ABSTRACT
Background: Low temperature pose significant challenges to peach cultivation, causing severe damage to peach buds and restricting production and distribution. Ethylene, an important phytohormone, plays a critical role in enhancing plant cold resistance. Structural genes and transcription factors involved in ethylene biosynthesis and signal transduction pathways are associated with cold resistance. However, no research has specifically addressed their roles in peach cold resistance. Methods: In this study, we aimed for cold-resistance gene discovery in cold-sensitive peach cultivar "21Shiji" (21SJ) and cold-resistance cultivar "Shijizhixing" (SJZX) using RNA-seq and gas chromatography. Results: The findings revealed that under cold stress conditions, ethylene biosynthesis in "SJZX" was significantly induced. Subsequently, a structural gene, PpACO1-1, involved in ethylene biosynthesis in peach buds was significantly upregulated and showed a higher correlation with ethylene release rate. To identify potential transcription factors associated with PpACO1-1 expression and ethylene signal transduction, weighted gene co-expression network analysis was conducted using RNA-seq data. Four transcription factors: PpERF2, PpNAC078, PpWRKY65 and PpbHLH112, were identified. Conclusion: These findings provide valuable theoretical insights for investigating the regulatory mechanisms of peach cold resistance and guiding breeding strategies.
ABSTRACT
BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.
Subject(s)
Fluorescent Dyes , Gold , Hypochlorous Acid , Levonorgestrel , Zebrafish , Humans , Gold/chemistry , HeLa Cells , Hypochlorous Acid/analysis , Animals , Hep G2 Cells , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Levonorgestrel/chemistry , Optical Imaging , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/analysis , Metal Nanoparticles/chemistryABSTRACT
BACKGROUND: Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs). RESULTS: We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4-/- mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice. CONCLUSIONS: Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.
ABSTRACT
With the addition of Bluetooth AOA/AOD direction-finding capabilities in the Bluetooth 5.1 protocol and the introduction of antenna array technology into the Bluetooth platform to further enhance positioning accuracy, Bluetooth has gradually become a research hotspot in the field of indoor positioning due to its standard protocol specifications, rich application ecosystem, and outstanding advantages such as low power consumption and low cost compared to other indoor positioning technologies. However, current indoor positioning based on Bluetooth AOA/AOD suffers from overly simplistic core algorithm implementations. When facing different application scenarios, the standalone AOA or AOD algorithms exhibit weak applicability, and they also encounter challenges such as poor positioning accuracy, insufficient real-time performance, and significant effects of multipath propagation. These existing problems and deficiencies render Bluetooth lacking an efficient implementation solution for indoor positioning. Therefore, this paper proposes a study on Bluetooth AOA and AOD indoor positioning algorithms. Through an analysis of the principles of Bluetooth's newly added direction-finding functionality and combined with research on array signal DOA estimation algorithms, the paper ultimately integrates the least squares algorithm to optimize positioning errors in terms of accuracy and incorporates an anti-multipath interference algorithm to address the impacts of multipath effects in different scenarios. Experimental testing demonstrates that the indoor positioning algorithms applicable to Bluetooth AOA and AOD can effectively mitigate accuracy errors and overcome multipath effects, exhibiting strong applicability and significant improvements in real-time performance.
ABSTRACT
Open wounds are susceptible to bacterial infections, and antibiotics are commonly used to treat these infections. However, widespread use of antibiotics will easily induce bacterial resistance. Green antibacterial agents serve as excellent alternative for antibiotics in infection therapy. In this work, polydopamine (PDA) was used to modify the surface of ZIF-8, which not only enhances the water stability of Zeolitic imidazolate framework-8(ZIF-8) but also improves its photocatalytic and photothermal capabilities. ZIF-8@PDA was incorporated into carboxylated chitosan (CCS) films as an antibacterial agent, the resulting ZIF-8@PDA-CCS films exhibit excellent ionic/photocatalytic/photothermal antibacterial performance. The film exhibited an impressive 99% in vitro bacterial inhibition rate. After treatment with ZIF-8@PDA-CCS, the bacteria in infected wounds can be completely suppressed. These findings suggest that ZIF-8@PDA-CCS could serve as a potentional antibacterial dressing.
ABSTRACT
The testis serves as the reproductive gland in male mammals, primarily tasked with the production of sperm and synthesis of androgens. A complex signaling network consisting of various cell types, including germ cells, Sertoli cells, and Leydig cells, supports the structure and maintains the function of the testis. Apart from the hypothalamic-pituitary-gonadal axis, various sex hormones and cytokines are also implicated in the regulation of testicular function. The fibroblast growth factor (FGF) represents a crucial class of active cytokines that stimulate cell proliferation, induce tissue differentiation, and govern organ development. This review summarizes the molecular mechanisms of FGF regulating testicular development and spermatogenesis and maintaining male fertility.
Subject(s)
Fibroblast Growth Factors , Spermatogenesis , Testis , Male , Spermatogenesis/physiology , Testis/metabolism , Testis/physiology , Humans , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/physiology , Animals , Reproduction/physiologyABSTRACT
BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Male , Female , Middle Aged , Prognosis , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Aged , ROC Curve , Retrospective Studies , Kaplan-Meier Estimate , Adult , Risk FactorsABSTRACT
Recently synthesized two-dimensional (2D) monolayer quasi-hexagonal-phase fullerene (qHPC60) demonstrates excellent thermodynamic stability. Within this monolayer, each fullerene cluster is surrounded by six adjacent C60 cages along an equatorial plane and is connected by both C-C single bonds and [2 + 2] cycloaddition bonds that serve as bridges. In this study, we investigate the stability mechanism of the 2D qHPC60 monolayer by examining the electronic structure and chemical bonding through state-of-the-art theoretical methodologies. Density functional theory (DFT) studies reveal that 2D qHPC60 possesses a moderate direct electronic band gap of 1.46 eV, close to the experimental value (1.6 eV). It is found that the intermolecular bridge bonds play a crucial role in enhancing the charge flow and redistribution among C60 cages, leading to the formation of dual π-aromaticity within the C60 sphere and stabilizing the 2D framework structure. Furthermore, we identify a series of delocalized superatom molecular orbitals (SAMOs) within the 2D qHPC60 monolayer, exhibiting atomic orbital-like behavior and hybridization to form nearly free-electron (NFE) bands with σ/π bonding and σ*/π* antibonding properties. Our findings provide insights into the design and potential applications of NFE bands derived from SAMOs in 2D qHPC60 monolayers.
ABSTRACT
BACKGROUND: Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. PURPOSE: The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. STUDY DESIGN AND METHODS: Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. RESULTS: In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. CONCLUSION: ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.
ABSTRACT
Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver-α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and in vivo studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mechanistic target of rapamycin complex 1, another ErbB3 downstream effector signal transducer and activator of transcription 3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mechanistic target of rapamycin complex 1 and signal transducer and activator of transcription 3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver-α cells axis that regulates aminoacidemia.
ABSTRACT
This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An in vitro NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.
Subject(s)
Apoptosis , Early Growth Response Protein 1 , Intervertebral Disc Degeneration , Nucleus Pulposus , Oxidative Stress , Receptors, Thyroid Hormone , Adult , Animals , Female , Humans , Male , Middle Aged , Rats , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Early Growth Response Protein 1/metabolism , Early Growth Response Protein 1/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/pathology , Nerve Tissue Proteins , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Rats, Sprague-Dawley , Receptors, Steroid/metabolism , Receptors, Steroid/genetics , Receptors, Thyroid Hormone/metabolism , Receptors, Thyroid Hormone/genetics , Up-RegulationABSTRACT
BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.
Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Laparoscopy , Liver Neoplasms , Postoperative Complications , Propensity Score , Robotic Surgical Procedures , Humans , Carcinoma, Hepatocellular/surgery , Hepatectomy/adverse effects , Hepatectomy/methods , Liver Neoplasms/surgery , Male , Laparoscopy/adverse effects , Female , Robotic Surgical Procedures/adverse effects , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome , Aged , Databases, Factual , Length of Stay , Risk Factors , Time Factors , Risk Assessment , AdultABSTRACT
The pervasive global issue of population aging has led to a growing demand for health monitoring, while the advent of electronic wearable devices has greatly alleviated the strain on the industry. However, these devices come with inherent limitations, such as electromagnetic radiation, complex structures, and high prices. Herein, a Solaris silicone rubber-integrated PMMA polymer optical fiber (S-POF) intelligent insole sensing system has been developed for remote, portable, cost-effective, and real-time gait monitoring. The system is capable of sensitively converting the pressure of key points on the sole into changes in light intensity with correlation coefficients of 0.995, 0.952, and 0.910. The S-POF sensing structure demonstrates excellent durability with a 4.8% variation in output after 10,000 cycles and provides stable feedback for bending angles. It also exhibits water resistance and temperature resistance within a certain range. Its multichannel multiplexing framework allows a smartphone to monitor multiple S-POF channels simultaneously, meeting the requirements of convenience for daily care. Also, the system can efficiently and accurately provide parameters such as pressure, step cadence, and pressure distribution, enabling the analysis of gait phases and patterns with errors of only 4.16% and 6.25% for the stance phase (STP) and the swing phase (SWP), respectively. Likewise, after comparing various AI models, an S-POF channel-based gait pattern recognition technique has been proposed with a high accuracy of up to 96.87%. Such experimental results demonstrate that the system is promising to further promote the development of rehabilitation and healthcare.
Subject(s)
Wearable Electronic Devices , Humans , Gait/physiology , Smartphone , Artificial Intelligence , Shoes , Optical FibersABSTRACT
Disulfiram (DSF) metabolites exhibit antitumor properties when bound to Cu2+. This combination also promotes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. In this study, CuO2 served as a carrier for DSF, forming a dual-drug delivery system with Cu2+ and DSF encapsulated in polydopamine (PDA). In the final delivery system, CuO2 (DSF-CuO2@PDA) was hydrolyzed at the tumor site, releasing both Cu2+ and H2O2. Cu2+ reacts with DSF metabolites to form Bis(diethyldithiocarbamate)-Cu (CuET), which triggers a Fenton-like reaction that generates ROS. Chemotherapy and chemodynamic therapy exhibited significant tumor-suppressive capabilities, with an inhibition rate of 61 %. In addition, the DSF-CuO2@PDA complex demonstrated superlative tumor-targeting ability and biocompatibility.
Subject(s)
Antineoplastic Agents , Copper , Disulfiram , Drug Carriers , Disulfiram/pharmacology , Disulfiram/chemistry , Copper/chemistry , Copper/pharmacology , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Animals , Mice , Polymers/chemistry , Polymers/pharmacology , Cell Survival/drug effects , Cell Line, Tumor , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Indoles/chemistry , Indoles/pharmacology , Particle Size , Cell Proliferation/drug effects , Surface Properties , Drug Screening Assays, AntitumorABSTRACT
The aberrant activation of RAS/RAF/MEK/ERK signaling is important for KIT mutation-mediated tumorigenesis of gastrointestinal stromal tumor (GIST). In this study, we found that inhibition of RAF1 suppresses the activation of both wild-type KIT and primary KIT mutations in GIST, with primary KIT mutations showing greater sensitivity. This suggests a positive feedback loop between KIT and RAF1, wherein RAF1 facilitates KIT signaling. We further demonstrated that RAF1 associates with KIT and the kinase activity of RAF1 is necessary for its contribution to KIT activation. Accordingly, inhibition of RAF1 suppressed cell survival, proliferation, and cell cycle progression in vitro mediated by both wild-type KIT and primary KIT mutations. Inhibition of RAF1 in vivo suppressed GIST growth in a transgenic mouse model carrying germline KIT/V558A mutation, showing a similar treatment efficiency as imatinib, the first-line targeted therapeutic drug of GIST, while the combination use of imatinib and RAF1 inhibitor further suppressed tumor growth. Acquisition of drug-resistant secondary mutation of KIT is a major cause of treatment failure of GIST following targeted therapy. Like wild-type KIT and primary KIT mutations, inhibition of RAF1 suppressed the activation of secondary KIT mutation, and the cell survival, proliferation, cell cycle progression in vitro, and tumor growth in vivo mediated by secondary KIT mutation. However, the activation of secondary KIT mutation is less dependent on RAF1 compared with that of primary KIT mutations. Taken together, our results revealed that RAF1 facilitates KIT signaling and KIT mutation-mediated tumorigenesis of GIST, providing a rationale for further investigation into the use of RAF1 inhibitors alone or in combination with KIT inhibitor in the treatment of GIST, particularly in cases resistant to KIT inhibitors.
Subject(s)
Gastrointestinal Stromal Tumors , Proto-Oncogene Proteins c-kit , Proto-Oncogene Proteins c-raf , Signal Transduction , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/metabolism , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-kit/metabolism , Animals , Proto-Oncogene Proteins c-raf/metabolism , Proto-Oncogene Proteins c-raf/genetics , Humans , Mice , Mice, Transgenic , Cell Proliferation , Cell Line, Tumor , Mutation , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/metabolismABSTRACT
Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.
Subject(s)
Aging , Genomics , Proteomics , Regenerative Medicine , Aging/physiology , Humans , Regenerative Medicine/methods , Regenerative Medicine/trends , Genomics/methods , Proteomics/methods , Metabolomics/methods , Epigenomics/methods , MultiomicsABSTRACT
AIM: To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction (SMILE) with different myopic diopters. METHODS: Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study. Patients were allocated into three groups based on the preoperative spherical equivalent (SE): low myopia (SE≥-3.00 D), moderate myopia (-3.00 D>SE>-6.00 D) and high myopia (SE≤-6.00 D). Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times (1wk, 1, 3, 6mo, and 1y). Posterior mean elevation (PME) at 25 predetermined points of 3 concentric circles (2-, 4-, and 6-mm diameter) above the best fit sphere was analyzed. RESULTS: All surgeries were completed uneventfully and no ectasia was found through the observation. The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively (1mo: P=0.017; 3mo: P=0.018). The effect of time on ΔPME was statistically significant (2-mm ring: P=0.001; 4-mm ring: P<0.001; 6-mm ring: P<0.001). The effect of different corneal locations on ΔPME was significant except 1wk postoperatively (1mo: P=0.000; 3mo: P=0.000; 6mo: P=0.001; 1y: P=0.001). Posterior corneal stability was linearly correlated with SE, central corneal thickness, ablation depth, residual bed thickness, percent ablation depth and percent stromal bed thickness. CONCLUSION: The posterior corneal surface changes dynamically after SMILE. No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery. SMILE has good stability, accuracy, safety and predictability.
ABSTRACT
BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.