The novel role of LDHA/LDHB in the prognostic value and tumor-immune infiltration in clear cell renal cell carcinoma

Lactate dehydrogenase (LDH) is a crucial glycolytic enzyme which mediates the metabolic plasticity of cancer cells, however its clinical significance in renal cell carcinoma (RCC) is poorly understood. Herein, we examined the prognostic significance of the two primary components of LDH, i.e., LDHA and LDHB, in clear cell RCC (ccRCC) patients and further explored their association with immune infiltration in ccRCC. In this study, the expression levels of LDHA and LDHB were examined in ccRCC and adjacent normal tissues by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, and western blotting (WB) analyses, and their prognostic values were estimated in 150 ccRCC and 30 adjacent normal tissues by immunohistochemistry (IHC) analysis. The relationship to immune infiltration of LDHA and LDHB genes was further investigated using tumor immune estimation resource 2 (TIMER2) and Tumor-Immune System Interactions and DrugBank (TISIDB) databases, respectively. Public databases and WB analyses demonstrated higher LDHA and lower LDHB in ccRCC than in non-tumor tissues. IHC analysis revealed that LDHA and LDHB expression profiles were significantly associated with tumor grade, stage, size, and overall survival (OS). Univariate survival analysis displayed that high grade, advanced stage, large tumor, metastasis, high LDHA, and low LDHB expression were significantly associated with a poorer OS, and multivariate analysis revealed tumor stage and LDHB were identified as independent predictors for OS in patients with ccRCC. Further TIMER2 and TISIDB analyses demonstrated that LDHA and LDHB expression was significantly related to multiple immune cells and immune inhibitors in over 500 ccRCC patients. These findings revealed that LDHB was an independent favorable predictor, and LDHA and LDHB correlated with tumor immune infiltrates in ccRCC patients, which indicated LDHA/LDHB could be implicated in the tumorigenesis of ccRCC and might be potential therapeutic targets for patients with ccRCC

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.</p

Author Correction:Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts (Nature Genetics, (2021), 53, 1, (86-99), 10.1038/s41588-020-00750-6)

This paper was originally published without open access. As of the date of this correction, the paper is available online as an open-access paper under a Creative Commons Attribution 4.0 International License. *Lists of authors and their affiliations appear online

Closed Loop Control of Melt Pool Width in Laser Directed Energy Deposition Process Based on PSO-LQR

A closed-loop controller was proposed to adjust the laser power to maintain melt pool stability based on the linear quadratic regulator (LQR) control theory. The melt pool width acquisition system was built based on complementary metal oxide semiconductor (CMOS), and the captured melt pool image was processed using an image processing algorithm to obtain the melt pool width. The laser power was used as the input variable and the melt pool width as the output variable. The state space spatial model was identified using the subspace method to identify the experimental data. The LQR controller was designed based on the state space equation, to improve the controller&#x2019;s performance and reduce the hassle of selecting the weighting matrix ${Q}$ in LQR. A particle swarm optimization (PSO) algorithm was used to optimize the control weighting matrix globally, and the optimal control weighting matrix was obtained. The controller performance was evaluated by constant-width and variable-width thin-wall deposition samples, and the results showed that the algorithm is simple, efficient, and able to maintain the melt pool width stable in real-time. It can effectively reduce reliance on manual experience

Research on the Optimized Operation of Hybrid Wind and Battery Energy Storage System Based on Peak-Valley Electricity Price

The combined operation of hybrid wind power and a battery energy storage system can be used to convert cheap valley energy to expensive peak energy, thus improving the economic benefits of wind farms. Considering the peak–valley electricity price, an optimization model of the economic benefits of a combined wind–storage system was developed. A charging/discharging strategy of the battery storage system was proposed to maximize the economic benefits of the combined wind–storage system based on the forecast wind power. The maximal economic benefits were obtained based on scenario analysis, taking into account the wind-power forecast error, and costs associated with the loss of battery life, battery operation, and maintenance. Case simulation results highlight the effectiveness of the proposed model. The results show that the hybrid wind–storage system is not only able to convert cheap electricity in the valley period into expensive electricity in the peak period, thus resulting in higher economic benefits, but can also balance the deviation between actual output and plans for the wind power generator to decrease the loss penalty. The analyzed examples show that, following an increase in the deviation of the forecast wind power, the profit of the combined wind–storage system can increase by up to 45% using the charging/discharging strategy, compared with a wind farm that does not utilize energy storage. In addition, the profit of the combined wind–storage system can increase by up to 16% compared with separate systems, following an increase in the deviation penalty deviation coefficient

Residual Stress and Distortion Prediction for Laser Directed Energy Deposition Based on Cyclic Heat Transfer Model

Predicting the residual stress and distortion caused by inhomogeneous temperature fields in the laser directed energy deposition (LDED) process is a challenging task. This study proposes a novel thermodynamic coupling simulation method based on the cyclic heat transfer model to accurately predict temperature, stress, and distortion evolution during the deposition process. The model effectively calculates the layer-by-layer superposition of thermal effects and cyclic accumulation of thermal stress during the deposition process, leading to improved prediction accuracy for temperature, residual stress, and distortion. Initially, the heat source model, the cyclic heat transfer model, and the thermoelastic matrix are established. The thermoelastic constitutive equation and the equilibrium differential equation are formulated to capture the actual process characteristics of the LDED accurately in order to achieve the thermodynamic coupling solution. Then, numerical simulations are performed on a typical model specimen, with simulation parameters consistent with the actual deposition parameters. Finally, the predicted results are validated through actual deposition experiments, and the temperature, stress, and distortion history are analyzed. The results demonstrate that the cyclic thermodynamic coupling model proposed in this study can effectively predict the deposited components&#x2019; temperature, residual stress, and distortion evolution. This study establishes a crucial foundation for achieving precision and performance control in the deposition process and reducing residual stress and distortion in the components

Targeting Hippo pathway: A novel strategy for Helicobacter pylori-induced gastric cancer treatment

The Hippo pathway plays an important role in cell proliferation, apoptosis, and differentiation; it is a crucial regulatory pathway in organ development and tumor growth. Infection with Helicobacter pylori (H. pylori) increases the risk of developing gastric cancer. In recent years, significant progress has been made in understanding the mechanisms by which H. pylori infection promotes the development and progression of gastric cancer via the Hippo pathway. Exploring the Hippo pathway molecules may yield new diagnostic and therapeutic targets for H. pylori-induced gastric cancer. The current article reviews the composition and regulatory mechanism of the Hippo pathway, as well as the research progress of the Hippo pathway in the occurrence and development of H. pylori-related gastric cancer, in order to provide a broader perspective for the study and prevention of gastric cancer

Effectiveness and Efficiency of Externally Bonded CFRP Sheets for Shear Strengthening of RC Beam-Column Joints

To develop feasible carbon fiber reinforced polymer (CFRP) retrofit schemes for the shear strengthening of real three-dimensional reinforced concrete (RC) beam-column joints, a series of parameters in relation to the contributions of the CFRP sheets externally bonded to joint panels was numerically investigated in this study. The parameters include CFRP reinforcement ratio, CFRP layout, transverse beam-to-joint panel width ratio, transverse beam-to-joint panel height ratio, location of transverse beam, and number of transverse beams. Strengthening efficiency, a new dimensionless index, was introduced to evaluate the residual effect of a CFRP-strengthening system weakened by the presence of transverse beams in comparison with the increase in joint shear capacity in relation to the one-way counterpart. The results obtained from 44 nonlinear finite element models, which were calibrated against experimental observations, confirmed the effectiveness of the CFRP strengthening technique with regard to the relatively wide ranges of the parameters. The significant differences among the roles of the parameters were revealed, and the reasons behind the differences were analyzed. Furthermore, the shear mechanism of the CFRP-retrofitted joint panels was discussed with the proposed strut-and-tie model

Rational Design of a Unique Ternary Structure for Highly Photocatalytic Nitrobenzene Reduction

The rational design and controllable synthesis of TiO₂ and noble metal composite photocatalysts represent an unprecedented challenge for developing the solar-driven reduction of nitrobenzene (NB) to aminobenzene (AB), owing to the recombination over the interface between the noble metals and TiO₂, which is harmful to the conversion efficiency of NB to AB. Here, we design a unique ternary structure (the high separation of TiO₂ and Pt nanoparticles on the surface of reduced graphene oxide (RGO)) through the sol–gel and microwave-assisted strategies. The substrate of RGO can be used as an “electric wire” to effectively transfer the photogenerated electrons from the isolated TiO₂ nanocrystals to the isolated Pt nanoparticles, which greatly decreases the interface recombination between TiO₂ and Pt and further improves the conversion efficiency of NB to AB under the solar light irradiation. We anticipate our research provides a new way to overcome the interface recombination on the binary photocatalysts in the photocatalytic reaction

Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo–YAP1 pathway

Abstract Background Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. Methods The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. Results GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models. Conclusions Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC