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.

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*

Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Objective To analyze the effect of Xiaozhi Decoction in the treatment of hyperlipidemiain different classification of physical constitution in TCM.Methods We screened 206 patients with Hyperlipidemia in our hospital and had been treated with drugs during May 2020 to March 2023.Totally 103 patients in the TCM group were treated with Xiaozhi Decoction,103 patients in the western medicine group were treated with atorvastatin.Selected total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and liver transaminase before and after a period of treatment.The non-high-density lipoprotein cholesterol(non-HDL-C)will be calculated,too.Results In the Phlegm-Dampness constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,TG and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in TC,LDL-C,non-HDL-C(P<0.05).In the Qi-Deficiency constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in non-HDL-C(P<0.05).In the Blood-Stasis constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the western medicine group only(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).In the Yin-Yang Harmony constitution,TC and non-HDL-C decreased significantly both in the TCM group(P<0.05).TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).Conclusion Xiaozhi Decoction is superior to the the atorvastatin in the treatment of hyperlipidemia for the Phlegm-Dampness constitution and Qi-deficiency constitution groups.But it is not superior to the atorvastatin in the treatment of hyperlipidemia for the Blood-Stasis constitution and Yin-Yang Harmony constitution groups.

Zinc oxide nanowires were hydrothermally synthesized on the surface of an Au cylindrical spiral formed by manually spiraling an Au fiber around an optical fiber core, glucose oxidase was immobilized on these nanowires by physical adsorption, and then a spirally hierarchical structure-based glucose enzymatic electrode was obtained. The surface morphologies of the spirally hierarchical structures and corresponding enzymatic electrodes were extracted, and the electrochemical performances of the enzymatic electrodes were characterized. It was concluded that the synthesizing parameters of zinc oxide nanowires significantly affected the surface morphologies and glucose oxidase immobilization on the spirally hierarchical structures, and further the performances of related glucose sensors. With Zn2﹢concentration of the growth solution set at 25 mmol/L, the roughness of surface morphology was determined to be 0. 10 μm and correlation length 0. 29 μm, resulting in a better immobilization of glucose oxidase upon zinc oxide nanowires. In this case the sensitivity of the glucose sensor was determined to be 2. 15 μA/(mmol/L·cm2), the linear range was 0-4. 50 mmol/L, the low detection limit was 9. 20 μmol/L and Michaelis-Menten constant was 3. 68 mmol/L. The results not only benefit the batch production of the spirally hierarchical structure-based enzymatic electrodes, but also significantly improve the performances of the glucose sensors.