Long-Term Follow-Up of Patients Undergoing Thalidomide Therapy for Transfusion-Dependent ß-Thalassaemia: A Single-Center Experience.

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent ß-thalassemia (TDT). Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed. Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed. Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.

Using multiomics to explore the weight differences between genders in Muscovy ducks.

Sexual dimorphism in poultry, especially in Muscovy ducks, is a proven phenomenon characterized by significant differences in body weight, growth patterns, and gene expression between male and female individuals. However, there is a dearth of research on the candidate genes and mechanisms underlying these weight differences. We selected 301 Muscovy ducks and recorded their weekly body weights from birth. We utilized 3 non-linear growth models (Logistic, Bertalanffy, and Gompertz) to fit the growth curve of Muscovy ducks, it was found that the logistic model was the most suitable model for describing the growth curve of Muscovy ducks. The results from the logistic model showed that the inflection point of male Muscovy ducks occurred at a later age, and they had a heavier mature body weight than female Muscovy ducks. At 10 wk of age, we collected Muscovy duck breast muscle tissues for transcriptome sequencing (RNA-seq). To exclude the impact of weight difference, 185 differentially expressed genes (DEGs), such as PPAR, FABP3, PLIN1, and FOXO1, were screened. These DEGs were predominantly enriched in terms related to mitochondria, lipids, and nucleic acids. In addition, the gut microbiota has the ability to influence host physiology through the regulation of multiple processes, including playing a crucial role in host muscle growth and development. We randomly selected male and female Muscovy ducks for 16S rRNA sequencing analysis of their cecal microbiota. The results showed that there were significant differences in the composition of cecal microbiota between male and female Muscovy ducks. At the genus level, the relative abundance of Enterenecus and CAG_269 were lower in males compared to females, while Lawsonibacter, Parabacteroides_B, Streptococcus, UBA2658, Caccousia, and Butyricimonas were higher in males than in females. In summary, this study provides a scientific theoretical basis for revealing the different growth patterns of male and female Muscovy ducks, and offers explanations from both the molecular level and microbiological perspectives.

The Role of CXCL11 and its Receptors in Cancer: Prospective but Challenging Clinical Targets.

Chemokine ligand 11 is a member of the CXC chemokine family and exerts its biological function mainly through binding to CXCR3 and CXCR7. The CXCL11 gene is ubiquitously overexpressed in various human malignant tumors; however, its specific mechanisms vary among different cancer types. Recent studies have found that CXCL11 is involved in the activation of multiple oncogenic signaling pathways and is closely related to tumorigenesis, progression, chemotherapy tolerance, immunotherapy efficacy, and poor prognosis. Depending on the specific expression of its receptor subtype, CXCL11 also has a complex 2-fold role in tumours; therefore, directly targeting the structure-function of CXCL11 and its receptors may be a challenging task. In this review, we summarize the biological functions of CXCL11 and its receptors and their roles in various types of malignant tumors and point out the directions for clinical applications.

CXCL11 is found in many types of cancer and affects how cancer cells grow and respond to treatments. This paper delves into the intricate dance between CXCL11 and its receptors in various types of cancer. Like a versatile actor playing different roles on stage, CXCL11 can either promote or hinder cancer growth depending on its interaction with specific receptors. Understanding how CXCL11 works could help develop new treatments for cancer, but it's a complex challenge because CXCL11 can have different effects depending on the type of cancer and which receptors it binds to.

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future Applications.

Native vertebral osteomyelitis, also termed spondylodiscitis, is an antibiotic-resistant disease that requires long-term treatment. Without proper treatment, NVO can lead to severe nerve damage or even death. Therefore, it is important to accurately diagnose the cause of NVO, especially in spontaneous cases. Infectious NVO is characterized by the involvement of 2 adjacent vertebrae and intervertebral discs, and common infectious agents include Staphylococcus aureus, Mycobacterium tuberculosis, Brucella abortus, and fungi. Clinical symptoms are generally nonspecific, and early diagnosis and appropriate treatment can prevent irreversible sequelae. Advances in pathologic histologic imaging have led physicians to look more forward to being able to differentiate between tuberculous and septic spinal discitis. Therefore, research in identifying and differentiating the imaging features of these 4 common NVOs is essential. Due to the diagnostic difficulties, clinical and radiologic diagnosis is the mainstay of provisional diagnosis. With the advent of the big data era and the emergence of convolutional neural network algorithms for deep learning, the application of artificial intelligence (AI) technology in orthopedic imaging diagnosis has gradually increased. AI can assist physicians in imaging review, effectively reduce the workload of physicians, and improve diagnostic accuracy. Therefore, it is necessary to present the latest clinical research on NVO and the outlook for future AI applications.

Erratum: Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD: Erratum.

[This corrects the article DOI: 10.7150/ijbs.71809.].

Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

Unbiased and Signal-Weakening Photoelectrochemical Hexavalent Chromium Sensing via a CuO Film Photocathode.

Photoelectrochemical (PEC) sensors show great potential for the detection of heavy metal ions because of their low background noise, high sensitivity, and ease of integration. However, the detection limit is relatively high for hexavalent chromium (Cr(VI)) monitoring in addition to the requirement of an external bias. Herein, a CuO film is readily synthesized as the photoactive material via reactive sputtering and thermal annealing in the construction of a PEC sensing photocathode for Cr(VI) monitoring. A different mechanism (i.e., Signal-Weakening PEC sensing) is confirmed by examining the electrochemical impedance and photocurrent response of different CuO film photoelectrodes prepared with the same conditions in contact with various solutions containing concentration-varying Cr(VI) for different durations. The detection of Cr(VI) is successfully achieved with the Signal-Weakening PEC response; a drop of photocathode signal with an increasing Cr(VI) concentration from the steric hindrance effect of the in situ formed Cr(OH)3 precipitates. The photocurrent of the optimized CuO film photocathode linearly declines as the concentration of Cr(VI) increases from 0.08 to 20 µM, with a detection limit down to 2.8 nM (Signal/Noise = 3) and a fitted sensitivity of 4.22 µA·µM-1. Moreover, this proposed sensing route shows operation simplicity, satisfactory selectivity, and reproducibility.

TAT gene polymorphism and its relationship with production traits in Muscovy ducks (Cairina Moschata).

In a previous study, the laying pattern of Muscovy duck was explored by macro-fitting the laying curve of Muscovy duck, and transcriptome sequencing technique of the ovarian tissues was used to screen the egg-related gene "TAT." Moreover, recent results have shown that TAT is expressed in organs such as oviduct, ovary, and testis. The objective of this study is to examine the effect of TAT gene on egg production traits of Muscovy ducks. First, the expression levels of TAT gene in highest producing (HP) and lowest producing (LP) in 3 tissues related to reproduction were examined, and the results indicated that the expression of TAT gene in hypothalamus was significantly different between HP and LP groups. Then, 6 SNP loci (g. 120G>T, g, 122G>A, g, 254G> A, g. 270C >T, g, 312G>A, and g. 341C>A) were detected in TAT gene. Further, association analysis between the six SNP loci of TAT gene and egg production traits of 652 individual Muscovy ducks was done. The results showed that g. 254G>A and g. 270C>T were significantly correlated (P < 0.05 or 0.001) with the egg production traits of Muscovy ducks. This study elucidated the molecular mechanism that TAT gene might be regulating the egg production traits of Muscovy ducks.

HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis.

Nasopharyngeal carcinoma (NPC), as one of the most prevalent malignancies in the head and neck region, still lacks a complete understanding of its pathogenesis. Presently, radiotherapy, concurrent chemoradiotherapy, and targeted therapy stand as the primary modalities for treating NPC. With advancements in medicine, the cure rates for nasopharyngeal carcinoma have been steadily increasing. Nevertheless, recurrence and metastasis persist as the primary reasons for treatment failure. Consequently, a profound exploration of the molecular mechanisms underlying the occurrence and progression of nasopharyngeal carcinoma, along with the exploration of corresponding therapeutic approaches, becomes particularly imperative in the quest for comprehensive solutions to combat this disease. High mobility group AT-hook 2 (HMGA2) is a pivotal protein capable of altering chromatin structure, regulating gene expression, and influencing transcriptional activity. In the realm of cancer research, HMGA2 exhibits widespread dysregulation, playing a crucial role in nearly all malignant tumors. It is implicated in various tumorigenic processes, including cell cycle regulation, cell proliferation, epithelial-mesenchymal transition, angiogenesis, tumor invasion, metastasis, and drug resistance. Additionally, HMGA2 serves as a molecular marker and an independent prognostic factor in certain malignancies. Recent studies have increasingly unveiled the critical role of HMGA2 in nasopharyngeal carcinoma (NPC), particularly in promoting malignant progression, correlating with tumor resistance, and serving as an independent adverse prognostic factor. This review focuses on elucidating the oncogenic role of HMGA2 in NPC, suggesting its potential association with chemotherapy resistance in NPC, and proposing its candidacy as an independent factor in nasopharyngeal carcinoma prognosis assessment.

Research Note: Association of single nucleotide polymorphism of AKT3 with egg production traits in White Muscovy ducks (Cairina moschata).

Prior studies on transcriptomes of hypothalamus and ovary revealed that AKT3 is one of the candidate genes that might affect egg production in White Muscovy ducks. The role of AKT3 in the uterus during reproductive processes cannot be overemphasized. However, functional role of this gene in the tissues and on egg production traits of Muscovy ducks remains unknown. To identify the relationship between AKT3 and egg production traits in ducks, relative expression profile was first examined prior to identifying the variants within AKT3 that may underscore egg production traits [age at first egg (AFE), number of eggs at 300 d (N300D), and number of eggs at 59 wk (N59W)] in 549 ducks. The mRNA expression of AKT3 gene in high producing (HP) ducks was significantly higher than low producing (LP) ducks in the ovary, oviduct, and hypothalamus (P < 0.05 or 0.001). Three variants in AKT3 (C-3631A, C-3766T, and C-3953T) and high linkage block between C-3766T and C-3953T which are significantly (P < 0.05) associated with N300D and N59W were discovered. This study elucidates novel knowledge on the molecular mechanism of AKT3 that might be regulating egg production traits in Muscovy ducks.

Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD.

Overcoming energy stress is a critical step for cells in solid tumors. Under this stress microenvironment, cancer cells significantly alter their energy metabolism to maintain cell survival and even metastasis. Our previous studies have shown that thioredoxin-1 (Trx-1) expression is increased in colorectal cancer (CRC) and promotes cell proliferation. However, the exact role and mechanism of how Trx-1 is involved in energy stress are still unknown. Here, we observed that glucose deprivation of CRC cells led to cell death and promoted the migration and invasion, accompanied by upregulation of Trx-1. Increased Trx-1 supported CRC cell survival under glucose deprivation. Whereas knockdown of Trx-1 sensitized CRC cells to glucose deprivation-induced cell death and reversed glucose deprivation-induced migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we identified glucose-6-phosphate dehydrogenase (G6PD) interacting with Trx-1 by HuPortTM human protein chip, co-IP and co-localization. Trx-1 promoted G6PD protein expression and activity under glucose deprivation, thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) generation. Moreover, G6PD knockdown sensitized CRC cells to glucose deprivation-induced cell death and suppressed glucose deprivation-induced migration, invasion, and EMT. Inhibition of Trx-1 and G6PD, together with inhibition of glycolysis using 2-deoxy-D-glucose (2DG), resulted in significant anti-tumor effects in CRC xenografts in vivo. These findings demonstrate a novel mechanism and may represent a new effective therapeutic regimen for CRC.

A prediction model for sulcus-to-sulcus diameter in myopic eyes: a 1466-sample retrospective study.

BACKGROUND: To establish and verify the accuracy and reliability of a sulcus-to-sulcus diameter (STS) prediction model. METHODS: In this retrospective study, the prediction formula was established with the data from 1466 eyes from 733 subjects from July 2020 to April 2021 and verified with the data from 278 eyes from 139 subjects between May 2021 and June 2021. Each subject was measured with a Pentacam, IOLMaster 700, OPD-Scan III, and ultrasound biomicroscope. The prediction formulas were established with multiple linear regression, and intergroup correlation coefficients (ICCs) and Bland-Altman tests were used to assess the agreement between the predicted and actual STS (actual STS was measured by UBM). RESULTS: The explanatory variables relevant to the horizontal STS (STSH) were the Pentacam white-to-white diameter (WTWP; standardized partial regression coefficient [ß] = 0.330; p < 0.001), the flat K value (ß = -0.211; p < 0.001), and the anterior corneal diameter (ACD) (ß = 0.178; p < 0.001). The corresponding multiple regression equation was : STSH (mm) = 8.061 + 0.510 × WTWP - 0.090 × Flat K value + 0.430 × ACD. The explanatory variables relevant to the vertical STS (STSV) were the WTWP (ß = 0.435; p < 0.001), the steep K value (ß = -0.271; p < 0.001), and the ACD (ß = 0.187; p < 0.001). The corresponding multiple regression equation was : STSV (mm) = 8.540 + 0.492 × WTWP - 0.075 × Steep K value + 0.329 × ACD. The bias of the predicted to the actual STSH was - 0.021, with 95% limits of agreement (95% LoA) from - 0.499 to 0.457. The bias of the predicted to the actual STSV was 0.057, with 95% LoA from - 0.462 to 0.575. The ICC was 0.883 between the predicted and actual STSH and 0.859 between the predicted and actual STSV. CONCLUSIONS: The Pentacam-measured WTW, the K value and the ACD are important for predicting the STS diameter. The prediction model has good accuracy and reliability. TRIAL REGISTRATION: Not applicable.

DNA comethylation analysis reveals a functional association between BRCA1 and sperm DNA fragmentation.

OBJECTIVES: To identify the DNA comethylation patterns associated with sperm DNA fragmentation (SDF) and to explore the potential associations of hub genes with SDF. DESIGN: Prospective study. SETTING: University-affiliated reproductive medicine center. PATIENT(S): A total of 300 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comethylation network analysis based on the genome-wide methylation profile of spermatozoal DNA from 20 men was performed to identify hub modules and genes involved in SDF. Human spermatozoa were used for targeted bisulfite amplicon sequencing (267 men) or droplet digital polymerase chain reaction (45 men). The potential role of Brca1 in DNA damage was explored in mouse GC2 spermatocyte cells. Oxidative damage to spermatocytes was modeled by incubating GC2 cells with H2O2 (25 mM) for 90 minutes. RESULT(S): BRCA1 was identified as a hub gene in SDF. Promoter hypermethylation of BRCA1 was observed in those samples with a high DNA fragmentation index (DFI) compared to those with a low DFI. Concomitantly, BRCA1 mRNA expression was lower in samples with a high DFI than with a low DFI. In the GC2 cell model, Brca1 knockdown reduced cell proliferation and increased sensitivity to oxidative stress. Moreover, it increased double-strand breaks and decreased the protein levels of the DNA repair genes MRE11 and RAD51. CONCLUSION(S): A prominent cluster of comethylated patterns associated with SDF was identified. BRCA1 may be the hub gene involved in sperm DNA damage.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Deoxyribonucleic acid methylation signatures in sperm deoxyribonucleic acid fragmentation.

OBJECTIVE: To evaluate Deoxyribonucleic acid (DNA) methylation patterns in sperm from men with differential levels of sperm DNA fragmentation index (DFI). DESIGN: Prospective study. SETTING: University-affiliated reproductive medicine center. PATIENT(S): A total of 278 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genome-wide DNA methylation analysis was performed using Infinium MethylationEPIC BeadChip on spermatozoal DNA from 20 male patients. Differentially methylated regions (DMRs) were identified and validated using targeted bisulfite amplicon sequencing in spermatozoal DNA from 266 males. RESULT(S): Unsupervised hierarchical clustering analysis revealed three main clusters corresponding to sperm DFI levels (low, medium, or high). Between-cluster comparisons identified 959 (medium-low), 738 (high-medium), and 937 (high-low) DMRs. Sixty-six DMRs were validated in the 266-sample cohort, of which nine CpG fragments corresponding to nine genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1, and TEX12) exhibited significantly altered methylation in those with high DFI (≥25%) compared with those with low DFI (<25%). CONCLUSION(S): We identified and validated a distinct DNA methylation signature associated with sperm DNA damage in a large, unselected cohort. These results indicate that sperm DNA damage may affect DNA methylation patterns in human sperm.

Hypothalamic and ovarian transcriptome profiling reveals potential candidate genes in low and high egg production of white Muscovy ducks (Cairina moschata).

In China, the low egg production rate is a major challenge to Muscovy duck farmers. Hypothalamus and ovary play essential role in egg production of birds. However, there are little or no reports from these tissues to identify potential candidate genes responsible for egg production in White Muscovy ducks. A total of 1,537 laying ducks were raised; the egg production traits which include age at first egg (days), number of eggs at 300 d, and number of eggs at 59 wk were recorded. Moreover, 4 lowest (LP) and 4 highest producing (HP) were selected at 59 wk of age, respectively. To understand the mechanism of egg laying regulation, we sequenced the hypothalamus and ovary transcriptome profiles in LP and HP using RNA-Seq. The results showed that the number of eggs at 300 d and number of eggs at 59 wk in the HP were significantly more (P < 0.001) than the LP ducks. In total, 106.98G clean bases were generated from 16 libraries with an average of 6.68G clean bases for each library. Further analysis showed 569 and 2,259 differentially expressed genes (DEGs) were identified in the hypothalamus and ovary between LP and HP, respectively. The KEGG pathway enrichment analysis revealed 114 and 139 pathways in the hypothalamus and ovary, respectively which includes Calcium signaling pathway, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway, Apoptosis and Apelin signaling pathways that are involved in egg production. Based on the GO terms and KEGG pathways results, 10 potential candidate genes (P2RX1, LPAR2, ADORA1, FN1, AKT3, ADCY5, ADCY8, MAP3K8, PXN, and PTTG1) were identified to be responsible for egg production. Further, protein-protein interaction was analyzed to show the relationship between these candidate genes. Therefore, this study provides useful information on transcriptome of hypothalamus and ovary of LP and HP Muscovy ducks.

Short-term changes in and preoperative factors affecting vaulting after posterior chamber phakic Implantable Collamer Lens implantation.

BACKGROUND: To describe the very early vault changes in the first month after Implantable Collamer Lens (ICL) implantation and to evaluate the effect of preoperative biometric factors on vault. METHODS: Eighty-three eyes from eighty-three subjects with complete data who met follow-up requirements were recruited in this retrospective study between May 2019 and March 2020. We quantitatively assessed the postoperative vault at 2 h, 1 day, 1 week, and 1 month following implantation. Associations between the postoperative vault and age, ICL size, spherical equivalent (SE), axial length (AL), central corneal thickness (CCT), flat keratometry (K), steep K, mean K, anterior chamber depth (ACD), crystalline lens thickness (LT), white-to-white (WTW) diameter obtained by three devices, horizontal and vertical sulcus-to-sulcus (STS) diameter, bright and dark pupil sizes (BPS and DPS) and DPS-BPS were investigated using Spearman's correlation analysis and stepwise multiple regression analysis. RESULTS: The mean vault values at 2 h, 1 day, 1 week, and 1 month after ICL implantation were 672.05 ± 30.72, 389.15 ± 28.33, 517.23 ± 30.76 and 530.12 ± 30.22 µm, respectively. Significant differences were found in the vault values at 2 h, 1 day and 1 week after the operation. The ICL size (ß = 0.942; p < 0.001), followed by horizontal STS (ß = -0.517; p < 0.001), crystalline LT (ß = -0.376; p < 0.001) and vertical STS (ß = -0.257; p = 0.017), significantly influenced the vault at 1 month after the operation. The multiple regression equation was expressed as follows: central vault (µm) = -1369.05 + 657.121 × ICL size- 287.408 × horizontal STS - 432.497 × crystalline LT - 137.33 × vertical STS (adjusted R2 = 0.643). CONCLUSIONS: After ICL implantation, the vault decreased and then increased, but it did not return to the vault value 2 h after surgery. The ICL size, horizontal and vertical STS and crystalline LT are key factors for predicting postoperative vaulting.

Exosome-transmitted miRNA-335-5p promotes colorectal cancer invasion and metastasis by facilitating EMT via targeting RASA1.

Exosomal microRNA (miRNA) secretion has been characterized as a vital factor in intercellular communication among cancer cells. However, little is known about cancer-secreted miRNAs specifically involved in metastasis of colorectal cancer (CRC). Here, we found that exosomes derived from metastatic CRC cell line SW620 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells. The profiling of exosome miRNAs revealed that microRNA (miR)-335-5p was highly expressed in exosomes from metastatic SW620 cells compared to those derived from primary SW480 cells. miR-335-5p was transmitted from metastatic SW620 cells to CRC cells via exosomes and promoted migration, invasion, and EMT of CRC cells. Moreover, exosome-transmitted miRNA-335-5p promotes CRC cell invasion and metastasis by facilitating EMT via targeting RAS p21 protein activator 1 (RASA1). Overexpression of RASA1 abolished the promotive effects of exosomal miR-335-5p on CRC cell migration, invasion, and EMT. Collectively, our data revealed that exosomal miR-335-5p derived from metastatic CRC cells promotes CRC cell invasion and metastasis by facilitating EMT via targeting RASA1, which may serve as a potential therapeutic target for CRC metastasis.

BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism.

Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited cisplatin- or BCAT1-mediated autophagy and increased cisplatin sensitivity by activating mTOR signaling in cancer cells. Moreover, inhibition of autophagy by chloroquine increased cisplatin sensitivity in vivo. Also, the knockdown of BCAT1 or the administration of leucine activated mTOR signaling, inhibited autophagy, and increased cisplatin sensitivity in cancer cells in vivo. These findings demonstrate a new mechanism, revealing that BCAT1 decreases cisplatin sensitivity in cancer cells by inducing mTOR-mediated autophagy via branched-chain amino acid leucine metabolism, providing an attractive pharmacological target to improve the effectiveness of chemotherapy.