Search Results (153)

Background: Previous research has suggested that modulated electro-hyperthermia (mEHT) can be used to induce anti-tumor immune effects and to extend patient survival. The use of mEHT in advanced pancreatic cancer is beneficial; however, its immune-mediating effects were never investigated. Methods: A retrospective observational study was conducted. Leukocyte counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and granulocyte-to-lymphocyte ratio (GLR) were measured at baseline, midpoint, and after mEHT treatment. Results: A total of 73 mEHT treated pancreatic cancer patients were included. The time elapsed between tumor diagnosis and the first mEHT treatment was 4.40 ± 5.70 months. While no change could be observed between the baseline and the first follow-up visits, the total white blood cell (WBC), neutrophil, and granulocyte count, CRP, NLR, and GLR were significantly higher at the second follow-up compared to both previous visits. Higher levels of the latter parameters following the last mEHT treatment were signaling significantly poor prognostic signs, and so were their longitudinal changes. Conclusions: After the initiation of mEHT, immune markers stabilize with the treatment, but this positive effect is eroded over time by progressive disease. Monitoring the changes in these markers and the occurrence of their increase is a prognostic marker of shorter survival. Full article

As the country that emits the most carbon in the world, China needs significant and urgent changes in carbon emission control in the transportation sector in order to achieve the goals of reaching peak carbon emissions before 2030 and achieving carbon neutrality by 2060. Therefore, the promotion of new energy vehicles has become the key factor to achieve these two objectives. For the reason that the comprehensive transportation cost directly affects the end customer’s choice of heavy truck models, this work compares the advantages, disadvantages, and economic feasibility of diesel, liquefied natural gas (LNG), electric, hydrogen, and methanol heavy trucks from a total life cycle cost and end-user perspective under various scenarios. The study results show that when the prices of diesel, LNG, electricity, and methanol fuels are at their highest, and the price of hydrogen is 35 CNY/kg, the total life cycle cost of the five types of heavy trucks from highest to lowest are hydrogen heavy trucks (HHT), methanol heavy trucks (MHT), diesel heavy trucks (DHT), electric heavy trucks (EHT), and LNG heavy trucks (LNGHT), ignoring the adverse effects of cold environments on car batteries. When the prices of diesel, LNG, electricity, and methanol fuels are at average or lowest levels, and the price of hydrogen is 30 CNY/kg or 25 CNY/kg, the life cycle cost of the five heavy trucks from highest to lowest are HHT, DHT, MHT, EHT, and LNGHT. When considering the impact of cold environments, even with lower electricity prices, EHT struggle to be economical when LNG prices are low. If the electricity price is above 1 CNY/kWh, regardless of the impact of cold environments, the economic viability of EHT is lower than that of HHT with a purchase cost of 500,000 CNY and a hydrogen price of 25 CNY/kg. Simultaneously, an exhaustive competitiveness analysis of heavy trucks powered by diverse energy sources highlights the specific categories of heavy trucks that ought to be prioritized for development during various periods and the challenges they confront. Finally, based on the analysis results and future development trends, the corresponding policy recommendations are proposed to facilitate high decarbonization in the transportation sector. Full article

Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95–98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8–11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96–2.48) for IFN-based therapy, 4.27% (95% CI 2.93–6.2) for DAA and 0.89% (95% CI 0.4–1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment. Full article

Numerous preclinical results have been verified, and clinical results have validated the advantages of modulated electro-hyperthermia (mEHT). This method uses the nonthermal effects of the electric field in addition to thermal energy absorption. Modulation helps with precisely targeting and immunogenically destroying malignant cells, which could have a vaccination-like abscopal effect. A new additional modulation (high-power pulsing) further develops the abilities of the mEHT. My objective is to present the advantages of pulsed treatment and how it fits into the mEHT therapy. Pulsed treatment increases the efficacy of destroying the selected tumor cells; it is active deeper in the body, at least tripling the penetration of the energy delivery. Due to the constant pulse amplitude, the dosing of the absorbed energy is more controllable. The induced blood flow for reoxygenation and drug delivery is high enough but not as high as increasing the risk of the dissemination of malignant cells. The short pulses have reduced surface absorption, making the treatment safer, and the increased power in the pulses allows the reduction of the treatment time needed to provide the necessary dose. Full article

Compact, energy-efficient, and autonomous wireless sensor nodes offer incredible versatility for various applications across different environments. Although these devices transmit and receive real-time data, efficient energy storage (ES) is crucial for their operation, especially in remote or hard-to-reach locations. Rechargeable batteries are commonly used, although they often have limited storage capacity. To address this, ultra-low-power design techniques (ULPDT) can be implemented to reduce energy consumption and prolong battery life. The Energy Harvesting Technique (EHT) enables perpetual operation in an eco-friendly manner, but may not fully replace batteries due to its intermittent nature and limited power generation. To ensure uninterrupted power supply, devices such as ES and power management unit (PMU) are needed. This review focuses on the importance of minimizing power consumption and maximizing energy efficiency to improve the autonomy and longevity of these sensor nodes. It examines current advancements, challenges, and future direction in ULPDT, ES, PMU, wireless communication protocols, and EHT to develop and implement robust and eco-friendly technology solutions for practical and long-lasting use in real-world scenarios. Full article

Hydrogen energy is now a crucial technological option for decarbonizing energy systems. Comprehensive utilization is a typical mode of hydrogen energy deployment, leveraging its excellent conversion capabilities. Hydrogen is often used in combination with electrical and thermal energy. However, current hydrogen utilization modes are relatively singular, resulting in low energy utilization efficiency and high wind curtailment rates. To improve energy utilization efficiency and promote the development of hydrogen energy, we discuss three utilization modes of hydrogen energy, including hydrogen storage, integration into a fuel cell and gas turbine hybrid power generation system, and hydrogen methanation. We propose a hydrogen energy system with multimodal utilization and integrate it into an electrolytic hydrogen–thermal integrated energy system (EHT-IES). A mixed-integer linear programming (MILP) optimization scheduling model for the EHT-IES is developed and solved using the Cplex solver to improve the operational feasibility of the EHT-IES, focusing on minimizing economic costs and reducing wind curtailment rates. Case studies in northwest China verify the effectiveness of the proposed model. By comparing various utilization modes, energy storage methods, and scenarios, this study demonstrated that integrating a hydrogen energy system with multimodal utilization into the EHT-IES offers significant technical benefits. It enhances energy utilization efficiency and promotes the absorption of wind energy, thereby increasing the flexibility of the EHT-IES. Full article

At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification. Full article

Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions. Full article

The present study aimed to evaluate the effect of nanoemulsions using combined synthetic anthelmintics, thiabendazole (TBZ), levamisole (LEV), and ivermectin (IVM), with carvacryl acetate (CA) against Haemonchus contortus, and also tested the presence and absence of alginate (ALG). The anthelmintic effect of the CA/TBZ nanoemulsion was evaluated in the egg hatch test (EHT). The effects of CA/IVM and CA/LEV nanoemulsions were evaluated in the larval development test (LDT). The emulsions CA/TBZ/ALG and CA/TBZ showed a multimodal profile, with most particles on the nanometric scale. The encapsulation efficiency in CA/TBZ/ALG was 80.25%, and that in CA/LEV/ALG was 89.73%. In the EHT, CA/TBZ and CA/TBZ/ALG showed mean combination indices (CIs) of 0.55 and 0.36, respectively, demonstrating synergism in both. In LDT, CA/IVM had an average CI of 0.75, and CA/LEV and CA/LEV/ALG showed CI values of 0.4 and 0.93, respectively. It was concluded that CA/TBZ showed a synergistic interaction, and CA/TBZ/ALG showed an enhanced effect. In addition, the matrix brought stability to the product, encouraging its improvement to obtain higher efficacy. Full article

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment. Full article

Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue. Full article

When plants are exposed to salt stress, endogenous hormones are essential for their responses through biosynthesis and signal transduction pathways. However, the roles of endogenous hormones in two cliff species (Opisthopappus taihangensis and Opisthopappus longilobus (Opisthopappus genus)) in the Taihang Mountains under salt stress have not been investigated to date. Following different time treatments under 500 mM salt concentrations, 239 differentially expressed gene (DEG)-related endogenous hormones were identified that exhibited four change trends, which in Profile 47 were upregulated in both species. The C-DEG genes of AUX, GA, JA, BR, ETH, and ABA endogenous hormones were significantly enriched in Opisthopappus taihangensis (O. taihangensis) and Opisthopappus longilobus (O. longilobus). During the responsive process, mainly AUX, GA, and JA biosynthesis and signal transduction were triggered in the two species. Subsequently, crosstalk further influenced BR, EHT, ABA, and MAPK signal transduction pathways to improve the salt resistance of the two species. Within the protein–protein interactions (PPI), seven proteins exhibited the highest interactions, which primarily involved two downregulated genes (SAUR and GA3ox) and eight upregulated genes (ACX, MFP2, JAZ, BRI1, BAK1, ETR, EIN2, and SNRK2) of the above pathways. The more upregulated expression of ZEP (in the ABA biosynthesis pathway), DELLA (in the GA signaling pathway), ABF (in the ABA signaling pathway), and ERF1 (in the ETH signaling pathway) in O. taihangensis revealed that it had a relatively higher salt resistance than O. longilobus. This revealed that the responsive patterns to salt stress between the two species had both similarities and differences. The results of this investigation shed light on the potential adaptive mechanisms of O. taihangensis and O. longilobus under cliff environments, while laying a foundation for the study of other cliff species in the Taihang Mountains. Full article

The human heart lacks significant regenerative capacity; thus, the solution to heart failure (HF) remains organ donation, requiring surgery and immunosuppression. The demand for constructed cardiac tissues (CCTs) to model and treat disease continues to grow. Recent advances in induced pluripotent stem cell (iPSC) manipulation, CRISPR gene editing, and 3D tissue culture have enabled a boom in iPSC-derived CCTs (iPSC-CCTs) with diverse cell types and architecture. Compared with 2D-cultured cells, iPSC-CCTs better recapitulate heart biology, demonstrating the potential to advance organ modeling, drug discovery, and regenerative medicine, though iPSC-CCTs could benefit from better methods to faithfully mimic heart physiology and electrophysiology. Here, we summarize advances in iPSC-CCTs and future developments in the vascularization, immunization, and maturation of iPSC-CCTs for study and therapy. Full article

This article presents the results of evaluating the possibility of conducting radio astronomy studies in the windows of atmospheric transparency ~100, ~230, and ~350 GHz using the optical Big Telescope Alt-Azimuthal (BTA) of the Special Astrophysical Observatory of the Russian Academy of Sciences (SAO RAS). A list of some promising astronomical tasks is proposed. The astroclimat conditions at the BTA site and possible optical, cryogenic, and mechanical interfaces for mounting a superconducting radio receiver at the focus of the optical telescope are considered. As a receiving system, arrays of detectors cooled to ~0.3 K based on the superconductor–insulator–normal metal–insulator–superconductor (SINIS) structure are proposed. The implementation of the project will make it possible to use the BTA site of the SAO RAS not only to solve some astronomical problems (it is possible to consider the implementation of a single observatory, the VLBI (very-long-baseline interferometry) mode in the Suffa, EHT (Event Horizon Telescope), and Millimetron projects), but it will also be used to test various cryogenic detectors in a real observatory. Full article

The dissolution of wool yarns in the ionic liquid 1-ethyl-3-methyl-imidazolium acetate [C2mim][OAc] has been investigated. Wool yarns were submerged into [C2mim][OAc] and dissolved for various times and temperatures before coagulating with water. Optical microscopy was used to track the yarn’s cross-sectional area. We propose that there are two competing dissolution processes, one rate-limited by disulfide bonds at low temperatures (LTs), and a second by hydrogen bonds at high temperatures (HTs), with a crossover point between the two regimes at 70 ℃. The corresponding activation energies were E_LT = 127 ± 9 kJ/mol and E_HT = 34 ± 1 kJ/mol. The remaining area of the dissolved wool yarn could be shifted via time–temperature superposition to plot a single master curve of area against time for both regions. Finally, the dissolution could be modelled by a diffusion process, giving self-diffusion coefficients for the [C2mim][OAc] ions (0.64–15.31 × 10⁻¹³ m²/s). Full article