To discuss the effect of round window drill-out for otosclerosis cases with radiographic evidence of round window obliteration. Four adult patients (5 ears) were included with audiometric findings of a mixed hearing loss and radiographic evidence of otosclerosis causing round window obliteration. Round window obliterative disease was addressed with a formal round window drill-out (RWD) by opening the lumen of the basal turn of the cochlea with a micro drill. The opening was then reconstructed with fascia to recreate a 2-window system. Feasibility, Δ pure-tone air conduction thresholds, and Δ pure-tone average air-bone gap (PTA-ABG). Three (60%) ears underwent primary or revision stapedectomy with RWD, 1 (20%) ear underwent delayed RWD years after stapedectomy, and 1 (20%) ear underwent RWD without stapedectomy. Median preoperative PTA-ABG was 31.3 dB. One patient (2 ears) had significant benefit with PTA-ABG improvements of 45 dB (left) and 30 dB (right). Two patients (2 ears) had a small improvement in PTA-ABG (2.5 dB, 1.3 dB), whereas 1 patient (1 ear) had worsening in PTA-ABG (2.5 dB). Patients suffering from severe mixed hearing loss due to advanced otosclerosis may benefit from formal RWD to facilitate hearing aid use as an alternative to cochlear implantation.
In many cultures, snakes are perceived in a markedly negative light, causing hostile attitudes, fear and phobias in people, which often leads to their persecution and killing. Studies on human perceptions of snakes are typically survey-based, while people's ability to detect them is usually conducted under controlled artificial conditions. Studies that simulate natural circumstances of human-snake encounters, however, remain scarce. The present study recreated natural human-snake encounters by conducting in situ experiments with viper models and carcasses, in order to assess tourists' ability to detect vipers (Vipera berus and Vipera ammodytes) and to evaluate their reactions. Most people did not detect the vipers when they were placed on the tourist paths, and almost none detected vipers positioned in the grass next to the paths. On the paths, adult vipers were detected significantly more often than juveniles. Most tourists showed interest and no signs of fear during their encounters with the vipers, while a very small number of people exhibited strong fear or aggressive behavior. Tourists were more likely to display no interest and moderate fear toward adult vipers than toward juveniles. Most participants were able either to correctly identify the species or at least recognize that the snake was venomous. These results demonstrate that this innovative approach provides valuable insights into different aspects of human-snake interactions and highlight the usefulness of snake models in such studies.
Autism Spectrum Disorder (ASD) has been linked to disturbance of the coordinated transcriptional mechanisms that govern neurogenesis, neuronal differentiation, and synaptic maturation in human cortical development. Nevertheless, the regulatory networks and cellular heterogeneity that underlie these processes are still poorly understood. Using an in vitro human cortical development dataset (GSE210960), single-cell RNA sequencing (scRNA-seq) and systems biology techniques were used to examine neurodevelopmental pathways associated with ASD. Different cellular populations representing neural progenitors and differentiated neuronal states were resolved by Seurat-based preprocessing and clustering, and developmental progressions from progenitor cells towards adult neuronal lineages were recreated using trajectory inference. Key biological processes linked to RNA splicing, energy consumption, and the formation of neural projections were found by differential expression and gene set enrichment analysis. Highly connected hub genes, such as RACK1 and NRXN1, which are essential for synaptic signalling and neuronal development and have been linked to an increased risk of ASD, were given priority in protein-protein interaction network analysis. Stable binding of tretinoin (all-trans-retinoic acid) to RACK1 was discovered by virtual drug screening, molecular docking, and molecular dynamics simulations. This was corroborated by favourable docking scores and persistent conformational stability across a 100 ns simulation. All things considered, these results offer a systems-level single-cell transcriptomic framework for locating potential molecular targets and neurodevelopmental pathways related to ASD.
This study examined and illustrated real-world risks of unintended patient-level data egress from Trusted Research Environments (TREs) and Secure Data Environments (SDEs), using synthetic data to recreate cases encountered in PIONEER, the HDR UK Hub in Acute Care. Synthetic datasets with demographics and NEWS2 vital signs were created using SciPy and NumPy for two fictitious populations. These datasets were transformed for machine-learning and embedded into various formats to simulate potential egress scenarios. Three worked examples include binary serialisation of data, binary serialisation of complex objects, and plain text mark-up reports. Initial screening of exported files included checking reported sizes. While absolute size alone cannot confirm patient-level data, unusually large files can signal the need for closer inspection. In several cases, this prompted manual review that uncovered sensitive information. File size is therefore a useful signal within a layered egress checking process, not a diagnostic measure. Standard tools like Python or R do not warn of hidden data, reinforcing the need for explicit egress policies and independent verification. Converting binary formats only works for recognized code libraries and requires ongoing maintenance. Manual inspection alongside automation remains essential to identify and remove embedded data. These cases highlight the complexities in identifying and preventing identifiable data egress from TREs. Key insights include clear guidance for researchers, the limitations of binary serialisation for egress due to security vulnerabilities, and the importance of plain-text data exports for ease of verification.
The extracellular matrix (ECM) provides a dynamic microenvironment that regulates cell proliferation, migration, and tissue remodeling during wound healing. However, replicating the structural and functional complexity and ECM heterogeneity of native skin ECM remains challenging with conventional single-material hydrogels. Recent advances in multimaterial 3D bioprinting have enabled the spatial integration of diverse biomaterials within a single construct. Lignocellulose has attracted increasing attention as a promising biomaterial for recreating key structural features of the native ECM because of its fibrous architecture, mechanical strength, and biocompatibility. This review offers a comprehensive and integrated perspective on the use of lignocellulose-based multimaterial printing to recreate ECM-mimicking architectures, an underexplored area at the intersection of biomaterials and biofabrication. The roles of cellulose, hemicellulose, and lignin in printability, scaffold stability, porosity, bioactivity, and wound-healing performance are discussed. Representative studies have demonstrated that lignocellulose-based multimaterial bioinks provide porous architectures that support cell adhesion, proliferation, and tissue regeneration. These benefits are accompanied by improved mechanical performance, as cellulose nanofibers exhibit elastic moduli exceeding 100 GPa, and lignin-containing hydrogels have achieved compressive moduli of up to 135 kPa. Such mechanical advantages make lignocellulosic materials particularly attractive for fabricating ECM-mimicking scaffolds that require long-term structural integrity. Finally, key design considerations and current limitations associated with lignocellulose-based multimaterial bioprinting are critically discussed. A framework for the rational design of lignocellulose-based multimaterial bioinks is presented, together with future directions toward gradient and adaptive scaffolds, smart wound dressings, and advanced wound-healing applications.
In cancer cells, septins assemble into enigmatic higher-order structures of 300-700 nanometers, including long needle-like filaments, thick perinuclear rings, and cytoplasmic bundles or aggregates. The absence of genetic or pharmacological tools to recapitulate these architectures in-vitro has impeded mechanistic studies of their formation, function, and therapeutic targeting. Here, first, determining the overexpression of septin-2 in epithelial ovarian cancer (EOC) and its association with increased mortalities and dependencies, we select SKOV-3 ovarian cancer cells as a tractable model in which septin supramolecular assemblies can be recreated in-vitro and interrogated. This system shows that the forchlorfenuron (FCF) analog UR214-9 remodels septin architecture, converting co-expressed human septin octamers (SEPT2-SEPT6-SEPT7-SEPT9-SEPT9-SEPT7-SEPT6-SEPT2) into large cytoplasmic aggregates. In parallel, transiently expressed SEPT2 is reorganized into septin-rich noodle-like filaments, perinuclear rings, and web-like networks encircling the nucleus upon UR214-9 treatment. Mechanistically, UR214-9 disrupts the incorporation of SEPT2, SEPT7, and SEPT9 into canonical septin hetero-octamers, resulting in assembly-defective or imperfect oligomers that preferentially reorganize into these aberrant higher-order structures. This aggregation likely prevents septin-2 migration during interphase-to-cleavage furrow transition in NRK-49F-SEPT2-EGFP homozygous cells and impacts SKOV-3 cytokinesis, cell proliferation, adhesion and invasion and migration while sparing ceramide transport to the Golgi, preserving ER and cis-Golgi structure. These effects manifested in reduced growth of ovarian, endometrial and breast cancer xenografts without attracting significant off-target engagements per the global transcriptomic analysis of JIMT1 breast cancer and PANC-1 pancreatic cells. UR214-9 treated animals showed observable safety in animals. Thus, a tool to recreate aberrant septin structures and identification of septins as a druggable cytoskeletal target for ovarian, endometrial, breast and pancreatic cancer by perturbing their hetero-octamerization assembly is presented. We provide a method to reconstruct the higher-order septin architecture observed in cancer cells, to study their assembly and functions. Intriguingly, cancer cells tolerate hetero-oligomeric septins lacking specific subunits, suggesting that compositionally deficient oligomers are not efficiently targeted for degradation, unlike unincorporated septin monomers in normal cells. This tolerance may enable accumulation of structurally aberrant septin complexes acquiring long-needles, rings or thick-aggregates in disease cells. We further show that septin oligomerization can be pharmacologically perturbed. By integrating structural, cellular, and energetic readouts using in-silico techniques, we establish a quantitative framework for septin-targeted modulation, generating UR214-9 as a new chemotype that disrupts septin oligomeric assembly via preventing incorporation of SEPT2/7/9, into canonical hetero-octamers, causes defects in cytokinesis, altered cell migration, viability, and remodels septin-actin architectures, ultimately impairing tumor cell growth. Thus, pharmacological targeting of septin assembly represents a tractable strategy to perturb septin-dependent cellular processes in cancer and neurodegenerative diseases with reported septin dysregulation.
Stress granules (SGs) are biomolecular condensates that form transiently in the cytosol of mammalian cells in response to stress. Dysregulation of their assembly or disassembly is implicated in human age-related diseases. While phase separation is the key process underlying SG assembly, understanding of their function, composition and regulation in response to physiological stimuli is limited. This knowledge gap reflects the challenge of gaining comprehensive and quantitative insights into the dynamic regulation of the complex composition of SGs at the single-cell level. Here we present an emulsion-based microfluidics method to overcome this limitation. "Cytosolic extracts-in-oil droplets" (CEODs) recreate a confined active cytosolic milieu that undergoes phase separation and SG formation in response to stress under physiological conditions. This approach led to the discovery of seven previously unrecognised SG components involved in signalling pathways. CEODs provide a versatile and cost-effective screening platform for future mechanistic and therapeutic studies.
Meiosis is a key stage in the sexual reproduction of eukaryotes. It ensures the continuity of genetic information from generation to generation, while also generating the necessary genetic diversity for the survival and evolution of species. Meiotic progression is often compromised in hybrids between related subspecies, resulting in hybrid sterility and irreversible reproductive isolation. However, most genetic studies to date have not focused on the meiotic phenotypes of hybrid sterility and their molecular mechanisms. This review examines the genetic architecture, as well as the meiotic and molecular phenotypes, of hybrid sterility in the house mouse (Mus musculus) and other mammals. House mice subspecies provide the most widely understood mammalian model of hybrid sterility because of their recent evolutionary divergence, powerful genetic tools and comprehensive cytology of individual meiotic stages. We emphasize the potential impact of meiotic surveillance mechanisms, checkpoint pathways, particularly those leading to the meiotic sex chromosome inactivation and we draw parallels between intraspecific genic and chromosomal sterility and intersubspecific hybrid sterility. Finally, we review the Prdm9-Mir465 incompatibility system, the only vertebrate hybrid sterility model for which the three major genetic components necessary and sufficient to recreate the hybrid sterility genome have been identified. This three-part genetic architecture links Prdm9-dependent meiotic recombination hotspot activation, heterosubspecific homolog pairing, and microRNA-mediated meiotic checkpoint regulation to spermatogenic arrest and male sterility. MiR-465 is apparently the first microRNA which functions as a guardian of the pachytene checkpoint.
Fatty acid synthase (FASN) is a key rate-limited, dimeric multi-enzyme complex in the de novo lipogenesis pathway. Each FASN monomer contains seven catalytic domains, which coordinate the stepwise conversion of acetyl-CoA into fatty acids. While FASN has been extensively studied in cultured cells, particularly for its oncogenic role, its functions in the germline and early embryonic development remain elusive. A major challenge is that the FASN dysfunction typically causes embryonic lethality in animal models, which complicates detailed functional analysis and the identification of compensatory genetic interactors during development. To overcome this limitation and identify novel genetic suppressors of the FASN gene, we utilized a temperature-sensitive allele, fasn-1(g43ts) (A1424T), in the genetically tractable model Caenorhabditis elegans, to conduct unbiased forward genetic screens. We isolated 22 suppressor lines that significantly restored embryonic viability in the fasn-1(g43ts) mutant at the non-permissive temperature. Using a combination of MIP-MAP genomic mapping and a customized bioinformatic pipeline, we identified six mutations in the ptr-6 gene, which encodes a protein containing a patched domain associated with the Hedgehog-like signaling pathway. To validate this genetic suppression, we recreated one of the loss-of-function mutations, ptr-6[W701*], in the fasn-1(g43ts) background using CRISPR/Cas9 gene editing. Notably, ptr-6[W701*] robustly rescued the embryonic lethality and permeability defects caused by fasn-1 loss-of-function. Taken together, our findings expand the genetic regulatory network of fatty acid synthase during early embryogenesis and highlight ptr-6 and Hedgehog-like signaling pathway as potential genetic modifiers of FASN-associated developmental and metabolic disorders.
The Low Vision Assessment in Virtual Reality project aims to create performance assessments of activities of daily living for a broad low vision population in virtual reality. In this study, our goal is to validate representative virtual reality activities against matching real-world activities to create standardized activities of daily living in virtual reality. Experiments were conducted in a rehabilitation space with a kitchen and living room, which was recreated in virtual reality with photorealistic rendering. We created 25 activities in Unity based on our previously developed visual functioning questionnaire and performed a validation study.
Neural mass models (NMMs) are often used to help understand the circuitry that underpins observed brain dynamics in basic and clinical research. A key step is to fuse models with data so that model parameter values can be inferred for a given data set-a process called model fitting or model calibration. This can shed light on putative physiological mechanisms underlying the observed signals. Calibration is notoriously challenging in biology since models are often non-identifiable, high-dimensional, and nonlinear. Established methods such as dynamic causal modelling (DCM) circumvent some of these issues, for example, by incorporating prior information and employing fast local search methods in the space of feasible parameter values ("parameter space"). However, it is pertinent to better understand the potential limitations of these methods so that we can increase our confidence in the use of models to interpret brain activity, and to develop new approaches as required. Here, we use tools from dynamical systems theory to illustrate some of the complexities of model calibration in an archetypal NMM. We use this information to motivate the use of calibration methods that work across large regions of parameter space, rather than focusing on informative priors or localised search methods. We subsequently evaluate the performance of approximate Bayesian computation (ABC) and evolutionary search metaheuristics (ESMs) for mapping feasible sets of parameters for which an NMM can recreate electroencephalographic recordings during an eyes-closed resting state. Our results demonstrate the superiority of ESMs in terms of computational efficiency and accuracy. Furthermore, we elucidate potential reasons why ESMs are able to perform better than ABC, that is, that they are less susceptible to biases induced by the complexity of underlying cost landscapes. These results highlight the importance of incorporating ESMs in future efforts to model brain dynamics.
The lymphatic system is central to immune surveillance, coordinating antigen transport, and immune cell trafficking. While in vivo studies have revealed key aspects of lymphatic and lymph node biology, their complexity has motivated the development of in vitro platforms that enable controlled interrogation of specific immune processes. This review presents a tiered framework for organizing engineered lymphatic and lymph node models based on increasing architectural and functional complexity. Tier 1 models employ two-dimensional lymphatic endothelial monolayers to investigate immune cell docking, chemokine presentation, and junctional regulation. Tier 2 systems incorporate three-dimensional matrices and stromal organization to recreate lymphoid microenvironments, including lymph node scaffolds and immune organoids that support lymphocyte positioning and antigen handling under static conditions. Tier 3 platforms integrate microfluidic perfusion and compartmentalization to model lymphatic transport, flow-dependent endothelial behavior, and immune trafficking in dynamic lymphatic systems. Collectively, these models define the experimental landscape of in vitro lymphatic immunity.
B-cell acute lymphoblastic leukemia (B-ALL) disrupts the architecture and function of the bone marrow niche. However, current in vitro and in vivo models fail to fully capture the spatial, biochemical, and mechanical complexity of the native microenvironment. Here, we present a biomimetic bone marrow on-a-chip that integrates organ-on-a-chip technology, 3D hydrogel culture, and computational modeling to recreate the perivascular, central, and endosteal niches of human bone marrow. The Computational Fluid Dynamics (CFD) was used to guide the design and operation of the microdevice by predicting physiological interstitial flow within the culture system, enabling consistent mechanical stimuli as in vivo under conditions compatible with bone marrow physiology. The microdevice was fabricated using high-resolution 3D printing and soft lithography, and incorporates phaseguide structures for hydrogel confinement, the establishment of three distinct niches and continuous perfusion. Co-cultures of endothelial, stromal, osteoblast, and leukemic cells were maintained in a type I collagen matrix under dynamic conditions. The platform supported high cell viability and enabled compartmentalized spatial organization of multicellular co-cultures. The presence of leukemic cells was associated with changes in soluble signaling molecules within the microenvironment, including increased levels of cytokines, chemokines, and growth factors such as IL-10, IL-13, TNF-α, CCL2, CCL3, CCL5, FGF, G-CSF, and GM-CSF. These patterns are consistent with signaling processes linked to immunoregulation, leukemic supportive signaling, and therapeutic resistance in B-ALL. Together, these findings indicate that the bone-marrow-on-a-chip captures relevant aspects of niche-associated signaling and provides a versatile platform for investigating leukemia microenvironment interactions, with potential in drug screening and preclinical model development.
Minimally invasive ventral hernia repair has traditionally been performed using intraperitoneal onlay mesh (IPOM). Although effective, IPOM places mesh within the peritoneal cavity, with potential risks related to adhesions and mesh-bowel interaction. Enhanced-view totally extraperitoneal (eTEP) repair recreates the retromuscular (Rives-Stoppa) plane using a laparoscopic approach and may reduce these concerns. A prospective, observational study was conducted on n = 24 adult patients undergoing eTEP retrorectus ventral hernia repair. Perioperative outcomes, post-operative pain (Visual Analogue Scale), complications, quality of life (Carolinas Comfort Scale; HerQLes) and abdominal wall function (double-leg lowering and trunk-raising tests) were assessed at 7 days, 1 month and 3 months. The mean age was 45.6 ± 13.7 years; 54.2% were women. Mean operative time was 167.0 ± 28.7 min; no intraoperative visceral or vascular injury occurred. Surgical-site infection and seroma occurred in one patient each (4.2%) at 7 days and resolved by 1 month. Pain peaked in the early post-operative period and declined significantly over the follow-up (repeated-measures analysis of variance P < 0.001). Both CCS and HerQLes scores improved significantly at 1 and 3 months ( P < 0.001), with parallel improvement in abdominal wall function tests ( P < 0.001). In this early experience, eTEP retrorectus repair was feasible and safe with low early morbidity, significant improvement in patient-reported outcomes and improved abdominal wall function over 3 months. Larger comparative studies with longer follow-up are warranted.
Extensive upper-limb soft-tissue defects may exceed the surface area achievable with conventional free flaps, making reconstruction challenging when durable coverage and functional preservation are required. We describe a novel reconstructive strategy to extend soft-tissue coverage based on secondary flap-to-flap neovascularization in which a pedicled flap achieves secondary vascular independence through neovascularization from the free flap skin paddle via the subdermal vascular plexus, thereby enabling delayed division without additional microsurgical anastomoses. A 64-year-old man developed necrotizing fasciitis of the right upper limb following an insect bite. After repeated surgical debridements, a massive circumferential forearm defect extending to the elbow was associated with extensive tissue loss of the dorsal hand, first web space, and palm. A 45 × 11 cm chimeric anterolateral thigh-tensor fascia latae (ALT-TFL) free flap was harvested and anastomosed to the radial vessels, providing stable coverage of exposed extensor tendons and neurovascular structures. An ipsilateral pedicled 20 × 15 cm groin flap was inset onto the ALT skin paddle and subsequently divided, defatted, and wrapped around the thumb to recreate the first web space and resurface the palm. At 18-month follow-up, soft-tissue coverage remained stable, with complete flap survival, no recurrence of infection, and good functional recovery. Unlike sequential or conventional free-flap reconstruction, this approach does not require additional arterial inflow or flow-through anastomoses, relying instead on secondary flap-to-flap neovascularization. It may therefore represent a relevant strategy to extend reconstructive coverage beyond conventional flap dimensions in extensive upper-limb defects.
Respiratory viral infections pose persistent global health threats, yet traditionalin vitroand animal models inadequately recapitulate human tissue microenvironments. Organ-on-a-chip technology integrates microfluidic engineering with cell biology to recreate three-dimensional architectures, mechanical forces, and multicellular interactions of the human respiratory system. This review systematically summarizes recent advances in organ-on-a-chip platforms for modeling respiratory viral infections and host immune responses. We highlight their unique capabilities in simulating alveolar-capillary barriers, lymphoid follicle formation, and multi-organ axes including lung-brain and gut-lung communication. Furthermore, we discuss applications in antiviral drug screening, vaccine evaluation, and personalized medicine, while addressing current challenges and future directions toward standardized, multi-organ integrated, and intelligently monitored systems.
Enterovirus D68 (EV-D68) is a non-polio enterovirus that can cause a polio-like paralysis condition, acute flaccid myelitis (AFM). EV-D68-associated AFM cases waned in the US after 2018, and the reasons for this are unknown. It has recently been demonstrated that EV-D68 containing point mutations in viral structural proteins VP1 and VP3 resulted in decreased paralysis in different neonatal mouse models. However, phenotypes of these mutations in a human multicellular central nervous system (CNS) model are unknown. We hypothesize that mutations in VP1 and VP3 will similarly direct neurotropism in human spinal cord organoids (hSCOs). To investigate this, we recreated viruses with mutations in VP3 (I88V) or VP1 (L1I/N2D/T98A/E283K or L1P/V148A/K282R) and infected hSCOs. We found that VP3 I88V and VP1 L1I/N2D/T98A/E283K resulted in decreased titer and viral protein staining, consistent with attenuated neurovirulence in previously published murine models. We also found through immunofluorescence that VP1 L1P/V148/K282R mutations altered cellular tropism, primarily infecting glial cells rather than neuronal cells. When these mutations were combined, their effects on neurotropism were not additive. Sequence analysis of recently circulating EV-D68 strains reveals that VP3 I88 and VP1 E283 have remained the dominant amino acid residues since 2014, whereas VP1 sites 1, 2, and 98 have higher population diversity, indicating that these residues may be contributing to newly reduced neurovirulence after 2018.
This paper attempts to recreate and reconstruct the process of 'translation-transformation-application' of arsenical knowledge in the late Qing Dynasty by examining the four representative medical translations: An Outline of Western Medicine (Xi Yi Lue Lun), Explanations of Western Medicine (Xi Yi Lue Shi), Universal Prescriptions (Wan Guo Yao Fang), and A Compendium of Western Drugs (Xi Yao Da Cheng). It was found that in terms of nomenclature, the early coexistence of heterogeneous vernacular names such as Xin () and Xin Shi () underwent evolution and adjustment within medical texts, eventually coexisting with chemical nomenclature such as Shen (、). This resulted in a hybrid terminology system that integrated traditional experiences with modern chemical elements. In terms of dosage forms and quantity, arsenicals expanded from a single medicinal liquor into five major categories - solution, ointments, solids, pastes, and pills. This evolution presented a trajectory from an early phase of 'extensive collection' to a later phase of 'simplified consolidation' based on chemical classification. In terms of chemistry and toxicology, the translated works helped to establish a quantifiable and verifiable framework of modern pharmacology for substances long regarded as 'poisons' initially by successively introduced experimental detection techniques (such as the Marsh test), valence-based classifications, and semi-sinicized chemical formulas. In terms of authoritative citation, translators attempted to establish a chemical basis for arsenicals, facilitating their transformation from empirical poisons into 'scientific drugs' by drawing extensively on experimental data from European and American chemists and physicians. This study argues that the transfer of Western arsenical knowledge in the late Qing Dynasty was a process of continuous communication between translators and the medical community by introducing the knowledge and local practice rather than a simple linear process of scientization. 本文以《西医略论》《西医略释》《万国药方》《西药大成》4种代表性医学译著为核心史料，重构晚清砷剂知识的“译—化—用”全过程。研究发现：命名上，由早期俗名杂陈“信”“信石”，经医学文本的沿革与调整，最终与化学命名“鉮”“信金”并置，形成兼容传统经验与现代化学元素的复合术语体系；剂型与数量上，从单一药酒扩展至药水、油膏、固体、糊剂、丸剂5大类，呈现出从早期广搜博采，向后期基于化学分类的精简归并转变；化学与毒理上，译本先后引入实验检测技术（如马尔施试验）、化合价分类与类汉字化学式，首次将“毒药”确立了可量化、可验证的近代药物学框架；权威引证上，译者通过大量援引欧美化学家、医师的实验数据，为砷剂确立起化学依据，促成其由经验毒药向“科学药物”转型。本研究以期证明，晚清西药砷剂的知识迁移并非线性科学化，而是翻译者与医学界在知识引进与本土实践中不断磨合的过程。.
The anatomical complexity and distinctive tissue environment of the human oral cavity pose major challenges to modeling oral infection and host-microbe interactions in preclinical laboratory settings. Here we present a bioengineered oral microphysiological system comprising vascularized human gingival tissue integrated with tooth analogs that together recreate a functional unit of the human oral cavity. We incorporated Streptococcus mutans and Candida albicans into this system to model cross-kingdom biofilm formation, microbial dissemination, and host-microbial interactions at the gingival-tooth interface. Single-cell RNA sequencing and global metabolomics analysis revealed that fungal colonization induces epithelial-to-mesenchymal transition associated with distinct transcriptional and metabolic signatures. Our platform also allowed us to simulate SARS-CoV-2 infection and examine gingival responses to live-virus challenge. Finally, we integrated the engineered gingival tissue with controlled human saliva flow to show that hyposalivation potentiates the pathogenic capacity of fungal infection. This work demonstrates the potential of oral microphysiological systems as an experimental platform for in vitro modeling and mechanistic investigation of host-microbe interactions under controlled, human-relevant conditions.
Social determinants of health (SDH), non-medical factors that shape health and care access, play a critical role in perioperative safety and surgical outcomes. However, anaesthesiology residency programmes often lack structured training on communicating about and addressing SDH during routine clinical encounters. We developed a simulation-based curriculum to enhance anaesthesiology trainees' preparedness in recognising and responding to SDH-related challenges in perioperative care. An educational intervention consisting of three simulated perioperative case scenarios was integrated into an existing residency training course. Standardised patients were used to recreate realistic social and clinical challenges encountered in preoperative clinic, obstetric and paediatric settings. Sessions were followed by facilitated debriefings including the acting resident, observing peers, and a simulation faculty member to reflect on performance and key learning points. Post-simulation surveys assessed residents' perceived confidence, communication skills and awareness of institutional support resources related to SDH. Quantitative responses were summarised using descriptive statistics, and open-ended items elicited qualitative feedback. 42 anaesthesiology residents participated in this pilot. Following the intervention, residents reported increased confidence engaging patients and caregivers in discussions about social needs, improved familiarity with resource pathways such as social work and care coordination, and improved preparedness for sensitive conversations. Participants described the scenarios as authentic, relevant to clinical practice and valuable for observing peer communication approaches. This pilot project suggests that simulation may be a feasible and acceptable approach for introducing SDH-focused communication training in anaesthesiology education. Integrating realistic scenarios into perioperative curricula may help residents develop skills needed to identify social barriers and collaborate with interdisciplinary partners to promote equitable care.