Structurally disordered MoSe2 with rich 1T phase as a universal platform for enhanced photocatalytic hydrogen production.

The improvement of surface reactivity in noble-metal-free cocatalysts is crucial for the development of efficient and cost-effective photocatalytic systems. However, the influence of crystallinity on catalytic efficacy has received limited attention. Herein, we report the utilization of structurally disordered MoSe2 with abundant 1T phase as a versatile cocatalyst for photocatalytic hydrogen evolution. Using MoSe2/carbon nitride (CN) hybrids as a case study, it is demonstrated that amorphous MoSe2 significantly enhances the hydrogen evolution rate of CN, achieving up to 11.37 µmol h-1, surpassing both low crystallinity (8.24 µmol h-1) and high crystallinity MoSe2 (3.86 µmol h-1). Experimental analysis indicates that the disordered structure of amorphous MoSe2, characterized by coordination-unsaturated surface sites and a rich 1T phase with abundant active sites at the basal plane, predominantly facilitates the conversion of surface-bound protons to hydrogen. Conversely, the heightened charge transfer capacity of the highly crystalline counterpart plays a minor role in enhancing practical catalytic performance. This approach is applicable for enhancing the photocatalytic hydrogen evolution performance of various semiconducting photocatalysts, including CdS, TiO2, and ZnIn2S4, thereby offering novel insights into the advancement of high-performance non-precious catalysts through phase engineering.

A New Method Used to Enhance the SPAIR Image of the Spine MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is a handy diagnostic tool for orthopedic disorders, particularly spinal and joint diseases. METHODS: The lumbar intervertebral disc is visible in the T1 and T2 weight sequences of the spine MRI, which aids in diagnosing lumbar disc herniation, lumbar spine tuberculosis, lumbar spine tumors, and other conditions. The lumbar intervertebral disc cannot be seen accurately in the Spectral Attenuated Inversion Recovery (SPAIR) due to weaknesses in the fat and frequency offset parameters, which is not conducive to developing the intelligence diagnosis model of medical image. RESULTS: In order to solve this problem, we propose a composite framework, which is first to use the contrast limited adaptive histogram equalization (CLAHE) method to enhance the SPAIR image contrast of the spine MRI and then use the non-local means method to remove the noise of the image to ensure that the image contrast is uniform without losing details. We employ the Information Entropy (IE), Peak signal-to-noise ratio (PSNR), and feature similarity index measure (FSIM) to quantify image quality after enhancement by the composite framework. CONCLUSION: The outcomes of the experiments' output images and quantitative data indicate that our composite framework is better than others.

Impact of human serum albumin level on symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To investigate the impact of human serum albumin (HSA) levels on symptomatic cerebral vasospasm (SCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively reviewed the medical records. SCVS was defined as the development of a new neurological deterioration when the cause was considered to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. The aSAH patients were divided into two groups: those with SCVS (group 1) and those without SCVS (group 2). The HSA level data on the 1st, 2nd, and 3rd day after admission was collected. Multivariate logistical regression and receiver operating characteristic (ROC) analysis were performed to evaluate the ability of HSA level to predict the development of SCVS. RESULTS: A total of 270 patients were included in our study, of which 74 (27.4%) developed SCVS. The average and lowest HSA levels were lower in group 1 (P < 0.001). In univariate logistic regression, white blood cell count, neutrophil count, and average and lowest HSA levels were associated with SCVS. After adjustment for age, CT Fisher grade, Hunt-Hess grade, and WFNS grade, both the average and lowest HSA levels remained independent predictors of SCVS (P < 0.001). The CT Fisher grade was confirmed to be an independent predictor of SCVS across each model. ROC analysis revealed that the lowest HSA level was a better predictor for SCVS than average HSA level and CT Fisher grade. CONCLUSION: Clinicians are encouraged to measure HSA levels for the first 3 days after admission to predict the occurrence of SCVS after aSAH.

MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head.

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin-eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Clinical value of the low-grade inflammation score in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Multiple inflammatory biomarkers have been shown to predict symptomatic cerebral vasospasm (SCVS) and poor functional outcome in patients with aneurysmal subarachnoid hemorrhage. However, the impact of the low-grade inflammation (LGI) score, which can reflect the synergistic effects of five individual inflammatory biomarkers on SCVS and poor functional outcome on aneurysmal subarachnoid hemorrhage (aSAH), has not yet been well established. The aim of this study was to evaluate the impact of the LGI score on SCVS and poor functional outcome in aSAH patients. METHODS: The LGI score was calculated as the sum of 10 quantiles of each individual inflammatory biomarker. The association of the LGI score with the risk of SCVS and poor functional outcome was analyzed with multivariate logistical regression. RESULTS: A total of 270 eligible aSAH patients were included in this study: 74 (27.4%) had SCVS, and 79 (29.3%) had poor functional outcomes. After adjusting for confounders, a higher LGI score was revealed to independently predict SCVS (OR, 1.083; 95% CI, 1.011-1.161; P = 0.024) and poor functional outcome (OR, 1.132; 95% CI, 1.023-1.252; P = 0.016), and the second and third tertile group had higher risk of SCVS than lowest tertile group (OR, 2.826; 95% CI, 1.090-7.327; P = 0.033) (OR, 3.243; 95% CI, 1.258-8.358; P = 0.015). The receiver operating characteristic (ROC) curve uncovered the ability of the LGI score to distinguish patients with and without SCVS (area under the curve [AUC] = 0.746; 95% CI, 0.690-0.797; P < 0.001) and poor functional outcomes (area under the curve [AUC] = 0.799; 95% CI, 0.746-0.845; P < 0.001), the predictive value of LGI on SCVS and poor functional outcome is superior than PLT, NLR and WBC, but there was no statistical difference between LGI and CRP for predicting SCVS (P = 0.567) and poor functional outcome (P = 0.171). CONCLUSIONS: A higher LGI which represents severe low grade inflammation status is associated with SCVS and poor functional outcome at 3 months after aSAH.

Inference for sparse linear regression based on the leave-one-covariate-out solution path.

We propose a new measure of variable importance in high-dimensional regression based on the change in the LASSO solution path when one covariate is left out. The proposed procedure provides a novel way to calculate variable importance and conduct variable screening. In addition, our procedure allows for the construction of p-values for testing whether each coe cient is equal to zero as well as for testing hypotheses involving multiple regression coefficients simultaneously; bootstrap techniques are used to construct the null distribution. For low-dimensional linear models, our method can achieve higher power than the t-test. Extensive simulations are provided to show the effectiveness of our method. In the high-dimensional setting, our proposed solution path based test achieves greater power than some other recently developed high-dimensional inference methods. We extend our method to logistic regression and demonstrate in simulation that our leave-one-covariate-out solution path tests can provide accurate p-values.

Patients' caring experience during procedures under regional anesthesia in Mainland China: A phenomenology study.

Background: Although regional anesthesia is common, the procedure results in feelings of uncertainty and anxiety in some patients. Increased care is needed for these patients under general anesthesia. Few studies have focused on the intraoperative caring experience of patients during regional anesthesia. This study focused on the caring experience of patients during procedures involving regional anesthesia. Methods: The descriptive phenomenology method of Husserl was employed. Semi-structured interviews were conducted with a purposive sample in five Grade III-A hospitals in Zhengzhou City, Henan Province. The seven-step analysis method of Colaizzi was applied for the analysis, summation, and theme refinement of the interview data. Results: A total of 14 patients from five hospitals participated in the interviews. Four domains and 16 themes emerged during analysis: be informed (about the operation site, progression of the operation, informed in advance, receive explanation for abnormal experience); take care of my body (painless, gentle movements, special care); be protected (work seriously, favorable atmosphere, skilled, authority); and treated as an individual (pay attention, accompany, ask for opinions, encourage patient expression, humorous). Conclusion: Patients during procedure under regional anesthesia had specific caring experiences relative to other patients. Medical staff should recognize the importance of regional anesthesia patients' intraoperative caring experience. Hospital administrators should offer support to allow healthcare staff to provide targeted caring for patients during procedure under regional anesthesia.

Attack-resilient distributed adaptive secondary control for heterogeneous battery energy storage systems in islanded AC microgrids.

For battery energy storage systems (BESSs) in islanded AC microgrids, distributed control strategy provides an effective and flexible means to implement frequency restoration, proportional active power sharing and state of charge (SoC) balancing. Nevertheless, the distributed control system is susceptible to potential cyber attacks that break the synchronization and stability. To mitigate those effects, this paper presents an attack-resilient distributed adaptive secondary control for heterogeneous BESSs in islanded AC microgrids. The proposed control method can guarantee the consensuses on BESSs' frequency, active power and SoC simultaneously in the presence of actuator attacks, which only uses the local and neighbor's information. Specifically, the resilience is improved significantly by introducing the dynamic control gains with adaptive updating laws. Furthermore, the stability analysis is applied to assure the robustness. Lastly, the effectiveness of the above discussed conclusions is validated and compared by case studies on an islanded AC microgrid testing system.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Effect of different carbon sources on sulfate reduction and microbial community structure in bioelectrochemical systems.

Microbial electrolysis cells (MECs) have rapidly developed into a promising technology to treat sulfate-rich wastewater that lacks electron donors. Hence, a better understanding of the effect on the microbial community structure caused by different sources in bioelectrochemical systems is required. This study sought to investigate the effect of different carbon sources (NaHCO3, ethanol, and acetate were employed as sole carbon source respectively) on the performance of sulfate-reducing biocathodes. The sulfate reduction efficiency enhanced by the bioelectrochemical systems was 8.09 - 11.57% higher than that of open-circuit reference experiments. Furthermore, the optimum carbon source was ethanol with a maximum sulfate reduction rate of 170 mg L-1 d-1 in the bioelectrochemical systems. The different carbon sources induced significant differences in sulfate reduction efficiency as demonstrated by the application of a micro-electrical field. Microbial community structure and network analysis revealed that all three kinds of carbon source systems enriched large proportions of sulfate-reducing bacteria and electroactive bacteria but were significantly distinct in composition. The dominant sulfate-reducing bacteria that use NaHCO3 and acetate as carbon sources were Desulfobacter and Desulfobulbus, whereas those that use ethanol as carbon source were Desulfomicrobium and Desulfovibrio. Our results suggest that ethanol is a more suitable carbon source for sulfate reduction in bioelectrochemical systems.

Changes in stiffness of the specific regions of knee extensor mechanism after static stretching.

Decreased muscle stiffness could reduce musculotendinous injury risk in sports and rehabilitation settings. Static stretching (SS) has been used to increase the flexibility of muscles and reduce muscle stiffness, but the effects of SS on the stiffness of specific regions of the knee extensor mechanism are unclear. The quadriceps femoris and patellar tendon are essential components of the knee extensor mechanism and play an important role in knee motion. Therefore, we explored the acute and prolonged effects of SS on the stiffness of the quadriceps femoris and patellar tendon and knee flexion range of motion (ROM). Thirty healthy male subjects participated in the study. Three 60-s SS with 30-s intervals were conducted in right knee flexion with 30° hip extension. We measured the ROM and stiffness of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) and the proximal-(PPT), middle-(MPT), and distal-(DPT) region stiffness of the patellar tendon before and immediately after SS intervention, or 5 and 10 min after SS. The stiffness of the quadriceps muscle and patellar tendon were measured using MyotonPRO, and the knee flexion ROM was evaluated using a medical goniometer. Our outcomes showed that the ROM was increased after SS intervention in all-time conditions (p < 0.01). Additionally, the results showed that the stiffness of RF (p < 0.01) and PPT (p = 0.03) were decreased immediately after SS intervention. These results suggested that SS intervention could be useful to increase knee flexion ROM and temporarily reduce the stiffness of specific regions of the knee extensor mechanism.

Global Trends and Research Hotspots of Exercise for Intervening Diabetes: A Bibliometric Analysis.

Background: Diabetes is a chronic metabolic disease characterized by hyperglycemia that often occurs in adults. Many studies have indicated that exercise is beneficial to the medical management of diabetes. Bibliometric analysis can help investigators to identify the current research concerns to guide future research directions. Nevertheless, the overview bibliometric analysis of this global research topic related to exercise and diabetes is lacking. The present bibliometric study aimed to investigate development trends and research hotspots of exercise and diabetes research and provide researchers with new perspectives in further studies. Materials and Methods: The articles and reviews regarding exercise and diabetes between 2000 and 2020 were retrieved from the Web of Science Core Collection. The scientometrics analytical tool CiteSpace software was used to analyze the cooperation among countries/institutions/journals/authors, analysis of co-occurrence keywords, keywords bursts, and references. Results: In all, 3,029 peer-reviewed papers were found with a persistently increased tendency over time. The most prolific country and institution were the USA (965) and Univ Alberta (76), respectively. Diabetes Care published most papers (178) and was the most co-cited journal (2,630). Riddell MC had the most publications (53), and Sigal RJ was the most influential author (503 cited times). Colberg et al.'s paper (co-citation counts: 183) showed the strongest citation bursts by the end of 2020, which was the most representative reference. The four research focuses were mellitus, exercise, physical activity, and glycemic control. The two frontiers trends were sedentary behavior and stress. The combination of aerobic and resistance training can effectively improve glycemic control, decrease HbA1c levels, enhance cardiorespiratory fitness, improve lipid levels, and decrease the demand for non-insulin antihyperglycemic agents. Conclusions: This study offers a scientific perspective on exercise and diabetes research and provides investigators with valuable information to detect the current research condition, hotspots, and emerging trends for further study.

Guaranteed cost positive consensus for multi-agent systems with multiple time-varying delays and MDADT switching.

This paper investigates the guaranteed cost positive consensus for linear multi-agent systems (MASs) with multiple time-varying delays and switching topologies. First, necessary and sufficient conditions for the positivity of the focused system are given. The positive consensus criterion and switching signals are derived by combining multiple Lyapunov-Krasovskii functionals with mode-dependent average dwell time approaches. Then, the guaranteed cost positive consensus is studied via the state errors among neighbouring agents and control inputs. It realizes a trade-off between the consensus regulation performance and the control energy consumption of MASs. Particularly, the determined upper bound of the cost function depends merely on the initial conditions of the agents and is independent of the switching movements. Finally, simulation results are given to validate the proposed control scheme.

SOCS1, the feedback regulator of STAT1/3, inhibits the osteogenic differentiation of rat bone marrow mesenchymal stem cells.

Our study showed that Signal transducer and activator of transcription (STAT)1 and STAT3 phosphorylation was firstly upregulated in the early stage of osteogenic differentiation (OD), and quickly eliminated in hours. Following with phosphorylation of STAT1/3, its downstream feedback regulator Suppressor of cytokine signaling 1 (SOCS1) protein also underwent a quick elevation. Further activation and deactivation of STAT1/3, by administrated with Colivelin and Nifuroxazide in Bone mesenchymal stem cells (BMSCs), increased and decreased SOCS1 expression, inhibited and promoted OD of BMSCs, respectively, as evidenced by Alizarin staining, alkaline phosphatase (ALP) activity, and determination of Run-related transcription factor 2 (RUNX2), Osteocalcin (OCN), ALP, and Bone sialoprotein (BSP). In addition, administration of Colivelin and Nifuroxazide caused and blocked inflammation and apoptosis of BMSCs. To further elucidate the role of STAT1/3-SOCS1 regulatory loop on OD of BMSCs, we overexpressed or silenced SOCS1 in BMSCs during OD. WB data showed that overexpression of SOCS1 repressed STAT1/3 phosphorylation, and knockdown of SOCS1 increased the phosphorylated STAT1/3. Further mechanism study showed that OD of BMSCs was elevated or reduced by SOCS1 overexpression or knockdown, respectively. The findings presenting indicated that the STAT1/3-SOCS1 axis may be exploited as an innovative strategy to enhance osteogenesis in regenerative medicine.

CircTYW1 serves as a sponge for microRNA-380 in accelerating neurological recovery following spinal cord injury via regulating FGF9.

As one of the most severe kinds of neurological damage, spinal cord injury (SCI) contributes to persistent motor dysfunction and involves a large repertoire of gene alterations. The participation of circular RNAs (circRNAs) in neurological recovery following SCI needs to be clarified. In the current work, we attempted to assess the function of hsa_circRNA_0003962/circTYW1 and its underlying mechanism in SCI. By accessing the GEO repository, the expression of circTYW1, microRNA-380 (miR-380), and FGF9 in SCI and sham-operated rats was evaluated. PC12 cells after oxygen-glucose deprivation (OGD) treatment were prepared to mimic the SCI model. circTYW1 and FGF9 were poorly expressed, whereas miR-380 was highly expressed in the spinal cord tissues of SCI rats. circTYW1 promoted neurological recovery in SCI rats and inhibited apoptosis in spinal cord tissues. In PC12 cells exposed to OGD, circTYW1 suppressed PC12 cell apoptosis; however, miR-380 overexpression reversed the protective effect of circTYW1 on PC12 cells. Also, circTYW1 promoted FGF9 expression through competitively binding to miR-380, which activated the ERK1/2 signaling. In summary, our results demonstrated that declines in circTYW1 prevented SCI rats from neurological recovery by regulating the miR-380/FGF9/ERK1/2 axis, which might provide new understanding for SCI treatment.

microRNA-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats.

AIMS: The involvement of several microRNAs (miRNAs) in osteogenic differentiation has been indicated recently. Also, exosomes, derived from different cells, could shuttle specific miRNAs to other cell systems. Nevertheless, the effect and mechanism of microRNA-935 (miR-935)-containing exosomes in osteoblasts remain basically unclear. The current work was set to inspect the relevance of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-exo) carrying miR-935 to osteoporotic rats. METHODS: The extracted BMSCs and purchased osteoblasts were cultured, followed by exosome isolation and identification. After cell grouping, osteoblasts were co-cultured with BMSCs. CCK-8, alizarin red staining as well as ALP staining were performed to detect osteoblast proliferation and activity. The binding connection between miR-935 and signal transducer and activator of transcription 1 (STAT1) was measured by dual-luciferase reporter gene assays. The expression profiles of miR-935, STAT1 and osteoblast-related proteins were assessed by RT-qPCR and Western blot. A rat model with osteoporosis was induced, and the BMD, BV/TV, Tb.N, Tb.Th and Tb.Sp values in rat bone tissues were observed by Micro-CT. RESULTS: BMSC-exo inhibited STAT1 levels by the delivery of miR-935 into osteoblasts, while STAT1 silencing promoted ALP activity in osteoblasts and mineralized nodules. STAT1 was identified as a target gene of miR-935. Moreover, in vivo experiments showed that in ovariectomized rats, silencing of miR-935 significantly reduced BMD, BV/TV, Tb.N, Tb.Th and increased Tb.Sp. CONCLUSION: BMSC-exo carry miR-935 to promote osteoblast proliferation and differentiation through targeting STAT1.

PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy-induced osteoporosis mouse model.

There is now increasing evidence which suggests a key role for osteoblast apoptosis in the pathogenesis of postmenopausal osteoporosis. Here, we evaluated the role and mechanism of proteasome 26S subunit, ATPase (PSMC) 6, a protein that is highly expressed in bone. Gene expression pattern had been extracted based on database of Gene Expression Omnibus (GEO). GEO2R was employed for analyses, while the DAVID database was adopted to further analyze the gene ontology (GO) as well as Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment. Then, the Search Tool Retrieval of Interacting Genes (STRING) was utilized to carry out interaction regulatory network for the top 200 differentially expressed genes (DEGs). A key gene, called PSMC6, was identified by Cytoscape 3.6.0. The OVX osteoporosis model was established in female C57BL/6 mice by full bilateral ovariectomy. According to our findings, PSMC6 gene knockout would elevate bone mineral density (BMD) and the phosphorylation level of PI3K protein and increased the protein level of cleaved caspase-3/-9 in OVX osteoporosis mice. Further, MTT, bromodeoxyuridine, and flow cytometry assays revealed that PSMC6 inhibition promoted the progression of cell cycle and cell proliferation, whereas, PSMC6 overexpression promoted the apoptosis and inhibited cell cycle progression and cell proliferation in vitro. Besides, we found that PI3K activation significantly decreased PSMC6-induced osteoblast apoptosis and promoted cell proliferation through regulating the protein levels of p53, cyclinD1, and cleaved caspase-3/9. In conclusion, PSMC6 aggravated the degree of OVX-induced osteoporosis by inhibiting the PI3K/AKT signal transduction pathway, thereby promoting the apoptosis of osteoblasts.

Fatigue correlates with sleep disturbances in Parkinson disease.

BACKGROUND: Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients. METHODS: Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances. RESULTS: Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score. CONCLUSION: Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

MicroRNA-181a exerts anti-inflammatory effects via inhibition of the ERK pathway in mice with intervertebral disc degeneration.

Enzymatic decomposition of extracellular matrix and possibly local inflammation may cause intervertebral disc degeneration (IDD). MicroRNAs have been reported to correlate with the development of IDD. In this experiment, we aim at finding out the role of miR-181a in the inflammation of IDD and the underlying mechanism. The targeting relationship between miR-181a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was verified. Following the establishment of IDD mouse models, disc height index (DHI) and the change of DHI (%DHI) were measured. The functional role of miR-181a in IDD was determined using ectopic expression and depletion and reporter assay experiments. Expression of miR-181a, TRAIL, extracellular signal-regulated kinase (ERK) pathway-related genes and inflammatory factors was evaluated. Also, the expression of collagen I and collagen II was observed. miR-181a directly targeted TRAIL. IDD mice exhibited significant degeneration of the intervertebral disc. miR-181a was downregulated while TRAIL was upregulated in mice with IDD. miR-181a upregulation and the ERK pathway inhibition could reduce expression of TRAIL, ERK pathway-related genes, inflammatory factors, and collagen I, but promote collagen II expression. Our results reveal that upregulation of miR-181a protects against inflammatory response by inactivating the ERK pathway via suppression of TRAIL in IDD mice. These results point to miR-181a as a potential therapeutic target for the clinical management of IDD.

LncRNA NKILA integrates RXFP1/AKT and NF-κB signalling to regulate osteogenesis of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are previously found to have potential capacity to differentiate into osteocytes when exposed to specific stimuli. However, the detailed molecular mechanism during this progress remains largely unknown. In the current study, we characterized the lncRNA NKILA as a crucial positive regulator for osteogenesis of MSCs. NKILA attenuation significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. More interestingly, we defined that NKILA is functionally involved in the regulation of RXFP1/PI3K-AKT and NF-κB signalling. Knockdown of NKILA dramatically down-regulates the expression of RXFP1 and then reduces the activity of AKT, a downstream regulator of RXFP1 signalling which is widely accepted as an activator of osteogenesis. Moreover, we identify NF-κB as another critical regulator implicated in NKILA-mediated osteogenic differentiation. Inhibition of NF-κB can induce the expression of RUNX2, a master transcription factor of osteogenesis, in a HDAC2-mediated deacetylation manner. Thus, this study illustrates the regulatory function of NKILA in osteogenesis through distinct signalling pathways, therefore providing a new insight into searching for new molecular targets for bone tissue repair and regeneration.