Correlation between pupillary size and depth of focus after the implantation of extended depth of focus intraocular lenses.

PURPOSE: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size. METHODS: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA). RESULTS: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient).

The antimicrobial property of JY-1, a complex mixture of Traditional Chinese Medicine, is linked to it abilities to suppress biofilm formation and disrupt membrane permeability.

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.

Identification, characterisation and expression analysis of peanut sugar invertase genes reveal their vital roles in response to abiotic stress.

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.

Breast cancer cells have an increased ferroptosis risk induced by system xc- blockade after deliberately downregulating CYTL1 to mediate malignancy.

Cytokine-like protein 1 (CYTL1) expression is deliberately downregulated during the progression of multiple types of cancers, especially breast cancer. However, the metabolic characteristics of cancer progression remain unclear. Here, we uncovered a risk of breast cancer cells harboring low CYTL1 expression, which is metabolically controlled during malignant progression. We performed metabolism comparison and revealed that breast cancer cells with low CYTL1 expression have highly suppressed transsulfuration activity that is driven by cystathionine ß-synthase (CBS) and contributes to de novo cysteine synthesis. Mechanistically, CYTL1 activated Nrf2 by promoting autophagic Keap1 degradation, and Nrf2 subsequently transactivated CBS expression. Due to the lack of cellular cysteine synthesis, breast cancer cells with low CYTL1 expression showed hypersensitivity to system xc- blockade-induced ferroptosis in vitro and in vivo. Silencing CBS counteracted CYTL1-mediated ferroptosis resistance. Our results show the importance of exogeneous cysteine in breast cancer cells with low CYTL1 expression and highlight a potential metabolic vulnerability to target.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Deep learning-based analysis of infrared fundus photography for automated diagnosis of diabetic retinopathy with cataracts.

PURPOSE: To develop deep learning-based networks for the diagnosis of diabetic retinopathy (DR) with cataracts based on infrared fundus images. SETTING: Shanghai General Hospital, Shanghai Eye Disease Prevention & Treatment Center, Shanghai, China. DESIGN: Development and evaluation of an artificial intelligence (AI) diagnostic method. METHODS: A total of 10 665 infrared fundus images from 4553 patients with diabetes were used to train and test the model. For image quality assessment, left and right eye classification, DR diagnosis and grading, and segmentation of 3 DR lesions, an end-to-end software using EfficientNet and UNet was developed. The accuracy and performance of the software in comparison to human experts was evaluated. RESULTS: The model achieved an accuracy of 75.31% for left and right eye classification, 100% for DR grading and diagnosis tasks, and 73.67% for internal test set, with corresponding areas under the curve (AUCs) of 0.88, 1.00, and 0.89, respectively. For DR lesion segmentation, the AUCs of hemorrhagic, microangioma, and exudative lesions were 0.86, 0.66, and 0.84, respectively. In addition, a contrast test of human-machine film reading confirmed the software's high sensitivity (96.3%) and specificity (90.0%) and consistency with the manual film reading group (κ = 0.869, P < .001). This easily deployable software generated reports quickly and promoted efficient DR screening with cataracts in clinical and community settings. CONCLUSIONS: AI-assisted software can perform automatic analysis of infrared fundus images and has substantial application value for the diagnosis of DR patients with cataracts.

Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.

Construction of Ternary Bismuth-Based Heterojunction by Using (BiO)2 CO3 as Electron Bridge for Highly Efficient Degradation of Phenol.

Inspired by nature, it has been considered an effective approach to design artificial photosynthetic system by fabricating Z-scheme photocatalysts to eliminate environmental issues and alleviate the global energy crisis. However, the development of low cost, environment-friendly, and high-efficient photocatalysts by utilizing solar energy still confronts huge challenge. Herein, we constructed a Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 ternary heterojunction via a facile solvothermal method and calcination approach and used it as a photocatalyst for the degradation of phenol. The optimized Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 heterojunction delivers a considerable activity for phenol photodegradation with an impressive removal efficiency of 98.8 % and about total organic carbon (TOC) of 68 % within 180 min under visible-light irradiation. The excellent photocatalytic activity was ascribed to the formation of a Z-scheme heterojunction, more importantly, the presence of (BiO)2 CO3 as an electron bridge greatly shortens the migration distance of photogenerated electron from ECB of Bi2 O3 to EVB of Bi2 MoO6 , thus prolonging the lifetime of photogenerated electrons, which is verified by trapping experiments, electron spin-resonance spectroscopy (ESR) results, and density functional theory (DFT) calculations. This work provides a potential strategy to fabricate highly efficient Bi-based Z-scheme photocatalysts with wide application prospects in solar-to-fuel conversion and environmental protection.

Indolocarbazole alkaloid Loonamycin A inhibits triple-negative breast cancer cell stemness and Notch signalling.

OBJECTIVES: Enrichment for therapy-resistant cancer stem cells hampers the treatment of triple-negative breast cancer. Targeting these cells via suppression of Notch signalling can be a potential therapeutic strategy. This study aimed to uncover the mode of action of a new indolocarbazole alkaloid loonamycin A against this incurable disease. METHODS: The anticancer effects were examined in triple-negative breast cancer cells using in vitro methods, including cell viability and proliferation assays, wound-healing assay, flow cytometry and mammosphere formation assay. RNA-seq technology was used to analyse the gene expression profiles in loonamycin A-treated cells. Real-time RT-PCR and western blot were to evaluate the inhibition of Notch signalling. KEY FINDINGS: Loonamycin A has stronger cytotoxicity than its structural analog rebeccamycin. Besides inhibiting cell proliferation and migration, loonamycin A reduced CD44high/CD24low/- sub-population, mammosphere formation, as well as the expression of stemness-associated genes. Co-administration of loonamycin A enhanced antitumour effects of paclitaxel by inducing apoptosis. RNA sequencing results showed that loonamycin A treatment caused the inhibition of Notch signalling, accompanied by the decreased expression of Notch1 and its targeted genes. CONCLUSIONS: These results reveal a novel bioactivity of indolocarbazole-type alkaloids and provide a promising Notch-inhibiting small molecular candidate for triple-negative breast cancer therapy.

Constitutive expression of AtSINA2 from Arabidopsis improves grain yield, seed oil and drought tolerance in transgenic soybean.

The SEVEN IN Absentia (SINA), a typical member of the RING E3 ligase family, plays a crucial role in plant growth, development and response to abiotic stress. However, its biological functions in oil crops are still unknown. Previously, we reported that overexpression of AtSINA2 in Arabidopsis positively regulated the drought tolerance of transgenic plants. In this work, we demonstrate that ectopic expression of AtSINA2 in soybean improved the shoot growth, grain yield, drought tolerance and seed oil content in transgenic plants. Compared to wild type, transgenic soybean produced greater shoot biomass and grain yield, and showed improved seed oil and drought tolerance. Physiological analyses exhibited that the increased drought tolerance of transgenic plants was accompanied with a higher chlorophyll content, and a lower malondialdehyde accumulation and water loss during drought stress. Further transcriptomic analyses revealed that the expressions of genes related to plant growth, flowering and stress response were up- or down-regulated in transgenic soybean under both normal and drought stress conditions. Our findings imply that AtSINA2 improved both agricultural production and drought tolerance, and it can be used as a candidate gene for the genetic engineering of new soybean cultivars with improved grain yield and drought resistance.

Combining bioinspired nanochannels with ferrocene doped MoS2 nanoplates: Application to ratiometric electrochemical detection of let-7a.

Sensitive and accurate detection of tumor suppressor genes is vastly important to the related therapeutic research. Herein, a ratiometric electrochemical method for let-7a detection was established by integrating a ferrocene (Fc) doped MoS2 nanoplates modified electrode into the nanochannels-based biosensing platform. The ratiometric signal was developed by the redox current of methylene blue (MB) which reflects the target recognition occurred into the nanochannels and the redox current of Fc which corrects the slight signal deviation caused by some analyte-independent factors. And thus, the ratio of peak current of MB and Fc (IMB/IFc) measured at differential pulse voltammogram varied precisely with the increment of the concentration of let-7a incubated in the bioinspired nanochannels. The strategy of spherical DNAzyme induced deposition in nanochannels was utilized to further amplify the signal. Under optimal conditions, a wide linear dynamic range of 50 aM to 10 pM spanning five orders of magnitude was obtained. The developed electrochemical method, with attomole level of detection limit, was successfully applied to the determination of let-7a in human serum and tumor cells. The study not only offers a new route for reliable nucleic acid detection, but also provides an excellent opportunity to extend the application of the two-dimensional transition-metal dichalcogenides.

A plant-derived glucocorticoid receptor modulator with potency to attenuate the side effects of glucocorticoid therapy.

BACKGROUND AND PURPOSE: Continuous efforts have been made to move towards maintaining the beneficial anti-inflammatory functions of glucocorticoids (GCs) while minimizing side effects. Here, we investigated the selective glucocorticoid receptor (GR) modulator-like properties of a plant-derived compound caesaldekarin e (CA-e). EXPERIMENTAL APPROACH: The therapeutic efficacy of CA-e was evaluated in several mouse models, including dextran sulfate sodium-induced colitis, ovalbumin-induced lung allergic inflammation, imiquimod-induced psoriasis-like skin inflammation and skin atrophy. The action of CA-e targeting the GR was analysed using molecular docking, cellular thermal shift assays and microscale thermophoresis. Other methods included DNA-protein pull-down assays and mass spectrometry. KEY RESULTS: CA-e selectively inhibited positive GC response element ((+) GRE)-mediated direct transactivation while maintaining and even enhancing the anti-inflammatory effects of treatment with dexamethasone. CA-e, alone and in combination with dexamethasone, efficiently alleviated inflammation in several mouse models with milder side effects compared with dexamethasone alone. Mechanistically, CA-e inhibited the formation of dimers by binding to the dimerization interface located in the ligand-binding domain of GR and facilitated embryonic ectoderm development that is involved in the regulation of transcriptional repression to compete for binding to (+) GRE, eventually leading to the repression of (+) GRE-regulated genes. In addition, CA-e repressed NF-κB-dependent genes by enhancing the interaction between GR and p65. CONCLUSIONS AND IMPLICATIONS: Our results reveal that CA-e is a novel GR modulator with strong potency to attenuate the side effects of GC therapy and can be used as a potential molecular tool for deciphering GR signalling.

Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer.

Chemoresistance remains a major obstacle to successful treatment of triple negative breast cancer (TNBC). Identification of druggable vulnerabilities is an important aim for TNBC therapy. Here, we report that SERCA2 expression correlates with TNBC progression in human patients, which promotes TNBC cell proliferation, migration and chemoresistance. Mechanistically, SERCA2 interacts with LC3B via LIR motif, facilitating WIPI2-independent autophagosome formation to induce autophagy. Autophagy-mediated SERCA2 degradation induces SERCA2 transactivation through a Ca2+/CaMKK/CREB-1 feedback. Moreover, we found that SERCA2-targeting small molecule RL71 enhances SERCA2-LC3B interaction and induces excessive autophagic cell death. The increase in SERCA2 expression predisposes TNBC cells to RL71-induced autophagic cell death in vitro and in vivo. This study elucidates a mechanism by which TNBC cells maintain their high autophagy activity to induce chemoresistance, and suggests increased SERCA2 expression as a druggable vulnerability for TNBC.

Sustainability Assessment of Water Resources Use in 31 Provinces in China: A Combination Method of Entropy Weight and Cloud Model.

As a fundamental and strategic resource, water is a crucial controlling element of ecosystem and natural environment and it plays an irreplaceable role in maintaining and promoting the sustainable development of the economy and society. To achieve the sustainable development of society, the economy and ecology, it is necessary to assess and improve the sustainability of water resources use. Based on the Human-Resource-Nature approach, this paper constructed an indicator system for the sustainability assessment of water resources use (ISSAWRU) in China from three perspectives: water resources condition, socio-economy and ecological environment. A five-level hierarchy of assessment indicators was established. Based on the entropy weight method and the cloud model which took both fuzziness and randomness into account, this paper established an entropy-cloud-based assessment model for the sustainability assessment of water resources use in 31 provinces in China in 2019. The assessment results were compared with results obtained by the TOPSIS method to test their reliability. Finally, a comprehensive and in-depth analysis of the sustainability of water resources use in China was conducted. According to the results, water resources per capita had a weighting of 0.306 and the greatest impact on the sustainable use of water resources. In addition, water structure, agricultural water use efficiency, forest coverage, and so on, had a significant impact on the sustainable use of water resources in China. The overall level of sustainability of water resources use in 31 provinces in China was not high-42% of the regions have unsustainable water resources use and there was a clear spatial distribution trend. The sustainability level of water resources use was higher in the southeast and economically developed regions. Therefore, each region should develop measures to guarantee water security based on the local conditions. This research helps policy makers to figure out the contributing factors associated with sustainability of water resources use and to set relevant rules and regulations to promote the use of water resources in a sustainable way.

Quantitative changes in iris and retinal blood flow after femtosecond laser-assisted in situ keratomileusis and small-incision lenticule extraction.

Purpose: To investigate the quantitative changes in iris and retinal blood flow indices after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE). Methods: Seventy-nine patients who underwent FS-LASIK or SMILE were enrolled between July 2020 and September 2020. Participants were followed-up 1 day pre-operatively and 1 week, 1 month, 3 months post-operatively. Optical coherence tomography angiography (OCTA) was used to acquire and quantify the iris and retinal blood flow indices. Results: The iris vessel area density (VAD) and vessel skeleton density (VSD) decreased on post-operative day 1 but recovered on day 7. In both cases, the pupil diameter was positively associated with the post-operative iris blood flow indices (p = 0.0013, p = 0.0002). The retinal VAD and VSD in the superficial and deep capillary plexuses decreased after surgery and failed to recover after 90 days. The SMILE group showed significantly lower iris and retinal blood flow indices than the FS-LASIK group. For both procedures, axial length (p = 0.0345, p = 0.0499), spherical equivalence (p = 0.0063, p = 0.0070), and suction duration (p = 0.0025, p = 0.0130) were negatively correlated with the post-operative VAD and VSD. Conclusions: The SMILE and FS-LASIK procedures induced a short-term decrease in the iris and retinal blood flow indices, although patients finally showed full visual recovery. This phenomenon should be carefully considered, especially in patients prone to anterior segment lesions.

Self-Expandable Metal Stent as a Bridge to Surgery for Left-Sided Acute Malignant Colorectal Obstruction: Optimal Timing for Elective Surgery.

Objectives: This randomized, single-center, retrospective, comparative cohort study is aimed at investigating the optimal time interval from self-expandable metal stent (SEMS) placement to surgery and potential risk factors for complications in patients with acute malignant colorectal obstruction. Methods: A total of 64 patients with left-sided acute malignant colorectal obstruction treated with SEMS placement and subsequent surgery between January 2013 and September 2020 were enrolled and allocated to a case group (SEMS placing time ≤ 14 days; n = 19 patients) and a control group (SEMS placing time > 14 days; n = 45 patients). The primary outcome was the difference in baseline information, patients' conditions during surgery, and postoperative conditions between the two groups. The secondary outcome included potential risk factors of postoperative complications. The propensity score matching (PSM) and super learner (SL) methods were used to eliminate multiple confounding factors of baseline data. A cohort of 21 samples was used for external validation, comprising 6 cases and 15 controls. Results: A significant difference was observed between the two groups in intraoperative blood loss (P = 0.009), postoperative hospital stay (P = 0.002), postoperative complications (Clavien-Dindo grading ≥ II) (P < 0.001), stoma creation (P < 0.001), and primary anastomosis (P < 0.001). After a 1 : 3 PSM analysis, no statistically significant differences between eight confounding variables of the two groups were observed (P > 0.05). Caliper set as 0.2 multiple logistic regression analysis showed that the potential risk factor for postoperative complications was SEMS placing time (RR = 0.109, 95% confidence interval (CI) = 0.028-0.433; P = 0.002), indicating that SEMS placing time > 14 days was an independent risk factor for postoperative complications in bridge-to-surgery (BTS) setting. The area under the AUC curve was 76.7% and validated using the validation cohort. Conclusions: Long duration of SEMS placement (>14 days) may not influence surgical difficulty but could increase the risk of postoperative complications.

Quantitative changes in iris vasculature and blood flow in patients with different refractive errors.

PURPOSE: To evaluate the association between microvascular changes in the iris and refractive errors. METHODS: A cross-sectional case study. Seventy eyes from 70 patients with refractive errors were enrolled. Iris microvasculature was analyzed using optical coherence tomography angiography (OCTA). We divided the iris images into three regions and calculated the vessel area density (VAD) and vessel skeleton density (VSD) of the inner one-third, inner two-thirds, and the entirety of the iris. RESULTS: The VADs and VSDs of the different regions were significantly different. The VAD and VSD of the inner one-third of the iris were higher than those of the other regions. The iris blood vessels were denser near the pupil margin, and blood vessels from the iris root to the pupil edge were radially distributed. The VAD and VSD of patients with mild hyperopia and emmetropia were higher than those of patients with moderate and high myopia. As the spherical equivalent increased, the VAD and VSD of the iris increased. Neither age nor sex contributed to significant differences in VAD and VSD. CONCLUSION: Quantitative changes in iris microvasculature may indicate the development of myopia.

Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer.

Loss-of-function mutations frequently occur in tumor suppressor genes, i.e., p53, during the malignant progression of various cancers. Whether any intrinsic suppressor carries a rare mutation is largely unknown. Here, we demonstrate that intracellular cytokine-like protein 1 (CYTL1) plays a key role in preventing the robust glycolytic switching characteristic of breast cancer. A low intracellular CYTL1 level, not its mutation, is required for metabolic reprogramming. Breast cancer cells expressing an intracellular form of CYTL1 lacking a 1-22 aa signal peptide, ΔCYTL1, show significantly attenuated glucose uptake and lactate production, which is linked to the inhibition of cell growth and metastasis in vitro and in vivo. Mechanistically, CYTL1 competitively binds the N-terminal sequence of NDUFV1 to block MDM2-mediated degradation by the proteasome, leading to the stability of the NDUFV1 protein. In addition to inducing increased NAD+ levels, NDUFV1 interacts with Src to attenuate LDHA phosphorylation at tyrosine 10 and reduce lactate production. Our results reveal, for the first time, that CYTL1 is a novel tumor suppressor. Its function in reversing metabolic reprogramming toward glycolysis may be very important for the development of novel antitumor strategies.

Outcomes of the Haigis-L formula for calculating intraocular lens power in extreme long axis eyes after myopic laser in situ keratomileusis.

PURPOSE: To evaluate the accuracy of refractive prediction by the Haigis-L formula compared to four other IOL power calculation formulas in eyes with extremely long axial lengths (AL > 29.0 mm) after LASIK. SETTING: Shanghai Eye Disease and Prevention Treatment Center, Shanghai, China. DESIGN: Retrospective case series. METHODS: Twenty-nine eyes from 19 patients were available for analysis. The primary outcome measure was the arithmetic refractive prediction error (RPE), defined as the difference between the actual postoperative refractive error and the intended formula-derived refractive target. The main outcome measure was the median absolute refraction prediction error (MedAE). The accuracy of the Haigis-L was compared with Barrett True K No History, Shammas-PL, SRK/Tcorrected K, and Holladay 2corrected K methods to calculate IOL power. RESULTS: The Haigis-L formula had a significantly larger MedAE than Shammas-PL and SRK/Tcorrected K formulas (P = 0.005 and P = 0.015, respectively), a smaller percentage of eyes within ±1.50 diopter (D) of predicted error in refraction compared with Shammas-PL and SRK/Tcorrected K formulas (P = 0.014 and P = 0.005, respectively). The refractive prediction errors of 6 eyes with corneal keratometry of less than 35 D by Haigis-L all had more than 1.95 D of myopic overestimation, while none of the other four methods resulted in an absolute error over 1.95 D. CONCLUSIONS: The Haigis-L formula was relatively accurate in predicting extreme long axis (>29.0 mm) eyes after myopic LASIK surgery but less accurate for eyes with extremely flat corneas (<35 D). SRK/Tcorrected K and Shammas-PL performed better than the other methods for refractive prediction in this type of eyes. SYNOPSIS: Haigis-L performed worse than SRK/Tcorrected K and Shammas-PL in predicting IOL power in extremely long axis (>29.0 mm) eyes after myopic LASIK, especially with extremely flat corneas (K < 35 D).

Ultrasound Cycloplasty in Chinese Glaucoma Patients: Results of a 6-Month Prospective Clinical Study.

PURPOSE: The aim of this study was to evaluate the short-term efficacy and safety of ultrasound cycloplasty (UCP) procedure in Chinese glaucoma patients. METHODS: As a single-center, prospective, noncomparative study, 23 eyes of 23 patients suffering from glaucoma with uncontrolled intraocular pressure (IOP) ≥21 mm Hg underwent a multidose UCP treatment with the activations of 6, 8, or10 sectors. Types of glaucoma include primary open-angle glaucoma (7/23), primary angle closure glaucoma (PACG) (9/23), and secondary glaucoma (SG) (7/23). A complete ophthalmic examination including intraocular pressure (IOP) measurements was performed before UCP procedure and at 1 day, 1 month, 3 months, and 6 months after the procedure. An IOP reduction of ≥20% and IOP >5 mm Hg without increasing hypotensive medication at the follow-up visit was defined as therapeutic success. The postoperative complications were also recorded and compared to baseline for safety evaluation. RESULTS: The mean baseline IOP of 23 treated eyes was 37.2 ± 12.1 mm Hg. The IOP reduction after UCP procedure was 23, 49, 33, and 34% at 1 day, 1 month, 3 months, and 6 months, respectively. Thus, the corresponding overall therapeutic success rates reached 61% (14/23), 83% (19/23), 65% (15/23), and 61% (14/23), respectively. Baseline IOPs of 8- and 10-sector groups (37.0 ± 9.9 mm Hg and 50.1 ± 12.2 mm Hg) were significantly higher than that of 6 sector groups (30.1 ± 8.2 mm Hg). Therapeutic success rates of 6-, 8-, and 10-sector groups reached 44% (4/9), 56% (5/9), and 100% (5/5), respectively. There were the highest percentage of IOP reduction (50 and 41%) and therapeutic success rate (6/7; 86% and 7/9; 78%) in the SG group and PACG group, respectively. In addition, preoperative ocular pain symptoms of 4 patients were all disappeared within 1 week after UCP. No serious intraoperative or postoperative complications occurred. CONCLUSION: UCP procedure is an effective and well-tolerated treatment to reduce IOP in Chinese glaucoma patients, which offered a novel alternative for glaucoma treatment.