Senile cataracts and oxidative stress

AbstractIn numerous epidemiological and animal models, it can be inferred that oxidative stress is a key factor in cataract formation. Production of reactive oxygen species and reduction of endogenous antioxidants both contribute to cataract formation. In the cataractogenous process, lens proteins lose sulfhydryl groups and become thiolated or cross-linked by disulfide bonds. The resultant high molecular weight aggregates become insoluble and affect lens transparency. All these are consequences of changes in the redox state. A mixed protein-thiol and protein-protein disulfide bond precedes the morphological changes of cataract. Normally, sustained high levels of reduced glutathione provide a protective effect, while depletion of glutathione causes damage to epithelial cells and fiber cells. UV rays in the ambient environment evoke reactive oxygen species formation and also contribute to cataracts. The reduction in free UV filters and increase in their binding to lens proteins make the lens more predisposed to UV damage and oxidation. In the aqueous humor of cataract lenses, there is a decrease in antioxidant enzymes and increase in nitric oxide, which demonstrates the relationship between oxidative stress and cataracts. Though surgical intervention is the standard treatment for cataracts, experimental medical therapies for cataracts are under extensive investigation. Carnosine, a pro-drug of carnosine-N-acetylcarnosine, bendazac, ascorbic acid, and aldose reductase inhibitors are under therapeutic evaluation, and prevention of cataract formation may be possible in the future

Scaling laws for non-Hermitian skin effect with long-range couplings

Recent years have witnessed a surge of research on the non-Hermitian skin effect (NHSE) in one-dimensional lattices with finite-range couplings. In this work, we show that the long-range couplings that decay as $1/l^{\alpha}$ at distance $l$ can fundamentally modify the behavior of NHSE and the scaling of quantum entanglement in the presence of nonreciprocity. At $\alpha=0$, the nonlocality of couplings gives rise to the scale-free skin modes, whose localization length is proportional to the system size. Increasing the exponent $\alpha$ drives a complex-to-real spectral transition and a crossover from a scale-free to constant localization length. Furthermore, the scaling of nonequilibrium steady-state entanglement entropy exhibits a subextensive law due to the nonlocality and the complex spectrum, in contrast to an area law arising from NHSE. Our results provide a theoretical understanding on the interplay between long-range couplings and non-Hermiticity.Comment: 6 pages, 4 figure

M-SpeechCLIP: Leveraging Large-Scale, Pre-Trained Models for Multilingual Speech to Image Retrieval

This work investigates the use of large-scale, pre-trained models (CLIP and HuBERT) for multilingual speech-image retrieval. For non-English speech-image retrieval, we outperform the current state-of-the-art performance by a wide margin when training separate models for each language, and show that a single model which processes speech in all three languages still achieves retrieval scores comparable with the prior state-of-the-art. We identify key differences in model behavior and performance between English and non-English settings, presumably attributable to the English-only pre-training of CLIP and HuBERT. Finally, we show that our models can be used for mono- and cross-lingual speech-text retrieval and cross-lingual speech-speech retrieval, despite never having seen any parallel speech-text or speech-speech data during training.Comment: Submitted to ICASSP 202

Nitroprusside modulates pulmonary vein arrhythmogenic activity

<p>Abstract</p> <p>Background</p> <p>Pulmonary veins (PVs) are the most important sources of ectopic beats with the initiation of paroxysmal atrial fibrillation, or the foci of ectopic atrial tachycardia and focal atrial fibrillation. Elimination of nitric oxide (NO) enhances cardiac triggered activity, and NO can decrease PV arrhythmogensis through mechano-electrical feedback. However, it is not clear whether NO may have direct electrophysiological effects on PV cardiomyocytes. This study is aimed to study the effects of nitroprusside (NO donor), on the ionic currents and arrhythmogenic activity of single cardiomyocytes from the PVs.</p> <p>Methods</p> <p>Single PV cardiomyocytes were isolated from the canine PVs. The action potential and ionic currents were investigated in isolated single canine PV cardiomyocytes before and after sodium nitroprusside (80 μM,) using the whole-cell patch clamp technique.</p> <p>Results</p> <p>Nitroprusside decreased PV cardiomyocytes spontaneous beating rates from 1.7 ± 0.3 Hz to 0.5 ± 0.4 Hz in 9 cells (P < 0.05); suppressed delayed afterdepolarization in 4 (80%) of 5 PV cardiomyocytes. Nitroprusside inhibited L-type calcium currents, transient outward currents and transient inward current, but increased delayed rectified potassium currents.</p> <p>Conclusion</p> <p>Nitroprusside regulates the electrical activity of PV cardiomyocytes, which suggests that NO may play a role in PV arrhythmogenesis.</p

Bizarre parosteal osteochondromatous proliferation on a phalanx with periosteal erosion

SummaryBizarre parosteal osteochondromatous proliferation (BPOP) is an uncommon benign hand tumor with a high rate of local recurrence, marked proliferative activity, and an atypical histological appearance. The aim of this paper is to present a rare and illustrative example of BPOP with periosteal erosion. A 64-year-old male presented with a 10-year history of a mass, measuring approximately 3 cm in diameter, on the dorsal aspect of the right index finger. On physical examination, the mass was hard, indolent, and located at the level of the proximal phalanx. Roentgenograms displayed a soft tissue mass over the right index finger with erosion of the periosteum. Magnetic resonance imaging revealed a few well-defined lobulated tumors over the right index finger proximal interphalangeal joint with periosteal reaction. The soft tissue tumors were excised and found to have soft consistencies. Pathological findings demonstrated that the tumor was compatible with BPOP. BPOP is a benign but locally aggressive fibro-osseous mass yielding radiographic findings that bear striking clinical similarities to those of other diseases, such as osteochondroma, osteosarcoma, and myositis ossificans. As the radiographic findings of BPOP are equivocal, the differential diagnosis must be based on the pathological results. With this case report, we aim to inform physicians that a hand tumor with an aggressive clinical picture may be benign in origin

Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy

BACKGROUND: Although cytotoxic T lymphocytes (CTLs) play a major role in eradicating cancer cells during immunotherapy, the cancer-associated immunosuppressive microenvironment often limits the success of such therapies. Therefore, the simultaneous induction of cancer-specific CTLs and reversal of the immunosuppressive tumor microenvironment may be more effectively achieved through a single therapeutic vaccine. A recombinant lipoprotein with intrinsic Toll-like receptor 2 (TLR2) agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety (rlipo-E7m) has been demonstrated to induce robust CTL responses against small tumors. This treatment in combination with other TLR agonists is able to eliminate large tumors. METHODS: Mouse bone marrow-derived dendritic cells (DCs) were employed to determine the synergistic production of pro-inflammatory cytokines upon combination of rlipo-E7m and other TLR agonists. Antigen-specific CTL responses were investigated using immunospots or in vivo cytolytic assays after immunization in mice. Mice bearing various tumor sizes were used to evaluate the anti-tumor effects of the formulation. Specific subpopulations of immunosuppressive cells in the tumor infiltrate were quantitatively determined by flow cytometry. RESULTS: We demonstrate that a TLR9 agonist (unmethylated CpG oligodeoxynucleotide, CpG ODN) enhances CTL responses and eradicates large tumors when combined with rlipo-E7m. Moreover, combined treatment with rlipo-E7m and CpG ODN effectively increases tumor infiltration by CTLs and reduces the numbers of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment. CONCLUSION: These findings suggest that the dramatic anti-tumor effects of the recombinant lipoprotein together with CpG ODN may reflect the amplification of CTL responses and the repression of the immunosuppressive environment. This promising approach could be applied for the development of additional therapeutic cancer vaccines

The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma