In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, ...kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential ...mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.
Due to the unpredictability of global events such as a COVID-19 pandemic, it is necessary to prepare for a crisis management strategy at the macro-level in each country to respond to crises that ...bring about social change. This study is designed to discover critical priorities and agendas in crisis management in Saudi Arabia by grasping the most recent social issues of the COVID-19 pandemic addressed in the most trusted media sources. The data were collected from news media (Saudi Press Agency and Al Arabiya) and social media (Twitter and YouTube) in big data from February to August 2020, then analyzed through semantic network analysis. This study provides the uncanny and marvelous power to help any individual, organization, even society, and country to be more innovative and proactive by acquiring trend, agenda-based approaches into uncertain future crises using advanced technology in big data. This research also shows how a country can use those big data to detect “key social issues” and then make a subsequent strategy or decision-making system to develop a public communication or new policy in future events. Accordingly, this study provides meaningful and insightful implications for managing a coming crisis and social change, ensuring stability and sustainability at the micro- and macro-level.
Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in ...bone remodeling has not yet been elucidated in detail.
We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin
OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1β signaling. The ectopic expression of parkin in Parkin
OCPs limited the increase in dentin resorption induced by IL-1β, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity.
These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity.
Summary Background In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung ...Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. Methods We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. Findings 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% 23/117 vs 5% 3/58 in group B vs 1% 4/500 in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days IQR 4–8 vs 11 days 6–12; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. Interpretation Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Funding None.
In the present report, three different shapes of chitosan-capped gold nanoparticles (nanospheres, nanostars, and nanorods) were synthesized to investigate the effects of shape on cytotoxicity and ...cellular uptake in cancer cells. Green tea extract was utilized as a reducing agent to reduce gold salts to gold nanospheres. Gold nanostars were prepared using an as-prepared nanosphere solution as a seed solution. Gold nanorods were synthesized using a conventional method. All three types of gold nanoparticles showed their characteristic surface plasmon resonance bands upon UV-visible spectrophotometry. In high-resolution transmission electron microscopy images, lattice structures were clearly observed in all three shapes, confirming the crystalline nature of the nanoparticles. All three colloidal solutions of gold nanoparticles retained colloidal stability in various solutions. To assess cytotoxicity, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed on four cancer cell lines. The cytotoxicity was the highest in nanorods, followed by nanostars and finally nanospheres. The cellular uptake of gold nanoparticles in human hepatocyte carcinoma cells (HepG2) was measured, and the results followed the order nanospheres > nanorods > nanostars. The outcomes of the current study may assist in the shape design of gold nanoparticles for therapeutic applications as drug delivery vehicles in the field of nanomedicine.
Dysregulation of MLL complex-mediated histone methylation plays a pivotal role in gene expression associated with diseases, but little is known about cellular factors modulating MLL complex activity. ...Here, we report that SON, previously known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation. SON binds to DNA near transcription start sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and transcriptional repression. Importantly, alternatively spliced short isoforms of SON are markedly upregulated in acute myeloid leukemia. The short isoforms compete with full-length SON for chromatin occupancy but lack the menin-binding ability, thereby antagonizing full-length SON function in transcriptional repression while not impairing full-length SON-mediated RNA splicing. Furthermore, overexpression of a short isoform of SON enhances replating potential of hematopoietic progenitors. Our findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpression as a marker indicating aberrant transcriptional initiation in leukemia.
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•SON negatively controls H3K4me3 and the MLL1/2 complex at transcription start sites•SON interacts with menin and inhibits MLL-menin interaction•Short SON isoforms generated by alternative splicing are upregulated in AML•Short isoforms lacking menin-binding ability attenuate full-length SON function
Kim et al. demonstrate that SON and its splice variants control MLL complex-mediated transcriptional initiation. Full-length SON binds menin and inhibits MLL complex assembly, decreasing H3K4me3. Short, alternatively spliced SON isoforms are upregulated in acute myeloid leukemia and antagonize full-length SON function.
To evaluate the influence of myoma characteristics on cesarean myomectomy and to demonstrate its additional advantages.
Retrospective data were collected from 292 women with myomas who had undergone ...cesarean section at Kangnam Sacred Heart Hospital between 2007 and 2019. We performed subgroup analysis according to the type, weight, number, and size of myomas. Preoperative and postoperative hemoglobin levels, operative time, estimated blood loss, length of hospital stay, incidence of transfusion, uterine artery embolization, ligation, hysterectomy, and postoperative complications were compared among subgroups.
There were 119 patients who had cesarean myomectomy and 173 who had cesarean section only. An increase in postoperative hospitalization and operation time was observed in the cesarean myomectomy group compared to that in the caesarean section only group (mean difference, 0.7 days, p = 0.01, 13.5 minutes, p <0.001). Estimated blood loss, hemoglobin differences, and transfusion rates were higher in the cesarean myomectomy than in the cesarean section only group. There were no differences in postoperative complications (fever, bladder injury, and ileus) between the two groups. No hysterectomy cases were reported in the cesarean myomectomy group. In subgroup analysis, the larger and heavier the myoma, the higher the risk of bleeding that led to transfusion. Estimated blood loss, differences in hemoglobin, and transfusion rate increased depending on myoma size and weight. A significant increase in postoperative hospitalization was observed in women with larger and heavier myomas. However, there was no statistical difference among the three types of myomas.
In cesarean myomectomy, larger (≥ 10 cm), and heavier myomas (≥ 500 g), were associated with postoperative outcomes, but not the number or type of myoma. The safety of cesarean myomectomy is not inferior to that of caesarean section only, considering its positive effects such as gynecological symptom relief and avoidance of the next surgery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Textile-based sensors can perceive and respond to environmental stimuli in daily life, and hence are critical components of wearable devices. Herein, self-powered triboelectric wearable sensors are ...fabricated using polyvinylidene fluoride (PVDF) fibers stitched by using a sewing machine. The excellent mechanical properties of dry-jet wet spun PVDF fibers allow the use of a sewing machine to stitch them into diverse programmable textile patterns on various fabric substrates. Such stitches can provide remarkable triboelectric signals when in contact with the opposing surfaces of commercial fabrics, since PVDF has higher electron affinity than other polymers. In addition, PVDF stitch-based triboelectric sensors are flexible, lightweight, wearable, washable, and comfortable. Furthermore, they can detect a broad pressure range (326 Pa to 326 kPa), which is unachievable with conventional textile force sensors, enabling diverse pressure-sensor applications. To demonstrate their use in wearable devices, a smart glove and joint pads are fabricated based on PVDF stitch-based triboelectric sensors. These wearable sensors enable the detection of and distinguishing diverse hand gestures and body motions by generating intrinsic signal patterns for the specific gesture and motions. These sensors also enable real-time self-powered pulse signal monitoring. This work demonstrates a feasible fabrication approach to realize stitched textile sensors using a sewing machine, with many possible e-textile applications.
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier ...integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
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