Ubiquitylation plays key roles in DNA damage signal transduction. The current model envisions that lysine63-linked ubiquitin chains, via the concerted action of E3 ubiquitin ligases RNF8-RNF168, are ...built at DNA double-strand breaks (DSBs) to effectively assemble DNA damage-repair factors for proper checkpoint control and DNA repair. We found that RNF168 is a short-lived protein that is stabilized by the deubiquitylating enzyme USP34 in response to DNA damage. In the absence of USP34, RNF168 is rapidly degraded, resulting in attenuated DSB-associated ubiquitylation, defective recruitment of BRCA1 and 53BP1 and compromised cell survival after ionizing radiation. We propose that USP34 promotes a feed-forward loop to enforce ubiquitin signaling at DSBs and highlight critical roles of ubiquitin dynamics in genome stability maintenance.
Abstract
Background
To investigate the surgical outcomes of implantable collamer lens (ICL) implantation in eyes with residual myopia after primary laser vision correction (LVC) surgeries.
Methods
...This study included patients who underwent ICL implantation and had a history of LVC surgery, including photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK). Visual acuity and refractive error were assessed pre and 3-months postoperatively and the efficacy and safety indices calculated accordingly.
Results
A total of 30 eyes of 17 patients were included in this study. At 3 months, the mean logMAR uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were − 0.03 ± 0.11 (include logMAR), − 0.04 ± 0.09 (include logMAR), and − 0.06 ± 0.33 diopters (D), respectively. The 3-month Snellen UDVA was better than 20/20 for 83% of eyes, and 97% of eyes showed an unchanged or improved CDVA after surgery. The mean efficacy and safety indices were 1.11 ± 0.22 and 1.13 ± 0.20, respectively. Further, 93 and 100% of eyes were within ±0.5 and ± 1.0 D of the attempted spherical equivalent refraction, respectively.
Conclusions
ICL implantation in eyes with myopic regression after previous LVC surgery showed safe, effective, and predictable outcomes.
Trial registration
retrospectively registered.
After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of ...patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.
Depression is common in women with much research focusing on hormonal changes and menopausal symptoms but with little exploration of psychosocial problems in midlife. This study investigates the ...prevalence of clinically relevant depressive symptoms in midlife Chinese women and its association with psychosocial factors.
A cross-sectional, community-based household survey of women aged 45 to 64 years of age was conducted in Hong Kong from September 2010 to March 2011. The structured questionnaire included demographic data, educational status, marital status and household income, as well as perceived current stressful events and significant life events in the past 12 months. Information on clinically relevant depressive symptoms was measured by the validated chinese Patient Health Questionnaire (PHQ-9).
A total of 402 participants were recruited in the study period. Of the 393 women who completed the questionnaire, the prevalence of clinically relevant depressive symptoms (PHQ-9 score≧10) was 11.0%. In multiple regression analysis, being single/divorced/separated/widowed, having an educational level of primary school level or below, having multiple chronic diseases, loss of hobby or loss of close social support in the past 12 months in midlife were associated with clinically relevant depressive symptoms.
Correlates of clinically relevant depressive symptoms in midlife Chinese women can be used to identify those at increased risk and potentiate further studies to explore early psychosocial and community interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To achieve a high concentration of dopants over <inline-formula> <tex-math notation="LaTeX">{1} \times {10}^{{20}} </tex-math></inline-formula> cm −3 on germanium (Ge), co-doping with phosphorus (P) ...and antimony (Sb) by plasma assisted atomic layer deposition (PALD) and a subsequent annealing process rapid thermal annealing process (RTP) or flash lamp annealing process (FLP) are proposed and investigated. We found that the PALD stacked co-doping (PO x /SiO y and Sb 2 O 5 ) films were uniformly deposited. Using the conventional RTP method led to a low doping concentration (<inline-formula> <tex-math notation="LaTeX"> < {3}\times {10}^{{19}}\mathrm {cm}^{-{3}} </tex-math></inline-formula>). However, FLP with a Xenon (Xe) lamp (lamp duration: 3 ms; energy density: 56 J/cm 2 ) raised the surface temperature to nearly 800 °C. Furthermore, high concentrations of both P and Sb (<inline-formula> <tex-math notation="LaTeX">> 1\times 10^{{20}}\mathrm {cm}^{-{3}} </tex-math></inline-formula>) were achieved at the surface. Our findings suggest that the FLP with high energy in a short amount of time (~3ms) can create the peak power effect and the co-doping effect. The evidence shows that these effects contribute to enhancing n-type doping levels in the Ge structure.
While dimensional change under thermal loading dictates various device failure mechanisms in soft materials, the interplay between microstructures and thermal expansion remains underexplored. Here, ...we develop a novel method to directly probe the thermal expansion for nanoscale polymer films using an atomic force microscope as well as confining active thermal volume. In a model system, spin-coated poly(methyl methacrylate), we find that the in-plane thermal expansion is enhanced by 20-fold compared to that along the out-of-plane directions in confined dimensions. Our molecular dynamics simulations show that the collective motion of side groups along backbone chains uniquely drives the enhancement of thermal expansion anisotropy of polymers in the nanoscale limit. This work unveils the intimate role of the microstructure of polymer films on its thermal–mechanical interaction, paving a route to judiciously enhance the reliability in a broad range of thin-film devices.
Objective
Metabolic bariatric procedures are potentially efficacious treatment options in patients with type 2 diabetes mellitus (T2DM). Previous meta‐analyses focused on individual operative ...approaches rather than the mechanistic pathways behind different bariatric procedures. This updated network meta‐analysis aimed to synthesize new evidence and comparatively evaluate the efficacy of metabolic surgery against restrictive procedures and standard first‐line treatment for patients with T2DM.
Methods
Embase, MEDLINE, and trial registries were searched for randomized controlled trials on bariatric surgeries in patients with T2DM on September 3, 2021. A Bayesian network meta‐analysis was conducted. The primary outcome was T2DM remission. Secondary outcomes included changes in BMI, lipoprotein levels, and blood pressure.
Results
Thirty‐two articles were included. Metabolic surgery was statistically superior to restrictive procedures (risk ratio RR: 2.57, 95% credibility intervals CrI: 1.36‐5.43), medical therapy (RR: 35.29, 95% Crl: 10.56‐183.23), and lifestyle intervention (RR: 40.51, 95% Crl: 5.32‐402.59) in T2DM remission. Metabolic surgery significantly lowered BMI and blood pressure compared with other interventions. Restrictive procedures significantly increased high‐density lipoprotein compared with metabolic surgery. Lifestyle intervention and metabolic surgery were statistically superior to restrictive procedures in reducing low‐density lipoprotein.
Conclusions
The superiority in diabetes remission and favorable metabolic profile support the choice of metabolic surgery over restrictive bariatric procedures.
The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human ...bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3'UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p.
Sixty-one SARS coronavirus genomic sequences derived from the early, middle, and late phases of the severe acute respiratory syndrome (SARS) epidemic were analyzed together with two viral sequences ...from palm civets. Genotypes characteristic of each phase were discovered, and the earliest genotypes were similar to the animal SARS-like coronaviruses. Major deletions were observed in the Orf8 region of the genome, both at the start and the end of the epidemic. The neutral mutation rate of the viral genome was constant but the amino acid substitution rate of the coding sequences slowed during the course of the epidemic. The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization.
Enhanced coupling of material properties offers new fundamental insights and routes to multifunctional devices. In this context 5d oxides provide new paradigms of cooperative interactions that drive ...novel emergent behaviour. This is exemplified in osmates that host metal-insulator transitions where magnetic order appears intimately entwined. Here we consider such a material, the 5d perovskite NaOsO3, and observe a coupling between spin and phonon manifested in a frequency shift of 40 cm(-1), the largest measured in any material. The anomalous modes are shown to involve solely Os-O interactions and magnetism is revealed as the driving microscopic mechanism for the phonon renormalization. The magnitude of the coupling in NaOsO3 is primarily due to a property common to all 5d materials: the large spatial extent of the ion. This allows magnetism to couple to phonons on an unprecedented scale and in general offers multiple new routes to enhanced coupled phenomena in 5d materials.
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