Identification of novel immune-related signatures for keloid diagnosis and treatment: insights from integrated bulk RNA-seq and scRNA-seq analysis.

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

Fundamentals and Recent Progress in Magnetic Field Assisted CO2 Capture and Conversion.

CO2 capture and conversion technology are highly promising technologies that definitely play a part in the journey towards carbon neutrality. Releasing CO2 by mild stimulation and the development of high efficiency catalytic processes are urgently needed. The magnetic field, as a thermodynamic parameter independent of temperature and pressure, is vital in the enhancement of CO2 capture and conversion process. In this review, the recent progress of magnetic field-enhanced CO2 capture and conversion is comprehensively summarized. The theoretical fundamentals of magnetic field on CO2 adsorption, release and catalytic reduction process are discussed, including the magnetothermal, magnetohydrodynamic, spin selection, Lorentz forces, magnetoresistance and spin relaxation effects. Additionally, a thorough review of the current progress of the enhancement strategies of magnetic field coupled with a variety of fields (including thermal, electricity, and light) is summarized in the aspect of CO2 related process. Finally, the challenges and prospects associated with the utilization of magnetic field-assisted techniques in the construction of CO2 capture and conversion systems are proposed. This review offers a reference value for the future design of catalysts, mechanistic investigations, and practical implementation for magnetic field enhanced CO2 capture and conversion.

Improving Accuracy of In-The-Bag Intraocular Lens Power Calculation in Adult Eyes with Unilateral Subluxated Lenses by Using the Anterior Chamber Depth of the Unaffected Eye.

INTRODUCTION: This study aimed to determine the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculations for cataractous eyes and refractive outcomes using the unaffected fellow eye's ACD in subluxated crystalline lenses. METHODS: The predicted postoperative spherical equivalent (SE) calculated using the Kane formula with and without fellow eye's ACD in 202 cataract patients was compared. Refractive outcomes of the newer formulas (the Kane, Barrett Universal II [BUII], and Pearl-DGS formulas) with affected eye's ACD and with unaffected fellow eye's ACD were compared in 33 eyes with lens subluxation (the affected eye) undergoing in-the-bag IOL implantation. The SD of the prediction error (PE) was assessed using the heteroscedastic method. RESULTS: In 202 paired cataractous eyes, no marked ACD difference was found bilaterally; the predicted SE obtained without the fellow eye's ACD was comparable with that calculated with the fellow eye one (p = 0.90), with a mean absolute difference of 0.03 ± 0.03 D. With the affected eye AL, keratometry, and ACD, the median absolute error (MedAE) was 0.38-0.64 D, and the percentage of PE within ±0.50 D was 30.30-57.58%. The unaffected eye's ACD improved the results (MedAE, 0.35-0.49 D; the percentage of PE within ±0.50 D, 54.55-63.64%). The SDs of the BUII (0.82 D) and Pearl-DGS formulas (0.87 D) with the affected eye's ACD were significantly larger than those of the Kane and Pearl-DGS formulas (both 0.69 D) with the unaffected eye's ACD. CONCLUSION: Bilateral ACD was interchangeable in IOL power calculation for cataractous eyes when using the Kane formula. Unaffected eye's ACD in lieu of affected eye's ACD can enhance the accuracy of newer formulas in patients with unilateral subluxated lenses undergoing in-the-bag IOL implantation.

BPIFB1 promotes metastasis of hormone receptor-positive breast cancer via inducing macrophage M2-like polarization.

Metastasis is an important factor affecting the prognosis of hormone receptor-positive breast cancer (BC). However, the molecular basis for migration and invasion of tumor cells remains poorly understood. Here, we identify that bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1), which plays an important role in innate immunity, is significantly elevated in breast cancer and associated with lymph node metastasis. High expression of BPIFB1 and its coding mRNA are significantly associated with poor prognosis of hormone receptor-positive BC. Using enrichment analysis and constructing immune infiltration evaluation, we predict the potential ability of BPIFB1 to promote macrophage M2 polarization. Finally, we demonstrate that BPIFB1 promotes the metastasis of hormone receptor-positive BC by stimulating the M2-like polarization of macrophages via the establishment of BC tumor cells/THP1 co-culture system, qPCR, Transwell assay, and animal experiments. To our knowledge, this is the first report on the role of BPIFB1 as a tumor promoter by activating the macrophage M2 polarization in hormone receptor-positive breast carcinoma. Together, these results provide novel insights into the mechanism of BPIFB1 in BC.

Photothermal CO-PROX reaction over ternary CuCoMnOx spinel oxide catalysts: the effect of the copper dopant and thermal treatment.

The purification of carbon monoxide in H2-rich streams is an urgent problem for the practical application of fuel cells, and requires the development of efficient and economical catalysts for the preferential oxidation of CO (CO-PROX). In the present work, a facile solid phase synthesis method followed by an impregnation method were adopted to prepare a ternary CuCoMnOx spinel oxide, which shows superior catalytic performance with CO conversion of 90% for photothermal CO-PROX at 250 mW cm-2. The dopant of copper species leads to the incorporation of Cu ions into the CoMnOx spinel lattice forming a ternary CuCoMnOx spinel oxide. The appropriate calcination temperature (300 °C) contributes to the generation of abundant oxygen vacancies and strong synergetic Cu-Co-Mn interactions, which are conducive to the mobility of oxygen species to participate in CO oxidation reactions. On the other hand, the highest photocurrent response of CuCoMnOx-300 also promotes the photo-oxidation activity of CO due to the high carrier concentration and efficient carrier separation. In addition, the in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) confirmed that doping copper species could enhance the CO adsorption capacity of the catalyst due to the generation of Cu+ species, which significantly increased the CO oxidation activity of the CuCoMnOx spinel oxide. The present work provides a promising and eco-friendly solution to remove the trace CO in H2-rich gas over CuCoMnOx ternary spinel oxide with solar light as the only energy source.

Survival Outcomes of Breast-Conserving Therapy versus Mastectomy in Early-Stage Breast Cancer, Including Centrally Located Breast Cancer: A SEER-Based Study.

Purpose: This study aims to analyze the survival outcomes of breast cancer (BC) patients, especially centrally located breast cancer (CLBC) patients undergoing breast-conserving therapy (BCT) or mastectomy. Methods: Surveillance, epidemiology, and end results (SEER) data of patients with T1-T2 invasive ductal or lobular breast cancer receiving BCT or mastectomy were reviewed. We used X-tile software to convert continuous variables to categorical variables. Chi-square tests were utilized to compare baseline information. The multivariate logistic regression model was performed to evaluate the relationship between predictive variables and treatment choice. Survival outcomes were visualized by Kaplan-Meier curves and cumulative incidence function curves and compared using multivariate analyses, including the Cox proportional hazards model and competing risks model. Propensity score matching was performed to alleviate the effects of baseline differences on survival outcomes. Result: A total of 180,495 patients were enrolled in this study. The breast preservation rates fluctuated around 60% from 2000 to 2015. Clinical features including invasive ductal carcinoma (IDC), lower histologic grade, smaller tumor size, fewer lymph node metastases, positive ER and PR status, and chemotherapy use were independently correlated with BCT in both BC and CLBC cohorts. In all the classic Cox models and competing risks models, BCT was an independent favorable prognostic factor for BC, including CLBC patients in most subgroups. In addition, despite the low breast-conserving rate compared with tumors located in the other areas, CLBC did not impair the prognosis of BCT patients. Conclusion: BCT is optional and preferable for most early-stage BC, including CLBC patients.

A Pyramid Semi-Autoregressive Transformer with Rich Semantics for Sign Language Production.

As a typical sequence to sequence task, sign language production (SLP) aims to automatically translate spoken language sentences into the corresponding sign language sequences. The existing SLP methods can be classified into two categories: autoregressive and non-autoregressive SLP. The autoregressive methods suffer from high latency and error accumulation caused by the long-term dependence between current output and the previous poses. And non-autoregressive methods suffer from repetition and omission during the parallel decoding process. To remedy these issues in SLP, we propose a novel method named Pyramid Semi-Autoregressive Transformer with Rich Semantics (PSAT-RS) in this paper. In PSAT-RS, we first introduce a pyramid Semi-Autoregressive mechanism with dividing target sequence into groups in a coarse-to-fine manner, which globally keeps the autoregressive property while locally generating target frames. Meanwhile, the relaxed masked attention mechanism is adopted to make the decoder not only capture the pose sequences in the previous groups, but also pay attention to the current group. Finally, considering the importance of spatial-temporal information, we also design a Rich Semantics embedding (RS) module to encode the sequential information both on time dimension and spatial displacement into the same high-dimensional space. This significantly improves the coordination of joints motion, making the generated sign language videos more natural. Results of our experiments conducted on RWTH-PHOENIX-Weather-2014T and CSL datasets show that the proposed PSAT-RS is competitive to the state-of-the-art autoregressive and non-autoregressive SLP models, achieving a better trade-off between speed and accuracy.

A three-dimensional CoNi-MOF nanosheet array-based immunosensor for sensitive monitoring of human chorionic gonadotropin with core-shell ZnNi-MOF@Nile Blue nanotags.

A CoNi-based metal-organic framework (CoNi-MOF) nanosheet array is synthesized by the treatment of a CoNi layered double hydroxide nanosheet array on Ni foam with 3,5-diaminobenzoic acid. The CoNi-MOF nanosheet array with amino and carboxyl groups can be used to capture the human chorionic gonadotropin (HCG) primary antibody (HCG Ab1). Nile Blue decorated ZnNi-MOF (NB@ZnNi-MOF) spheres immobilized with HCG secondary antibodies (HCG Ab2) are used for signal amplification. When HCG exists in an analytical sample, a sandwich structure is formed and an electrochemical signal is produced. The analytical signal generated during the detection is caused by the conversion of Co(ii) and Co(iii) in the CoNi-MOF nanosheet array. The Nile Blue of the NB@ZnNi-MOF sphere, as a kind of redox-active species, is responsible for the electrochemical signal amplification in the immunosensor. On the basis of the above advantages, the HCG immunosensor exhibits a lower limit of detection (1.85 × 10-3 mIU mL-1) and a wide linear range from 0.005 mIU mL-1 to 250 mIU mL-1. Additionally, this immunosensor is used to quantitatively detect HCG in human blood serum and shows good correlations with the standard enzyme-linked immunosorbent assay (ELISA), providing a high value on clinical diagnosis.

Copper(II) 1,4-naphthalenedicarboxylate on copper foam nanowire arrays for electrochemical immunosensing of the prostate specific antigen.

Nanowires of copper(II)-based metal-organic frameworks (Cu-MOFs) of type Cu(II)(1,4-naphthalenedicarboxylic acid) (1,4-NDC) were deposited on the surface of a copper foam by immersion of Cu(OH)2 nanowires in a solution of 1,4-NDC. An electrochemical immunosensor for the prostate specific antigen (PSA) is obtained by using the nanowire arrays as a redox signal probe. The signal is generated by the conversion of Cu(I) and Cu(II) of Cu-MOFs nanowires. Cu(1,4-NDC) nanowires contain many uncoordinated carboxyl groups which can bind to the amino groups of the PSA antibody. When PSA antibody binds to PSA antigen during an immune response, the current signal will decrease due to the electrical insulation of PSA antigen. The decrease of current is directly proportional to the increase of PSA concentration. The immunosensor, best operated at a voltage of typically -0.08 V (vs. Ag/AgCl), has a low limit of detection (4.4 fg·mL-1) and a wide linear range (0.1 pg·mL-1 to 20 ng·mL-1). This meets the demands of clinical diagnosis (with values <4 ng·mL-1) in serum. The method was applied to the determination of PSA in spiked serum. Graphical abstractSchematic representation of the in-situ growth of ordered Cu-MOFs wrapped with Cu(OH)2 nanowires, building the core-shell structure as the 3D electrode. A novel electrochemical immunosensor for PSA detection has been exploited, using the Cu-MOFs nanowire arrays on Cu foam as a redox signal probe for the first time.

Meta-analysis of the efficacy and safety of integrated Chinese and Western medicine in the treatment of acute myeloid leukaemia in elderly people.

Objective: To systematically evaluate the effectiveness and safety of integrated Chinese and Western medicine in the treatment of acute myeloid leukaemia (AML) in elderly people. Method: The Cochrane Library, PubMed, Web of Science, Excerpta Medica Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Data and VIP Data databases were systematically searched from database inception to 30 June 2023 to identify cases of AML treatment with and without integrated Chinese and Western medicine. Fixed- and random-effect models were used to pool the main results, and the pooled risk ratio (RR) with a 95 % confidence interval (CI) was used as the effect indicator. Results: Eleven randomized controlled trial (RCT) involving 828 patients were finally included. The meta-analysis results showed that the overall response efficiency of integrated Chinese and Western medicine in treating myeloid leukaemia in elderly people was better than that of Western medicine alone (RR = 1.23, 95 % CI: 1.13, 1.33, p ＜ 0.001). There was significant difference in the complete remission rate between the two groups (RR = 1.38, 95 % CI: 1.15, 1.65, p ＜ 0.001). The incidence of myelosuppression (RR = 0.49, 95 % CI: 0.32, 0.75, p = 0.001), hepatic and renal insufficiency (RR = 0.43, 95 % CI: 0.29, 0.66, p ＜ 0.001), infection (RR = 0.26, 95 % CI: 0.17, 0.40, p ＜ 0.001) and gastrointestinal discomfort (RR = 0.31, 95 % CI: 0.22, 0.46, p ＜ 0.001) of integrated Chinese and Western medicine were significantly lower than that of Western medicine alone. Conclusion: Compared with Western medicine alone, the application of integrated traditional Chinese and Western medicine can improve the total clinical remission rate and reduce adverse effects following chemotherapy. However, more high-quality results of randomised controlled trials and analysis are needed to confirm the findings.

Machine learning identifies the role of SMAD6 in the prognosis and drug susceptibility in bladder cancer.

BACKGROUND: Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. METHODS: We collected and screened genes related to the TGF-ß signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. RESULTS: We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. CONCLUSION: Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.

Decomposition of metal-organic complexes and metal recovery in wastewater: A systematic review and meta-synthesis.

Metals are rarely found as free ions in natural and anthropogenic environments, but they are often associated with organic matter and minerals. Under the context of circular economy, metals should be recycled, yet they are difficult to extract for their complex forms in real situations. Based on the protocols of review methodology and the analysis of VOS viewer, there are few reviews on the properties of metal-organic complexes, decomplexation methods, the effect of coexisting ions, the pH influence, and metal recovery methods for the increasingly complicated metal-organic complexes wastewater. Conventional treatment methods such as flocculation, adsorption, biological degradation, and ion exchange fail to decompose metal-organic complexes completely without causing secondary pollution in wastewater. To enhance comprehension of the behavior and morphology exhibited by metal-organic complexes within aqueous solutions, we presented the molecular structure and properties of metal-organic complexes, the decomplexation mechanisms that encompassed both radical and non-radical oxidizing species, including hydroxyl radical (OH), sulfate radical (SO˙4-), superoxide radical (O˙2-), hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen (1O2). More importantly, we reviewed novel aspects that have not been covered by previous reviews considering the impact of operational parameters and coexisting ions. Finally, the potential avenues and challenges were proposed for future research.

Cylindrical granules in the development of mesalazine solid formulations (â ¡): The contribution of high aspect ratio to favorable tabletability.

Recently, cylindrical granules have been applied in pharmaceutical fields and their aspect ratio (AR) is considered an important factor in the manufacturing process. However, the relationships between AR and the tableting process were seldom reported. This study aims to clarify the role of AR in the tableting process of cylindrical granules. First, mesalazine cylindrical granules with different AR were extruded, and their physical attributes were then comprehensively characterized. Subsequently, their compression behaviors and tableting performances were systematically assessed. Notably, it was found that the cylindrical granules with high AR possessed good anti-deformation capacity and favorable tabletability. Finally, the dissolution test suggested that tablets compressed from cylindrical granules with higher AR showed lower dissolution rates. Collectively, findings in this study identified that the AR of cylindrical granules was a critical factor in the tableting process and provided valuable guidance for the application of these granules in oral solid formulations.

Tumor microenvironment sensitization via dual-catalysis of carbon-based nanoenzyme for enhanced photodynamic therapy.

Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.

Tailoring Localized Electrolyte via a Dual-Functional Protein Membrane toward Stable Zn Anodes.

Considerable attention has been by far paid to stabilizing metallic Zn anodes, where side reactions and dendrite formation still remain detrimental to their practical advancement. Electrolyte modification or protected layer design is widely reported; nonetheless, an effective maneuver to synergize both tactics has been rarely explored. Herein, we propose a localized electrolyte optimization via the introduction of a dual-functional biomass modificator over the Zn anode. Instrumental characterization in conjunction with molecular dynamics simulation indicates local solvation structure transformation owing to the limitation of bound water with intermolecular hydrogen bonds, effectively suppressing hydrogen evolutions. Meanwhile, the optimized nucleation throughout the protein membrane allows uniform Zn deposition. Accordingly, the symmetric cell exhibits an elongated lifespan of 3280 h at 1.0 mA cm-2/1.0 mAh cm-2, while the capacity retention of the full cell sustains 91.1% after 2000 cycles at 5.0 A g-1. The localized electrolyte tailoring via protein membrane introduction might offer insights into operational metal anode protection.

Identification of a novel ferroptosis-inducing micropeptide in bladder cancer.

Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.

Dendrite-Free and High-Rate Potassium Metal Batteries Sustained by an Inorganic-Rich SEI.

Potassium metal battery is an appealing candidate for future energy storage. However, its application is plagued by the notorious dendrite proliferation at the anode side, which entails the formation of vulnerable solid electrolyte interphase (SEI) and non-uniform potassium deposition on the current collector. Here, this work reports a dual-modification design of aluminum current collector to render dendrite-free potassium anodes with favorable reversibility. This work achieves to modulate the electronic structure of the designed current collector and accordingly attain an SEI architecture with robust inorganic-rich constituents, which is evidenced by detailed cryo-EM inspection and X-ray depth profiling. The thus-produced SEI manages to expedite ionic conductivity and guide homogeneous potassium deposition. Compared to the potassium metal cells assembled using typical aluminum current collector, cells based on the designed current collector realize improved rate capability (maintaining 400 h under 50 mA cm-2 ) and low-temperature durability (stable operation at -50 °C). Moreover, scalable production of the current collector allows for the sustainable construction of high-safety potassium metal batteries, with the potential for reducing the manufacturing cost.

The e1a3 BCR-ABL1 fusion transcript in Philadelphia chromosome-positive acute lymphoblastic leukaemia: a case report.

ABSTRACTThe Philadelphia (Ph) chromosome results from the formation of breakpoint cluster region (BCR)-Abelson 1 (ABL1) fusion gene (BCR-ABL1). The most common type of adult acute lymphoblastic leukaemia (ALL) is Ph chromosome-positive (Ph+); Ph+ ALL has an incidence of 25%∼30%. Several types of BCR-ABL1 fusion transcripts have been reported, including e1a2, e13a2 and e14a2. In addition, some rare BCR-ABL1 transcripts, such as e1a3, have been reported in chronic myeloid leukaemia. However, until now, the presence of e1a3 BCR-ABL1 fusion transcripts has only been reported in a few cases of ALL. In this study, a rare e1a3 BCR-ABL1 fusion transcript was found in a patient diagnosed with Ph+ ALL. However, the patient also suffered from severe agranulocytosis with pulmonary infection and died after being transferred to the intensive care unit before the significance of the presence of e1a3 BCR-ABL1 fusion transcript could be determined. In conclusion, e1a3 BCR-ABL1 fusion transcripts related to Ph+ ALL cases need to be better identified, and appropriate treatment strategies must be designed for such cases.

Flapless and Conjunctiva-Sparing Technique for Transscleral Fixation of Intraocular Lens to Correct Refractive Errors in Eyes without Adequate Capsular Support.

Purpose: To evaluate refractive outcomes, intraocular lens (IOL) power calculation, and IOL position following a novel conjunctiva-sparing transscleral fixation technique. Methods: Forty-one eyes of 40 patients managed with a flapless transscleral-sutured technique were included. Preoperative and postoperative refractive errors (spherical equivalents, SE) were compared. IOL position was assessed on the Scheimpflug images. IOL power was calculated by SRK/T, Holladay 1, and Hoffer Q formulas. Results: The mean age was 57.39 ± 14.83 years (range: 26 to 79 years), and the mean follow-up was 7.46 ± 6.42 months (range: 1 to 24 months). Surgical indications were aphakia (n = 14), subluxated lenses (n = 3), and IOL dislocation (n = 24). The SE was 4.50 ± 6.38 diopter (D) (range: -3.75 to 13.75 D) preoperatively and -1.68 ± 1.57 D (range: -5.50 to 1.13 D) postoperatively (P < 0.001). The mean tilt angle and decentration were 2.90° ± 1.93° (range: 0.39° to 9.10°) and 0.23 ± 0.19 mm (range: 0.02 to 0.94 mm) vertically, and 1.75° ± 1.41° (range: 0.24° to 7.65°) and 0.18 ± 0.19 mm (range: 0.02 to 1.06 mm) horizontally, which were clinically insignificant. All three IOL formulas produced myopic errors (range: -0.29 to -0.50 D). The SRK/T had the lowest median absolute error (0.55 D), followed by the Holladay 1 (0.70 D) and the Hoffer Q (0.74 D). The three formulas had the same percentage of prediction errors (PEs) within ±0.5 D (43.48%), while the Hoffer Q had the highest percentage of PEs within ±1.0 D (82.61%). Conclusion: The present technique can serve as an alternative approach for transscleral IOL fixation and refractive correction in eyes with compromised capsular support, ensuring the stability of IOLs and reasonable IOL power calculation accuracy.

HO-1-Mediated Autophagic Restoration Protects Lens Epithelial Cells Against Oxidative Stress and Cellular Senescence.

Purpose: Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy. Here, we investigate the crosstalk among HO-1, oxidative stress, and cellular senescence in mouse lens epithelial cells (LECs). Methods: The gene expression of HO-1, p21, LC3, and p62 was measured in human samples. The protective properties of HO-1 were examined in hydrogen peroxide (H2O2)-damaged LECs. Autophagic flux was examined by Western blot and mRFP-GFP-LC3 assay. Western blotting and lysotracker staining were used to analyze lysosomal function. Flow cytometry was used to detect intracellular reactive oxygen species and analyze cell cycle. Senescence-associated ß-galactosidase assay was used to determine cellular senescence. The crosstalk between HO-1 and transcription factor EB (TFEB) was further observed in TFEB-knockdown cells. The TFEB binding site in the promoter region of Hmox1 was predicted by the Jasper website and was confirmed by chromatin immunoprecipitation assay. Results: HO-1 gene expression decreased in LECs of patients with age-related nuclear cataract, whereas mRNA expression levels of p21, LC3, and p62 increased. Upon H2O2-induced oxidative stress, LECs showed the characteristics of autophagic flux blockade, lysosomal dysfunction, and premature senescence. Interestingly, HO-1 significantly restored the impaired autophagic flux and lysosomal function and delayed cellular senescence. TFEB gene silencing greatly reduced the HO-1-mediated autophagic restoration, leading to a failure to prevent LECs from oxidative stress and premature senescence. Conclusions: We demonstrated HO-1 effects on restoring autophagic flux and delaying cellular senescence under oxidative stress in LECs, which are dependent on TFEB.