Epigenetic control of Topoisomerase 1 activity presents a cancer vulnerability.

DNA transactions introduce torsional constraints that pose an inherent risk to genome integrity. While topoisomerase 1 (TOP1) activity is essential for removing DNA supercoiling, aberrant stabilization of TOP1:DNA cleavage complexes (TOP1ccs) can result in cytotoxic DNA lesions. What protects genomic hot spots of topological stress from aberrant TOP1 activity remains unknown. Here, we identify chromatin context as an essential means to coordinate TOP1cc resolution. Through its ability to bind poly(ADP-ribose) (PAR), a protein modification required for TOP1cc repair, the histone variant macroH2A1.1 establishes a TOP1-permissive chromatin environment, while the alternatively spliced macroH2A1.2 isoform is unable to bind PAR or protect from TOP1ccs. By visualizing transcription-induced topological stress in single cells, we find that macroH2A1.1 facilitates PAR-dependent recruitment of the TOP1cc repair effector XRCC1 to protect from ssDNA damage. Impaired macroH2A1.1 splicing, a frequent cancer feature, was predictive of increased sensitivity to TOP1 poisons in a pharmaco-genomic screen in breast cancer cells, and macroH2A1.1 inactivation mirrored this effect. Consistent with this, low macroH2A1.1 expression correlated with improved survival in cancer patients treated with TOP1 inhibitors. We propose that macroH2A1 alternative splicing serves as an epigenetic modulator of TOP1-associated genome maintenance and a potential cancer vulnerability.

Molecular dynamics simulations of the effect of static electric field on progressive ice formation.

Ice accumulation under static electric fields presents a significant hazard to transmission lines and power grids. Contemporary computational studies of electrofreezing predominantly probed excessive electric fields (109 V/m) that are significantly higher than those typically encountered in proximity to transmission lines. To elucidate the influence of realistic electric fields (105 V/m) on ice crystallization, we run extensive molecular dynamics (MD) simulations across dual ice-water coexistence systems. Three aspects of work were accordingly examined. First, we investigated the influence of the effect of static electric fields, with a strength of 105 V/m, along three orthogonal axes on the phase transition during the encountered freezing and melting processes. Second, we established the mechanism of how the direction of an electric field, the initial ice crystallography, and the adjacent crystal planes influence the solidification process. Third, the results of our MD simulations were further post-processed to determine the dipole moment, radial distribution, and angle distribution resulting from the static electric field. Our results indicate that while weak electric fields do not cause complete polarization of liquid water molecules, they can induce a transition to a more structured ice-like geometry of the water molecules at the ice-water interphase region, particularly when applied perpendicular to the ice-water interphase. Notably, the interface adjacent to cubic ice exhibits a greater response to the electric fields than that adjacent to hexagonal ice. This is attributable to the intrinsic differences in their original hydrogen bonding networks.

Temperature Self-Limited Intelligent Thermo-chemotherapeutic Lipid Nanosystem for P-gp Reversal Time Window Matched Pulse Treatment of MDR Tumor.

Mild photothermal therapy (PTT) shows the potential for chemosensitization by tumor-localized P-glycoprotein (P-gp) modulation. However, conventional mild PTT struggles with real-time uniform temperature control, obscuring the temperature-performance relationship and resulting in thermal damage. Besides, the time-performance relationship and the underlying mechanism of mild PTT-mediated P-gp reversal remains elusive. Herein, we developed a temperature self-limiting lipid nanosystem (RFE@PD) that integrated a reversible organic heat generator (metal-phenolic complexes) and metal chelator (deferiprone, DFP) encapsulated phase change material. Upon NIR irradiation, RFE@PD released DFP for blocking ligand-metal charge transfer to self-limit temperature below 45 °C, and rapidly reduced P-gp within 3 h via Ubiquitin-proteasome degradation. Consequently, the DOX·HCl-loaded thermo-chemotherapeutic lipid nanosystem (RFE@PD-DOX) led to dramatically improved drug accumulation and 5-fold chemosensitization in MCF-7/ADR tumor models by synchronizing P-gp reversal and drug pulse liberation, achieving a tumor inhibition ratio of 82.42%. This lipid nanosystem integrated with "intrinsic temperature-control" and "temperature-responsive pulse release" casts new light on MDR tumor therapy.

Research on transformer fault diagnosis method based on ACGAN and CGWO-LSSVM.

This paper proposes a transformer fault diagnosis method based on ACGAN and CGWO-LSSVM to address the problem of misjudgment and low diagnostic accuracy caused by the small number and uneven distribution of some fault samples in transformer fault diagnosis. Firstly, generate adversarial networks through auxiliary classification conditions, The ACGAN method expands a small and imbalanced number of samples to obtain balanced and expanded data; Secondly, the non coding ratio method is used to construct the characteristics of dissolved gases in oil, and kernel principal component analysis is used, KPCA method for feature fusion; Finally, using the improved cubic gray wolf optimization algorithm, CGWO for least square support vector machines, optimize the parameters of the LSSVM model and construct a transformer fault diagnosis model. The results show that the proposed method has a low false alarm rate and a diagnostic accuracy of 97.66%, compared to IGOA-LSSVM the IChOA-LSSVM and PSO-LSSVM methods improved accuracy by 0.12, 1.76, and 2.58%, respectively. This method has been proven to solve the problems of misjudgment and low diagnostic accuracy caused by small sample sizes and uneven distribution. It is suitable for multi classification fault diagnosis of transformer imbalanced datasets and is superior to other methods.

A coordinative modular assembly-constructed self-reinforced nano-therapeutic agent for effective antitumor-immune activation.

Immunosuppressive microenvironment and poor immunogenicity are two stumbling blocks in anti-tumor immune activation. Tumor associated macrophages (TAMs) play crucial roles in immunosuppressive microenvironment, while immunogenic cell death (ICD) is a typical strategy to boost immunogenicity. Herein, we developed a coordinative modular assembly-based self-reinforced nanoparticle, (CaO2/TA)-(Fe3+/BSA) which integrated CaO2, Fe3+-tannic acid coordinated networks and albumin under the instruction of molecular dynamics simulation. (CaO2/TA)-(Fe3+/BSA) could significantly enhance Fenton reaction through Fe3+ self-reduction and H2O2 self-sufficiency, and simultaneously increased intracellular accumulation of Ca2+. The self-augmented Fenton reaction with sufficient reactive oxygen species effectively repolarized TAMs and elicited ICD with Ca2+ overload. Besides, (CaO2/TA)-(Fe3+/BSA) was confirmed to self-reinforce deep tumor drug delivery by "treatment-delivery" positive feedback based on gp60-mediated transcytosis and M2-like macrophages repolarization-mediated perfusion promotion. Resultantly, (CaO2/TA)-(Fe3+/BSA) effectively alleviated immunosuppression, provoked local and systemic immune response and potentiated anti-PD-1 antibody therapy. Our strategy highlights a facile and controllable approach to construct penetrated effective antitumor nano-immunotherapeutic agent.

Transformer fault diagnosis method based on TLR-ADASYN balanced dataset.

As the cornerstone of transmission and distribution equipment, power transformer plays a very important role in ensuring the safe operation of power system. At present, the technology of dissolved gas analysis (DGA) has been widely used in fault diagnosis of oil-immersed transformer. However, in the actual scene, the limited number of transformer fault samples and the uneven distribution of different fault types often lead to low overall fault detection accuracy or a few types of fault misjudgment. Therefore, a transformer fault diagnosis method based on TLR-ADASYN balanced data set is presented. This method effectively addresses the issue of samples imbalance, reducing the impact on misjudgment caused by a few samples. It delves deeply into the correlation between the ratio of dissolved gas content in oil and fault type, eliminating redundant informations and reducing characteristic dimensions. The diagnostic model SO-RF (Snake Optimization-Random Forest) is established, achieving a diagnostic accuracy rate of 97.06%. This enables online diagnosis of transformers. Comparative analyses using different sampling methods, various features, and diverse diagnostic models were conducted to validate the effectiveness of the proposed method. In conclusion, validation was conducted using a public dataset, and the results demonstrate that the proposed method in this paper exhibits strong generalization capabilities.

Nanoscale Adsorption, Assembly, and Deionization Dynamics Recorded by Optical Fiber Sensors.

Capacitive deionization in environmental decontamination has been widely studied and now requires intensive development to support large-scale deployment. Porous nanomaterials have been demonstrated to play pivotal roles in determining decontamination efficiency and manipulating nanomaterials to form functional architecture has been one of the most exciting challenges. Such nanostructure engineering and environmental applications highlight the importance of observing, recording, and studying basically electrical-assisted charge/ion/particle adsorption and assembly behaviors localized at charged interfaces. In addition, it is generally desirable to increase the sorption capacity and reduce the energy cost, which increase the requirement for recording collective dynamic and performance properties that stem from nanoscale deionization dynamics. Herein, we show how a single optical fiber can serve as an in situ and multifunctional opto-electrochemical platform for addressing these issues. The surface plasmon resonance signals allow the in situ spectral observation of nanoscale dynamic behaviors at the electrode-electrolyte interface. The parallel and complementary optical-electrical sensing signals enable the single probe but multifunctional recording of electrokinetic phenomena and electrosorption processes. As a proof of concept, we experimentally decipher the interfacial adsorption and assembly behaviors of anisotropic metal-organic framework nanoparticles at a charged surface and decouple the interfacial capacitive deionization within an assembled metal-organic framework nanocoating by visualizing its dynamic and energy consumption properties, including the adsorptive capacity, removal efficiency, kinetic properties, charge, specific energy consumption, and charge efficiency. This simple "all-in-fiber" opto-electrochemical platform offers intriguing opportunities to provide in situ and multidimensional insights into interfacial adsorption, assembly, and deionization dynamics information, which may contribute to understanding the underlying assembly rules and the exploring structure-deionization performance correlations for the development of tailor-made nanohybrid electrode coatings for deionization applications.

Alfuzosin ameliorates diabetes by boosting PGK1 activity in diabetic mice.

AIMS: Diabetes mellitus (DM) has become a global problem, causing a huge economic burden. The purpose of this study is to find a new potential method and mechanism for the treatment of DM. MAIN METHODS: The oxidation, glycation and insulin resistance cell models were built to screen the potential anti-diabetic chemicals. Then the DM mice were induced by the combination of high-fat diet (HFD) and intraperitoneal injection of streptozotocin (50 mg/kg) for five days. The alfuzosin (1.2 mg/kg) was administered by intraperitoneal injection once daily for sequential 12 weeks. Fasting blood glucose, blood lipid, oxidative stress and key markers of glucose metabolism were detected. PGK1/AKT/GLUT4 pathway related proteins were analyzed by Western blot. KEY FINDINGS: Alfuzosin ameliorated oxidative stress, glycative stress and insulin resistance in HepG2 cells. Further, in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, alfuzosin reduced fasting blood glucose, improved insulin sensitivity. Mechanically, alfuzosin activated PGK1 directly to stimulate the protein kinase B (AKT) signaling pathway, thus facilitating glucose uptake as well as improving insulin resistance. SIGNIFICANCE: The present finding has shed a new light on the treatment of DM and provides validation for PGK1 as a therapeutic target for DM.

Sulfathiazole treats type 2 diabetes by restoring metabolism through activating CYP19A1.

Globally, diabetes mellitus has been a major epidemic bringing metabolic and endocrine disorders. Currently, 1 in 11 adults suffers from diabetes mellitus, among the patients >90% contract type 2 diabetes mellitus (T2DM). Therefore, it is urgent to develop new drugs that effectively prevent and treat type 2 diabetes through new targets. With high-throughput screening, we found that sulfathiazole decreased the blood glucose and improved glucose metabolism in T2DM mice. Notably, we discovered that sulfathiazole treated T2DM by activating CYP19A1 protein to synthesize estrogen. Collectively, sulfathiazole along with CYP19A1 target bring new promise for the better therapy of T2DM.

Quinacrine attenuates diet-induced obesity by inhibiting adipogenesis via activation of AMPK signaling.

Obesity, a global epidemic chronic metabolic disease, urgently demands novel therapies. As an antimalarial drug, quinacrine has not been reported for its anti-obesity effect to our knowledge. This study aimed to explore the ability of quinacrine to attenuate obesity. In an in vitro adipogenic model, quinacrine exhibited an outstanding suppression on adipogenesis of 3T3-L1 cells, mainly by activating the AMPK (Adenosine 5'-monophosphate (AMP)-activated protein kinase) signaling pathway to regulate preadipocytes differentiation and lipid accumulation. In addition, C57BL/6N female mice were fed with high-fat diet and high-fructose water for 14 weeks to establish an obesity model, followed by oral administration of quinacrine or orlistat. After 9 weeks of treatment, quinacrine significantly reduced the body weight and energy intake, ameliorated the impaired glucose tolerance and restored the homeostasis of serum lipids. Also, quinacrine improved lipid profile and optimized the expression of AMPK signaling pathway related proteins in livers and adipose tissues of obese mice. Quinacrine reverses obesity through activating AMPK phosphorylation to down-regulate adipogenesis, along with lowering the risk of type 2 diabetes and atherosclerosis. It should be a novel application for the treatment of obesity and its associated diseases.

Primaquine activates Keratin 7 to treat diabetes and its complications.

Background: The global prevalence of type 2 diabetes mellitus (T2DM) raises the rates of its complications, such as diabetic nephropathy and cardiovascular diseases. To conquer the complications, new strategies to reverse the deterioration of T2DM are urgently needed. In this project, we aimed to examine the hypoglycemic effect of primaquine and explore its specific target. Methods: In vitro T2DM insulin resistance model was built in HepG2 cells to screen the potential anti-diabetic chemicals. On the other hand, the potential protein targets were explored by molecular docking. Accordingly, we chose C57BL/6 N mice to establish T2DM model to verify the effect of the chemicals on anti-hyperglycemia and diabetic complications. Results: By targeting the Keratin 7 (K7) to activate EGFR/Akt glucose metabolism signaling pathway, primaquine poses a potent hypoglycemic effect. The level of acetyl-CoA is enhanced markedly, supporting that primaquine upregulates the aerobic glycolysis. Moreover, primaquine ameliorates kidney function by reducing the secretion of urinary proteins and creatinine, especially for the urea nitrogen which is significantly decreased compared to no-treatment T2DM mice. Notably, primaquine restores the level of plasma low-density lipoprotein cholesterol (LDL-C) nearly to normal, minimizing the incidence of cardiovascular diseases. Conclusions: We find that primaquine may reverse the dysregulated metabolism to prevent diabetic complications by stimulating EGFR/Akt signaling axis, shedding new light on the therapy of T2DM. Graphical abstract: Insulin resistance is characterized by reduced p-Akt and glucose metabolism, dominated by anaerobic glycolysis. Primaquine activates the complex made of K7 and EGFR, further stimulating Akt phosphorylation. Then, p-Akt promotes the aerobic glucose metabolism and upregulates Ac-CoA to mobilize TCA cycle, improving insulin sensitivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01135-8.

Lamivudine remedies alcoholism by activating acetaldehyde dehydrogenase.

Acute ethanol intoxication has become an alarming health problem. In the present study, we discover the beneficial effect of lamivudine on alcoholism in mice. Our results indicate that lamivudine decreases serum alcohol concentration dramatically, and potently activates acetaldehyde dehydrogenase (ALDH) to accelerate the conversion of acetaldehyde to acetic acid, which is finally metabolized by tricarboxylic acid cycle to be CO2 and H2O. Also, lamivudine significantly improves symptoms post drinking, such as prolonging alcohol tolerance time and shortening sobering time, as well as reducing the death rate. This work will provide new strategies for the prevention and treatment of acute alcoholism.

Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice.

AIMS: Diabetes mellitus (DM) is a major global health threat characterized by insulin resistance. A new tactic to ameliorate insulin resistance, thereby reversing the exacerbation of DM, is urgently needed. The work is aiming to provide a new strategy for DM treatment as well as to identify new targets. MAIN METHODS: C57BL/6 N mice were raised with high-fat diet (HFD) and infused with streptozotocin (STZ) to induce diabetes. The blood glucose, serum insulin, blood lipid and oxidative stress were detected. In vitro insulin resistance model experiment has been made to examine the molecular mechanisms underlying anti-diabetic effect of potential active chemicals in human hepatocellular carcinoma cells (HepG2). KEY FINDINGS: Acyclovir, an antiviral nucleotide analog, alleviates insulin resistance by reducing blood lipids as well as oxidative stress and elevating insulin sensitivity on diabetic mice, which is in accord with results in the insulin resistance model of HepG2 cells. Mechanically, acyclovir stimulates pyruvate kinase M1 (PKM1) directly to activate adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Sirtuin1 (SIRT1) signaling pathway, thus improving insulin resistance. SIGNIFICANCE: The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.

The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents.

Stroke is the second leading cause of death worldwide and the leading cause of long-term disability that seriously endangers health and quality of human life. Tissue-type fibrinogen activator is currently the only drug approved by FDA for the treatment of ischemic stroke. Neuroprotection is theoretically a common strategy for the treatment of both ischemic and hemorrhagic stroke; therefore, the development of neuroprotective agent has been the focus of research. However, no ideal neuroprotective drug is clinically available. Phosphoglycerate kinase-1 (PGK1) activator has the effect of inhibiting apoptosis and protecting tissue damage, and therefore could be a potential neuroprotective agent. To obtain effective PGK1 activators, we virtually screened a large chemical database and their evaluated the efficacy by the Drosophila oxidative stress model, PGK1 enzymatic activity assay, and oxygen-glucose stripping reperfusion (OGD/R) model. The results showed that compounds 7979989, Z112553128 and AK-693/21087020 are potential PGK1 activators with protective effects against PQ-induced oxidative stress in the Drosophila model and could effectively ameliorate apoptosis induced by OGD/R-induced neuronal cell injury. Additionally, compounds 7979989 and Z112553128 are effective in alleviating LPS-induced cellular inflammation. This study indicated that these compounds are promising lead compounds that provide theoretical and material basis to the neuroprotective drug discovery.

The differential roles of lexical and sublexical processing during spoken-word recognition in clear and in noise.

Successful spoken-word recognition relies on interplay between lexical and sublexical processing. Previous research demonstrated that listeners readily shift between more lexically-biased and more sublexically-biased modes of processing in response to the situational context in which language comprehension takes place. Recognizing words in the presence of background noise reduces the perceptual evidence for the speech signal and - compared to the clear - results in greater uncertainty. It has been proposed that, when dealing with greater uncertainty, listeners rely more strongly on sublexical processing. The present study tested this proposal using behavioral and electroencephalography (EEG) measures. We reasoned that such an adjustment would be reflected in changes in the effects of variables predicting recognition performance with loci at lexical and sublexical levels, respectively. We presented native speakers of Dutch with words featuring substantial variability in (1) word frequency (locus at lexical level), (2) phonological neighborhood density (loci at lexical and sublexical levels) and (3) phonotactic probability (locus at sublexical level). Each participant heard each word in noise (presented at one of three signal-to-noise ratios) and in the clear and performed a two-stage lexical decision and transcription task while EEG was recorded. Using linear mixed-effects analyses, we observed behavioral evidence that listeners relied more strongly on sublexical processing when speech quality decreased. Mixed-effects modelling of the EEG signal in the clear condition showed that sublexical effects were reflected in early modulations of ERP components (e.g., within the first 300 msec post word onset). In noise, EEG effects occurred later and involved multiple regions activated in parallel. Taken together, we found evidence - especially in the behavioral data - supporting previous accounts that the presence of background noise induces a stronger reliance on sublexical processing.

Laser-Induced Corrugated Graphene Films for Integrated Multimodal Sensors.

Microstructures play a dominant role in flexible electronics to improve the performance of the devices, including sensitivity, durability, stretchability, and so on. However, the complicated and expensive fabrication process of these microstructures extremely hampers the large-scale application of high-performance devices. Herein, we propose a novel method to fabricate flexible graphene-based sensors with a 3D microstructure by generating laser-induced graphene (LIG) on the 3D printed polyether ether ketone corrugated substrate, which is referred to as CLIG. Based on that, two integrated piezoresistive sensors are developed to monitor the precise strain and pressure signals. Contributed to the 3D corrugated graphene structure, the sensitivities of strain and pressure sensors can be up to 2203.5 and 678.2 kPa-1, respectively. In particular, the CLIG-based strain sensor exhibits a high resolution to the microdeformation (small as 1 µm or 0.01% strain) and remarkable durability (15,000 cycles); meanwhile, the pressure sensor presents a remarkable working range (1-500 kPa) and fast response time (24 ms). Furthermore, the CLIG-based sensors provide a stable data source in the applications of human-motion monitoring, pressure array, and self-sensing soft robotic systems. High accuracy allows CLIG sensors to recognize more subtle signals, such as pulse, swallowing, gesture distinction of human, and movement status of soft robotics. Overall, this technology shows a promising strategy to fabricate high-performance sensors with high efficiency and low cost.

Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders.

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes.

Background: Disinfectant products are often used on environmental surfaces (e.g. countertops, patient beds) and patient care equipment in healthcare facilities to help prevent the transmission of healthcare-associated infections. Ready-to-use (RTU) disinfectants in the form of pre-wetted towelettes are increasingly popular among healthcare facilities. Currently, the EPA does not require disinfectant manufacturers to include a recommended maximum surface area per towelette on their product labels. The objective of this study was to investigate the efficacy of disinfectant towelette products on a hard non-porous surface across different coverage areas using a quantitative EPA method. We hypothesized that there would be significant differences in the efficacy of disinfectant towelette products, and that the greater surface area(s) wiped would result in reduced bactericidal efficacy. Methods: This study tested ten disinfectant towelette products against Staphylococcus aureus strain ATCC CRM-6538 and Pseudomonas aeruginosa strain ATCC 15442 on Formica surfaces. Defined surface areas were wiped and the towelette weighed before and after wiping to determine the amount of liquid released. Bactericidal efficacy testing was also performed after wiping following standard EPA protocols. Results: We found that disinfectant product, area of surface wiped, and strain impacted the bactericidal efficacy achieved. Disinfectant product type and area of surface wiped significantly impacted the percent of liquid released per ft2from the towelette. Conclusion: Overall, bactericidal efficacy varied by towelette product, surface area wiped, and strain. This study also found that wiping larger surface areas may lead to decreased bactericidal efficacy. Further research is needed to test its implication.

Investigation of Sensitivities and Drift Effects of the Arrayed Flexible Chloride Sensor Based on RuO2/GO at Different Temperatures.

We investigate the temperature effect on sensing characteristics and drift effect of an arrayed flexible ruthenium dioxide (RuO2)/graphene oxide (GO) chloride sensor at different solution temperatures between 10 °C and 50 °C. The average sensor sensitivities according to our experimental results were 28.2 ± 1.4 mV/pCl (10 °C), 42.5 ± 2.0 mV/pCl (20 °C), 47.1 ± 1.8 mV/pCl (30 °C), 54.1 ± 2.01 mV/pCl (40 °C) and 46.6 ± 2.1 mV/pCl (50 °C). We found the drift effects of an arrayed flexible RuO2/GO chloride sensor in a 1 M NaCl solution to be between 8.2 mV/h and 2.5 mV/h with solution temperatures from 10 °C to 50 °C.