Decreased miR-486-5p is involved in LPS-induced HTR-8/SVneo cell dysfunction by promoting Smad2 expression.

Placenta-associated pathologies, including early pregnancy loss (EPL) and preeclampsia (PE), share a common phenomenon of insufficient extravillous trophoblasts (EVTs) invasion. It was previously observed that down-regulated miR-486-5p expression inhibited the invasion of EVTs, and a decreased peripheral miR-486-5p was associated with EPL. However, the exact roles of miR-486-5p played in pathogenesis of EPL, as well as the molecular pathway underlying roles of miR-486-5p in EVTs invasion, remains poorly understood. In this study, a decreased miR-486-5p expression in uterine embryo implantation site at gestation day (GD) 8.5, and an increased expression of Smad2, a target of miR-486-5p, were observed in the lipopolysaccharide (LPS)-induced EPL mouse model. The invasion and viability of immortalized human EVTs line, HTR-8/SVneo, were inhibited by LPS, accompanied with a reduced miR-486-5p expression. LPS showed a promoting effect on the Smad2 expression, of which could be attenuated by miR-486-5p mimics. And the down-regulated Smad2 could effectively restore the impaired invasion and viability of HTR-8/SVneo cells caused by LPS or miR-486-5p inhibitor. Furthermore, LPS could promote the TNFα production in HTR-8/SVneo cells, whereas both of siSmad and miR-486-5p mimics could reverse such an effect. By analyzing the human decidua single-cell RNA sequencing and transcriptome datasets derived from the Gene Expression Omnibus, it was found that, compared to control early pregnant women, the Smad2 expression was significantly increased in recurrent miscarriages (RM) patients. Collectively, these data suggested that, decreased miR-486-5p expression might lead to EPL at least partially by inhibiting invasion and/or promoting TNFα production of EVTs via targeting Smad2.

MNSFß promotes LPS-induced TNFα expression by increasing the localization of RC3H1 to stress granules, and the interfering peptide HEPN2 reduces TNFα production by disrupting the MNSFß-RC3H1 interaction in macrophages.

Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.

A layered metastructure for privacy protection based on the Brewster angle.

In this paper, a kind of layered metastructure (LMS) is proposed by stacking multi-layer dielectric plates. By adjusting the dielectric constant of medium A (set as εi), the Brewster angle (BA) of incident electromagnetic waves (EMWs) has been directly selected. At the same time, the operating band of the above angle selection (AS) can be extended to the whole visible light band (VLB) which covers 400 nm to 700 nm according to Bragg reflection. After careful design, two ranges of BAs that cross 0° to 42° and 0° to 60° have been realized in the VLB, which is defined as privacy protection (PP) in this paper. Compared with previous reports, this accomplishment improves transmissivity at small angles and covers a large band. Also, the gradient thickness of the proposed LMS can be changed arbitrarily according to the needs of operating bands, which undoubtedly expands the actual operating scenarios. The obtained results can offer some help to the design of directional devices in industry production, the PP of daily life, and so on.

Water flush boosts performance of elemental sulfur-based denitrification packed-bed systems: Optimization and mechanisms.

Despite the promising potential of elemental sulfur-based denitrification (ESDeN) packed-bed progresses, challenges such as excessive biofilm growth and gas entrapment persist, leading to denitrification deterioration. Water flush (WF) is recognized as an effective strategy, yet its effects remain underexplored. To address this knowledge gap, this study systematically investigated WF effects on ESDeN packed-bed denitrification. Results demonstrated that controlling WF effectively regulated denitrification, achieving superior and stable rates. Compared to no WF (0.45 kgN·m-3·d-1), rates improved by 1.20 âˆ¼ 1.56 times under low-frequency (weekly WF, 0.54 kgN·m-3·d-1) and low-intensity WF (0.54 âˆ¼ 0.70 kgN·m-3·d-1). High-frequency (hours WF) and high-intensity WF (30 & 50 m/h) further amplified denitrification rates by 1.73 âˆ¼ 2.29 times. The enhanced denitrifications under low-frequency/intensity WF were mainly attributed to prolonged actual hydraulic retention time (AHRT), while high-frequency/intensity WF improved both AHRT prolonging and biofilm thinning, facilitating mass transfer. This study offers a promising avenue for fine-tuning denitrification rates via strategic WF adjustments.

Estrogen-related receptor, a molecular target against lepidoptera pests.

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.

Associations between Physical Activity and the Incidence of Cerebrovascular Disease or All-Cause Mortality among 146,742 Older Adults: A 13-Year Prospective Cohort Study.

OBJECTIVES: Although studies have indicated that physical activity (PA) is related to cardiovascular disease, the specific association between PA and incident cerebrovascular disease (CBVD) remains uncertain. The current study aimed to investigate the associations between PA levels and the CBVD incidence or all-cause mortality. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: Older participants (aged >60 years) from the UK Biobank. METHODS: The baseline PA was classified as total, light, moderate, and vigorous PA based on the metabolic equivalent-minutes per week (MET-min/wk) and considered as exposures, whereas CBVD incidence and all-cause mortality were considered as the outcomes. Cox proportional hazards were used to calculate the hazard ratios (HRs) and 95% CIs for the influence of the association between PA and CBVD incidence and all-cause mortality. RESULTS: A total of 146,742 participants aged 60 years and older were included. During a median follow-up period of 13.5 years (interquartile range of 12.8-14.2), 9338 older individuals developed CBVD and 3033 death were recorded (including 767 CBVD-related deaths). High volumes of PA were consistently associated with lower risks of CBVD and all-cause mortality. The lowest risk of CBVD incidence was observed at 2001-2500 MET-min/wk of total PA (HR 0.61, 95% CI 0.53-0.70), and the lowest risk of all-cause mortality was observed at 2501-5000 MET-min/wk (HR 0.52, 95% CI 0.43-0.63) in older adults. Total PA at 2001-2500 MET-min/wk significantly reduced the CBVD incidence in older women (HR 0.57, 95% CI 0.46-0.71), which was more pronounced than that in older men (HR for 2001-2500 MET-min/wk: 0.64, 95% CI 0.50-0.77). CONCLUSIONS AND IMPLICATIONS: Total PA at 2001-2500 MET-min/wk significantly reduced the risk of incident CBVD and all-cause mortality in adults aged >60 years, although the extents of risk reduction vary in men and women.

A novel LVPA-UNet network for target volume automatic delineation: An MRI case study of nasopharyngeal carcinoma.

Accurate delineation of Gross Tumor Volume (GTV) is crucial for radiotherapy. Deep learning-driven GTV segmentation technologies excel in rapidly and accurately delineating GTV, providing a basis for radiologists in formulating radiation plans. The existing 2D and 3D segmentation models of GTV based on deep learning are limited by the loss of spatial features and anisotropy respectively, and are both affected by the variability of tumor characteristics, blurred boundaries, and background interference. All these factors seriously affect the segmentation performance. To address the above issues, a Layer-Volume Parallel Attention (LVPA)-UNet model based on 2D-3D architecture has been proposed in this study, in which three strategies are introduced. Firstly, 2D and 3D workflows are introduced in the LVPA-UNet. They work in parallel and can guide each other. Both the fine features of each slice of 2D MRI and the 3D anatomical structure and spatial features of the tumor can be extracted by them. Secondly, parallel multi-branch depth-wise strip convolutions adapt the model to tumors of varying shapes and sizes within slices and volumetric spaces, and achieve refined processing of blurred boundaries. Lastly, a Layer-Channel Attention mechanism is proposed to adaptively adjust the weights of slices and channels according to their different tumor information, and then to highlight slices and channels with tumor. The experiments by LVPA-UNet on 1010 nasopharyngeal carcinoma (NPC) MRI datasets from three centers show a DSC of 0.7907, precision of 0.7929, recall of 0.8025, and HD95 of 1.8702 mm, outperforming eight typical models. Compared to the baseline model, it improves DSC by 2.14 %, precision by 2.96 %, and recall by 1.01 %, while reducing HD95 by 0.5434 mm. Consequently, while ensuring the efficiency of segmentation through deep learning, LVPA-UNet is able to provide superior GTV delineation results for radiotherapy and offer technical support for precision medicine.

Increased miR-3074-5p expression promotes M1 polarization and pyroptosis of macrophages via ERα/NLRP3 pathway and induces adverse pregnancy outcomes in mice.

Decidual macrophages (dMϕs) play critical roles in regulation of immune-microhomeostasis at maternal-fetal interface during pregnancy, but the underlying molecular mechanisms are still unclear. In this study, it was found that litter size and fetal weight were significantly reduced, whereas the rate of embryo resorption was increased in miR-3074-5p knock-in (3074-KI) pregnant mice, compared to that of wild-type (WT) pregnant mice. Plasma levels of pro-inflammatory cytokines in 3074-KI pregnant mice were also significantly elevated compared to WT pregnant mice at GD7.5. The quantity of M1-Mϕs in uterine tissues of 3074-KI pregnant mice was significantly increased compared to WT pregnant mice at GD13.5. Estrogen receptor-α (ERα) was validated to be a target of miR-3074-5p. Either miR-3074-5p overexpression or ERα knockdown promoted transcriptional activity of NF-κB/p65, induced M1-polarization and pyroptosis of THP1-derived Mϕs, accompanied with increased intracellular levels of cleaved Caspase-1, cleaved IL-1ß, NLRP3, cleaved GSDMD and ASC aggregation. Furthermore, ERα could not only bind to NLRP3 or ASC directly, but also inhibit the interaction between NLRP3 and ASC. The endometrial miR-3074-5p expression level at the middle secretory stage of repeated implantation failure (RIF) patients was significantly decreased compared to that of control fertile women. These data indicated that miR-3074-5p could promote M1 polarization and pyroptosis of Mϕs via activation of NLRP3 inflammasome by targeting ERα, and the dysregulation of miR-3074-5p expression in dMϕs might damage the embryo implantation and placentation by interfering with inflammatory microenvironment at the maternal-fetal interface during early pregnancy.

Associations between back pain incidence, and physical activity and sedentary behaviours: A prospective cohort study with data from over 365,000 participants.

OBJECTIVE: To examine the associations between (i) various types of physical activity and the risk of back pain incidence, and (ii) the influence of substituting sedentary behaviours with physical activities on back pain incidence. DESIGN: A prospective cohort study. METHODS: We analyzed UK Biobank data collected from 365,307 participants who were free of back pain at baseline. The exposures were total, light, moderate and vigorous physical activity, and sedentary behaviours. The outcome was back pain incidence. The main statistical models were the Cox proportional hazard model and the isotemporal substitution model. RESULTS: In the follow-up time (median, 12.97 years; inter-quartile range, 12.10-13.71), 25,189 individuals developed back pain. The associations between all types of physical activity and incident back pain were significantly non-linear (p < 0.001) among the general population and other subgroups. High physical activity was associated with a decreased risk of back pain compared with no physical activity. The lowest risk occurred in the 1801-2400 MET-min/week subgroup of total physical activity (HR 0.64, 95% CI 0.59-0.69), approximately consisting of 1200, 600, and 600 MET-min/week of light, moderate and vigorous physical activity, respectively. Extremely high vigorous physical activity was related to high risk, specifically in males (HR 1.13, 95% CI 1.02-1.25). Replacing 1 hour/day of sedentary behaviours with an equal time of physical activity reduced the risk of incident back pain by 2%-8% (p < 0.05). CONCLUSION: Physical activity was related to a reduced risk of back pain incidence (except over-high vigorous physical activity). Substituting sedentary behaviours with physical activities reduced the risk of future back pain.

Demographic and clinical characteristics associated with failure of physical therapy in chronic low back pain: a secondary analysis from a randomized controlled trial.

BACKGROUND: The effect of physical therapy on pain and disability alleviation in patients with chronic low back pain (cLBP) has been demonstrated, but the risk factors for treatment failure remain unknown. AIM: To explore the associations of baseline demographic and clinical characteristics with treatment failure after physical therapy intervention for cLBP. DESIGN: A secondary analysis of a single-blind randomized clinical trial. SETTING: A rehabilitation hospital. POPULATION: A total of 98 patients with cLBP completed the 12-month measurement. METHODS: Patients were randomly grouped into 3-month therapeutic aquatic exercise or physical therapy modalities. The primary outcome was treatment failure, which was defined as a decrease in the numeric rating scale to less than 2.0 points at 12-month follow-up. Associations between baseline demographic and clinical characteristics with risk of treatment failure were assessed by logistic regressions. RESULTS: The pain intensity in the failure cases was alleviated after 3-month intervention but continuously increased at 6- and 12-month follow-up (P<0.05). Old age was significantly associated with an increased risk of treatment failure (adjusted OR 3.26, 95% CI 1.11-9.60). Compared with those receiving physical therapy modalities, the patients receiving therapeutic aquatic exercise had less risk of treatment failure (adjusted OR 0.19, 95% CI 0.08-0.47), and age (P=0.022) was a modifier for this association. CONCLUSIONS: Compared with younger ones, older patients with cLBP had a higher risk of treatment failure after physical therapy and gained a stronger benefit of long-term pain alleviation from therapeutic aquatic exercise. CLINICAL REHABILITATION IMPACT: Therapeutic aquatic exercise is an effective therapy for cLBP and more helpful for preventing treatment failure than physical therapy modalities, especially for older patients.

Improved efficiency and stability using a novel elemental sulfur-based moving-bed denitrification process.

Elemental sulfur-based denitrification (ESDeN) technology is known as a cost-saving alternative to its heterotrophic counterpart for nutrient removal from organic-deficient water. However, the traditional fixed-bed reactor (FixBR), as an extensively used process, suffers from a low denitrification rate and even performance deterioration during long-term operation. Herein, we proposed a novel elemental sulfur-based denitrifying moving-bed reactor (ESDeN-MovBR), in which a screw rotator was employed to drive the filled sulfur particles to be microfluidized vertically (a state of vertical-loop movement). Our results showed that the ESDeN-MovBR realized much superior and more stable denitrification performance compared to the ESDeN-FixBR, as indicated by 3.09-fold higher denitrification rate and over one order of magnitude lower intermediates (NO2- and N2O) yield, which could last for over 100 days. Further research revealed that the microfluidization of sulfur particles facilitated the expelling of nitrogen bubbles and excessive biomass, resulting in the prolongation of actual hydraulic retention time by over 80 % and could partially explain the higher denitrification rate in ESDeN-MovBR. The remaining contribution to the improvement of denitrification rate was suggested to be result from changes in biofilm properties, in which the biofilm thickness of ESDeN-MovBR was found to be 3.29 times thinner yet enriched with 2.52 times more autotrophic denitrifiers. This study offered a completely new solution to boost up the denitrification performance of ESDeN technology and provided in-depth evidence for the necessity of biofilm thickness control in such technology.

Insights into the response of nitrogen metabolism to sulfamethoxazole contamination in constructed wetlands with varied substrates.

This study conducted an analysis of the variations in nitrogen metabolism pathways within constructed wetlands (CWs) using zeolite (CW-Z), ceramsite (CW-C), and lava (CW-L) under high concentration sulfamethoxazole (SMX) stress. The introduction of SMX hindered the formation of hydrogen bonds on the substrate surfaces; however, these surfaces still maintained a dense and thick biofilm. CW-Z exhibited superior removal efficiencies for ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) compared to CW-C and CW-L, with removal rates of 92.54 ± 2.88 % and 89.39 ± 6.74 %, respectively. Interestingly, the proportion of genes involved in nitrification, denitrification and nitrate reduction genes in CW-C (36.05 %) were higher than that in CW-C (29.81 %) and CW-L (29.70 %) but the interactions among nitrogen functional bacteria in CW-Z were much more complex. Further analysis of the nitrogen metabolism pathway indicated that under CW-Z enhanced dissimilatory nitrate reduction SMX stress, while CW-L enhanced assimilatory nitrate reduction process compared to CW-C.

Reliability and Validity of the Star Excursion Balance Test for Evaluating Dynamic Balance of Upper Extremities.

BACKGROUND: Upper extremity (UE) dynamic balance is a significant physical fitness ability, which includes high-level neuromuscular proprioception, joint mobility, force, and coordination. The evaluation methods of UE dynamic balance are insufficient and lack experimental support. The Star Excursion Balance Test (SEBT) is a reliable assessment of dynamic balance and injury risk of the lower extremity. HYPOTHESIS: The UE-SEBT is a reliable and reproducible approach for evaluating dynamic balance of UEs. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: This cross-sectional study recruited 65 healthy adults. All participants were required to complete UE-SEBT, UE Y-balance test (UE-YBT), maximal voluntary isometric contraction (MVIC) of UE, closed kinetic chain UE stability test (CKCUEST), trunk flexor endurance test (TFET), trunk extensor endurance test (TEET), and lateral trunk endurance test (LTET). Intra- and inter-rater reliability and the correlation of UE-SEBT with other outcomes were measured. RESULTS: Among the participants, the intra- and interoperator reliability of UE-SEBT in all directions and composite score achieved a moderate-to-excellent (intraclass correlation coefficients [ICC], 0.729-0.946) reliability. For validity, the UE-SEBT had a moderate to very strong correlation with UE-YBT (r = 0.315-0.755, P < 0.01) and a strong correlation with CKCUEST (r = 0.4-0.67, P < 0.01). Furthermore, the UE-SEBT performance showed weak-to-strong correlations with MVIC (r = 0.26-0.43, P < 0.05). UE-SEBT was also correlated with LTET, TEET, and TFET to varying degrees. CONCLUSION: UE-SEBT has good reliability and validity to assess UE dynamic balance compared with other tests. CLINICAL RELEVANCE: UE-SEBT can be used as a clinical assessment method to evaluate UE dynamic balance and injury prevention.

MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage.

Dysfunction of extravillous trophoblasts (EVTs) might cause early pregnancy failure by interfering with embryo implantation and/or placentation. We previously reported that the villus miR-3074-5p expression level was increased, whereas the peripheral level of GDF15, a predict target gene of miR-3074-5p, was decreased in recurrent miscarriages (RM) patients, and miR-3074-5p could enhance apoptosis but reduce invasion of human extravillous trophoblast cells (EVTs). The aim of this study was to further explore roles of miR-3074-5p/GDF15 pathway in regulation of EVTs function. It was validated that GDF15 was not the direct target of miR-3074-5p, whereas EIF2S1, an upstream regulator of GDF15 maturation and secretion, was the direct target of miR-3074-5p. The villus expression levels of GDF15 and EIF2S1 were significantly decreased in RM patients. Knockdown of GDF15 expression presented inhibitory effects on proliferation, migration, and invasion of HTR8/SVneo cells. Up-regulated miR-3074-5p expression led to the significant decreased GDF15 expression in HTR8/SVneo cells, and this effect could be efficiently reversed by the overexpression of EIF2S1. Meanwhile, the suppressive effects of miR-3074-5p on proliferation, migration, and invasion of HTR8/SVneo cells could be intercepted by the treatment of recombinant human GDF15 protein. Collectively, these data suggested that miR-3074-5p could reduce GDF15 production via targeting inhibition of EIF2S1 expression, and the deficiency in GDF15 function might lead to the early pregnancy loss by attenuating proliferation and invasion of EVTs.

Association between smoking and incident back pain: A prospective cohort study with 438 510 participants.

Background: Although smoking is a known potential contributor to back pain, there is still a lack of quantitative studies on the effects of different doses on back pain (BP) occurrence, including a lack of a longitudinal cohorts. To address this gap, we aimed to investigate the association between various smoking-related exposures and back pain incidence to advance global efforts toward smoking cessation and guide primary prevention of BP. Methods: In this prospective cohort study, we retrieved data on 438 510 patients from the UK Biobank who were free of back pain and who were recruited in 2006-2010, and followed them up from baseline through 1 April 2022. We extracted data on smoking-related exposures, including smoking status (SS), number of cigarettes smoked daily (CPD), and pack-years of own smoking (PY) and examined back pain incidence as an outcome. We used a Cox proportional hazard model adjusted for several covariates, multiple imputation methods, and population attribution fraction. Results: During the median follow-up of 12.98 years, 31 467 participants developed BP, with incidence rates in former and current smokers of 1.13 (95% confidence interval (CI) = 1.10-1.16, P < 0.000) and 1.50 (95% CI = 1.45-1.56, P < 0.000), respectively. The hazard ratios (HRs) of participants who smoked more than 30 CPD and those with more than 30 PY were 1.45 (95% CI = 1.36-1.55, P < 0.000) and 1.45 (95% CI = 1.40-1.50, P < 0.000), respectively. Relative to male, female smokers were at more risk of developing BP. Not smoking, quitting smoking, and reducing CPD and PY could lower the BP risk by 7.8%, 5.4%, 9.8%, and 18.0%, respectively. Conclusions: Ever smoking, higher cigarette consumption daily, and increased smoking intensity were associated with an increased BP risk. This association was stronger in female smokers. Not smoking, smoking cessation, and reducing smoking volume and intensity were effective measures to prevent BP occurrence.

The effect and mechanism of motor control exercise on low back pain: a narrative review.

Low back pain (LBP) is a common symptom that can occur in all ages. It is the first common cause of disability globally and is associated with over 60 million disability-adjusted life-years in a single year. Motor control exercise (MCE) has obtained increasing attention in treating LBP. However, the findings from distinct meta-analyses differed and some even reached controversial conclusions. More importantly, how MCE improves LBP-related symptoms remains unclear. The primary aim of this study is to describe the possible improvement mechanisms of MCE on LBP from brain, biochemistry, inflammatory, and neuromuscular aspects. The secondary aim is to further conclude its effectiveness and clinical application. Further understanding of mechanisms and effectiveness could be instructive for future LBP treatments and provide more information for clinicians when making prescriptions. MCE is effective in alleviating pain and disability among patients with acute and chronic LBP. Notably, the evidence for acute LBP is relatively low-quality and limited. MCE might be more effective for patients with specific LBP characteristics, especially those with pre-diagnosis of impaired transversus abdominis recruitment, intermediate pain intensity, and longer MCE training duration. MCE could remap brain representation and reverse negative brain alternation, induce exercise-induced hypoalgesia, mediate anti-inflammatory response, retain normal activation, and improve morphological deficits.

BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity.

BACKGROUND: Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. METHODS: Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. RESULTS: A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. CONCLUSION: Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.

Validity and reliability of upper extremity star excursion balance test in adolescent swimmers.

Background: Upper limb balance is one of the important physical fitness parameters for all populations, especially overhead athletes like swimmers. Upper extremity star excursion balance test (UESEBT) is a comprehensive dynamic balance assessment, this study aims to explore the reliability and validity of UESEBT among adolescent swimmers. Methods: This cross-sectional study recruited 70 adolescent swimmers. All participants were required to complete UESEBT, upper quarter Y-balance test (UQYBT), maximal isometric strength (MIS) tests in upper limb, closed kinetic chain upper extremity stability test (CKCUEST), trunk flexor endurance test (TFET) and lateral trunk endurance test (LTET). The intra- and inter-operator reliability and the correlation of UESEBT with other physical performances were conducted. Results: For reliability, the intra- and inter-operator reliability of all directions and composite score were high-to-excellent (ICC = 0.706-1.000) among all participants. For validity, the UESEBT has a moderate-to-strong correlation with UQYBT (r = 0.42-0.72, p < 0.001), and a weak-to moderate one with CKCUEST (r = 0.25-0.42, p < 0.05). Furthermore, the UESEBT performance showed weak-to-moderate correlations with MIS (r = 0.24-0.44, p < 0.05). UESEBT was correlated to LTET (r = 0.24-0.33, p < 0.05) whereas no relationship was found with TFET. Conclusions: UESEBT was a reliable and valid tool to screen upper extremity dynamic balance among adolescent swimmers. UESEBT provides more detailed information in eight directions to assess the upper limb sport performance. Further study should explore the prediction ability of UESEBT for injury.

Ferrostatin-1 Inhibits Toll-Like Receptor 4/NF-κB Signaling to Alleviate Intervertebral Disc Degeneration in Rats.

Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, is implicated in intervertebral disc degeneration (IDD). The current study explored the role of Fer-1 in IDD via the toll-like receptor 4 (TLR4)/NF-κB signaling pathway. IDD-related gene expression microarray GSE124272 and high-throughput sequencing data set GSE175710 were obtained through the Gene Expression Omnibus database. Differentially expressed genes in IDD were identified, followed by implementation of protein-protein interaction network analysis and receiver operating characteristic curve analysis. The main pathways in IDD were obtained through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses, and target genes of Fer-1 were obtained through PubChem and PharmMapper websites. Finally, GPX4, FTH, and TLR4 expression was determined in a IDD rat model. Three key co-expression modules involved in IDD were obtained through Weighted Gene Co-Expression Network Analysis. Thirteen differentially expressed genes were found to be associated with IDD, and eight key genes (TLR4, BCL2A1, CXCL1, IL1R1, NAMPT, SOCS3, XCL1, and IRAK3) were found to affect IDD. These eight key genes had the diagnostic potential for IDD. The NF-κB signaling pathway was shown to play a predominant role in IDD development. Network pharmacologic analysis indicated a role of Fer-1 in suppressing ferroptosis and ameliorating IDD via the TLR4/NF-κB signaling pathway, which was verified by an in vivo animal experiment. The study showed that Fer-1 down-regulates TLR4 to inactivate NF-κB signaling pathway, suppressing ferroptosis and ultimately alleviating IDD in rats.

Pressure pain threshold and somatosensory abnormalities in different ages and functional conditions of post-stroke elderly.

BACKGROUND: Somatosensory deficits and abnormal pain sensitivity are highly prevalent among stroke survivors, which negatively impacts their quality of life and recovery process. However, the factors for pressure pain threshold (PPT) and somatosensory abnormalities in post-stroke elderly remain unknown. The aim of this study was to explore the effects of age, side and other functional conditions, such as spasticity and motor functions, on PPT and sensory abnormalities among elderly after stroke. METHODS: The cross-sectional study finally included 43 post-stroke elderly aged over 60 and assessed the PPT of 14 bilateral muscles widely located in the whole body by using a digital force gage. Meanwhile, spasticity, motor function, joint pain and activity of daily living (ADL) were evaluated by the Modified Ashworth scale, Fugl-Meyer, and Barthel Index, respectively. All participants were divided into higher-aged and lower-aged groups based on the median age of all of them. RESULTS: Higher age tended to be associated with higher sensitivity but not significant except for one upper limb muscle, and the affected side showed significantly higher PPTs than the unaffected side in three out of seven muscles (p < 0.05). Furthermore, the somatosensory abnormalities in the affected side, particularly hypoalgesia, were more frequent in higher-aged than lower-aged patients in most assessed muscles. Meanwhile, patients with spasticity showed more increment of PPTs in affected muscles around the knee joint than patients without spasticity (p < 0.05). Patients with better motor functions, less joint pain and higher ADL performed less bilateral differences of PPTs than other patients in some muscles (p < 0.05). CONCLUSIONS: The age and side differences of mechanical pain sensitivity were found among post-stroke elderly. Older patients show higher sensitivity in both sides compared with the younger ones, and the affected side of the elder shows more somatosensory abnormalities, particularly hypoalgesia, than that of the younger ones. Post-stroke elderly in good functional conditions, such as normal muscle tone, better physical function and daily activities, and less joint pain, seems to have more equal pain sensitivity between both sides than those in poor conditions.