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6,857 result(s) for "Li, Sha"
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The controversy of klotho as a potential biomarker in chronic kidney disease
Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD). Klotho has been postulated as a candidate biomarker in the evaluation of CKD. However, the evidence for the clinical significance of the relationship between Klotho and kidney function, CKD stage, adverse kidney and/or non-kidney outcomes, and CKD-MBD remains inconsistent and in some areas, contradictory. Therefore, there is uncertainty as to whether Klotho is a potential biomarker in CKD; a general consensus regarding the clinical significance of Klotho in CKD has not been reached, and there is limited evidence synthesis in this area. To address this, we have systematically assessed the areas of controversy, focusing on the inconsistencies in the evidence base. We used a PICOM strategy to search for relevant studies and the Newcastle–Ottawa Scale scoring to evaluate included publications. We reviewed the inconsistent clinical findings based on the relationship of Klotho with CKD stage, kidney and/or non-kidney adverse outcomes, and CKD-MBD in human studies. Subsequently, we assessed the underlying sources of the controversies and highlighted future directions to resolve these inconsistencies and clarify whether Klotho has a role as a biomarker in clinical practice in CKD.
Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1
Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5′monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.
Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4
Objectives Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. Materials and Methods An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. Results Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. Conclusions Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement. Mechanical force in vivo induced periodontal ligament stem cell proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation. The activation of TRPV4 in PDLSCs under mechanical force contributes to the changes in their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation, and immunoregulation and modulates bone remodelling during tooth movement.
ABC2A: A Straightforward and Fast Method for the Accurate Backmapping of RNA Coarse-Grained Models to All-Atom Structures
RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30–692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.
Velocity-resolved Reverberation Mapping of Changing-look Active Galactic Nucleus NGC 4151 during Outburst Stage: Evidence for Kinematics Evolution of Broad-line Region
Changing-look active galactic nucleus NGC 4151, which has attracted a lot of attention, is undergoing the second dramatic outburst stage in its evolutionary history. To investigate the geometry and kinematics of the broad-line region (BLR), and measure the mass of supermassive black hole in NGC 4151, we perform a 7 month photometric and spectroscopic monitoring program in 2020–2021, using the 2.4 m telescope at Lijiang Observatory. We successfully measure the time lags of the responses from broad Hα, Hβ, Hγ, He i, and He ii emission lines to continuum variation, which are 7.63−2.62+1.85 , 6.21−1.13+1.41 , 5.67−1.94+1.65 , 1.59−1.11+0.86 , and 0.46−1.06+1.22 days, respectively, following radial stratification. The ratios of time lags among these lines are 1.23: 1.00: 0.91: 0.26: 0.07. We find that the continuum lag between the ultraviolet and optical bands can significantly affect the lag measurements of He i and He ii. Virial and infalling gas motions coexist in this campaign, which is different from previous results, implying the evolutionary kinematics of BLR. Based on our measurements and previous ones in the literature, we confirm that the BLR of NGC 4151 is basically virialized. Finally, we compute the black hole mass through multiple lines, and the measurement from Hβ to be 3.94−0.72+0.90×107M⊙ , which is consistent with previous results. The corresponding accretion rate is 0.02−0.01+0.01LEddc−2 , implying a sub-Eddington accretor.
Mid-Upper Arm Circumference as an Alternative Screening Instrument to Appendicular Skeletal Muscle Mass Index for Diagnosing Sarcopenia
Mid-upper arm circumference (MUAC) is a simple, noninvasive anthropometric indicator. This study evaluated the applicability of MUAC as an alternative screening instrument to appendicular skeletal muscle mass index (ASMI) for detecting sarcopenia, and determined the optimal MUAC cutoff values. A total of 4509 subjects ≥50 years of age from the West China Health and Aging Trend study were included in the present study. ASM was measured by bioelectrical impedance analysis. MUAC, calf circumference (CC), and grip strength were evaluated and the Short Physical Performance Battery and 3-m timed up-and-go test were administered. Low muscle mass was diagnosed based on Asian Working Group for Sarcopenia 2019 (AWGS2019) and updated European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. ASMI was positively correlated with MUAC in both men (r=0.726, P<0.001) and women (r=0.698, P<0.001). The area under the receiver operating characteristic curve (AUC) for MUAC as an indicator of low muscle mass in men and women was 0.86 (95% confidence interval [CI]: 0.85-0.88) and 0.85 (95% CI: 0.84-0.86), respectively, according to AWGS2019 criteria; and 0.86 (95% CI: 0.85-0.88) and 0.86 (95% CI: 0.85-0.88), respectively, according to EWGSOP2 criteria. Optimal MUAC cutoff values for predicting low muscle mass were ≤28.6 cm for men and ≤27.5 cm for women. There was no significant difference between the AUCs of MUAC and CC in men according to the 2 reference standards (P=0.809), whereas the AUC of CC was superior to that of MUAC in women according to AWGS2019 (P<0.001) and EWGSOP2 (P=0.008) criteria. MUAC is strongly correlated with ASMI among community-dwelling middle-aged and older adults in China. MUAC can be used as a simple screening instrument to ASMI for diagnosing sarcopenia, especially in men.
Effectiveness of a nurse-led Mindfulness-based Tai Chi Chuan (MTCC) program on Posttraumatic Growth and perceived stress and anxiety of breast cancer survivors
The posttraumatic growth level of breast cancer survivors may decrease as time goes on. A nurse-led MTCC programme facilitates significant improvements in the posttraumatic growth level of breast cancer survivors. With the development of positive psychology, posttraumatic growth research on cancer patients has attracted increasing attention from researchers. It is immensely important to effectively increase the posttraumatic growth level of cancer patients and improve their quality of life. To investigate the effectiveness of a nurse-led mindfulness-based Tai Chi Chuan (MTCC) programme for increasing posttraumatic growth (PTG) and decreasing the perceived stress and anxiety of breast cancer survivors. A RCT was conducted. Participants were randomly assigned to either the MTCC group or the control group. The programme included 59 women with stage I-III breast cancer. Participants in the intervention group participated in a nurse-led 8-week, twice a week, one-hour per day mindfulness-based exercise programme. The effectiveness of the intervention was measured three times (T1 - before intervention; T2 - after intervention; T3 - one year after intervention) using validated scales, including the PTG inventory (PTGI), Perceived Stress Scale (PSS), and Self-rating Anxiety Scale (SAS). A repeated-measure analysis of variance model was used to analyse the data. Compared with the wait-list control group, the PTG level in the MTCC group was much higher after the 8-week intervention and the follow-up (F = 374.98, P < .000). The results showed that MTCC increased the level of PTG, and the effect persisted 1 year after intervention. In addition, PSS (F = 55.22, P < .000) and SAS (F = 148.92, P < .000) scores were significantly decreased at T2 and T3. The research preliminarily revealed that the MTCC programme was simple, effective, and more suitable to clinical nurses which should be recommended to cancer survivors to promote their recovery.
AT2021aeuk: A Repeating Partial Tidal Disruption Event Candidate in a Narrow-line Seyfert 1 Galaxy
A black hole (BH) can tear apart a star that ventures within its tidal radius, producing a luminous flare as the stellar debris falls back, known as a tidal disruption event (TDE). While TDEs in quiescent galaxies are relatively well understood, identifying TDEs in active galactic nuclei (AGNs) still remains a significant challenge. We present the discovery of AT2021aeuk, a transient exhibiting dual flares within around 3 yr in a narrow-line Seyfert 1 galaxy. Multiwavelength observations triggered during the second flare in 2023 revealed an extraordinary X-ray V-shaped light curve, strongly anticorrelated with the optical light curve and accompanied by a lag of ∼40 days. This behavior is inconsistent with both supernova and pure AGN origins. In addition, a new broad component emerges in the Balmer lines during the second flare, showing a clear reverberation signal to the continuum variation. We propose that the dual flare may be linked to a repeating partial TDE (rpTDE), where the second flare results from a collision between the TDE stream and the inner accretion disk, triggering an optical flare while simultaneously partially destroying the X-ray corona. However, other mechanisms, such as a stellar-mass BH merger within an accretion disk, could produce similar phenomena, which we cannot entirely rule out. The Vera C. Rubin Observatory will be a powerful tool for further investigating the nature of such events in the future.
Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study
Background Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. Methods We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level ( P  < 5 × 10 –8 ) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. Results The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07–1.43, P  = 0.0045), 1.08 (95% CI 1.01–1.17, P  = 0.0175), 0.94 (95% CI 0.67–1.30, P  = 0.6891), 1.29 (95% CI 0.88–1.89, P  = 0.1922), 1.23 (95% CI 0.85–1.78, P  = 0.2623), and 1.04 (95% CI 0.76–1.42, P  = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92–1.20, P  = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96–1.26, P  = 0.1725) and 0.84 (95% CI 0.69–1.02, P  = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08–1.58, P  = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11–1.43, P  = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05–1.23, P  = 0.0021) were associated with BPH after the adjustment of BMI. Conclusion This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.