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As the main type of renal cell carcinoma (RCC), clear cell RCC (ccRCC) is often associated with the deletion or mutation of the von Hippel Lindau (VHL) gene, enhancement of glucose and lipid metabolism, and heterogeneity of the tumor microenvironment. VHL alterations in RCC cells lead to the activation of hypoxia-inducible factors and their downstream target vascular endothelial growth factor, and to the reprogramming of multiple cell death pathways and metabolic weakness, including ferroptosis, which are associated with targeted therapy or immunotherapy. The changes in biological metabolites (e.g., iron and lipids) support ferroptosis as a potential therapeutic strategy for RCC, while iron metabolism and ferroptosis regulation have been examined as anti-RCC agents in numerous studies, and various ferroptosis-related molecules have been shown to be related to the metastasis and prognosis of ccRCC. For example, glutathione peroxidase 4 and glutaminase inhibitors can inhibit pyrimidine synthesis and increase reactive oxygen species levels in VHL-deficient RCC cells. In addition, the release of damage-associated molecular patterns by tumor cells undergoing ferroptosis also mediates antitumor immunity, and immune therapy can synergize with targeted therapy or radiotherapy through ferroptosis. However, Inducing ferroptosis not only suppresses cancer, but also promotes cancer development due to its potential negative effects on anti-cancer immunity. Therefore, ferroptosis and various tumor microenviroment-related molecules may co-occur during the development and treatment of RCC, and further understanding of the interactions, core targets, and related drugs of ferroptosis may provide new combination drug strategies for RCC treatment. Here we summarize the key genes and compounds on ferroptosis and RCC in order to envision future treatment strategies and to provide sufficient information for overcoming RCC resistance through ferroptosis.

The DC voltage level of photovoltaic and PEDF applications have continuously advanced, reaching up to DC3000V. This presents new requirements for DC circuit breakers operating at higher voltages (>DC1500V) to ensure effective fault protection in the DC side. Based on this, a self-powered hybrid DC circuit breaker with synergistic effect of step-down and divided current is proposed. This innovative design utilizes the voltage of main branch to trigger IGBT conduction, eliminating the need for an additional trigger circuit. The interruption characteristics is analyzed by simulation. The reactor and shunt resistance effectively reduce the peak currents of both main and transfer branches. This approach significantly mitigates the voltage stress on the mechanical switch, reduces the risk of post-arc reignition, and shortens the interruption time. The circuit breaker topology proposed enables the DC arc interruption at larger current and higher voltage, serving as the valuable guide for the implementation of hybrid DC circuit breakers in renewable energy power systems.

Abstract Background With social transformation, rapid economic development and deepening awareness of psychological health in China, people’s demand for psychological health services is becoming increasingly urgent. A key challenge for Chinese medical organizations is to train enough qualified psychological care nurses. A greater understanding of psychological care competences (PCC) can help in clinical nurse selection, training, and assessment. Objective To develop a PCC framework for Chinese nurses and obtain a consensus on the framework among experts. Methods A descriptive mixed methods study was designed consisting of a literature review and semi-structured interviews followed by three Delphi rounds. The experts (n = 16) involved were nurses, nursing managers and educators from nine Chinese provinces with a specific interest in psychological care. Descriptive statistics assisted in data analysis. Results Using the Iceberg Model as a theoretical foundation, five main dimensions and associated subdomains were integrated from 39 chosen articles. The semi-structured interviews with 24 nursing managers and nurses confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the initial PCC framework. After three Delphi rounds, the experts reached consensus on the PCC framework, including five domains (knowledge, skills, professional ethics, personal traits, internal motivations) and 22 subdomains with connotations. The response rate (RR) values for the three rounds of consultation were 80.00%, 87.50% and 92.86%, the composite reliability (Cr) values were 0.89–0.90, and the Kendall coordination coefficients were 0.155-0.200 (P

Computational Pathology (CPath) is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field’s future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath. For updated information on this survey review paper and accessing to the original model cards repository, please refer to GitHub. Updated version of this draft can also be found from arXiv.

Poorly preserved tracks have limited ichnotaxonomic or biotaxon utility, but may reveal useful information about the paleoenvironment, behavior and track taphonomy. Eight mostly parallel to sub parallel trackway segments (T1–T8) were registered on a truncation surface in the Lower Cretaceous Luohe Formation of Shaanxi Province. These attest to the passage of several bipeds, probably all theropods, in a paleo-contour-parallel, south-north direction in an arid setting. Quality of preservation in these trackways is poor, but notably superior in two additional trackways (T9–T10) on a foreset surface. Trackway T9 indicates a didactyl trackmaker, probably a deinonychosaurian, heading north to south. This is the 13th report of deinonychosaurian tracks from the Lower Cretaceous of China. If any or all the eight south-north oriented trackway segments represent continuations of other segments in the same trackways, the total number of individual trackmakers heading in this direction may have been as low as three. Although the trackway pattern and sedimentological evidence could indicate a physically controlled pathway influencing the direction taken by these trackmakers, the possibility that the trackways also represented small social or gregarious group cannot be ruled out.

In this study, the effect and mechanism of a dynamic axial magnetic field on a preconditioned single-wire Z-pinch were investigated experimentally and theoretically. Optical diagnostic methods, including shadowgraphy, interferometry, Faraday rotation, and Thomson scattering, have been used to measure the parameters of magnetized plasmas. Compression of the azimuthal and axial magnetic fields was observed, and the suppression of the plasma instability was recorded and analyzed. The results showed that an external axial magnetic field could reduce the plasma instability and non-uniformity, but prolong the implosion time and weaken the compression ratio. In the implosion process with an axial magnetic field, the plasma rotated at a speed similar to that of imploding, which could be regarded as a stabilization method. A simplified model of the diffusion and compression processes of a dynamic axial magnetic field was developed to investigate the conditions for maximizing the amplitude of the axial magnetic field. Subsequently, the snowplow model was used to calculate the effect of axial magnetic fields on the implosion process and energy conversion.

Nutrient availability, in particular the availability of sugar [carbon (C)] and nitrogen (N), is important for the regulation of plant metabolism and development. In addition to independent utilization of C and N nutrients, plants sense and respond to the balance of C and N nutrients (C/N-nutrient) available to them. High C/low N-nutrient stress has been shown to arrest early post-germinative growth while promoting progression to senescence in Arabidopsis. Although several signaling components of the C/N-nutrient response have been identified, the inclusive molecular basis of plant C/N-nutrient response remains unclear. This proteome analysis evaluated phosphorylation dynamics in response to high C/low N-nutrient stress. Phosphoproteomics under conditions of C/N-nutrient stress showed a global change in the phosphorylation status of proteins, including plasma membrane H+-ATPase, carbon and nitrogen metabolic enzymes and signaling proteins such as protein kinases and transcription factors. Further analyses suggested that SNF1-related protein kinase 1 (SnRK1) is involved in primary C/N-nutrient signal mediation via the transcriptional regulation of C/N-regulatory kinases. We also identified a leucine-rich repeat receptor-like kinase with extracellular malectin-like domain, named as LMK1, which was shown to possess cell death induction activity in plant leaves. These results provide important insight into the C/N-nutrient signaling pathways connecting nutrition stress to various cellular and physiological processes in plants.

Recently, the C4F7N/CO2 mixture has been highly considered as a promising SF6 alternative due to its low greenhouse effect and excellent electrical performance. Apart from its dielectric strength and arc-quenching capability, the decomposition characteristics of C4F7N/CO2 also play an important role in its future applications in gas-insulated electrical equipment. Therefore, decomposition experiments of the C4F7N/CO2 mixture were carried out under multiple AC discharge breakdowns by using a needle-to-plate electrode configuration. The compositions of the gas mixture before and after breakdowns were detected by using a gas chromatography-mass spectrometer. The results show that a trace amount of C3HF7 exists in the C4F7N product; the decomposition of the C4F7N/CO2 mixture mainly produces CO, CF4, CO2, C2F4, C2F6, C3F8, CF3CN, C3F6, C4F6, C4F10, C2F5CN, C2N2, HCN, C2F3CN, and HF. As the number of breakdowns increases, the content of most decomposition products increases significantly, while the content of C3HF7 decreases. The possible formation pathways of the decomposition products were determined, and the corresponding reaction enthalpies were calculated by quantum chemistry calculation. Relevant results not only reveal the decomposition characteristics of C4F7N/CO2 under AC breakdowns but also help us to better understand the corresponding physicochemical mechanisms, which will provide a good reference for stable operation and safe maintenance in applications.

Abstract Background Reg IV is a member of the regenerating gene family and has been demonstrated to be overexpressed in gastric cancer. However, the functional mechanism of Reg IV in gastric cancer is still unclear. Methods Expression of Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and SOX9 were transfected into human gastric cancer cells and the protein and mRNA levels of Reg IV and SOX9 were investigated by western blot and real-time PCR. The invasion and migration ability of gastric cancer cells with overexpressed Reg IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers and wound healing assay. Results The Reg IV and SOX9 protein expression levels were both significantly higher in gastric cancer tissues compared with adjacent tissues (p = 0.022, p = 0.003). Reg IV protein expression significantly correlated with tumor invasion depth (p

The dynamics of wire array Z pinches are greatly affected by the initial state of the wires, which can be preconditioned by a prepulse current. Recent advances in experimental research on preconditioned wire array Z pinches at Xi’an Jiaotong University are presented in this paper. Single-wire explosion experiments were carried out to check the state of the preconditioning and to obtain the current parameters needed for wire gasification. Double-wire explosion experiments were conducted to investigate the temporal evolution of the density distribution of the two gasified wires. Based on the results of these experiments, a double-pulse Z-pinch facility, Qin-1, in which a 10 kA prepulse current was coupled with the 0.8 MA main current was designed and constructed. Wire arrays of different wire materials, including silver and tungsten, can be preconditioned by the prepulse current to a gaseous state. Implosion of the two preconditioned aluminum wires exhibited no ablation and little trailing mass.

While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported "compound 52" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA) model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors.