The intricate anatomical architecture and complex dynamic physiological barriers of the eye severely restrict the intraocular bioavailability of ophthalmic drugs. The limited absorption efficiency of conventional eye drops(<5%)and the highly invasive nature of intravitreal injections remain persistent bottlenecks in ophthalmic therapeutics. Driven by the convergence of materials science and biomedical engineering, intelligent stimuli-responsive drug delivery systems offer revolutionary strategies to overcome these physiological barriers and achieve spatiotemporally controlled drug release. These systems leverage specific recognition and response capabilities targeted at pathological microenvironments or exogenous physical fields. This article systematically reviews recent advances in this domain, providing an in-depth analysis of the physicochemical mechanisms underlying various stimuli-responsive carriers from the perspectives of polymer phase transition thermodynamics and chemical bond cleavage kinetics. By synthesizing preclinical and clinical research data on major ocular diseases, including glaucoma, age-related macular degeneration, and intraocular infections, the significant advantages of these intelligent systems were demonstrated. Highlighted benefits include prolonged ocular surface retention, biomarker-triggered on-demand release, and minimized systemic toxicity. Finally, this review critically analyzes the challenges of translating these complex formulations to the clinic, specifically regarding sterile scale-up manufacturing and regulatory approval pathways, while providing perspectives on future development.

Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications. In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner. However, existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes, thereby hindering a comprehensive understanding of their interactions. Here, we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria, respectively. Using a key oral pathobiont, Fusobacterium nucleatum, as the primary test bed, we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes. Compared to conventional models, this system enhanced bacterial invasion, elevated intracellular bacterial loads, and elicited more robust host pro-inflammatory responses, including increased secretion of CXCL10, IL-6, and IL-8. In addition, the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens. Finally, we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont, Porphyromonas gingivalis. These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics, offering a physiologically relevant approach to advance oral and systemic health research.
Coculture Techniques/methods* ; Humans ; Fusobacterium nucleatum/physiology* ; Gingiva/microbiology* ; Keratinocytes/microbiology* ; Host Microbial Interactions ; Mouth/microbiology* ; Host-Pathogen Interactions ; Epithelial Cells/microbiology* ; Cells, Cultured ; Porphyromonas gingivalis

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Major depressive disorder (MDD) is a common mental disorder characterized by long-term low mood, anhedonia, and may even lead to suicidal behavior. The development and progression of MDD involves a range of pathological alterations in the central nervous system, including dysfunction of synaptic transmission, hyper-activation of neuroinflammation, and diminished neurogenesis. The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in brain regions associated with depression, and can regulate physiological activities such as neuroinflammation, neurogenesis, and synaptic transmission efficacy. Hence, the TRPV1 channel should be implicated in the pathogenesis of depression and be considered as a promising candidate for antidepressant treatment. This paper provides an overview of the structure and function of TRPV1 channel, with a focus on elucidating the potential mechanism of action of TRPV1 channel in depression, and explores its research trajectory and development prospects in the context of depression therapy.

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Major depressive disorder (MDD) is a common mental disorder characterized by long-term low mood, anhedonia, and may even lead to suicidal behavior. The development and progression of MDD involves a range of pathological alterations in the central nervous system, including dysfunction of synaptic transmission, hyper-activation of neuroinflammation, and diminished neurogenesis. The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in brain regions associated with depression, and can regulate physiological activities such as neuroinflammation, neurogenesis, and synaptic transmission efficacy. Hence, the TRPV1 channel should be implicated in the pathogenesis of depression and be considered as a promising candidate for antidepressant treatment. This paper provides an overview of the structure and function of TRPV1 channel, with a focus on elucidating the potential mechanism of action of TRPV1 channel in depression, and explores its research trajectory and development prospects in the context of depression therapy.

Objective:To evaluate the clinical effect of orbital fat releasing and repositioning through supra-suborbicularis oculi fat (SOOF) in lower eyelid blepharoplasty.Methods:The authors retrospectively analyzed the clinical data of patients who received lower eyelid blepharoplasty in the Department of Plastic Surgery, Beijing Tsinghua Changgung Hospital from January 2017 to January 2023. Lower eyelid blepharoplasty with orbital fat releasing and repositioning through supra-SOOF was performed. The tear trough ligament and orbicularis retaining ligament were released between the orbicularis oculi muscle and SOOF via skin approach. Orbital septal fat was released to this space, lateral fat flap was fixed to the SOOF capsule, medial fat flap was fixed to the superficial fascia of the levator labii superioris muscle, orbital septum was repositioned, and lateral canthus was suspended. After the operation, lower eyelid morphology and complications were evaluated.Results:A total of 58 patients were enrolled, including 8 males and 50 females with the age of (49.8 ± 10.4) years (32 to 70 years). All patients had obvious lower eyelid bags on both sides, combining the tear trough deformity and (or) palabromalar groove. Fifty-seven patients were followed up for (29.1 ± 16.9) months (6-67 months). All patients were satisfied with the operation. The appearance of lower eyelid was greatly improved, with elimination of fat prominence and tear trough deformity. Mild lower eyelid ectropion was observed two cases 1 week after the operation, and were relieved by moderate massage 2 weeks postoperatively. In one case, mild lower eyelid retraction was observed 1 month postoperatively, with no complaint of discomfort or further treatments. Bulbar conjunctival hemorrhage occurred in 1 case and recovered without further interventions.Conclusion:Lower eyelid blepharoplasty with orbital fat releasing and reposting through supra-SOOF can effectively release the tear trough ligament and the orbicularis retaining ligament, with stronger fat fixation and less surgical difficulty. After the operation, eyelid contour was flat and tight with fewer complications and higher patient satisfaction.

Objective To investigate the value of contrast-enhanced ultrasound(CEUS)combined with shear wave elastography(SWE)in the diagnosis of liver tumors.Methods This study was conducted according to the PRISMA guideline,with a PROSPERO registration number of CRD42023491288.PubMed,Embase,the Cochrane Library,CNKI,VIP,and Wanfang Data were searched for articles on CEUS combined with SWE in the diagnosis of liver tumors published from January 2000 to October 2023,and a total of 12 articles were included,with 1 328 patients in total.The QUADAS-2 tool was used to assess the quality of the articles included.Stata 15.0 software was used to calculate pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio,and heterogeneity.The summary receiver operating characteristic(SROC)curve was plotted,and the area under the SROC curve(AUC)was calculated.Results There were 1 457 lesions for the patients included,among whom there were 764 malignant lesions and 693 benign lesions,with a positive rate of 52.44%and a negative rate of 47.56%.Calculations obtained a pooled sensitivity of 0.94(95%confidence interval[CI]:0.91—0.96),a specificity of 0.92(95%CI:0.87—0.95),a positive likelihood ratio of 12.00(95%CI:7.40—19.40),a negative likelihood ratio of 0.06(95%CI:0.04—0.10),and a diagnostic odds ratio of 191(95%CI:87—417).The tests for heterogeneity showed Q=54.78,df=11.00,P<0.001,and I2=79.92%(95%CI:69.18%—90.66%),with an AUC of 0.98.Conclusion CEUS combined with SWE has a relatively high diagnostic value for benign and malignant liver tumors and thus holds promise for clinical application.