Extended depth of focus IOL in eyes with different axial myopia and targeted refraction.

AIM: To evaluate the objective visual outcomes following implantation of extended depth of focus intraocular lens (EDOF IOL) in individuals with varying axial lengths (AL) and targeted refraction. METHODS: This retrospective study comprised age-matched eyes that underwent implantation of the EDOF IOL. Eyes were categorized based on AL into groups: control group with AL < 26 mm; high myopia group with AL ≥ 26 mm. Each group was then subdivided based on postoperative spherical equivalent (SE). Follow-up at three months included assessment of uncorrected visual acuity at different distances, contrast sensitivity (CS), refractive outcomes, and spectacle independence. RESULTS: Overall, this study included 100 eyes from 100 patients, comprising 50 males (50.00%) and 50 females (50.00%), with 20 eyes in each group. In the control group, the uncorrected distance visual acuity (UDVA) at 5 and 3 m (m) in the - 1.50 to -0.75 group was inferior to that of the - 0.75 to 0.00 group (P = 0.004). Conversely, the uncorrected near visual acuity (UNVA) at 33 cm in the - 1.50 to -0.75 group was superior to that of the - 0.75 to 0.00 group (P = 0.005). Within the high myopia group, the UDVA at 5 and 3 m in the - 2.25 to -1.50 group was worse than in the - 0.75 to 0.00 group (P = 0.009 and 0.008, respectively). However, the UNVA at 33 cm in the - 2.25 to -1.50 group was better than in the - 0.75 to 0.00 group (P = 0.020). No significant differences were observed among the groups for corrected distance visual acuity (CDVA) (P > 0.05). Additionally, in the high myopia group, the CS of the - 2.25 to -1.50 group was lower compared to that of the - 0.75 to 0.00 group (P = 0.017). Among high myopia patients, 90.00% with refraction ranging from - 1.50 to -0.75 reported achieving overall spectacle independence. CONCLUSIONS: Implantation of extended depth of focus intraocular lenses (IOLs) yields satisfactory visual and refractive outcomes in eyes with axial myopia. Among high myopia patients, a refraction ranging from - 1.50 to -0.75 diopters achieves superior visual quality compared to other postoperative myopic diopters.

Featured lncRNA-based signature for discriminating prognosis and progression of hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been implicated in carcinogenesis and progression of hepatocellular carcinoma (HCC). This study aimed to identify a robust lncRNA signature for predicting the survival of HCC patients. We performed an integrated analysis of the lncRNA expression profiling in The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma database to identify the prognosis-related lncRNA for the HCC. The HCC cohort was randomly divided into a training set (n = 250) and a testing set (n = 113). Following a two-step screening, we identified an 18-lncRNA signature risk score. The high-risk subgroups had significantly shorter survival time than the low-risk group in both the training set (P < 0.0001) and the testing set (P = 0.005). Stratification analysis revealed that the prognostic value of the lncRNA-based signature was independent of the tumor stage and pathologic stage. The area under the receiver operating characteristic curve (AUROC) of the 18-lncRNA signature risk score was 0.826 (95%CI, 0.764-0.888), 0.817 (95%CI, 0.759-0.876), and 0.799 (95%CI, 0.731-0.867) for 1-year, 3-year, and 5-year follow-up, respectively. Bioinformatics analyses indicated that the 18 lncRNA might mediate cell cycle, DNA replication processes, and canonical cancer-related pathways, in which MCM3AP-AS1 was a potential target for HCC. In conclusion, the 18-lncRNA signature was a robust predictive biomarker for the prognosis and progression of HCC.

Ubiquitination-specific protease 7 enhances stemness of hepatocellular carcinoma by stabilizing basic transcription factor 3.

This study aims to explore the molecular regulation mechanism of ubiquitination-specific protease 7 (USP7) in facilitating the stemness properties of hepatocellular carcinoma (HCC). Gain-of-function and loss-of-function assays were conducted in SK-Hep1 and HepG2 cells transfected with USP7 overexpression/knockdown plasmids and USP7 inhibitor P22077. The proliferation, migration, invasion, and self-renewal capacity of hepatocellular carcinoma cells were detected by CCK-8, colony formation, Transwell, scratch, and tumor sphere formation, respectively. MS was performed to identify the potential substrate of USP7 following P22077 treatment. Co-IP assay was used to verify the interaction between USP7 and basic transcription factor 3 (BTF3) in HCC cells. The overexpression of USP7 could promote the proliferation, migration, invasion, and colony formation capacity of SK-Hep1 and HepG2 cells. Additionally, ectopic UPS7 enhanced the epithelial-mesenchymal transition (EMT) and stem-like characteristics of the HCC cells. In contrast, USP7 depletion by knockdown of USP7 or administrating inhibitor P22077 significantly inhibited these malignant phenotypes of SK-Hep1 and HepG2 cells. Following MS analysis, BTF3 was identified as a potential substrate for USP7. USP7 could interact with BTF3 and upregulate its protein level, while USP7 depletion significantly upregulated the ubiquitination levels. Overexpression of BTF3 partially rescue the inhibitory effects of USP7 depletion on the malignant phenotypes and stemness properties of SK-Hep1 and HepG2 cells. USP7 can promote the stemness and malignant phenotype of HCC by stabilizing BTF3.

Identifying Dental Pulp Stem Cell as A Novel Therapeutic Strategy for Digestive Diseases.

Mesenchymal stem cells (MSCs) have been identified as potential therapeutics for various diseases. In contrast to other sources of MSCs, dental stem cells (DSCs) have received increased attention due to their high activity and easy accessibility. Among them, dental pulp stem cells (DPSCs) exhibit superior self-renewal, multipotency, immunomodulatory, and regenerative capacities. Following their inspiring performance in animal models and clinical trials, DPSCs show pharmacological potential in regenerative medicine. In this review, we have generalized the sources, heterogeneity, and biological characteristics of DPSCs, as well as compared them with other types of dental stem cells. In addition, we summarized the application of DPSCs in digestive diseases (such as liver, esophageal, and intestinal diseases), highlighting their regenerative and pharmacological potential based on the existing preclinical and clinical evidence. Specifically, DPSCs can be> home to injured or inflamed tissues and exert repair and regeneration functions by> facilitating immune regulation, anti-inflammation, and directional differentiation. Although DPSCs have a rosy prospect, future studies should handle the underlying drawbacks and pave the way for the identification of DPSCs as novel regenerative medicine.

Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKß/Nrf2/HO-1 Signal Axis.

Antioxidants represent a potential therapy for cerebral ischemia-reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H2O2)-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKß) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKß plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKß phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKß/Nrf2/HO-1 signal axis. Inhibition of IKKß phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.

Pressure-induced Fermi resonance between fundamental modes in phthalic anhydride.

In situhigh-pressure Raman spectra of phthalic anhydride (PA) have been measured up to 16 GPa through diamond anvil cell technique. The results show that all the Raman bands are blue-shifted with the increase of pressure, accompanied by appearance of some new bands. A Fermi resonance phenomenon of the two Raman fundamental modes of PA at 773 cm-1and 801 cm-1is proposed at pressures above 6.6 GPa, where a possible first-order phase transition occurs. The pressure-induced changes of Fermi resonance parameters, e.g., intensity ratio, coupling coefficient and frequency gap of unperturbed transition, are discussed.

Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain.

BACKGROUND: Toxoplasma gondii is a zoonotic pathogen that causes toxoplasmosis and leads to serious public health problems in developing countries. However, current clinical therapeutic drugs have some disadvantages, such as serious side effects, a long course of treatment and the emergence of drug-resistant strains. The urgent need to identify novel anti-Toxoplasma drugs has initiated the effective strategy of repurposing well-characterized drugs. As a principled screening for the identification of effective compounds against Toxoplasma gondii, in the current study, a collection of 666 compounds were screened for their ability to significantly inhibit Toxoplasma growth. METHODS: The inhibition of parasite growth was determined using a luminescence-based ß-galactosidase activity assay. Meanwhile, the effect of compounds on the viability of host cells was measured using CCK8. To assess the inhibition of the selected compounds on discrete steps of the T. gondii lytic cycle, the invasion, intracellular proliferation and egress abilities were evaluated. Finally, a murine infection model of toxoplasmosis was used to monitor the protective efficacy of drugs against acute infection of a highly virulent RH strain. RESULTS: A total of 68 compounds demonstrated more than 70% parasite growth inhibition. After excluding compounds that impaired host cell viability, we further characterized two compounds, NVP-AEW541 and GSK-J4 HCl, which had IC50 values for parasite growth of 1.17 µM and 2.37 µM, respectively. In addition, both compounds showed low toxicity to the host cell. Furthermore, we demonstrated that NVP-AEW541 inhibits tachyzoite invasion, while GSK-J4 HCl inhibits intracellular tachyzoite proliferation by halting cell cycle progression from G1 to S phase. These findings prompted us to analyse the efficacy of the two compounds in vivo by using established mouse models of acute toxoplasmosis. In addition to prolonging the survival time of mice acutely infected with T. gondii, both compounds had a remarkable ability to reduce the parasite burden of tissues. CONCLUSIONS: Our findings suggest that both NVP-AEW541 and GSK-J4 could be potentially repurposed as candidate drugs against T. gondii infection.

Improvement of extracellular secretion efficiency of Bacillus naganoensis pullulanase from recombinant Escherichia coli: Peptide fusion and cell wall modification.

Pullulanases are well-known starch-debranching enzymes that are widely used for hydrolysis of a-1,6-glycosidic linkages in starch, pullulan, amylopectin, and other oligosaccharides. Escherichia coli is a popular heterologous expression host for generating target enzymes. However, cells have to be disrupted to obtain the target enzyme due to the weak extracellular secretion of E. coli. In order to facilitate subsequent characterization and application of pullulanase, improving its secretion efficiency from E. coli is a major challenge that must first be solved. Considering the transport mechanism involving signal peptide as well as permeability of the cell wall, we adopted two strategies to improve the extracellular secretion of pullulanase from E. coli: (1) fusion of a negatively charged peptide at the N-terminal of the target enzyme to guide it out of the membrane of E. coli and (2) modification of the composition of the cell wall to increase its permeability. In this study, both strategies showed positive influence on the extracellular secretion of pullulanase. After fusing a negatively charged peptide at the N-terminal, the extracellular enzymatic activity increased by more than 4 times compared to the pullulanase without peptide fusion. By modifying the permeability of the cell wall, the extracellular enzymatic activity increased by 12 times. In addition, the two strategies were also used to improve the secretion efficiency of the truncated pullulanase ΔN106, which has higher enzymatic activity than the full-length protein. The strategies employed have valuable implications for increasing the extracellular secretion efficiency of target proteins from recombinant E. coli.