Biomedical subjects
Publications and source records attributed to Bo Yu.
Systematic comparison of Cas12i gene-editing tools in tomato identifies Cas-SF01 as the most efficient variant, achieving editing efficiencies comparable to conventional Cas9 at some genomic sites and providing a compact, highly specific, and versatile tool for studying gene function, engineering fruit metabolism, and developing improved tomato varieties through precision breeding.
BACKGROUND: Isolated male epispadias (IME) is a rare congenital malformation. Surgical repair aims to improve urinary function, correct penile curvature, reconstruct the urethra and glans, and preserve future sexual function. Because available series are small, the influence of anatomical subtype and operative technique on outcome remains incompletely defined. OBJECTIVE: To report single-center outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs for IME, with attention to anatomical subtype, complications, and age-appropriate continence outcomes. METHODS: We retrospectively reviewed boys with IME who underwent primary urethral reconstruction in my hospital, Capital Medical University, from May 2005 to June 2024. Data were locked on 30 June 2024. Primary outcomes were postoperative complications graded by the Clavien-Dindo system and urinary continence at last follow-up in patients aged 5 years or older. Secondary outcomes included improvement of preoperative incontinence, ICIQ score, subsequent bladder neck reconstruction, penile appearance/residual curvature when documented, and patient/parent-reported sexual function. RESULTS: Sixty-seven patients were included: 35 underwent modified Cantwell-Ransley repair and 32 underwent Thiersch-Duplay repair. The cohort included 26 glanular (38.8%), 23 penile (34.3%), and 18 penopubic (26.9%) cases. Median age at surgery was 28 months in both groups. Median age at last follow-up was 92.8 months (IQR 63.9-108.4) after modified Cantwell-Ransley repair and 137.9 months (IQR 77.9-172.6) after Thiersch-Duplay repair (P = 0.011). Procedure distribution differed by meatal location (P = 0.036), although penopubic cases were treated with both procedures. Total complications occurred in 5/35 and 5/32 patients, respectively. Formal continence analysis included 26 modified Cantwell-Ransley patients and 27 Thiersch-Duplay patients aged 5 years or older. Postoperative urinary incontinence persisted in 14/26 (53.8%) and 12/27 (44.4%), respectively. Among age-eligible patients with preoperative incontinence, any improvement was documented in 13/20 (65.0%) and 14/17 (82.4%), and complete remission occurred in 6/20 (30.0%) and 5/17 (29.4%), respectively. Three patients, all with penopubic epispadias treated with Thiersch-Duplay repair, subsequently underwent bladder neck reconstruction for persistent incontinence. Erectile function data were available in 37/67 patients (55.2%). CONCLUSIONS: In this large single-center retrospective cohort, Thiersch-Duplay and modified Cantwell-Ransley repairs had comparable overall complication rates. Continence and reoperation patterns were strongly influenced by anatomical subtype, with penopubic epispadias representing the highest-risk group. These findings support individualized, anatomy-conscious operative planning and prospective evaluation of standardized selection criteria, rather than a single prescriptive algorithm. CLINICAL/TRANSLATIONAL IMPLICATION: This series supports standardized reporting of anatomical subtype, age-appropriate continence outcomes, and graded complications when counseling families and comparing outcomes across centers. LEVEL OF EVIDENCE: Level III.
Cyclic voltammetry and impedance spectroscopy were employed to probe the responsive properties of polyelectrolyte brushes. Poly[(dimethylamino)ethyl methacrylate] (PDMAEMA) brushes over 100 nm thick on gold substrates were synthesized via surface-initiated atom-transfer radical polymerization and quaternized with methane iodide to obtain cationic brushes (Q-PDMAEMA). Q-PDMAEMA brushes respond to electrolytes by exhibiting swollen and collapsed states. Swollen brushes allow good permeability of electroactive probes, while collapsed states block electron transport. Electrolytes have different impacts on the electrochemical properties of Q-PDMAEMA. Some salts (NaNO3) cause brush collapse due to charge screening, while others such as those with more hydrophobic anions (ClO4-, PF6-, and Tf2N-) induce brush collapse because of solubility changes. The collapsed brushes exhibit intrinsically different resistance as probed with impedance. Charged screened brushes retain good permeability to electroactive probes. Strongly coordinating hydrophobic anions lead to insoluble brushes, resulting in a high resistance. These results show that electrochemical impedance spectroscopy is a powerful technique to probe the properties and structure of polyelectrolyte brushes.
This article describes a general synthetic route to laterally distinctive multicomponent polymer brushes on gold. The procedure involves repeated surface patterning using microcontact printing (muCP) of initiator-terminated thiols without backfilling with inert thiols and surface-initiated atomic transfer radical polymerization steps. In between brush growth, the remaining initiator moieties are deactivated to avoid reinitiation on existing brushes. Optical and fluorescence microscopy, atomic force microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy have been used to characterize every step of this procedure. We found that brushes can be grown from initiator-modified surfaces that contain bare gold areas and that these areas remain available for further patterning using muCP. To demonstrate the flexibility of this approach, surfaces containing four different polymer brushes in patterns ranging from 2 x 4 microm lines to 20 x 20 microm squares were fabricated. The range of chemical functionalities incorporated includes cationic and anionic polyelectrolytes, as well as thermally responsive polymers.
Although classic Fabry's disease results in multiple causes of death, the cardiac variant of Fabry's disease affects only the cardiac system and results in initial symmetric left ventricular (LV) hypertrophy and later LV dysfunction, asymmetric basal posterior LV wall thinning, restrictive mitral flow, and functional mitral regurgitation with end-stage chronic heart failure (CHF), leading to death. The purpose of this study was to investigate whether these findings predict prognoses in patients with cardiac Fabry's disease. In 13 consecutive men with cardiac Fabry's disease, LV wall thickness, the ejection fraction, mitral E-wave deceleration time, the LV Tei index, and functional mitral regurgitation were measured by echocardiography. Patients were followed for 5 to 96 months (mean 41 +/- 9). Eight patients developed New York Heart Association class III CHF, and 6 experienced cardiac death. A LV Tei index >0.60 and basal posterior LV wall thinning with a ratio of ventricular septal to posterior wall thickness >1.3 significantly preceded CHF and death (Tei index: 4.4 and 5.1 years; posterior wall thinning: 4.0 and 4.7 years), respectively (p <0.05). In conclusion, an increased LV Tei index and asymmetric basal posterior LV wall thinning are important echocardiographic findings that precede CHF and cardiac death in patients with cardiac Fabry's disease.
We evaluated pathomechanisms and systemic manifestations of Alzheimer disease (AD), an aging-related dementing neurodegenerative disorder, by expression profiling. Blood mononuclear cell (BMC) transcriptomes of sporadic AD subjects and aged-matched normal elderly controls (NEC) were compared using the human NIA microarray. Relative to the NEC samples, the Alzheimer BMC exhibited a significant decline in the expression of genes concerned with cytoskeletal maintenance, cellular trafficking, cellular stress response, redox homeostasis, transcription and DNA repair. We observed decreased expression of several genes which may impact amyloid-beta production and the processing of the microtubule-associated protein tau. The microarray results were validated by quantitative real time PCR and revealed gender differences in the levels of altered gene expression. Our findings attest to the systemic nature of gene dys-regulation in sporadic AD, implicate disruption of cytoskeletal integrity, DNA repair mechanisms and cellular defenses in this condition, and suggest novel pathways of beta-amyloid deposition in this disease. BMC are highly accessible and may reflect molecular events germane to the neuropathophysiology of AD.
In biocatalytic conversions, substrates and products may display inhibitory or toxic effects on the biocatalyst. Rhodococcus erythropolis 1awq could further remove sulfur from hydrodesulfurized diesel oil, and the biodesulfurization was enhanced by the surfactant Tween 80. Tween 80 was shown to decrease the product concentration associated with the cells, reducing product inhibition.
The gene cassette encoding enzymes responsible for degrading carbazole to anthranilic acid was introduced into a dibenzothiophene degrader. The resultant strain, Rhodococcus erythropolis XPDN, could simultaneously transform the model pollutants dibenzothiophene, carbazole, and dibenzofuran to nontoxic metabolites and may have an application potential for bioremediation.
Carbazole, carbazoles with monomethyl or dimethyls substituted on different positions (C(1)-carbazoles or C(2)-carbazoles), and benzocarbazoles, as toxic and mutagenic components of petroleum and creosote contamination, were biodegradable by an isolated bacterial strain Pseudomonas sp. XLDN4-9. C(1)-carbazoles were degraded in preference to carbazole and C(2)-carbazoles. The biodegradation of C(1)-carbazoles or C(2)-carbazoles was influenced by the positions of methyl substitutions. Among C(1)-carbazole isomers, 1-methyl carbazole was the most susceptible. C(2)-carbazole isomers with substitutions on the same benzo-nucleus were more susceptible at a concentration of less than 3.4 microg g(-1) petroleum, especially when harboring one substitution on position 1. In particular, 1,5-dimethyl carbazole was the most recalcitrant dimethyl isomer.
Sulfur (S), nitrogen (N) and oxygen (O) heterocycles are among the most potent environmental pollutants. Microbial degradation of these pollutants is attracting more and more attention because such bioprocesses are environmentally friendly. The biotechnological potential of these processes is being investigated, for example, to achieve better sulfur removal by immobilized biocatalysts with magnetite nanoparticles or by solvent-tolerant bacteria, and to obtain valuable intermediates from these heterocycles. Other recent advances have demonstrated the mechanisms of angular dioxygenation of nitrogen heterocycles by microbes. However, these technologies are not yet available for large-scale applications so future research must investigate proper modifications for industrial applications of these processes. This review focuses on recent progress in understanding how microbes degrade S, N and O heterocycles.
BACKGROUND: Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. METHODS AND RESULTS: In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased (P<0.01), whereas PML tethering significantly worsened (P<0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering (P<0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR (r2=0.60, P<0.0001), increased PML tethering was the primary determinant of late MR (r2=0.75, P<0.0001). CONCLUSIONS: Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.
OBJECTIVE: To evaluate the clinical effects of different catheter ablation strategies in the treatment of typical atrial flutter complicated with paroxysmal atrial fibrillation (PAF). [CTIA, pulmonary vein segmental isolation (PVSI), CTIA + PVI] to the patients coexisted with typical atrial flutter and PAF. METHODS: 66 patients with typical atrial flutter complicated with PAF were divided into 3 groups: Group A (n = 30), undergoing cavotricuspid isthmus ablation, (CTIA), Group B (n = 17), undergoing pulmonary vein segmental isolation, (PVSI), and Group C (n = 19), undergoing CTIA + PVSI. Follow-up was conducted for 30.5 weeks +/- 10.4 weeks. The clinical curative effects, operation safety, and complication were evaluated. RESULTS: The recurrence rate of typical atrial flutter within 12 weeks after operation of Groups A and C were 13.3% and 10.5% respectively, both significantly lower than that of Group B (52.9%, both P < 0.05) without no significant difference between Group A and Group C (P > 0.05). The recurrence rate of typical atrial flutter within 36 weeks after operation of the Groups A, B, and C were 10%, 11.8%, and 10.5% respectively, without significant differences among these 3 groups (all P > 0.05). The recurrence rates of PAF within 12 weeks and 30 weeks after operation of Groups B and C were 29.4% and 31.6%, and 23.5% and 26.3% respectively, all significantly lower than those of Group A (46.7% and 73.3% respectively, all P < 0.05) without significant o differences between Groups B and C. CONCLUSION: In patients with both typical atrial flutter and PAF, pure CTIA has a good effect on typical atrial flutter, whereas the PAF recurrence rate is higher; Pure PVSI has a good control of typical atrial flutter while curing PAF; PVSI + CTIA only reduces the early recurrence of typical atrial flutter, however, has no advantage in long-term follow up.
OBJECTIVE: To examine the role of liver X receptors (LXRs) in lipid metabolism in cultured mouse mesangial cells. METHODS: To determine whether LXRalpha and LXRbeta are expressed in the kidney, RT-PCR and western blot assay were utilized. Cultured mesangial cells were treated with either vehicle or LXR agonist TO901317(10 micromol/L) for 24 hours. Real-time PCR analysis was used to detect ABCA1 and ABCG1 expressions. Cells were also transfected with a human ABCA1 promoter driven luciferase reporter plasmid and then stimulated with or without TO901317 for 24 hours. In order to determine the effect of TO901317 on protein expression of ABCA1, LXRalpha adenovirus was used to overexpress LXRalpha in the cultured cells. Finally, [3H] cholesterol efflux assay was performed to evaluate the efflux of cholesterol upon TO901317 stimulation. RESULTS: Both LXRalpha and LXRbeta were expressed in the kidney, freshly isolated glomeruli and mesangial cells. After treatment with TO901317, both ABCA1 and ABCG1 expressions were induced. Moreover, ABCA1 protein level was increased after the cells were simultaneously treated with LXRalpha-adenovirus and TO901317. The cholesterol efflux was also significantly enhanced after TO901317 treatment. CONCLUSION: LXRalpha and LXRbeta were functionally expressed in mouse mesangial cells. Activation of LXRs enhanced cholesterol efflux possibly through upregulating ABCA1 and ABCG1 expressions in mesangial cells. Therefore, LXR agonist might ameliorate lipid accumulation and reduce related cell injury in mesangial cells.
OBJECTIVE: To observe the lethal effect of multidrug resistance gene (MDR1) antisense RNA combined with oxaliplatin and 5-FU on drug-resistant rectal carcinoma cells. METHODS: PC-MDR1 plasmid including MDR1 was constructed with gene cloning techniques. The drug-resistant cancer cells (8348R) were transferred with the plasmids, and the positive neoplasm cells were selected with G418. Green fluorescent protein (GFP) gene was used as a reporting gene to monitor the gene transfer efficiency under the influence of oxaliplatin and 5-FU. The cytotoxicity and therapeutic effects of MDR1 anti-sense RNA combined with oxaliplatin and 5-FU were evaluated by colony-forming rate and MTT assay. RESULTS: A significant decrease of biological activity was observed in 8348R cells transferred with PC-MDR1, cell cycles were blocked in S phase, or in G2/M phase, and apoptosis rate of the cells increased. With treatment of oxaliplatin, the plasmid transfer efficiency in the drug-resistant cancer cells was improved about 18 times. Using an IC(50) dose of oxaliplatin and 5-FU combined with (MDR1) anti-sense RNA, 75 percent of 8348R cells were killed, which was significant higher than that of the control cells. CONCLUSIONS: Combined MDR1 antisense RNA with oxaliplatin and 5-FU has a synergistic effect of killing drug-resistant cancer cells and may be a promising method for treating drug-resistant rectal carcinoma.
In this communication we report the first preparation of ionic liquid-modified carbon nanotubes with reversibly switchable solubility between aqueous and organic solvents, induced by anion exchange.
BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes if an appropriate cellular environment is provided. Notch signals exchanged between neighboring cells through the Notch receptor can eventually dictate cell differentiation. In our study, we show that MSC differentiation into cardiomyocytes is dependent on the Notch signal. METHODS: We created a myocardial infarction model in rat by coronary ligation, administered direct intramyocardial injection of DAPI-labeled MSC immediately, and observed the differentiation of MSCs after 14 days by immunofluorescence staining against troponin T. We cultured MSCs and cardiomyocytes in four ways, respectively, in vitro. (1) MSCs cocultured with cardiomyocytes obtained from neonatal rat ventricles in a ratio of 1:10. (2) The two types of cells were cultured in two chambers separated by a semipermeable membrane as indirect coculture group. (3) Notch receptor-soluble jagged1 protein was added to indirect coculture group. (4) Both jagged1 protein and gamma-secretase inhibitor-DAPT were added to indirect coculture group. Two weeks later, we observed the differentiation percentage, respectively, by immunofluorescence staining. RESULTS: We found the differentiation of MSCs which were close to cardiomyocytes in vivo. The differentiation percentage of the four cell culture group was 30.13+/-2.16%, 12.52+/-1.18%, 26.33+/-2.20%, and 13.08+/-1.15%. CONCLUSIONS: MSCs can differentiate into cardiomyocytes in vitro and in vivo if a cardiomyocyte microenvironment is provided. 2. Cell-to-cell interaction is very important for the differentiation of MSCs into cardiomyocytes. 3. Jagged1 protein can activate Notch signal and enhance the differentiation of MSC into cardiomyocyte, while the effect can be inhibited by DAPT.
Rhodococcus erythropolis XP could grow well with condensed thiophenes, mono-thiophenic compounds and mercaptans present in gasoline. Rhodococcus erythropolis XP was also capable of efficiently degrading the condensed thiophenes in resting cell as well as biphasic reactions in which n-octane served as a model oil phase. Free whole cells of R. erythropolis XP were adopted to desulfurize fluid catalytic cracking (FCC) and straight-run (SR) gasoline oils. About 30% of the sulfur content of FCC gasoline and 85% of sulfur in SR gasoline were reduced, respectively. Gas chromatography analysis with atomic emission detection also showed depletion of sulfur compounds in SR gasoline. Rhodococcus erythropolis XP could partly resist the toxicity of gasoline and had an application potential to biodesulfurization of gasoline.
Biphasic systems can overcome the problem of low productivity in conventional media and have been exploited for biocatalysis. Solvent-tolerant microorganisms are useful in biotransformation with whole cells in biphasic reactions. A solvent-tolerant desulfurizing bacterium, Pseudomonas putida A4, was constructed by introducing the biodesulfurizing gene cluster dszABCD, which was from Rhodococcus erythropolis XP, into the solvent-tolerant strain P. putida Idaho. Biphasic reactions were performed to investigate the desulfurization of various sulfur-containing heterocyclic compounds in the presence of various organic solvents. P. putida A4 had the same substrate range as R. erythropolis XP and could degrade dibenzothiophene at a specific rate of 1.29 mM g (dry weight) of cells(-1) h(-1) for the first 2 h in the presence of 10% (vol/vol) p-xylene. P. putida A4 was also able to degrade dibenzothiophene in the presence of many other organic solvents at a concentration of 10% (vol/vol). This study is a significant step in the exploration of the biotechnological potential of novel biocatalysts for developing an efficient biodesulfurization process in biphasic reaction mixtures containing toxic organic solvents.