Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial ...lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A "high" TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a "high" score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A "high" 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11-0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To investigate the effect of muscle strength exercise training (MSET) on lean mass (LM) gain and muscle hypertrophy in older patients with lower extremity osteoarthritis (OA).
Methods
A ...comprehensive search of online databases was performed on April 20, 2019. Randomized controlled trials (RCTs) that reported the effects of MSET on LM, muscle thickness, and cross‐sectional area (CSA) in older patients with OA were identified. A risk of bias assessment and meta‐analysis were performed for the included RCTs.
Results
We included 19 RCTs with a median Physiotherapy Evidence Database score of 6 of 10 (range 3–7). In total, data from 1,195 patients (65% women, 85% with knee OA) with a mean age of 62.1 years (range 40–86 years) were analyzed. MSET resulted in significantly higher LM gain (standardized mean difference SMD 0.49 95% confidence interval (95% CI) 0.28, 0.71, P < 0.00001) than did the nonexercise controls. Meta‐analysis results revealed significantly positive effects of MSET on muscle thickness (SMD 0.82 95% CI 0.20, 1.43, P = 0.009) and CSA (SMD 0.80 95% CI 0.25, 1.35, P = 0.004) compared with nonexercise controls. No significant effects in favor of MSET were observed for any muscle outcome compared with exercise controls. Five RCTs reported nonsevere adverse events in response to MSET, whereas no RCTs reported severe events.
Conclusion
MSET is effective in increasing LM and muscle size in older adults with OA. Clinicians should incorporate MSET into their management of patients at risk of low muscle mass to maximize health status, particularly for older individuals with OA.
Abstract
Photocatalytic water splitting is attracting considerable interest because it enables the conversion of solar energy into hydrogen for use as a zero-emission fuel or chemical feedstock. ...Herein, we present a universal approach for inserting hydrophilic non-conjugated segments into the main-chain of conjugated polymers to produce a series of discontinuously conjugated polymer photocatalysts. Water can effectively be brought into the interior through these hydrophilic non-conjugated segments, resulting in effective water/polymer interfaces inside the bulk discontinuously conjugated polymers in both thin-film and solution. Discontinuously conjugated polymer with 10 mol% hexaethylene glycol-based hydrophilic segments achieves an apparent quantum yield of 17.82% under 460 nm monochromatic light irradiation in solution and a hydrogen evolution rate of 16.8 mmol m
−2
h
−1
in thin-film. Molecular dynamics simulations show a trend similar to that in experiments, corroborating that main-chain engineering increases the possibility of a water/polymer interaction. By introducing non-conjugated hydrophilic segments, the effective conjugation length is not altered, allowing discontinuously conjugated polymers to remain efficient photocatalysis.
Abstract
Background
Dysregulated long noncoding RNA (lncRNA) expression with increased apoptosis has been demonstrated in systemic lupus erythematosus (SLE) patients with alveolar hemorrhage (AH). ...SNHG16, a lncRNA, can enhance pulmonary inflammation by sponging microRNAs, and upregulate toll-like receptor 4 (TLR4) expression via stabilizing its mRNAs. TRAF6, a TLR4 downstream signal transducer, can induce autophagy and NETosis formation. In this study, we investigated whether SNHG16 could regulate TLR4-mediated autophagy and NETosis formation in SLE-associated AH.
Methods
Expression of SNHG16, TLR4 and TRAF6 and cell death processes were examined in lung tissues and peripheral blood (PB) leukocytes from AH patients associated with SLE and other autoimmune diseases, and in the lungs and spleen from a pristane-induced C57BL/6 mouse AH model. SNHG16-overexpressed or -silenced alveolar and myelocytic cells were stimulated with lipopolysaccharide (LPS), a TLR4 agonist, for analyzing autophagy and NETosis, respectively. Pristane-injected mice received the intra-pulmonary delivery of lentivirus (LV)-SNHG16 for overexpression and prophylactic/therapeutic infusion of short hairpin RNA (shRNA) targeting SNHG16 to evaluate the effects on AH. Renal SNHG16 expression was also examined in lupus nephritis (LN) patients and a pristane-induced BALB/c mouse LN model.
Results
Up-regulated SNHG16, TLR4 and TRAF6 expression with increased autophagy and NETosis was demonstrated in the SLE-AH lungs. In such patients, up-regulated SNHG16, TLR4 and TRAF6 expression was found in PB mononuclear cells with increased autophagy and in PB neutrophils with increased NETosis. There were up-regulated TLR4 expression and increased LPS-induced autophagy and NETosis in SNHG16-overexpressed cells, while down-regulated TLR4 expression and decreased LPS-induced autophagy and NETosis in SNHG16-silenced cells. Pristane-injected lung tissues had up-regulated SNHG16, TLR4/TRAF6 levels and increased in situ autophagy and NETosis formation. Intra-pulmonary LV-SNHG16 delivery enhanced AH through up-regulating TLR4/TRAF6 expression with increased cell death processes, while intra-pulmonary prophylactic and early therapeutic sh-SNHG16 delivery suppressed AH by down-regulating TLR4/TRAF6 expression with reduced such processes. In addition, there was decreased renal SNHG16 expression in LN patients and mice.
Conclusions
Our results demonstrate that lncRNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in the human and mouse AH lungs, and provide a therapeutic potential of intra-pulmonary delivery of shRNA targeting SNHG16 in this SLE-related lethal manifestation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their ...widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H
O)
to Zn(H
O)
before approaching the zinc surface. The exposed zinc ion in Zn(H
O)
provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol
. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm
, 10 mAh cm
) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.
We used nationwide population-based data to identify optimal hospital and surgeon volume thresholds and to discover the effects of these volume thresholds on operative mortality and length of stay ...(LOS) for coronary artery bypass surgery (CABG).
Retrospective cohort study.
General acute care hospitals throughout Taiwan.
A total of 12,892 CABG patients admitted between 2011 and 2015 were extracted from Taiwan National Health Insurance claims data.
Operative mortality and LOS. Restricted cubic splines were applied to discover the optimal hospital and surgeon volume thresholds needed to reduce operative mortality. Generalized estimating equation regression modeling, Cox proportional-hazards modeling and instrumental variables analysis were employed to examine the effects of hospital and surgeon volume thresholds on the operative mortality and LOS.
The volume thresholds for hospitals and surgeons were 55 cases and 5 cases per year, respectively. Patients who underwent CABG from hospitals that did not reach the volume threshold had higher operative mortality than those who received CABG from hospitals that did reach the volume threshold. Patients who underwent CABG with surgeons who did not reach the volume threshold had higher operative mortality and LOS than those who underwent CABG with surgeons who did reach the volume threshold.
This is the first study to identify the optimal hospital and surgeon volume thresholds for reducing operative mortality and LOS. This supports policies regionalizing CABG at high-volume hospitals. Identifying volume thresholds could help patients, providers, and policymakers provide optimal care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the ...interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19.
Synopsis
Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.
The ACE2‐Fc fusion protein can form a dimer that mimics a humanized antibody and specifically binds to the SARS‐CoV‐2 Spike protein.
The ACE2‐Fc fusion protein abrogates virus replication by blocking SARS‐CoV‐2 entry in clinical isolates.
The peptidase activity of ACE2‐Fc enables the decoy antibody to reduce angiotensin II‐mediated cytokine cascade.
After binding to Spike‐expressing target cells, ACE2‐Fc activates degranulation of NK cells.
Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.
Psychological stress increases risk of gastrointestinal tract diseases. However, the mechanism behind stress-induced gastrointestinal injury is not well understood. The objective of our study is to ...elucidate the putative mechanism of stress-induced gastrointestinal injury and develop an intervention strategy. To achieve this, we employed the restraint stress mouse model, a well-established method to study the pathophysiological changes associated with psychological stress in mice. By orally administering gut-nonabsorbable Evans blue dye and monitoring its plasma levels, we were able to track the progression of gastrointestinal injury in live mice. Additionally, flow cytometry was utilized to assess the viability, death, and inflammatory status of splenic leukocytes, providing insights into the stress-induced impact on the innate immune system associated with stress-induced gastrointestinal injury. Our findings reveal that neutrophils represent the primary innate immune leukocyte lineage responsible for stress-induced inflammation. Splenic neutrophils exhibited elevated expression levels of the pro-inflammatory cytokine IL-1, cellular reactive oxygen species, mitochondrial burden, and cell death following stress challenge compared to other innate immune cells such as macrophages, monocytes, and dendritic cells. Regulated cell death analysis indicated that NETosis is the predominant stress-induced cell death response among other analyzed regulated cell death pathways. NETosis culminates in the formation and release of neutrophil extracellular traps, which play a crucial role in modulating inflammation by binding to pathogens. Treatment with the NETosis inhibitor GSK484 rescued stress-induced neutrophil extracellular trap release and gastrointestinal injury, highlighting the involvement of neutrophil extracellular traps in stress-induced gastrointestinal inflammation. Our results suggest that neutrophil NETosis could serve as a promising drug target for managing psychological stress-induced gastrointestinal injuries.
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