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Biomedical subjects

Bo Lei

Publications and source records attributed to Bo Lei.

At least 19 recordsLinked to original sources

Oncotype DX-guided vs physician-directed chemotherapy and survival in HR+/HER2- breast cancer.

BACKGROUND: Oncotype DX testing guides adjuvant chemotherapy decisions in early-stage hormone receptor-positive/HER2-negative breast cancer, but testing is not universally performed, and outcomes associated with genomic-informed versus clinicopathologic-based chemotherapy decision pathways remain unclear. METHODS: Using the 2022 National Cancer Database Breast Participant User File, we identified women diagnosed from 2010 to 2022 with pathologic T1b-T2, node-negative, hormone receptor-positive/HER2-negative invasive breast cancer who received adjuvant chemotherapy and endocrine therapy. Patients were classified into an Oncotype-guided group, defined by Oncotype DX testing with a recurrence score of 26 or higher, and a physician-directed group, defined by receipt of chemotherapy without genomic testing. The primary outcome was overall survival. Analyses used multivariable Cox models, logistic-IPTW and MLP-IPTW, restricted mean survival time analysis, and a Bayesian latent confounding survival model. RESULTS: Among 56,625 women, 27,278 were in the Oncotype-guided group and 29,347 in the physician-directed group. Median ages were 59 and 56 years, respectively. The Oncotype-guided group had more favorable overall survival than the physician-directed group in multivariable Cox analysis (HR, 0.906; 95% CI, 0.856-0.959; P&#x202f;<&#x202f;0.001), with similar findings in IPTW analyses. The association was concentrated among patients aged 56 years or older (HR, 0.866; 95% CI, 0.809-0.927; P&#x202f;<&#x202f;0.001). The Bayesian model showed no strong residual confounding signal. CONCLUSIONS: Among chemotherapy-treated women, an Oncotype-guided pathway was associated with more favorable overall survival than a physician-directed pathway, particularly among older patients, which indicating prognostic heterogeneity selected using genomic versus conventional clinicopathologic information.

Humans↗

Spectral attenuation of the mouse, rat, pig and human lenses from wavelengths 360 nm to 1020 nm.

The transmission spectrum of the lens is essential to calculate irradiance at the surface of the retina. Although the mouse is a common model for ophthalmic research, there is little information on the transmission of the mouse lens. Attenuation by the lens is partly dependent on lens thickness; however, the attenuation coefficient is independent of lens thickness. In this study, we measured the attenuation coefficients of the albino and pigmented mouse lens as well as those of the rat, pig, and human lenses, and provide a composite equation that describes the attenuation coefficients in the ultraviolet and visible bandwidths (360-700 nm). In the near infrared region (700-1020 nm), water absorption must be included to explain the measurements.

Absorption↗

Ocular phenotype in a mouse gene knockout model for infantile neuronal ceroid lipofuscinosis.

Mutations in the human protein palmitoyl thioesterase-1 (PPT-1) gene result in an autosomal recessive neurodegenerative disorder designated neuronal ceroid lipofuscinosis (NCL), type CLN1, or infantile NCL. Among the symptoms of the CLN1 disease are accumulation of autofluorescent lysosomal storage bodies in neurons and other cell types, seizures, motor and cognitive decline, blindness, and premature death. Development of an effective therapy for this disorder will be greatly assisted by the availability of suitable animal models. A mouse PPT-1 gene knockout model has recently been generated. Studies were performed to determine whether the mouse model exhibits ocular features of the human CLN1 disorder. A progressive accumulation of autofluorescent storage material in all layers of the retina was observed in the PPT-1 knockout mice. Accompanying the storage body accumulation was a modest loss of cells with nuclei in the outer and inner nuclear layers. As indicated by electroretinogram (ERG) responses, retinal function was only mildly impaired at 4 months of age but was severely impaired by 8 months, despite only modest changes in retinal morphology. The pupillary light reflex (PLR), on the other hand, was exaggerated in the knockout mice. The apparent anomaly between the ERG and the PLR findings suggests that disease-related PLR changes may be due to changes in extraocular signal processing. The pronounced ocular phenotype in the PPT-1 knockout mice makes these animals a good model for testing therapeutic interventions for treatment of the human CLN1 disorder.

Adaptor Proteins, Signal Transducing↗

Ultraviolet light-induced and green light-induced transient pupillary light reflex in mice.

PURPOSE: To study UV light-induced and green light-induced pupillary light reflex (PLR) in mice and to measure the illumination thresholds of rod-mediated and cone-mediated PLR responses. METHODS: We measured dark-adapted transient PLR- in C57BL/6 mice elicited with ultraviolet and green light over an intensity range of 9 log units. To assist in isolating the responses mediated by rods and cones, we studied the PLRs in mouse models presenting pure cone and pure rod functions. We also characterized ERG signals in these mice under the same experimental conditions. RESULTS: The UV light-induced transient PLR has identical intensity-response curves as green light-induced PLR in all the three mice strains. The threshold (5% PLR) of rod-driven PLR is 107 approximately 108 photons cm2 s-1, which is 1 approximately 2 log units lower than the dark-adapted ERG b-wave. The threshold of cone-driven PLR is approximately 1012.5 photons cm-2 s-1 and is similar to that of the cone ERG. CONCLUSIONS: We demonstrated that mice have PLR responses under UV stimulation. The cone-elicited PLRs have a threshold that is approximately 5 log units higher than that of rod-elicited PLR at both UV and green wavelengths. We observed a divergence between the spectra responses in PLR and ERG. However, the mechanism and implications of this phenomenon are yet to be identified.

Animals↗

Study of rod- and cone-driven oscillatory potentials in mice.

PURPOSE: To characterize rod- and cone-driven oscillatory potentials (OPs) in mice. METHODS: Dark- and light-adapted electroretinograms (ERGs) were obtained in three mouse models: wild-type C57BL/6J mouse, cone photoreceptor function loss 1 (cpfl1) mouse, and rhodopsin knockout (rho-/-) mouse. A Butterworth filter was used to extract OPs from ERG signals. Latencies were calculated from the extracted OPs. Major frequency components were determined from OP power spectra computed using fast Fourier transform (FFT). The total power of the OP signal (an alternative measurement of amplitude) was calculated by numerically integrating the area enclosed by its frequency spectra, which is analogous to the total energy of mechanical vibration. RESULTS: In C57BL/6J mice, dark- and light-adapted OPs had distinctly different peak frequencies (100 to 120 Hz and 70 to 85 Hz, respectively). In cpfl1 mice which possess pure rod ERGs, dark-adapted OPs had a peak frequency similar to those of the wild-type mice, whereas light-adapted ERGs and OPs were not detectable. In rho-/- mice with pure cone functions, both dark-adapted and light-adapted OPs had peak frequencies of 70 to 90 Hz, which were similar to those obtained from light-adapted OPs in wild-type mice. The total power of cone-driven OPs was less than 5% that of rod-driven OPs. In time-domain, cone-driven OPs occurred approximately 13 ms after rod-driven OPs. CONCLUSIONS: Cone- and rod-driven OPs exhibit significantly different characteristics in peak frequency, latency, and total power. By using these characteristics, it is possible to differentiate cone- and rod-driven OPs in mouse models. Understanding these OP features is essential for analyzing OPs.

Animals↗

Efficient synthesis and electronic studies of core-shell nanowires based on colossal magnetoresistive manganites.

We report our recent study on the pulsed laser deposition process in the synthesis of colossal magnetoresistive MgO/LaCaMnO3 and MgO/LaSrMnO3 core-shell nanowires. A highly efficient process has been developed by depositing an epitaxial layer of manganite onto randomly oriented MgO nanowires grown on SiO2/Si substrates. In addition, in-depth studies revealed that the sample-target distance played a critical role in determining the core-shell nanowire quality. The MgO/LaCaMnO3 and MgO/LaSrMnO3 nanowires opened up the unique opportunity to explore a number of intriguing physical properties at the nanoscale. Remarkable metal-insulator phase transitions and pronounced colossal magnetoresistance have been observed in both LaCaMnO3 and LaSrMnO3 nanostructures.

Journal Article↗

Complementary detection of prostate-specific antigen using In2O3 nanowires and carbon nanotubes.

We report complementary detection of prostate-specific antigen (PSA) using n-type In2O3 nanowires and p-type carbon nanotubes. Our innovation involves developing an approach to covalently attach antibodies to In2O3 NW surfaces via the onsite surface synthesis of phosphonic acid-succinylimide ester. Electronic measurements under dry conditions revealed complementary response for In2O3 NW and SWNT devices after the binding of PSA. Real-time detection in solution has also been demonstrated for PSA down to 5 ng/mL, a benchmark concentration significant for clinical diagnosis of prostate cancer, which is the most frequently diagnosed cancer.

Indium↗

Behavioral assessment in mouse models of neuronal ceroid lipofuscinosis using a light-cued T-maze.

Learning impairment is a common feature of the neuronal ceroid lipofuscinoses (NCL), a family of lysosomal storage disorders associated with progressive neurodegeneration. Murine models for the neuronal ceroid lipofuscinoses include the well-characterized motor neuron degeneration (mnd/mnd) model for one variant of late infantile NCL (CLN8), and the more recently generated models for the infantile (CLN1) and juvenile (CLN3) forms of NCL. To determine whether these mouse models exhibit behavioral deficits analogous to the learning impairment characteristic of the human disorders, the performance of these animals on an associative learning task was assessed. The abilities of affected and normal control mice to associate a light stimulus with a food reward were evaluated in 14-16-week-old animals using a T-maze. Normal mice were able to reach a criterion for having learned to make the association within a mean of 9.4 trials. The CLN8 and CLN3 mice, on the other hand, required means of 26.2 and 27.5 trials, respectively, to reach the same performance criterion (p<0.05), whereas none of the CLN1 mice were able to reach the criterion within a limit of 30 trials. The poor performance of the mutant mice did not appear to result from impaired retinal function; mice of all three strains exhibited retinal electrophysiological responses to dim light flashes and displayed robust pupillary light reflexes. Associative learning deficits appear to be an early disease phenotype in the NCL mouse models that will be useful for assessing the efficacy of therapeutic interventions such as gene or stem cell therapies.

Analysis of Variance↗

Selective functionalization of In2O3 nanowire mat devices for biosensing applications.

A strategy to covalently attach biological molecules to the electrochemically active surface of indium oxide nanowire (In2O3 NW) mat devices is presented. A self-assembled monolayer (SAM) of 4-(1,4-dihydroxybenzene)butyl phosphonic acid (HQ-PA) was generated on an indium tin oxide (ITO)-coated glass and In2O3 NWs surface. The chemical steps required for surface derivatization were optimized on an ITO surface prior to modifying the In2O3 NWs. The hydroquinone group contained in the HQ-PA SAM was electrochemically oxidized to quinone (Q-PA) at +330 mV. The monolayer of Q-PA was allowed to react with a thiol-terminated DNA. The DNA was paired to its complementary strand tagged with a fluorescence dye. Attachment of DNA was verified using fluorescence microscopy. A device was subsequently prepared on a SiO2-supported mat of In2O3 NWs by depositing gold electrodes on the mat surface. The reaction strategy optimized on ITO was applied to this In2O3 NW-based device. Arrays of In2O3 NWs on a single substrate were electrochemically activated in a selective manner to Q-PA. Activated In2O3 NWs underwent reaction with HS-DNA and gave a positive fluorescence response after pairing with the dye-DNA. The unactivated In2O3 NWs gave no response, thus demonstrating selective functionalization of an In2O3 NW array. This can be considered a key step for the future fabrication of large-scale, inexpensive, nanoscale biosensors.

Biosensing Techniques↗

Single crystalline magnetite nanotubes.

We descried a method to synthesize single crystalline Fe3O4 nanotubes by wet-etching the MgO inner cores of MgO/Fe3O4 core-shell nanowires. Homogeneous Fe3O4 nanotubes with controllable length, diameter, and wall thickness have been obtained. Resistivity of the Fe3O4 nanotubes was estimated to be approximately 4 x 10-2 Omega cm at room temperature. Magnetoresistance of approximately 1% was observed at T = 77 K when a magnetic field of B = 0.7 T was applied. The synthetic strategy presented here may be extended to a variety of materials such as YBCO, PZT, and LCMO which should provide ideal candidates for fundamental studies of superconductivity, piezoelectricity, and ferromagnetism in nanoscale structures.

Ferrosoferric Oxide↗

Electroretinographic effects of an intravitreal injection of triamcinolone in rabbit retina.

OBJECTIVE: To investigate the clinical, histologic, and electroretinographic effects of intravitreal injection of triamcinolone acetonide suspension in the rabbit retina. METHODS: Three groups of 6 rabbits each received intravitreal injections. Group 1 received 4 mg of triamcinolone acetonide, group 2 received an equal volume (0.1 mL) of the corticosteroid supernatant, and group 3 received 4 mg of triamcinolone acetonide with the supernatant replaced with balanced salt solution. Uninjected left eyes served as controls. Electroretinograms were obtained at baseline and at 3 to 4 and 6 to 7 days after injection of triamcinolone. Enucleated eyes were examined histologically. RESULTS: Ocular examination revealed no differences among the 3 groups. When subjected to stimulation with moderate to high flash intensities, eyes that had received intravitreal injections of triamcinolone (groups 1 and 3) had a 10% to 25% increase in dark-adapted a- and b-wave electroretinographic amplitudes. No histologic differences were observed between injected and control eyes. CONCLUSIONS: Intravitreal injection of 4 mg of triamcinolone acetonide does not cause a toxic reaction in the rabbit retina after 7 days. Triamcinolone therapy may augment the rod-driven electroretinographic responses, suggesting a mechanism by which visual function may improve. Clinical Relevance Evaluation of the toxic effects of triamcinolone is useful because of increased applications of intravitreal injection.

Animals↗

Electrophysiologic differentiation of homozygous and heterozygous Abyssinian-crossbred cats with late-onset hereditary retinal degeneration.

OBJECTIVE: To develop a method to electrophysiologically differentiate heterozygous-carrier Abyssinian-crossbred cats from homozygous-affected Abyssinian-crossbred cats before clinical onset of inherited rod-cone retinal degeneration. ANIMALS: 14 back-crossed Abyssinian-crossbred cats of unknown genotype (homozygous or heterozygous) for inherited rod-cone retinal degeneration, 24 age-matched mixed-breed control cats, 6 age-matched heterozygous Abyssinian-crossbred cats, and 6 homozygous Abyssinian cats. PROCEDURE: Electroretinography (ERG) of heterozygous and homozygous cats revealed differences, especially for scotopic recordings. Frequent ophthalmoscopy and ERG (2 to 5 times; at intervals of 3 to 6 months) of back-crossed cats were performed. Amplitudes and implicit times were analyzed by use of a graphic representation of results. Ratios for amplitudes of the b-waves to amplitudes of the a-waves (b-wave:a-wave) were compared. RESULTS: 8 back-crossed cats had decreased a-wave amplitudes, increased b-wave implicit times, and abnormal ERG waveforms. Values for the b-wave:a-wave for the highest scotopic light intensity were significantly higher for those same 8 cats. CONCLUSIONS AND CLINICAL RELEVANCE: The 8 back-crossed Abyssinian-crossbred cats with abnormal results developed fundus changes over time consistent with disease. A graphic representation of ERG results can be used to differentiate between genotypes prior to funduscopic changes. Values for the b-wave:a-wave ratio provide confirmation. These ERG analyses may be applied clinically in the diagnosis of retinal degenerations in various species. IMPACT FOR HUMAN MEDICINE: Cats with hereditary rod-cone degeneration may be a useful model for comparative studies in relation to retinitis pigmentosa in humans. Similar evaluations of ERG results could possibly be used for humans with suspected generalized retinal degeneration.

Animals↗

[Biomass and carbon storage of ground bryophytes under six types of young coniferous forest plantations].

This paper studied the biomass and carbon storage of the ground bryophytes under young Picea balfouriana (P), Pinus tabulaeformis (Y), Pinus armandii (H), Larix kaempferi (L), Picea balfouriana-Pinus tabulaeformis (P-Y), and Pinus tabulaeformis-Pinus armandii (Y-H) forest plantations in the upper reach of Minjiang River, Sichuan Province. The results showed that total biomass and carbon storage of ground bryophytes were relatively low, being 3.11 - 460.36 kg x hm(-2) and 1.12 +/- 0.03 x 168.95 +/- 0.92 kg x hm(-2), respectively. On plot level, only the bryophyte biomass between forest P and others, and the carbon storage between forest L and others were significantly different. The ground bryophyte had the highest biomass and carbon storage under forest P, while the lowest ones under forest H. Comprehensive analysis suggested that forest type and its structural feature might be the important factors determining the biomass and carbon storage of ground bryophytes, and thinning was an important measure to improve ground bryophyte growth and biomass production.

Biomass↗

charge storage behavior of nanowire transistors functionalized with bis(terpyridine)-Fe(II) molecules: dependence on molecular structure.

We studied the influence of three bis(terpyridine)-Fe(II) molecules-(X-tpy)2FeCl2 (X = H (1), SAc (2), and 4-phenyl-SAc (3)-on charge storage of a nanowire transistor. The molecules were assembled on the surface of an indium oxide nanowire that forms the conduction channel of the transistor. We found that the charge storage characteristics of such a device strongly depends on the structure of the terpyridine ligand: both retention time (tau) and threshold voltage shift (DeltaVth) increased in the order of 1 < 2 < 3, with tau of 200 s, 12 h, and 287 h and DeltaVth at 4.8, 12, and 28 V, respectively. Furthermore, when we placed the devices with molecules 1 and 3 in a vacuum and recorded the I-Vg curves in a two-day period, we observed higher hysteresis stability for device with molecule 3. For example, DeltaVth was reduced from 4.8 to 1.7 V for the device with molecule 1, while there was no reduction in DeltaVth for the device with molecule 2. These results suggest that thiolate headgroup and/or longer ligand length raises the charge tunneling barrier and results in longer charge retention and wider, more stable memory window. This work demonstrates the potential of chemical synthesis toward tailored device characteristics.

Journal Article↗

Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology.

PURPOSE: ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor (CNTF). METHODS: Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days. RESULTS: Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas. CONCLUSIONS: CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities.

Animals↗

Neuroprotection of photoreceptors by minocycline in light-induced retinal degeneration.

PURPOSE: Microglial cells have been found to play pivotal roles in various neuronal degenerative diseases such as Parkinson's and Alzheimer's diseases. Minocycline, a microglial inhibitor, has recently been shown to be neuroprotective in various models of cerebral ischemia and degenerative diseases of the brain. This study was conducted to evaluate the neuroprotective effect of minocycline and the role of microglia in light-induced retinal degeneration. METHODS: BALB/cJ mice were exposed to intense green light for 3 hours and observed during 1, 3, or 7 days of dark recovery. The animals received intraperitoneal injections of minocycline or vehicle 1 day before exposure to light for 2, 4, or 8 days, depending on the periods of survival. Morphologic, morphometric, immunohistochemical, and electrophysiological studies were performed to evaluate the efficacy of minocycline in the amelioration of light-induced retinal degeneration and the possible involvement of microglial cells. RESULTS: Minocycline treatment provided marked amelioration in the loss of photoreceptors in light-induced retinal degeneration, as evidenced by morphologic, morphometric, and electrophysiologic criteria. Morphologically, the minocycline-treated group showed markedly better preservation of the outer retina after exposure to light. Morphometrically, at 7 days after exposure to light, in the minocycline-treated animals, 89.1% of the normal-appearing photoreceptor nuclei remained, but in the retinas of the vehicle-control group only 38.0% of these nuclei remained. This difference was statistically significant (P < 0.001). At 7 days after exposure to light electroretinography (ERG) showed that minocycline significantly preserved the amplitudes of dark-adapted a- and b-wave and light-adapted b-wave, which were all significantly reduced after exposure to light. Concomitant with this protective effect, at 3 days after exposure to light, the CD11b(+) microglial cells in the outer nuclear layer (ONL) and subretinal space in the minocycline-treated group were significantly decreased (by 63.5%) when compared with those in the light-exposed, vehicle-treated control group (P < 0.01). CONCLUSIONS: Minocycline is neuroprotective against light-induced loss of photoreceptors, possibly through the inhibition of retinal microglial activation.

Animals↗

Distribution of cadmium-binding components in flax (Linum usitatissimum L.) seed.

The distribution of cadmium- (Cd-) binding components in flaxseed (cultivar NorMan) containing 0.526 ppm (ng/mg) Cd was investigated. Proteins extracted from dehulled, defatted flaxseed were fractionated by anion-exchange and size-exclusion chromatography. The contents of Cd and other metals, UV/visible spectral characteristics, and amino acid compositions of these fractions were analyzed. Over 66% of the eluted Cd was recovered by 0.1 M NaCl elution from DEAE-Sephacel, in a thiol-rich fraction representing only 7% of the extracted proteins. Sephadex G50 size-exclusion chromatography of this 0.1 M NaCl fraction concentrated most of the Cd in a low-molecular-weight peak eluting at V(t). About 72% of the extracted flaxseed proteins eluted from DEAE-Sephacel at 0.25 M NaCl and contained only 25% of the eluted Cd. Because the major Cd-binding fraction is a minor constituent of flaxseed, these results indicate the potential to isolate flaxseed's major storage protein with a low Cd content.

Amino Acids↗