Double Superconducting Dome of Quasi Two-Dimensional TaS2 in Non-Centrosymmetric van der Waals Heterostructure.

Two-dimensional van der Waals heterostructures (2D-vdWHs) based on transition metal dichalcogenides (TMDs) provide unparalleled control over electronic properties. However, the interlayer coupling is challenged by the interfacial misalignment and defects, which hinders a comprehensive understanding of the intertwined electronic orders, especially superconductivity and charge density wave (CDW). Here, by using pressure to regulate the interlayer coupling of non-centrosymmetric 6R-TaS2 vdWHs, we observe an unprecedented phase diagram in TMDs. This phase diagram encompasses successive suppression of the original CDW states from alternating H-layer and T-layer configurations, the emergence and disappearance of a new CDW-like state, and a double superconducting dome induced by different interlayer coupling effects. These results not only illuminate the crucial role of interlayer coupling in shaping the complex phase diagram of TMD systems but also pave a new avenue for the creation of a novel family of bulk heterostructures with customized 2D properties.

Glaucocalyxin A delays the progression of OA by inhibiting NF-κB and MAPK signaling pathways.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint condition marked by inflammation and cartilage breakdown. Currently, there is a dearth of treatment medications that can clearly slow the course of OA. Glaucocalyxin A (GLA) is a diterpene chemical identified and extracted from Rabdosia japonica with antithrombotic, anticoagulant, anti-tumor, anti-inflammatory, anti-oxidant, and other pharmacological properties. Previous research has linked inflammation to abnormalities in the homeostasis of the extracellular matrix (ECM). Although GLA has been shown to have anti-inflammatory qualities, its effects on the progression of OA are unknown. As a result, the goal of this study was to see if GLA could slow the course of OA. METHODS: ATDC5 cells were stimulated by IL-1ß to create an inflammatory chondrocyte damage model. Quantitative polymerase chain reaction, Western Blot, high-density culture, and immunofluorescence were used to detect the expression levels of associated gene phenotypes. We also created a mouse model of OA induced by destabilization of the medial meniscus (DMM) instability, and GLA was administered intraperitoneally once every two days for eight weeks. Mice knee specimens were stained with hematoxylin-eosin, Safranin O/fast green, and immunohistochemical, and the Osteoarthritis Research Society International grade system and Mankin's score were used to assess the protective effect of GLA on cartilage. RESULTS: In vitro and in vivo, we explored the effects and molecular processes of GLA as a therapy for OA. The findings demonstrated that GLA might reduce the expression of associated inflammatory mediators and protect the ECM by inhibiting the NF-κB and MAPK signaling pathways. Animal research revealed that GLA could protect against the DMM-induced OA model mice by stabilizing ECM. CONCLUSION: Taken together, our findings show that GLA has a protective impact on cartilage throughout OA progression, implying that GLA could be employed as a possible therapeutic agent for OA, thus giving a new therapeutic method for the treatment of OA.

Perimeter monitoring of urban buried pipeline threated by construction activities based on distributed fiber optic sensing and real-time object detection.

Urban construction activities seriously jeopardize the security of buried pipeline. Distributed optical fiber vibration monitoring is one of the most promising ways to prevent third-party threats, of which the biggest challenge is to quickly and accurately detect rare abnormal events from extremely large amounts of time-space raw data. By analogy with image recognition, the task here is similar to object detection if considering the time-space optical signals as the grayscale images and the abnormal events as the objects. Given this, what we believe to be a novel monitoring method is proposed, which consists of two Faster R-CNN models, a max pooling layer and a monitoring strategy. In the field tests, the 86-hour optical vibration signals for 5.25 km distance are recognized within 6.6 minutes with the recognition rate of 98.85% for construction activities, and only two false alarms are issued. The proposed method can reduce the recognition time by 99.59% compared to the CNN-based method.

Development and validation of multiple linear regression models for predicting total hip arthroplasty acetabular prosthesis.

PURPOSE: To establish a multivariate linear equation to predict the diameter (outer diameter) of the acetabular prosthesis used in total hip arthroplasty. METHODS: A cohort of 258 individuals who underwent THA at our medical facility were included in this study. The independent variables encompassed the patients' height, weight, foot length, gender, age, and surgical access. The dependent variable in this study was the diameter of the acetabular prosthesis utilized during the surgical procedure. The entire cohort dataset was randomly partitioned into a training cohort and a validation cohort, with a ratio of 7:3, employing the SPSS 26.0 software. Pearson correlation analysis was conducted to examine the relationships between the patients' height, weight, foot length, gender, age, surgical access, and the diameter of the acetabular prosthesis in the training cohort. Additionally, a multiple linear regression equation was developed using the independent variables from the training cohort and the diameter of the acetabular prosthesis as the dependent variable. This equation aimed to predict the diameter of the acetabular prosthesis based on the patients' characteristics. The accuracy of the equation was evaluated by substituting the data of the validation cohort into the multiple linear equation. The predicted acetabular prosthesis diameters were then compared with the actual diameters used in the operation. RESULTS: The correlation analysis conducted on the training cohort revealed that surgical access (r = 0.054) and age (r = -0.120) exhibited no significant correlation with the diameter of the acetabular prosthesis utilized during the intraoperative procedure. Conversely, height (r = 0.687), weight (r = 0.654), foot length (r = 0.687), and sex (r = 0.354) demonstrated a significant correlation with the diameter of the acetabular prosthesis used intraoperatively. Furthermore, a predictive equation, denoted as Y (acetabular prosthesis diameter in mm) = 20.592 + 0.548 × foot length (cm) + 0.083 × height (cm) + 0.077 × weight (kg), was derived. This equation accurately predicted the diameter within one size with an accuracy rate of 64.94% and within two sizes with an accuracy rate of 94.81%. CONCLUSION: Anthropometric data can accurately predict the diameter of acetabular prosthesis during total hip arthroplasty.

Mechanism of lysine oxidase-like 1 promoting synovial inflammation mediating rheumatoid arthritis development.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes great distress to patients and society. Early diagnosis is the key to the successful treatment of RA. The basement membrane, one of the oldest tissue structures, is localized under the epithelium. Its complex composition and rich biological functions have made it a focus of research in recent years, while basement membrane-associated genetic variants are involved in most human disease processes. The aim of this study is to find new diagnostic biomarkers for RA and explore their role and possible mechanism in rheumatoid arthritis. The GSE12021, GSE55235 and GSE55457 datasets were downloaded from the GEO database. Their fraction associated with basement membrane genes was analyzed and differentially expressed genes between the disease and normal groups were explored. We identified two basement membrane-associated genes, lysine oxidase-like 1 (LOXL1) and discoid peptide receptor 2 (DDR2). Focusing on the more interesting LOXL1, we found that LOXL1 expression was significantly elevated in the synovium of patients with rheumatoid arthritis, and LOXL1 mRNA and protein levels were elevated in tumor necrosis factor α-stimulated human synovial sarcoma cells (SW982). And LOXL1 knockdown inhibited tumor necrosis factor α-induced inhibition in SW982 cells expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6). Interestingly, knockdown of LOXL1 inhibited the phosphorylation of PI3K and AKT. In summary, LOXL1 may become a novel diagnostic gene for RA, and knockdown of LoxL1 may inhibit synovial inflammation by affecting PI3K/AKT pathway.

The TGFß1/SMADs/Snail1 signaling axis mediates pericyte-derived fibrous scar formation after spinal cord injury.

AIMS: The deposition of fibrous scars after spinal cord injury (SCI) affects axon regeneration and the recovery of sensorimotor function. It has been reported that microvascular pericytes in the neurovascular unit are the main source of myofibroblasts after SCI, but the specific molecular targets that regulate pericyte participation in the formation of fibrous scars remain to be clarified. METHODS: In this study, a rat model of spinal cord dorsal hemisection injury was used. After SCI, epigallocatechin gallate (EGCG) was intraperitoneally injected to block the TGFß1 signaling pathway or LV-Snail1-shRNA was immediately injected near the core of the injury using a microsyringe to silence Snail1 expression. Western blotting and RT-qPCR were used to analyze protein expression and transcription levels in tissues. Nissl staining and immunofluorescence analysis were used to analyze neuronal cell viability, scar tissue, and axon regeneration after SCI. Finally, the recovery of hind limb function after SCI was evaluated. RESULTS: The results showed that targeted inhibition of Snail1 could block TGFß1-induced pericyte-myofibroblast differentiation in vitro. In vivo experiments showed that timely blockade of Snail1 could reduce fibrous scar deposition after SCI, promote axon regeneration, improve neuronal survival, and facilitate the recovery of lower limb motor function. CONCLUSION: In summary, Snail1 promotes the deposition of fibrous scars and inhibits axonal regeneration after SCI by inducing the differentiation of pericytes into myofibroblasts. Snail1 may be a promising therapeutic target for SCI.

ADRM1/RPN13 attenuates cartilage extracellular matrix degradation via enhancing UCH37-mediated ALK5 deubiquitination.

Osteoarthritis (OA) is the most common age-related joint disorder with no effective therapy, and its specific pathological mechanism remains to be fully clarified. Adhesion-regulating molecule 1 (ADRM1) has been proven to be involved in OA progression as a favorable gene. However, the exact mechanism of ADRM1 involved in OA were unknown. Here, we showed that the ADRM1 expression decreased in human OA cartilage, destabilization of the medial meniscus (DMM)-induced mouse OA cartilage, and interleukin (IL)-1ß-induced primary mouse articular chondrocytes. Global knockout (KO) ADRM1 in cartilage or ADRM1 inhibitor (RA190) could accelerate the disorders of extracellular matrix (ECM) homeostasis, thereby accelerated DMM-induced cartilage degeneration, whereas overexpression of ADRM1 protected mice from DMM-induced OA development by maintaining the homeostasis of articular cartilage. The molecular mechanism study revealed that ADRM1 could upregulate ubiquitin carboxy-terminal hydrolase 37 (UCH37) expression and bind to UCH37 to activate its deubiquitination activity. Subsequently, increased and activated UCH37 enhanced activin receptor-like kinase 5 (ALK5) deubiquitination to stabilize ALK5 expression, thereby maintaining ECM homeostasis and attenuating cartilage degeneration. These findings indicated that ADRM1 could attenuate cartilage degeneration via enhancing UCH37-mediated ALK5 deubiquitination. Overexpression of ADRM1 in OA cartilage may provide a promising OA therapeutic strategy.

Identification of several inflammation-related genes based on bioinformatics and experiments.

BACKGROUND: Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in osteoarthritis, thereby making anti-inflammatory treatments promising in clinical outcomes. Therefore, it is of diagnostic and therapeutic significance to explore more inflammatory genes. METHOD: In this study, appropriate datasets were first acquired through gene set enrichment analysis (GSEA), followed by inflammation-related genes through weighted gene coexpression network analysis (WGCNA). Two machine learning algorithms (random forest-RF and support vector machine-recursive feature elimination, SVM-RFE) were used to capture the hub genes. In addition, two genes negatively associated with inflammation and osteoarthritis were identified. Afterwards, these genes were verified through experiments and network pharmacology. Due to the association between inflammation and many diseases, the expression levels of the above genes in various inflammatory diseases were determined through literature and experiments. RESULT: Two hub genes closely related to osteoarthritis and inflammation were obtained, namely, lysyl oxidase-like 1 (LOXL1) and pituitary tumour-transforming gene (PTTG1), which were shown to be highly expressed in osteoarthritis according to the literature and experiments. However, the expression levels of receptor expression-enhancing protein (REEP5) and cell division cycle protein 14B (CDC14B) remained unchanged in osteoarthritis. This finding was consistent with our verification from the literature and experiments that some genes were highly expressed in numerous inflammation-related diseases, while REEP5 and CDC14B were almost unchanged. Meanwhile, taking PTTG1 as an example, we found that inhibition of PTTG1 expression could suppress the expression of inflammatory factors and protect the extracellular matrix through the microtubule-associated protein kinase (MAPK) signalling pathway. CONCLUSIONS: LOXL1 and PTTG1 were highly expressed in some inflammation-related diseases, while that of REEP5 and CDC14B were almost unchanged. PTTG1 may be a potential target for the treatment of osteoarthritis.

Secoisolariciresinol diglucoside Ameliorates Osteoarthritis via Nuclear factor-erythroid 2-related factor-2/ nuclear factor kappa B Pathway: In vitro and in vivo experiments.

Osteoarthritis (OA) is an age-related joint disease in which inflammation and extracellular matrix (ECM) degradation play a crucial role in the destruction of articular cartilage. Secoisolariciresinol diglucoside (SDG), the main lignan in wholegrain flaxseed, which has been reported to remarkably suppress inflammation and oxidative stress, may have potential therapeutic value in OA. In this study, the effect and mechanism of SDG against cartilage degeneration were verified in the destabilization of the medial meniscus (DMM) and collagen-induced (CIA) arthritis models and interleukin-1ß (IL-1ß)-stimulated osteoarthritis chondrocyte models. From our experiments, SDG treatment downregulated the expression of pro-inflammatory factors induced by IL-1ß in vitro, including inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Additionally, SDG promoted the expression of collagen II (COL2A1) and SRY-related high-mobility-group-box gene 9(SOX9), while suppressing the expression of a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5) and matrix metalloproteinases 13(MMP13), which leads to catabolism. Consistently, in vivo, SDG has been identified to have chondroprotective effects in DMM-induced and collagen-induced arthritis models. Mechanistically, SDG exerted its anti-inflammation and anti-ECM degradation effects by activating the Nrf2/HO-1 pathway and inhibiting the nuclear factor kappa B (NF-κB) pathway. In conclusion, SDG ameliorates the progression of OA via the Nrf2/NF-κB pathway, which indicates that SDG may have therapeutic potential for OA.

Transoropharyngeal closed reduction for traumatic atlantoaxial dislocation: a novel technique for fast and precise reduction.

PURPOSE: The aim of this study is to introduce a new technique for the rapid and accurate reduction of traumatic atlantoaxial dislocation (TAAD) and to investigate its radiological and clinical outcomes. METHODS: The clinical outcomes of 18 patients who were diagnosed with acute TAAD and underwent rapid transoropharyngeal closed reduction in our hospital were retrospectively analyzed from January 2015 to December 2020. Following general anaesthesia, all patients were immediately treated with oropharyngeal reduction under somatosensory evoked potential monitoring. The Japanese Orthopedic Association score, neck disability index and visual analog scale score for neck pain were used to evaluate clinical efficacy. Atlantodental distance, posterior atlantodental interval, and the clivus-canal angle were used to assess reduction and spinal cord compression. RESULTS: The mean follow-up time was 23.3 months, with a range of 13-38 months. No neurovascular injury occurred during the operations. For all patients, the closed reduction method through the oropharynx under general anaesthesia was successful, and the success rate of reduction was 100%. All patients recovered uneventfully with marked improvement in clinical outcomes and imaging parameters (P < 0.01). Two patients developed mild postoperative dysphagia. One patient developed postoperative fever and pulmonary infection. CONCLUSION: Rapid trans-oropharyngeal closed reduction can safely, effectively, and rapidly reduce acute TAAD. This method provides a new strategy for treatment of the condition.

A comprehensive pan-cancer analysis unveiling the oncogenic effect of plant homeodomain finger protein 14 (PHF14) in human tumors.

The plant homeodomain (PHD) finger refers to a protein motif that plays a key role in the recognition and translation of histone modification marks by promoting gene transcriptional activation and silencing. As an important member of the PHD family, the plant homeodomain finger protein 14 (PHF14) affects the biological behavior of cells as a regulatory factor. Several emerging studies have demonstrated that PHF14 expression is closely associated with the development of some cancers, but there is still no feasible pan-cancer analysis. Based on existing datasets from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we performed a systematic analysis of the oncogenic role of the PHF14 gene in 33 human cancers. The expression level of PHF14 was significantly different between different types of tumors and adjacent normal tissues, and the expression or genetic alteration of PHF14 gene was closely related to the prognosis of most cancer patients. Levels of cancer-associated fibroblasts (CAFs) infiltration in various cancer types were also observed to correlate with PHF14 expression. In some tumors, PFH14 may play a role in tumor immunity by regulating the expression levels of immune checkpoint genes. In addition, the results of enrichment analysis showed that the main biological activities of PHF14 were related to various signaling pathways or chromatin complex effects. In conclusion, our pan-cancer research shows that the expression level of PHF14 is closely related to the carcinogenesis and prognosis of certain tumors, which needs to be further verified by more experiments and more in-depth mechanism exploration.

Modulating Charge-Density Wave Order and Superconductivity from Two Alternative Stacked Monolayers in a Bulk 4Hb-TaSe2 Heterostructure via Pressure.

Two-dimensional (2D) van der Waals heterostructures (VDWHs) containing a charge-density wave (CDW) and superconductivity (SC) have revealed rich tunability in their properties, which provide a new route for optimizing their novel exotic states. The interaction between SC and CDW is critical to its properties; however, understanding this interaction within VDWHs is very limited. A comprehensive in situ study and theoretical calculation on bulk 4Hb-TaSe2 VDWHs consisting of alternately stacking 1T-TaSe2 and 1H-TaSe2 monolayers are investigated under high pressure. Surprisingly, the superconductivity competes with the intralayer and adjacent-layer CDW order in 4Hb-TaSe2, which results in substantially and continually boosted superconductivity under compression. Upon total suppression of the CDW, the superconductivity in the individual layers responds differently to the charge transfer. Our results provide an excellent method to efficiently tune the interplay between SC and CDW in VDWHs and a new avenue for designing materials with tailored properties.

Surfactin suppresses osteoclastogenesis via the NF-κB signaling pathway, promotes osteogenic differentiation in vitro, and inhibits oestrogen deficiency-induced bone loss in vivo.

BACKGROUND: Fractures caused by osteoporosis (OP) are one of the main causes of death in the elderly, bringing a heavy burden to the country and society. The imbalance between osteoblast-mediated osteogenesis and osteoclast-mediated bone resorption is an important cause of OP. Therefore, finding drugs that can regulate this dynamic balance can be an important way to treat osteoporosis. Surfactin is a highly effective biosurfactant derived from Bacillus subtilis and it has been proven to have various pharmacological effects in previous studies, but its effect on bone metabolism remains unknown. Here, we performed a study on the role and mechanism of Surfactin in inhibiting osteoclastogenesis and its possible mechanism as well as the role in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: We investigated the effect of Surfactin on osteoclast differentiation and osteogenic differentiation in vitro and in vivo. The effect of Surfactin on the activity of osteoclastogenesis and osteogenesis was verified by CCK-8 assay, quantitative Real-time polymerase chain reaction (qPCR) and Western blotting analysis were used to verify the effect of Surfactin on osteoclast and osteogenic differentiation-specific genes and proteins. The effect of Surfactin on TRAP、ALP activity and mineral deposition was verified by TRAP、ALP and ARS staining. We then used an ovariectomy-induced osteoporosis mice model to observe the effect of Surfactin in vivo. RESULTS: Surfactin is noncytotoxic to BMMs, RAW264.7, and BMSCs. And it can effectively inhibit osteoclastogenesis and promote osteogenic differentiation. Moreover, we found that Surfactin can inhibit the differentiation of osteoclasts through the NF-κB signaling pathway. Surfactin can also alleviate bone loss in ovariectomy-induced osteoporosis mice. CONCLUSIONS: Our results suggest that Surfactin can inhibit osteoclastogenesis through the NF-κB signaling pathway, promote the osteogenic differentiation of BMSCs, and also can effectively alleviate bone loss in ovariectomy-induced osteoporosis mice.

lncRNA SERPINB9P1 Regulates SIRT6 Mediated Osteogenic Differentiation of BMSCs via miR-545-3p.

Evidence has shown that the altered osteogenic differentiation of human bone marrow stromal cells (BMSCs) under pathological conditions, such as osteoporosis, lead to the imbalance of bone tissue generation and destruction. Recent studies have indicated that long noncoding RNAs may play a role in regulating BMSCs osteogenic differentiation. This contributed to our impetus to move forward with the investigation of the function of lncRNA SERPINB9P1 in osteogenic differentiation of BMSCs and the potential mechanisms involved. Osteogenic differentiation of BMSCs was induced by osteogenic medium. Relative expression of lncRNA SERPINB9P1 and miR-545-3p were tested by qRT-PCR. Osteogenic mineralization was examined by Alizarin S Red staining, ALP staining, and ALP activity assay. Expression of osteoblastic markers were detected by Western blot. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays were performed to test the interaction between lncRNA SERPINB9P1 and miR-545-3p. BMSCs osteogenic differentiation resulted in LncRNA SERPINB9P1 overexpression while miR-545-3p inhibition. Functional assays suggest that knockdown of lncRNA SERPINB9P1 or overexpression of miR-545-3p both inhibit BMSC osteogenic differentiation. lncRNA SERPINB9P1 was proven to regulate the osteogenic differentiation of BMSCs by altering SIRT6 expression through its suppressive effects on miR-545-3p. lncRNA SERPINB9P1 promotes osteogenic differentiation of BMSCs through the miR-545-3p/SIRT6 pathway.

Targeted inhibition of TXNRD1 prevents cartilage extracellular matrix degeneration by activating Nrf2 pathway in osteoarthritis.

Osteoarthritis, a prevalent orthopedic disease, can affect the elderly and causes impairment. The degradation and aberrant homeostasis of cartilage extracellular matrix figure pivotally in the progression of osteoarthritis. Thioredoxin systems plays a role in a wide range of biological processes, including cell proliferation, apoptosis, and oxidative stress. The present study aimed to investigate the unique function and underlying pathophysiological mechanism of TXNRD1 in chondrocytes. An upregulated expression of TXNRD1 was observed in the articular cartilage of osteoarthritis patients compared with normal articular cartilage. Furthermore, in vitro experiments showed that the expression of TXNRD1 was also abnormally increased in IL-1ß-induced primary mouse chondrocytes. Silencing TXNRD1 using siRNA in chondrocytes could effectively inhibit the expression of ADAMTS5 and MMP13, and enhance the expression of COL2A1 and SOX9. The same was true for auranofin, an inhibitor of TXNRD1. This phenomenon indicated that inhibition of TXNRD1 attenuated il-1ß-induced metabolic imbalance of extracellular matrix (ECM) and the progression of chondrocyte osteoarthritis. Further mechanism analysis revealed that the activation of Nrf2 signaling pathway and the expression of heme oxygenase-1 (HO-1) were increased upon TXNRD1 inhibition. Furthermore, auranofin was found to attenuate DMM-induced osteoarthritis progression in vivo. Therefore, the pharmacological downregulation of TXNRD1 may provide an effective novel therapy for OA.

Development and validation of a prognostic nomogram for bone metastasis from lung cancer: A large population-based study.

Background: Bone is one of the most common metastatic sites of advanced lung cancer, and the median survival time is significantly shorter than that of patients without metastasis. This study aimed to identify prognostic factors associated with survival and construct a practical nomogram to predict overall survival (OS) in lung cancer patients with bone metastasis (BM). Methods: We extracted the patients with BM from lung cancer between 2011 and 2015 from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regressions were performed to identify independent prognostic factors for OS. The variables screened by multivariate Cox regression analysis were used to construct the prognostic nomogram. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results: A total of 7861 patients were included in this study and were randomly divided into training (n=5505) and validation (n=2356) cohorts using R software in a ratio of 7:3. Cox regression analysis showed that age, sex, race, grade, tumor size, histological type, T stage, N stage, surgery, brain metastasis, liver metastasis, chemotherapy and radiotherapy were independent prognostic factors for OS. The C-index was 0.723 (95% CI: 0.697-0.749) in the training cohorts and 0.738 (95% CI: 0.698-0.778) in the validation cohorts. The AUC of both the training cohorts and the validation cohorts at 3-month (0.842 vs 0.859), 6-month (0.793 vs 0.814), and 1-year (0.776 vs 0.788) showed good predictive performance, and the calibration curves also demonstrated the reliability and stability of the model. Conclusions: The nomogram associated with the prognosis of BM from lung cancer was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.

Pressure Engineering Promising Transparent Oxides with Large Conductivity Enhancement and Strong Thermal Stability.

Transparent conducting oxides (TCO) with high electrical conductivity and high visible light transparency are desired for a wide range of high-impact engineering. Yet, usually, a compromise must be made between conductivity and transparency, limiting the practical application of a TCO to the next level. Furthermore, TCO performance is highly sensitive to composition, so conventional synthesis methods, such as chemical doping, cannot unravel the mysteries of the quantitative structure-performance relationship. Thus, improving the fundamental understanding or creating materials-by-design has limited success. Here, a strategy is proposed to modulate the lattice and electronic and optical properties precisely by applying pressure on a TCO. Strikingly, after compression-decompression treatment on the indium titanium oxides (ITiO), a highly transparent and metastable phase with two orders of magnitude enhancement in conductivity is synthesized from an irreversible phase transition. Moreover, this phase possesses previously unattainable filter efficiency on hazardous blue light up to 600 °C, providing potential for healthcare-related applications with strong thermal stability up to 200 °C. These results demonstrate that pressure engineering is a clean and effective tool for tailoring functional materials that are not achievable by other means, providing an exciting alternative property-tuning dimension in materials science.

Exosomal CTCF Confers Cisplatin Resistance in Osteosarcoma by Promoting Autophagy via the IGF2-AS/miR-579-3p/MSH6 Axis.

Cancer-derived exosomes participate in carcinogenesis and progression of cancers, including metastasis and drug-resistance. Of note, CTCF has been suggested to induce drug resistance in various cancers. Herein, we aim to investigate the role of cisplatin- (CDDP-) resistant osteosarcoma- (OS-) derived exosomal CTCF in OS cell resistance to CDDP and its mechanistic basis. Differentially expressed transcription factors, long noncoding RNAs (lncRNAs), miRNAs, and genes in OS were retrieved using bioinformatics approaches. Exosomes were extracted from CDDP-resistant OS cells and then cocultured with parental OS cells, followed by lentiviral transduction to manipulate the expression of CTCF, IGF2-AS, miR-579-3p, and MSH6. We assessed the in vitro and in vivo effects on malignant phenotypes, autophagy, CDDP sensitivity, and tumor formation of OS cells. It was established that CTCF and IGF2-AS were highly expressed in CDDP-resistant OS cells, and the CDDP-resistant OS cell-derived exosomal CTCF enhanced IGF2-AS transcription. CDDP-resistant OS-derived exosomes transmitted CTCF to OS cells and increased CDDP resistance in OS cells by activating an autophagy-dependent pathway. Mechanistically, CTCF activated IGF2-AS transcription and IGF2-AS competitively bound to miR-579-3p to upregulate MSH6 expression. Additionally, the promoting function of exosomal CTCF-mediated IGF2-AS/miR-579-3p/MSH6 in OS cell resistance to CDDP was confirmed in vivo. Taken together, CDDP-resistant OS-derived exosomal CTCF enhanced resistance of OS cells to CDDP via activating the autophagy-dependent pathway, providing a potential therapeutic consideration for OS treatment.

Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo.

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

A web-based calculator for predicting the prognosis of patients with sarcoma on the basis of antioxidant gene signatures.

BACKGROUND: Oxidative stress plays a critical role in tumorigenesis, tumor development, and resistance to therapy. A systematic analysis of the interactions between antioxidant gene expression and the prognosis of patients with sarcoma is lacking but urgently needed. METHODS: Gene expression and clinical data of patients with sarcoma were derived from The Cancer Genome Atlas Sarcoma (training cohort) and Gene Expression Omnibus (validation cohorts) databases. Least absolute shrinkage, selection operator regression, and Cox regression were used to develop prognostic signatures for overall survival (OS) and disease-free survival (DFS). Based on the signatures and clinical features, two nomograms for predicting 2-, 4-, and 6-year OS and DFS were established. RESULTS: On the basis of the training cohort, we identified five-gene (CHAC2, GPX5, GSTK1, PXDN, and S100A9) and six-gene (GGTLC2, GLO1, GPX7, GSTK1, GSTM5, and IPCEF1) signatures for predicting OS and DFS, respectively, in patients with sarcoma. Kaplan-Meier survival analysis of the training and validation cohorts revealed that patients in the high-risk group had a significantly poorer prognosis than those in the low-risk group. On the basis of the signatures and other independent risk factors, we established two models for predicting OS and DFS that showed excellent calibration and discrimination. For the convenience of clinical application, we built web-based calculators (OS: https://quankun.shinyapps.io/sarcDFS/). CONCLUSIONS: The antioxidant gene signature models established in this study can be novel prognostic predictors for sarcoma.