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Background Fractures are the prevalent traumatic conditions encountered in orthopedic practices. The rising incidence of fractures has emerged as a pressing global health concern. Although the majority of individuals with fractures experience complete recovery of bone structure and function, approximately 10% of those with fractures exhibit delayed fracture healing (DFH). The objective of this investigation was to explore the function and underlying mechanisms of LINC00941 in the advancement of DFH, as well as its involvement in the regulation of osteoblastic differentiation by regulating the miR-335-5p/KAT7 axis. Methods The expression levels of LINC00941, miR-335-5p, KAT7 and osteoblast differentiation-related markers were assessed using RT-qPCR. The proliferation of MC3T3-E1 cells was evaluated through the CCK-8 assay, and cell apoptosis was analyzed via flow cytometry. The targeted regulatory relationships between LINC00941 and miR-335-5p, as well as between miR-335-5p and KAT7 were verified by a dual-luciferase reporter gene assay. Result The expression of LINC00941 was significantly up regulated, while miR-335-5p exhibited a notable downregulation in DFH patients, both of LINC00941 and miR-335-5p have been identified as potential predicted markers for DFH. Furthermore, LINC00941 has been demonstrated to inhibit osteoblast proliferation, promote apoptosis, and suppress osteoblast differentiation through the regulation of the miR-335-5p/KAT7 axis. Conclusion LINC00941/ miR-335-5p/KAT7 axis may be a therapeutic target for DFH.

Reversible resistive switching induced by an electric field in oxide-based resistive switching memory shows a promising application in future information storage and processing. It is believed that there are some local conductive filaments formed and ruptured in the resistive switching process. However, as a fundamental question, how electron transports in the formed conductive filament is still under debate due to the difficulty to directly characterize its physical and electrical properties. Here we investigate the intrinsic electronic transport mechanism in such conductive filament by measuring thermoelectric Seebeck effects. We show that the small-polaron hopping model can well describe the electronic transport process for all resistance states, although the corresponding temperature-dependent resistance behaviours are contrary. Moreover, at low resistance states, we observe a clear semiconductor–metal transition around 150 K. These results provide insight in understanding resistive switching process and establish a basic framework for modelling resistive switching behaviour. Oxide-based resistive switching memory is known to depend on the formation and rupture of a conducting filament, although the mechanism behind this remains debated. Here, the authors measure the Seebeck effect to understand the intrinsic electronic transport mechanism in the conducting filament.

Gasdermin E (GSDME) is known as a key executive protein of pro-inflammatory pyroptosis. However, the function diversity of GSDME needs further investigation. Here, we show that GSDME expression is downregulated in kidney tissues after cisplatin treatment without detectable N-terminal fragment. Global and tubule-specific Gsdme deficiency aggravates cisplatin-induced renal injury. Mechanistically, loss of GSDME in proximal tubular cells facilitates the recruitment of OGT to the CUL4B-DDB1-WDR26 E3 ubiquitin ligase complex, promoting OGT degradation and subsequently reducing STAT3 O-GlcNAcylation. This post-translational shift enhances STAT3 phosphorylation and induces upregulation of its downstream target gene, S100a7a . Elevated S100A7A promotes macrophage infiltration via RAGE activation, amplifying renal inflammation. Tubule-specific depleting S100a7a improves renal function and reduces renal injury and inflammation. These findings uncover a protective, non-pyroptotic function of GSDME in modulating O-GlcNAcylation and STAT3-S100A7A-RAGE signaling to maintain renal homeostasis under cisplatin stress in male mice. Gasdermin E (GSDME) is abundantly expressed, but its physiological function remains unclear. Here, the authors show a non-pyroptotic function of GSDME in limiting renal inflammation during cisplatin nephrotoxicity by regulating O-GlcNAcylation and STAT3-S100A7A-RAGE signaling.

Background Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown. Methods In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The “ESTIMATE” package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug. Results Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments. Conclusion The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.

The ponkan (Citrus reticulata Blanco cv. Ponkan), an important citrus crop, is increasingly threatened by soil acidification. This study evaluated the efficacy of various soil amendments, including lime alone (L), lime with gypsum and organic fertilizer (LGOF), lime plus K2CO3 (LK), and lime with chicken manure ash (LCMA), in mitigating soil acidification and improving ponkan seedling growth. Surface-applied lime raised topsoil pH and acid buffering capacity while reducing exchangeable Al. However, combined amendments (LGOF, LK, LCMA) more effectively alleviated acidity throughout the soil profile. They significantly increased pH and buffering capacity, decreased exchangeable H and Al in the 20–40 cm layer, and elevated exchangeable base cations (K+, Ca2+, Mg2+). These changes reduced Al content in roots, stems, and leaves, promoted deeper root growth, and increased biomass and nutrient uptake (N, P, K). Physiologically, combined amendments enhanced photosynthetic performance (chlorophyll, Pn, ΦPSII) and increased activity of key metabolic enzymes (Rubisco, SS, SPS, NR, GS), promoting sucrose, starch, and protein accumulation. LK rapidly raised subsoil pH and potassium levels, ideal for K-deficient orchards. LGOF and LCMA improved overall fertility by supplying Ca and Mg, with LGOF additionally enhancing soil structure in poorly structured acidic soils.

Background Osteoarthritis is a chronic disease mainly involving the damage of articular cartilage and the whole articular tissue, which is the main cause of disability in the elderly. To explore more effective treatment measures, this study analyzed the regulatory role and molecular mechanism of lncRNA LINC00665 (LINC00665) in the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), providing a valuable theoretical basis for the pathogenesis and patient treatment of osteoarthritis. Methods Osteoarthritis tissues and healthy tissues were obtained from 52 patients with osteoarthritis and 34 amputated patients without osteoarthritis, and the levels of LINC00665 and miR-214-3p were assessed by RT-qPCR. BMSCs were cultured and induced chondrogenic differentiation. The proliferation ability of BMSCs was detected by CCK-8 method, and the apoptosis level of BMSCs was evaluated by flow cytometry. The content of proteoglycan-glycosaminoglycan (GAG) in cartilage matrix was determined by Alcian blue staining. In addition, the binding relationship between LINC00665 and miR-214-3p was verified by luciferase reporter assay, and the molecular mechanism was further analyzed. Results In osteoarthritis tissues, LINC00665 was elevated and miR-214-3p was down-regulated. With the chondrogenic differentiation of BMSCs, the level of GAG increased, and LINC00665 expression gradually decreased, while miR-214-3p level was on the contrary. After transfection of pcDNA3.1-LINC00665 in BMSCs, cell proliferation capacity was decreased, apoptosis rate was increased, and GAG content was reduced. Moreover, LINC00665 sponged miR-214-3p and negatively regulate its expression. Transfection of pcDNA3.1-LINC00665-miR-214-3p mimic changed the regulation of pcDNA3.1-LINC00665 on the viability and chondrogenic differentiation of BMSCs. Conclusions Overexpression of lncRNA LINC00665 inhibited the proliferation and chondrogenic differentiation of BMSCs by targeting miR-214-3p. The LINC00665/miR-214-3p axis may improve joint damage and alleviate the progression of osteoarthritis.

Tumor tissues exhibit significantly lower oxygen partial pressure compared to normal tissues, leading to hypoxia in the tumor microenvironment and result in resistance to tumor treatments. Strategies to mitigate hypoxia include enhancing blood perfusion and oxygen supply, for example,by decomposing hydrogen peroxide within the tumor. Improving hypoxia in the tumor microenvironment could potentially improve the efficacy of cancer treatments. Previous studies have demonstrated that ultrasound of appropriate intensity when combined with microbubbles, can improve tumor blood perfusion. However, its effects on tumor hypoxia remain unclear. This study aimed to assess the effects of low-frequency non-focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify the optimal ultrasound parameters for alleviating tumor hypoxia. Rabbits with VX2 tumors received ultrasound and microbubble treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue blood perfusion before and after treatment were observed by contrast enhanced ultrasound (CEUS). The changes in tumor tissue hypoxia before and after treatment were observed by measuring oxygen partial pressure directly with in tumor tissue and immunohistochemical staining for hypoxia-inducible factor-1α (HIF-1α). Results indicated that low frequency, non-focused ultrasound at 0.5 MPa/20 Hz and 0.5 MPa/40 Hz, when combined with microbubbles, could increase tumor tissue blood perfusion and improve the hypoxia in tumor tissues. This study provides a new method for improving hypoxia in the tumor microenvironment (TME) which could potentially improve the cancer treatments resistance.

Objective Surgical site infection (SSI) after spinal surgery is still a persistent worldwide health concern as it is a worrying and devastating complication. The number of samples in previous studies is limited and the role of conservative antibiotic therapy has not been established. This study aims to evaluate the clinical efficacy and feasibility of empirical antibiotic treatment for suspected early‐onset deep spinal SSI. Methods We conducted a retrospective study to identify all cases with suspected early‐onset deep SSI after lumbar instrumented surgery between January 2009 and December 2018. We evaluated the potential risks for antibiotic treatment, examined the antibiotic treatment failure rate, and applied logistic regression analysis to assess the risk factors for empirical antibiotic treatment failure. Results Over the past 10 years, 45 patients matched the inclusion criteria. The success rate of antibiotic treatment was 62.2% (28/45). Of the 17 patients who failed antibiotic treatment, 16 were cured after a debridement intervention and the remaining one required removal of the internal fixation before recovery. On univariate analysis, risk factors for antibiotic treatment failure included age, increasing or persisting back pain, wound dehiscence, localized swelling, and time to SSI (cut‐off: 10 days). Multivariate analysis revealed that infection occurring 10 days after primary surgery and wound dehiscence were independent risk factors for antibiotic treatment failure. Conclusion Appropriate antibiotic treatment is an alternative strategy for suspected early‐onset deep SSI after lumbar instrumented surgery. Antibiotic treatment for suspected SSI occurring within 10 days after primary surgery may improve the success rate of antibiotic intervention. Patients with wound dehiscence have a significantly higher likelihood of requiring surgical intervention. Empirical antibiotic treatment is an alternative strategy for suspected early‐onset SSI. Wound dehiscence and infection occurring 10 days after primary surgery were highly suggested for aggressive surgical intervention. Antibiotic treatment prior to surgical debridement did not increase the difficulty of surgical intervention.

Dynamic Joule heating effect of reset process in conductive-bridge random access memory (CBRAM) was investigated theoretically. By introducing the geometry effect of conductive filament (CF), the temperature and electric field distributions in the transient state in both one-dimen-sional and three-dimensional cases were discussed in detail. We found that the CF’s geometry plays an important role in the transient Joule heating process, and the transient thermal effect turns increasingly significant with increasing applied voltage in reset procedure. The proposed position where CF ruptures is between the location of temperature peak and narrow end of the CF rather than the point of temperature peak in the cone-shaped CF system. It is more interesting that the rupture of CF possibly occurs in transient process, before steady-state is established.

BackgroundRibosomal protein L38 (RPL38) was found upregulated in osteoarthritic peripheral blood mononuclear cells, however, its role in progression of osteoarthritis has not been characterized.MethodsThe protein levels of RPL38 and SOCS2 in cartilage tissues from OA patients and controls were detected with Western blotting. IL-1β was used to stimulate primary chondrocytes to establish an OA cell model, and RPL38 siRNA (si-RPL38) was transfected into chondrocytes to investigate the effect of RPL38 knockdown on cell viability, apoptosis, inflammatory factor secretion and extracellular matrix degradation. Then, the mechanism that RPL38 regulate the SOCS2 expression and SOCS2-induced chondrocyte dysfunction was explored. The methyltransferase-like 3 (METTL3)-mediated m6A modification of SOCS2 mRNA was confirmed, and the interaction of RPL38 and METTL3 was verified. Moreover, the effects of SOCS2 overexpression on IL-1β-induced chondrocyte dysfunction and SOCS2 knockdown on the restoration of chondrocyte function by siRPL38 were investigated. Finally, RPL38 was knocked down in vivo and its role in OA progression was validated.ResultsRPL38 was upregulated and SOCS2 was downregulated in OA cartilages. RPL38 knockdown or SOCS2 overexpression either attenuated IL-1β-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation. RPL38 directly interacted with METTL3 and it inhibited SOCS2 expression through METTL3-mediated m6A modification. SOCS2 knockdown activated the JAK2/STAT3 proinflammatory pathway and reversed the effects of RPL38 knockdown on IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation. RPL38 knockdown alleviated cartilage tissue damage and ECM degradation in OA mice.ConclusionRPL38 knockdown inhibited osteoarthritic chondrocyte dysfunction and alleviated OA progression through promoting METTL3-m6A-mediated SOCS2 expression.