defined synbiotics, and direct postbiotic supplementation is associated with symptom improvement, although the evidence base remains preliminary, and have been proposed as candidate prognostic biomarkers. This narrative review synthesizes 2022 to 2026 mechanistic and clinical evidence on SCFA-producing psychobiotics in mood disorders; integrates these findings within a clinical nutrition framework that positions dietary fiber, microbiota-accessible carbohydrates, and targeted psychobiotic supplementation as legitimate adjuncts to conventional psychopharmacology; and discusses the translational challenges of strain specificity, dosing variability, and precision-psychobiotic medicine. Nevertheless, current evidence remains dominated by preclinical models, with human trials constrained by size, duration, and number.

Electrocatalytically amplified electrochemical immunosensing is a powerful strategy for sensitive and interference-free detection of biomarkers. Herein, we report a high-performance electrochemical immunosensor enabled by a hierarchical hybrid architecture comprising Ru nanodots anchored on titanium oxynitride nanoflakes dispersed on graphene oxide (Ru/TiON-GO), linked via APTES to biorecognition building blocks. The engineered heterostructure exhibits advanced electrocatalytic activity, arising from synergistic electronic coupling between Ru nanodots and the highly conductive TiON-GO support, effectively promoting interfacial electron transport between the electrocatalytic surface and the [Fe(CN)6]3-/4- redox probe. Leveraging this electrocatalytic platform, a prostate-specific antigen (PSA) impedimetric immunosensor was constructed, achieving a limit of detection of 0.06 ng mL-1 (2.3 pM) and a wide linear response covering clinically relevant concentration range. The immunosensor demonstrates excellent selectivity in human serum, operating in interference-free mode even in the presence of common coexisting biomolecules, highlighting suitability for medical diagnostics. Density functional theory calculations further elucidate the origin of the enhanced electrocatalytic performance, with charge density difference plots and density of states analysis revealing Ru-driven electron redistribution and increased density of states near the Fermi level. This work establishes the Ru/TiON-GO nanocomposite as a robust electrocatalytic platform for advanced immunosensing applications, paving the way toward next-generation electrochemical diagnostic devices.

ALK rearrangements are rare in gastric cancer, and their therapeutic relevance remains poorly defined. While ALK inhibitors have demonstrated efficacy in lung cancer and other malignancies, data in gastric tumors are limited. We report a 52-year-old woman with metastatic gastric adenocarcinoma harboring a rare SPTBN1-ALK fusion detected at a low variant allele frequency (0.65%). The tumor was negative for HER2 amplification, microsatellite instability, and PD-L1 expression. After failure of chemotherapy combined with immunotherapy, treatment with the ALK inhibitor iruplinalkib resulted in rapid clinical improvement and a durable partial response lasting approximately 14 months. Serial next-generation sequencing at progression demonstrated enrichment of the fusion-positive clone (variant allele frequency increased to 5.94%), accompanied by expansion of TP53-mutant alleles and acquisition of additional genomic alterations. Subsequent histologic transformation to small-cell neuroendocrine carcinoma was observed, with loss of RB expression and markedly elevated Ki-67. No canonical ALK kinase domain resistance mutations were detected, suggesting a non-on-target resistance mechanism. This case highlights that even low-allele-frequency ALK fusions may have important clinical relevance in gastric cancer and may identify patients who could benefit from ALK-targeted therapy. It also illustrates the dynamic evolutionary trajectory of oncogene-driven tumors under therapeutic pressure, with histologic transformation to small-cell neuroendocrine carcinoma that may reflect lineage plasticity. Comprehensive genomic profiling and longitudinal molecular monitoring may facilitate the identification of rare actionable alterations and improve understanding of resistance mechanisms in advanced gastric cancer.

Wide-bandgap transparency and large optical anisotropy are mutually exclusive in most solar-blind birefringent crystals, severely limiting the miniaturization of solar-blind polarization optics. Here, we show that this long-standing trade-off can be broken by a complementary hydrogen-bond co-assembly strategy, in which interstitial water molecules act as directional locks to compress the dihedral angles between urea building blocks and align their dipole moments. This yields two crystals, C2H5N3O2 and its hydrated derivative C2H5N3O2·0.75 H2O, which deliver birefringence values of 0.224 and 0.283 at 546 nm while maintaining absorption edges of 210 and 202 nm in the solar-blind ultraviolet region, respectively. The hydrated phase achieves a 2.5-fold birefringence enhancement over pristine urea, overcoming the inherent anisotropy bottleneck of the classical hydrogen-bonded network. Our findings establish a rational paradigm, from excellent structural units to the ordered arrangement of complementary weak bonds, and then to outstanding optical anisotropy, showing that weak interactions can actively regulate polar units to drive birefringence close to its theoretical limit, offering a widely applicable design platform for the next generation of solar-blind photonic materials.

The detection of single particles or molecules represents a critical milestone in the development of biosensing technologies. Optical sensors based on quasi-bound states in the continuum (qBICs) have primarily focused on detecting global refractive index changes, whereas detection of local refractive index perturbations, such as the binding of a nanometer-sized molecule on a surface, remains elusive because of limited quality (Q) factors and relatively large mode volumes. Here, we demonstrate low-contrast BIC metasurfaces that can perform sensing with a virus-sized single-nanoparticle resolution. The qBIC resonance operating at the critical coupling condition exhibits an experimental Q factor of 4.5 × 104 in heavy water. The strong interactions between the localized electric field and polystyrene nanoparticles with a diameter of 100 nm enable the experimental observation of step-like resonance wavelength shifts, serving as signatures of individual particle binding events. Furthermore, binding-induced modifications to the qBIC resonance alter the optical confinement and asymmetry factor, inducing changes not only in the resonance wavelength but also in the linewidth and amplitude with single-particle sensitivity. Combined with position-insensitive response and free-space accessible features, low-contrast BIC metasurfaces provide a user-friendly platform for next-generation single-nanoparticle sensing integrated with microfluidic systems.

Hypertension has traditionally been defined and managed according to brachial blood pressure levels. Although this pressure-centric strategy has significantly reduced cardiovascular morbidity and mortality, substantial residual risk persists even among patients who achieve recommended blood pressure targets. Emerging evidence indicates that hypertension is fundamentally a systemic disorder of the vascular wall, in which endothelial dysfunction, oxidative stress, immune activation, microvascular remodeling, and progressive arterial stiffening not only result from elevated pressure but also actively drive its initiation and progression. Endothelial nitric oxide deficiency, redox imbalance with endothelial nitric oxide synthase uncoupling, T helper 17 cell-mediated inflammation, and mineralocorticoid receptor-dependent vascular signaling collectively promote increased vascular tone and structural remodeling. Microvascular rarefaction elevates peripheral resistance, while large-artery stiffening augments central pulsatile load and accelerates target organ injury. These interconnected processes create a self-reinforcing network that sustains hypertension beyond simple hemodynamic elevation. In this review, I propose a shift from a pressure-centric to a vessel-centric paradigm of hypertension. I describe mechanistically defined vascular phenotypes, discuss macrovascular and microvascular assessment strategies, and explore therapeutic approaches aimed at vascular restoration in addition to blood pressure reduction. I further examine the concepts of vascular age, residual risk, and precision vascular medicine, and consider future integration of artificial intelligence and vascular endpoints into clinical trials. Recognizing vascular dysfunction as a central determinant of hypertension may refine risk stratification, redefine therapeutic success, and represent the next frontier in cardiovascular medicine. Beyond Blood Pressure: Vascular Function as the Central Determinant and Therapeutic Target in Hypertension. FMD indicates flow-mediated vasodilation, RHI reactive hyperemia index, cFPWV carotid-femoral pulse wave velocity, baPWV brachial-ankle PWV, CAVI cardio ankle vascular index, Nox nitrite/nitrate, ADMA asymmeteric dimethylarginen, RAAS renin-angiotensin-aldosterone system, SGLT2 sodium-glucose cotransporter 2, NO nitric oxide.

Porous carbons are indispensable for supercapacitors and as hosts for silicon anodes in next-generation lithium-ion batteries, yet their commercialization is crippled by the low carbon yield of phenolic resin precursors. What fundamentally controls the yield and how to improve it have long puzzled both academia and industry. Here, we address the root cause by systematically tuning the formaldehyde-to-phenol (F/P) molar ratio. We discover that the methylene bridge density in the cured resin is the key determinant of carbon yield. At the optimal F/P ratio of 2.0, the resin achieves the most complete crosslinked network, boosting the porous carbon yield from below 36% (PC-1.0) to 47.15% (PC-2.0), without compromising pore development. PC-2.0 retains a high specific surface area of 2580.6 m2·g-1 and delivers an outstanding specific capacitance of 371.8 F·g-1 at 0.5 A·g-1. Moreover, it exhibits a high capacitance retention of 95.76% after 10 000 cycles at a current density of 10 A·g-1, demonstrating competitive advantages over various electrode materials reported in recent years. Quantitative analysis confirms a strong positive correlation between methylene content and yield, solving the long-standing puzzle. This work provides a simple, scalable strategy to break the yield-performance trade-off, reducing raw material cost by 16.47% compared with commercial resin.

Clinical AI has advanced rapidly for bounded in-visit tasks such as prediction, documentation, and message generation, yet many costly failures in care occur outside the encounter when follow-up, handoffs, and communication break down. We argue that the next challenge for clinical AI is not only better task performance, but better operational follow-through across the care journey. We propose the PACT framework (Patient-centered, AI-enabled Continuity and Timely action) that reframes clinical AI as a health system function designed to support continuity, completion, escalation, and equity across pre-visit, visit, and post-visit care. The PACT framework specifies the operational elements required for accountable action, including ownership, communication channels, confirmation rules, escalation pathways, and outcome measures. We illustrate its practical use through post-visit coordination, a high-impact setting in which health systems can test workflow integration, monitoring, and tiered human support.

We report a rare survival case of anthrax meningoencephalitis in a 56-year-old male from a low-incidence region. The patient presented with nasal discharge, fever, headache, and rapid onset of coma following the slaughter of a diseased cow. Physical examination revealed a characteristic ulcerative eschar on the right index finger, while laboratory investigations showed significant leukocytosis and hemorrhagic cerebrospinal fluid (CSF) characterized by elevated protein and decreased glucose levels. Although initial microscopy misidentified the pathogen as Bacillus cereus, metagenomic next-generation sequencing (mNGS) of the CSF confirmed Bacillus anthracis within 48 hours. This rapid molecular diagnosis enabled a timely switch to a CDC-recommended combination regimen, initially with quadruple therapy (penicillin G, ciprofloxacin, amikacin, and linezolid) followed by optimization to triple therapy (penicillin G, levofloxacin, and linezolid) during the ICU stay, ultimately leading to the patient's full neurological recovery. This case underscores that the synergistic use of rapid mNGS-based diagnosis and appropriate combination therapy is critical for achieving survival in anthrax meningoencephalitis.

Alpha-mannosidosis is a rare lysosomal storage disease caused by a deficiency of the enzyme alpha-mannosidase. It manifests as a continuous spectrum of signs and symptoms characterized by dysmorphic features, skeletal abnormalities, delayed psychomotor and speech development, impaired hearing, and psychiatric involvement. When suspected, alpha-mannosidosis must be confirmed by biochemical and molecular testing, namely, assessment of blood levels of alpha-mannosidase in leukocytes or fibroblasts and Sanger or next-generation sequencing of the MAN2B1 gene. The disease must be diagnosed and treatment started as quickly as possible, since the long-term prognosis for untreated patients is very poor. Enzyme replacement therapy (ERT, human recombinant alpha-mannosidase) has replaced allogeneic stem cell transplant as the mainstay of therapy, thus improving disease-related outcomes with, for example, reduced serum oligosaccharide levels, greater functional capacity, and improved quality of life, all with a good safety profile. We report the seventh case of alpha-mannosidosis in Spain. The patient was a 3.5-year-old girl assessed in the clinical genetics department for developmental delay and marked dysmorphic features (trigonocephaly, exophthalmos, hypertelorism, and a flat nasal bridge). Radiography revealed shortening and thickening of the long bones, as well as metopic and coronal synostosis. Craniosynostosis was treated with surgery. Assessment of alpha-mannosidase revealed complete absence of enzymatic activity. Genetic analysis revealed the homozygous pathogenic variant of MAN2B1, c.2248C>T, which is associated with alpha-mannosidosis. ERT is the only currently available pharmacological option for treating children with mild-to-moderate alpha-mannosidosis. Without ERT, patients' quality of life would be impaired, and their prognosis would worsen significantly.

High-temperature electrochemical conversion of carbon dioxide to carbon monoxide in solid oxide electrolysis cells (SOECs) has been considered a highly promising strategy for efficient carbon utilization and sustainable energy storage. Among various cathode materials, perovskite oxides have attracted significant attention owing to their structural versatility, redox stability, and physicochemical compatibility with electrolytes. However, their intrinsically limited catalytic activity for CO2 electrolysis remains a major challenge, limiting their practical application. This article systematically reviews the modification strategies for perovskite-based cathodes for carbon dioxide electrolysis in SOECs and provides a comprehensive perspective on them. These strategies are classified into three categories: bulk structure engineering, surface modification engineering, and interface catalytic engineering. Their roles in tuning electronic structure, defect chemistry, catalytic activity, and interfacial processes are critically discussed. Finally, the conclusions and future research directions are highlighted, providing insights into the rational design of next-generation perovskite cathodes with enhanced activity, durability, and scalability for practical SOEC applications.

To investigate the predictive value of peripheral blood cfDNA breast cancer gene mutation profiling for postoperative pathological malignancy in BI-RADS 4 breast nodules. Clinical data from 212 patients with BI-RADS 4 breast nodules at our hospital from January 2020 to January 2024 were retrospectively collected. Patients were divided into benign group (128 cases) and malignant group (84 cases) according to postoperative pathological results. Peripheral venous blood was collected within 1 week before surgery, cfDNA was extracted and targeted next-generation sequencing (NGS, coverage depth 500-1,000&#xd7;) of 49 breast cancer-related genes was performed. cfDNA concentration, tumor mutation burden (TMB), mutation allele frequency (MAF), gene-specific mutation detection rates (BRCA1, TP53, ESR1, ERBB2, PIK3CA, etc.), and a composite Gene Mutation Score (GMS) were analyzed. Multivariate logistic regression analysis was used to identify independent predictors of postoperative pathological malignancy, and ROC curves were plotted to evaluate predictive efficacy. The malignant group had higher cfDNA concentration (14.3 &#xb1; 5.8 vs. 8.6 &#xb1; 3.2&#xa0;ng/mL, P < 0.001) and TMB [2.86 (1.54,4.72) vs. 0.42 (0.28,0.68) mut/Mb, P < 0.001] than the benign group, while overall mutation detection rate (2.18% &#xb1; 0.63% vs. 2.84% &#xb1; 0.52%, P < 0.001), mutation coverage in promoter/regulatory regions of key driver genes (36.2 &#xb1; 9.5 vs. 45.6 &#xb1; 8.3 RPK, P < 0.001), and GMS (0.95 &#xb1; 0.74 vs. 1.82 &#xb1; 0.68, P < 0.001) were lower in the malignant group, indicating distinct mutation patterns. Mutation rates in BRCA1, TP53, ESR1, and ERBB2 in the malignant group were significantly higher than those in the benign group (P < 0.001). G3 grade patients had higher TMB and lower GMS, BRCA1/TP53 MAF, and regulatory region coverage than G1/G2 grade patients (P < 0.05). Multivariate logistic regression analysis showed that age (OR = 1.058, 95%CI: 1.021-1.096), BI-RADS classification (OR = 2.874, 95%CI: 1.643-5.027), TMB (OR = 4.326, 95%CI: 2.214-8.452), and GMS (OR = 0.178, 95%CI: 0.082-0.388) were independent predictors of postoperative pathological malignancy (P < 0.05). The combined model (age + BI-RADS classification + TMB + GMS) had an AUC of 0.923 (95%CI: 0.884-0.962), sensitivity of 88.1%, specificity of 89.1%, positive predictive value of 84.1%, and negative predictive value of 91.8%, superior to single indicators (P < 0.001). cfDNA breast cancer gene mutation profiling has good predictive value for postoperative pathological malignancy in BI-RADS 4 breast nodules, with TMB and GMS being independent predictors. The combined model integrating clinical, imaging, and gene mutation features demonstrates excellent predictive efficacy and can provide a non-invasive, accurate assessment tool for preoperative risk stratification of BI-RADS 4 lesions.

The rapid commercialization of generative artificial intelligence (AI), along with the maturation of quantum technologies has raised a question: can quantum-powered neural networks become the next major shift in large language model (LLM) technology? This naturally leads to another misconception that quantum systems will replace classical LLMs. In this study, both architectures are compared in a contrastive manner in terms of mathematics. The data reveals that identical dynamics that help classical systems learn natural language distributions constrain its ability to use efficient sampling of quantum-mechanical spaces. Performing complexity-theoretic separations (i.e., the widely believed but unproven conjecture that BPP &#x2286; BQP) and a 2025 preprint reporting experimental demonstrations of quantum advantage for generative tasks we conclude that quantum utility is unlikely to lie in tasks involving natural language processing under current architectures, but rather in certain computational subroutines. We then suggest a hybrid quantum-classical architecture as the best direction to take in the future, as it has the advantages of both paradigms. This is done by studying a case study that optimizes retrieval-augmented generation (RAG) pipelines with Grover's search algorithm.

Understanding how lipid nanocarriers behave inside cells is key to improving nucleic acid and protein therapies. However, direct visualization of intracellular trafficking mechanisms is challenging because liposomes possess low intrinsic electron density and highly dynamic and flexible structural features. In this study, we present Lipo-Gold, a hybrid nanosystem consisting of clinically relevant liposomes containing multiple intraluminal small gold nanoparticles (AuNPs) and demonstrate its utility for nanoscale-resolution investigation of intracellular delivery pathways. Using an optimized adaptation of a stepwise in situ reduction strategy, specifically tailored to a cholesterol-containing lipid formulation, we generated multiple nonspace-filling AuNPs (15-20 nm) within each vesicle without altering the bilayer structure, surface charge, or colloidal stability, and overall vesicle architecture. Comprehensive physicochemical characterization, including dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy (TEM), along with cellular uptake investigations by flow cytometry and confocal microscopy, demonstrates that Lipo-Gold retains the same biological identity and cellular interaction profile as the corresponding unmodified liposomes. In HeLa cells, Lipo-Gold also exhibits similar uptake kinetics and intracellular trafficking behavior comparable to unloaded vesicles. The intraluminal AuNPs generate strong electron contrast, enabling direct visualization of intracellular nanoscale transport events, including endocytic uptake, vesicle maturation, and subcellular confinement. Correlative light-electron microscopy (CLEM) further enabled spatial overlap between fluorescent liposome signals and electron-dense AuNP clusters, providing a multimodal imaging platform with nanometric structural resolution. Across all examined sections, AuNPs remained confined to membrane-bound endosomal compartments, with no evidence of cytosolic dispersion, consistent with the expected behavior of anionic, nonfusogenic liposomes. By combining fluorescence tracking with high-resolution structural imaging while preserving native liposome-cell interactions, Lipo-Gold offers a valuable tool for investigating intracellular delivery barriers and for guiding the rational development of next-generation lipid-based therapeutics.