Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Identification of Dof transcription factors in Dendrobium huoshanense and expression pattern under abiotic stresses.

Introduction: DNA-binding with one finger (Dof) transcription factors (TFs) are a unique family of TFs found in higher plants that regulate plant responses to light, hormones, and abiotic stresses. The specific involvement of Dof genes in the response to environmental stresses remains unknown in D. huoshanense. Methods: A total of 22 Dof family genes were identified from the D. huoshanense genome. Results: Chromosome location analysis showed that DhDof genes were distributed on 12 chromosomes, with the largest number of Dof genes located on chromosome 8. The phylogenetic tree revealed that DhDofs could be categorized into 11 distinct subgroups. In addition to the common groups, DhDof4, DhDof5, DhDof17, and the AtDof1.4 ortholog were clustered into the B3 subgroup. Group E was a newly identified branch, among which DhDof6, DhDof7, DhDof8, and DhDof9 were in an independent branch. The conserved motifs and gene structure revealed the differences in motif number and composition of DhDofs. The dof domain near the N-terminus was highly conserved and contained a C2-C2-type zinc finger structure linked with four cysteines. Microsynteny and interspecies collinearity revealed gene duplication events and phylogenetic tree among DhDofs. Large-scale gene duplication had not occurred among the DhDofs genes and only in one pair of genes on chromosome 13. Synteny blocks were found more often between D. huoshanense and its relatives and less often between Oryza sativa and Arabidopsis thaliana. Selection pressure analysis indicated that DhDof genes were subject to purifying selection. Expression profiles and correlation analyses revealed that the Dof gene under hormone treatments showed several different expression patterns. DhDof20 and DhDof21 had the highest expression levels and were co-expressed under MeJA induction. The cis-acting element analysis revealed that each DhDof had several regulatory elements involved in plant growth as well as abiotic stresses. qRT-PCR analysis demonstrated that DhDof2 was the main ABA-responsive gene and DhDof7 was the main cold stress-related gene. IAA suppressed the expression of some Dof candidates, and SA inhibited most of the candidate genes. Discussion: Our results may provide new insights for the further investigation of the Dof genes and the screening of the core stress-resistance genes.

Cardiac Resolvin D2 ameliorates sepsis-induced cardiomyopathy via inhibiting Caspase-11/GSDMD dependent pyroptosis.

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is common complication in septic patients with a high mortality and is characterized by an abnormal inflammation response, which was precisely regulated by endogenous specialized pro-resolving mediators (SPMs). However, the metabolic changes of cardiac SPMs during SICM and the roles of SPMs subset in the development of SICM remain unknown. METHODS: In this work, the SPMs concentration was assessed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) of SICM mice and SICM patients. The cardiac function was measured by echocardiography after the treatment of a SPMs subset, termed Resolvin D2 (RvD2). Caspase-11-/-, GSDMD-/- and double deficient (Caspase-11-/-GSDMD-/-) mice were used to clarify the mechanisms of RvD2 in SICM. RESULTS: We found that endogenous cardiac SPMs were disorders and RvD2 was decreased significantly and correlated with left ventricular ejection fraction (LVEF) and ß-BNP, cTnT in Lipopolysaccharide/Cecum ligation and puncture (CLP) induced SICM models. Treatment with RvD2 attenuated lethality, cardiac dysfunction and cardiomyocytes death during SICM. Mechanistically, RvD2 alleviated SICM via inhibiting Caspase-11/GSDMD-mediated cardiomyocytes pyroptosis. Finally, the plasma levels of RvD2 were also decreased and significantly correlated with IL-1ß, ß-BNP, cTnT and LVEF in patients with SICM. Of note, plasma RvD2 level is indicator of SICM patients from healthy controls or sepsis patients. CONCLUSION: These findings suggest that decreased cardiac RvD2 may involve in the pathogenesis of SICM. In addition, treatment with RvD2 represents a novel therapeutic strategy for SICM by inhibiting cardiomyocytes pyroptosis.

KNSTRN Is a Prognostic Biomarker That Is Correlated with Immune Infiltration in Breast Cancer and Promotes Cell Cycle and Proliferation.

Kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) promotes the progression of bladder cancer and lung adenocarcinoma. However, its expression and biological function in breast cancer remain largely unknown. Therefore, this study aimed to analyze KNSTRN expression, prognoses, correlation with immune infiltration, expression-associated genes, and regulated signaling pathways to characterize its role in regulating the cell cycle using both bioinformatics and in vitro functional experiments. Analyses of The Cancer Genome Atlas, Gene Expression Omnibus, TIMER, and The Human Protein Atlas databases revealed a significant upregulation of KNSTRN transcript and protein levels in breast cancer. Kaplan-Meier survival analyses demonstrated a significant association between high expression of KNSTRN and poor overall survival, relapse-free survival, post-progression survival, and distant metastases-free survival in patients with breast cancer. Furthermore, multivariate Cox regression analyses confirmed that KNSTRN is an independent prognostic factor for breast cancer. Immune infiltration analysis indicated a positive correlation between KNSTRN expression and T regulatory cell infiltration while showing a negative correlation with Tgd and natural killer cell infiltration. Gene set enrichment analysis along with single-cell transcriptome data analysis suggested that KNSTRN promoted cell cycle progression by regulating the expression of key cell cycle proteins. The overexpression and silencing of KNSTRN in vitro, respectively, promoted and inhibited the proliferation of breast cancer cells. The overexpression of KNSTRN enhanced the expression of key cell cycle regulators, including CDK4, CDK6, and cyclin D3, thereby accelerating the G1/S phase transition and leading to aberrant proliferation of breast cancer cells. In conclusion, our study demonstrates that KNSTRN functions as an oncogene in breast cancer by regulating immune response, promoting G1/S transition, and facilitating breast cancer cell proliferation. Moreover, KNSTRN has potential as a molecular biomarker for diagnostic and prognostic prediction in breast cancer.

Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS.

The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.

Fucosyltransferase 9 promotes neuronal differentiation and functional recovery after spinal cord injury by suppressing the activation of Notch signaling.

Individuals with spinal cord injury (SCI) suffer from permanent disabilities such as severe motor, sensory and autonomic dysfunction. Neural stem cell transplantation has proven to be a potential strategy to promote regeneration of the spinal cord, since NSCs can produce neurotrophic growth factors and differentiate into mature neurons to reconstruct the injured site. However, it is necessary to optimize the differentiation of NSCs before transplantation to achieve a better regenerative outcome. Inhibition of Notch signaling leads to a transition from NSCs to neurons, while the underlying mechanism remains inadequately understood. Our results demonstrate that overexpression of fucosyltransferase 9 (Fut9), which is upregulated by Wnt4, promotes neuronal differentiation by suppressing the activation of Notch signaling through disruption of furin-like enzyme activity during S1 cleavage. In an in vivo study, Fut9-modified NSCs efficiently differentiates into neurons to promote functional and histological recovery after SCI. Our research provides insight into the mechanisms of Notch signaling and a potential treatment strategy for SCI.

Analgesic effectiveness of serratus anterior plane block in patients undergoing video-assisted thoracoscopic surgery: a systematic review and updated meta-analysis of randomized controlled trials.

BACKGROUND: Serratus anterior plane block (SAPB) is a promising regional technique for analgesia in thoracic surgery. Till now, several randomized controlled trials (RCTs) have explored the effectiveness of SAPB for postoperative pain control in patients undergoing video-assisted thoracoscopic surgery (VATS), but the sample sizes were small and conclusions remained in controversy. Therefore, we conducted the present systematic review and meta-analysis. METHODS: RCTs evaluating the analgesic performance of SAPB, comparing to control methods (no block, placebo or local infiltration anesthesia), in patients undergoing VATS were searched in PubMed, EMBASE, Web of Science and Cochrane Library from inception to December 31, 2022. Mean difference (MD) and corresponding 95% confidence interval (95%CI) were calculated for postoperative pain scores at various time points, postoperative opioid consumption and length of hospital stay. Pooled relative risk (RR) with 95%CI were calculated for the risk of postoperative nausea and vomiting (PONV) and dizziness. A random-effect model was applied. RESULTS: A total of 12 RCTs (837 participants) were finally included. Compared to control group, SAPB had significant reductions of postoperative pain scores at 2 h (MD = -1.58, 95%CI: -1.86 to -1.31, P < 0.001), 6 h (MD = -2.06, 95%CI: -2.74 to -1.38, P < 0.001), 12 h (MD = -1.72, 95%CI: -2.30 to -1.14, P < 0.001) and 24 h (MD = -1.03, 95%CI: -1.55 to -0.52, P < 0.001), respectively. Moreover, SAPB conferred a fewer postoperative opioid consumption (MD = -7.3 mg of intravenous morphine equivalent, 95%CI: -10.16 to -4.44, P < 0.001) and lower incidence of PONV (RR = 0.56, 95%CI: 0.41 to 0.77, P < 0.001). There was no difference between both groups regarding length of hospital stay and risk of dizziness. CONCLUSION: SAPB shows an excellent performance in postoperative pain management in patients undergoing VATS by reducing pains scores, postoperative opioid consumption and incidence of PONV. However, due to huge heterogeneity, more well-designed, large-scale RCTs are needed to verify these findings in the future.

Macrophage in liver Fibrosis: Identities and mechanisms.

Liver fibrosis is a chronic disease characterized by the deposition of extracellular matrix and continuous loss of tissues that perform liver functions. Macrophages are crucial modulators of innate immunity and play important roles in liver fibrogenesis. Macrophages comprise heterogeneous subpopulations that exhibit different cellular functions. Understanding the identity and function of these cells is essential for understanding the mechanisms of liver fibrogenesis. According to different definitions, liver macrophages are divided into M1/M2 macrophages or monocyte-derived macrophages/Kupffer cells. Classic M1/M2 phenotyping corresponds to pro- or anti-inflammatory effects, and, therefore, influences the degree of fibrosis in later phases. In contrast, the origin of the macrophages is closely associated with their replenishment and activation during liver fibrosis. These two classifications of macrophages depict the function and dynamics of liver-infiltrating macrophages. However, neither description properly elucidates the positive or negative role of macrophages in liver fibrosis. Critical tissue cells mediating liver fibrosis include hepatic stellate cells and hepatic fibroblasts, with hepatic stellate cells being of particular interest because of their close association with macrophages in liver fibrosis. However, the molecular biological descriptions of macrophages are inconsistent between mice and humans, warranting further investigations. In liver fibrosis, macrophages can secrete various pro-fibrotic cytokines, such as TGF-ß, Galectin-3 and interleukins (ILs), and fibrosis-inhibiting cytokines, such as IL10. These different secretions may be associated with the specific identity and spatiotemporal characteristics of macrophages. Furthermore, during fibrosis dissipation, macrophages may degrade extracellular matrix by secreting matrix metalloproteinases (MMPs). Notably, using macrophages as therapeutic targets in liver fibrosis has been explored. The current therapeutic approaches for liver fibrosis can by categorized as follows: treatment with macrophage-related molecules and macrophage infusion therapy. Although there have been limited studies, macrophages have shown reliable potential for liver fibrosis treatment. In this review, we focu on the identity and function of macrophages and their relationship to the progression and regression of liver fibrosis.

Experimental Study on Coaxial Waterjet-Assisted Laser Scanning Machining of Nickel-Based Special Alloy.

The problems of the recast layer, oxide layer, and heat-affected zone (HAZ) in conventional laser machining seriously impact material properties. Coaxial waterjet-assisted laser scanning machining (CWALSM) can reduce the conduction and accumulation of heat in laser machining by the high specific heat capacity of water and can realize the machining of nickel-based special alloy with almost no thermal damage. With the developed experimental setup, the laser ablation threshold and drilling experiments of the K4002 nickel-based special alloy were carried out. The effects of various factors on the thermal damage thickness were studied with an orthogonal experiment. Experimental results have indicated that the ablation threshold of K4002 nickel-based special alloy by a single pulse is 4.15 J/cm2. The orthogonal experiment results have shown that the effects of each factor on the thermal damage thickness are in the order of laser pulse frequency, waterjet speed, pulse overlap rate, laser pulse energy, and focal plane position. When the laser pulse energy is 0.21 mJ, the laser pulse frequency is 1 kHz, the pulse overlap is 55%, the focal plane position is 1 mm, and the waterjet speed is 6.98 m/s, no thermal damage machining can be achieved. In addition, a comparative experiment with laser drilling in the air was carried out under the same conditions. The results have shown that compared with laser machining in the air, the thermal damage thickness of CWALSM is smaller than 1 µm, and the hole taper is reduced by 106%. There is no accumulation and burr around the hole entrance, and the thermal damage thickness range is 0-0.996 µm. Furthermore, the thermal damage thickness range of laser machining in the air is 0.499-2.394 µm. It has also been found that the thermal damage thickness is greatest at the entrance to the hole, decreasing as the distance from the entrance increases.

Transplantation of Wnt4-modified neural stem cells mediate M2 polarization to improve inflammatory micro-environment of spinal cord injury.

Neural stem cells (NSCs) transplantation has been considered as a potential strategy to reconnect the neural circuit after spinal cord injury (SCI) but the therapeutic effect was still unsatisfied because of the poor inflammatory micro-environment of SCI. Previous study reported that neuroprotection and inflammatory immunomodulation were considered to be most important mechanism of NSCs transplantation. In addition, Wnt4 has been considered to be neurogenesis and anti-inflammatory so that it would be an essential assistant agent for NSCs transplantation. Our single cells sequence indicates that macrophages are the most important contributor of inflammatory response after SCI and the interaction between macrophages and astrocytes may be the most crucial to inflammatory microenvironment of SCI. We further report the first piece of evidence to confirm the interaction between Wnt4-modified NSCs and macrophages using NSCs-macrophages co-cultured system. Wnt4-modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages through suppression of TLR4/NF-κB signal pathway; furthermore, M2 cells promote neuronal differentiation of NSCs through MAPK/JNK signal pathway. In vivo, transplantation of Wnt4-modified NSCs improves inflammatory micro-environment through induce M2 polarization and inhibits M1 polarization of macrophages to promote axonal regeneration and tissue repair. The current study indicated that transplantation of Wnt4-modified NSCs mediates M2 polarization of macrophages to promote spinal cord injury repair. Our novel findings would provide more insight of SCI and help with identification of novel treatment strategy.

Effects of Scanning Speed on the Polished Surface Quality of Mold Steel by Dual-Beam Coupling Nanosecond Laser.

In this paper, a novel dual-beam coupled nanosecond laser was used to polish S136D mold steel. The effects of scanning speed, total fluence, spot overlap ratio, and SPSN on surface quality were analyzed. The polished surface roughness Ra without ultrasonic cleaning is too large due to slag, splash, and dust produced by laser polishing. When scanning speed is 1250 mm/min, surface roughness Ra with ultrasonic cleaning is reduced from the original surface 1.92 µm to 0.72 µm, and the surface roughness Ra is reduced by 62.50%. When the Ftot is 35.38 J/cm2, the minimum value of surface roughness Ra is 0.72 µm. If the total fluence is higher or lower, it is not conducive to reducing the surface roughness, the total fluence is higher, and there is a polished surface with SOM phenomenon. The polished surface with spot overlap ratio of 98.55% has a smooth morphology, and a minimum value of surface roughness Ra of 0.41 µm. When the specimen is inclined at a certain angle, the high-magnification camera captures color on the polished surface. It is found that the microscopic texture of molten material flow trace and polishing scanning track is obvious. Polished surface is mainly distributed with Fe, Cr, C, and O elements. The surface material processing speed per unit time is low, and the polishing surface quality is improved less. The maximum surface roughness Ra is 1.98 µm. The minimum Ra of polished surface with smoother morphology is 0.41 µm, and surface profile height is basically the same. The research results show that the new dual-beam coupled nanosecond laser polishing technology can improve surface quality of materials. This research work provides process guidance for laser polishing effect analysis and mechanism innovation.

ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/ß-catenin pathway.

Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly expressed in breast cancer tissues and cell lines. Higher level of ZNF276 correlated with poor prognosis. Gain-of and loss-of function suggested that ZNF276 is essential for the proliferation, migration and invasion of breast cancer cells in vitro and metastasis in vivo. RNA-sequencing and CUT&Tag assay revealed that ZNF276 controlled a variety of growth and metastasis-related genes expression. ZNF276 transcriptionally promoted the expression of CYP1B1 by directly binds to the promoter region of the CYP1B1 through its C2H2 domain. ZNF276 facilitated the translocation of ß-catenin from cytoplasm to nucleus through CYP1B1, leading to the upregulation of cyclin D1 and c-Myc, and the activation of the Wnt/ß-catenin pathway. Knockdown of CYP1B1 significantly blocked the ZNF276-mediated effects on cell proliferation, migration and invasion. Lastly, ZNF276 interacted with MAGEB2 which enhanced the binding of ZNF276 at the CYP1B1 promoter, promoted CYP1B1 expression and Wnt signaling activation. Collectively, these findings highlight the oncogenic role of ZNF276 on breast cancer cell proliferation and metastasis. Targeting ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients.

WKYMVm/FPR2 Alleviates Spinal Cord Injury by Attenuating the Inflammatory Response of Microglia.

Spinal cord injury (SCI) is a common traumatic disease of the nervous system. The pathophysiological process of SCI includes primary injury and secondary injuries. An excessive inflammatory response leads to secondary tissue damage, which in turn exacerbates cellular and organ dysfunction. Due to the irreversibility of primary injury, current research on SCI mainly focuses on secondary injury, and the inflammatory response is considered the primary target. Thus, modulating the inflammatory response has been suggested as a new strategy for the treatment of SCI. In this study, microglial cell lines, primary microglia, and a rat SCI model were used, and we found that WKYMVm/FPR2 plays an anti-inflammatory role and reduces tissue damage after SCI by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways. FPR2 was activated by WKYMVm, suppressing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by inhibiting M1 microglial polarization. Moreover, FPR2 activation by WKYMVm could reduce structural disorders and neuronal loss in SCI rats. Overall, this study illustrated that the activation of FPR2 by WKYMVm repressed M1 microglial polarization by suppressing the ERK1/2 and NF-κB signaling pathways to alleviate tissue damage and locomotor decline after SCI. These findings provide further insight into SCI and help identify novel treatment strategies.

CBLC inhibits the proliferation and metastasis of breast cancer cells via ubiquitination and degradation of CTTN.

The E3 ubiquitin ligase is an important regulator of cell signaling and proteostasis and is tightly controlled in many diseases, including cancer. Our study aimed to investigate the biological role of the E3 ubiquitin ligase CBLC in breast cancer and elucidate the specific mechanistic network underlying CBLC-mediated target substrate degradation, cell proliferation and metastasis. Here, we showed that CBLC expression was higher in breast cancer tissues and cells than that in normal tissues and cells. Higher expression of CBLC predicted a better prognosis for breast cancer patients. CBLC inhibited the proliferation, migration and invasion of breast cancer cells. Co-IP and immunofluorescence co-localization assays demonstrated that CBLC interacted with CTTN in the cytoplasm. CBLC promoted the degradation of CTTN through the ubiquitin-proteasome pathway without affecting its mRNA level. The inhibitory effect of CBLC on breast cancer cell proliferation, migration and invasion could partly be reversed by CTTN. Taken together, our study clarified the biological role of CBLC as a tumor suppressor and discovered its functional substrate, providing a molecular basis for CBLC/CTTN as a potential therapeutic target in breast cancer.

Unilateral percutaneous vertebroplasty for osteoporotic lumbar compression fractures: a comparative study between transverse process root-pedicle approach and conventional transpedicular approach.

PURPOSE: Percutaneous vertebroplasty (PVP) is a routine operation for the treatment of osteoporotic lumbar compression fractures (OLCFs). As is well known, unilateral puncture is a common method. However, with the conventional transpedicular approach (CTPA), the cement may be asymmetrically dispersed, so some surgeons use the transverse process root-pedicle approach (TPRPA). The objective of this study was to compare the clinical results and bone cement distribution of PVP for OLCF with unilateral TPRPA and CTPA to identify the advantages and disadvantages of the two surgical options. PATIENTS AND METHODS: From January 2016 to June 2019, seventy-two elderly patients who underwent unilateral PVP for single-level OLCF were retrospectively reviewed. Operation time, injection amount and type of bone cement distribution, and bone cement leakage and surgical complications were recorded. The visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were used to evaluate the clinical results. All patients were followed up for more than 12 months, and the assessment was based primarily on clinical and radiological outcomes. RESULTS: There were significant differences in the surgical time and the volume and the type of bone cement distribution and the lost of operative vertebra height between the two groups. However, there was no significant difference in bone cement leakage. Moreover, there were no significant differences in VAS and ODI between the two groups at 2 days and 12 months after the operation. CONCLUSIONS: Unilateral TPRPA and CTPA are practical and feasible methods in PVP for the treatment of OLCF, and they have similar clinical effects. However, TPRPA has the advantages of a better distribution of bone cement and a shorter operation time and a better maintenance effect of injured vertebra height, without increasing the rate of bone cement leakage.

S100A4 is activated by RhoA and catalyses the polymerization of non-muscle myosin, adhesion complex assembly and contraction in airway smooth muscle.

KEY POINTS: S100A4 is expressed in many tissues, including smooth muscle (SM), but its physiologic function is unknown. S100A4 regulates the motility of metastatic cancer cells by binding to non-muscle (NM) myosin II. Contractile stimulation causes the polymerization of NM myosin in airway SM, which is necessary for tension development. NM myosin regulates the assembly of adhesion junction signalling complexes (adhesomes) that catalyse actin polymerization. In airway SM, ACh (acetylcholine) stimulated the binding of S100A4 to the NM myosin heavy chain, which was catalysed by RhoA GTPase via the RhoA-binding protein, rhotekin. The binding of S100A4 to NM myosin was required for NM myosin polymerization, adhesome assembly and actin polymerization. S100A4 plays a critical function in the regulation of airway SM contraction by catalysing NM myosin filament assembly. The interaction of S100A4 with NM myosin may also play an important role in the physiologic function of other tissues. ABSTRACT: S100A4 binds to the heavy chain of non-muscle (NM) myosin II and can regulate the motility of crawling cells. S100A4 is widely expressed in many tissues including smooth muscle (SM), although its role in the regulation of their physiologic function is not known. We hypothesized that S100A4 contributes to the regulation of contraction in airway SM by regulating a pool of NM myosin II at the cell cortex. NM myosin II undergoes polymerization in airway SM and regulates contraction by catalysing the assembly of integrin-associated adhesome complexes that activate pathways that catalyse actin polymerization. ACh stimulated the interaction of S100A4 with NM myosin II in airway SM at the cell cortex and catalysed NM myosin filament assembly. RhoA GTPase regulated the activation of S100A4 via rhotekin, which facilitated the formation of a complex between RhoA, S100A4 and NM myosin II. The depletion of S100A4, RhoA or rhotekin from airway SM tissues using short hairpin RNA or small interfering RNA prevented NM myosin II polymerization as well as the recruitment of vinculin and paxillin to adhesome signalling complexes in response to ACh, and inhibited actin polymerization and tension development. S100A4 depletion did not affect ACh-stimulated SM myosin regulatory light chain phosphorylation. The results show that S100A4 plays a critical role in tension development in airway SM tissue by catalysing NM myosin filament assembly, and that the interaction of S100A4 with NM myosin in response to contractile stimulation is activated by RhoA GTPase. These results may be broadly relevant to the physiologic function of S100A4 in other cell and tissue types.

S100A4 is secreted by airway smooth muscle tissues and activates inflammatory signaling pathways via receptors for advanced glycation end products.

S100A4 is a low-molecular-mass (12 kDa) EF-hand Ca2+-binding S100 protein that is expressed in a broad range of normal tissue and cell types. S100A4 can be secreted from some cells to act in an autocrine or paracrine fashion on target cells and tissues. S100A4 has been reported in the extracellular fluids of subjects with several inflammatory diseases, including asthma. Airway smooth muscle plays a critical role in airway inflammation by synthesizing and secreting inflammatory cytokines. We hypothesized that S100A4 may play an immunomodulatory role in airway smooth muscle. Trachealis smooth muscle tissues were stimulated with recombinant His-S100A4, and the effects on inflammatory responses were evaluated. S100A4 induced the activation of Akt and NF-κB and stimulated eotaxin secretion. It also increased the expression of RAGE and endogenous S100A4 in airway tissues. Stimulation of airway smooth muscle tissues with IL-13 or TNF-α induced the secretion of S100A4 from the tissues and promoted the expression of endogenous receptors for advanced glycation end products (RAGE) and S100A4. The role of RAGE in mediating the responses to S100A4A was evaluated by expressing a mutant nonfunctional RAGE (RAGEΔcyto) in tracheal muscle tissues and by treating tissues with a RAGE inhibitor. S100A4 did not activate NF-κB or Akt in tissues that were expressing RAGEΔcyto or treated with a RAGE inhibitor, indicating that S100A4 mediates its effects by acting on RAGE. Our results demonstrate that inflammatory mediators stimulate the synthesis and secretion of S100A4 in airway smooth muscle tissues and that extracellular S100A4 acts via RAGE to mediate airway smooth muscle inflammation.

Sarcopenia as a predictor of mortality in women with breast cancer: a meta-analysis and systematic review.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Recently, studies have been published with inconsistent findings regarding whether sarcopenia is a risk factor for mortality in breast cancer patients. Therefore, the aim of this systematic review and meta-analysis was to systematically assess and quantify sarcopenia as a risk factor for mortality in breast cancer patients. METHODS: In a systematic literature review of PubMed, EMBASE, and the Cochrane CENTRAL Library, we searched for observational studies written in English (from database inception until April 30, 2019) that reported an association between sarcopenia and breast cancer in women who were 18 years or older. RESULTS: A total of six studies (5497 participants) were included in this meta-analysis. Breast cancer patients with sarcopenia were associated with a significantly higher risk of mortality, compared to breast cancer patients without sarcopenia (pooled HR-hazard ratio = 1.71, 95% CI: 1.25-2.33, I2 = 59.1%). In addition, the results of age subgroup analysis showed that participants younger than 55 years with sarcopenia had a lower risk of mortality than participants aged 55 years and older with sarcopenia (pooled HR = 1.46, 95% CI: 1.24-1.72 versus pooled HR = 1.99, 95% CI: 1.05-3.78), whereas both have an increased risk of mortality compared to non-sarcopenic patients. Subgroup analyses regarding stage at diagnosis revealed an increased risk of mortality in non-metastatic patients compared to participants without sarcopenia (pooled HR = 1.91, 95% CI: 1.32-2.78), whereas the association was not significant in metastatic breast cancer patients. Other subgroup analyses were performed using different follow-up periods (> 5 years versus ≤5 years) and the results were different (pooled HR = 1.81, 95% CI: 1.23-2.65 versus pooled HR = 1.70, 95% CI: 0.80-3.62). CONCLUSIONS: The present study found that sarcopenia is a risk factor for mortality among female early breast cancer patients. It is imperative that more research into specific interventions aimed at treating sarcopenia be conducted in the near future in order to provide evidence which could lead to decreased mortality rates in breast cancer patients.

Preparation and Repeated Repairability Evaluation of Sunflower Oil-Type Microencapsulated Filling Materials.

Cracks are the main challenges for asphalt pavement, which should be timely repaired. One of the most commonly used repairing methods is to fill the binding materials into cracks, but the repeated repairing ability is insufficient. The self-healing microcapsule technologies provide the potentials for enhancing the repeated repairing ability of filling materials. Therefore, the microcapsule core material was selected from sunflower oil in this study, and the capsular wall material was selected from melamine-urea-formaldehyde resin, which was used to prepare the microcapsule by using in-situ polymerization method. Three kinds of microcapsules with different particle sizes were prepared by adjusting the emulsifier dosage and core wall ratio. The microstructure, molecular structure, thermal stability, and dispersion features were further studied, and the effects of microcapsules with different particle sizes on the repeated repairability of the filling materials were evaluated via the fatiguerepair-fatigue test. In addition, the traditional regenerative microcapsules were compared to determine the optimal particle size range for sunflower oil microcapsules. According to the experimental research, it was thus concluded that the emulsion droplet size distribution was most concentrated when the emulsifier content was 0.7%; and when the core-wall ratio was 1.3:1, the microcapsules had uniform particle size and good dispersion effect. When the microcapsule emulsification rate was 900 rpm and microcapsule content was 2%, then the repeated repair effect for the microcapsule crack filling materials was optimal. The sunflower oil type microcapsule therefore meets the filling temperature requirement for the filler.