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In recent years, interest has increased in the use of microorganisms to obtain additional valuable resources for green and sustainable development. Preliminary functional analyses have indicated that members of the family Thermoactinomycetaceae have good application potential for the production of novel specific enzymes, high-value bioactive compounds, novel secondary metabolites and the promotion of efficient biomass conversion. Therefore, they can be considered a new class of microbial resources with potentially high value. However, the lack of culture and culture-independent techniques coupled with the uncertain taxonomic status of the family Thermoactinomycetaceae, has made exploring these potential applications challenging. This paper reviews the distribution characteristics and functional properties of the family Thermoactinomycetaceae, providing a detailed interpretation of the potential application value of this group and proposing a set of systematic resource development strategies based on a combination of culture-dependent and culture-independent strategies to exploit its potential for resource applications.

BackgroundLow back pain resulting from intervertebral disc degeneration (IVDD) represents a significant global social problem. There are notable differences in the distribution of lymphatic vessels (LV) in normal and pathological intervertebral discs. Nevertheless, the molecular mechanisms of lymphatics-associated genes (LAGs) in the development of IVDD remain unclear. An in-depth exploration of this area will help to reveal the biological and clinical significance of LAGs in IVDD and may lead to the search for new therapeutic targets for IVDD.MethodsData sets were obtained from the Gene Expression Omnibus (GEO) database. Following quality control and normalization, the datasets (GSE153761, GSE147383, and GSE124272) were merged to form the training set, with GSE150408 serving as the validation set. LAGs from GeneCards, MSigDB, Gene Ontology, and KEGG database. The Venn diagram was employed to identify differentially expressed lymphatic-associated genes (DELAGs) that were differentially expressed in the normal and IVDD groups. Subsequently, four machine learning algorithms (SVM-RFE, Random Forest, XGB, and GLM) were used to select the method to construct the diagnostic model. The receiver operating characteristic (ROC) curve, nomogram, and Decision Curve Analysis (DCA) were used to evaluate the model effect. In addition, we constructed a potential drug regulatory network and competitive endogenous RNA (ceRNA) network for key LAGs.ResultsA total of 15 differentially expressed LAGs were identified. By comparing four machine learning methods, the top five genes of importance in the XGB model (MET, HHIP, SPRY1, CSF1, TOX) were identified as lymphatics-associated gene diagnostic signatures. This signature was used to predict the diagnosis of IVDD with strong accuracy and an area under curve (AUC) value of 0.938. Furthermore, the diagnostic model was validated in an external dataset (GSE150408), with an AUC value of 0.772. The nomogram and DCA further prove that the diagnosis model has good performance and predictive value. Additionally, drug regulatory networks and ceRNA networks were constructed, revealing potential therapeutic drugs and post-transcriptional regulatory mechanisms.ConclusionWe developed and validated a lymphatics-associated genes diagnostic model by machine learning algorithms that effectively identify IVDD patients. These five key LAGs may be potential therapeutic targets for IVDD patients.

Abstract Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Abstract Background The forearm/wrist squeeze/compression test has been used to examine digital flexor tendon injuries with varied names. Furthermore, the test has not been minutely described and its mechanism remains unclear. We renamed the test the “distal forearm squeeze test”. The purpose of this study was to elaborate on the test and elucidate the mechanism. Methods Two patients with digital flexor tendons ruptured in zone 3 and zone 1 respectively and 50 outpatients with intact digital tendons underwent the test. Then the test was performed on 3 chickens under 4 conditions. First, when the digital flexor and extensor tendons were all intact. Second, after the flexor tendons of the third toe were transected. Third, after the flexor tendons of all toes of the foot were transected. Finally, after the flexor and extensor tendons of all toes of the foot were transected. Results In the patient with digital flexor tendons ruptured in zone 3, the test showed that the injured digit was flexed slightly while the uninjured digits were flexed obviously. In the patient with digital flexor tendon ruptured in zone 1, after separate stabilization of the proximal interphalangeal (PIP) joints of the injured and uninjured fingers in extension, the test showed that the distal interphalangeal joint of the patient’s injured finger had no response, while those of the uninjured fingers were flexed. All 50 subjects showed clenched or half-clenched hands in response to the test. The test showed that all toes were flexed when the digital tendons of the chicken were intact. All toes were flexed except the third toe after the flexor tendons of the third toe were transected. All toes were extended after all the digital flexor tendons were transected. All toes had no response after all the digital flexor and extensor tendons were transected. Conclusions The distal forearm squeeze test is valuable in examining digital flexor tendon injuries. If only the flexor digitorum profundus tendon is examined, the PIP joint of the finger should be stabilized in extension during the test.

Abstract Background Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease. Methods In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice. Results The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl− efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model. Conclusions Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.

Intervertebral disk (IVD) degeneration (IVDD) is a main factor in lower back pain, and immunomodulation plays a vital role in disease progression. The IVD is an immune privileged organ, and immunosuppressive molecules in tissues reduce immune cell (mainly monocytes/macrophages and mast cells) infiltration, and these cells can release proinflammatory cytokines and chemokines, disrupting the IVD microenvironment and leading to disease progression. Improving the inflammatory microenvironment in the IVD through immunomodulation during IVDD may be a promising therapeutic strategy. This article reviews the normal physiology of the IVD and its degenerative mechanisms, focusing on IVDD-related immunomodulation, including innate immune responses involving Toll-like receptors, NOD-like receptors and the complement system and adaptive immune responses that regulate cellular and humoral immunity, as well as IVDD-associated immunomodulatory therapies, which mainly include mesenchymal stem cell therapies, small molecule therapies, growth factor therapies, scaffolds, and gene therapy, to provide new strategies for the treatment of IVDD.

Abstract Background Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and endoscopic lumbar interbody fusion (Endo-LIF) are both minimally invasive interbody fusion procedures for lumbar degenerative diseases. In this study, we attempted to compare the clinical efficacy and postoperative outcomes of MIS-TLIF and Endo-LIF for lumbar degenerative diseases. Methods The study cohort comprised 99 patients with lumbar degenerative diseases treated by MIS-TLIF or Endo-LIF from January 2019 to July 2021. The clinical outcomes (visual analogue scale (VAS), Oswestry disability index (ODI), and MacNab criteria) preoperatively, 1 month postoperatively, 3 months postoperatively, and 1 year postoperatively were compared between the two groups. Results There were no significant differences between the two groups in sex, age, disease duration, affected spine segment, and complications (P > 0.05). The operation time was significantly longer in the Endo-LIF group than the MIS-TLIF group (155.25 ± 12.57 vs. 123.14 ± 14.50 min; P 0.05), the VAS for lower back pain was lower in the Endo-LIF group than the MIS-TLIF group at each postoperative timepoint. The MacNab criteria showed that the improvement rate was 92.2% in the MIS-TLIF group and 91.7% in the Endo-LIF group, with no significant difference between the two groups (P > 0.05). Conclusions There were no significant differences in short-term surgical outcomes between the MIS-TLIF and Endo-LIF groups. Compared with the MIS-TLIF group, the Endo-LIF group incurred less damage to surrounding tissues, experienced less intraoperative blood loss, and had less lower back pain, which is more conducive to recovery.

BackgroundIntracerebral hemorrhage is a common disease, but cases of intracerebral hemorrhage with brucellosis are very rare. Here, we are presenting a case of a 60-year-old male patient diagnosed with brucellosis who has a right basal ganglia hemorrhage ruptured into bilateral lateral ventricles.Case presentationA 60-year-old male patient with symptoms of intracerebral hemorrhage who had no common risk factors for intracerebral hemorrhage, but having been diagnosed with brucellosis 2 months earlier and telling a shepherd history for 3 years. Cranial computed tomography (CT) and cranial magnetic resonance angiography (MRA) revealed that an intracerebral hemorrhage in the right basal ganglia had broken into bilateral lateral ventricles, and a Brucella serology test was positive. The patient's condition improved significantly after receiving bilateral lateral ventricle cone drainage, hematoma cavity cone drainage and anti-brucellosis treatment.ConclusionsHerein, we discuss the possible mechanisms and clinical implications between brucellosis and intracerebral hemorrhage. This case suggests whether we can use brucellosis as a routine examination for disease diagnosis and prevention in patients with intracerebral hemorrhage from pastoral areas.

Intervertebral disc (IVD) degeneration (IVDD) has been considered the dominant factor in low back pain (LBP), and its etiological mechanisms are complex and not yet fully elucidated. To date, the treatment of IVDD has mainly focused on relieving clinical symptoms and cannot fundamentally solve the problem. Recently, a novel microsphere-based therapeutic strategy has held promise for IVD regeneration and has yielded encouraging results with in vitro experiments and animal models. With excellent injectability, biocompatibility, and biodegradability, this microsphere carrier allows for targeted delivery and controlled release of drugs, gene regulatory sequences, and other bioactive substances and supports cell implantation and directed differentiation, aiming to improve the disease state of IVD at the source. This review discusses the possible mechanisms of IVDD and the limitations of current therapies, focusing on the application of microsphere delivery systems in IVDD, including targeted delivery of active substances and drugs, cellular therapy, and gene therapy, and attempts to provide a new understanding for the treatment of IVDD.

In this paper, the radiation characteristics and active structural acoustic control of a submerged cylindrical shell at low frequencies are investigated. First, the coupled vibro-acoustic equations for a submerged finite cylindrical shell are solved by a modal decomposition method, and the radiation impedance is obtained by the fast Fourier transform. The modal shapes of the first ten acoustic radiation modes and the structure-dependent radiation modes are presented. The relationships between the vibration modes and the radiation modes as well as the contributions of the radiation modes to the radiated sound power are given at low frequencies. Finally, active structural acoustic control of a submerged finite cylindrical shell is investigated by considering the fluid-structure coupled interactions. The physical mechanism of the active control is discussed based on the relationship between the vibration and radiation modes. The results showed that, at low frequencies, only the first several radiation modes contributed to the sound power radiated from a submerged finite cylindrical shell excited by a radial point force. By determining the radiation modes that dominate the contribution to the radiated sound, the physical mechanism of the active control is explained, providing a potential tool to allow active control of the vibro-acoustic responses of submerged structures more effectively.

Abstract Background The treatment of lumbar infectious spondylitis is controversial. In this study, we attempted to demonstrate that unilateral percutaneous endoscopic debridement with physiologic saline and negative pressure drainage postoperatively may achieve a satisfactory result in lumbar infectious spondylitis. Methods We retrospectively analyzed 17 patients with lumbar infectious spondylitis who underwent percutaneous endoscopic debridement and drainage (PEDD) through a posterolateral transforaminal approach. Each biopsy specimen was submitted without delay after surgery and examined for microorganisms and evaluated histopathologically. Patients were assessed by careful physical examination, MacNab criteria, Oswestry Disability Index (ODI), visual analog scale (VAS), regular serological tests, imaging studies for clinical function, and patient satisfaction. Results Of the 17 patients, 14 (82.4%) had satisfactory relief of their back pain according to MacNab criteria at 1 week after PEDD. Three patients (17.6%) who had advanced infections with multilevel involvement and paraspinal abscesses underwent anterior debridement and autograft interbody fusion with instrumentation within 2 weeks. However, there were no other severe surgery-related complications. Causative bacteria were identified in most cases, and Staphylococcus aureus was the most prevalent strain. Conclusions Unilateral PEDD with physiological saline or empirical antibiotics did not disrupt lumbar stability and avoided the important intraspinal structures such as the dural sac and nerve roots. It not only had a high rate of identification of the causative pathogen, but also provided effective infection control and pain relief. PEDD may be a useful technique for treatment of lumbar infectious spondylodiscitis patients who have no severe deformities and are unable to undergo the conventional anterior surgery due to poor health or advanced age.

Background/Aims: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. Methods: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κβ signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κβ promoter luciferase reporter plasmid. The expression and activation of NF-κβ Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κβ signaling after the down-regulation of CXCR4 in osteosarcoma cells. Results: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κβ signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. Conclusions: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κβ signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

Abstract Background Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI. Methods SCI was performed using an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining. Mitochondrial dysfunction was determined by quantitative real-time polymerase chain reaction (qPCR), western blot, and detection of mitochondrial membrane potential level. Microglia/macrophage activation and astrocytic response were evaluated by immunofluorescence labeling. Results Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11-7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage, and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines. Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation, neutrophils infiltration, and reactive gliosis, as well as mitochondrial dysfunction. Conclusions Collectively, our results demonstrate that pharmacologic suppression of NLRP3 inflammasome activation controls neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity of spinal cord damage, and improves neurological recovery after SCI. These data strongly indicate that the NLRP3 inflammasome is a vital contributor to the secondary damage of SCI in mice.

We aimed to study the anti-tumor effects of triptolide on osteosarcoma and the related molecular mechanisms. The cell viability, apoptosis portion, tumor size, tumor weight, and invasion of osteosarcoma cells were determined. The relative level of microRNA-181 in osteosarcoma tissues and the adjacent tissues was determined by quantitative real-time reverse transcription polymerase chain reaction. The target gene of microRNA-181a was determined and verified by luciferase report assay. At last, osteosarcoma cells were treated with triptolide and triptolide + microRNA-181a mimics to verify the relationship between triptolide and microRNA-181a. Triptolide inhibited the cell viability, promoted the apoptosis, decreased the tumor size and weight, and reduced the invasion of osteosarcoma cells. The level of microRNA-181a in osteosarcoma cells decreased significantly after treating with triptolide, and the relative level of microRNA-181a in osteosarcoma tissues was markedly higher than that in the adjacent tissues. PTEN was reported and verified the direct target gene of microRNA-181a. The overexpression of microRNA-181a decreased the inhibition of triptolide on osteosarcoma proliferation and promotion on osteosarcoma apoptosis. In conclusion, triptolide inhibited cell growth and invasion of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.

Background: Neuroinflammatory responses involve the activation of the interleukin (IL) -1β and IL-18. Processing and activation of the pro-inflammatory IL require NLRP3 inflammasome activation. Rutin can protect spinal cord against damage, but the potential mechanisms underlying remain unknown. Here, we investigated the molecular mechanisms of rutin-mediated neuroprotection in a rat model of spinal cord injury (SCI)., Materials and Methods: One hundred twenty female Sprague-Dawley rats were randomly assigned to four groups: sham group, SCI group, SCI + Rutin50 group, and the SCI + Rutin100 group. The influences of rutin on inflammatory marker levels, histologic alterations, and locomotion scale were analyzed., Results: SCI significantly increased the expression of the NLRP3, ASC, IL-1β, IL-18, and tumor necrosis factor-alpha. Rutin significantly reduced the levels of reactive oxygen species, malondialdehyde, NLRP3, ASC, caspase-1, IL-1β, IL-18, and tumor necrosis factor-alpha. Furthermore, rutin administration significantly attenuated histologic alteration and improved locomotion recovery., Conclusions: Our data provide clear evidence that rutin attenuates tissue damage and improves locomotion recovery, and the mechanism may be related to the alleviation of inflammation and oxidative stress., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bone formation, which is inhibited by particulate wear debris, is a pathological factor that contributes to periprosthetic osteolysis. Although the nuclear factor of activated T cells c1 (NFATc1) is known to be involved in osteoblast differentiation, and its effect on osteoblasts in response to wear particles remains unclear. In this study, we investigated the role of NFATc1 in the regulation of osteoblastic differentiation of rat calvaria (RC) cells (a cell-culture model comprising many osteoprogenitors) that were challenged with titanium (Ti) particles. The results showed that the Ti particles inhibited osteoblastic differentiation and mineralization of RC cells. NFATc1 plays a critical role in the Ti-particle inhibition process of the osteoblastic differentiation in RC cells. Inactivation of NFATc1 by the 11R-VIVIT peptide potently enhanced osteoblast differentiation and mineralization inhibition by the Ti particles. The 11R-VIVIT peptide does not have a toxic effect on the RC cells. On the basis of these data, we conclude that inactivation of NFATc1 by the 11R-VIVIT peptide may provide a promising therapeutic target for the treatment of periprosthetic osteolysis by increasing bone formation., (© 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.)