Synergistic anticancer effects of SMYD2 inhibitor BAY-598 and doxorubicin in non-small cell lung cancer.

Background: Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC. Methods: The human non-small cell lung cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy. Results: BAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts. Conclusions: Our findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.

COMBINED APPLICATION OF B-SCAN ULTRASONOGRAPHY AND EYE-STEERING ULTRAWIDE FIELD IMAGING TO IMPROVE THE DETECTION OF RETINAL TEARS BEFORE CATARACT SURGERY.

PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.

MOFs-Based Nanoagents Enable Sequential Damage to Cancer-Associated Fibroblast and Tumor Cells for Phototriggered Tumor Microenvironment Regulation.

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.

Challenges of refractive cataract surgery in the era of myopia epidemic: a mini-review.

Myopia is the leading cause of visual impairment in the world. With ever-increasing prevalence in these years, it creates an alarming global epidemic. In addition to the difficulty in seeing distant objects, myopia also increases the risk of cataract and advances its onset, greatly affecting the productivity of myopes of working age. Cataract management in myopic eyes, especially highly myopic eyes is originally more complicated than that in normal eyes, whereas the growing population of cataract with myopia, increasing popularity of corneal and lens based refractive surgery, and rising demand for spectacle independence after cataract surgery all further pose unprecedented challenges to ophthalmologists. Previous history of corneal refractive surgery and existence of implantable collamer lens will both affect the accuracy of biometry including measurement of corneal curvature and axial length before cataract surgery, which may result in larger intraocular lens (IOL) power prediction errors and a compromise in the surgical outcome especially in a refractive cataract surgery. A prudent choice of formula for cataract patients with different characteristics is essential in improving this condition. Besides, the characteristics of myopic eyes might affect the long-term stability of IOL, which is important for the maintenance of visual outcomes especially after the implantation of premium IOLs, thus a proper selection of IOL accordingly is crucial. In this mini-review, we provide an overview of the impact of myopia epidemic on treatment for cataract and to discuss new challenges that surgeons may encounter in the foreseeable future when planning refractive cataract surgery for myopic patients.

A Targeted Exosome Therapeutic Confers Both CfDNA Scavenging and Macrophage Polarization for Ameliorating Rheumatoid Arthritis.

Only a minority of rheumatoid arthritis (RA) patients achieve disease remission, so the exploration of additional pathogenic factors and the development of new therapeutics are needed. Here, strong correlations among the cell-free DNA (cfDNA) level and the inflammatory response in clinical synovial fluid samples and RA disease activity are discovered. The important role of cfDNA in disease development in a collagen-induced arthritis (CIA) murine model is also demonstrated. Building on these findings, a novel therapeutic based on anti-inflammatory (M2) macrophage-derived exosomes as chassis, that are modified with both oligolysine and matrix metalloproteinase (MMP)-cleavable polyethylene glycol (PEG) on the membrane, is developed. After intravenous injection, PEG-enabled prolonged circulation and C─C motif chemokine ligand-directed accumulation together result in enrichment at inflamed joints. Following subsequent MMP cleavage, the positively charged oligolysine is exposed for cfDNA scavenging, while exosomes induce M2 polarization. By using a classical CIA murine model and a newly established CIA canine model, it is demonstrated that the rationally designed exosome therapeutic substantially suppresses inflammation in joints and provides strong chondroprotection and osteoprotection, revealing its potential for effective CIA amelioration.

Generation of whole tumor cell vaccine for on-demand manipulation of immune responses against cancer under near-infrared laser irradiation.

The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.

Role of Optic Nerve Head Characteristics in Predicting Intraocular Pressure Spikes after Cataract Surgery in Highly Myopic Eyes.

INTRODUCTION: To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. METHODS: Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. RESULTS: In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05). CONCLUSION: Female patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes. TRIAL REGISTRATION: This study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www. CLINICALTRIALS: gov (accession number NCT03062085).

Visual and patient-reported outcomes of a diffractive trifocal intraocular lens in highly myopic eyes: a prospective multicenter study.

BACKGROUND: To investigate the visual and patient-reported outcomes of a diffractive trifocal intraocular lens (IOL) in highly myopic eyes. METHODS: Patients with planned cataract removal by phacoemulsification and implantation of a trifocal IOL (AT LISA tri 839MP) were enrolled in the prospective, multicenter cohort study. Patients were allocated into three groups according to their axial length (AL): control group, AL < 26 mm; high myopia group, AL 26-28 mm; extreme myopia group, AL ≥ 28 mm. At 3 months post-surgery, data for 456 eyes of 456 patients were collected, including visual acuity, defocus curve, contrast sensitivity (CS), visual quality, spectacle independence, and overall satisfaction. RESULTS: After surgery, the uncorrected distance visual acuity improved from 0.59 ± 0.41 to 0.06 ± 0.12 logMAR (P < 0.001). In all three groups, about 60% of eyes achieved uncorrected near and intermediate visual acuity of 0.10 logMAR or better, but significantly fewer eyes in the extreme myopia group achieved uncorrected distance visual acuity of 0.10 logMAR or better (P < 0.05). Defocus curves revealed that the visual acuity was significantly worse in the extreme myopia group than others at 0.00, - 0.50, and - 2.00 diopters (P < 0.05). CS did not differ between the control and high myopia groups but was significantly lower in the extreme myopia group at 3 cycles per degree. The extreme myopia group also had greater higher-order aberrations and coma, lower modulation transfer functions and VF-14 scores, more glare and halos, worse spectacle independence at far distance, and consequently lower patient satisfaction than others (all P < 0.05). CONCLUSIONS: In eyes with a high degree of myopia (AL < 28 mm), trifocal IOLs have been shown to provide similar visual outcomes to those in non-myopic eyes. However, in extremely myopic eyes, acceptable results may be obtained with trifocal IOLs, but a reduced level of uncorrected distance vision is expected.

Correction of Asymmetric Bowtie Corneal Astigmatism with a Toric Intraocular Lens: Outcomes and Accuracy of Measurement Modes.

The outcomes of toric intraocular lens (IOL) implantation in correcting asymmetric bowtie corneal astigmatism remain uncertain. The accurate measurement of corneal astigmatism is essential for surgical planning. In this prospective cohort study, patients with asymmetric or symmetric bowtie corneal astigmatism who underwent toric IOL implantation were recruited. Preoperative corneal astigmatism was measured with an IOLMaster and Pentacam (including the simulated keratometry (SimK), total corneal refractive power (TCRP), and wavefront aberration (WFA) modes). At 3 months after surgery, the refractive outcomes and residual astigmatic refractive errors were compared with patients with symmetric bowtie astigmatism. The prediction errors (the differences between the calculated actual corneal astigmatism and the measured corneal astigmatism) were compared among the different measurement modes in the asymmetric group. There were no differences in residual astigmatism between the asymmetric and symmetric groups. However, the mean absolute residual astigmatic refractive error was greater in the asymmetric group than in the symmetric group (0.72 ± 0.42 D vs. 0.53 ± 0.24 D, p = 0.043). In the asymmetric group, the mean absolute prediction errors for the IOLMaster, SimK, TCRP and WFA modes were 0.53 ± 0.40, 0.56 ± 0.47, 0.68 ± 0.52, and 0.43 ± 0.40 D, respectively. The Pentacam WFA mode was the most accurate mode (p < 0.05). The absolute prediction error of the WFA mode was positively correlated with the total corneal irregular astigmatism higher-order aberrations and coma (r = 0.416 and r = 0.473, respectively; both p < 0.05). Our study suggests toric IOL implantation effectively corrected asymmetric bowtie corneal astigmatism. The Pentacam WFA mode may be the most accurate measurement mode, although its accuracy decreased as asymmetry increased.

Tolerance to lens tilt and decentration of two multifocal intraocular lenses: using the quick contrast sensitivity function method.

BACKGROUND: Quick contrast sensitivity function (qCSF) method is an advanced quick method for contrast sensitivity function (CSF) evaluation. This study evaluated the contrast sensitivity (CS) of eyes undergoing cataract surgery with multifocal intraocular lens (IOL) implantation and its tolerance to IOL tilt and IOL decentration using the qCSF method. METHODS: Patients undergoing uneventful phacoemulsification and a trifocal IOL (Zeiss AT LISA tri 839MP, Carl Zeiss, Germany) or an extended depth-of-focus (EDOF) IOL (Tecnis Symfony ZXR00, Johnson & Johnsons, USA) implantation were included. Monocular contrast sensitivity was measured using the qCSF method at one month post-surgery. IOL tilt and decentration were measured using an optical aberrometer (OPD-Scan III, NIDEK, Japan). RESULTS: Seventy-two patients/eyes with the 839MP IOL and 64 patients/eyes with the ZXR00 IOL were included. Area under the log CSF (AULCSF) and CS acuity did not differ significantly between the two groups. The ZXR00 IOL group showed better CS at 1 cpd (1.137 ± 0.164 vs. 1.030 ± 0.183 logCS) and 1.5 cpd (1.163 ± 0.163 vs. 1.071 ± 0.161 logCS), while the 839MP IOL group had better CS at 6 cpd (0.855 ± 0.187 vs. 0.735 ± 0.363 logCS). In the 839MP IOL group, all CSF metrics were negatively correlated with IOL tilt (all P < 0.05), while in the ZXR00 IOL group, the CS at 3 cpd had no significant correlation with IOL tilt (P > 0.05). Among myopic eyes, fewer CSF metrics were negatively correlated with IOL tilt in the ZXR00 IOL group than in the 839MP IOL group. No significant correlation was found between CSF metrics and IOL decentration. CONCLUSIONS: The ZXR00 and the 839MP IOL groups presented comparable CSF. CS was negatively correlated with IOL tilt, instead of decentration in multifocal IOLs, particularly among myopic eyes. The ZXR00 IOL had better tolerance to IOL tilt in myopic eyes.

Chronic Inflammation Pathway NF-κB Cooperates with Epigenetic Reprogramming to Drive the Malignant Progression of Glioblastoma.

Without an effective strategy for targeted therapy, glioblastoma is still incurable with a median survival of only 15 months. Both chronic inflammation and epigenetic reprogramming are hallmarks of cancer. However, the mechanisms and consequences of their cooperation in glioblastoma remain unknown. Here, we discover that chronic inflammation governs H3K27me3 reprogramming in glioblastoma through the canonical NF-κB pathway to target EZH2. Being a crucial mediator of chronic inflammation, the canonical NF-κB signalling specifically directs the expression and redistribution of H3K27me3 but not H3K4me3, H3K9me3 and H3K36me3. Using RNA-seq screening to focus on genes encoding methyltransferases and demethylases of histone, we identify EZH2 as a key methyltransferase to control inflammation-triggered epigenetic reprogramming in gliomagenesis. Mechanistically, NF-κB selectively drives the expression of EZH2 by activating its transcription, consequently resulting in a global change in H3K27me3 expression and distribution. Furthermore, we find that co-activation of NF-κB and EZH2 confers the poorest clinical outcome, and that the risk for glioblastoma can be accurately molecularly stratified by NF-κB and EZH2. It is notable that NF-κB can potentially cooperate with EZH2 in more than one way, and most importantly, we demonstrate a Synergistic effect of cancer cells induced by combinatory inhibition of NF-κB and EZH2, which both are frequently over-activated in glioblastoma. In summary, we uncover a functional cooperation between chronic inflammation and epigenetic reprogramming in glioblastoma, combined targeting of which by inhibitors guaranteed in safety and availability furnishes a potent strategy for effective treatment of this fatal disease.

Polymeric micelle-based nanoagents enable phototriggering combined chemotherapy and photothermal therapy with high sensitivity.

A new type of polymeric nanomicelle-based nanoagent (denoted as PT@MFH hereafter) capable of the highly sensitive release of the chemotherapeutic drug paclitaxel (PTX) upon exposure to a near-infrared (NIR) laser trigger was developed. Specifically, PTX and a photothermal polymer (T-DPPT) were encapsulated in the cavity of nanomicelles, which were constructed from an amphiphilic block copolymer (PCL-PEEP) with a lower critical solution temperature (LCST) of ∼54 °C. Owing to the unprecedented ability of the T-DPPT moiety to harvest near-infrared light, with a mass extinction coefficient at 808 nm of up to ∼80.8 L g-1 cm-1, and convert NIR light to heat, with a photothermal conversion efficiency (η) of up to ∼70%, local hyperthermia was promptly realized via irradiation from an 808 nm laser with extraordinarily low output power. This enabled remarkable contrast in the local temperature and drug release between the "silent" state (prior to phototriggering) and the "activated" state (after phototriggering). This NIR-light-activated local hyperthermia and drug release presented the basis for combined chemotherapy and photothermal therapy (PTT) in antitumor treatment and displayed superb therapeutic efficacy. This pattern together with the high spatial precision imparted by laser triggering jointly contributed to the maximum combined antitumor efficacy to the tumor, while exhibiting minimal side effects on the normal tissues, as preliminarily verified in the in vivo experiment regarding the ability of PT@MFH to efficiently inhibit tumor growth in tumor-bearing model mice.

Sp1 induced gene TIMP1 is related to immune cell infiltration in glioblastoma.

Tumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.

Elevated urbanization-driven plant accumulation and human intake risks of polycyclic aromatic hydrocarbons in crops of peri-urban farmlands.

As an ubiquitous carcinogen, polycyclic aromatic hydrocarbons (PAHs) are closely related to anthropogenic activities. The process of urbanization leads to the spatial interlacing of farmlands and urbanized zones. However, field evidence on the influence of urbanization on the accumulation of PAHs in crops of peri-urban farmlands is lacking. This study comparatively investigated the urbanization-driven levels, compositions, and sources of PAHs in 120 paired plant and soil samples collected from the Yangtze River Delta in China and their species-specific human intake risks. The concentrations of PAHs in crops and soils in the peri-urban areas were 2407.92 ng g-1 and 546.64 ng g-1, respectively, which are significantly higher than those in the rural areas. The PAHs in the root were highly relevant to those in the soils (R2 = 0.63, p < 0.01), and the root bioconcentration factors were higher than 1.0, implying the contributions of root uptake to plant accumulations. However, the translocation factors in the peri-urban areas (1.57 ± 0.33) were higher than those in the rural areas (1.19 ± 0.14), indicating the enhanced influence through gaseous absorption. For the congeners, the 2- to 3-ring PAHs showed a higher plant accumulation potential than the 4- to 6-ring PAHs. Principal component analysis show that the PAHs in the peri-urban plants predominantly resulted from urbanization parameters, such as coal combustion, vehicle emissions, and biomass burning. The mean values of estimated dietary intake of PAHs from the consumption of peri-urban and rural crops were 9116 ng day-1 and 6601.83 ng day-1, respectively. The intake risks of different crops followed the order rice > cabbage > carrot > pea. Given the significant input of PAHs from urban to farmland, the influence of many anthropogenic pollutants arising from rapid urbanization should be considered when assessing the agricultural food safety.

Influence of IOL Weight on Long-Term IOL Stability in Highly Myopic Eyes.

Purpose: This study aimed to investigate the influence of intraocular lens (IOL) weight on long-term IOL stability in highly myopic eyes. Materials and Methods: A total of 205 highly myopic cataract eyes of 205 patients implanted with the MC X11 ASP (Group A, 86 eyes) or 920H IOL (Group B, 119 eyes) were included in this retrospective study. Eyes were divided into 3 subgroups according to the IOL power: low (≥-5 to <5 D), medium (≥5 to <14 D), and high (≥14 D) IOL power. At 3 years after surgery, IOL decentration and tilt, high-order aberrations, and anterior capsular opening (ACO) area were measured. The influence of IOL weight on long-term IOL stability was evaluated. Results: Group B had a significantly greater IOL weight than Group A (Group B vs. Group A: 28.31 ± 2.01 mg vs. 25.71 ± 4.62 mg, P < 0.001). Correspondingly, Group B presented significantly greater overall and inferior decentration than Group A, especially for low and medium IOL power (all P < 0.05). In both groups, overall and vertical decentration was significantly correlated with IOL weight (all P < 0.05). Group B showed a significantly greater ACO area than Group A (P < 0.05). Multivariate analysis showed that decentration in Group A was affected by IOL weight, while decentration in Group B was affected by IOL weight and AL. Conclusions: Higher IOL weight may lead to greater long-term IOL decentration in highly myopic eyes, while the haptic design may play a role in anterior capsular contraction.

Focus on Early COPD: Definition and Early Lung Development.

Chronic obstructive pulmonary disease (COPD) is a disease with high incidence rate and mortality rates worldwide. It is the third leading cause of death in the world. Nevertheless, little progress has been made in treating and preventing the disease. Under these circumstances, the concept of "early COPD" was proposed. Although this concept is not new, most health-care workers do not fully understand early COPD and tend to confuse it with mild COPD. In this review, we mainly discuss the definition of early COPD and the developmental trajectory of lung function. Although patients with early COPD have no symptoms, their lung function is already lower than that of normal people. A relatively complete definition is needed to identify this group of people. Reduced lung function is the diagnostic criterion for COPD, but lung development is a long-term dynamic process. In addition to smoking and air pollution, we should pay more attention to prenatal and childhood risk factors, for example, parents smoking, birth weight, preterm birth, mode of delivery, childhood respiratory infections and childhood asthma. Health-care workers need to be fully aware of early COPD, to reduce the morbidity of COPD and take effective measures to prevent these risk factors.

MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload.

Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

Associations between anterior segment parameters and rotational stability of a plate-haptic toric intraocular lens.

PURPOSE: To evaluate the associations between anterior segment parameters and the rotational stability of a plate-haptic toric intraocular lens (IOL). SETTING: Eye and Ear, Nose, Throat Hospital of Fudan University. DESIGN: Retrospective case series. METHODS: Patients who underwent uneventful phacoemulsification and plate-haptic toric IOL (AT TORBI 709M IOL) implantation were included. Preoperative axial length (AL) and anterior segment parameters, including the white-to-white (WTW) distance, anterior chamber depth (ACD), lens thickness (LT), and anterior segment length (ASL; the sum of ACD and LT) were recorded. IOL rotation, residual astigmatism (RAS), and visual acuity were evaluated 1 month postoperatively. The associations between the anterior segment parameters and IOL rotation were evaluated. RESULTS: A total of 102 eyes of 102 patients were included. The mean AL was 26.43 ± 2.65 mm (range 21.71-34.60 mm). The mean IOL rotation was 4.59 ± 3.18 degrees, and RAS was 0.62 ± 0.39 D postoperatively. No correlation was detected between AL, ACD, or LT and the rotation of the plate-haptic toric IOL (all P > .05). However, its rotation correlated positively with the WTW distance (r = 0.250, P = .011) and ASL (r = 0.214, P = .030). Backward stepwise multiple linear regression revealed that the WTW distance (ß = 2.142, P = .014) and ASL (ß = 2.060, P = .037) were independent predictors of plate-haptic toric IOL rotation. CONCLUSIONS: Plate-haptic toric IOLs rotate more in eyes with larger WTW distances and longer ASLs; therefore, toric IOL implantation should be performed with caution in eyes with these characteristics.

Distribution of Ocular Anterior and Posterior Segment Lengths Among a Cataract Surgical Population in Shanghai.

Purpose: To investigate the distributions of the ocular anterior and posterior segment lengths among a cataract surgical population in Shanghai. Design: Cross-sectional study. Methods: Ocular biometric parameters of 23,462 eyes of 23,462 cataract surgery candidates were reviewed. Axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) were obtained using IOL Master. Anterior segment length (ASL = ACD + LT), posterior segment length (PSL = AL - ASL) and the ratio of ASL to PSL (ASL/PSL) were calculated. Results: The mean ASL was 7.58 ± 0.39 mm, the mean PSL was 17.12 ± 2.64 mm. As the age grew, the ASL increased, and PSL increased firstly then decreased. Male subjects tended to have significantly longer ASL and shorter PSL than female subjects. With the increasing AL, the ASL was firstly decreased to trough at 20-22 mm AL group, then increased gradually, while the PSL increased rapidly. The ASL correlated positively with AL in normal, moderate and highly myopic eyes, negatively in short eyes. The PSL correlated positively with AL across the entire study population. The ASL/PSL was not constant in the eyes with different AL but had a relatively steep downward trend with the increasing AL in the short eyes, then decreased smoothly in normal, moderate and highly myopic eyes. Conclusions: In Chinese cataractous eyes, longer ASL and shorter PSL were associated with elder age and male gender. The change of ASL over AL was not linear, and the ASL was smallest in the eyes with AL of 20-22 mm. The elongation of the eyeball was mainly due to the extension of the posterior segment.