MRTO4 Enhances Glycolysis to Facilitate HCC Progression by Inhibiting ALDOB.

BACKGROUND MRT4 Homolog, Ribosome Maturation Factor (MRTO4) is often upregulated in cancer cells. However, its impact in hepatocellular carcinoma (HCC) is less well understood. Herein, we explored the prognostic and energy metabolism reprogramming role of MRTO4 in HCC. MATERIAL AND METHODS Clinical data were obtained from The Cancer Genome Atlas (TCGA), and the expression of MRTO4 in clinical samples was analyzed. The association between different variables and overall survival (OS) was studied, as well as their potential as independent prognostic factors, using Cox regression analysis. We constructed a nomogram including clinical pathological variables and MRTO4 expression to provide a predictive model for prognosis. Heatmaps, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the relationship between energy metabolism pathways and MRTO4. We used classic molecular biology research methods, including RT-qPCR, Western blotting, CCK8, TUNEL, Clone formation, Transwell assay, ELISA, and immunohistochemistry, to study the role of MRTO4 in promoting the progression of HCC through glycolysis regulation. RESULTS Our study showed that MRTO4 is an independent prognostic risk factor for HCC and that MRTO4 accelerates glycolysis of HCC cells, promotes proliferation and invasion, and suppresses apoptosis of HCC cells. The underlying mechanism involves MRTO4 promoting glycolysis and accelerating HCC by inhibiting ALDOB. CONCLUSIONS Our study revealed a novel mechanism by which MRTO4 promotes glycolysis and accelerates HCC progression, and suggests that inhibiting MRTO4 could be a potential therapeutic strategy for HCC.

Intravesical IR-780 instillation prevents radiation cystitis by protecting urothelial integrity.

PURPOSE: To explore an efficient preventive strategy for radiation cystitis. METHODS: We instilled IR-780 into the bladders of rats 1 h before bladder irradiation, and its bio-distribution was observed at different times. Bladders were then examined for pathogenic alterations and inflammation levels by day 3 and week 12 postirradiation, and the functional characteristics of the bladder were tested via cystometry by week 12. Human uroepithelial sv-huc-1 cells were used to determine the effect of IR-780 on cell viability, regardless of irradiation. We measured the intracellular levels of oxidative stress, DNA damage, apoptosis proportion, and the expression of antioxidant proteases and apoptotic caspases in IR-780 pretreated cells after radiation. RESULTS: IR-780 is localized in the urothelium after intravesical instillation in vivo. Ionizing radiation could induce acute impairment of the bladder urothelium and inflammation in the bladder on day 3. Fibrosis of the irradiated bladder progressed and eventually affected voiding function at 12 weeks. Treatment with IR-780 before irradiation ameliorated these changes. In vitro, IR-780 protected against cell viability and apoptosis of sv-huc-1 cells after irradiation. Additionally, IR-780 may assist in eliminating reactive oxygen species and repairing irradiation-induced DNA damage. CONCLUSION: Our data indicate that IR-780 can be used before irradiation to prevent acute urinary mucosal injury and late bladder dysfunction. Moreover, early urothelial impairment plays a significant role in radiation cystitis development.

Ent-Dihydrotucumanoic acid promotes apoptosis in PC-3 human prostate cancer cells.

Prostate cancer (PC) has become a disease that pose a serious threat to men's health and life. In recent years, due to the changes of environment, lifestyle and other factors, the incidence of PC has been increasing rapidly in recent years, which is a serious threat to men's health. Ent-Dihydrotucumanoic Acid (DTA) is a compound isolated from Asteraceae of gymnosperms, which has many pharmacological effects. The effect of DTA on the growth of tumor cell line was studied by CCK-8 method, mitochondrial membrane potential and apoptosis were detected by flow cytometry, apoptosis-related genes were detected by Western blot assay, and the absorptivity of Caspase-3 and Caspase-9 was measured by spectrophotometer. It was found that DTA induces apoptosis of human prostate cancer cell line PC3 through mitochondrial pathway, thus preventing the development of prostate cancer. It lays the experimental foundation for the further development of DTA.

Elevated Expression of NOTCH1 Associates with Lymph Node Metastasis of Gastric Cancer and Knock-Down of NOTCH1 Attenuates Tumor Cell Progression.

BACKGROUND Gastric cancer is the third leading cause of cancer-related death, while its molecular mechanism has not been fully clarified. This study aims to explore the role of Notch signaling in the pathogenesis of gastric cancer. MATERIAL AND METHODS A total of 64 patients with gastric cancer were enrolled. The expressions of NOTCH1 in tumor tissues and adjacent non-tumor tissues were detected by immunohistochemistry staining. The correlation between NOTCH1 expression and clinicopathological features of patients was analyzed. NOTCH1 was knocked down in gastric cancer cells. The effects of NOTCH1 blockade on cell proliferation, migration and cell cycle distribution were analyzed. The expressions of ERK1/2 and phospho-ERK1/2 (p-ERK1/2) were detected using western blotting. RESULTS Gastric cancer tissues expressed higher level of NOTCH1 than adjacent non-tumor tissues (P<0.05). The high level of NOTCH1 was found to be correlated with gender (male) and lymph node metastasis. However, the expression level of NOTCH1 did not affect the overall survival of patients with gastric cancer. NOTCH1 knock-down repressed the migration and proliferation of gastric cancer cells. Moreover, the cell cycle was arrested at G0/G1 phase by NOTCH1 blockade. The expressions of ERK1/2 and p-ERK1/2 decreased with NOTCH1 knock-down. Further inhibition of ERK1/2 signaling by a MEK1/2 inhibitor U0126 reduced the proliferation of AGS cells, which aggravated the inhibition effect of NOTCH1 knock-down on cell proliferation. CONCLUSIONS NOTCH1 may play an oncogenic role in gastric cancer. Inhibition of NOTCH1 can efficiently attenuate gastric cancer cell progression, probably in part through cross-talking with ERK1/2 signaling pathway.

Evaluation of short-term effectiveness of eight targeted agents combined with chemotherapy for treating esophageal-gastric junction adenocarcinoma: A network meta-analysis.

This study aimed to evaluate the short-term effectiveness of eight targeted agents (ramucirumab, bevacizumab, rilotumumab, panitumumab, cetuximab, trebananib, trastuzumab, matuzumab) plus chemotherapy in esophageal-gastric junction adenocarcinoma (EGJA) by a network meta-analysis (NMA). PubMed, Embase, and Cochrane Library databases were systematically retrieved for randomized clinical trials (RCTs) concerning targeted agents plus chemotherapy in the treatment of EGJA. This NMA combined both direct and indirect evidence to evaluate odds ratio (OR) and to draw the surface under the cumulative ranking curve (SUCRA). In total 11 RCTs with 3649 EGJA patients (1907 patients treated with targeted agents plus chemotherapy were regarded as the case group, and 1742 patients with placebo plus chemotherapy were assigned into the control group) were enrolled in this study. Targeted agents in terms of stable disease (SD), partial response (PR), disease control rate (DCR), and overall response ratio (ORR) with the SUCRA values of 0.838, 0.807, 0.934, and 0.793, respectively. Cetuximab and trastuzumab, with the SUCRA values of 0.884 and 0.758, came on top as the best outcomes for treating EGJA in terms of progressive disease (PD) and complete response (CR). Cluster analysis results indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA. Our findings indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA amongst the nine treatment regimens, which provided clinical guidance for clinicians in the treatment of EGJA.

MiR-340 affects gastric cancer cell proliferation, cycle, and apoptosis through regulating SOCS3/JAK-STAT signaling pathway.

OBJECTIVE: Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is closely related to tumorigenesis. Suppressors of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT signaling pathway. MiR-340 expression is significantly upregulated in gastric cancer (GC) tissue. This study investigated the role of miR-340 in regulating SOCS3 expression and affecting GC cell proliferation, cycle, and apoptosis. PATIENTS AND METHODS: Dual luciferase assay was used to verify the targeted relationship between miR-340 and SOCS3. GC tissue was collected from patients. Normal gastric mucosal tissue was selected as control. MiR-340, SOCS3, p-JAK, p-STAT3, and Survivin protein expressions were compared with GES-1 and MKN-28 cells. MKN-28 cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-340, pSicoR-Blank, and pSicoR-SOCS3 groups. Cell proliferation, cycle, and apoptosis were detected by flow cytometry. RESULTS: Bioinformatics analysis revealed the targeted relationship between miR-340 and the 3'-UTR of SOCS3 mRNA. Dual luciferase assay demonstrated that miR-340 regulated SOCS3 expression. MiR-340 level was significantly elevated, while SOCS3 level was obviously declined in GC tissue compared with normal mucosal tissue. MiR-340, p-JAK, p-STAT3, and Survivin expressions were upregulated, whereas SOCS3 expression was reduced in MKN-28 cells compared with that in GES-1 cells. Anti-miR-340 or pSicoR-SOCS3 transfection markedly increased SOCS3 expression, reduced p-JAK, p-STAT3, and Survivin levels, attenuated cell proliferation, arrested cell cycle, and enhanced cell apoptosis in MKN-28 cells. CONCLUSIONS: Downregulation of miR-340 inhibited GC cell proliferation, arrested cell cycle, and facilitated apoptosis through upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway.

MicroRNA-200b Impacts Breast Cancer Cell Migration and Invasion by Regulating Ezrin-Radixin-Moesin.

BACKGROUND Ezrin-radixin-moesin (ERM) plays an important role in multiple links of tumors. It also involved in breast cancer invasion and metastasis, and might be a potential biomarker of breast cancer. Another study suggested that ERM expression was regulated directly by miR-200c, and had a critical role in miR-200c suppressing cell migration. This study aimed to investigate the effect of miR-200b on ERM expression in a breast cancer cell line and its influence on invasion and metastasis ability in vitro. MATERIAL AND METHODS Breast cancer cell lines MCF-7 and MDA-MB-231 with different metastatic potentials were selected as a model. MiR-200b overexpression or inhibition was achieved by Lipofectamine™ 2000-mediated miRNA transfection. RT-PCR was used to test miR-200b level, while Western blot was selected to detect ERM protein expression. Wound healing assay and Transwell assay were performed to determine cell migration and invasion ability. RESULTS RT-PCR revealed that miR-200b level in MDA-MB-231 was obviously lower than that in MCF-7, while Western blot analysis showed that ERM expression was significantly higher. MiR-200b inhibition by transfection in MCF-7 markedly decreased miR-200b level, elevated ERM expression, and enhanced cell migration and invasion. MiR-200b overexpression in MDA-MB-231 obviously increased miR-200b level, reduced ERM expression, and weakened cell migration and invasion. CONCLUSIONS MiR-200b participates in breast cancer cell migration and invasion through regulating ERM in MCF-7 and MDA-MB-231.

LXR agonist regulates the carcinogenesis of PCa via the SOCS3 pathway.

BACKGROUND: Down-regulation of suppressor of cytokine signaling 3 (SOCS3) inhibits prostate cancer (PCa) cell growth. Liver X receptors (LXRs) agonists have been recently introduced for PCa treatment. We postulated that LXR may inhibit the carcinogenesis of PCa via the SOCS3 pathway. METHODS: LNCaP cells were cultured and transfected with SOCS3 small-interfering RNA (SOCS3-siRNA) and control small-interfering RNA (control-siRNA). Then cells were treated with LXR activator (GW3965). The expressions of PCa related transcript factors, e.g. transcription 3 (STAT3), nuclear factor kappa B (NF-κB) and activation protein 1(AP1) were detected by western blot assay. In vitro cell proliferation, cell migration, cell invasion and apoptosis were analysed. Nude mice were used for in vivo tumorgenesis. RESULTS: In cells treated with control-siRNA, GW3965 enhanced SOCS3 expression and significantly inhibited the phosphorylation of STAT3, NF-κB and AP1 expressions, accompanied by dramatically reduced cellular proliferation rate, immigration and invasion of cultured cells. In cells treated with SOCS3-siRNA, the inhibitory effects of LXR activator on the phosphorylation of STAT3 and expressions of NF-κB and AP1 were totally abolished. The cell proliferation rate, immigration and invasion were markedly elevated by SOCS3 gene mutation, even with GW3965 treatment. The in vivo tumorgenesis assay showed that GW3965 significantly reduced the tumor volumes in tumor-bearing nude mice receiving saline injection, but failed to limit the tumor volume in tumor-bearing nude mice receiving SOCS3 antibody injection. CONCLUSION: Our results provide evidence in support of the notion that LXR agonist may regulate the carcinogenesis of PCa via the SOCS3 pathway.

Tunable bulk polaritons of graphene-based hyperbolic metamaterials.

The tunable hyperbolic metamaterial (HMM) based on the graphene-dielectric layered structure at THz frequency is presented, and the surface and bulk polaritons of the graphene-based HMM are theoretically studied. It is found that the dispersions of the polaritons can be tuned by varying the Fermi energy of graphene sheets, the graphene-dielectric layers and the layer number of graphene sheets. In addition, the highly confined bulk polariton mode can be excited and is manifested in an attenuated total reflection configuration as a sharp drop in the reflectance. Such properties can be used in tunable optical reflection modulation with the assistance of bulk polaritons.

A reinforcement learning enhanced pseudo-inverse approach to self-collision avoidance of redundant robots.

Introduction: Redundant robots offer greater flexibility compared to non-redundant ones but are susceptible to increased collision risks when the end-effector approaches the robot's own links. Redundant degrees of freedom (DoFs) present an opportunity for collision avoidance; however, selecting an appropriate inverse kinematics (IK) solution remains challenging due to the infinite possible solutions. Methods: This study proposes a reinforcement learning (RL) enhanced pseudo-inverse approach to address self-collision avoidance in redundant robots. The RL agent is integrated into the redundancy resolution process of a pseudo-inverse method to determine a suitable IK solution for avoiding self-collisions during task execution. Additionally, an improved replay buffer is implemented to enhance the performance of the RL algorithm. Results: Simulations and experiments validate the effectiveness of the proposed method in reducing the risk of self-collision in redundant robots. Conclusion: The RL enhanced pseudo-inverse approach presented in this study demonstrates promising results in mitigating self-collision risks in redundant robots, highlighting its potential for enhancing safety and performance in robotic systems.

Exosomal IGFBP2 derived from highly metastatic promotes hepatocellular carcinoma metastasis by inducing epithelial mesenchymal transition.

Liver cancer metastasis is the main cause of death in liver cancer patients. Exosomes, which are small vesicles released by cancer cells, play a crucial role in the metastasis of cancer. The aim of this study was to investigate the effect of exosomes derived from high metastatic potential liver cancer cells acting as cell to cell communication on liver cancer metastasis. Bioinformatics analysis was used to obtain the differential expression of exosomal mRNAs from the plasma of both liver cancer patients and healthy volunteers. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and protein blot were employed to characterize the exosomes. The molecular mechanisms and were explored by conducting CCK8, Transwell, Tunel, RTqPCR, western blot, and immunofluorescence staining. We examined IGFBP2 special expression in the plasma exosomes of both liver cancer patients and healthy volunteers, and its presence was associated with a poor prognosis in liver cancer patients. Furthermore, we observed that exosomes from highly metastatic liver cancer cells (MHCC97H) contained high levels of IGFBP2 and could enhance the metastatic potential of less aggressive liver cancer cells (Hep3B). Additionally, we discovered that IGFBP2 in MHCC97H-derived exosomes activated ERK signaling pathway, which triggered epithelial-mesenchymal transition (EMT) in Hep3B cells. Our study underscores the significance of exosomal IGFBP2 from highly metastatic liver cancer cells as a driver of metastasis in less invasive liver cancer cells. This suggests that targeting IGFBP2 in exosomes could be a promising strategy for the treatment and prognosis of liver cancer patients.

Towards Semi-Autonomous Colon Screening Using an Electromagnetically Actuated Soft-Tethered Colonoscope Based on Visual Servo Control.

OBJECTIVE: Conventional colonoscopy using a flexible colonoscope remains two major limitations, including patient discomfort and difficult manipulations for surgeons. Robotic colonoscopes have been developed to conduct colonoscopy in a patient-friendly manner. However, most robotic colonoscopes still maintain nonintuitive and difficult manipulations, which limits their clinical applications. In this paper, we demonstrated visual servo-based semi-autonomous manipulations of an electromagnetic actuated soft-tethered (EAST) colonoscope, which aims to lower difficulties of robotic colonoscope manipulations. METHODS: Kinematic modeling of EAST colonoscope is conducted, with an adaptive visual servo controller established. Template matching method and a lumen and polyp detection model are developed to enable semi-autonomous manipulations, including region-of-interest automatic tracking and autonomous navigation with automatic polyp detection. RESULTS: The EAST colonoscope demonstrates visual servoing with an average convergence time of around 2.5 s and performs disturbance rejection within 3.0 s. Semi-autonomous manipulations were conducted in both a commercialized colonoscopy simulator and an ex-vivo porcine colon to show the efficacy of reducing the user workload compared to manual control. CONCLUSION: The EAST colonoscope can perform visual servoing and semi-autonomous manipulations with the developed methods in both laboratory and ex-vivo environments. SIGNIFICANCE: The proposed solutions and techniques improve the autonomy level of robotic colonoscopes and reduce user workloads, which promotes the development and clinical translation of robotic colonoscopy.

PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/ß-catenin pathway.

Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.

Association between kidney stones and poor sleep factors in U.S. adults.

The purpose of our study is to examine the correlation between sleep factors and the prevalence of kidney stones in US adults. A total of 34,679 participants from the National Health and Nutrition Examination Survey 2007 to 2018 were included in the analyses. Sleep data collection included: presleep factors (difficulty falling asleep, sleep onset latency), intra-sleep factors (risk index of obstructive sleep apnea, restless leg syndrome, difficulty maintaining sleep), post-sleep factors (daytime sleepiness, non-restorative sleep), sleep schedule and duration, and sleep quality. Logistic regression models were used to analyze the correlation between sleep factors and the prevalence of kidney stones. Among the 34,679 participants, the overall incidence of kidney stones was 9.3%. The presence of presleep factors (difficulty falling asleep [odds ratios [OR], 1.680; 95% CI, 1.310-2.150], prolonged sleep onset latency [OR, 1.320; 95% CI, 1.020-1.700]), intra-sleep factors (higher risk index of obstructive sleep apnea [OR, 1.750; 95% CI, 1.500-2.050], restless leg syndrome [OR, 1.520; 95% CI, 1.150-1.990], difficulty maintaining sleep [OR, 1.430; 95% CI, 1.130-1.810]), post-sleep factors (daytime sleepiness [OR, 1.430; 95% CI, 1.220-1.680], non-restorative sleep [OR, 1.400; 95% CI, 1.110-1.760]), short sleep duration (OR, 1.190; 95% CI, 1.080-1.310), mediate sleep quality (OR, 1.140; 95% CI, 1.020-1.290), and poor sleep quality (OR, 1.500; 95% CI, 1.310-1.720) are linked to the occurrence of kidney stones. However, short sleep onset latency, bedtime and wake-up time were not significantly associated with the prevalence of kidney stones. These findings showed positive associations between higher kidney stone prevalence and poor sleep factors.

Platelet-derived growth factor-BB increases expression of connexin 43 in an extracellular-regulated protein kinase-dependent manner in bladder smooth muscle cells.

OBJECTIVES: To investigate whether platelet-derived growth factor-BB induces the upregulation of connexin 43 in bladder smooth muscle cells and to examine the involved signaling pathway. METHODS: Bladder smooth muscle cells were exposed to platelet-derived growth factor-BB in the presence or absence of p38 mitogen-activated protein kinase, c-jun amino-terminal kinase or extracellular-regulated protein kinase inhibitors. Transfection of bladder smooth muscle cells with specific small interference ribonucleic acid against platelet-derived growth factor receptor-ß gene expression was also carried out to investigate whether platelet-derived growth factor receptor-ß was involved in the signaling pathway. Expression of messenger ribonucleic acid and protein for connexin 43 was measured by real time polymerase chain reaction and western blot. RESULTS: The addition of platelet-derived growth factor-BB in cultured bladder smooth muscle cells caused the significant upregulation of connexin 43, and the activation of extracellular-regulated protein kinase, c-jun amino-terminal kinase and p38 mitogen-activated protein kinase compared with the control group. This action of platelet-derived growth factor-BB could be abolished by the pretreatment of bladder smooth muscle cells with the extracellular-regulated protein kinase inhibitor PD98059, whereas p38 mitogen-activated protein kinase and c-jun amino-terminal kinase inhibitors did not have any effect on this. Platelet-derived growth factor-BB could induce the activation of platelet-derived growth factor receptor-ß. Transfection of bladder smooth muscle cells with small interference ribonucleic acid specific for platelet-derived growth factor receptor-ß gene resulted in the potent suppression of gene expression and inhibition of extracellular-regulated protein kinase activation, as well as upregulation of connexin 43 induced by platelet-derived growth factor-BB. CONCLUSIONS: Platelet-derived growth factor-BB upregulates connexin 43 expression through the activation of extracellular-regulated protein kinase and platelet-derived growth factor receptor-ß signaling pathways. This finding suggests that this signaling pathway might provide a potential target to manipulate detrusor overactivity.

A Dini-Derivative-Aided Zeroing Neural Network for Time-Variant Quadratic Programming Involving Multi-Type Constraints With Robotic Applications.

Time-variant quadratic programming (QP) with multi-type constraints including equality, inequality, and bound constraints is ubiquitous in practice. In the literature, there exist a few zeroing neural networks (ZNNs) that are applicable to time-variant QPs with multi-type constraints. These ZNN solvers involve continuous and differentiable elements for handling inequality and/or bound constraints, and they possess their own drawbacks such as the failure in solving problems, the approximated optimal solutions, and the boring and sometimes difficult process of tuning parameters. Differing from the existing ZNN solvers, this article aims to propose a novel ZNN solver for time-variant QPs with multi-type constraints based on a continuous but not differentiable projection operator that is deemed unsuitable for designing ZNN solvers in the community, due to the lack of the required time derivative information. To achieve the aforementioned aim, the upper right-hand Dini derivative of the projection operator with respect to its input is introduced to serve as a mode switcher, leading to a novel ZNN solver, termed Dini-derivative-aided ZNN (Dini-ZNN). In theory, the convergent optimal solution of the Dini-ZNN solver is rigorously analyzed and proved. Comparative validations are performed, verifying the effectiveness of the Dini-ZNN solver that has merits such as guaranteed capability to solve problems, high solution accuracy, and no extra hyperparameter to be tuned. To illustrate potential applications, the Dini-ZNN solver is successfully applied to kinematic control of a joint-constrained robot with simulation and experimentation conducted.

Can the Exemption of the New Energy Vehicle Purchase Tax Policy Induce Technological Innovation of Automobile Companies?

Implementing industrial policies to develop the new energy vehicle industry and improve technological innovation related to new energy vehicles is essential for countries dealing with environmental pollution and climate change. This paper first examines the impact of a demand-side industry policy related to new energy vehicles on the technological innovation level of supply-side vehicle enterprises. Regarding the new energy vehicle purchase tax exemption policy implemented by the Chinese government in 2014 as a quasi-experiment, this paper constructs a multi-period difference-in-differences (DID) model to identify the impact of the demand-side preferential tax policy on the technological innovation level of vehicle enterprises. In our DID design, 178 enterprises are in the treatment group and 166 enterprises in the control group, with 3,440 balanced panel data of observations. The results show that this policy can significantly promote the technological innovation of new energy vehicle enterprises. This promotion effect is greater in magnitude in large-scale enterprises, high-tech enterprises, and enterprises producing passenger vehicles. Theoretically, we believe that the demand-side tax exemption policy mainly indirectly promotes the technological innovation level of automobile enterprises through the signal channel and profit channel.

A Novel Neural Approach to Infinity-Norm Joint-Velocity Minimization of Kinematically Redundant Robots Under Joint Limits.

Generally, the infinity-norm joint-velocity minimization (INVM) of physically constrained kinematically redundant robots can be formulated as time-variant linear programming (TVLP) with equality and inequality constraints. Zeroing neural network (ZNN) is an effective neural method for solving equality-constrained TVLP. For inequality-constrained TVLP, however, existing ZNNs become incompetent due to the lack of relevant derivative information and the inability to handle inequality constraints. Currently, there is no capable ZNN in the literature that has achieved the INVM of redundant robots under joint limits. To fill this gap, a classical INVM scheme is first introduced in this article. Then, a new joint-limit handling technique is proposed and employed to convert the INVM scheme into a unified TVLP with full derivative information. By using a perturbed Fisher-Burmeister function, the TVLP is further converted into a nonlinear equation. These conversion techniques lay a foundation for the success of designing a capable ZNN. To solve the nonlinear equation and the TVLP, a novel continuous-time ZNN (CTZNN) is designed and its corresponding discrete-time ZNN (DTZNN) is established using an extrapolated backward differentiation formula. Theoretical analysis is rigorously conducted to prove the convergence of the neural approach. Numerical studies are performed by comparing the DTZNN solver and the state-of-the-art (SOTA) linear programming (LP) solvers. Comparative results show that the DTZNN consumes the least computing time and can be a powerful alternative to the SOTA solvers. The DTZNN and the INVM scheme are finally applied to control two kinematically redundant robots. Both simulative and experimental results show that the robots successfully accomplish user-specified path-tracking tasks, verifying the effectiveness and practicability of the proposed neural approach and the INVM scheme equipped with the new joint-limit handling technique.

Heavy metal mobility in contaminated sediments under seawater acidification.

The behavior of heavy metals in contaminated sediment is of ecological significance considering the change of pH caused by ocean acidification. This study investigated the mobility of Cd, Cu, Ni, Pb, Fe, and Mn under experimental conditions for seawater acidification via enrichment of CO2 gas at different reaction set-ups. The results indicated that the concerned metals behaved differently in the water compared to the sediment. The heavy metals were considerably transferred from sediment to seawater, and the resultant intensity was controlled by the degree of acidification and the chemical state of specific metals. Moreover, labile fractions of heavy metals in sediments were more susceptible to acidification than other fractions. These findings were observed and confirmed using real-time monitoring conducted via the diffusion gradient technique (DGT). Overall, the results of this study provided new insights into exploring the coupling risk of heavy metals with ocean acidification.

Hyperbaric oxygen enhanced the chemotherapy of mitochondrial targeting molecule IR-780 in bladder cancer.

BACKGROUND: Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. MATERIAL AND METHODS: The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. RESULTS: IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. CONCLUSION: We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.