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Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.

Sewer networks (SNs) are susceptible to various factors that can lead to failures, resulting in economic losses and environmental pollution. Data-driven approaches based on sewage flow monitoring enhance the awareness and maintenance capabilities of SNs. However, the current research lacks early warning systems for flow anomalies. This presents a challenge for the application of supervised methods, primarily due to the scarcity of anomalous flow datasets. Even with the availability of such datasets, the effectiveness of these methods may vary due to environmental differences, since SNs are situated in diverse environments. Therefore, effectively achieving early warnings for anomalies in unlabeled flow data is a challenge that must be addressed in the field of flow monitoring. To address this challenge, we propose a detection method for effectively warning of anomalies in flow data. Since anomalies typically result in significant deviations from normal data, early warnings can be achieved by comparing the differences between current and historical data. The key to this early warning lies in establishing an adaptive threshold for detecting abnormal data changes. Our detection method employs an unsupervised bagging-based multi-anomaly detection algorithm to detect such abnormal data changes. Experiments conducted on Erhai Lake SNs flow data demonstrate that our method can predict anomalies 5-15 minutes in advance with a precision of 80.00%, a recall of 66.67%, and an F1 score of 0.73. Our approach not only achieves cost-effective and timely anomalies detection but also overcomes the challenges associated with limited dataset availability, making it applicable to various other industries.

Abstract Background Inflammation and immunity are two main characteristics of tumor microenvironment (TME). Interferon-gamma (IFN-γ) is generally considered as a pro-inflammatory cytokine which mediates anti-tumor immune response. Recently, IFN-γ was also reported to play a protumorigenic role. However, the mechanisms of tumor-promoting effect induced by IFN-γ remain unclear. Methods The expression of leukocyte antigen-E (HLA-E), IFN-γ, CD3 and CD56 in clinical samples of ovarian cancer was detected by mutiplexed immunohistochemistry. The mechanism to induce HLA-E overexpression by IFN-γ was explored using human ovarian cancer cell lines through western blot and flow cytometry. We further clarify the role of overexpressed-HLA-E on natural killer (NK)-mediated cell lysis. Results We found that IFN-γ could upregulate HLA-E protein expression through activating of JAK/STAT1 signaling pathway, and increase cell surface HLA-E level through enhancing proteasome activity. We also observed that only high levels of membrane HLA-E expression contributed to the inhibition of NK-mediated cytotoxicity. We showed that progression-free survival (PFS) of ovarian cancer patients was negatively correlated with IFN-γ expression in their tumor tissues, due to more tumor infiltrating NK cells compared with T lymphocytes. Conclusions Our study revealed the protumorigenic role of IFN-γ by upregulation of HLA-E expression and rendering tumors less susceptible to immune attack. We also provided a novel insight into the relationship between tumor microenvironment and immune evasion.

In order to evaluate the recognition effect of different clustering algorithms on thunderstorm system, further improve the ability of lightning nowcasting, in this study, with the ground-based lightning location data and radar reflectivity data, three different clustering algorithms for thunderstorm identification are analyzed for a thunderstorm case in the region of 114°-117°E, 27°-30°N and during the time window of 19∶15 BT to 20∶57 BT on 21 September, 2018. The performance of these three algorithms, which are density-based spatial clustering of application with noise (DBSCAN), clustering by fast search and find of density peaks (CFSFDP) and extended clustering by fast search and find of density peaks (E_CFSFDP) are compared and discussed. Here are the results. (1) The DBSCAN algorithm has a higher accuracy of classification and identification when the distributions of lightning location show clear patterns and different clusters are apart from each other, but the accuracy will be low when the density of each lightning data cluster is uneven or the distances between different clusters are very large. (2) the CFSFDP algorithm works when each cluster in the data sets has one single density peak, otherwise, when there are no density peaks, CFSFDP will be failed. (3) The E_CFSFDP algorithm can solve the "no density peaks" issue of the CFSFDP algorithm, and the distribution of lightning location has little effect on the clustering method. Generally, the accuracy of the thunderstorm identification based on the E_CFSFDP algorithm is significantly higher than that of the DBSCAN and CFSFDP algorithms.

Abstract Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the “direct” reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0–4.0 nm. They exhibited well-separated dual emission in the visible region (500–590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from − 23.9 to − 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.

Abstract Breast cancer is one of the leading causes of mortality among women. Triple-negative breast cancer (TNBC) is responsible for a large percentage of all breast cancer deaths in women. This study demonstrated the function of Myb-like, SWIRM, and MPN domains 1 (MYSM1), an H2A deubiquitinase (DUB), in TNBC. MYSM1 expression was drastically decreased in breast cancer, especially in TNBC, suggesting a potential anticancer effect. Overexpressing and suppressing MYSM1 expression in TNBC cell lines led to significant biological changes in cell proliferation. Furthermore, MYSM1 overexpression increased cisplatin-induced apoptosis, which might be attributed to RSK3 inactivation and the subsequently decreased phosphorylation of Bcl-2 antagonist of cell death (BAD) (Ser 112). The findings suggest that MYSM1 is a potential target for regulating cell apoptosis and suppressing resistance to cisplatin in TNBC.

Abstract Background Drug resistance and recurrence are main contributors to the poor prognosis of ovarian cancer. Cisplatin is a platinum compound which is widely used in the treatment of various solid tumors including ovarian cancer. Up to now, the mechanism of cisplatin resistance in ovarian cancer is unclear. Threonine and tyrosine kinase (TTK), an integral part of the spindle assembly checkpoint, may be a potential new target associated with chemotherapy sensitivity. Results TTK was up-regulated in the cisplatin-resistant ovarian cancer cell line. Down-regulation of TTK could recover the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin treatment. Mechanistically, the PI3K/AKT signaling pathway was activated in cisplatin-resistant cells, and this pathway would be affected by TTK expression. Furthermore, TTK was highly expressed in the tissues of ovarian cancer patients, especially those acquired resistance to cisplatin. Conclusions Our study revealed that TTK may be a promising therapeutic target for cisplatin-resistant ovarian cancer.

Abstract Serous ovarian cancer (SOC) is the most common women cancer and the leading cause of cancer-related mortality among the gynaecological malignancies. Although effective chemotherapeutics combined with surgery are developed for the treatment, the five-year survival rate is unsatisfactory due to chemoresistance. To overcome this shortcoming of chemotherapy, we established taxol and carboplatin resistant SOC cell lines for the understandings of the molecular and cellular mechanisms of chemoresistance. Here, we found that these chemoresistant cell lines showed less viability and proliferation, due to more cells arrested at G0/G1 phase. Glutathione-S-transferases-theta1 (GSTT1) was significantly upregulated in these chemoresistant cells, along with other chemoresistant genes. Meanwhile, GSTT1 expression was also significantly upregulated in the SOC patient tissues after taxol treatment, indicating this upregulation was physiologically relevant to chemotherapy. Further, suppression of GSTT1 expression by shRNA in SOC cell lines led to more sensitivity to drug treatment, through increasing divided cells and promoting cell death. Moreover, the expression of DNA topoisomerase 1 (Topo I) was in synergy with that of GSTT1 in the chemoresistant cells, and GSTT1 can bind to Topo I in vitro, which suggested GSTT1 could function through DNA repair mechanism during chemoresistance. In summary, our data imply that GSTT1 may be a potential biomarker or indicator of drug resistance in serous ovarian cancer.

Abstract Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Here, we illustrated that the expression of SIRT4 is markedly reduced in cancerous tissues, and closely associated with malignancy stage, grade, and prognosis. In ccRCC cells, SIRT4 exerted its proapoptotic activity through enhancing intracellular reactive oxygen species (ROS). Heme oxygenase-1 (HO-1) is part of an endogenous defense system against oxidative stress. Nevertheless, overexpression of SIRT4 hindered the upregulation of HO-1 in von Hippel–Lindau (VHL)-proficient cells and repressed its expression in VHL-deficient cells. This discrepancy indicated that competent VHL withstands the inhibitory role of SIRT4 on HIF-1α/HO-1. Functionally, overexpression of HO-1 counteracted the promotional effects of SIRT4 on ROS accumulation and apoptosis. Mechanistically, SIRT4 modulates ROS and HO-1 expression via accommodating p38-MAPK phosphorylation. By contrast, downregulation of p38-MAPK by SB203580 decreased intracellular ROS level and enhanced the expression of HO-1. Collectively, this work revealed a potential role for SIRT4 in the stimulation of ROS and the modulation of apoptosis. SIRT4/HO-1 may act as a potential therapeutic target, especially in VHL-deficient ccRCCs.

Considering the deferred and risk-free interest rates, this paper focuses on the impact of fairness concern on optimal strategies about pricing, green levels and sales effort in manufacturer-led green supply chain. The results show that in the scenario with fairness neutral, the optimal benefit under decentralized decision is always less than the centralized decision, and the risk-free interest rate is larger, the difference between the two is more obvious. While in the scenario with fairness concern, the fairness degree, product greening efficiency and the return on sales work together on the greenness, sales efforts and pricing decision of the product under the condition that the Nash-negotiation solution is used as a fair reference point. Although fairness concern behavior always achieves utility fairness by harming the other party’s revenue, the overall utility of the supply chain will grow to some extent under the manufacturer’s fairness-concern behavior, which is in stark contrast to the impact of retailer’s fairness concern.

Background: Caldesmon gene (CALD1) plays an important role in many cellular functions. Some researchers have found the correlation between CALD1 expression and prognosis of gastrointestinal cancer (GI), but the association with tumor-infiltrating lymphocytes (TILs) still unclear. Methods: The expression of CALD1 in different human tumor was analyzed by Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The correlations between CALD1 and prognosis in types cancer were explored by Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The association between CALD1 expression and tumor immune cell infiltration was further analyzed via TIMER and GEPIA databases. Results: The CALD1 expressions in types cancer between tumor tissues and adjacent normal tissues were significantly different. The high expression of CALD1 was related with poor overall survival (OS) of patients with gastric cancer, especially in gastric cancer patients at N1, N2 and N3 stages. The expression of CALD1 was positively associated with immune-infiltrated, such as CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells (DCs) in gastric cancer. Conclusions: CALD1 was considerably a key role in prognosis of patients with gastric cancer. The expression level of CALD1 is significantly associated with immune-infiltrated in gastric cancer. Furthermore, CALD1 expression may be involved in regulating tumor-associated macrophages (TAMs), dendritic cells, exhausted T cells and regulatory T cells in gastric cancer. These findings suggest that CALD1 could be utilized as a marker of prognosis and immune infiltration in gastric cancer.

Fluid–structure interaction (FSI) is a frequent and unstable inherent phenomenon in water conveyance systems. Especially in a system with a surge chamber, valve closing and the subsequent water level oscillation in the surge chamber are the excitation source of the hydraulic transient process. Water-hammer-induced FSI has not been considered in preceding research, and the results without FSI justify further investigations. In this study, an FSI eight-equation model is presented to capture its influence. Both the elbow pipe and surge chamber are treated as boundary conditions, and solved using the finite volume method (FVM). After verifying the feasibility of using FVM to solve FSI, friction, Poisson, and junction couplings are discussed in detail to separately reveal the influence of a surge chamber, tow elbows, and a valve on FSI. Results indicated that the major mechanisms of coupling are junction coupling and Poisson coupling. The former occurs in the surge chamber and elbows. Meanwhile, a stronger pressure pulsation is produced at the valve, resulting in a more complex FSI response in the water conveyance system. Poisson coupling and junction coupling are the main factors contributing to a large amount of local transilience emerging on the dynamic pressure curves. Moreover, frictional coupling leads to the lower amplitudes of transilience. These results indicate that the transilience is induced by the water hammer–structure interaction and plays important roles in the orifice optimization in the surge chamber.