Breast cancer-targeted therapy and doxorubicin multidrug resistance are reversed via macrophage membrane-camouflaged liposomes.

Medication therapy is the primary treatment for breast cancer. However, many patients develop multidrug resistance (MDR), which complicates treatment and reduces its effectiveness. To address this, a novel approach was developed by combining the chemotherapeutic drug, doxorubicin (DOX), and the MDR reversal agent, tetrandrine (Tet), within degradable liposomes covered with macrophage membranes to create MM@DOX-Tet nanoparticles (NPs). These NPs effectively reversed MDR in breast cancer cells, with an eight-fold increase compared to a DOX-Tet mixture and a three-fold increase compared to DOX-Tet NPs alone. When modified with macrophage membranes, these NPs enhance tumor targeting and cell uptake, thereby significantly reducing cancer cell viability. In animal studies, MM@DOX-Tet NPs outperformed single and conventional therapies, efficiently targeted tumors, and suppressed tumor growth. Furthermore, dual-layer encapsulation prevents drug leakage and increases drug accumulation at the tumor sites. Our study introduces MM@DOX-Tet NPs as a potential nano-drug system for overcoming MDR during breast cancer treatment.

Inducing disulfidptosis in tumors:potential pathways and significance.

Regulated cell death (RCD) is crucial for the elimination of abnormal cells. In recent years, strategies aimed at inducing RCD, particularly apoptosis, have become increasingly important in cancer therapy. However, the ability of tumor cells to evade apoptosis has led to treatment resistance and relapse, prompting extensive research into alternative death processes in cancer cells. A recent study identified a novel form of RCD known as disulfidptosis, which is linked to disulfide stress. Cancer cells import cystine from the extracellular environment via solute carrier family 7 member 11 (SLC7A11) and convert it to cysteine using nicotinamide adenine dinucleotide phosphate (NADPH). When NADPH is deficient or its utilization is impaired, cystine accumulates, leading to the formation of disulfide bonds in the actin cytoskeleton, triggering disulfidptosis. Disulfidptosis reveals a metabolic vulnerability in tumors, offering new insights into cancer therapy strategies. This review provides a detailed overview of the mechanisms underlying disulfidptosis, the current research progress, and limitations. It also highlights innovative strategies for inducing disulfidptosis and explores the potential of combining these approaches with traditional cancer therapies, particularly immunotherapy, to expedite clinical translation.

Unraveling the drivers of inequality in primary health-care resource distribution: Evidence from Guangzhou, China.

Background: Primary health-care (PHC) resource plays a critical role in addressing challenges related to healthcare accessibility and costs, as well as implementing a graded diagnosis and treatment system. This study aims to analyze the extent and components of inequality in PHC resource allocation in Guangzhou. Methods: By utilizing data from the Annual Report on Healthcare Institutions for community and township health centers in Guangzhou from 2012 to 2020, this paper analyses the distribution of human, material and financial resources. It examines inequities in health resource allocation using the Gini coefficient. Additionally, it investigates the internal structure of overall inequality through the two-stage nested Theil decomposition method and explores the influencing mechanisms of inequality using the concentration index decomposition method. Results: The findings indicate that between 2012 and 2020, except for beds in 2018 and 2019, the Gini coefficients for resource allocation relative to population size remained below 0.3. Moreover, the Gini coefficient for geographical area ranged from 0.1228 to 0.3481. The two-stage nested Theil decomposition results reveal that within-district disparity contributes the most to the overall inequality, exceeding 46 %. The Concentration indexes show negative values, and the decomposition analysis highlights the significant contribution of the number of individuals served (over 72 %) to the inequality in health resource allocation. Conclusion: At the administrative district level, the allocation of PHC resources in Guangzhou demonstrates overall equity, with within-district inequality identified as the primary contributor to the overall inequality. The distribution of PHC resources in Guangzhou follows a pro-poor pattern. The key factors influencing equity enhancement in PHC resource allocation in Guangzhou include the number of individuals served, the presence of township health centers among institution types, the number of hospital admissions per capita, and the proportion of children aged 0-3.

Molecular design and functional outcomes of RTP and TADF traits in isomers.

This study reports the synthesis and photophysical analysis of three isomeric compounds, namely 3Fmo, 3Fmm, and 3Fmp, which were engineered using carbazole as the electron donor, phthalimide as the electron acceptor, and a benzene ring as the bridging moiety. Among these, 3Fmm was distinguished by its ability to exhibit immediate room-temperature white phosphorescence following the cessation of UV illumination, whereas 3Fmo and 3Fmp demonstrated TADF properties. Crystallographic analysis revealed unique intermolecular π-π stacking interactions within 3Fmm, absent in the other two isomers. Advanced TD-DFT computations indicated that such π-π stacking in 3Fmm not only facilitates intersystem crossing but also effectively reduces the free volume within the crystal, leading to a decrease in non-radiative transitions. These molecular interactions promote the manifestation of room-temperature phosphorescence. Furthermore, leveraging the superior luminescent properties of 3Fmo, the compound was successfully utilized in cellular imaging, where it achieved excellent imaging results, showcasing its potential for biomedical applications.

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation.

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Aberrant individual large-scale functional network connectivity and topology in chronic insomnia disorder with and without depression.

Insomnia is increasingly prevalent with significant associations with depression. Delineating specific neural circuits for chronic insomnia disorder (CID) with and without depressive symptoms is fundamental to develop precision diagnosis and treatment. In this study, we examine static, dynamic and network topology changes of individual large-scale functional network for CID with (CID-D) and without depression to reveal their specific neural underpinnings. Seventeen individual-specific functional brain networks are obtained using a regularized nonnegative matrix factorization technique. Disorders-shared and -specific differences in static and dynamic large-scale functional network connectivities within or between the cognitive control network, dorsal attention network, visual network, limbic network, and default mode network are found for CID and CID-D. Additionally, CID and CID-D groups showed compromised network topological architecture including reduced small-world properties, clustering coefficients and modularity indicating decreased network efficiency and impaired functional segregation. Moreover, the altered neuroimaging indices show significant associations with clinical manifestations and could serve as effective neuromarkers to distinguish among healthy controls, CID and CID-D. Taken together, these findings provide novel insights into the neural basis of CID and CID-D, which may facilitate developing new diagnostic and therapeutic approaches.

Microbial inoculants using spent mushroom substrates as carriers improve soil multifunctionality and plant growth by changing soil microbial community structure.

Peat is typically used as a carrier for microbial inoculants; however, due to its non-renewable nature alternatives need to be identified as reliable and renewable carriers for mineral-solubilizing inoculants. In pot experiments, solid microbial inoculants were comprised of peat (P), biochar (BC), and spent mushroom substrates (SMS) using Medicago sativa L. as experimental materials, and the purpose of this study is to assess the effect of solid microbial inoculants on soil multifunctionality and plant growth. The results revealed that the SMS microbial inoculant had the greatest positive impact on plant biomass and significantly stimulated soil multifunctionality which is typically managed or assessed based on various soil functions or processes that are crucial for sustaining productivity, in contrast to the peat microbial inoculant, particularly at a supply level of 100 g/pot. There was no significant correlation between soil multifunctionality and bacterial/fungal microbial diversity. However, according to the co-occurrence network of bacteria and fungi, soil multifunctionality was intimately correlated with the biodiversity of the main ecological clusters (modules) of bacteria and fungi, rather than to the entire soil microbial community structure. The keystone species of module hubs and connectors play critical roles in maintaining the stability of ecological clusters of microbial co-occurrence networks and linkages between ecological clusters. Soil pH is a major predictor of changes in plant biomass, and leads to changes therein by affecting the major ecological clusters of bacterial and fungal co-occurrence networks. These results suggested that SMS may serve as a good alternative to peat as a carrier of mineral-solubilizing microorganisms to maintain soil multifunctionality and promote plant growth.

Abnormal large-scale resting-state functional networks in anti-N-methyl-D-aspartate receptor encephalitis.

Background: Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks. Methods: Resting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA). Results: Compared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN). Conclusion: Patients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

Electroacupuncture alleviates sciatic nerve injury and inhibits autophagy in rats.

BACKGROUND: Sciatic nerve injury is a common form of peripheral nerve injury (PNI). It has been suggested that electroacupuncture (EA) stimulation at GB30 and ST36 can improve nerve dysfunction post-PNI. Autophagy is an important factor in the regeneration of sciatic nerves and recovery of motor function. Therefore, we investigated the biological effects of EA and examined whether these were mediated by autophagy in sciatic nerve injury. METHODS: Mechanical clamping of the sciatic nerve in Sprague-Dawley rats was performed to establish an experimental model of sciatic nerve injury. EA stimulation was administered once daily for 15 min for seven consecutive days beginning 1 week after successful modeling. The recovery of sciatic nerve function was examined via the sciatic functional index (SFI) test. Morphometric analysis was conducted by staining nerve samples with toluidine blue. Autophagy-associated protein levels were measured via Western blotting. RESULTS: EA stimulation at GB30 and ST36 significantly increased the number of myelinated fibers, axonal and fiber diameters, and the thickness of the myelin sheath in our rat model of sciatic nerve injury. In addition, EA stimulation greatly facilitated nerve regeneration following sciatic nerve injury. Moreover, sciatic nerve injury-induced autophagy was inhibited by EA stimulation. CONCLUSION: EA facilitates recovery of injured sciatic nerves and inhibits autophagy in a rat model.

Ultra-microstructure analysis and model development of bamboo fiber cell walls.

Bamboo fiber cell walls are crucial mechanical load-bearing units in plants, significantly influencing their physical and mechanical properties. This study explored the multi-layered structure and microfibril orientation of typical moso bamboo fiber with two broad layers. The microfibrils in the primary cell wall exhibited a disordered mesh-like structure with a microfibril angle (MFA) of 90°. The alternating narrow and broad layers in the secondary walls constituted the growth cycle layer together. Within this structure, the microfibrils were oriented in both Z-helices and S-helices. In the narrow layers, the MFA transitioned gradually from outer to inner layers, ranging from approximately 70° to 30°. Conversely, the broad layers had smaller MFA, ranging from about 5° to 20°. Finally, a typical model of multi-layered microfibril orientation of 4-year-old moso bamboo fiber cells was proposed.

Progression Patterns and Risk Factors of Axial Elongation in Young Adults With Nonpathologic High Myopia: Three-Year Large Longitudinal Cohort Follow-Up.

PURPOSE: To investigate the progression patterns and risk factors of axial elongation in young adults with nonpathologic high myopia. DESIGN: Prospective, clinical observational cohort study with 2- to 4-year follow-up. METHODS: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with nonpathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records). Annual axial elongation was calculated via linear mixed-effect models. The associated risk factors of axial elongation were determined by ordinal logistic regression analysis, with generalized estimate equations for eliminating an interocular correlation bias. RESULTS: Based on 5359 times of AL measurements, the annual axial elongation of participants (mean [SD] age 31.39 [9.22] years) was 0.03 mm/year (95% confidence interval [CI], 0.03-0.04; P < .001) during a 30.23 (6.06) months' follow-up. Severe (>0.1 mm/year), moderate (0.05-0.09 mm/year), mild (0-0.049 mm/year), and nil (≤0 mm/year) elongation was observed in 122 (11.7%), 211 (20.2%), 417 (40.0%), and 293 (28.1%) eyes. The following risk factors were significantly associated with axial elongation: baseline AL ≥ 28 mm (odds ratio [OR], 4.23; 95% CI, 2.95-6.06; P < .001); age < 40 years (OR, 1.64; 95% CI, 1.18-2.28; P = .003); axial asymmetry (OR, 2.04; 95% CI, 1.26-3.29; P = .003), and women (OR, 1.52; 95% CI, 1.13-2.2.05; P = .006). Using antiglaucoma medications was a protective factor (OR, 0.46; 95% CI, 0.27-0.79; P = .005), which slowed 75% of axial elongation from 0.04 (0.06) to 0.01 (0.06) mm/y (P < .001). CONCLUSIONS: Axial elongation continued in young adults with nonpathologic myopia. Risk factors included longer baseline AL and axial asymmetry, younger age, and woman. Topical use of antiglaucoma medications may be useful to reduce ongoing axial elongation.

Revealing Changes in Celecoxib Nanostructured Lipid Carrier's Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS.

Purpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions. Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats. Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug's half-life in vivo. Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug's in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.

[Retracted] MicroRNA­195 inhibits the behavior of cervical cancer tumors by directly targeting HDGF.

[This retracts the article DOI: 10.3892/ol.2017.6210.].

Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.

Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice.

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Heterogeneity of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells in mice.

OBJECTIVES: This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells (CNCs) in mice. METHODS: The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day (E)8.0-E9.25 were collected for histological observation. We performed immunostaining to compare green fluorescent protein (GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5. Single-cell RNA sequencing (scRNA-seq) was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5. Real time fluorescence quantitative polymerase chain reaction (q-PCR) was performed to validate the differential genes. RESULTS: Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch, respectively, at E8.0. Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues, the former had higher expression in palate and tongue. The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentiation and ossification, while Wnt1-Cre-marked CNCs participated in limb development, cell migration, and ossification. The q-PCR data also confirmed the results of gene ontology analysis. CONCLUSIONS: Pax2-Cre mice are perfect experimental animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

Non­m6A RNA modifications in haematological malignancies.

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6-methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non-m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non-m6A RNA modifications. In this review, we mainly focus on the roles and implications of non-m6A RNA modifications, including N4-acetylcytidine, pseudouridylation, 5-methylcytosine, adenosine to inosine editing, 2'-O-methylation, N1-methyladenosine and N7-methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non-m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non-m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non-m6A modifiers in blood cancer.

Effect of intraocular pressure reduction on progressive high myopia (PHM study): study protocol of a randomised controlled trial.

BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.

Achievement of efficient thermally activated delayed fluorescence materials based on 1,8-naphthalimide derivatives exhibiting piezochromic and thermochromic luminescence.

In this study, we developed a D-A type imide derivative based on 1,8-naphthalimide, NI-mPCz, which exhibited outstanding thermally activated delayed fluorescence (TADF) properties. Additionally, it demonstrates characteristics of piezochromic and thermochromic luminescence. The thermochromic luminescence observed is attributed to crystalline transformations occurring during the heating process, as evidenced by differential scanning calorimetry (DSC) and microscopic examinations. Moreover, the good compatibility of NI-mPCz with HeLa cells and its excellent imaging performance indicate its potential for application in the field of biological imaging. These results provide valuable insights for the design and development of new organic electronic and bioimaging materials with high-efficiency TADF characteristics.