Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.

Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.

TME-Related Biomimetic Strategies Against Cancer.

The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer­associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.

2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer.

Nuclear atypia, including altered nuclear size, contour, and chromatin organization, is ubiquitous in cancer cells. Atypical primary nuclei and micronuclei can rupture during interphase; however, the frequency, causes, and consequences of nuclear rupture are unknown in most cancers. We demonstrate that nuclear envelope rupture is surprisingly common in many human cancers, particularly glioblastoma. Using highly-multiplexed 2D and super-resolution 3D-imaging of glioblastoma tissues and patient-derived xenografts and cells, we link primary nuclear rupture with reduced lamin A/C and micronuclear rupture with reduced lamin B1. Moreover, ruptured glioblastoma cells activate cGAS-STING-signaling involved in innate immunity. We observe that local patterning of cell states influences tumor spatial organization and is linked to both lamin expression and rupture frequency, with neural-progenitor-cell-like states exhibiting the lowest lamin A/C levels and greatest susceptibility to primary nuclear rupture. Our study reveals that nuclear instability is a core feature of cancer, and links nuclear integrity, cell state, and immune signaling.

IGF2BP1-mediated N6-methyladenosine modification promotes intrahepatic cholangiocarcinoma progression.

N6-methyladenosine (m6A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m6A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA.

Human endoderm stem cells reverse inflammation-related acute liver failure through cystatin SN-mediated inhibition of interferon signaling.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.

Use of different ligand modification liposomes to evaluate the anti-liver tumor activity of cantharidin.

In this study, cantharidin(CTD), a bioactive terpenoid in traditional Chinese medicine cantharidin, was selected as a model component to construct novel nano liposome delivery systems for hepatocellular carcinoma therapy. Previous studies have shown that although cantharidin has definite curative effects on primary liver cancer, it is associated with numerous toxic and side effects. Therefore, based on the glycyrrhetinic acid (GA) binding site and the asialoglycoprotein receptor (ASGPR) on the hepatocyte membrane, the surface of CTD liposomes was modified with stearyl alcohol galactoside (SA-Gal) or/and the newly synthesized 3-succinic-30-stearyl deoxyglycyrrhetinic acid (11-DGA-Suc) ligands, and the physicochemical properties, pharmacokinetics, in vivo and in vitro anti-liver tumor activity and its mechanism of modified liposomes were investigated. Compared to CTD-lip, SA-Gal-CTD-lip, and 11-DGA-Suc + SA-Gal-CTD-lip, 11-DGA-Suc-CTD-lip showed stronger cytotoxicity and increased inhibition of HepG2 cell migration had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells was arrested mainly at G0/G1phase and G2/M phase. The results of in vivo pharmacokinetic experiments revealed that the distribution of modified liposomes in the liver was significantly increased compared with that of unmodified liposome. In vivo tumor inhibition experiment showed that 11-DGA-Suc-CTD-lip had excellent tumor inhibition, and the tumor inhibition rates was 80.96%. The 11-DGA-Suc-CTD-lip group also displayed the strongest proliferation inhibition with the lowest proliferation index of 7% in PCNA assay and the highest apoptotic index of 49% in TUNEL assay. Taken together, our findings provide a promising solution for improving the targeting of nano liposomes and further demonstrates the encouraging potential of poor solubility and high toxicity drugs applicable to tumor therapy.

Immediate or Delayed Sequential Bilateral ICL Surgery: a Survey of Chinese Ophthalmologists.

INTRODUCTION: In China, the demand for implantable collamer lens (ICL) surgery is booming. Immediate sequential bilateral ICL surgery (ISBICLS) benefits patients and clinics, but it remains controversial and lacks standardization. We aim to investigate the prevalence of, factors for, and surgeon attitudes toward ISBICLS. METHODS: In this cross-sectional survey study, an electronic questionnaire about the practice and attitudes toward performing ISBICLS or delayed sequential bilateral ICL surgery (DSBICLS) was distributed to 792 qualified ICL surgeons in Mainland China, between 4 April and 22 April 2022. RESULTS: A total of 531 surgeons (66.79%) from 30 provinces in Mainland China responded. Among them, 374 (67.23%) were currently performing ISBICLS. Fifty-two percent (277) of surgeons reported performing ISBICLS more than 50% of the time, while 85.05% of surgeons chose to perform the second eye surgery 1 day after the first eye surgery. Seventy percent (248) of surgeons performing ISBICLS chose to perform the second eye surgery less than 30 min after the first eye surgery. Surgeons who started ICL surgery earlier (before 2010, OR = 2.772, 95% CI = 1.290-5.957, P = 0.009; 2011-2013, OR = 2.479, 95% CI = 1.060-5.800, P = 0.036), completed one-eye ICL surgery faster (< 3 min, OR = 3.936, 95% CI = 1.505-10.293, P = 0.005) and modified the second eye ICL selection less frequently (1-25%, OR = 0.203, 95% CI = 0.054-0.771, P = 0.019; 26-50%, OR = 0.173, 95% CI = 0.041-0.726, P = 0.017; 51-75%, OR = 0.299, 95% CI = 0.041-0.726, P = 0.123; 76-100%, OR = 0.163, 95% CI = 0.039-0.688, P = 0.014) tended to perform ISBICLS. No significant association was found among clinical settings, preoperative measurement devices, and hospital policies with performing ISBICLS. Regarding their attitudes toward ISBICLS, 54.63% preferred ISBICLS and 45.37% preferred DSBICLS. The main supporting reasons were patient convenience (98.64%), faster vision rehabilitation (73.56%), and improved perioperative compliance (73.22%). The concerns regarding ISBICLS included the risk of endophthalmitis (62.22%), lack of recommendation in expert consensus (61.67%), and decreased vault predictability (60.93%). The most common desires for further adoption were expert consensus on surgical criteria and patient indicators for ISBICLS (82.3%). CONCLUSIONS: ISBICLS has been gradually adopted in Mainland China, but has not been widely accepted as a routine procedure. Surgeons' experience and skills mainly influence whether ISBICLS is performed. Further research is needed to explore standardized protocols to prevent endophthalmitis, the appropriate time interval of two eye surgery, and requisitions for surgeon skills.

The association between dairy products consumption and prostate cancer risk: a systematic review and meta-analysis.

In this study, we conducted a meta-analysis to estimate the relationship between the consumption of dairy products and the risk of prostate cancer. We searched PubMed, Embase and Cochrane databases for relevant articles and identified a total of thirty-three cohort studies between 1989 and 2020. The qualities of included studies were assessed using Newcastle-Ottawa scale. Pooled adjusted relative risks (RR) with 95 % CI were calculated. We performed subgroup analyses stratified by dairy type, prostate cancer type, follow-up years, treatment era, collection times, adjustment for confounders and geographic location. In the subgroup analysis stratified by prostate cancer type, the pooled RR were 0·98 (95 % CI 0·94, 1·03) in the advanced group, 1·10 (95 % CI 0·98, 1·24) in the non-advanced group and 0·92 (95 % CI 0·84, 1·00) in the fatal group. In the dose-response analysis, a positive association for the risk of prostate cancer was observed for total dairy products 400 g/d (RR: 1·02; 95 % CI 1·00, 1·03), total milk 200 g/d (RR: 1·02; 95 % CI 1·01, 1·03), cheese 40 g/d (RR: 1·01; 95 % CI 1·00, 1·03) and butter 50 g/d (RR: 1·03; 95 % CI 1·01, 1·05). A decreased risk was observed for the intake of whole milk 100 g/d (RR: 0·97; 95 % CI 0·96, 0·99). Our meta-analysis suggests that high intakes of dairy products may be associated with an increased risk of prostate cancer; however, since many of the studies were affected by prostate-specific antigen (PSA) screening bias, additional studies with an adjustment of PSA screening are needed.

Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma.

Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75-110 nm with size dispersion (PDI) within the range of 0.19-0.50 and zeta-potential approximately -10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability-their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.

Safety and anterior chamber structure of evolution implantable Collamer lens implantation with short white-to-white corneal diameters.

Introduction: To evaluate the safety and anterior chamber structure of implantation of the Evolution (EVO) implantable Collamer lens (EVO-ICL) in patients with short white-to-white (WTW) corneal diameters. Materials and methods: The study population was divided into two groups: the experimental group (34 eyes of 34 patients) with WTW corneal diameters of ≤10.6 mm and the control group (59 eyes of 59 patients) with WTW corneal diameters of >10.6 mm. The outcome measures included uncorrected distance visual acuity, corrected distance visual acuity, refractive power, intraocular pressure (IOP), anterior chamber angle, depth, volume, and vault. Results: The safety indices of the experimental and control groups were 1.17 ± 0.30 and 1.12 ± 0.14, respectively (P > 0.05); the effectiveness indices were 1.16 ± 0.31 and 1.07 ± 0.17, respectively (P > 0.05). The simulation curves of the expected and actual corrections in the experimental and control groups were y = 0.9876x - 0.0927 and y = 0.9799x + 0.0343, respectively. There were no significant differences between the IOPs and anterior chamber structures of the two groups (P > 0.05). The average vaults of the experimental and control groups were 395.76 ± 155.32 and 389.49 ± 135.01 µm, respectively (P > 0.05). Conclusion: EVO-ICL implantation in patients with short WTW corneal diameters (≤ 10.6 mm) was determined to be a safe, effective, and predictable method for correcting myopia. The changes in the anterior chamber structure were still within normal limits after the surgery, the IOP remained stable, and the ideal vault was achieved after the surgery.

Lysophosphatidic acid protects cervical cancer HeLa cells from apoptosis induced by doxorubicin hydrochloride.

Cervical cancer is one of the most common types of gynecological tumors. Lysophosphatidic acid (LPA), as a bioactive lipid medium, plays an important role in numerous physiological and pathophysiological processes, including the stimulation of cell migration and tumor cell invasion. LPA is increased in the plasma of patients with cervical cancer. Doxorubicin hydrochloride (DOX) is used as a first-line drug in the treatment of cervical cancer in clinics, however, the effect and molecular mechanism of LPA on DOX-induced apoptosis in cervical cancer cells remain unclear. Therefore, the present study aimed to explore the effect and underlying molecular mechanism of LPA on DOX-induced apoptosis in cervical cancer cells. HeLa cells were treated as a control group or with LPA (10 µmol/l), DOX (4 µmol/l) or LPA (10 µmol/l) + DOX (4 µmol/l) for 24 h. Using transmission electron microscopy the results demonstrated that LPA reduced cell death and the degree of chromatin aggregation in DOX-induced HeLa cells. Reverse transcription-quantitative PCR demonstrated that LPA significantly downregulated caspase-3 mRNA expression levels in DOX-induced HeLa cells. Moreover, western blotting demonstrated that LPA significantly reduced caspase-3 and cleaved caspase-3 protein expression levels in DOX-induced HeLa, C33A and SiHa cells. Furthermore, flow cytometry demonstrated that LPA may prevent apoptosis in DOX-induced HeLa cells (P<0.05). Using dichloro-dihydro-fluorescein diacetate assay, it was demonstrated that LPA significantly reduced the intracellular ROS levels induced by DOX. In summary, the present study indicated that LPA may protect HeLa cells from apoptosis induced by DOX. These findings have provided experimental evidence that LPA may be a potential therapeutic target for the treatment of cervical cancer.

Nano Drug Delivery System for Tumor Immunotherapy: Next-Generation Therapeutics.

Tumor immunotherapy is an artificial stimulation of the immune system to enhance anti-cancer response. It has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing in recent years, and many treatments are in clinical and preclinical stages. Despite this progress, the special tumor heterogeneity and immunosuppressive microenvironment of solid tumors made immunotherapy in the majority of cancer cases difficult. Therefore, understanding how to improve the intratumoral enrichment degree and the response rate of various immunotherapy drugs is key to improve efficacy and control adverse reactions. With the development of materials science and nanotechnology, advanced biomaterials such as nanoparticle and drug delivery systems like T-cell delivery therapy can improve effectiveness of immunotherapy while reducing the toxic side effects on non-target cells, which offers innovative ideas for improving immunity therapeutic effectiveness. In this review, we discuss the mechanism of tumor cell immune escape and focus on current immunotherapy (such as cytokine immunotherapy, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus, and other new types of immunity) and its challenges as well as the latest nanotechnology (such as bionic nanoparticles, self-assembled nanoparticles, deformable nanoparticles, photothermal effect nanoparticles, stimuli-responsive nanoparticles, and other types) applications in cancer immunotherapy.

Preoperative localization of sentinel lymph nodes using percutaneous contrast-enhanced ultrasonography in patients with breast cancer.

Background: This study aimed to investigate the feasibility of preoperative identification of sentinel lymph nodes (SLNs) by contrast-enhanced ultrasound (CEUS) for patients with breast cancer. Methods: The patients with T1-T2N0M0 breast cancer who were scheduled for primary surgical treatment were recruited. All the patients had received a periareolar intradermal injection of an ultrasonic contrast agent (SonoVue, Bracco, Milan, Italy) followed by an ultrasound to identify contrast-enhanced SLNs. A guidewire was deployed to localize the SLN. Methylene blue stain was used to help trace SLNs during the operation. The identification rate and accuracy rate were recorded. The number of SLNs labeled by two methods was counted and compared using Wilcoxon testing. Results: A total of 366 SLNs were detected in 72 patients by methylene blue intraoperatively, with a median of 5 lymph nodes [interquartile range (IQR), 4-6] per patient. A total of 95 SLNs were detected in 63 patients (87.5%) by CEUS, with a median of 1 lymph node (IQR, 1-2) per patient. The number of SLNs detected by CEUS was significantly less than that labeled by the methylene blue staining method (Z=-7.362, P=0000). Pathology confirmed 12 single metastases in all the lymph nodes examined, 10 of which were the only lymph node identified by CEUS. Conclusions: Periareolar intradermal injection of an ultrasonic contrast agent was an effective and convenient supplementary to localize SLNs. The technique was expected to improve the accuracy of axillary staging with minor surgical trauma and postoperative complications.

Pathological and imaging features of Paget's disease and nipple adenoma: a comparative study.

BACKGROUND: Both Paget's disease (PD) and nipple adenoma (NA) are rare lesions occurred on nipple and share some similarities in clinical manifestations, but there are have different pathological manifestations and imaging findings. This study analyzed the clinicopathological and imaging features of PD in nipple and NA to improve our knowledge about these two diseases and to provide guidance for clinical diagnosis and treatment. METHODS: Retrospectively analyzed 99 female patients confirmed by surgery and pathology from January 2014 to December 2018. The features of imaging examination included 95 cases of breast ultrasound, 83 cases of breast X-ray and 24 cases of magnetic resonance imaging (MRI) were analyzed and compered the detection rate and diagnostic accuracy. RESULTS: The 99 patients consisted of 76 patients with PD and 23 patients with NA. Despite the similarity of clinical manifestations between PD and NA, the pathological features of these diseases were completely different. Differences in various imaging manifestations were found to facilitate differential diagnosis. Breast X-ray and ultrasound can discover the nipple areola changes such as mass and calcification, but some cases still show negative. Breast MRI can clearly show the areola lesions of nipple PD and NA, accurately evaluate the degree and size of breast lesions, and help clinicians choose appropriate and personalized diagnosis and treatment methods. CONCLUSIONS: The combination of multiple breast imaging examinations (including X-ray, ultrasound, and MRI) can improve the diagnosis of PD and NA and play a guiding role in the options for clinical treatment.

FOXM1-induced TYMS upregulation promotes the progression of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the major causes of cancer-related death. Thymidylate synthase (TYMS) catalyzes the methylation of deoxy guanosine to deoxy thymidylate, which is a crucial gene for DNA repair and replication. Thus, TYMS was reported to be closely associated with developing a variety of tumors, but it has been poorly studied in HCC. MATERIALS AND METHODS: We used the cell counting kit-8 (CCK-8), BrdU, and CFSE assay to measure cell proliferation. The flow cytometry assay and the TUNEL assay were used for assessing cell apoptosis. The flow cytometry assay was used to analyze the cell cycle. The Transwell invasion assay and the wound healing assay were conducted to determine the invasive ability of the cells. RT-qPCR and Western blot analyses were performed to evaluate the mRNA and protein expression levels of specific genes, respectively. RESULTS: TYMS was found to be upregulated in both HCC cells and patient samples. High expression of TYMS was associated with an unfavorable prognosis in HCC patients based on the TCGA-LIHC dataset. Cell proliferation, apoptosis, and invasion assays revealed that TYMS promoted the proliferation and invasion of HCC cells as well as inhibited apoptosis. In addition, TYMS is a downstream target of FOXM1. TYMS knockdown reversed the 5-FU resistance caused by FOXM1 overexpression and re-sensitized HCC cells to 5-FU treatment. CONCLUSION: This study suggested that TYMS serves as an oncogene in HCC, and targeting the FOXM1-TYMS axis may help improve the survival of HCC patients as well as provide new insights for treating advanced HCC patients.

Five-year outcomes of EVO implantable collamer lens implantation for the correction of high myopia and super high myopia.

BACKGROUND: To evaluate the long-term safety, efficacy, predictability, and stability of implantable collamer lens with a central hole (EVO ICL) implantation for correcting high myopia (HM) and super high myopia (SHM). METHODS: This prospective study evaluated 83 eyes of 46 patients who were divided into groups based on their spherical equivalent refractive error (SE): HM group (- 12 D ≤ SE < - 6 D) and SHM group (SE < - 12 D). They were followed up for 5 years after ICL implantation; assessments of uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refractive error, axial length, intraocular pressure, corneal endothelial cell density, and vault were conducted, and a questionnaire was administered. RESUITS: At 5 years postoperatively, the safety indices of the HM and SHM groups were 1.03 ± 0.10 and 1.32 ± 0.39, and the efficacy indices were 0.83 ± 0.25 and 0.86 ± 0.32, respectively. In the HM group, 60.47% and 79.07% of the eyes were within ± 0.50 D and ± 1.00 D of the attempted correction, while it was achieved for 22.50% and 47.50% of the eyes in the SHM group, respectively. The SE of the HM group decreased from - 9.72 ± 1.41 D preoperatively to 0.04 ± 0.39 D 1 month postoperatively and - 0.67 ± 0.57 D 5 years postoperatively, while in the SHM group, it decreased from - 15.78 ± 3.06 D preoperatively to - 0.69 ± 0.97 D 1 month postoperatively and - 1.74 ± 1.19 D 5 years postoperatively. CONCLUSION: EVO ICL implantation is safe, effective, and predictable for correcting HM and SHM. CDVA improved more after surgery for SHM, but the growth of axial length still needs attention.

Radiation­induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues.

Thoracic radiotherapy increases the risk of radiation­induced heart damage (RIHD); however, the molecular mechanisms underlying these changes are not fully understood. The aim of the present study was to investigate the effects of radiation on the mouse heart using high­throughput proteomics. Male C57BL/6J mice were used to establish a model of RIHD by exposing the entire heart to 16 Gy high­energy X­rays, and cardiac injuries were verified using a cardiac echocardiogram, as well as by measuring serum brain natriuretic peptide levels and conducting H&E and Masson staining 5 months after irradiation. Proteomics experiments were performed using the heart apex of 5­month irradiated mice and control mice that underwent sham­irradiation. The most significantly differentially expressed proteins were enriched in 'cardiac fibrosis' and 'energy metabolism'. Next, the cardiac fibrosis and changes to energy metabolism were confirmed using immunohistochemistry staining and western blotting. Extracellular matrix proteins, such as collagen type 1 α 1 chain, collagen type III α 1 chain, vimentin and CCCTC­binding factor, along with metabolism­related proteins, such as fatty acid synthase and solute carrier family 25 member 1, exhibited upregulated expression following exposure to ionizing radiation. Additionally, the myocardial mitochondria inner membranes were injured, along with a decrease in ATP levels and the accumulation of lactic acid in the irradiated heart tissues. These results suggest that the high doses of ionizing radiation used lead to structural remodeling, functional injury and fibrotic alterations in the mouse heart. Radiation­induced mitochondrial damage and metabolic alterations of the cardiac tissue may thus be a pathogenic mechanism of RIHD.

Increased Levels of Serum Glycosylated Hemoglobin are Associated with Depressive Symptoms in a Population with Cancer (≥49 Years): An Antidepressant-Stratified Analysis.

PURPOSE: Patients with cancer tend to have a high prevalence of depressive symptoms. The direct relationship between serum glycosylated hemoglobin (GHb) levels and depressive symptoms in cancer patients is still uncertain. We aimed to evaluate the association with serum GHb levels with depressive symptoms in the population (aged ≥49 years) with cancer. PATIENTS AND METHODS: Longitudinal data in 204 participants with cancer obtained from The Irish LongituDinal Study on Ageing (TILDA) were used to investigate the association of serum GHb levels with depressive symptoms. RESULTS: Our results suggested a positive and significant association between serum GHb levels and depression score, independent of age, gender, body mass index (BMI), currently married, education, smoking status, drink alcohol, systolic and diastolic blood pressure (BP), physical activity, self-reported cardiovascular diseases and laboratory measurement in participants with cancer (coefficient =0.141, P<0.001; Model 2) at baseline (wave 1). Higher GHb levels did associate with higher prevalence of depressive symptoms in participants with cancer (OR=2.100, 95% CI 1.105-5.036, P=0.004; Model 2) after adjustment for these same confounding factors in wave 1 was made. Stratified analysis further showed that these significant associations were interfered by antidepressants. Sensitivity analysis showed that higher serum GHb levels in subjects with cancer were linked to higher prevalence of depression events during a follow-up of 4 years. CONCLUSION: Our results found a significant association between elevated serum GHb levels and increased risk of depressive symptoms in the population aged ≥49 years with cancer after confounding factors were adjusted.

Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT.

The epithelial-mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they coregulate a set of cassette exon events, with the majority showing discordant splicing regulation. Discordant splicing events regulated by hnRNPM show a positive correlation with splicing during EMT; however, concordant events do not, indicating the role of hnRNPM in regulating alternative splicing during EMT is more complex than previously understood. Motif enrichment analysis near hnRNPM-ESRP1 coregulated exons identifies guanine-uridine rich motifs downstream from hnRNPM-repressed and ESRP1-enhanced exons, supporting a general model of competitive binding to these cis-elements to antagonize alternative splicing. The set of coregulated exons are enriched in genes associated with cell migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of coregulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtyping. This study identifies complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts.