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Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed to examine the inhibitory effect of metformin in osteosarcoma. Herein, we demonstrated that metformin treatment blocked proliferation progression by causing accumulation of G2/M phase in U2OS and 143B cells. Furthermore, metformin treatment triggered programmed cell death process in osteosarcoma cell lines. Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125. Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment. Lastly, metformin could inhibit osteosarcoma growth under safe dose . Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma. This metformin-induced pathway provides further insights into its antitumor potential molecular mechanism and illuminates potential cancer targets for osteosarcoma.

Kalman smoothing algorithms are widely used in offline data processing in target tracking systems to improve filter calculations accuracy. The essence is weight averaging in forward and backward Kalman filters. When there is an abnormal dynamic model in the system, the adaptive Kalman filter algorithm can reduce its impact on the filter results to a certain extent. Nevertheless, because there are various methods for selecting adaptive factors and all of them are complicated, it is difficult to select the optimal adaptive factors. Therefore, the forward filter and backward filter results are suboptimal when a dynamic model abnormality occurs, which, in turn, causes the smoothing accuracy to decrease after the weighted average before and after this abnormality. We propose an improved forward and backward adaptive smoothing (IFBAS) algorithm. During the smoothing process, adaptive factors of the forward adaptive Kalman filter and the backward adaptive Kalman filter are used to modify the covariance information twice to reduce the influence of suboptimal filter information on smoothing accuracy. We apply the IFBAS algorithm to the GPS/INS integrated navigation system and data postprocessing of the GNSS network. The results of simulation experiments and time series of IGS station analysis examples show that the IFBAS algorithm can effectively suppress the influence of abnormal dynamic models and improve smoothing accuracy.

The South-to-North Water Diversion Project in China is the world’s largest water transfer project, aiming to address water shortages in northern China by channeling water from the water-rich southern regions. Water resources in Tianjin have long been in severe deficit, with excessive groundwater extraction causing significant surface subsidence, negatively impacting urban infrastructure and economic development. As a result, Tianjin has become a key beneficiary of this water diversion project. To investigate the current situation of surface subsidence, we obtained the vertical displacement time series from 21 GNSS stations across Tianjin from 2011 to 2021 and analyzed overall subsidence changes and rehabilitation status. Results indicate that no clear surface subsidence was observed in the northern regions of Tianjin due to groundwater extraction mainly in unconfined aquifers. The southwestern region experienced the most significant surface subsidence due to overexploitation of deep groundwater, with peak cumulative subsidence exceeding 600 mm during the study period. The central, eastern, and southeastern coastal regions also faced severe surface subsidence with cumulative amounts ranging from 100 mm to 400 mm. The alleviation of subsidence predominantly benefits from continuous water supply from the South to North Water Diversion Project, which resulted in most stations significantly slowing down or even stabilizing their settlement rates after 2018. Therefore, the South-to-North Water Diversion Project plays a crucial role in addressing the persistent water resource shortage and mitigating long-term surface subsidence in Tianjin by ensuring a continuous water supply and significantly reducing the need for groundwater extraction. Our findings indicate positive measures, such as water diversion projects and water management policies, can serve as valuable references for other regions around the world facing similar water scarcity and groundwater overexploitation.

No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma. We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18–75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn, ChiCTR-OIC-17013586. Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4–19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0–11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3–43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3–34) according to RECIST and 18 months (3–33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed. To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma. None.

Background Breast cancer is the most common malignancy among women worldwide, characterized by complex molecular and cellular heterogeneity. Despite advances in diagnosis and treatment, there is an urgent need to identify reliable biomarkers and therapeutic targets to improve early detection and personalized therapy. The OAS (2′-5′-oligoadenylate synthetase) family genes, known for their roles in antiviral immunity, have emerged as potential regulators in cancer biology. This study aimed to explore the diagnostic and functional relevance of OAS family genes in breast cancer. Methodology Breast cancer cell lines and controls were cultured under specific conditions, and DNA and RNA were extracted for downstream analyses. RT-qPCR, bisulfite sequencing, and Western blotting were employed to assess gene expression, promoter methylation, and knockdown efficiency of OAS family genes. Functional assays, including CCK-8, colony formation, and wound healing, evaluated cellular behaviors, while bioinformatics tools (UALCAN, GEPIA, HPA, OncoDB, cBioPortal, and others) validated findings and explored correlations with clinical data. Results The OAS family genes (OAS1, OAS2, OAS3, and OASL) were found to be significantly upregulated in breast cancer cell lines and tissues compared to normal controls. This overexpression was strongly associated with reduced promoter methylation. Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy, with area under the curve (AUC) values exceeding 0.93 for all four genes. Increased OAS expression correlated with advanced cancer stages and poor overall survival in breast cancer patients. Functional analysis revealed their involvement in critical biological processes, including immune modulation and oncogenic pathways. Silencing OAS genes in breast cancer cells significantly inhibited cell proliferation and colony formation, while unexpectedly enhancing migratory capacity. Additionally, correlations with immune cell infiltration, molecular subtypes, and drug sensitivity highlighted their potential roles in the tumor microenvironment and therapeutic response. Conclusion The findings of this study established OAS family genes as potential biomarkers and key players in breast cancer progression, offering promise as diagnostic biomarkers and therapeutic targets to address unmet clinical needs.

Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro‐bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra‐articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra‐small size (≈5 nm) selenium‐doped carbon quantum dots (Se‐CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP‐Se‐CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro‐bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H‐vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra‐small quantum dots facilitate the efficient penetration of articular SB and regulate chondro‐bone metabolism for OA treatment. Restoring chondro‐bone balance is crucial for OA treatment. Traditional intra‐articular injections cannot directly break through the cartilage barrier to reach subchondral bone. SCT@AHAMA microspheres is developed by combining Se‐CQDs with TPP and AHAMA. These micro/nano hydrogel microspheres, containing ultra‐small quantum dots, efficiently penetrate subchondral bone and regulate chondro‐bone metabolism, offering potential osteoarthritis treatment.

In this paper, a deep learning-based traffic state discrimination method is proposed to detect traffic congestion at urban intersections. The detection algorithm includes two parts, global speed detection and a traffic state discrimination algorithm. Firstly, the region of interest (ROI) is selected as the road intersection from the input image of the You Only Look Once (YOLO) v3 object detection algorithm for vehicle target detection. The Lucas-Kanade (LK) optical flow method is employed to calculate the vehicle speed. Then, the corresponding intersection state can be obtained based on the vehicle speed and the discrimination algorithm. The detection of the vehicle takes the position information obtained by YOLOv3 as the input of the LK optical flow algorithm and forms an optical flow vector to complete the vehicle speed detection. Experimental results show that the detection algorithm can detect the vehicle speed and traffic state discrimination method can judge the traffic state accurately, which has a strong anti-interference ability and meets the practical application requirements.

Background Low temperature is a limiting factor of rice productivity and geographical distribution. Wild rice ( Oryza rufipogon Griff.) is an important germplasm resource for rice improvement. It has superior tolerance to many abiotic stresses, including cold stress, but little is known about the mechanism underlying its resistance to cold. Results This study elucidated the molecular genetic mechanisms of wild rice in tolerating low temperature. Comprehensive transcriptome profiles of two rice genotypes (cold-sensitive ce 253 and cold-tolerant Y12–4) at the germinating stage under cold stress were comparatively analyzed. A total of 42.44–68.71 million readings were obtained, resulting in the alignment of 29,128 and 30,131 genes in genotypes 253 and Y12–4, respectively. Many common and differentially expressed genes (DEGs) were analyzed in the cold-sensitive and cold-tolerant genotypes. Results showed more upregulated DEGs in the cold-tolerant genotype than in the cold-sensitive genotype at four stages under cold stress. Gene ontology enrichment analyses based on cellular process, metabolic process, response stimulus, membrane part, and catalytic activity indicated more upregulated genes than downregulated ones in the cold-tolerant genotype than in the cold-sensitive genotype. Quantitative real-time polymerase chain reaction was performed on seven randomly selected DEGs to confirm the RNA Sequencing (RNA-seq) data. These genes showed similar expression patterns corresponding with the RNA-Seq method. Weighted gene co-expression network analysis (WGCNA) revealed Y12–4 showed more positive genes than 253 under cold stress. We also explored the cold tolerance gene LTG5 (Low Temperature Growth 5) encoding a UDP-glucosyltransferase. The overexpression of the LTG5 gene conferred cold tolerance to indica rice. Conclusion Gene resources related to cold stress from wild rice can be valuable for improving the cold tolerance of crops.

We introduce a new hydrological index that enables assessment of extreme events every few days from the GRACE Follow‐On (GRACE‐FO) satellite mission. The Mass Change Index (MCI) was developed by standardizing instantaneous satellite gravity anomalies computed directly from orbit perturbations. It is based on hydrology‐related gravity change, namely, total water storage change, and thus equally sensitive to wet and dry anomalies. The key innovation of MCI is its sensitivity to instantaneous mass changes as opposed to monthly mean changes. GRACE‐FO's ground track permits MCI retrievals every 5–6 days in most low and mid latitude regions. We demonstrate the application of MCI to investigate hydrological extremes in the middle‐lower Yangtze River Basin (MLYRB). MCI detects extreme wet conditions (standardized index of 2.0–3.0) along the Yangtze River mainstream related to the catastrophic flood in 2020, consistent with daily streamflow observations. In contrast, a typical GRACE‐FO based monthly drought index significantly underestimates the severity of the event and misidentifies timing of the onset. MCI also detects extreme dry conditions (−2.0 to −2.5) prevailing within MLYRB, related to the unprecedented heatwave and drought event during the summer of 2022. A streamflow index and the monthly drought index both underestimate the severity of the event. MCI retains information in intersatellite range measurements that may be lost when processing monthly gravity solutions. It can also be processed more rapidly, increasing its potential value for hydrological monitoring systems and other operational applications.

Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional landscape of CS and the mechanisms by which key genes contribute to chemotherapy resistance could be a crucial step in overcoming this challenge. To address this, we developed a single-cell transcriptional map of CS, comparing it with OS and normal cancellous bone. Our analysis revealed a specific increase in KDEL receptor 1 (KDELR1) expression in CS, which was closely associated with CS prognosis, tumor aggressiveness, and drug resistance. KDELR1 plays a key role in regulating membrane protein processing and secretion, as well as contributing to tumor extracellular matrix (ECM) formation and drug resistance. Further investigation using mass spectrometry proteomics and transcriptomics uncovered KDELR1’s involvement in modulating the Hippo-YAP pathway activity in CS cells. The KDELR1-Integrin-PLCγ-YAP1 axis emerges as a critical process mediating drug resistance and malignant behavior in CS, offering novel insights and potential therapeutic targets for CS treatment.